Culture

New research led by the University of Cambridge suggests that autism can be detected at 18-30 months using the Quantitative Checklist for Autism in Toddlers (Q-CHAT), but it is not possible to identify every child at a young age who will later be diagnosed as autistic. The results are published today in The BMJ Paediatrics Open.

The team at the Autism Research Centre in Cambridge conducted a prospective population screening study of nearly 4,000 toddlers using a parent-report instrument they developed, called the Quantitative Checklist for Autism in Toddlers (Q-CHAT). Toddlers were screened at 18 months and followed up at 4 years.

The Q-CHAT is a revision of the original CHAT first published by the same authors in the 1990s. It retains the key items but includes additional items that examine language development, repetitive and sensory behaviours, as well as other aspects of social communication behaviour. Each of the 25 items contains a range of response options, allowing for the endorsement of a reduced rate of key behaviours. In effect, this 'dimensionalises' each item (using a five-point scale of frequency), allowing for variability in responses and a better understanding of the distributions across the specific traits. The revision was motivated by trying to improve on the accuracy of screening toddlers for autism.

In the new research, in phase one, 13,070 caregivers were invited to complete the Q-CHAT about their child at 18-30 months. 3,770 caregivers returned the Q-CHAT, of whom 121 were invited for an autism diagnostic assessment.

In phase two, the sample was followed up when the children were 4, using the Childhood Autism Screening Test (CAST), and a checklist enquiring whether any of the children had been referred or diagnosed with any developmental conditions, including autism. Autism assessments were made using internationally recognized methods.

The sensitivity (the proportion of autistic children correctly identified by the Q-CHAT as being autistic) of the Q-CHAT in predicting autism at phase two is 44%, and the specificity (the proportion of children who are not autistic and who are correctly identified by the Q-CHAT as not being autistic) is 98%. Results also showed that the 'positive predictive value' (the proportion whose screened positive on the Q-CHAT who were found to be autistic) is 28%.

This study demonstrates that early detection and diagnosis of autism is possible using the Q-CHAT, since all 11 children who were classified as autistic scored at or above the cut-point of 39. The Q-CHAT did not identify all children during toddlerhood who were later diagnosed with autism at age 4. This likely reflects that some autistic children do not show symptoms of sufficient severity until later in childhood.

In other studies the team have found some autistic people do not receive a diagnosis until their teens or even adulthood, perhaps because family support cushions the need for a diagnosis until social demands increase, for example at transition to secondary school or transition to adulthood.

Dr Carrie Allison, Director of Research Strategy at the Autism Research Centre, and who led the study, said: "This study tells us that autism can be detected during the toddler years, and that other children may only be identified as autistic later. Repeat screening and surveillance across development may be a better approach rather than relying on a single time-point."

Professor Tony Charman, Professor of Clinical Child Psychology at Kings College London, and a member of the team, said: "Screening for autism in infancy means that children can be fast-tracked into early intervention, which we know can lead to better outcomes for many children. This is an exciting advance because most other autism screening measures in toddlers have not been subject to rigorous population studies of this kind."

Professor Sir Simon Baron-Cohen, Director of the Autism Research Centre and a member of the team, said: "25 years ago our team was the first to show autism could be screened and diagnosed as young as 18 months of age. This new study shows how our original screening instrument - the CHAT - has been revised into a better instrument - the Q-CHAT, which can pick up children who need an autism diagnosis. Early detection means happier, healthier, children and families because they can be targeted with support."

Northwestern University engineers have developed the first full, three-dimensional (3D), dynamic simulation of a rat's complete whisker system, offering rare, realistic insight into how rats obtain tactile information.

Called WHISKiT, the new model incorporates 60 individual whiskers, which are each anatomically, spatially and geometrically correct. The technology could help researchers predict how whiskers activate different sensory cells to influence which signals are sent to the brain as well as provide new insights into the mysterious nature of human touch.

The research was published last week in the Proceedings of the National Academy of Sciences.

With just a brush of their whiskers, rats can extract detailed information from their environments, including an object's distance, orientation, shape and texture. This keen ability makes the rat's sensory system ideal for studying the relationship between mechanics (the moving whisker) and sensory input (touch signals sent to the brain).

But while the rat whisker system is a widely used simplified model system in sensory neuroscience, it's challenging to study an animal's nervous system as it moves to interact with its natural environment.

"We cannot measure the signals at the base of a real rat's whisker using current technology because, as soon as you embed a sensor, it interferes with the signals themselves," said Northwestern's Mitra Hartmann, the study's senior author. "The only way we can really capture a rat actively sensing its environment under natural conditions is to simulate it."

With potential to overcome these challenges, simulations have become an increasingly important component of neuroscience. By developing WHISKiT, the study authors now have the first complete model of tactile input to a moving sensory system, which shows how rats actively "whisk" and passively sense their complex 3D environments.

"Because none of the individual whiskers works in isolation, WHISKiT is crucial to understanding how the brain processes incoming tactile sensory information," said Nadina Zweifel, the paper's first author. "It's equivalent to a tactile 'camera' that can capture the mechanical signals an animal may acquire while using the whiskers to interact with the environment. That way, we believe that our tool considerably widens the range of possibilities for computational and experimental studies in the future."

Hartmann is a professor of biomedical and mechanical engineering at Northwestern's McCormick School of Engineering, where she is a member of the Center for Robotics and Biosystems and the Northwestern University Interdepartmental Neuroscience program. Zweifel is a Ph.D. candidate in Hartmann's laboratory.

To develop the new WHISKiT model, the Northwestern team combined more than a decade's worth of experimental data from Hartmann's lab. Because every whisker is slightly different, her group previously calculated the proper geometry (including arc, base diameter and slope) for individual whiskers. After validating models for individual whiskers, the researchers combined the whiskers into a full array.

The resulting model considers the geometry, spatial arrangement and movement of all 60 whiskers (30 on each side) on a rat's face. Each whisker is embedded in a follicle, where the mechanical signals are generated at the base.

WHISKiT also incorporates new data collected from 3D scans that Zweifel captured of rats' natural environments, including in urban alleys, around dumpsters and at drain pipes, across the cities of Chicago and Evanston. The model simulates rats in these natural environments ("whisking" around a drain pipe, for example) as well as in laboratory settings. The researchers found that each typical, exploratory scenario generates a unique pattern of data.

"The tactile signals associated with exploring a complicated drain pipe or dumpster are very different from those associated with exploring a blank wall," Hartmann explained.

The researchers next plan to use the simulation to address several long-standing questions, including how rats can use touch to distinguish between stationary and moving objects and how active whisking compares to passive sensing.

Bat conversations might be light on substance, according to researchers from the University of Cincinnati.

Echoes from bats are so simple that a sound file of their calls can be compressed 90% without losing much information, according to a study published in the journal PLOS Computational Biology.

The study demonstrates how bats have evolved to rely on redundancy in their navigational "language" to help them stay oriented in their complex three-dimensional world.

"If you can make decisions with little information, everything becomes simpler. That's nice because you don't need a lot of complex neural machinery to process and store that information," study co-author Dieter Vanderelst said.

UC researchers suspected that the calls of bats contain redundant information and that bats might use efficient encoding strategies to extract the most relevant information from their echoes. Many natural stimuli encountered by animals have a lot of redundancy. Efficient neural encoding retains essential information while reducing this redundancy.

To test their hypothesis, they built their own "bat on a stick," a tripod-mounted device that emits a pulse of sound sweeping from 30 to 70 kilohertz, a frequency range used by many bats. By comparison, human speech typically ranges from 125 to 300 hertz (or 0.125 to 0.3 kHz).

More than 1,000 echoes were captured in distinct indoor and outdoor environments such as in a barn, in different-sized rooms, among bushes and tree branches and in a garden.

Researchers converted the recorded echoes to a graph of the sound, called a cochleogram. Then they subjected these graphs to 25 filters -- essentially compressing the data. They trained a neural network, a computer system modeled on the human brain, to determine if the filtered graphs still contained enough information to complete a number of sonar-based tasks known to be performed by bats.

They found that the neural network correctly identified the location of the echoes even when the cochleogram was stripped of as much as 90% of its data.

"What that tells us is you can compress that data and still do what you need to do. It also means if you're a bat, you can do this efficiently," said Vanderelst, an assistant professor in UC's College of Arts and Sciences and in the College of Engineering and Applied Science.

Vanderelst said researchers often can infer what bats are doing just by listening to their calls.

"Even if you don't see the bat, you can tell with a high degree of certainty what a bat is doing," he said. "If it calls more frequently, it's looking for something. If the calls are spread out, it's cruising or studying something far away."

Bats produce their ultrasonic calls with a larynx much like ours. But what a voice box. It can contract 200 times a second, making it the fastest known muscle in all mammals.

The nighttime forest can be deafening to people because of its chorus of frogs and drone of insects. But Vanderelst said the ultrasonic frequency by comparison is pretty quiet, allowing bats to hear their own chittering calls that bounce off tree branches and other obstacles during echolocation.

While bats use different chirps for navigating than for communicating with each other, Vanderelst said they're all pretty simple. But human language has lots of built-in redundancy as well, Vanderelst said.

Fr xmpl, cn y rd ths sntnc wth mssng vwls?

"Take out a lot of letters in a sentence and it's still readable," Vanderelst said.

UC graduate Adarsh Chitradurga Achutha, Vanderelst's student, was the study's lead author. Co-authors include Vanderelst's mentor Herbert Peremans at the University of Antwerp, Belgium, and bat expert Uwe Firzlaff with the University of Munich, Germany.

The way bats perceive the world is fascinating both from biological and engineering perspectives, Vanderelst said.

"It's like a riddle, looking at something that shouldn't be able to do what it does. So the question is how?" he said. "It's given me an appreciation for the elegant efficiency underlying this system."

Researchers at Vanderbilt University Medical Center (VUMC) and the Baylor College of Medicine in Houston, Texas, have taken a big step toward developing targeted treatments and vaccines against a family of viruses that attacks the gastrointestinal tract.

Each year in the United States circulating strains of the human norovirus are responsible for approximately 20 million cases of acute gastroenteritis. Hallmark symptoms include severe abdominal cramping, diarrhea and vomiting.

Several vaccine candidates are in clinical trials, but it is unclear how effective they will be, given the periodic emergence of novel norovirus variants. Developing broadly effective vaccines will require an understanding of the genetic diversity of the virus and the mechanisms by which the immune system can neutralize it.

Reporting this week in the journal Nature Communications, the researchers isolated a panel of human monoclonal antibodies from subjects with a history of acute gastroenteritis that are cross-reactive and which neutralize a broad range of norovirus variants in laboratory tests.

They describe a conserved, antigenic site on the norovirus that could be used to reformulate vaccine candidates so that they are broadly effective against circulating viral strains. The monoclonal antibodies also could be used to treat or prevent norovirus infection directly or as diagnostic reagents, they added.

Leading the research were the paper's corresponding authors, James Crowe Jr., MD, director of the Vanderbilt Vaccine Center, and B.V. Venkataram Prasad, PhD, the Alvin Romansky Chair in Biochemistry, in collaboration with Mary Estes, PhD, the Cullen Chair and professor of virology at Baylor College of Medicine.

First authors of the paper were Gabriela Alvarado, PhD, formerly of the Crowe lab, now at the National Institute of Allergy and Infectious Diseases, and Wilhelm Salmen, a graduate student in the Prasad lab.

"We were surprised to find naturally occurring antibodies that recognized so many different noroviruses," said Crowe, the Ann Scott Carell Chair and professor of Pediatrics and Pathology, Microbiology & Immunology at VUMC.

"Previously, many experts thought that this would not be possible because of the extreme sequence diversity in the various groups and types of noroviruses in circulation," he said. "The human immune system continues to surprise us in its capacity to recognize diverse virus variants."

"One of the fascinating aspects of this study was the unexpected finding of where the human antibody attacks the virus for neutralization," Prasad said.

"It is exciting to now have human monoclonal antibodies that neutralize many norovirus variants," added Estes.

WHAT:

A new study published in Nature Communications suggests that gene therapy delivered into the brain may be safe and effective in treating aromatic L-amino acid decarboxylase (AADC) deficiency. AADC deficiency is a rare neurological disorder that develops in infancy and leads to near absent levels of certain brain chemicals, serotonin and dopamine, that are critical for movement, behavior, and sleep. Children with the disorder have severe developmental, mood dysfunction including irritability, and motor disabilities including problems with talking and walking as well as sleep disturbances. Worldwide there have been approximately 135 cases of this disease reported.

In the study, led by Krystof Bankiewicz, M.D., Ph.D., professor of neurological surgery at Ohio State College of Medicine in Columbus, and his colleagues, seven children received infusions of the DDC gene that was packaged in an adenovirus for delivery into brain cells. The DDC gene is incorporated into the cells' DNA and provides instructions for the cell to make AADC, the enzyme that is necessary to produce serotonin and dopamine. The research team used magnetic resonance imaging to guide the accurate placement of the gene therapy into two specific areas of the midbrain.

Positron emission tomography (PET) scans performed three and 24 months after the surgery revealed that the gene therapy led to the production of dopamine in the deep brain structures involved in motor control. In addition, levels of a dopamine metabolite significantly increased in the spinal fluid.

The therapy resulted in clinical improvement of symptoms. Oculogyric crises, abnormal upward movements of the eyeballs, often with involuntary movements of the head, neck and body, that can last for hours and are a hallmark of the disease, completely went away in 6 of 7 participants. In some of the children, improvement was seen as early as nine days after treatment. One participant continued to experience oculogyric crises, but they were less frequent and severe.

All of the children exhibited improvements in movement and motor function. Following the surgery, parents of a majority of participants reported their children were sleeping better and mood disturbances, including irritability, had improved. Progress was also observed in feeding behavior, the ability to sit independently, and in speaking. Two of the children were able to walk with support within 18 months after receiving the gene therapy.

The gene therapy was well tolerated by all participants and no adverse side effects were reported. At three to four weeks following surgery, all participants exhibited irritability, sleep problems, and involuntary movements, but those effects were temporary. One of the children died unexpectedly seven months after the surgery. The cause of death was unknown but assessed to be due to the underlying primary disease.

As the Covid-19 pandemic raged, news reports show that sales of electronic air cleaners have surged due to concerns about airborne disease transmission. But a research team at the Georgia Institute of Technology has found that the benefits to indoor air quality of one type of purifying system can be offset by the generation of other pollutants that are harmful to health.

Led by Associate Professor Nga Lee "Sally" Ng in Georgia Tech's School of Chemical and Biomolecular Engineering and the School of Earth and Atmospheric Sciences, the team evaluated the effect of a hydroxyl radical generator in an office setting. Hydroxyl radicals react with odors and pollutants, decomposing them, and hydroxyl radical generators have been marketed to inactivate pathogens such as coronaviruses.

However, Ng's study found that in the process of cleaning the air, the hydroxyl radicals generated by the device reacted with volatile organic compounds present in the indoor space. This led to chemical reactions that quickly formed organic acids and secondary organic aerosols that can cause health problems. Secondary organic aerosols is a major component of PM2.5 (particulate matter with a diameter smaller than 2.5 ?m), and exposure to PM2.5 has been associated with cardiopulmonary diseases and millions of deaths per year.

The paper, "Formation of oxidized gases and secondary organic aerosol from a commercial oxidant-generating electronic air cleaner," is published in the journal Environmental Science and Technology Letters.

While the pandemic has made various types of electronic cleaners increasingly popular, Ng explained that consumers are probably not aware of the secondary chemistry taking place in the air, with the pollutants generated not being directly emitted by the cleaning device itself.

"There are increasing concerns regarding the use of electronic air cleaners as these devices can potentially generate unintended byproducts via oxidation chemistry similar to that in the atmosphere," Ng said.

Two types of air cleaning technologies are commonly used to remove indoor pollutants such as particles or volatile organic compounds and to inactivate pathogens: mechanical filtration and electronic air cleaners that generate ions, reactive species, or other chemical products such as photocatalytic oxidation, plasma, and oxidant-generating equipment (e.g., ozone, hydroxyl radical), among others.

Ng's team selected a hydroxyl generator for the study. They measured the oxygenated volatile organic compounds and the chemical composition of particles generated by the device in an office on the Georgia Tech campus.

While previous research reported pollutant formation from various electronic air cleaners (ionizers, plasma systems, photocatalytic systems with ultraviolet lamps, etc.), Ng believes that her team's study is the first to monitor the chemical composition of secondary pollutants in both gas and particle phases during the operation of an electronic device that dissipates oxidants in a real-world setting.

Advanced instrumentation made Ng's study possible. Gas-phase organic compounds were measured using a high-resolution time-of-flight chemical ionization mass spectrometer, purchased through a National Science Foundation major instrumentation grant. The study received support from Georgia Tech's Covid-19 Rapid Response fund.

Ng noted that future studies on air cleaning technology should not be limited to inactivation of viruses or reduction of volatile organic compounds, but should also evaluate potential oxidation chemistry and the formation of unintended harmful gaseous and particulate chemicals.

"More studies need to be conducted on the effects of these devices in a variety of environments," Ng said.

"Electronic air cleaners greatly rose in prominence because of the pandemic, and now there are a lot of these devices out there. Millions of dollars are being spent on these devices by businesses and schools. The market is huge.

"Our results show that care must be taken when choosing an adequate and appropriate air cleaning technology for a particular environment and task," she said.

Ng stressed the importance of future studies concerning the unintended effects of electronic purifiers, as these devices are not currently well regulated and do not have testing standards.

"There needs to be more peer-reviewed scientific data on electronic air cleaners," Ng said. "We hope that additional studies will lead to more government guidelines and regulation."

A team of researchers from the University of Maryland has 3D printed a soft robotic hand that is agile enough to play Nintendo's Super Mario Bros. - and win!

The feat, highlighted on the front cover of the latest issue of Science Advances, demonstrates a promising innovation in the field of soft robotics, which centers on creating new types of flexible, inflatable robots that are powered using water or air rather than electricity. The inherent safety and adaptability of soft robots has sparked interest in their use for applications like prosthetics and biomedical devices. Unfortunately, controlling the fluids that make these soft robots bend and move has been especially difficult - until now.

The key breakthrough by the team, led by University of Maryland assistant professor of mechanical engineering Ryan D. Sochol, was the ability to 3D print fully assembled soft robots with integrated fluidic circuits in a single step.

"Previously, each finger of a soft robotic hand would typically need its own control line, which can limit portability and usefulness," explains co-first author Joshua Hubbard, who performed the research during his time as an undergraduate researcher in Sochol's Bioinspired Advanced Manufacturing (BAM) Laboratory at UMD. "But by 3D printing the soft robotic hand with our integrated fluidic transistors, it can play Nintendo based on just one pressure input."

As a demonstration, the team designed an integrated fluidic circuit that allowed the hand to operate in response to the strength of a single control pressure. For example, applying a low pressure caused only the first finger to press the Nintendo controller to make Mario walk, while a high pressure led to Mario jumping. Guided by a set program that autonomously switched between off, low, medium, and high pressures, the robotic hand was able to press the buttons on the controller to successfully complete the first level of Super Mario Bros. in less than 90 seconds.

"Recently, several groups have tried to harness fluidic circuits to enhance the autonomy of soft robots," said recent Ph.D. graduate and co-first author of the study Ruben Acevedo, "but the methods for building and integrating those fluidic circuits with the robots can take days to weeks, with a high degree of manual labor and technical skill."

To overcome these barriers, the team turned to "PolyJet 3D Printing," which is like using a color printer, but with many layers of multi-material 'inks' stacked on top of one another in 3D.

"Within the span of one day and with minor labor, researchers can now go from pressing start on a 3D printer to having complete soft robots - including all of the soft actuators, fluidic circuit elements, and body features - ready to use," said study co-author Kristen Edwards.

The choice to validate their strategy by beating the first level of Super Mario Bros. in real time was motivated by science just as much as it was by fun. Because the video game's timing and level make-up are established, and just a single mistake can lead to an immediate game over, playing Mario provided a new means for evaluating soft robot performance that is uniquely challenging in a manner not typically tackled in the field.

In addition to the Nintendo-playing robotic hand, Sochol's team also reported terrapin turtle-inspired soft robots in their paper. The terrapin happens to be UMD's official mascot, and all of the team's soft robots were printed at UMD's Terrapin Works 3D Printing Hub.

Another important benefit of the team's strategy is that it's open source, with the paper open access for anyone to read as well as a link in the supplementary materials to a GitHub with all of the electronic design files from their work.

"We are freely sharing all of our design files so that anyone can readily download, modify on demand, and 3D print - whether with their own printer or through a printing service like us - all of the soft robots and fluidic circuit elements from our work," said Sochol. "It is our hope that this open-source 3D printing strategy will broaden accessibility, dissemination, reproducibility, and adoption of soft robots with integrated fluidic circuits and, in turn, accelerate advancement in the field."

At present, the team is exploring the use of their technique for biomedical applications including rehabilitation devices, surgical tools, and customizable prosthetics. As Sochol is a faculty affiliate of the Fischell Department of Bioengineering as well as a member of both the Maryland Robotics Center and the Robert E. Fischell Institute for Biomedical Devices, the team has an exceptional environment to continue advancing their strategy to address pressing challenges in biomedical fields.

Evolution is often portrayed as a tree, with new species branching off from existing lineages, never again to meet. The truth however is often much messier. In the case of adaptive radiation, in which species diversify rapidly to fill different ecological niches, it can be difficult to resolve relationships, and the phylogeny (i.e. evolutionary tree) may look more like a bush than a tree. This is because lineages may continue to interbreed as new species are established, and/or they may diverge and then re-hybridize, resulting in genetically mixed populations (known as admixture). Even after species diverge, the introduction of genes from one species to another (known as introgression) can occur. All of this results in a network of related species, rather than a simple tree. The extent to which these processes occur and their evolutionary and genomic impacts are not well understood, partially due to the "tree-like" assumptions of the models that are used to construct phylogenies. In a new study in Genome Biology and Evolution titled "Rampant genome-wide admixture across the Heliconius radiation," Krzysztof Kozak of the University of Cambridge and colleagues demonstrate the key role that interspecific gene flow played in the continent-wide adaptive radiation of the Heliconius butterflies. This study adds to the rich literature on Heliconius, a genus that provided some of the earliest evidence for the theory of evolution thanks to their distinctive wing patterns and colors, which help warn predators of their toxic nature.

According to Kozak and his co-authors, "the Neotropical Heliconius butterflies present an excellent opportunity to study the incidence and importance of gene flow in a recent adaptive radiation, due to the natural propensity of Heliconius and the sister genus Eueides to produce hybrids in the wild." In addition, the genes controlling their wing patterns are likely to be prime targets for selection and introgression, allowing different poisonous species to mimic each other and thus reinforcing the warning signal to predators.

The study included genomic data from 145 individuals, representing 40 of the 47 recognized Heliconius species and 6 of the 12 Eueides species, allowing a comprehensive investigation into departures from a strict tree model. The analysis revealed several discrepancies in the evolutionary history of individual genes, suggesting the possibility of extensive gene flow among lineages. Overall, the authors uncovered 13 instances of interspecific gene flow across the phylogeny, revealing a pattern of gene sharing that includes all of the major clades of Heliconius. "We found that gene flow between species, previously documented in a few closely related species, has been common across the group for millions of years," notes Dr. Kozak, "including both existing and ancestral lineages."

Intriguingly, when analyzing genes known to be involved in wing pattern and color, the authors found evidence for complex patterns of gene flow across several lineages, supporting previous reports and also identifying new cases of introgression. According to Dr. Kozak, "this provides further strong evidence that hybridization has been an important mechanism in the evolution of wing patterns, with sharing of relevant genes among many lineages allowing Heliconius to warn off avian predators." This makes Heliconius one of only a few known examples of a lineage that has experienced adaptive introgression of multiple genes across several different species.

In the future, Dr. Kozak and colleagues plan to use what they have learned about Heliconius to model their phylogenies as networks, rather than trees, allowing them to better understand the evolution of other butterfly traits, "from spatial learning to diverse arrays of pheromones and defensive toxins." In addition, they hope to relate their results to the geographic distribution of Heliconius: "We need to explore geographic variation and study both the incidence of hybridization (individuals of different species mating) and the levels of gene flow (genomic signature of mixing) between various populations, which so far has been done only for a few species." This type of work is likely to pose a considerable challenge, however, as many species and populations of Heliconius are rare and found only in remote locations, necessitating considerable field work.

As comprehensive genomic data sets continue to expand, Dr. Kozak hopes to investigate other organisms to see how widespread such interspecific gene flow may be. "As always in evolutionary biology, we need to ask how much our conclusions apply to other taxa. Very few butterflies, or insects indeed, have so far been studied in this depth: it remains to be seen how much evidence for genome-wide admixture we can find throughout the extreme diversity of insects."

ATLANTA--An oral prodrug developed by a team of scientists led by Binghe Wang, Regents' Professor of Chemistry at Georgia State University, delivers carbon monoxide to protect against acute kidney injury, according to a new paper published in Chemical Science.

Although carbon monoxide (CO) gas is toxic in large doses, scientists have discovered it can have beneficial effects by reducing inflammation and protecting cells against injury. Previous studies have demonstrated the protective effects of CO against injury in the kidneys, lungs, gastrointestinal tract and liver, among other organs. For the past five years, Wang and his collaborators have worked to design a safe way to deliver CO to human patients via prodrugs -- inactive compounds that must undergo a chemical process in the body before releasing the active pharmacological agent.

Wang's team developed prodrugs that allow for oral administration of CO using two common artificial sweeteners -- saccharine (an ingredient in Sweet'N Low) and acesulfame (an ingredient in Splenda) -- as "carrier" molecules. They designed the molecules to release CO in the process of decomposition, which is triggered by exposure to water. These are the first examples of orally active, organic CO prodrugs using a benign carrier that is approved by the Food & Drug Administration with a demonstrated safety profile.

"It's difficult to deliver a gas, much less a poisonous gas, as a therapeutic to patients, and this work represents a pivotal step forward in developing alternative delivery forms," said Wang, senior author of the paper and a Georgia Research Alliance Eminent Scholar. "We wanted to work with a carrier that has a very well characterized safety profile, which confers a higher degree of certainty that it will be safe to use in a pill for human consumption."

Of the two prodrugs, the scientists tested one, CO-306, for pharmacological efficacy against acute kidney damage. The researchers administered CO-306, which uses saccharine as a carrier molecule, to mice and found it reduced biomarkers associated with kidney injury, indicating it could be developed into a viable therapy. The mouse model mimicked the mechanisms of kidney tissue damage that occur in patients with extensive muscle damage, sickle cell disease, a common type of malaria, cardiopulmonary bypass surgery and severe sepsis.

Wang and his collaborators at Georgia State's Center for Diagnostics and Therapeutics, Vanderbilt University, Harvard Medical School and the University of Mississippi plan to conduct more extensive animal model studies and safety assessments on CO-306 before progressing to human clinical studies. They also plan to test CO-306 for efficacy against other types of organ injuries.

Wang says CO-based therapies particularly hold promise as a method of reducing the likelihood of organ damage during transplantation and improving outcomes for transplant patients.

"Science shows that exposing organs to CO gas can help preserve organs and prevent them from deteriorating during the process of transplantation," he said. "Now we need to demonstrate that these prodrugs can have a similar effect."

Imagine an orange cat. Now, imagine the same cat, but with coal-black fur. Now, imagine the cat strutting along the Great Wall of China. Doing this, a quick series of neuron activations in your brain will come up with variations of the picture presented, based on your previous knowledge of the world.

In other words, as humans, it's easy to envision an object with different attributes. But, despite advances in deep neural networks that match or surpass human performance in certain tasks, computers still struggle with the very human skill of "imagination."

Now, a USC research team has developed an AI that uses human-like capabilities to imagine a never-before-seen object with different attributes. The paper, titled Zero-Shot Synthesis with Group-Supervised Learning, was published in the 2021 International Conference on Learning Representations on May 7.

"We were inspired by human visual generalization capabilities to try to simulate human imagination in machines," said the study's lead author Yunhao Ge, a computer science PhD student working under the supervision of Laurent Itti, a computer science professor.

"Humans can separate their learned knowledge by attributes--for instance, shape, pose, position, color--and then recombine them to imagine a new object. Our paper attempts to simulate this process using neural networks."

AI's generalization problem

For instance, say you want to create an AI system that generates images of cars. Ideally, you would provide the algorithm with a few images of a car, and it would be able to generate many types of cars--from Porsches to Pontiacs to pick-up trucks--in any color, from multiple angles.

This is one of the long-sought goals of AI: creating models that can extrapolate. This means that, given a few examples, the model should be able to extract the underlying rules and apply them to a vast range of novel examples it hasn't seen before. But machines are most commonly trained on sample features, pixels for instance, without taking into account the object's attributes.

The science of imagination

In this new study, the researchers attempt to overcome this limitation using a concept called disentanglement. Disentanglement can be used to generate deepfakes, for instance, by disentangling human face movements and identity. By doing this, said Ge, "people can synthesize new images and videos that substitute the original person's identity with another person, but keep the original movement."

Similarly, the new approach takes a group of sample images--rather than one sample at a time as traditional algorithms have done--and mines the similarity between them to achieve something called "controllable disentangled representation learning."

Then, it recombines this knowledge to achieve "controllable novel image synthesis," or what you might call imagination. "For instance, take the Transformer movie as an example" said Ge, "It can take the shape of Megatron car, the color and pose of a yellow Bumblebee car, and the background of New York's Times Square. The result will be a Bumblebee-colored Megatron car driving in Times Square, even if this sample was not witnessed during the training session."

This is similar to how we as humans extrapolate: when a human sees a color from one object, we can easily apply it to any other object by substituting the original color with the new one. Using their technique, the group generated a new dataset containing 1.56 million images that could help future research in the field.

Understanding the world

While disentanglement is not a new idea, the researchers say their framework can be compatible with nearly any type of data or knowledge. This widens the opportunity for applications. For instance, disentangling race and gender-related knowledge to make fairer AI by removing sensitive attributes from the equation altogether.

In the field of medicine, it could help doctors and biologists discover more useful drugs by disentangling the medicine function from other properties, and then recombining them to synthesize new medicine. Imbuing machines with imagination could also help create safer AI by, for instance, allowing autonomous vehicles to imagine and avoid dangerous scenarios previously unseen during training.

"Deep learning has already demonstrated unsurpassed performance and promise in many domains, but all too often this has happened through shallow mimicry, and without a deeper understanding of the separate attributes that make each object unique," said Laurent Itti, a professor of computer science. "This new disentanglement approach, for the first time, truly unleashes a new sense of imagination in A.I. systems, bringing them closer to humans' understanding of the world."

Engineers at UC Riverside have unveiled an air-powered computer memory that can be used to control soft robots. The innovation overcomes one of the biggest obstacles to advancing soft robotics: the fundamental mismatch between pneumatics and electronics. The work is published in the open-access journal, PLOS One.

Pneumatic soft robots use pressurized air to move soft, rubbery limbs and grippers and are superior to traditional rigid robots for performing delicate tasks. They are also safer for humans to be around. Baymax, the healthcare companion robot in the 2014 animated Disney film, Big Hero 6, is a pneumatic robot for good reason.

But existing systems for controlling pneumatic soft robots still use electronic valves and computers to maintain the position of the robot's moving parts. These electronic parts add considerable cost, size, and power demands to soft robots, limiting their feasibility.

To advance soft robotics toward the future, a team led by bioengineering doctoral student Shane Hoang, his advisor, bioengineering professor William Grover, computer science professor Philip Brisk, and mechanical engineering professor Konstantinos Karydis, looked back to the past.

"Pneumatic logic" predates electronic computers and once provided advanced levels of control in a variety of products, from thermostats and other components of climate control systems to player pianos in the early 1900s. In pneumatic logic, air, not electricity, flows through circuits or channels and air pressure is used to represent on/off or true/false. In modern computers, these logical states are represented by 1 and 0 in code to trigger or end electrical charges.

Pneumatic soft robots need a way to remember and maintain the positions of their moving parts. The researchers realized that if they could create a pneumatic logic "memory" for a soft robot, they could eliminate the electronic memory currently used for that purpose.

The researchers made their pneumatic random-access memory, or RAM, chip using microfluidic valves instead of electronic transistors. The microfluidic valves were originally designed to control the flow of liquids on microfluidic chips, but they can also control the flow of air. The valves remain sealed against a pressure differential even when disconnected from an air supply line, creating trapped pressure differentials that function as memories and maintain the states of a robot's actuators. Dense arrays of these valves can perform advanced operations and reduce the expensive, bulky, and power-consuming electronic hardware typically used to control pneumatic robots.

After modifying the microfluidic valves to handle larger air flow rates, the team produced an 8-bit pneumatic RAM chip able to control larger and faster-moving soft robots, and incorporated it into a pair of 3D-printed rubber hands. The pneumatic RAM uses atmospheric-pressure air to represent a "0" or FALSE value, and vacuum to represent a "1" or TRUE value. The soft robotic fingers are extended when connected to atmospheric pressure and contracted when connected to vacuum.

By varying the combinations of atmospheric pressure and vacuum within the channels on the RAM chip, the researchers were able to make the robot play notes, chords, and even a whole song--"Mary Had a Little Lamb" --on a piano. Click here to view a video of the robot playing piano.

In theory, this system could be used to operate other robots without any electronic hardware and only a battery-powered pump to create a vacuum. The researchers note that without positive pressure anywhere in the system--only normal atmospheric air pressure-- there is no risk of accidental overpressurization and violent failure of the robot or its control system. Robots using this technology would be especially safe for delicate use on or around humans, such as wearable devices for infants with motor impairments.

Researchers at University of California San Diego School of Medicine and Rady Children's Institute for Genomic Medicine have produced a stem cell model that demonstrates a potential route of entry of SARS-CoV-2, the virus that causes COVID-19, into the human brain.

The findings are published in the July 9, 2021 online issue of Nature Medicine.

"Clinical and epidemiological observations suggest that the brain can become involved in SARS-CoV-2 infection," said senior author Joseph Gleeson, MD, Rady Professor of Neuroscience at UC San Diego School of Medicine and director of neuroscience research at the Rady Children's Institute for Genomic Medicine.

"The prospect of COVID19-induced brain damage has become a primary concern in cases of 'long COVID,' but human neurons in culture are not susceptible to infection. Prior publications suggest that the cells that make the spinal fluid could become infected with SARS-CoV-2, but other routes of entry seemed likely."

Gleeson and colleagues, who included both neuroscientists and infectious disease specialists, confirmed that human neural cells are resistant to SARS-CoV-2 infection. However, recent studies hinted that other types of brain cells might serve as a 'Trojan horse.'

Pericytes are specialized cells that wrap around blood vessels -- and carry the SARS-CoV2 receptor. The researchers introduced pericytes into three-dimensional neural cell cultures -- brain organoids -- to create "assembloids," a more sophisticated stem cell model of the human body. These assembloids contained many types of brain cells in addition to pericytes, and showed robust infection by SARS-CoV-2.

The coronavirus was able to infect the pericytes, which served as localized factories for production of SARS-CoV-2. These locally produced SARS-CoV-2 could then spread to other cell types, leading to widespread damage. With this improved model system, they found that the supporting cells known as astrocytes were the main target of this secondary infection.

The results, said Gleeson, indicate that one potential route of SARS-CoV-2 into the brain is through the blood vessels, where SARS-CoV-2 can infect pericytes, and then SARS-CoV-2 can spread to other types of brain cells.

"Alternatively, the infected pericytes could lead to inflammation of the blood vessels, followed by clotting, stroke or hemorrhages, complications that are observed in many patients with SARS-CoV-2 who are hospitalized in intensive care units."

Researchers now plan to focus on developing improved assembloids that contain not just pericytes, but also blood vessels capable of pumping blood to better model the intact human brain. Through these models, Gleeson said, greater insight into infectious disease and other human brain disease could emerge.

A potentially life-saving treatment for heart attack victims has been discovered from a very unlikely source - the venom of one of the world's deadliest spiders.

A drug candidate developed from a molecule found in the venom of the Fraser Island (K'gari) funnel web spider can prevent damage caused by a heart attack and extend the life of donor hearts used for organ transplants.

The discovery was made by a team led by Dr Nathan Palpant and Professor Glenn King from The University of Queensland (UQ) and Professor Peter Macdonald from the Victor Chang Cardiac Research Institute.

Dr Palpant, from UQ's Institute for Molecular Bioscience (IMB), said the drug candidate worked by stopping a 'death signal' sent from the heart in the wake of an attack.

"After a heart attack, blood flow to the heart is reduced, resulting in a lack of oxygen to heart muscle," Dr Palpant said.

"The lack of oxygen causes the cell environment to become acidic, which combine to send a message for heart cells to die."

"Despite decades of research, no one has been able to develop a drug that stops this death signal in heart cells, which is one of the reasons why heart disease continues to be the leading cause of death in the world."

Dr Palpant tested the drug candidate, a protein called Hi1a, using beating human heart cells exposed to heart attack stresses to see if the drug improved their survival.

"The Hi1a protein from spider venom blocks acid-sensing ion channels in the heart, so the death message is blocked, cell death is reduced, and we see improved heart cell survival."

There are currently no drugs in clinical use that prevent the damage caused by heart attacks.

Victor Chang Cardiac Research Institute's Professor Macdonald said this incredible result had been decades in the making.

"This will not only help the hundreds of thousands of people who have a heart attack every year around the world, it could also increase the number and quality of donor hearts, which will give hope to those waiting on the transplant list," said Professor MacDonald.

Professor MacDonald, who is also a senior cardiologist at St Vincent's Hospital in Sydney, added: "The survival of heart cells is vital in heart transplants -- treating hearts with Hi1a and reducing cell death will increase how far the heart can be transported and improve the likelihood of a successful transplant.

"Usually, if the donor heart has stopped beating for more than 30 minutes before retrieval, the heart can't be used - even if we can buy an extra 10 minutes, that could make the difference between someone having a heart and someone missing out. For people who are literally on death's door, this could be life-changing."

The discovery builds on earlier work by Professor King, who identified a small protein in the venom of the Fraser Island (K'gari) funnel-web spider that was shown to markedly improve recovery from stroke.

"We discovered this small protein, Hi1a, amazingly reduces damage to the brain even when it is given up to eight hours after stroke onset," Professor King said.

"It made sense to also test Hi1a on heart cells, because like the brain, the heart is one of the most sensitive organs in the body to the loss of blood flow and lack of oxygen.

"For heart attack victims, our vision for the future is that Hi1a could be administered by first responders in the ambulance, which would really change the health outcomes of heart disease."

"This is particularly important in rural and remote parts of Australia where patients and treating hospitals can be long distances apart - and when every second counts."

Also, this could help for the transfer of donor hearts for cardiac transplantation - allowing these donor hearts to be transported over longer distances and therefore increasing the network of available donors and recipients.

The protein has been tested in human heart cells, and the team are aiming for human clinical trials for both stroke and heart disease within 2-3 years.

The Heart Foundation's General Manager of Heart Health and Research, Bill Stavreski, welcomed the findings.

"About 57,000 Australians have a heart attack every year, and many result in permanent damage to the heart muscle, leading to heart failure, disability and reduced quality of life - while more investigation is needed, this research may lead to a new way of reversing this damage in heart attack survivors."

A team of astronomers has released new observations of nearby galaxies that resemble colourful cosmic fireworks. The images, obtained with the European Southern Observatory's Very Large Telescope (ESO's VLT), show different components of the galaxies in distinct colours, allowing astronomers to pinpoint the locations of young stars and the gas they warm up around them. By combining these new observations with data from the Atacama Large Millimeter/submillimeter Array (ALMA), in which ESO is a partner, the team is helping shed new light on what triggers gas to form stars.

Astronomers know that stars are born in clouds of gas, but what sets off star formation, and how galaxies as a whole play into it, remains a mystery. To understand this process, a team of researchers has observed various nearby galaxies with powerful telescopes on the ground and in space, scanning the different galactic regions involved in stellar births.

"For the first time we are resolving individual units of star formation over a wide range of locations and environments in a sample that well represents the different types of galaxies," says Eric Emsellem, an astronomer at ESO in Germany and lead of the VLT-based observations conducted as part of the Physics at High Angular resolution in Nearby GalaxieS (PHANGS) project. "We can directly observe the gas that gives birth to stars, we see the young stars themselves, and we witness their evolution through various phases."

Emsellem, who is also affiliated with the University of Lyon, France, and his team have now released their latest set of galactic scans, taken with the Multi-Unit Spectroscopic Explorer (MUSE) instrument on ESO's VLT in the Atacama Desert in Chile. They used MUSE to trace newborn stars and the warm gas around them, which is illuminated and heated up by the stars and acts as a smoking gun of ongoing star formation.

The new MUSE images are now being combined with observations of the same galaxies taken with ALMA and released earlier this year. ALMA, which is also located in Chile, is especially well suited to mapping cold gas clouds -- the parts of galaxies that provide the raw material out of which stars form.

By combining MUSE and ALMA images astronomers can examine the galactic regions where star formation is happening, compared to where it is expected to happen, so as to better understand what triggers, boosts or holds back the birth of new stars. The resulting images are stunning, offering a spectacularly colourful insight into stellar nurseries in our neighbouring galaxies.

"There are many mysteries we want to unravel," says Kathryn Kreckel from the University of Heidelberg in Germany and PHANGS team member. "Are stars more often born in specific regions of their host galaxies -- and, if so, why? And after stars are born how does their evolution influence the formation of new generations of stars?"

Astronomers will now be able to answer these questions thanks to the wealth of MUSE and ALMA data the PHANGS team have obtained. MUSE collects spectra -- the "bar codes" astronomers scan to unveil the properties and nature of cosmic objects -- at every single location within its field of view, thus providing much richer information than traditional instruments. For the PHANGS project, MUSE observed 30 000 nebulae of warm gas and collected about 15 million spectra of different galactic regions. The ALMA observations, on the other hand, allowed astronomers to map around 100 000 cold-gas regions across 90 nearby galaxies, producing an unprecedentedly sharp atlas of stellar nurseries in the close Universe.

In addition to ALMA and MUSE, the PHANGS project also features observations from the NASA/ESA Hubble Space Telescope. The various observatories were selected to allow the team to scan our galactic neighbours at different wavelengths (visible, near-infrared and radio), with each wavelength range unveiling distinct parts of the observed galaxies. "Their combination allows us to probe the various stages of stellar birth -- from the formation of the stellar nurseries to the onset of star formation itself and the final destruction of the nurseries by the newly born stars -- in more detail than is possible with individual observations," says PHANGS team member Francesco Belfiore from INAF-Arcetri in Florence, Italy. "PHANGS is the first time we have been able to assemble such a complete view, taking images sharp enough to see the individual clouds, stars, and nebulae that signify forming stars."

The work carried out by the PHANGS project will be further honed by upcoming telescopes and instruments, such as NASA's James Webb Space Telescope. The data obtained in this way will lay further groundwork for observations with ESO's future Extremely Large Telescope (ELT), which will start operating later this decade and will enable an even more detailed look at the structures of stellar nurseries.

"As amazing as PHANGS is, the resolution of the maps that we produce is just sufficient to identify and separate individual star-forming clouds, but not good enough to see what's happening inside them in detail," pointed out Eva Schinnerer, a research group leader at the Max Planck Institute for Astronomy in Germany and principal investigator of the PHANGS project, under which the new observations were conducted. "New observational efforts by our team and others are pushing the boundary in this direction, so we have decades of exciting discoveries ahead of us."

Byron Bay (16/7/2021) - A new study from WCS and WWF reveals that nearly 20 percent of tropical Intact Forest Landscapes (IFLs) overlap with concessions for extractive industries such as mining, oil and gas. The total area of overlap is 376,449 square miles (975,000 square kilometers), about the size of Egypt. Mining concessions overlap most with tropical IFLs, at 11.33 percent of the total area, while oil and gas concessions overlap with 7.85 percent of the total area.

IFLs are globally important for conserving biodiversity and fighting climate change. These landscapes represent some of the last places on Earth that still contain species assemblages at near-natural levels of abundance. According to 2013 estimates, 549 million acres of intact tropical forests remain. Only 20 percent of tropical forests can be considered "intact," but those areas store some 40 percent of the above-ground carbon found in all tropical forests. At least 35 percent of intact forests are home to, and protected by, politically and economically marginalized Indigenous Peoples.

Despite intact forests' extraordinary value for biodiversity and humanity, they are declining at an alarming rate, with over 7 percent of their total area lost between 2000 and 2013. While the growth of extractive industries is recognized as a threat to IFLs, the extent of this threat has not been well understood prior to this study.

The authors calculated the spatial overlap of extractive concessions - specifically, mining, and oil and gas - with IFL datasets in three tropical regions: South America, Asia-Pacific, and Central Africa. Of these regions, Central Africa's IFLs had the highest overlap with extractive concessions (26 percent). In addition, they identified the specific stages of extractive projects overlapping with IFLs, and found that most leases are in the exploration stage.

Said Dr. Hedley Grantham, lead author of the study. "Many of these extractive projects are still in the early stages. While this could imply a significant future threat to IFLs, it also means there is an opportunity to mitigate potential impacts before they occur."

The authors recommend that companies incorporate avoidance planning in the design phase of extractive projects, taking into account the most important intact forest areas. Ideally, coordination with governments will allow for landscape-scale planning. The authors encourage governments not to allocate extractives concessions within IFLs where possible. With the appropriate planning, future impacts to these crucial ecosystems can be avoided.

The study is published in Frontiers in Forests and Global Change.

WCS is a member of Forests for Life (FFL), a partnership with Re:wild, United Nations Development Programme, World Resources Institute and Rainforest Foundation Norway. Working with national governments, Indigenous Peoples, local communities and others, FFL has two aims - to place ecological integrity at the heart of managing and conserving the world's forests and to halt and reverse declines in integrity across 1 billion hectares of the most intact forests worldwide.

WCS is a proud partner of Trillion Trees, a joint venture between BirdLife International, WCS, and WWF to urgently speed up and scale up the positive power of forests, helping the world protect and restore one trillion trees by 2050.