Culture

Using the supersharp radio "vision" of the National Science Foundation's continent-wide Very Long Baseline Array (VLBA), astronomers have discovered a Saturn-sized planet closely orbiting a small, cool star 35 light-years from Earth. This is the first discovery of an extrasolar planet with a radio telescope using a technique that requires extremely precise measurements of a star's position in the sky, and only the second planet discovery for that technique and for radio telescopes.

The technique has long been known, but has proven difficult to use. It involves tracking the star's actual motion in space, then detecting a minuscule "wobble" in that motion caused by the gravitational effect of the planet. The star and the planet orbit a location that represents the center of mass for both combined. The planet is revealed indirectly if that location, called the barycenter, is far enough from the star's center to cause a wobble detectable by a telescope.

This technique, called the astrometric technique, is expected to be particularly good for detecting Jupiter-like planets in orbits distant from the star. This is because when a massive planet orbits a star, the wobble produced in the star increases with a larger separation between the planet and the star, and at a given distance from the star, the more massive the planet, the larger the wobble produced.

Starting in June of 2018 and continuing for a year and a half, the astronomers tracked a star called TVLM 513-46546, a cool dwarf with less than a tenth the mass of our Sun. In addition, they used data from nine previous VLBA observations of the star between March 2010 and August 2011.

Extensive analysis of the data from those time periods revealed a telltale wobble in the star's motion indicating the presence of a planet comparable in mass to Saturn, orbiting the star once every 221 days. This planet is closer to the star than Mercury is to the Sun.

Small, cool stars like TVLM 513-46546 are the most numerous stellar type in our Milky Way Galaxy, and many of them have been found to have smaller planets, comparable to Earth and Mars.

"Giant planets, like Jupiter and Saturn, are expected to be rare around small stars like this one, and the astrometric technique is best at finding Jupiter-like planets in wide orbits, so we were surprised to find a lower mass, Saturn-like planet in a relatively compact orbit. We expected to find a more massive planet, similar to Jupiter, in a wider orbit," said Salvador Curiel, of the National Autonomous University of Mexico. "Detecting the orbital motions of this sub-Jupiter mass planetary companion in such a compact orbit was a great challenge," he added.

More than 4,200 planets have been discovered orbiting stars other than the Sun, but the planet around TVLM 513-46546 is only the second to be found using the astrometric technique. Another, very successful method, called the radial velocity technique, also relies on the gravitational effect of the planet upon the star. That technique detects the slight acceleration of the star, either toward or away from Earth, caused by the star's motion around the barycenter.

"Our method complements the radial velocity method which is more sensitive to planets orbiting in close orbits, while ours is more sensitive to massive planets in orbits further away from the star," said Gisela Ortiz-Leon of the Max Planck Institute for Radio Astronomy in Germany. "Indeed, these other techniques have found only a few planets with characteristics such as planet mass, orbital size, and host star mass, similar to the planet we found. We believe that the VLBA, and the astrometry technique in general, could reveal many more similar planets."

A third technique, called the transit method, also very successful, detects the slight dimming of the star's light when a planet passes in front of it, as seen from Earth.

The astrometric method has been successful for detecting nearby binary star systems, and was recognized as early as the 19th Century as a potential means of discovering extrasolar planets. Over the years, a number of such discoveries were announced, then failed to survive further scrutiny. The difficulty has been that the stellar wobble produced by a planet is so small when seen from Earth that it requires extraordinary precision in the positional measurements.

"The VLBA, with antennas separated by as much as 5,000 miles, provided us with the great resolving power and extremely high precision needed for this discovery," said Amy Mioduszewski, of the National Radio Astronomy Observatory. "In addition, improvements that have been made to the VLBA's sensitivity gave us the data quality that made it possible to do this work now," she added.

Researchers at Yale University School of Medicine have developed a new mouse model to study SARS-CoV-2 infection and disease and to accelerate testing of novel treatments and vaccines against the novel coronavirus. The study, published today in the Journal of Experimental Medicine (JEM), also suggests that, rather than protecting the lungs, key antiviral signaling proteins may actually cause much of the tissue damage associated with COVID-19.

Animal models that recapitulate SARS-CoV-2 infection and disease are urgently needed to help researchers understand the virus, develop therapies, and identify potential vaccine candidates. Mice are the most widely used laboratory animals, but they cannot be infected with SARS-CoV-2 because the virus is unable to employ the mouse version of ACE2, the cell surface receptor protein that the virus uses to enter human cells.

SARS-CoV-2 can infect mice genetically engineered to produce the human version of ACE2. However, the availability of these animals is low and limited to a single mouse strain, preventing researchers from investigating how the virus impacts mice that are immunocompromised or obese, conditions that significantly increase the fatality rate in humans.

In the new study, a team of researchers led by Akiko Iwasaki at Yale University School of Medicine developed an alternative mouse model of SARS-CoV-2 infection in which the animals are first infected with a different, harmless virus carrying the human ACE2 gene. Mice infected with this virus produce the human ACE2 protein and can then be infected with SARS-CoV-2. Iwasaki and colleagues found that SARS-CoV-2 can replicate in these mice and induce an inflammatory response similar to that observed in COVID-19 patients, where a wide variety of immune cells are activated and recruited to the lungs. "In addition, the infected mice also rapidly develop neutralizing antibodies against SARS-CoV-2," Iwasaki says.

The body's response to viral infection often depends on signaling molecules called type I interferons that can activate immune cells and induce the production of antiviral proteins and antibodies. But too much type I interferon, especially when the production is delayed, can lead to excessive inflammation and tissue damage. Indeed, while type I interferon signaling protects against the related coronavirus MERS-CoV, it causes lung damage in response to SARS-CoV-1, the virus responsible for a previous coronavirus outbreak in 2002-2003.

The role of type I interferons in COVID-19 is currently unclear. Iwasaki and colleagues found that, similar to COVID-19 patients, mice infected with SARS-CoV-2 activate a large number of genes associated with type I interferon signaling. The researchers then used their model system to infect mice lacking key components of the type I interferon pathway and found that they were no worse at controlling SARS-CoV-2 infection. However, these animals recruited fewer inflammatory immune cells into their lungs. "These results indicate that type I interferons do not restrict SARS-CoV-2 replication, but they may play a pathological role in COVID-19 respiratory inflammation," Iwasaki says. "This is especially concerning because type I interferons are currently being used as a treatment for COVID-19. The early timing of the IFN treatment will be important for it to provide protection and benefit."

Iwasaki adds, "The mouse model we developed offers a broadly available and highly adaptable animal model to understand critical aspects of SARS-CoV-2 viral infection, replication, pathogenesis, and protection using authentic patient-derived virus. The model provides a vital platform for testing prophylactic and therapeutic strategies to combat COVID-19."

Biomedical engineers at Duke University have shown that different strains of the same bacterial pathogen can be distinguished by a machine learning analysis of their growth dynamics alone, which can then also accurately predict other traits such as resistance to antibiotics. The demonstration could point to methods for identifying diseases and predicting their behaviors that are faster, simpler, less expensive and more accurate than current standard techniques.

The results appear online on August 3 in the Proceedings of the National Academy of Sciences.

For most of the history of microbiology, bacteria identification has relied on growing cultures and analyzing the physical traits and behaviors of the resulting bacterial colony. It wasn't until recently that scientists could simply run a genetic test.

Genetic sequencing, however, isn't universally available and can often take a long time. And even with the ability to sequence entire genomes, it can be difficult to tie specific genetic variations to different behaviors in the real world.

For example, even though researchers know the genetic mutations that help shield/protect bacteria from beta-lactam antibiotics--the most commonly used antibiotic in the world--sometimes the DNA isn't the whole story. While a single resistant bacteria usually can't survive a dose of antibiotics on its own, large populations often can.

Lingchong You, professor of biomedical engineering at Duke, and his graduate student, Carolyn Zhang, wondered if a new twist on older methods might work better. Maybe they could amplify one specific physical characteristic and use it to not only identify the pathogen, but to make an educated guess about other traits such as antibiotic resistance.

"We thought that the slight variance in the genes between strains of bacteria might have a subtle effect on their metabolism," You said. "But because bacterial growth is exponential, that subtle effect could be amplified enough for us to take advantage of it. To me, that notion is somewhat intuitive, but I was surprised at how well it actually worked."

How quickly a bacterial culture grows in a laboratory depends on the richness of the media it is growing in and its chemical environment. But as the population grows, the culture consumes nutrients and produces chemical byproducts. Even if different strains start with the exact same environmental conditions, subtle differences in how they grow and influence their surroundings accumulate over time.

In the study, You and Zhang took more than 200 strains of bacterial pathogens, most of which were variations of E. coli, put them into identical growth environments, and carefully measured their population density as it increased. Because of their slight genetic differences, the cultures grew in fits and starts, each possessing a unique temporal fluctuation pattern. The researchers then fed the growth dynamics data into a machine learning program, which taught itself to identify and match the growth profiles to the different strains.

To their surprise, it worked really well.

"Using growth data from only one initial condition, the model was able to identify a particular strain with more than 92 percent accuracy," You said. "And when we used four different starting environments instead of one, that accuracy rose to about 98 percent."

Taking this idea one step further, You and Zhang then looked to see if they could use growth dynamic profiles to predict another phenotype--antibiotic resistance.

The researchers once again loaded a machine learning program with the growth dynamic profiles from all but one of the various strains, along with data about their resilience to four different antibiotics. They then tested to see if the resulting model could predict the final strain's antibiotic resistances from its growth profile. To bulk up their dataset, they repeated this process for all of the other strains.

The results showed that the growth dynamic profile alone could successfully predict a strain's resistance to antibiotics 60 to 75 percent of the time.

"This is actually on par or better than some of the current techniques in the literature, including many that use genetic sequencing data," said You. "And this was just a proof of principle. We believe that with higher-resolution data of the growth dynamics, we could do an even better job in the long term."

The researchers also looked to see if the strains exhibiting similar growth curves also had similar genetic profiles. As it turns out, the two are completely uncorrelated, demonstrating once again how difficult it can be to map cellular traits and behaviors to specific stretches of DNA.

Moving forward, You plans to optimize the growth curve procedure to reduce the time it takes to identify a strain from 2 to 3 days to perhaps 12 hours. He's also planning on using high-definition cameras to see if mapping how bacterial colonies grow in space in a Petri dish can help make the process even more accurate.

From lowering your risk of obesity and cardiovascular disease to improving your concentration and overall daily performance, sleep has been proven to play a critical role in our health. In a new study, researchers at University of California San Diego School of Medicine report that sleep may also help people to learn continuously through their lifetime.

Writing in the August 4, 2020 online issue of eLife, researchers used computational models capable of simulating different brain states, such as sleep and awake, to examine how sleep consolidates newly encoded memories and prevents damage to old memories.

"The brain is very busy when we sleep, repeating what we have learned during the day. Sleep helps reorganize memories and presents them in the most efficient way. Our findings suggest that memories are dynamic, not static. In other words, memories, even old memories, are not final. Sleep constantly updates them," said Maksim Bazhenov, PhD, lead author of the study and professor of medicine at UC San Diego. "We predict that during the sleep cycle, both old and new memories are spontaneously replayed, which prevents forgetting and increases recall performance."

Bazhenov said that memory replay during sleep plays a protective role against forgetting by allowing the same populations of neurons to store multiple interfering memories. "We learn many new things on a daily basis and those memories compete with old memories. To accommodate all memories, we need sleep."

For example, imagine learning how to navigate to a parking lot by going left at one stop sign and right at one traffic light. The next day, you have to learn how to get to a different parking lot using different directions. Bazhenov said sleep consolidates those memories to allow recollection of both.

"When you play tennis, you have a certain muscle memory. If you then learn how to play golf, you have to learn how to move the same muscles in a different way. Sleep makes sure that learning golf does not erase how to play tennis and makes it possible for different memories to coexist in the brain," said Bazhenov.

The authors suggest that the restorative value of sleep may be what is lacking in current state-of-the-art computer systems that power self-driving cars and recognize images with performances that far exceed humans. However, these artificial intelligence systems lack the ability to learn continuously and will forget old knowledge when new information is learned. "We may need to add a sleep-like state to computer and robotic systems to prevent forgetting after new learning and to make them able to learn continuously," said Bazhenov.

Bazhenov said the study results could lead to developing new stimulation techniques during sleep to improve memory and learning. This may be particularly important in older adults or persons suffering from learning disabilities.

"While sleep is certainly involved in many important brain and body functions, it may be critical for making possible what we call human intelligence -- the ability to learn continuously from experience, to create new knowledge and to adapt as the world changes around us," said Bazhenov.

FAIRFAX, Va. -- A new study presented today at the Society of NeuroInterventional Surgery's (SNIS) 17th Annual Meeting serves as the first prospective validation of the Rapid Arterial Occlusion Evaluation (RACE) scale in accurately identifying a severe clot stroke called a Large Vessel Occlusion (LVO) by U.S.-based EMS personnel in a pre-hospital setting.

The study, Prospective, Multi-centered, EMS-administered, Pre-hospital Validation Study of the Rapid Arterial Occlusion Evaluation (RACE) Scale for Detecting Large Vessel Occlusion Stroke in the United States Compared to the Original RACE Validation Study from Spain: A Subanalysis of the PREDICT Study, evaluated 232 adult patients suspected of having a stroke by U.S.-based EMS who were transported to a participating comprehensive stroke center. All patients had the RACE scale administered prospectively and their results recorded in a secure web-based database.

The RACE scale was previously validated by EMS in Spain for accurately identifying this type of life-threatening condition and has been widely adopted in the United States. The health care infrastructure and EMS systems differ significantly between the two countries; the validity of the results from the Spanish study when applied to U.S. systems was untested prior to this study.

"Standardizing triage protocols is critical for improving stroke systems of care and improving outcomes for patients," said Dr. Robert F. James, senior author of the study and Professor and Vice Chair, Department of Neurosurgery, Indiana University School of Medicine. "The findings of this study advance the validity of the RACE scale, which will help EMS determine stroke severity in the field and ensure that patients receive proper care as soon as possible."

Rice is the most widely consumed staple food source for a large part of the world's population. It has now been confirmed that rice can contribute to prolonged low-level arsenic exposure leading to thousands of avoidable premature deaths per year.

Arsenic is well known acute poison, but it can also contribute to health problems, including cancers and cardiovascular diseases, if consumed at even relatively low concentrations over an extended period of time.

Compared to other staple foods, rice tends to concentrate inorganic arsenic. Across the globe, over three billion people consume rice as their major staple and the inorganic arsenic in that rice has been estimated by some to give rise to over 50,000 avoidable premature deaths per year.

A collaborating group of cross-Manchester researchers from The University of Manchester and The University of Salford have published new research exploring the relationship, in England and Wales, between the consumption of rice and cardiovascular diseases caused by arsenic exposure.

Their findings, published in the journal Science of the Total Environment, shows that - once corrected for the major factors known to contribute to cardiovascular disease (for example obesity, smoking, age, lack of income, lack of education) there is a significant association between elevated cardiovascular mortality, recorded at a local authority level, and the consumption of inorganic arsenic bearing rice.

Professor David Polya from The University of Manchester said: "The type of study undertaken, an ecological study, has many limitations, but is a relatively inexpensive way of determining if there is plausible link between increased consumption of inorganic arsenic bearing rice and increased risk of cardiovascular disease.

Professor Polya from The University of Manchester said "The study suggests that the highest 25 % of rice consumers in England and Wales may plausibly be at greater risks of cardiovascular mortality due to inorganic arsenic exposure compared to the lowest 25 % of rice consumers.

"The modelled increased risk is around 6 % (with a confidence interval for this figure of 2 % to 11 %). The increased risk modelled might also reflect in part a combination of the susceptibility, behaviours and treatment of those communities in England and Wales with relatively high rice diets."

While more robust types of study are required to confirm the result, given many of the beneficial effects otherwise of eating rice due to its high fibre content, the research team suggest that rather than avoid eating rice, people could consume rice varieties, such as basmati, and different types like polished rice (rather whole grain rice) which are known to typically have lower inorganic arsenic contents. Other positive behaviours would be to eat a balanced variety of staples, not just predominately rice.

Irvine, CA - August 4, 2020 - Researchers from the newly-established Center for Neural Circuit Mapping at the University of California, Irvine School of Medicine evaluate the properties of anterograde and retrograde viral tracers, comparing their strengths and limitations for use in neural circuit mapping. Results were published today as a primer in Neuron.

The article provides a comprehensive comparison of anterograde and retrograde viral and non-viral tracers for neural circuit analysis and describe neural circuit tracing history and background. It also examines the specific viruses used for neuroscience research, and provides essential information to guide other researchers on their choice of viral tracers.

Viral tracers are important tools for neuroanatomical mapping and genetic payload delivery. Genetically modified viruses allow for cell-type specific targeting, and overcome many limitations of non-viral tracers.

"A central goal of modern neuroscience research is to understand the cell-type specific connections between different regions of the brain and the detailed circuit organization within them," said lead author Xiangmin Xu, PhD, professor of anatomy and neurobiology, and director of the new Center for Neural Circuit Mapping. "Our primer evaluates currently applied anterograde and retrograde viral tracers and provides practical guidance on experimental uses, along with key technical and conceptual considerations for developing new safer and more effective anterograde trans-synaptic viral vectors for neural circuit analysis in multiple species."

Naturally occurring viruses have been used for neural circuit tracing for decades by exploiting the natural properties of viral propagation and transmission. Genetic modifications of such viruses have led to many improvements for neuroscience applications. In addition to anatomical mapping, genetically modified viral tracers have greatly facilitated functional studies of cell-type specific and circuit-specific neural networks in the brain.

Xu, along with other UCI School of Medicine investigators involved in the primer, including Rozanne Sandri-Goldin, PhD, chancellor's professor and chair of microbiology and molecular genetics, Todd Holmes, PhD, professor and vice chair of physiology and biophysics, and Bert Semler, PhD, distinguished professor of microbiology and molecular genetics and director for the UCI Center for Virus Research, recently launched the Center for Neural Circuit Mapping (CNCM) at the UCI School of Medicine. The CNCM focuses on neural circuit studies and new viral-genetic technology development. A critical component of the new center is the creation of a viral production facility to disseminate new molecular tools to the worldwide neuroscience community.

"Using new genetic-viral tools, our main goal with the CNCM is to advance the study of neural circuits using animal models to define mechanisms and pathways that underlie neurodevelopmental, neuropsychiatric and neurodegenerative disorders," said Xu. "Understanding the brain's neural circuitry is critical for successful translational progress in better treating these diseases."

Genes that are thought to play a role in how the SARS-CoV-2 virus infects our cells have been found to be active in embryos as early as during the second week of pregnancy, say scientists at the University of Cambridge and the California Institute of Technology (Caltech). The researchers say this could mean embryos are susceptible to COVID-19 if the mother gets sick, potentially affecting the chances of a successful pregnancy.

While initially recognised as causing respiratory disease, the SARS-CoV-2 virus, which causes COVID-19 disease, also affects many other organs. Advanced age and obesity are risk factors for complications but questions concerning the potential effects on fetal health and successful pregnancy for those infected with SARS-CoV-2 remain largely unanswered.

To examine the risks, a team of researchers used technology developed by Professor Magdalena Zernicka-Goetz at the University of Cambridge to culture human embryos through the stage they normally implant in the body of the mother to look at the activity - or 'expression' - of key genes in the embryo. Their findings are published today in the Royal Society's journal Open Biology.

On the surface of the SARS-CoV-2 virus are large 'spike' proteins. Spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. The virus manipulates the host cell's machinery to allow the virus to replicate and spread.

The researchers found patterns of expression of the genes ACE2, which provide the genetic code for the SARS-CoV-2 receptor, and TMPRSS2, which provides the code for a molecule that cleaves both the viral spike protein and the ACE2 receptor, allowing infection to occur. These genes were expressed during key stages of the embryo's development, and in parts of the embryo that go on to develop into tissues that interact with the maternal blood supply for nutrient exchange. Gene expression requires that the DNA code is first copied into an RNA message, which then directs the synthesis of the encoded protein. The study reports the finding of the RNA messengers.

Professor Magdalena Zernicka-Goetz, who holds positions at both the University of Cambridge and Caltech, said: "Our work suggests that the human embryo could be susceptible to COVID-19 as early as the second week of pregnancy if the mother gets sick.

"To know whether this really could happen, it now becomes very important to know whether the ACE2 and TMPRSS2 proteins are made and become correctly positioned at cell surfaces. If these next steps are also taking place, it is possible that the virus could be transmitted from the mother and infect the embryo's cells."

Professor David Glover, also from Cambridge and Caltech, added: "Genes encoding proteins that make cells susceptible to infection by this novel coronavirus become expressed very early on in the embryo's development. This is an important stage when the embryo attaches to the mother's womb and undertakes a major remodelling of all of its tissues and for the first time starts to grow. COVID-19 could affect the ability of the embryo to properly implant into the womb or could have implications for future fetal health."

The team say that further research is required using stem cell models and in non-human primates to better understand the risk. However, they say their findings emphasise the importance for women planning for a family to try to reduce their risk of infection.

"We don't want women to be unduly worried by these findings, but they do reinforce the importance of doing everything they can to minimise their risk of infection," said Bailey Weatherbee, a PhD student at the University of Cambridge.

LA JOLLA--(August 4, 2020) A drug candidate developed by Salk researchers, and previously shown to slow aging in brain cells, successfully reversed memory loss in a mouse model of inherited Alzheimer's disease. The new research, published online in July 2020 in the journal Redox Biology, also revealed that the drug, CMS121, works by changing how brain cells metabolize fatty molecules known as lipids.

"This was a more rigorous test of how well this compound would work in a therapeutic setting than our previous studies on it," says Pamela Maher, a senior staff scientist in the lab of Salk Professor David Schubert and the senior author of the new paper. "Based on the success of this study, we're now beginning to pursue clinical trials."

Over the last few decades, Maher has studied how a chemical called fisetin, found in fruits and vegetables, can improve memory and even prevent Alzheimer's-like disease in mice. More recently, the team synthesized different variants of fisetin and found that one, called CMS121, was especially effective at, improving the animals' memory, and slowing the degeneration of brain cells.

In the new study, Maher and colleagues tested the effect of CMS121 on mice that develop the equivalent of Alzheimer's disease. Maher's team gave a subset of the mice daily doses of CMS121 beginning at 9 months old--the equivalent of middle age in people, and after the mice have already begun to show learning and memory problems. The timing of the lab's treatment is akin to how a patient who visits the doctor for cognitive problems might be treated, the researchers say.

After three months on CMS121, at 12 months old, the mice--both treated and untreated--were given a battery of memory and behavior tests. In both types of tests, mice with Alzheimer's-like disease that had received the drug performed equally well as healthy control animals, while untreated mice with the disease performed more poorly.

To better understand the impact of CMS121, the team compared the levels of different molecules within the brains of the three groups of mice. They discovered that when it came to levels of lipids--fatty molecules that play key roles in cells throughout the body--mice with the disease had several differences compared to both healthy mice and those treated with CMS121. In particular, the researchers pinpointed differences in something known as lipid peroxidation--the degradation of lipids that produces free radical molecules that can go on to cause cell damage. Mice with Alzheimer's-like disease had higher levels of lipid peroxidation than either healthy mice or those treated with CMS121.

"That not only confirmed that lipid peroxidation is altered in Alzheimer's, but that this drug is actually normalizing those changes," says Salk postdoctoral fellow Gamze Ates, first author of the new paper.

The researchers went on to show that CMS121 lowered levels of a lipid-producing molecule called fatty acid synthetase (FASN), which, in turn, lowered levels of lipid peroxidation. When the group analyzed levels of FASN in brain samples from human patients who had died of Alzheimer's, they found that the patients had higher amounts of the FASN protein than similarly aged controls who were cognitively healthy, which suggests FASN could be a drug target for treating Alzheimer's disease.

While the group is pursuing clinical trials, they hope other researchers will explore additional compounds that may treat Alzheimer's by targeting FASN and lipid peroxidation.

"There has been a big struggle in the field right now to find targets to go after," says Maher. "So, identifying a new target in an unbiased way like this is really exciting and opens lots of doors."

NASA's Aqua satellite took images of the Apple Fire as it continued to spread north across the head of the Mill Creek Canyon, and east into the San Gorgonio Wilderness near San Bernardino, Calif. on Aug. 03, 2020. The fire is now burning into more wilderness (where vegetation is sparse) than wooded area limiting the intensity of the fire due to a lack of fuel. Continued fire activity is due to the record low moisture content of the vegetation fuel, high temperatures and low humidity throughout the area. The fire has grown to 26,850 acres and is 15% contained. The smoke from the fire has traveled almost 400 miles south affecting air quality. The smoke from the Apple fire is also commingling with the smoke from the Cassadore Springs and the Blue River 2 fires in Arizona. The cause of the fire which had been under investigation is now listed as "human caused." Several areas around the fire have been evacuated. Contact local officials for more details or go to the Inciweb page for the fire.

NASA's Aqua satellite was able to provide two images of the fire. On the left side of the slider is the true color image of the Apple fire and the right side of the slider shows the corrected reflectance bands that help distinguish the areas of the ground that have been burned. This combination of bands is most useful for distinguishing burn scars from naturally low vegetation or bare soil and enhancing floods. It can also be used to distinguish snow and ice from clouds.

Weather concerns continue in the area. Warm and dry conditions are ongoing with winds gusting to 20 mph. Mid-week the conditions will persist with slightly cooler temperatures and a slight increase in relative humidity.

WEST LAFAYETTE, Ind. -- About 50% of people who take the drug infliximab for inflammatory bowel diseases, such as Crohn's disease, end up becoming resistant or unresponsive to it.

Scientists might be able to catch problems like this one earlier in the drug development process, when drugs move from testing in animals to clinical trials, with a new computational model developed by researchers from Purdue University and Massachusetts Institute of Technology.

The researchers call the model "TransComp-R." In a study published in Science Signaling, they used the model to identify an overlooked biological mechanism possibly responsible for a patient's resistance to infliximab.

Such a mechanism is hard to catch in preclinical testing of new drugs because animal models of human diseases may have different biological processes driving disease or a response to therapy. This makes it difficult to translate observations from animal experiments to human biological contexts.

"This model could help better determine which drugs should move from animal testing to humans," said Doug Brubaker, a Purdue assistant professor of biomedical engineering, who led the development and testing of this model as a postdoctoral associate at MIT.

"If there is a reason why the drug would fail, such as a resistance mechanism that wasn't obvious from the animal studies, then this model would also potentially detect that and help guide how a clinical trial should be set up," he said.

TransComp-R consolidates thousands of measurements from an animal model to just a few data coordinates for comparing with humans. The dwindled-down data explain the most relevant sources of biological differences between the animal model and humans.

From there, scientists could train other sets of models to predict a human's response to therapy in terms of those data coordinates from an animal model.

For infliximab, data from a mouse model and human hadn't matched up because they were different types of biological measurements. The mouse model data came in the form of intestinal proteins, whereas data from patients were only available in the form of expressed genes, a discrepancy TransComp-R was able to address.

TransComp-R helped Brubaker's team to find links in the data pointing toward a resistance mechanism in humans.

The team collaborated with researchers from Vanderbilt University to test the predicted mechanism in intestinal biopsies from a Crohn's disease patient and then with experiments in human immune cells.

The researchers used single-cell sequencing of a sample from an infliximab-resistant Crohn's disease patient to identify the cell types expressing the genes related to the resistance mechanism predicted by TransComp-R.

They then treated immune cells with infliximab and an inhibitor of the receptor identified by the model to be part of the resistance mechanism. The experiment showed that inhibiting the receptor enhanced the anti-inflammatory effects of infliximab, enabling the drug to be more effective because it could better control inflammation.

With additional testing to figure out a way to more precisely measure the markers of this resistance mechanism, doctors could use information about the drug response to determine if a patient needs a different course of treatment.

Since this study, Brubaker has been working with his former research group at MIT to apply the mathematical framework behind TransComp-R to identify mouse models predictive of Alzheimer's disease biology and immune signatures of vaccine effectiveness in animal studies of COVID-19 vaccine candidates.

"The modeling framework itself can be repurposed to different kinds of animals, different disease areas and different questions," Brubaker said. "Figuring out when what we see in animals doesn't track with what's happening in humans could save a lot of time, cost and effort in the drug development process overall."

Philadelphia, August 4, 2020 - As school districts look ahead to a very different school year, pediatric infectious disease experts from across the United States convened to outline back-to-school safety guidelines for solid organ transplant (SOT) recipients. The group, led by Kevin J. Downes, MD, attending physician in the Division of Pediatric Infectious Diseases at Children's Hospital of Philadelphia (CHOP), published their recommendations today in the Journal of the Pediatric Infectious Diseases Society.

Throughout the COVID-19 pandemic, pediatric SOT patients have been categorized as high-risk due to their use of immunosuppressive medications, frequent presence of additional medical issues, and elevated risk for more severe outcomes from other viral respiratory infections. While there is no specific evidence that pediatric SOT recipients fare worse from COVID-19, parents of SOT patients are undoubtedly nervous to send their children back to school in the fall.

As a result, parents of transplant recipients need clear guidance regarding return to school decisions and what approaches, if any, they or their schools should take to protect their immunocompromised child. In addition to these health-related considerations, many are also weighing the notable academic, social, and emotional benefits of school attendance.

"We listened to the questions families brought to us, and to their transplant providers, and drafted a set of recommendations around their concerns," said Dr. Downes. "For the majority of pediatric SOT recipients, the benefits of attending school will probably outweigh the risks. However, the final decision is a matter of shared decision-making among families, transplant professionals, and educators, and depends on many factors, including the child's clinical risk, COVID-19 cases in the community, and preparedness of both the child and the school to adhere to recommended precautions to prevent viral transmission."

The consensus statements are grouped in three areas: 1) SOT patient-specific risk factors, 2) community transmission and public health responses, and 3) school-related interventions. Only questions pertaining to school attendance in kindergarten through 12th grade in U.S. schools were considered. Questions include topics related to masking, virtual learning, and infection prevention measures.

The COVID-19 pandemic has created unprecedented circumstances and unique challenges for vulnerable children around the world. While caregivers are grappling with difficult decisions regarding returning to schools, public health officials, local health departments, and school administrators are working hard to make returning to school as safe as possible. Dr. Downes and his colleagues fully support efforts to allow all children to safely return to in-person education this academic year and have provided recommendations for transplant patients, families, and providers to help meet this goal.

An early blood test could detect which babies deprived of oxygen at birth are at risk of serious neurodisabilities like cerebral palsy and epilepsy.

The prototype test looks for certain genes being switched on and off that are linked to long-term neurological issues. Further investigations of these genes may provide new targets for treating the brain damage before it becomes permanent.

The team behind the test, led by Imperial College London researchers in collaboration with groups in India, Italy and the USA, have published their findings today in the journal Scientific Reports.

The research was conducted in Indian hospitals, where there are around 0.5-1.0 million cases of birth asphyxia (oxygen deprivation) per year. Babies can suffer oxygen deprivation at birth for a number of reasons, including when the mother has too little oxygen in her blood, infection, or through complications with the umbilical cord during birth.

Following oxygen deprivation at birth, brain injury can develop over hours to months and affect different regions of the brain, resulting in a variety of potential neurodisabilities such as cerebral palsy, epilepsy, deafness or blindness.

This makes it hard to determine which babies are most at risk of complications and to design interventions that can prevent the worst outcomes.

Now, in preliminary study of 45 babies that experienced oxygen deprivation at birth, researchers have identified changes to a raft of genes in their blood that could identify those that go on to develop neurodisabilities.

The babies had their blood taken within six hours after birth and were followed up after 18 months old to see which had developed neurodisabilities. The blood was examined with next-generation sequencing to determine any difference in gene expression - the 'switching on or off' of genes - between those babies that developed neurodisabilities and those that didn't.

The team found 855 genes were expressed differently between the two groups, with two showing the most significant difference.

Examining these two genes in particular, and what processes their expression causes within cells, could lead to a deeper understanding of the causes of neurodisabilities prompted by oxygen deprivation, and potentially how to disrupt them, improving outcomes.

Lead author Dr Paolo Montaldo, from the Centre for Perinatal Neuroscience at Imperial, said: “We know that early intervention is key to preventing the worst outcomes in babies following oxygen deprivation, but knowing which babies need this help, and how best to help them, remains a challenge."

Senior author Professor Sudhin Thayyil, from the Centre for Perinatal Neuroscience at Imperial, said: “The results from these blood tests will allow us to gain more insight into disease mechanisms that are responsible for brain injury and allow us to develop new therapeutic interventions or improve those which are already available.”

The babies were part of a trial called Hypothermia for Encephalopathy in Low and middle-income countries (HELIX), which also examines the use of hypothermia (extreme cooling) on babies to prevent brain injuries developing following oxygen deprivation.

In higher-income countries this is known to reduce the chances of babies developing neurodisabilities, but in lower income settings cooling may not be feasible, and even with cooling 30 percent of babies still have adverse outcomes, so new therapies are still needed.

The team will next expand their blood testing study to a larger number of babies and examine the genes that appear to show the most difference between the groups.

Patients who suffer from thrombosis, pulmonary embolism or stroke are usually put on drugs that help their blood flow more smoothly through their body. Occupying a large section of the drug market, anticoagulants, or "blood thinners" as they are popularly known, can keep blood clots from forming or getting bigger, and can therefore help with recover from heart defects or prevent further complications.

But there is a catch: blood thinners work by blocking enzymes that help to stop bleeding after an injury. Because of this, virtually every blood thinner available today can lead to serious, and even life-threatening bleeding following an injury.

The problem remained unsolved until a few years ago, when a study was carried out on mice that had been genetically modified to be deficient in an enzyme that normally helps blood clot. The enzyme is called "coagulation factor XII" (FXII), and the mice without the enzyme had a very reduced risk of thrombosis without having bleeding side-effects. The discovery triggered a race for FXII inhibitors.

Finally, a synthetic inhibitor

Participating in the race, the Laboratory of Therapeutic Proteins and Peptides of Professor Christian Heinis at EPFL has developed the first synthetic inhibitor of FXII. The inhibitor has high potency, high selectivity, and is highly stable, with a plasma half-life of over 120 hours. Published in Nature Communications, the study is the result of an extensive collaboration with three other labs in Switzerland and the US.

"The FXII inhibitor is a variation of a cyclic peptide that we identified in a pool of more than a billion different peptides, using a technique named phage display," says Heinis. The researchers then improved the inhibitor by painstakingly replacing several of its natural amino acids with synthetic ones. "This wasn't a quick task; it took over six year and two generations of PhD students and post-docs to complete."

With a potent FXII inhibitor in hand, Heinis's group wanted to evaluate it in actual disease models. To do this, they teamed up with experts in blood and disease-modeling at the University Hospital of Bern (Inselspital) and the University of Bern.

Working with the group of Professor Anne Angellillo-Scherrer (Inselspital), they showed that the inhibitor efficiently blocks coagulation in a thrombosis model without increasing the bleeding risk. Then they assessed the inhibitor's pharmacokinetic properties with the group of Professor Robert Rieben (University of Bern). "Our collaboration found that it is possible to achieve bleeding-free anti-coagulation with a synthetic inhibitor," says Heinis.

Artificial lungs

"The new FXII inhibitor is a promising candidate for safe thromboprotection in artificial lungs, which are used to bridge the time between lung failure and lung transplantation," says Heinis. "In these devices, contact of blood proteins with artificial surfaces such as the membrane of the oxygenator or tubing can cause blood clotting." Known as 'contact activation', this can lead to severe complications or even death and limits the use of artificial lungs for longer than a few days or weeks.

To test the effectiveness of the FXII inhibitor in artificial lungs, Heinis's group turned to Professor Keith Cook at Carnegie Mellon University (US), an expert for artificial lung system engineering. Cook's group tested the inhibitor in an artificial lung model, and found that it efficiently reduced blood clotting, all without any bleeding side-effects.

The only problem is that the inhibitor has a relatively short retention time in the body: it's too small and the kidneys would filter it out. In the context of artificial lungs, this would mean constant infusion, since suppressing blood clotting for several days, weeks or months requires a long circulation time.

But Heinis is optimistic: "We're fixing this; we're currently engineering variants of the FXII inhibitor with a longer retention time."

LOS ANGELES (Aug. 4, 2020) - More than three years after a clinical trial was prematurely ended for failing to show progress in healing heart attack scars, a prominent peer-reviewed journal is publishing some surprising results showing that the heart cell treatment does benefit patients.

Data from the ALLSTAR study published Tuesday by the European Heart Journal showed that although infusions of allogeneic cardiac cells-called cardiosphere-derived cells or CDCs--did not appear to shrink the scar left on heart muscle after a heart attack, other data from the study show a clear benefit.

Compared with patients who received placebo treatment, patients randomized to receive CDC infusions showed a decrease in the volume of blood in the heart before and after it beats, indicating that the heart had not dilated, as it does progressively in heart failure.

"As it develops heart failure, the heart gets bigger and bigger, like a swelling balloon," said the study's lead author, Raj Makkar, MD, vice president of Cardiovascular Innovation and Intervention for Cedars-Sinai and the Stephen R. Corday, MD, chair in Interventional Cardiology. "One way we can measure the health of a heart is to measure the volume of blood it can hold. The bigger the volume, the more damaged the heart."

The newly analyzed data from the ALLSTAR study, which was sponsored by Capricor Therapeutics, showed that patients given a placebo had hearts that continued to swell, holding larger volumes of blood, while the patients who received CDC infusions had smaller hearts with lower volumes.

Results include:

The volume of blood held by the heart was essentially unchanged six months after CDC infusion, but increased by more than a teaspoonful in placebo patients.

A blood protein that measures heart failure severity was reduced in patients who had received CDCs, but not in placebo patients.

The chance that these findings were statistical flukes was only 2%.

"To me, these data are very reassuring that there really is therapeutic benefit," said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute. "There is a growing body of evidence that this cell treatment does work."

Results from the earlier CADUCEUS trial, published in The Lancet in 2014, showed that injecting CDCs into the hearts of heart attack survivors significantly reduced their heart attack scars. In 2017, however, the multicenter ALLSTAR study was prematurely halted after six months of data showed no decrease in heart attack scar size, but later analyses revealed the beneficial findings reported here.

"We think we may have chosen the wrong endpoint," said Marbán, the Mark S. Siegel Family Foundation Distinguished Professor, whose discoveries and technologies resulted in CDCs. "This happens in science because you have to design the trial a year or more before you begin, and sometimes you bet on the wrong horse ... but that doesn't necessarily mean the therapy is ineffective."

The cells used in the study were CAP-1002, Capricor Therapeutic's off-the-shelf, cardiosphere-derived cell (CDC) product candidate. Other clinical trials and case series, in which CDCs were used to treat advanced heart failure, Duchenne Muscular Dystrophy, and COVID-19, also demonstrated positive results. And new studies using CDCs are in the planning stages.

"California is known as the stem cell state, but few technologies being tested in California actually were developed here," said Shlomo Melmed, MB, ChB, executive vice president of Academic Affairs, dean of the Medical Faculty and professor of Medicine. "Increasing evidence-including the results of the large multicenter ALLSTAR trial-validates the potential utility of a cell product which was conceived by a faculty member at Cedars-Sinai, and first tested clinically here."