Culture

PITTSBURGH, Aug. 6, 2020 - New research by neuroscientists at the University of Pittsburgh and University of California San Francisco (UCSF) revealed that a simple, earbud-like device developed at UCSF that imperceptibly stimulates a key nerve leading to the brain could significantly improve the wearer's ability to learn the sounds of a new language. This device may have wide-ranging applications for boosting other kinds of learning as well.

Mandarin Chinese is considered one of the hardest languages for native English speakers to learn, in part because the language -- like many others around the world -- uses distinctive changes in pitch, called "tones," to change the meaning of words that otherwise sound the same. In the new study, published today in npj Science of Learning (a Nature partner journal), researchers significantly improved the ability of native English speakers to distinguish between Mandarin tones by using precisely timed, non-invasive stimulation of the vagus nerve -- the longest of the 12 cranial nerves that connect the brain to the rest of the body. What's more, vagus nerve stimulation allowed research participants to pick up some Mandarin tones twice as quickly.

"Showing that non-invasive peripheral nerve stimulation can make language learning easier potentially opens the door to improving cognitive performance across a wide range of domains," said lead author Fernando Llanos, Ph.D., a postdoctoral researcher in Pitt's Sound Brain Lab.

"This is one of the first demonstrations that non-invasive vagus nerve stimulation can enhance a complex cognitive skill like language learning in healthy people," said Matthew Leonard, Ph.D., an assistant professor, Department of Neurological Surgery, UCSF Weill Institute for Neurosciences, whose team developed the nerve stimulation device. Leonard is a senior author of the new study, alongside Bharath Chandrasekaran, Ph.D., professor and vice chair of research, Department of Communication Science and Disorders, Pitt School of Health and Rehabilitation Sciences, and director of the Sound Brain Lab.

Researchers used a non-invasive technique called transcutaneous vagus nerve stimulation (tVNS), in which a small stimulator is placed in the outer ear and can activate the vagus nerve using unnoticeable electrical pulses to stimulate one of the nerve's nearby branches.

For their study, the researchers recruited 36 native English-speaking adults and trained them to identify the four tones of Mandarin Chinese in examples of natural speech, using a set of tasks developed in the Sound Brain Lab to study the neurobiology of language learning.

Participants who received imperceptible tVNS paired with two Mandarin tones that are typically easier for English speakers to tell apart showed quick improvements in learning to distinguish these tones. By the end of the training, those participants were 13% better on average at classifying tones and reached peak performance twice as quickly as control participants who wore the tVNS device but never received stimulation.

"There's a general feeling that people can't learn the sound patterns of a new language in adulthood, but our work historically has shown that's not true for everyone," Chandrasekaran said. "In this study, we are seeing that tVNS reduces those individual differences more than any other intervention I've seen."

"This approach may be leveling the playing field of natural variability in language learning ability," added Leonard. "In general, people tend to get discouraged by how hard language learning can be, but if you could give someone 13% to 15% better results after their first session, maybe they'd be more likely to want to continue."

The researchers now are testing whether longer training sessions with tVNS can impact participants' ability to learn to discriminate two tones that are harder for English speakers to differentiate, which was not significantly improved in the current study.

Stimulation of the vagus nerve has been used to treat epilepsy for decades and has recently been linked to benefits for a wide range of issues ranging from depression to inflammatory disease, though exactly how these benefits are conferred remains unclear. But most of these findings have used invasive forms of stimulation involving an impulse generator implanted in the chest. By contrast, the ability to evoke significant boosts to learning using simple, non-invasive vagus nerve stimulation could lead to significantly cheaper and safer clinical and commercial applications.

The researchers suspect tVNS boosts learning by broadly enhancing neurotransmitter signaling across wide swaths of the brain to temporarily boost attention to the auditory stimulus being presented and promote long-term learning, though more research is needed to verify this mechanism.

"We're showing robust learning effects in a completely non-invasive and safe way, which potentially makes the technology scalable to a broader array of consumer and medical applications, such as rehabilitation after stroke," Chandrasekaran said. "Our next step is to understand the underlying neural mechanism and establish the ideal set of stimulation parameters that could maximize brain plasticity. We view tVNS as a potent tool that could enhance rehabilitation in individuals with brain damage."

Scientists from Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago discovered that a set of genes with decreased expression in individuals with Down syndrome may lead to clinical abnormalities in this population, such as poor muscle development and heart valve problems. Impairment in these same genes may also protect people with Down syndrome from developing solid tumors. Their findings were published in Scientific Reports.

"Our promising preliminary data carries strong potential for ultimately developing gene-targeted therapies to inhibit solid tumor growth in the general population," says co-lead author Yekaterina Galat, BS, Research Associate at the Manne Research Institute at Lurie Children's. "Our findings may also provide gene targets for therapies aimed at alleviating the clinical abnormalities in people with Down syndrome."

Down syndrome is a congenital genetic disorder that is associated with cognitive impairment, reduced muscle tone, heart defects, and other clinical anomalies. At the same time, individuals with Down syndrome have lower prevalence of solid tumor formation.

The study used skin samples from two patients with Down syndrome to create induced pluripotent stem cells that were then differentiated into endothelial cells, which build blood vessels and the vascular system, and mesodermal cells, which are responsible for connective tissues and muscle development. During the process of differentiation, in the progenitor phase, Manne Research Institute scientists discovered down-regulated genes that appear to be involved in the abnormal muscle development and heart problems that are common in people with Down syndrome.

By studying the role of these genes in biochemical pathways relevant to solid tumor development, they found that the decreased expression of such genes interferes with the processes needed for solid tumor formation and growth. These genes produced impeded cell movement, slower proliferation and reduced inflammatory response - creating a microenvironment that is not conducive to solid tumors. Genome-wide analyses was then performed to confirm these findings, using publicly available data from 11,000 patients.

"When we performed genomic analyses comparing mesodermal and endothelial cell lines, we were surprised to find that trisomy 21 impacted gene expression across the entire genome. Furthermore, the decreased expression of the genes we studied was consistent, and the large extent of their down-regulation was notable as well," says co-lead author Mariana Perepitchka, BA, Research Associate at the Manne Research Institute at Lurie Children's. "This significant down-regulation potentially creates conditions that are opposite of what solid tumors would need to take hold. So in a way, Down syndrome provides us with a non-traditional lens to study cancer development."

"We still need to validate our findings in an animal model," says senior author Vasil Galat, PhD, Director of Human iPS and Stem Cell Core at Manne Research Institute at Lurie Children's and Research Assistant Professor of Pathology at Northwestern University Feinberg School of Medicine. "The potential for gene-targeted therapies is very exciting, especially since it could help individuals born with Down syndrome and the general population battling cancer."

Tropical oceans and fisheries are threatened by climate change, generating impacts that will affect the sustainable development of both local economies and communities, and regions outside the tropics through 'telecoupling' of human-natural systems, such as seafood trade and distant-water fishing, says a scientific review from UBC and international researchers.

Seafood is the most highly traded food commodity globally, with tropical zone marine fisheries contributing more than 50 per cent of the global fish catch, an average of $USD 96 billion annually. Available scientific evidence consistently shows that tropical marine habitats, fish stocks and fisheries are most vulnerable to oceanic changes associated with climate change. However, the scientific review highlights that telecoupling, or linkages between distant human-natural systems, could generate cascades of climate change impacts from the tropics that propagate to other 'extra-' tropical natural systems and human communities globally.

"Telecoupling interactions between two or more linked areas over distance between tropical fisheries and elsewhere include distant-water fishing, the international seafood supply chain, transboundary fisheries resources and their governance would allow benefits derived from tropical fisheries to transfer to the people in the extratropical regions," said Vicky Lam, lead author and research associate in the UBC's Institute for the Oceans and Fisheries. "Although these linkages could enable the flow of benefits, including food, livelihoods and government revenue, from tropical fisheries to extratropical locations, their dependence on tropical fisheries also exposes them to the negative consequences of climate change in tropical regions. The effects of climate change on tropical fisheries also affect the profitability and employment opportunities of fish-processing industries in extratropical regions."

"Pacific Island countries and territories, for example, are expected to see a redistribution of skipjack and yellowfin tuna - their two most exported fish species - that could see decreased catches of between 10 and 40 per cent by 2050 in many countries such as Palau and the Solomon Islands, while catches are expected to increase by 15 to 20 per cent in Kiribati and the Cook Islands. This will have a tremendous effect on the economies of these small island developing states," said Rashid Sumaila, co-author and professor at UBC's Institute for the Oceans and Fisheries and School of Public Policy and Global Affairs. "There are similar projections in African nations, where climate-related changes are expected to decrease the value of landed catch by approximately 20 per cent by 2050, as well as reduce fisheries-related jobs by 50 per cent."

To reduce the effect of climate change on the benefits derived from tropical fisheries, both locally and in extra-tropical regions, the root causes of climate-driven problems in tropical fisheries need to be recognized and rectified. Effective and practical adaptation and mitigation solutions with stakeholder commitment and involvement, as well as supporting policies, are therefore necessary in the tropics.

"We already see that there are close linkages between the tropical regions and the extra-tropical nations through trade and distant-water fishing" said William Cheung, co-author and professor at UBC's Institute for the Oceans and Fisheries. "Solving climate change impacts in the tropics will benefit the whole world; this provides an additional argument for non-tropical countries to support climate mitigation and adaptation in tropical countries."

VANCOUVER, Wash. - Despite common perceptions that big cities have more violence, women living in small towns are most at risk of violence from current or former spouses and partners, according to a recent study by Washington State University criminologist Kathryn DuBois.

For the study, published in the Journal of Interpersonal Violence, DuBois analyzed the responses of more than 570,000 women from the National Crime Victimization Survey from 1994 to 2015. She found that women from small towns were 27% more likely to be victims of intimate partner violence than women from the center of big cities and 42% more likely than suburban women.

"In criminology, we often have this urban bias. We assume big cities are the worst and paint other places as idyllic," said DuBois, associate professor at WSU Vancouver. "We tend to think in a continuum from urban to suburban to rural, but for intimate partner violence, it's actually the suburban areas that are the safest, and small towns that have the highest risk."

The National Crime Victimization Survey collects information through a large sample of interviews about a range of personal crimes committed every year. Part of the intent of the survey is to uncover the "dark figure" of crime, DuBois said, those crimes that may not be reported to police.

While the survey defines many locations as simply urban or rural, DuBois analyzed the data by population density to delineate urban, suburban, small town and rural areas. Small towns were defined as urbanized portions of non-metropolitan counties with populations up to 50,000. They are distinct from suburban areas that exist just outside of big cities.

"Many surveys assume that everyone in those nonmetropolitan counties are the same, but there's a lot more heterogeneity across them," Dubois said.

DuBois originally undertook the study to try and reconcile the inconsistency between national surveys, which typically find rural areas have less or similar rates of intimate partner violence to urban areas--and ethnographic research, in-depth qualitative studies that have indicated that rural isolation can exacerbate gender-based violence.

While the study data cannot reveal the reasons behind the violence, the finding about the high rate of intimate partner violence in small towns indicates that there may be a different set of factors at play, DuBois said.

"Small towns have populations large enough to have the difficult problems of a big city, while at the same time these are some of the hardest hit areas economically, so they don't have specialized services and policing needed to deal with family violence," DuBois said.

Resource fishes--species targeted for human consumption--play a key role in reef ecosystems long before they end up on the dinner table. In Hawai?i, subsistence and recreational fishing of local resource fish represent more than half of the share of annual reef seafood consumption, while also playing a vital role in indigenous cultural life.

These same fishes also help reefs to stay healthy by removing algae from coral surfaces, which in turn, help coral recover from bleaching. Given the beneficial relationship between resource fishes and corals, determining how local pressures impact resource fish biomass is necessary for improving reef conservation and management.

In a new study investigating human impacts on resource fish biomass on the Island of Hawai?i, researchers from the Arizona State University Center for Global Discovery and Conservation Science (GDCS) and Hawai'i Division of Aquatic Resources (DAR) observed an alarming 45% decrease in fish biomass over a decade of surveys. The scientists proposed actionable solutions to mitigate future losses. The study was published today in Ecological Applications.

The researchers investigated the influence of local factors on the nearshore resource fisheries of West Hawai'i Island and compared the impact of distinct types of marine protections. They considered a range of factors including commercial and non-commercial fishing as well as nitrogen pollution from sewage disposal systems and golf courses. They also used ASU's Global Airborne Observatory to map the 3-D reef habitat to assess how it affects fish diversity, abundance, and biomass. The researchers analyzed extensive fish survey data collected by DAR between 2008 and 2018 at more than 300 sites spanning 180 km of coastline.

"Resource fish have been greatly reduced over the past decade in West Hawai'i. We see that negative impacts of nitrogen pollution can outweigh other habitat and land-use stresses on resource fish," said Dr. Shawna Foo, a postdoctoral researcher at GDCS and lead author of the study. Nitrogen effluent from sewage and golf courses contaminates nearshore waters, creating stress for corals and were a major driver of resource fish declines documented in the study.

Despite the long-term decline, the researchers also found that different types of management resulted in different levels of fish biomass. They found significantly greater fish abundance and biomass in areas that banned spearfishing compared to areas that did not, likely due to the fact that four of the five most common species from the surveys are primarily caught by spears. This finding was particularly true for ?scrapers' such as parrotfish.

The researchers also found that marine management areas with multiple bans on spearfishing, aquarium collection, and lay nets had the highest overall fish biomass compared to other managed or unmanaged areas, especially for herbivorous fish. Their findings are supported by a recent global analysis of marine management led by the University of Leeds, which reported higher fish biomass in areas where gear was limited to pole and line fishing. Those researchers recommended specific gear restrictions as a relevant management strategy to attain the dual objectives of supporting resource fish biomass recovery and satisfying stakeholders.

Greg Asner, GDCS director and co-author of the study noted, "These results are among the clearest to emerge for Hawai?i. Based on the long-term monitoring efforts of our Hawai?i DAR partners, we were able to ascertain unequivocal evidence for a decline in shallow reef fish populations along the famous Kona coast of Hawai?i Island. We were also able to connect both the decline and the remaining fish stocks to specific actions that can be taken now to enhance the fishery and protect reefs. This is a triple win for science, management, and the fisher community."

The study reinforces the urgent need to protect reef ecosystems from increasing threats of habitat degradation and climate change. Last year alone, ocean temperatures reached near-record levels, ushering in a coral bleaching event that resulted in coral loss across the Hawaiian archipelago. To protect resource fish biomass and aid reef resilience and recovery, regional management of multiple stressors is greatly needed. The researchers proposed to mitigate such future losses by banning and/or restricting specific fishing gear types and more aggressive management of land-based pollution.

"The collaboration with our partners at GDCS provides an incredible opportunity to combine state-of-the-art seascape level mapping with DAR's long-term coral reef monitoring to understand the links between marine and land management and coral reef health.", noted Brian Neilson, Administrator in charge of the Hawai?i Division of Aquatic Resources. "This study is critical for informing statewide management strategies to maintain important resource fish stocks and resilient reefs, as we face unprecedented climate-driven threats."

The quality of audit services suffers when an audit firm has clients from many different industries, according to new research from the University of Notre Dame.

If an audit office has a diversified client portfolio, it is more difficult to audit a particular type of client, according to "Audit Office Industry Diversity and Audit Quality," forthcoming in the Journal of Accounting, Auditing and Finance from Erik Beardsley, assistant professor of accountancy at Notre Dame's Mendoza College of Business, along with Nathan Goldman at North Carolina State University and Tom Omer at the University of Nebraska-Lincoln.

The study examined financial statement restatement rates for clients of audit offices from 2002 to 2015. Each firm they examined had data from a varying number of years, for a total of 35,265 observations in the dataset. "When the financial statements must be restated because of a material error, this means the audit team missed the error before statements were issued, indicating lower audit quality," Beardsley explained.

"Prior studies have examined different characteristics of audit firms or offices, but they have not considered the industry diversity of the client portfolio as a whole," he said. "For example, even if an audit office has a lot of clients in one industry, the overall industry diversity of the portfolio can harm the audit quality of all clients in the portfolio. This is likely because auditing a lot of different industries forces the auditor to spread their resources to a variety of different engagements rather than focus on particular types."

The study found that having an industry-diverse client base can harm audit quality for both small and large audit offices. Though a small office may not have many clients, if each is in a different industry, audit quality suffers. Likewise, even a large office with more resources is less effective at allocating those resources when the clients are more industry-diverse.

The study also determined that having a diverse client base can harm audit quality for industry specialists and non-industry specialists, where specialization is based on market share.

"An office could have a large market share in one industry, often due to one or two high-profile clients," Beardsley explained, "but still be considered industry-diverse if it also audits clients in a variety of other industries. We observed the adverse effect of industry diversity even among offices with large market share, meaning that having a large market share is not enough to counter balance the negative effects of industry diversity.

"However, we did not find the negative effect when there were clusters of three or more clients in the same industry," he continued, "suggesting that sufficient industry knowledge can occur from clusters of three or more clients in an industry."

The study could prove helpful for audit firms in making resource allocation and client retention decisions, as well as for audit committees to assess which auditor is their best fit.

AMHERST, Mass. - In an unexpected new finding, biochemists at the University of Massachusetts Amherst report observing that a damage-containment system in stressed bacteria can become overrun and blocked, but that this leads to cells responding by turning on very different pathways to make sure that normal growth continues.

Rilee Zeinert, a doctoral student in the Molecular and Cell Biology Program and his advisor, professor Peter Chien, report on their recent experiments and discovery about how bacteria switch gears to respond to different stresses but still maintain normal cell functions like DNA replication in the recent issue of the Cell journal, Molecular Cell. Other contributing authors include Benjamin Tu and Hamid Baniasadi at the University of Texas Southwestern Medical Center.

Chien says that because all cells must maintain normal growth even during stressful conditions and all cells contain clean-up proteases that degrade used proteins and other waste, similar regulation may be at work in other biological responses. He suggests, "Cancer cells also are constantly growing under protein stress conditions, so understanding how cells in general take advantage of protease competition to respond to stress leads to tempting speculations that we can inhibit similar pathways to block uncontrolled growth."

In bacteria, a protease known as Lon destroys damaged proteins to protect cells from their toxic consequences and degrades normal signaling proteins, as well. Stress that is toxic to proteins - causing misfolding, for example - prompts the bacteria not only to try to keep removing these damaged proteins, but to maintain processes like replicating DNA for normal growth. Zeinert studied the Lon protease and pathways it uses during cell stress, such as antibiotic attacks or extreme heat, to accomplish this.

In their new paper, the authors show that when bacteria are stressed, the increase in damaged proteins ends up temporarily swamping the Lon protease. This results in stabilization of signaling proteins that would normally be degraded by Lon, which sets off a cascade of responses, Chien explains.

He adds, "The misfolded proteins are canaries in the coal mines. When they build up so much that Lon is now blocked, the cells respond by turning on pathways needed to ensure growth." In particular, the cells increase the amount of deoxynucleotides - the 'DN' of DNA - building blocks that are needed for DNA replication."

Zeinert, Chien and colleagues discovered this new pathway unexpectedly when they were exploring the essential character of different genes that depend on the Lon protease. Chien recalls, "Rilee was using a new approach that looks at the fitness cost of each gene in different mutant backgrounds. Surprisingly, he found that loss of a normally essential deoxynucleotide synthesis gene was now tolerated in cells missing the Lon protease."

This meant that by decreasing Lon activity, cells would compensate by making more deoxynucleotides, a result the researchers confirmed with metabolomics, a procedure that measures hundreds of chemicals in a cell at once, he adds.

Chien explains, "The metabolomics told us that there was a substantial shift in all the building blocks for DNA synthesis when Lon activity was compromised. At the same time, we had seen that when cells are stressed they also seem to make more of these molecules." That connection led the researchers to determine that it was the damaged proteins arising from the stress causing a block of Lon activity that resulted in this response.

Chien, who is director of the Models to Medicine Center in the Institute of Applied Life Sciences at UMass Amherst, points out that this work was funded by the National Institute of General Medical Sciences in the form of a MIRA grant to Chien and the Chemistry-Biology Training Program, which also supported Zeinert. The MIRA program does not fund individual projects, but broad programs of basic discovery research, to encourage researchers to propose more long-term, innovative, creative projects and to worry less about short-term goals and results.

With its ability to yield parts with complex shapes and minimal waste, additive manufacturing has the potential to revolutionize the production of metallic components. That potential, however, is currently limited by one critical challenge: controlling defects in the process that can compromise the performance of 3D-printed materials.

A new paper in the journal Additive Manufacturing points to a possible breakthrough solution: Use temperature data at the time of production to predict the formation of subsurface defects so they can be addressed right then and there. A team of researchers at the U.S. Department of Energy’s (DOE) Argonne National Laboratory, together with a colleague now at Texas A&M University, discovered the possibility.

“Ultimately you would be able to print something and collect temperature data at the source and you could see if there were some abnormalities, and then fix them or start over,” said Aaron Greco, group manager for Argonne’s Interfacial Mechanics & Materials group in the Applied Materials Division (AMD) and a study author. “That’s the big-picture goal.”

For their research, the scientists used the extremely bright, high-powered X-rays at beamline 32-ID-B at Argonne’s Advanced Photon Source (APS), a Department of Energy Office of Science User Facility. They designed an experimental rig that allowed them to capture temperature data from a standard infrared camera viewing the printing process from above while they simultaneously used an X-ray beam taking a side-view to identify if porosity was forming below the surface.

Porosity refers to tiny, often microscopic “voids” that can occur during the laser printing process and that make a component prone to cracking and other failures.  

According to Noah Paulson, a computational materials scientist in the Applied Materials division and lead author on the paper, this work showed that there is in fact a correlation between surface temperature and porosity formation below.

“Having the top and side views at the same time is really powerful. With the side view, which is what is truly unique here with the APS setup, we could see that under certain processing conditions based on different time and temperature combinations porosity forms as the laser passes over,” Paulson said.

For example, the paper observed that thermal histories where the peak temperature is low and followed by a steady decline are likely to be correlated with low porosity. In contrast, thermal histories that start high, dip, and then later increase are more likely to indicate large porosity.

The scientists used machine learning algorithms to make sense out of the complex data and predict the formation of porosity from the thermal history. Paulson said that in comparison to the tools developed by tech giants that use millions of data points, this effort had to make do with a couple hundred. “This required that we develop a custom approach that made the best use of limited data,” he said.

While 3D printers typically come equipped with infrared cameras, the cost and complexity make it impossible to equip a commercial machine with the kind of X-ray technology that exists at the APS, which is one of the most powerful X-ray light sources in the world. But by designing a methodology to observe systems that already exist in 3D printers, that wouldn’t be necessary.

“By correlating the results from the APS with the less detailed results we can already get in actual printers using infrared technology, we can make claims about the quality of the printing without having to actually see below the surface,” explained co-author Ben Gould, a materials scientist in the AMD.

The ability to identify and correct defects at the time of printing would have important ramifications for the entire additive manufacturing industry because it would eliminate the need for costly and time-consuming inspections of each mass-produced component. In traditional manufacturing, the consistency of the process makes it unnecessary to scan every metallic component coming off of the production line.

“Right now, there’s a risk associated with 3D printing errors, so that means there’s a cost. That cost is inhibiting the widespread adoption of this technology,” Greco said. “To realize its full potential, we need to lower the risk to lower the cost.”

This effort is made all the more urgent in recognizing one of the key advantages that additive manufacturing has over traditional manufacturing. “We saw with the recent pandemic response how valuable it would be to be able to quickly adapt production to new designs and needs. 3D technology is very adaptable to those kinds of changes,” added Greco.  

Looking ahead, Gould said the research team was hopeful that what he called a “very, very good first step” would allow it to keep improving and expanding the model. “For machine learning, to build accurate models you need thousands and thousands of data points. For this experiment, we had 200. As we put in more data, the model will get more and more exact. But what we did find is very promising.”

Ottawa, August 5, 2020 - Zebrafish are a common aquarium species, of value to hobbyists and scientists alike. Researchers have now engineered an unusual change in them that has echoes of Jurassic Park--but looks alone are deceiving.

A research team studying jaw evolution in the earliest known vertebrates--fishes from around 400 million years ago--have found that a single-gene mutation in the toe-sized zebrafish produced a surprising lookalike of species long extinct.

The phenomenon revealed in their experiments, called developmental plasticity, explains why a real Jurassic Park will continue to remain a distant concept, best suited for cinematic storytelling rather than scientific reality.

"The plasticity we found in the mutants is a key to the great mystery," says Dr. Tetsuto Miyashita, now a palaeontologist at the Canadian Museum of Nature and formerly postdoctoral scholar at the University of Chicago. He led the research team that also included scientists at the Universities of Alberta and Southern California. The results are published today in the Journal of Experimental Biology.

Miyashita is interested in the evolution of key characteristics in vertebrates, of which jaws were one of the first critical developments. "We generally think evolution adds new things. For example, the first jaws evolved in fish 450 million years ago, giving them the ultimate competitive edge over other living creatures. Today, we would starve and suffocate without jaws. But sometimes evolution goes the opposite way. Take away something that's been there for millions of years, and it suddenly opens up new evolutionary directions. My idea is to see it in action."

To do this, Miyashita bred zebrafish that had a mutation in a gene that instructs cells to form a hinge joint of the jaw. The mutant zebrafish are born without a jaw joint so the upper and lower jaws fuse into one - creating a gaping mouth that cannot close. With their wide eyes and gaping mouth, Miyashita reckons they resemble the figure in Edward Munch's artwork "The Scream".

Surprisingly, Miyashita observed that these mutants swimming in the aquarium were able to survive and thrive - despite the lack of a hinged jaw with which to bite. "Instead of gulping for food, the fish chase it until the food ends up in their great gape," says Miyashita. "They seem unable to move the lips or close the mouth - these fish literally have their jaws dropped, fixed in that position."

The researchers observed that the skulls of the jawless mutants were remodelled with a shortened face, expanded cheeks, and massive neck muscles - similar features that first appeared in some of the earliest known jawless fishes during the Silurian and Devonian Periods nearly half a billion years ago.

Known as anaspids and thelodonts, these long-extinct fish that swam in ancient oceans are far removed from the zebrafish's line of ancestry. But like the mutant zebrafish, the fossils of these creatures show that they also lacked biting jaws and presumably had a similar feeding strategy.

It seems like a Jurassic Park moment, as if Miyashita created Devonian jawless fish out of modern ones. But, he explains, there is a more nuanced answer. "The resemblance is more a coincidence than by design. Anaspids and thelodonts are distant cousins half a billion generations removed, " he says. "Zebrafish didn't come from them, so cannot 'go back' to them."

In essence, the mutant zebrafish experiments suggest that genetic engineering does not enable restoring an ancestor. It only allows superficial convergence of characteristics that mutants develop by necessity. "The finding sets an unrealistically high bar for a Jurassic Park-like scenario. Engineered similarities are skin-deep, but origins and contents are completely different."

Miyashita notes the scientific phenomenon of developmental plasticity is why features of extinct organisms sometimes appear in lab-made mutants, as in the highly publicized case of 'dino-chickens.' Although these types of mutants are sometimes referenced as a rewinding of the evolutionary clock, plasticity means they are no more than coincidences.

That said, these initial experiments do offer insights for future scientific research--especially for how extinct jawless fishes (the predecessors of today's fishes) might have fed, breathed, and swam. The mutant zebrafish can be studied by biologists to explore further why evolution makes an occasional "leap". Understanding how jaw fusion occurs in the mutants may also break a path for a new treatment of certain joint diseases.

Miyashita started his new position at the Canadian Museum of Nature April 1, 2020 during the COVID pandemic. This followed post-doctoral work at the University of Chicago where he completed the zebrafish experiments. Scientists at the University of Alberta contributed CT scans and analysis of the skull morphology. Miyashita plans to carry on his work with the mutant zebrafish by establishing another working "Devonian" aquarium at the museum.

Scientists from the University of Adelaide and South Australian Museum have collaborated with Otago University, New Zealand and a global team to sequence the genome of the tuatara - a rare reptile whose ancestors once roamed the earth with dinosaurs.

The findings on this remarkable living, single species reptile, which originated in the Triassic period around 250 million years ago and is only found in New Zealand, have been published in Nature.

Professor David Adelson's lab of the University of Adelaide's Department of Molecular and Biomedical Science and Dr Terry Bertozzi of the South Australian Museum carried out key analysis of the tuatara genome that revealed an unusual architecture, half-way between mammal and reptile.

"The tuatara is the last surviving species of a reptile group that roamed the earth with the dinosaurs and remarkably, its genome shares features with those of mammals such as the platypus and echidna," said Professor Adelson.

The key contribution of Professor Adelson's lab and Dr Bertozzi was to demonstrate that some sequences of DNA that move or jump location, referred to as 'jumping genes', found in the tuatara are most similar to those found in platypus while others are more similar to those in lizards.

"The tuatara genome contained about 4% jumping genes that are common in reptiles, about 10% common in monotremes (platypus and echidna) and less than 1% common in placental mammals such as humans," said Professor Adelson.

"This was a highly unusual observation and indicated that the tuatara genome is an odd combination of both mammalian and reptilian components."

"The unusual sharing of both monotreme and reptile-like repetitive elements is a clear indication of shared ancestry albeit a long time ago," said Dr Bertozzi.

With no close relatives, the position of tuatara on the tree of life has long been contentious. The research places tuatara firmly in the branch shared with lizards and snakes, but they appear to have split off and been their own species for around 250 million years - an enormous amount of time given primates only originated around 65 million years ago, and hominids, from which humans descend, originated approximately six million years ago.

"It has been a privilege to be part of this project, which has been a true, historic collaboration with local iwi (Māori indigenous tribe) Ngātiwai. While this is largely fundamental science, I expect it to yield new ways of thinking about our own genome structure that may have relevance to our health," said Professor Adelson.

Stone fluted points dating back some 8,000 to 7,000 years ago, were discovered on archaeological sites in Manayzah, Yemen and Ad-Dahariz, Oman. Spearheads and arrowheads were found among these distinctive and technologically advanced projectile points. Until now, the prehistoric technique of fluting had been uncovered only on 13,000 to 10,000-year-old Native American sites. According to a study led by an international team of archaeologists from the CNRS (1), Inrap, Ohio State University and the Max Planck Institute for the Science of Human History, the difference in age and geographic location implies there is no connection between the populations who made them. This is therefore an example of cultural convergence for an invention which required highly-skilled expertise. And yet, despite similar fluting techniques, the final aim appears to be different. Whereas in the Americas the points were used to facilitate hafting, or attaching the point to a shaft, fluting in Arabia was possibly a mere display of knapping skills.

What The Study Says: Practice patterns for common ocular complaints during the initial stage of the COVID-19 pandemic are reported in this observational study among comprehensive U.S. ophthalmology practices.

Authors: Ajay E. Kuriyan, M.D., of Mid Atlantic Retina, Wills Eye Hospital, Thomas Jefferson University in Philadelphia, is the corresponding author.

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

(doi:10.1001/jamaophthalmol.2020.3237)

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

Gastric cancer is the third leading cause of cancer death worldwide, accounting for over 1,000,000 new cases and nearly 800,000 deaths per year. The poor prognosis of gastric cancer is largely due to the difficulty in early diagnosis of peritoneal metastasis.

Separation and characterization of cancer cells are essential for early diagnosis of peritoneal metastasis. However, due to the low content of cancer cells in patients' peritoneal lavages, traditional detection methods lack sensitivity and cannot satisfy clinical demand.

Researchers from the Shenyang Institute of Automation (SIA) of the Chinese Academy of Science (CAS) and City University of Hong Kong (CityU), in cooperation with doctors from the First Hospital of China Medical University, jointly proposed an optically induced electrokinetics (OEK) microfluidic method for label-free separation and characterization of gastric cancer cells.

Their study was published in Science Advances on August 5.

The researchers fabricated a novel OEK-based microfluidic chip to separate live gastric cancer cells from patients' ascites and characterize their electrical properties. They established polymerization model of cells and solution model of cell membrane capacitance.

The sizes and electrical characteristics between the gastric cancer cells and peritoneal lavage cells were significantly different. Thus the OEK method could theoretically separate gastric cancer cells from the ascites and peritoneal lavages.

Through experiments, the researchers separated gastric cancer cells from six patients' ascites with purity up to 71%. Compared with the traditional clinical peritoneal metastasis detection method, this new method solved the problem of low sensitivity.

It is also a label-free, non-destructive and rapid technique. The researchers could separate and collect gastric cancer cells in the OEK microfluidic chip in 5 minutes.

They also obtained the cell membrane capacitances of gastric cancer cells and peritoneal lavage cells. These digital data can be used as a bio-marker, as part of cellular information.

Experimental results in the study demonstrated that the proposed OEK method was capable of detection free cancer cells in ascites and could expedite diagnosis of peritoneal metastasis in gastric cancer.

BOSTON – A paper published today in the Journal of the American Geriatrics Society reported results of an initiative designed to enhance implementation of hospital mobility programs aimed at improving quality of care and outcomes for older patients. Sharon K. Inouye, M.D., M.P.H., Director of the Aging Brain Center in the Hinda and Arthur Marcus Institute for Aging Research at Hebrew SeniorLife, headed the effort and is the paper’s senior author, and her mentee, Songprod Jonathan Lorgunpai, M.D., Division of Geriatric Medicine, Mount Auburn Hospital, is the paper’s lead author.

Research shows that keeping older hospitalized patients confined to their beds often does more harm than good. Immobility contributes to poor patient outcomes, including increased risk of injurious falls, delirium, aspiration pneumonia, pressure ulcers, functional decline, prolonged length of stay, institutionalization, readmissions, increased healthcare costs, and mortality. Despite this reality, older adults are largely immobilized throughout their hospital stay. According to estimates in 2009 and 2013, patients spent more than 95 percent of their time in a bed or chair.

Protocols in place to prevent falls are a driving force behind this statistic. In 2008, the Centers for Medicare & Medicaid Services enacted new payment provisions that would no longer reimburse hospitals for diagnosis-related groups resulting from hospital-acquired conditions, including falls with injury. As an unintended consequence, many hospitals routinely use bed and chair alarms that discourage mobility as part of their fall prevention programs, despite large randomized clinical trials that have clearly demonstrated bed and chair alarms are ineffective at reducing falls.

As part of a 2016–2017 Health and Aging Policy Fellowship, Dr. Inouye worked with the Center for Medicare & Medicaid Innovation (CMMI) to develop a new care delivery model designed to promote quality improvement related to mobility in hospitals participating in CMMI’s bundled payment programs. The overarching goal of the initiative was to improve mobility and decrease use of bed and chair alarms with hospitalized older adults. To achieve this goal, Dr. Inouye and her team developed a Mobility Action Group (MACT) Change Package that provides a conceptual framework, roadmap, and step-by-step guide to help hospital mobility teams set and meet their mobilization goals.

The MACT Change Package provided more than 40 participating hospitals of varying sizes across the United States with an innovative framework of peer support, expert faculty, and resources to create a successful culture of mobility in the care of hospitalized older adults.

“The Change Package was an essential tool and starting point for each hospital, while the peer support and assistance they received through the group meetings proved to be another key factor in their success,” said Dr. Inouye.

Results indicate that successful implementation of mobility programs was achieved at most (76 percent) participating sites in medical, surgical, and intensive care units, with 43 percent of mobility programs fully implemented and an additional 33 percent partially implemented by the end of the active initiative. Most (54 percent) reported a high likelihood that their mobility program would continue long-term. There was a more than twofold increase in the proportion of patients who received at least three walks per day and a 1.8-fold reduction in the use of bed or chair alarms across sites.

“I’m greatly encouraged by the results of this effort,” said Dr. Lorgunpai, who is also an Instructor in Medicine at Harvard Medical School. “While additional study is needed to determine if this approach can improve patient outcomes such as decreased falls, functional decline, and readmissions, this initiative demonstrates that emphasizing system-wide change through a flexible approach can catalyze a culture of mobility in hospitals and improve care of older adults.”

Additional co-authors include:

Bruce Finke, M.D., Centers for Medicare and Medicaid Services, Department of Health and Human Services, Baltimore;

Isaac Burrows, M.P.H., Centers for Medicare and Medicaid Services, Department of Health and Human Services, Baltimore; Cigna Health and Life Insurance Company, Bloomfield, Conn.;

Cynthia J. Brown, M.D., M.P.H., Division of Gerontology, Geriatrics, and Palliative Care, University of Alabama at Birmingham, Ala; Birmingham/Atlanta Geriatric Research, Education, and Clinical Care Center, Veterans Affairs;

Fred H. Rubin, M.D., Division of Geriatric Medicine, University of Pittsburgh Medical Center Shadyside, Pittsburgh, Penn.;

Heidi R. Wierman, M.D., Division of Geriatric Medicine, Maine Medical Center, Portland, Maine; Tufts University School of Medicine, Boston, Mass.;

Susan J. Heisey, M.S.W., M.P.H., Aging Brain Center, Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, Mass.; Inova Health System, Falls Church, Va.;

Sarah Gartaganis, LIC.S.W., M.P.H., Aging Brain Center, Marcus Institute, Hebrew SeniorLife, Boston, Mass.;

Shari M. Ling, M.D., Centers for Medicare and Medicaid Services, Department of Health and Human Services, Baltimore;

Matthew Press, M.D., M.Sc., University of Pennsylvania Health System, Philadelphia, Penn.

This work was supported in part by the Health and Aging Policy Fellowship, and by technical support from the Hospital Elder Life Program. Dr. Inouye’s time was supported in part by grants no. R24AG054259 (SKI), K07AG041835 (SKI) from the National Institute on Aging, and by the Milton and Shirley F. Levy Family Chair at Hebrew SeniorLife/Harvard Medical School.

About the Hinda and Arthur Marcus Institute for Aging Research
Scientists at the Hinda and Arthur Marcus Institute seek to transform the human experience of aging by conducting research that will ensure a life of health, dignity, and productivity into advanced age. The Marcus Institute carries out rigorous studies that discover the mechanisms of age-related disease and disability; lead to the prevention, treatment, and cure of disease; advance the standard of care for older people; and inform public decision-making. For further information on the Hinda and Arthur Marcus Institute for Aging Research at Hebrew SeniorLife, please visit https://www.marcusinstituteforaging.org/.

About Hebrew SeniorLife
Hebrew SeniorLife, an affiliate of Harvard Medical School, is a national senior services leader uniquely dedicated to rethinking, researching, and redefining the possibilities of aging. Based in Boston, the nonprofit organization has provided communities and health care for seniors, research into aging, and education for geriatric care providers since 1903. For more information about Hebrew SeniorLife, visit http://www.hebrewseniorlife.org and our blog, or follow us on Facebook, Instagram, Twitter, and LinkedIn.

Journal

Journal of the American Geriatrics Society

For centuries, people around the world have used garlic as a spice, natural remedy, and pest deterrent - but they didn't know how powerful or pungent the heads of garlic were until they tasted them.

Video: https://video.vt.edu/media/1_h08qtb5q

But what if farmers were able to grow garlic and know exactly how potent it would be? What if buyers could pick their garlic based on its might?

A team of Virginia Tech researchers recently discovered a new step in the metabolic process that produces the enzyme allicin, which leads to garlic's delectable flavor and aroma, a finding that upends decades of previous scientific belief. Their work could boost the malodorous - yet delicious - characteristics that garlic-lovers the world over savor.

"This information changes the whole story about how garlic could be improved or we could make the compounds responsible of its unique flavor," said Hannah Valentino, a College of Agriculture and Life Sciences Ph.D. candidate. "This could lead to a new strain of garlic that would produce more flavor."

The discovery of this pathway opens the door for better control of production and more consistent crops, which would help farmers. Garlic could be sold as strong or weak, depending on consumer preferences.

The research was recently published in the Journal of Biological Chemistry.

When Valentino, an Institute for Critical Technology and Applied Science doctoral fellow, and her team set out to test the generally accepted biological process that creates allicin, they found it just didn't happen.

That's when the team of researchers set out to discover what was really happening in garlic.

As they peeled back the layers, they realized there was no fuel to power the previous accepted biological process that creates allicin.

"By using rational design, Hannah found a potential substrate," said Pablo Sobrado, professor of biochemistry in the College of Agriculture and Life Sciences and a member of the research team. "This is significant because by finding the metabolic pathway and understanding how the enzyme actually works and its structure gives us a blueprint of how allicin is created during biosynthesis."

Valentino and the team - which included undergraduate students - worked in the Sobrado Lab in the Fralin Life Sciences Institute directly with the substrates that comprise garlic, doing their work solely in vitro.

Hannah Valentino, left, and Pablo Sobrado, right, are conducting research that is laying the foundation for a future in which buyers can choose garlic based on its strength and flavor profile.

The researchers found that allicin, the component that gives garlic its smell and flavor, was produced by an entirely different biosynthetic process. Allyl-mercaptan reacts with flavin-containing monooxygenase, which then becomes allyl-sulfenic acid.

Importantly, the allicin levels can be tested, allowing farmers to know the strength of their crops without the need for genetic engineering. Greater flavor can simply be predicted, meaning powerful garlic could simply be bred or engineered.

"We have a basic understanding of the biosynthesis of allicin that it is involved in flavor and smell, but we also now understand an enzyme that we can try to modulate, or a modify, to increase or decrease the level of the flavor molecules based on these biological processes," Sobrado said.

Because of their work, the future awaits for fields of garlic harsh enough to keep even the most terrifying vampires at bay.