Culture

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.

Oncotarget published "Occurence of RAS reversion in metastatic colorectal cancer patients treated with bevacizumab" which reported that a disappearance of RAS mutations in the plasma of about 50% of mCRCs treated with bevacizumab-based chemotherapy has been reported.

Using next-generation sequencing and real-time PCR approaches, these authors characterized the primary tumor and paired liver metastases in 28 RAS mutant mCRCs.

RAS mutant alleles are at the same percentage in PT and liver metastases in the control group, while a significant reduction of the level of RAS mutations was detected in 57.1% of cases in group 1 and in 8.3% of cases in group 2. Differences among groups are statistically significant.

Most mCRC patients treated with bevacizumab-containing regimens experience a strong reduction of RAS mutant cells, suggesting bevacizumab as particularly active against RAS mutant cells.

This Oncotarget finding might have potential therapeutic implications, as anti-EGFR could be reconsidered in primarily RAS mutant patients reverted to a wild-type status after bevacizumab exposure.

Dr. Samantha Epistolio from The EOC said, "The overall survival (OS) for patients with metastatic colorectal cancer (mCRC) has markedly improved within the last 2 decades, reaching approximately 30 months."

Thus, it is crucial to perform an extended RAS and BRAF mutation analysis before considering EGFR inhibitors in mCRC patients.

In first-line, data support the use of anti-EGFR MoAbs in patients with left-sided, RAS and BRAF wild-type tumors, whilst bevacizumab is preferred in combination with chemo-doublets or -triplet in RAS/BRAF mutated tumors or RAS/BRAF wild-type right-sided primaries.

More recently, two intriguing studies showed that cetuximab sensitivity might be restored either in RAS/BRAF wild-type mCRC patients who acquired resistance to cetuximab-based therapy in first-line therapy or in those with primarily RAS mutated tumors treated with bevacizumab-containing regimens in second-line.

These studies may lead to the hypothesis that anti-angiogenic agents through action on RAS mutated cells could revert tumors from RAS mutant to RAS wild-type status, which theoretically could lead to the possibility to treat these patients with anti-EGFR MoAbs, otherwise precluded.

To substantiate these findings at tissue level, here they analyzed molecular changes in RAS mutated mCRC patients treated with chemotherapy alone or in combination with bevacizumab, by examining tumor tissue samples before and after the systemic therapy using two independent methodologies, next-generation sequencing and real-time PCR.

The Epistolio Research Team concluded in their Oncotarget Research Output, "this retrospective observational study, strongly suggests the existence of a link between bevacizumab exposure and RAS status changes in mCRC patients. In addition to other reports using liquid biopsies, our findings on tissue samples corroborate the hypothesis that bevacizumab could revert RAS mutant mCRC to a wild-type pattern, conceptually opening to the possibility to treat with anti-EGFR MoAbs mCRC patients otherwise excluded based on initial RAS mutated status."

COLUMBUS, Ohio - Although some people may yearn for sports to be free of political or racial divisiveness, a new study shows how impossible that dream may be.

Researchers found that Americans' views on two hot-button issues in sports were sharply divided by racial, ethnic and political identities. In addition, their opinions on topics unrelated to sports, like the Black Lives Matter (BLM) movement, also were linked to their beliefs about the two sports issues.

The study analyzed opinions on whether college athletes should be paid and whether it is acceptable for pro athletes to protest racial injustice by not standing during the national anthem.

The gap between Americans on those two topics was sometimes stark - there was an 82-percentage-point difference in whether people supported athletes protesting during the national anthem (a low of 13% to a high of 95%) depending on combinations of race, political orientation, voting intentions and beliefs about issues like BLM.

"Sports are and have increasingly become a central part of the culture wars," said Chris Knoester, co-author of the study and associate professor of sociology at The Ohio State University.

"Sports are not a neutral ground."

The study, published online recently in the journal Du Bois Review: Social Science Research on Race, was co-authored by Rachel Allison, associate professor of sociology at Mississippi State University, and David Ridpath, associate professor of sports administration at Ohio University.

While many people believe the political divide concerning sports found in this study is a modern phenomenon, it really is not, Allison said.

"We like to think that sport is all about fun and entertainment, what we like to do or watch outside of our 'real' lives at work or in our families, and so in a sphere somehow outside of politics," she said.

"But the history of sport shows that it has never been outside of the political. Our study shows that continues to be the case."

Data for the study came from the online Taking America's Pulse 2016 Class Survey, designed and run by researchers at Cornell University and the GfK Group. The survey included 1,461 Americans.

Overall, the study found white adults were particularly likely to be opposed to paying college athletes (69%) and protests during the national anthem (73%). Black adults were especially likely to be supportive, with only 29% and 32%, respectively, opposed to these rights for athletes.

Latino adults and other adults of color were generally more supportive of these rights for athletes than white adults, but not as supportive as Black adults.

"In large part, we think these racial and ethnic differences occur because paying college athletes and allowing protests during the national anthem are frequently seen as antiracist actions particularly supporting Black athletes," Knoester said.

Other results in the study support this, particularly those related to Americans' beliefs about two race-related issues outside of sports.

One issue was racial discrimination in education: Participants were asked whether white students, or Black and Latino students, are advantaged in U.S. educational institutions.

The second issue was BLM. Survey participants were asked whether BLM advocates for Black lives mattering more than other lives.

Participants' beliefs on these two issues were strongly linked to their views on paying colleges athletes and athlete protests, the study found. As expected, the impact of these beliefs was compounded by the race and ethnicity of those surveyed.

White adults who were upset about BLM and who believed Black and Latino students were advantaged in education had a 75% predicted probability of being opposed to athletes being paid and an 85% probability of being opposed to athletes protesting.

Meanwhile, Black adults who believed white students were advantaged and who supported BLM had a 28% predicted probability of opposing athlete payments and a 21% probability of opposing athlete protests.

Self-identified conservativism and intentions to vote for Donald Trump for president (the survey was done in the month before the 2016 election) were also strongly linked to opposing pay for college athletes and pro athlete protests. Liberals and those intending to vote for Hillary Clinton were much more supportive of athletes' rights on both issues.

"We found that race, ethnicity and political beliefs all were linked to views about these two sports issues," Ridpath said.

"While political views were important, they did not completely erase the effects of people's race and ethnicity."

For example, it wasn't just conservative white adults who opposed paying college athletes. White adults who identified as middle-of-the-road politically were also generally opposed to paying college athletes (a 66% predicted probability).

Meanwhile, Black adults with moderate political views had only a 35% probability of being opposed. Other people of color with moderate political views were about 50/50 on opposing payment to college athletes.

Combining various identities solidified opposition or support on these two issues, the study found.

For example, a Black adult who was extremely liberal, intended to vote for Clinton, who thought white students were advantaged in education and who didn't think BLM inappropriately valued Black lives had a 13% predicted probability of being opposed to athletes' protests during the national anthem.

Meanwhile, a white adult who was extremely conservative, intended to vote for Trump, thought white students were not advantaged and believed BLM inappropriately valued Black lives had a 95% predicted probability of being opposed to athlete protests.

Since the data in this study was collected, public opinions have appeared to shift somewhat toward the rights of college athletes to get paid and pro athletes to protest, Knoester said. And those shifts have translated into policy changes.

NCAA college athletes have recently been given the opportunity to financially benefit from their name, image and likeness.

And the International Olympic Committee recently gave athletes more scope to protest at the Tokyo games, although significant restrictions remain.

But the controversies are likely to persist, and politics and race will remain a presence in sports, Knoester said.

"Racial and political issues are a part of society, so they will be a part of sports," he said.

DALLAS, July 15, 2021 -- Statement Highlights:

The new scientific statement, "Primary Care of Adult Patients After Stroke," acknowledges the importance of primary care in the system of care for patients with stroke, summarizing the available literature and providing a roadmap for holistic, goal-directed and patient-centered care.

The statement is published today in Stroke, a journal of the American Stroke Association, a division of the American Heart Association.

Primary care professionals provide essential comprehensive and consistent care to patients after a stroke. Most people will seek guidance from their primary care team to reduce their high risk for recurrent stroke, prevent complications and optimize overall well-being. It outlines the need for comprehensive post-stroke management that includes engaging caregivers and family members to support the patient.

Stroke is a complex disease with many causes, consequences and treatments. According to the statement, approximately 800,000 U.S. adults will have a new stroke each year, and 10% will die within 30 days. At the time of their stroke, approximately 5% of patients younger than 55 years of age and 40% over 85 years have moderate disability. By 90 days after a stroke, new stroke-related disability of at least moderate severity develops in 10% of younger adults to 30% of adults over age 65 years. There are about 7 million adults in the U.S. living with stroke.

The first primary care appointment after a stroke should occur soon after discharge from the acute care or rehabilitation hospital, generally within 1-3 weeks. The current average interval to first medical visit for patients discharged home after stroke is 27 days. An earlier post-stroke visit may reduce hospital readmission and address inadvertent gaps in care that may exacerbate the high risk for stroke recurrence that marks the first three months after hospital discharge.

Screening at the first and all subsequent appointments should include assessing new or chronic risks for recurrent stroke such as high blood pressure, high cholesterol, diabetes, atrial fibrillation and blockage in the carotid or other arteries.

Additional screening is also important for complications including anxiety or depression, cognitive impairment, bone fracture and fall risk, osteoporosis, pressure ulcers and post-stroke seizures.

Specialist referrals should be recommended for any of these complications as appropriate.

"In this statement, we affirm in a new way the role of the primary care professional in caring for people with stroke. The core functions of primary care as a specialty include: 1) diagnosis and management of acute symptoms, 2) chronic disease management and 3) disease prevention," said Walter N. Kernan, M.D., chair of the statement writing group and a professor of medicine at Yale University School of Medicine, in New Haven, Conn. "Primary care professionals can ensure consistent and comprehensive care for the full needs of patients, including coordinating any additional care or services patients may need from community services providers or from subspecialty health care providers."

Patients who experience long COVID have reported more than 200 symptoms across 10 organ systems*, in the largest international study of 'long-haulers' to date, led by UCL scientists together with a patient-led research collaborative.

For the study, published in the Lancet's EClinicalMedicine, patient researchers who connected through the Body Politic online COVID-19 support group created a web-based survey designed to characterise the symptom profile and time course in patients with confirmed or suspected long COVID, along with the impact on daily life, work, and return to health.

With responses from 3,762 eligible participants from 56 countries, the researchers identified a total of 203 symptoms in 10 organ systems; of these, 66 symptoms were tracked for seven months. The most common symptoms were fatigue, post-exertional malaise (the worsening of symptoms after physical or mental exertion), and cognitive dysfunction, often called brain fog.

Of the diverse range of symptoms, others included: visual hallucinations, tremors, itchy skin, changes to the menstrual cycle, sexual dysfunction, heart palpitations, bladder control issues, shingles, memory loss, blurred vision, diarrhea, and tinnitus.

The research team, who have all had or continue to have long COVID, are now calling for clinical guidelines on assessing long COVID to be significantly widened beyond currently advised cardiovascular and respiratory function tests to include neuropsychiatric, neurological, and activity intolerance symptoms.

Furthermore, with large numbers of long haulers 'suffering in silence', the authors advocate that a national screening programme, accessible to anyone who thinks they have long COVID, should be undertaken. Given the heterogeneous (diverse) make-up of symptoms that affect multiple organ systems, it is only by detecting the root cause that patients will receive the correct treatment.

Explaining the study, senior author Dr Athena Akrami (neuroscientist at the Sainsbury Wellcome Centre at UCL) said: "While there has been a lot of public discussion around long COVID, there are few systematic studies investigating this population; hence relatively little is known about its range of symptoms, and their progression over time, the severity, and expected clinical course (longevity), its impact on daily functioning, and expected return to baseline health. In this unique approach, we have gone directly to 'long haulers' around the world in order to establish a foundation of evidence for medical investigation, improvement of care, and advocacy for the long COVID population. This is the most comprehensive characterisation of long COVID symptoms, so far."

The survey was open to those aged 18 or over who had experienced symptoms consistent with COVID-19, including those with and without positive SARS-CoV-2 test. It consisted of 257 questions.

In order to characterise long COVID symptoms over an extended duration, analysis of survey data was limited to respondents with illnesses lasting longer than 28 days and whose onset of symptoms occurred between December 2019 and May 2020, allowing analysis of symptoms from week one to month seven.

While the study did not estimate how common long COVID is overall, other studies have estimated that one in seven people have some symptoms 12 weeks after a positive test result (from the Office for National Statistics), or almost 30% of people 12 weeks after symptomatic disease (from Imperial College London's REACT study).

Survey summary

In this long COVID cohort, the probability of symptoms lasting beyond 35 weeks (eight months) was 91.8%. Of the 3,762 respondents, 3,608 (96%) reported symptoms beyond 90 days, 2,454 (65%) experienced symptoms for at least 180 days (six months) and only 233 had recovered.

In those who recovered in less than 90 days, the average number of symptoms (11.4 out of 66 symptoms that were measured over time) peaked at week two, and for those who did not recover in 90 days, the average number of symptoms (17.2) peaked at month two. Respondents with symptoms over six months experienced an average of 13.8 symptoms in month seven. During their illness, participants experienced an average of 55.9 symptoms (out of the longer list of 203 measured in the study), across an average of 9.1 organ systems.

89.1% of participants experienced relapses, with exercise, physical or mental activity, and stress as the main triggers. 45.2% reported requiring a reduced work schedule compared to pre-illness and 22.3% were not working at all at the time of the survey.

Dr Akrami said: "For the first time this study shines a light on the vast spectrum of symptoms, particularly neurological, prevalent and persistent in patients with long COVID.

"Memory and cognitive dysfunction, experienced by over 85% of respondents, were the most pervasive and persisting neurologic symptoms, equally common across all ages, and with substantial impact on work.

"Headaches, insomnia, vertigo, neuralgia, neuropsychiatric changes, tremors, sensitivity to noise and light, hallucinations (olfactory and other), tinnitus, and other sensorimotor symptoms were also all common, and may point to larger neurological issues involving both the central and peripheral nervous system.

"Along with the well-documented respiratory and cardiovascular symptoms, there is now a clear need to widen medical guidelines to assess a far wider range of symptoms when diagnosing long COVID. Furthermore, there are likely to be tens of thousands of long COVID patients suffering in silence, unsure that their symptoms are connected to COVID-19. Building on the network of long COVID clinics, which take GP referrals, we now believe a national programme could be rolled out into communities able to screen, diagnose and treat all those suspected of have long COVID symptoms."

The research team's future work will focus on emerging topics in long COVID: mental health outcomes, diagnostic and antibody testing, symptom clustering, and socioeconomic impact from the illness.

Study limitations

There are several limitations to this study. First, the retrospective nature of the study exposes the possibility of recall bias. Second, as the survey was distributed in online support groups, there exists a sampling bias toward long COVID patients who joined support groups and were active participants of the groups at the time the survey was published. Additionally, despite eight translations and inclusive outreach efforts, the demographics were strongly skewed towards English speaking (91.9%), white (85.3%) respondents.

Symptom prevalence - summary

Top three symptoms: Fatigue 98.3%, post-exertional malaise (PEM) 89.0%, and brain fog and cognitive dysfunction in 85.1% (3,203) of respondents.

The top three most debilitating symptoms listed by patients were: fatigue (2,652 patients), breathing issues (2,242), and cognitive dysfunction (1,274).

Symptoms remaining at six months

A total of 2,454 (65.2%) respondents were experiencing symptoms for at least six months. Over 50% experienced the following symptoms: fatigue (80%) post-exertional malaise (73.3%), cognitive dysfunction (58.4%), sensorimotor symptoms (55.7%), headaches (53.6%), and memory issues (51%). In addition, between 30%-50% of respondents were experiencing the following symptoms after six months of symptoms: insomnia, heart palpitations, muscle aches, shortness of breath, dizziness and balance issues, sleep and language issues, joint pain, tachycardia, and other sleep issues.

A small regulatory RNA found in many problematic bacteria, including Escherichia coli, appears to be responsible for managing the response of these bacteria to environmental stresses. Professor Charles Dozois from Institut national de la recherche scientifique (INRS) and doctoral student Hicham Bessaiah see a promising avenue for more effective treatment of antibiotic-resistant bacteria. Their results have been published in the journal PLOS Pathogens.

In conducting their work, the researchers and their team observed that the elimination of this regulatory RNA sequence had an effect on urinary tract infections related to E. coli. These infections are among the world's most common, especially in women, but they are sometimes hard to treat due to antibiotic resistance.

E. coli is normally found in the intestinal flora, but when it migrates to the bladder, the conditions there are completely different. The bacteria have to withstand the environmental stressors in order to cause a bladder infection. "Without the regulatory RNA, the bacteria is more sensitive to changes in the environment and loses its infectious capacity," explained the doctoral student.

Inhibiting the RNA sequence

The idea is to block the RNA and make the bacteria less infectious, especially in the case of chronic infection, which can lead to increased resistance to treatment. If the bacteria are less resistant to stress, it will be more vulnerable to the host's immune response. Regulation of the systems that make it virulent will also be disrupted.

"People with recurrent urinary tract infections take antibiotics regularly. This leads to resistance and limits treatment options, which is why it's important to find alternatives," explained Professor Dozois.

The relationship between virulence and stress isn't unique to urinary tract infections. The regulatory RNA sequence studied by the researchers is also found in a number of other major pathogenic bacteria. Given that the RNA seems to impact multiple functions, the research group is working to better understand the mechanisms of regulation before pursuing additional research on antibiotic-resistant strains of bacteria.

Combined perceptions of the risk and availability of cannabis influence the risk of cannabis use more than perceived risk and perceived availability alone, according to a new study at Columbia University Mailman School of Public Health. Researchers observed that those who perceived cannabis as low-risk and available were more likely to report using the drug in the past year and almost daily compared to those individuals who perceived cannabis as high-risk and unavailable. This is the first study to consider the joint effects of perceived risk and perceived availability. The results are published in the journal Drug and Alcohol Dependence.

"Our study described the evolution of joint perceptions of cannabis risk and availability from 2002-2018 and estimated the relationship between combined perceptions and past-year cannabis use, frequent use, and cannabis use disorder," said Natalie Levy, MPH, doctoral student in the Department of Epidemiology at Columbia Mailman School, and first author. "Studying perceived risk and availability in conjunction revealed more nuanced patterns than considering each perception in isolation.."

Using data on 949,285 participants from the National Surveys on Drug Use and Health from 2002-2018, researchers observed that the prevalence of perceiving cannabis use as low-risk doubled over this period while the prevalence of perceiving cannabis as available increased only marginally. When looking at joint categories of perceived risk and perceived availability, they found that prevalence of perceiving cannabis as both low-risk and available increased, from 17 percent in 2002 to 36 percent in 2018 while the proportion of the population perceiving cannabis as high-risk and available or high-risk and unavailable declined. By 2018, a larger proportion of the population perceived marijuana as low-risk and available (36 percent) than both high-risk and available and high-risk and unavailable, at 26 percent and 27 percent, respectively.

Individuals who perceived cannabis as low-risk were six times more likely to have used cannabis in the past-year than individuals who perceived the drug as high-risk. Similarly, individuals who perceived cannabis as available were five times more likely to have used cannabis in the past year than individuals who perceived it as unavailable. However, individuals who perceived marijuana as both low-risk and available were 22 times more likely to have used the drug in the past year than those who perceived cannabis as high-risk and unavailable.

In 2018, most individuals who reported no past-year cannabis use perceived cannabis as high-risk, whether or not they distinguished between its availability or non-availability. In contrast, the majority of individuals who used cannabis in the past year perceived the drug as low-risk and available and this perception rose to even higher levels among those reporting frequent use.

Cannabis perceptions also differed by gender. Overall, a larger proportion of males viewed cannabis as lower risk and more available compared with females, but patterns differed by age. "We found minimal differences in perceptions by gender in the 12-17-year age group while among all those 18 years of age and older, the prevalence of perceiving cannabis as low-risk and available was higher for males than females; perceiving cannabis as high-risk and unavailable was more common among females in every year," noted Levy.

"Our results provide an important starting point for exploring specific hypotheses regarding the effects of perceptions on individual cannabis outcomes and highlight the importance of exploring perceived risk and availability together," said Silvia Martins, MD, PhD, Columbia Mailman School associate professor of Epidemiology, director of the Substance Use Epidemiology Unit of the Department of Epidemiology, and senior author. "For example, our findings suggest that prevention efforts that focus only on the risks of cannabis use may be less effective among individuals who perceive cannabis as easily available.

"Trends in perceptions - especially among younger age groups -- may also identify priority groups for intervention," observed Levy. "Further understanding of these relationships is particularly important in light of rapidly changing cannabis policies, a contextual factor that may influence perceptions of both risk and availability of cannabis and subsequent use."

What The Study Did: In this observational study using data from the Veterans Health Administration for 2,344 U.S. veterans hospitalized with COVID-19, remdesivir treatment was associated with prolonged hospitalization but wasn't associated with improved survival.

Authors: Michael E. Ohl, M.D., M.S.P.H., of the Carver College of Medicine at the University of Iowa in Iowa City, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2021.14741)

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

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