Culture

For the first time, scientists at the Morgridge Institute for Research have generated near atomic resolution images of a major viral protein complex responsible for replicating the RNA genome of a member of the positive-strand RNA viruses, the large class of viruses that includes coronaviruses and many other pathogens.

The results should aid development of new types of antivirals and provide mechanistic insights into the virus life cycle.

"The rapidly advancing ability to visualize such crucial structures is game changing," says Paul Ahlquist, director of the John W. and Jeanne M. Rowe Center for Virology Research at the Morgridge Institute and professor of oncology and molecular virology at the University of Wisconsin-Madison. Other authors of the study included Nuruddin Unchwaniwala, Hong Zhan, Janice Pennington, Mark Horswill and Johan den Boon.

Using an advanced technique called cryoelectron microscope (cryo-EM) tomography, Ahlquist and his team built upon their previous work, which first revealed the existence of this crown-like viral RNA replication complex.

The new research, published July 20 in the Proceedings of the National Academy of Sciences (PNAS), shows the replication crown complex at a dramatically improved resolution of approximately 8.5 angstroms, which corresponds to the spacing of a few atoms.

"Cryo-EM has recently gone through a quantum leap in its capabilities," Ahlquist says. "In this study our research group combined multiple advances to greatly improve sample preparation, image acquisition and image processing, and to map the position of specific protein domains in the complex."

The positive-strand RNA viruses addressed in this work are the largest of six genetic classes of viruses and include many important pathogens such as the Zika, dengue and chikungunya viruses, as well as coronaviruses like SARS-CoV-2, cause of the current COVID-19 pandemic.

In each positive-strand RNA virus, most of the viral genes are devoted to a single process: replicating the viral RNA genome.

"Given this massive investment of resources, viral RNA genome replication is arguably one of the most important processes in infection, and It is already a major target for virus control," Ahlquist says.

Within an infected cell, viral RNA replication occurs at modified cellular membranes, often in association with spherules, virus-induced vesicles approximately 50-100 nanometers in size. Ahlquist and his team previously showed that in each such genome replication complex, a copy of the viral RNA genome or chromosome is protected inside the spherule vesicle to function as a replication template. The replication complex repeatedly copies this archival viral RNA chromosome to produce new progeny genomes that are released through a membranous neck on the vesicle into the cytoplasm, where they are incorporated as the payload of new infectious virions.

This prior work further showed that the key viral protein that induces the replication vesicles and copies the viral RNA resides in a striking ring or crown structure that sits atop the cytoplasmic side of the spherule neck that connects with the cytoplasm.

The new higher resolution cryo-EM images and complementary results show that the crown is composed of twelve copies of the key viral RNA replication protein arranged like staves in a barrel. Additionally, the images revealed zipper-like interactions that act like hoops on a barrel to join adjacent segments together to form the ring-like crown. These zippering interactions correspond well with multimerizing interactions that the Ahlquist group has previously mapped in this protein.

The viral RNA replication protein that forms the crown is an extremely large, multi-domain, multi-functional protein, nearly 1000 amino acids in size. This protein contains RNA polymerase and RNA capping domains-- two enzymatic domains that are conserved across numerous positive-strand RNA viruses for synthesizing new viral genome copies--plus other domains for multimerizing, binding membranes and other functions.

How these domains are physically organized in the crown structure is one of the most important issues for understanding how the replication complex functions, and was one of several strong motivations for defining the high-resolution crown structure.

Using an approach that combined a genetically engineered, site-specific tag with labeling by nanoscale gold particles visible in cryo-EM, the researchers found that the C-terminal polymerase end of the viral RNA replication protein is positioned at the apex of the crown, leaving the N-terminal capping domain at the bottom of the structure to interact with the membrane.

This apical position of the polymerase has important mechanistic implications for early steps in the replication process that recruit the starting viral RNA template into the complex and form the replication vesicle, as well as for later steps in which the template is copied to make new progeny genomes to be packaged into infectious virus particles. These results provide a strong foundation for further experiments to define the replication complex structure and function at even higher levels.

"We hope to continue to improve the RNA replication complex crown structure to provide additional important refinements in future," Ahlquist says. "We also hope to address growing indications from our work that conformational changes in these proteins are critical to their multiple functions."

"Such advances will reveal in increasing detail how these complexes assemble and operate, and thus how they might be best attacked," he adds. "These insights should provide the basis for novel, stronger antiviral mechanisms."

DURHAM, N.C. -- A chance mutation that led to spinal defects in a zebrafish has opened a little window into our own fishy past.

Rising fifth-year Duke graduate student Brianna Peskin, who started the project during her first-year rotation in Michel Bagnat's cell biology lab and "kinda kept coming back to it," was merely trying to figure out why this one mutation led to developmental issues in a zebrafish's spine.

What she found is that embryos of the mutant fish have a single-letter change in their DNA that alters the way they build the bones and other structures that make up their spine, leaving them with a shorter body and a tortured looking spine that contains clefts dividing their vertebrae in half.

The mutant fish are named spondo, short for spondylos which is Greek for spine, and also a reference to dispondyly, a condition where each vertebra has two bony arches not one.

But that's not the end of the story.

When Bagnat's research colleague Matthew Harris of Harvard Medical School showed some pictures of the mutant fish spine to a colleague in fish paleontology, Gloria Arratia at the University of Kansas, she immediately spotted that the mutants look a lot like fossil specimens of ancestral fish whose style of spine has gone out of fashion in most living fishes.

"And then they both got really excited because they were noticing these similarities between ancestral fossil specimens and our mutant," Peskin said.

The tiny mutation showed that both recipes for spine development are still to be found in the fish genome.

In the bony fish, known as teleosts, building the spine relies on a tube-like structure running the length of the developing embryo called the notochord. The notochord sets up the patterns that lead to articulated bones and cartilage in the developing spine by sending chemical signals that attract different molecules and cell types to different regions - bone parts here, cartilage parts there.

Human embryos start with a notochord too, but it doesn't pattern the bony vertebrae the way it does in teleosts; it ends up building the cartilage pucks between the bones, the intervertebral discs.

The gene that is mutated in spondo fish is unique to teleosts and the mutant fish's notochord doesn't set up the patterning the way it does in other fish. Rather, its patterning reverts to an ancestral form. So, this tiny difference in DNA may be where land animals like us parted company with our fish ancestors a very, very, very long time ago.

While the zebrafish (Danio rerio) has become a laboratory workhorse for all sorts of interesting studies, its usefulness as a model of human spine development has been in doubt because they grow their backbones differently.

But not anymore. The research team's new paper, which appears July 20 in Current Biology, shows that the difference between the way teleosts and land animals grow their spines comes down to signaling from the notochord, which was revealed by this single-letter change in the DNA.

And that, in turn, gives them the insight to study human spinal defects with these fast-growing, translucent fish, because the spondo mutants are sensitive to factors known to cause congenital scoliosis in human children, a curvature of the spine.

"This work not only gave us a glimpse into spine evolution, but also made us understand how the spine is put together in mammals," said Bagnat, who is an associate professor of Cell Biology in the Duke School of Medicine. "Moving forward, we'll be able to use mutations like spondo to unravel the complex genetics of scoliosis and other spine defects that are rooted in the biology of the notochord and have been intractable until now."

"Overall, what this study means is that notochord signals are key to establishing the spine. These signals have changed over evolutionary time and account for differences that exist in spine patterning strategies across vertebrates," Peskin said. "So we are all fish after all."

Argonne researchers quantify how to reduce emissions by farms changing their practices and adopting novel technologies.

Currently, the agriculture sector contributes significantly to the greenhouse gas (GHG) emissions in the United States, accounting for nine percent of the nation’s overall GHG emissions.  The practices that grain farmers use to produce their crops — managing fertility, tillage practice and crop rotations — influence the overall carbon footprint of U.S. agriculture.  By using sustainable practices, farmers could substantially reduce their carbon footprint and become a vital partner to the biofuel industry in its efforts to produce the lowest carbon fuels possible.

“This work is unique since we provide a complete quantification of carbon intensity (CI) for the cradle-to-farm-gate activities by conducting scenario-based analysis for selected farming practices that uses regionalized life cycle inventory data and a spatially explicit soil organic carbon modeling tool.” — Xinyu Liu, postdoctoral appointee

A recent study by researchers in the Energy Systems division at the U.S. Department of Energy’s (DOE’s) Argonne National Laboratory quantified how much farms might reduce emissions by changing their practices and adopting novel technologies. Xinyu Liu, a postdoctoral appointee, wrote about the pivotal research in Environmental Research Letters, published on July 20. She collaborated with Hoyoung Kwon, principal environmental scientist, and Michael Wang, manager of systems assessments, all of Argonne; and Daniel Northrup, a former contractor to DOE’s Advanced Research Projects Agency-Energy (ARPA-E), now with Benson Hill, a crop improvement company in St. Louis.

“This work is unique since we have quantified how the carbon intensity (CI) of corn feedstock would change with a wide range of farming practices and different farming regions. Besides the GHG emissions from manufacturing and applying farming inputs, we have also considered the impacts from soil organic carbon,” said Liu.

The research focused on the corn belt of Illinois, Indiana, Iowa, Minnesota, Nebraska, Ohio, Michigan, South Dakota and Wisconsin and showed how different farming practices affect feedstock CI. Sustainable farming professionals could implement lower CI practices, such as adopting conservation tillage, reducing nitrogen fertilizer use, and implementing cover crops, to reduce their carbon footprint, which could improve farm efficiency and help the environment. 

The Argonne team’s research has historically focused on the CI of biofuels, which is determined via the life-cycle analysis technique to account for the energy/material uses and emissions as feedstock is produced and converted to fuel. The technique is used by California Air Resources Board’s Low Carbon Fuel Standard (LCFS) program to calculate biofuel CI. Farms that reduce biofuel CI can generate LCFS credit, which has monetary value for biofuel producers and potentially for farmers supplying the lower carbon feedstocks. Biofuel producers can improve their overall CI score by rewarding feedstocks with lower CI, thereby further reducing the total CI of biofuels.

Currently, LCFS allows applications from individual biofuel conversion facilities, which resulted in significant investment and innovation in production processes to reduce CI. However, the board scores the CI for feedstocks based on a national average, regardless of the significant field-level variations in CI based on production practice. The Argonne work determines the source of the variation and suggests that a change in farming practice would lead to major emission reductions if implemented broadly.

“We conducted scenario-based CI analysis of corn ethanol, coupled with regionalized inventory data, for various farming practices to manage corn fields and identified key parameters affecting cradle-to-farm-gate GHG emissions,” said Liu. “The results demonstrate large spatial variations in CI for corn, and eventually for ethanol, due to farm input uses and land management practices.”

In addition to responding to electrical and chemical stimuli, many of the body's neural cells can also respond to mechanical effects, such as pressure or vibration. But these responses have been more difficult for researchers to study, because there has been no easily controllable method for inducing such mechanical stimulation of the cells. Now, researchers at MIT and elsewhere have found a new method for doing just that.

The finding might offer a step toward new kinds of therapeutic treatments, similar to electrically based neurostimulation that has been used to treat Parkinson's disease and other conditions. Unlike those systems, which require an external wire connection, the new system would be completely contact-free after an initial injection of particles, and could be reactivated at will through an externally applied magnetic field.

The finding is reported in the journal ACS Nano, in a paper by former MIT postdoc Danijela Gregurec, Alexander Senko PhD '19, Associate Professor Polina Anikeeva, and nine others at MIT, at Boston's Brigham and Women's Hospital, and in Spain.

The new method opens a new pathway for the stimulation of nerve cells within the body, which has so far almost entirely relied on either chemical pathways, through the use of pharmaceuticals, or on electrical pathways, which require invasive wires to deliver voltage into the body. This mechanical stimulation, which activates entirely different signaling pathways within the neurons themselves, could provide a significant area of study, the researchers say.

"An interesting thing about the nervous system is that neurons can actually detect forces," Senko says. "That's how your sense of touch works, and also your sense of hearing and balance." The team targeted a particular group of neurons within a structure known as the dorsal root ganglion, which forms an interface between the central and peripheral nervous systems, because these cells are particularly sensitive to mechanical forces.

The applications of the technique could be similar to those being developed in the field of bioelectronic medicines, Senko says, but those require electrodes that are typically much bigger and stiffer than the neurons being stimulated, limiting their precision and sometimes damaging cells.

The key to the new process was developing minuscule discs with an unusual magnetic property, which can cause them to start fluttering when subjected to a certain kind of varying magnetic field. Though the particles themselves are only 100 or so nanometers across, roughly a hundredth of the size of the neurons they are trying to stimulate, they can be made and injected in great quantities, so that collectively their effect is strong enough to activate the cell's pressure receptors. "We made nanoparticles that actually produce forces that cells can detect and respond to," Senko says.

Anikeeva says that conventional magnetic nanoparticles would have required impractically large magnetic fields to be activated, so finding materials that could provide sufficient force with just moderate magnetic activation was "a very hard problem." The solution proved to be a new kind of magnetic nanodiscs.

These discs, which are hundreds of nanometers in diameter, contain a vortex configuration of atomic spins when there are no external magnetic fields applied. This makes the particles behave as if they were not magnetic at all, making them exceptionally stable in solutions. When these discs are subjected to a very weak varying magnetic field of a few millitesla, with a low frequency of just several hertz, they switch to a state where the internal spins are all aligned in the disc plane. This allows these nanodiscs to act as levers -- wiggling up and down with the direction of the field.

Anikeeva, who is an associate professor in the departments of Materials Science and Engineering and Brain and Cognitive Sciences, says this work combines several disciplines, including new chemistry that led to development of these nanodiscs, along with electromagnetic effects and work on the biology of neurostimulation.

The team first considered using particles of a magnetic metal alloy that could provide the necessary forces, but these were not biocompatible materials, and they were prohibitively expensive. The researchers found a way to use particles made from hematite, a benign iron oxide, which can form the required disc shapes. The hematite was then converted into magnetite, which has the magnetic properties they needed and is known to be benign in the body. This chemical transformation from hematite to magnetite dramatically turns a blood-red tube of particles to jet black.

"We had to confirm that these particles indeed supported this really unusual spin state, this vortex," Gregurec says. They first tried out the newly developed nanoparticles and proved, using holographic imaging systems provided by colleagues in Spain, that the particles really did react as expected, providing the necessary forces to elicit responses from neurons. The results came in late December and "everyone thought that was a Christmas present," Anikeeva recalls, "when we got our first holograms, and we could really see that what we have theoretically predicted and chemically suspected actually was physically true."

The work is still in its infancy, she says. "This is a very first demonstration that it is possible to use these particles to transduce large forces to membranes of neurons in order to stimulate them."

She adds "that opens an entire field of possibilities. ... This means that anywhere in the nervous system where cells are sensitive to mechanical forces, and that's essentially any organ, we can now modulate the function of that organ." That brings science a step closer, she says, to the goal of bioelectronic medicine that can provide stimulation at the level of individual organs or parts of the body, without the need for drugs or electrodes.

The legalization of marijuana for Washington state adults may be thwarting a steady downward trend in teen marijuana use, according to new research from the University of Washington.

The longitudinal study of more than 230 teens and young adults finds that teens may be more likely to use marijuana following legalization -- with the proliferation of stores and increasing adult use of the drug -- than they otherwise would have been.

"When we think about marijuana legalization, a worry is that underage use may go up," said Jennifer Bailey, the study's lead author and principal investigator with the Social Development Research Group in the UW School of Social Work. "Early use and heavy use during adolescence can have a lot of negative health consequences, then and later in life, so we don't want teen use to be going up."

Bailey notes that before marijuana legalization, rates of teen marijuana use and other drug use had both been decreasing over the last couple of decades.

The study was published July 9 in the American Journal of Preventive Medicine.

Researchers examined whether marijuana legalization led to teen use of the drug, as well as teens' perceptions that the drug is harmful. Controlling for age, sex, race and parent education of the participants, researchers found that kids who entered their teens more recently were less likely to report they'd used marijuana in the past year. For example, 11% of kids born before 2000 reported using marijuana over the past year at age 15, but only 5% of kids born after 2000
said they used marijuana at age 15.

That finding goes along with the general downward trend in teen substance use. But it was after accounting for this trend that the effect of legalization showed up, Bailey said.

Controlling for the year when kids were born, teens interviewed after voter approval in 2012 of nonmedical marijuana were several times more likely to report they'd used marijuana in the past year. Bailey thinks this means that marijuana legalization may be working against the decreases in teen substance use seen in the recent past.

The new findings differ slightly from other studies showing that rates of underage marijuana use are holding steady or dropping a little after legalization. UW researchers say this may reflect methodology. The UW study was able to account for long-term trends in teen drug use by following kids born between 1989 and 2002 for 15 years and comparing kids who were teenagers before legalization to those who were teenagers after legalization. Other studies have used school-based or optional surveys to assess a larger population at once, and have not always accounted for long-term trends.
Those methods supply important information too, Bailey said. They just reflect a different angle on the issue. Broader, point-in-time surveys don't look at individual change.

"They can only see how a whole state changes over time," Bailey said. "Data like ours let you look at individuals and how drug use and behavior change over time, and then we can relate that to changes in policy."

The participants in the UW research are some of the children of participants in a larger and older longitudinal study: the Seattle Social Development Project. That study has followed hundreds of people -- since they were fifth-graders in Seattle elementary schools in the 1980s --to evaluate an assortment of conditions, behaviors and life choices. The results from interviews with 233 of their children, pre- and post-marijuana legalization, were included in this new study.

Child participants ranged in age from 1 to 13 years old when the study began in 2002; marijuana use was assessed from ages 10 to 20. Researchers found that children in the sample entering their teens more recently were more likely to perceive the drug as harmful. For example, 69% of 15-year-olds born before 2000 said regular marijuana use is harmful, but 77% of 15-year-olds born after 2000 said using marijuana regularly is harmful. Bailey attributes this to years of drug prevention and education efforts in schools and communities.

The study did not, however, find an overall association between marijuana legalization and teens' perceived harm from the drug. It could be that changing societal attitudes drive changes in marijuana laws, the authors noted, rather than that changing laws drive perceptions.

Researchers study the perception of harm because people are more likely to engage in a behavior they see as relatively risk-free, Bailey said. In the 1960s and 1970s, for instance, there was a generally low perception of harm from many drugs, and usage was higher than it was in subsequent decades, when perceived harm increased.

"People generally like to take care of themselves. They don't typically do things that carry risk of harm. Throughout the decades that we've been tracking marijuana use, this highly correlates with whether someone will use or not," she said.

The UW study also found no connection between marijuana legalization and teen cigarette smoking; the use of one substance often goes with the other, Bailey said. Teen smoking nationwide has declined precipitously for years, which has been attributed to higher taxes, greater restrictions and widespread public health marketing.

Researchers are watching closely to see whether recent dramatic increases in vaping among teens affect declines in teen smoking rates.

Similar studies in other states where marijuana has been legalized -- the participants in this study lived almost exclusively in Washington state -- could provide further evidence of links between laws and behavior, Bailey said. Currently, nearly a dozen states permit the sale of marijuana for nonmedical use; an additional 22 states allow the drug for medical purposes only.

Nonetheless, the UW findings can help inform prevention messages targeting teens and marijuana, Bailey said.

"A teen usage rate that holds steady isn't good enough if it would normally be going down. We need to devote more attention to prevention of adolescent use in the context of legalization because we want to keep the decreases we've been seeing before legalization was implemented," Bailey said.

SAN ANTONIO, Texas, USA -- Genes and cardiovascular health each contribute in an additive way to a person's risk of dementia, U.S. researchers including Sudha Seshadri, MD, and Claudia Satizabal, PhD, of The University of Texas Health Science Center at San Antonio (UT Health San Antonio) reported July 20 in the journal Neurology.

The study was conducted in 1,211 participants in the Framingham Heart Study and involved collaborators from Boston University.

Participants with a high genetic risk score based on common genetic variants, including having an allele called apolipoprotein E (APOE) ε4, were at a 2.6-fold higher risk of developing dementia than subjects who had a low risk score and did not carry the APOE ε4 allele.

Having favorable cardiovascular health, as defined by an index of the American Heart Association, was associated with a 0.45-fold lower risk of dementia compared to having unfavorable cardiovascular health, the study also showed.

"The connection between heart health and brain health becomes clearer with each finding," Dr. Seshadri, senior investigator in the Framingham Heart Study, said. She is professor of neurology in the Long School of Medicine at UT Health San Antonio and founding director of the university's Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases.

"We hope that the results of this study will send the public a message, and that message is to exercise, reduce stress and eat a healthy diet," Dr. Seshadri said. "Then, regardless of your genes, you have the potential to lower your risk of dementia."

"It is imperative to start today," Dr. Satizabal, assistant professor of population health sciences and Biggs Institute investigator, said. "It seems, from our findings, that having favorable cardiovascular health mitigates the risk of dementia in persons with high genetic risk."

Respiratory droplets from a cough or sneeze travel farther and last longer in humid, cold climates than in hot, dry ones, according to a study on droplet physics by an international team of engineers. The researchers incorporated this understanding of the impact of environmental factors on droplet spread into a new mathematical model that can be used to predict the early spread of respiratory viruses including COVID-19, and the role of respiratory droplets in that spread.

The team developed this new model to better understand the role that droplet clouds play in the spread of respiratory viruses. Their model is the first to be based on a fundamental approach taken to study chemical reactions called collision rate theory, which looks at the interaction and collision rates of a droplet cloud exhaled by an infected person with healthy people. Their work connects population-scale human interaction with their micro-scale droplet physics results on how far and fast droplets spread, and how long they last.

Their results were published June 30 in the journal Physics of Fluids.

"The basic fundamental form of a chemical reaction is two molecules are colliding. How frequently they're colliding will give you how fast the reaction progresses," said Abhishek Saha, a professor of mechanical engineering at the University of California San Diego, and one of the authors of the paper. "It's exactly the same here; how frequently healthy people are coming in contact with an infected droplet cloud can be a measure of how fast the disease can spread."

They found that, depending on weather conditions, some respiratory droplets travel between 8 feet and 13 feet away from their source before evaporating, without even accounting for wind. This means that without masks, six feet of social distance may not be enough to keep one person's exhalated particles from reaching someone else.

"Droplet physics are significantly dependent on weather," said Saha. "If you're in a colder, humid climate, droplets from a sneeze or cough are going to last longer and spread farther than if you're in a hot dry climate, where they'll get evaporated faster. We incorporated these parameters into our model of infection spread; they aren't included in existing models as far as we can tell."

The researchers hope that their more detailed model for rate of infection spread and droplet spread will help inform public health policies at a more local level, and can be used in the future to better understand the role of environmental factors in virus spread.

They found that at 35C (95F) and 40 percent relative humidity, a droplet can travel about 8 feet. However, at 5C (41F) and 80 percent humidity, a droplet can travel up to 12 feet. The team also found that droplets in the range of 14-48 microns possess higher risk as they take longer to evaporate and travel greater distances. Smaller droplets, on the other hand, evaporate within a fraction of a second, while droplets larger than 100 microns quickly settle to the ground due to weight.

This is further evidence of the importance of wearing masks, which would trap particles in this critical range.

The team of engineers from the UC San Diego Jacobs School of Engineering, University of Toronto and Indian Institute of Science are all experts in the aerodynamics and physics of droplets for applications including propulsion systems, combustion or thermal sprays. They turned their attention and expertise to droplets released when people sneeze, cough or talk when it became clear that COVID-19 is spread through these respiratory droplets. They applied existing models for chemical reactions and physics principles to droplets of a salt water solution--saliva is high in sodium chloride--which they studied in an ultrasonic levitator to determine the size, spread, and lifespan of these particles in various environmental conditions.

Many current pandemic models use fitting parameters to be able to apply the data to an entire population. The new model aims to change that.

"Our model is completely based on "first principles" by connecting physical laws that are well understood, so there is next to no fitting involved," said Swetaprovo Chaudhuri, professor at University of Toronto and a co-author. "Of course, we make idealized assumptions, and there are variabilities in some parameters, but as we improve each of the submodels with specific experiments and including the present best practices in epidemiology, maybe a first principles pandemic model with high predictive capability could be possible."

There are limitations to this new model, but the team is already working to increase the model's versatility.

"Our next step is to relax a few simplifications and to generalize the model by including different modes of transmission," said Saptarshi Basu, professor at the Indian Institute of Science and a co-author. "A set of experiments are also underway to investigate the respiratory droplets that settle on commonly touched surfaces."

(JACKSON, Wyo. - July 20, 2020) - In 2018, cyanobacteria from nutrient-rich waters in Lake Okeechobee were released down the Caloosahatchee river at the same time that red tides were gathering along the Florida west coast, potentially exposing coastal residents to a mixture of toxins. In 2018, releases of cyanobacterial-laden freshwater from Lake Okeechobee transported a large bloom of Microcystis cyanobacteria down the Caloosahatchee. Analysis of water samples showed high concentrations of microcystin-LR, sufficient to result in adverse human and animal health effects if ingested, based on the known toxicity of this cyanotoxin.

The microcystin liver toxin was being produced by Microcystis, while at the same time, potent neurotoxins called brevetoxin were released from the marine dinoflagellate Karenia brevis in the Gulf of Mexico. In addition, BMAA, a neurotoxin suspected of being linked to neurodegenerative diseases such as ALS and Alzheimer's disease, was detected in samples of cyanobacteria, dinoflagellates, and diatoms along the Caloosahatchee and west coast. Furthermore, cyanobacterial mats collected on the west coast in 2019 also showed high concentrations of BMAA to be present.
Together, these new findings highlight the potential for multiple, potentially toxic blooms to co-exist with unknown implications for human and animal health.

"We have been monitoring Florida waters for cyanobacterial toxins since the 2016 emergency release of Lake Okeechobee water down the St. Lucie River and the Caloosahatchee," Dr. James Metcalf, first author and Senior Research Scientist at the Brain Chemistry Labs in Jackson Hole reported. "We are concerned that cyanobacterial releases from Lake Okeechobee down these two rivers continue to occur."

Red tides have historically resulted in fish kills and seasonal respiratory irritation along the west coast of Florida, but this new discovery of multiple sources of cyanobacterial toxins occurring at the same time as red tides, requires further investigation says scientists.

"Together with our colleagues at the Miami Brain Endowment Bank, we have found that chronic dietary exposure of laboratory animals to the cyanobacterial toxin BMAA triggers early Alzheimer's and ALS neuropathology," explains Dr. Paul Alan Cox, Director of the Brain Chemistry Labs, " but we cannot predict the health impacts of chronic exposures to multiple toxins at the same time."

ITHACA, N.Y. - In a potential breakthrough in wearable sensing technology, researchers from Cornell University and the University of Wisconsin, Madison, have designed a wrist-mounted device that continuously tracks the entire human hand in 3D.

The bracelet, called FingerTrak, can sense and translate into 3D the many positions of the human hand, including 20 finger joint positions, using three or four miniature, low-resolution thermal cameras that read contours on the wrist. The device could be used in sign language translation, virtual reality, mobile health, human-robot interaction and other areas, the researchers said.

"This was a major discovery by our team - that by looking at your wrist contours, the technology could reconstruct in 3D, with keen accuracy, where your fingers are," said Cheng Zhang, assistant professor of information science and director of Cornell's new SciFi Lab, where FingerTrak was developed. "It's the first system to reconstruct your full hand posture based on the contours of the wrist."

Past wrist-mounted cameras have been considered too bulky and obtrusive for everyday use, and most could reconstruct only a few discrete hand gestures.

FingerTrak's breakthrough is a lightweight bracelet, allowing for free movement. Instead of using cameras to directly capture the position of the fingers, the focus of most prior research, FingerTrak uses a combination of thermal imaging and machine learning to virtually reconstruct the hand. The bracelet's four miniature, thermal cameras - each about the size of a pea - snap multiple "silhouette" images to form an outline of the hand.

A deep neural network then stitches these silhouette images together and reconstructs the virtual hand in 3D. Through this method, Zhang and his fellow researchers were able to capture the entire hand pose, even when the hand is holding an object.

While the technology has a wide range of possible uses, Zhang said the most promising is its potential application in sign language translation.

"Current sign language translation technology requires the user to either wear a glove or have a camera in the environment, both of which are cumbersome," he said. "This could really push the current technology into new areas."

FingerTrak could also have an impact on health care applications, specifically in monitoring disorders that affect fine-motor skills, said Yin Li, assistant professor of biostatistics and medical informatics at the University of Wisconsin, Madison School of Medicine and Public Health, who contributed to the software behind FingerTrak.

"How we move our hands and fingers often tells about our health condition," Li said. "A device like this might be used to better understand how the elderly use their hands in daily life, helping to detect early signs of diseases like Parkinson's and Alzheimer's."

"FingerTrak: Continuous 3D Hand Pose Tracking by Deep Learning Hand Silhouettes Captured by Miniature Thermal Cameras on Wrist," was published in the Proceedings of the Association for Computing Machinery on Interactive, Mobile, Wearable and Ubiquitous Technologies. It also will be presented at the 2020 ACM International Joint Conference on Pervasive and Ubiquitous Computing, taking place virtually Sept. 12-16.

Toddlers may not be able to describe their feelings of uncertainty, but a new study from the Center for Mind and Brain at the University of California, Davis provides evidence that toddlers may experience and deal with uncertainty in decision making in the same way as older children and adults.

"Little children show behaviors that suggest they can respond to uncertain situations. For example, they seem to hesitate or ask when they can't figure something out," said Simona Ghetti, professor of psychology at UC Davis. "But are these behaviors grounded in their evaluations of actual evidence? And how do very young children become aware they are uncertain?"

The new study, involving 160 toddlers from 25 to 32 months old, provides a window into how young children's minds work as they perform a task, she said. The work is published July 20 in Nature Human Behavior.

First author Sarah Leckey, graduate student in the Center for Mind and Brain, led the experimental work. In the study, 2-year-olds were shown pairs of images of animals or common objects, each mostly obscured by a grey square. They were asked to find one of the objects, for example "where is the elephant hiding?"

The task was carried out with both an eye-tracking device, where toddlers responded by pointing, and a touch screen, which allowed to collect their response speed. The experiment was conducted twice, with two groups of 80 children, to ensure reproducibility of the results.

Tracking gaze and behavior

By following the childrens' gaze with eye tracking and measuring how long it took them to come to decision, the researchers could see how the children gathered information before making a decision.

"We can look at behavior like how they are distributing their looks to find useful information, how they go back and forth between images, or whether they take extra time before responding," Leckey said.

Children spent longer deliberating on more difficult trials, when the images were more similar, and when they came to an incorrect decision. The researchers were able to further analyze the data using a type of model called a drift-diffusion model, never previously used in studies of such young children.

"We can see if they act as if they are more or less confident," she said. Ghetti believes that toddlers' responses to difficult decisions and their search for more information become the basis for eventually becoming aware of our uncertainty, which is fundamental to how we learn as older children and adults.

The need for pacemakers in Africa will rise as life expectancy and associated cardiovascular diseases increase; however, the pacing field, including appropriate training, facilities and devices, are not sufficient to meet future need, according to an Africa Heart Rhythm Association (AFHRA) statement published in the Journal of the American College of Cardiology.

According to the paper, a recent Pan-African Society of Cardiology found that pacemakers are not implanted in about 20% of African countries. In African countries that do perform pacing, sites and trained implanters are few, with 17 countries having fewer than five centers each. The median implantation rate in 2016 in Africa was 2.66%, which is 200-fold lower than Europe.

The statement examines four main barriers to pacing in Africa--lack of skilled implanters, lack of facilities for implantation, high cost of devices and lack of government support--and offers solutions for how to address these barriers. Researchers focus on improving local training and fellowship programs so trainees do not have to leave the continent for specialized instruction, collaborating with local governments to subsidize equipment, and ensuring quality assurance of implanting centers and clinicians through AFHRA oversight.

Preliminary data from researchers at the University of Cincinnati Cancer Center show that immunotherapy doesn't necessarily worsen complications for patients with both COVID-19 and cancer.

This data is being presented by Layne Weatherford, PhD, UC postdoctoral fellow, at the American Association for Cancer Research Virtual Meeting: COVID-19 and Cancer, Monday, July 20.

Weatherford works in the lab of Trisha Wise-Draper, PhD, an associate professor of medicine, Division of Hematology Oncology, at the UC College of Medicine, UC Health oncologist and medical director of the UC Cancer Center Clinical Trials Office.

"Many COVID-19 complications result from an overactive immune response, leading to an increased production of proteins called cytokines," Weatherford says. "Increased production of these proteins can cause issues like respiratory failure. Patients with cancer are more susceptible to COVID-19 infection as well as severe complications from it.

"Many patients with cancer are treated with immunotherapy, which activates the immune system against cancer to destroy it. In patients with both COVID-19 and cancer, our team thought that immunotherapy might increase the immune system response, which could already be overactive because of the COVID-19 infection."

Wise-Draper says researchers thought treating COVID-19 patients with cancer immunotherapy might result in worsening patients' health and overall outcomes.

"We are continuing to investigate whether immunotherapy causes an increased production of these proteins by immune cells from COVID-19 patients, but our initial findings are showing that immunotherapy is not significantly impacting it," she adds.

Researchers are conducting this study using blood samples from patients with cancer taken from the UC COVID-19 biorepository, which Kris Hudock, MD, assistant professor in the Division of Pulmonary, Critical Care and Sleep Medicine at the UC College of Medicine, oversees.

"We are examining how immune checkpoint inhibitors, drugs that allow immune cells to respond more strongly, in combination with other treatments, like chemotherapy or radiation, affect the immune cells of COVID-19 patients and patients with both COVID-19 and cancer," she says.

She and Weatherford add that their preliminary data show that an anti-diabetic drug, metformin, can reduce production of these proteins by immune cells of COVID-19 patients.

"These are promising, initial findings," Wise-Draper says. "Additional research is needed, but our results show that we might be able to treat COVID-19 complications with metformin or a similar drug one day."

A rock core from Petrified Forest National Park, Arizona, has given scientists a powerful new tool to understand how catastrophic events shaped Earth's ecosystems before the rise of the dinosaurs.

The quarter-mile core is from an important part of the Triassic Period when life on Earth endured a series of cataclysmic events: Our planet was struck at least three times by mountain-sized asteroids, chains of volcanoes erupted to choke the sky with greenhouse gases, and tectonic movement tore apart Earth's single supercontinent, Pangea.

Among the chaos, many plants and animals, including some of the long-snouted and armored reptiles that ruled Pangea throughout the Triassic, vanished in a possible shake-up of life on Earth that scientists have yet to explain.

The study, published July 20 in GSA Bulletin, offers scientists a foundation to explain the changes in the fossil record and determine how these events may have shaped life on Earth.

By determining the age of the rock core, researchers were able to piece together a continuous, unbroken stretch of Earth's history from 225 million to 209 million years ago. The timeline offers insight into what has been a geologic dark age and will help scientists investigate abrupt environmental changes from the peak of the Late Triassic and how they affected the plants and animals of the time.

"The core lets us wind the clock back 225 million years when Petrified Forest National Park was a tropical hothouse populated by crocodile-like reptiles and turkey-size early dinosaurs," said Cornelia Rasmussen, a postdoctoral researcher at the University of Texas Institute for Geophysics (UTIG), who led the analysis that determined the age of the core.

"We can now begin to interpret changes in the fossil record, such as whether changes in the plant and animal world at the time were caused by an asteroid impact or rather by slow geographic changes of the supercontinent drifting apart," she said.

Petrified Forest National Park's paleontologist Adam Marsh said that despite a rich collection of fossils from the period in North America, until now there was little information on the Late Triassic's timeline because most of what scientists knew came from studying outcrops of exposed rock pushed to the surface by tectonic movements.

"Outcrops are like broken pieces of a puzzle," said Marsh, who earned his Ph.D. from The University of Texas at Austin's Jackson School of Geosciences. "It is incredibly difficult to piece together a continuous timeline from their exposed and weathered faces."

Marsh was not an author of the study but is part of the larger scientific coring project. UTIG is a unit of the Jackson School.

The Petrified Forest National Park core overcomes the broken puzzle problem by recovering every layer in the order it was deposited. Like tree rings, scientists can then match those layers with the fossil and climate record.

To find the age of each layer, the researchers searched the rock core for tiny crystals of the mineral zircon, which are spewed into the sky during volcanic eruptions. Zircons are a date stamp for the sediments with which they are buried. Researchers then compared the age of the crystals with traces of ancient magnetism stored in the rocks to help develop a precise geologic timeline.

Geoscience is rarely so simple, however, and according to Rasmussen, the analysis of the core gave them two slightly different stories. One shows evidence that a shake-up in the species might not be connected to any single catastrophic event and could simply be part of the ordinary course of gradual evolution. The other shows a possible correlation between the change in the fossil record and a powerful asteroid impact, which left behind a crater in Canada over 62 miles wide.

For Marsh, the different findings are just part of the process to reach the truth.

"The two age models are not problematic and will help guide future studies," he said.

A new study identified 37 recently active volcanic structures on Venus. The study provides some of the best evidence yet that Venus is still a geologically active planet. A research paper on the work, which was conducted by researchers at the University of Maryland and the Institute of Geophysics at ETH Zurich, Switzerland, was published in the journal Nature Geoscience on July 20, 2020.

"This is the first time we are able to point to specific structures and say 'Look, this is not an ancient volcano but one that is active today, dormant perhaps, but not dead,'" said Laurent Montési, a professor of geology at UMD and co-author of the research paper. "This study significantly changes the view of Venus from a mostly inactive planet to one whose interior is still churning and can feed many active volcanoes."

Scientists have known for some time that Venus has a younger surface than planets like Mars and Mercury, which have cold interiors. Evidence of a warm interior and geologic activity dots the surface of the planet in the form of ring-like structures known as coronae, which form when plumes of hot material deep inside the planet rise through the mantle layer and crust. This is similar to the way mantle plumes formed the volcanic Hawaiian Islands.

But it was thought that the coronae on Venus were probably signs of ancient activity, and that Venus had cooled enough to slow geological activity in the planet's interior and harden the crust so much that any warm material from deep inside would not be able to puncture through. In addition, the exact processes by which mantle plumes formed coronae on Venus and the reasons for variation among coronae have been matters for debate.

In the new study, the researchers used numerical models of thermo-mechanic activity beneath the surface of Venus to create high-resolution, 3D simulations of coronae formation. Their simulations provide a more detailed view of the process than ever before.

The results helped Montési and his colleagues identify features that are present only in recently active coronae. The team was then able to match those features to those observed on the surface of Venus, revealing that some of the variation in coronae across the planet represents different stages of geological development. The study provides the first evidence that coronae on Venus are still evolving, indicating that the interior of the planet is still churning.

"The improved degree of realism in these models over previous studies makes it possible to identify several stages in corona evolution and define diagnostic geological features present only at currently active coronae," Montési said. "We are able to tell that at least 37 coronae have been very recently active."

The active coronae on Venus are clustered in a handful of locations, which suggests areas where the planet is most active, providing clues to the workings of the planet's interior. These results may help identify target areas where geologic instruments should be placed on future missions to Venus, such as Europe's EnVision that is scheduled to launch in 2032.

A group of international scientists have substantially lengthened the duration of time that a spin-orbit qubit in silicon can retain quantum information for, opening up a new pathway to make silicon quantum computers more scalable and functional.

Spin-orbit qubits have been investigated for over a decade as an option to scale up the number of qubits in a quantum computer, as they are easy to manipulate and couple over long distances. However, they have always shown very limited coherence times, far too short for quantum technologies.

The research published today in Nature Materials shows that long coherence times are possible when spin-orbit coupling is strong enough. In fact, the scientists demonstrated coherence times 10,000 times longer than previously recorded for spin-orbit qubits, making them an ideal candidate for scaling up silicon quantum computers.

"We turned the conventional wisdom on its head by demonstrating exceptionally long coherence times - ~10 milliseconds - and therefore, that spin-orbit qubits can be remarkably robust," says UNSW Professor Sven Rogge, Chief Investigator, Centre for Quantum Computation and Communication Technology (CQC2T), who led the research team.

Strong coupling is key

How stable a qubit is determines the length of time that it can preserve quantum information for.

In spin-orbit qubits information is stored on the spin of the electron as well as its motion - how it 'orbits' atoms in the lattice of the chip. It is the strength of the coupling between these two spins that keeps the qubit stable and less prone to being destroyed by electric noise in devices.

"The quantum information in most spin-orbit qubits is extremely fragile. Our spin-orbit qubit is special because quantum information stored in it is very robust," says lead author Dr Takashi Kobayashi, who performed the research at UNSW and is now at Tohoku University.

"The information is stored in the orientation of the spin and orbit of the electron, not just the spin. The circular orbit of the charged electron and the spin are locked together like gears due to the very strong attraction in the spin-orbit coupling.

"Increasing the strength of that spin-orbit coupling lets us achieve the significantly longer coherence times we've published today."

Engineering longer coherence times

To increase the coherence time, the researchers first created spin-orbit qubits by introducing impurities, called acceptor dopant atoms, in a silicon crystal. The team then modified the strain in the silicon lattice structure of the chip to generate different levels of spin-orbit coupling.

"The crystal is special because it only contains the isotope of silicon with no nuclear spin. This eliminates magnetic noise, and because it is strained sensitivity to electric noise is also reduced." Says Kobayashi.

"Our chip was fixed on to a material that at a low temperature stretches out the silicon - like a rubber band. Stretching the lattice to the correct tension allowed us to tune the spin-orbit coupling to the optimal value."

The end result produced coherence times over 10,000 times longer than previously found in spin-orbit qubits.

This means quantum information is preserved for much longer, allowing many more operations to be performed - an important stepping-stone for scaling up quantum computers.

Scaling up with spin-orbit coupling

For a quantum computer to outperform a classical computer, a large number of qubits need to work together to perform complex calculations.

"The stability of our spin-orbit qubit to electric fields is unique, proving a robust new pathway to make scalable quantum computers." Says co-author Joe Salfi, who performed the research at CQC2T and is now at the University of British Columbia.

The finding ultimately enables new ways of manipulating individual qubits and coupling qubits over much larger distances, which will make the chip fabrication process more flexible.

The electrical interaction also allows coupling to other quantum systems, opening up the prospects of hybrid quantum systems.

Earlier research published in Science Advances by the UNSW team showed spin-orbit coupling in silicon provides many advantages for scaling up to a large number of qubits.

"Spins in silicon are very attractive for scalable quantum information devices because they're stable and compatible with current computer processing techniques, making those devices easy to manufacture," says Prof. Rogge.

"Now that we've demonstrated long coherence times, spin-orbit qubits make a strong candidate for a large-scale quantum processor in silicon."