Earth

Researchers at the University of Maryland School of Medicine (UMSOM) and School of Pharmacy (UMSOP) have discovered new drug compounds to potentially treat the novel coronavirus that causes COVID-19. The compounds disrupt the functioning of a protein complex inside human cells that the researchers discovered is critical for the replication and survival of coronaviruses. This finding could lead to the development of new broad-spectrum antiviral drugs that target viruses such as influenza, Ebola and coronaviruses, according to a new study published today in the Proceedings of the National Academy of Sciences (PNAS) journal.

The protein complex, called SKI complex, is a group of human proteins that regulates various aspects of the normal functioning of a cell. In the new study, the researchers discovered that this complex also plays a crucial role in helping a virus replicate its genetic material, called RNA, within the cells it infects.

"We determined that disrupting the SKI complex keeps the virus from copying itself, which essentially destroys it," said study corresponding author Matthew Frieman, PhD, Associate Professor of Microbiology and Immunology at the UMSOM. "We also identified compounds that targeted the SKI complex, not only inhibiting coronaviruses but also influenza viruses and filoviruses, such as the one that causes Ebola."

He and his colleagues from the School of Pharmacy's Computer-Aided Drug Design Center and the Center for Biomolecular Therapeutics at the UMSOM used computer modeling to identify a binding site on the SKI complex and identified chemical compounds that could bind to this site. Subsequent experimental analysis showed these compounds to have antiviral activity against coronaviruses, influenza viruses, and filoviruses (such as Ebola). Researchers from the National Institute of Allergy and Infectious Diseases also participated in this study.

The study was funded by Emergent BioSolutions, a biopharmaceutical company based in Gaithersburg, MD.

"These findings present an important first step in identifying potential new antivirals that could be used to treat a broad number of deadly infectious diseases," said study lead author Stuart Weston, PhD, a research fellow at the UMSOM. Such drugs have the potential to treat infectious disease associated with future pandemics. Next steps include conducting animal studies to learn more about the safety and efficacy of these experimental compounds, which are not approved by the Food and Drug Administration.

In other research efforts funded by the federal government, Dr. Frieman and his team are rapidly testing hundreds of drugs, approved and marketed for other conditions, to see whether any can be repurposed to prevent or treat COVID-19.

"As we face a potentially long, hard winter with COVID-19, our researchers continue their sustained efforts to advance innovations," said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. "Basic research remains a vital part of this effort to leave us prepared for the next global pandemic."

Empagliflozin, a recently developed diabetes drug, can effectively treat and reverse heart failure in both diabetic and non-diabetic patients, according to researchers at the Icahn School of Medicine at Mount Sinai.

Their clinical trial showed that this medication can improve the heart's size, shape, and function, leading to better exercise capacity and quality of life, which will reduce hospitalizations for heart failure patients. The results were presented on Friday, November 13, at the American Heart Association Scientific Sessions 2020 and simultaneously published in the Journal of the American College of Cardiology.

"Our clinical trial's promising results show this diabetes drug can ameliorate lives of heart failure patients with reduced ejection fraction, enhance their exercise capacity, and improve their quality of life with little to no side effects. We expect this work will help lead to U.S. Food and Drug Administration approval of empagliflozin for this patient population in the coming months," said first author Carlos Santos-Gallego, MD, postdoctoral fellow at the Icahn School of Medicine at Mount Sinai.

"Our study also identifies why this drug is effective: because it improves heart function, something that has not been understood until now," Dr. Santos-Gallego said. "Many doctors are afraid of prescribing a drug they do not understand, and our findings will help clinicians feel more comfortable giving this to patients once approved. A cornerstone finding is that, although this drug was initially developed for diabetes, it is also incredibly effective in patients without diabetes."

Importantly, the researchers noted that the drug did not appear to cause hypoglycemia, or low blood sugar, in non-diabetic patients.

For the trial, known as "EMPATROPISM," researchers recruited 84 patients with chronic heart failure with reduced ejection fraction (EF)--the percentage of blood the left ventricle pumps with each contraction--and randomized them to treatment with empagliflozin or a placebo. All had baseline evaluations including cardiac magnetic resonance imaging, a cardiopulmonary exercise test on a bicycle wearing a face mask to text oxygen levels, a six-minute walk test, and quality-of-life questionnaires. Patients received treatment or placebo for six months, with some short safety visits at one and three months. At the six-month mark, patients went through the same tests.

Roughly 80 percent of the patients treated with empagliflozin showed significant improvement, and their hearts returned to near normal, the researchers found. This group had a 16.6 percent improvement in left ventricular ejection fraction at the six-month mark and their hearts pumped blood in a stronger way. Their hearts became smaller, less dilated because of less congestion and less fluid accumulation in the body, meaning that their heart failure became less severe, and the walls of the heart were less thick, meaning that the left ventricle could pump blood more easily. The placebo group showed no improvement; those patients either stayed at baseline or their condition got worse. They had a diminishing EF; their hearts were more dilated and thicker, and had an abnormal, more spherical, shape.

The study also showed that patients taking empagliflozin had roughly 10 percent improvement in their exercise levels, a statistically significant difference, while patients on the placebo arm showed no improvement. This demonstrated that the empagliflozin group became healthier, could do more everyday activities, and had an improved quality of life, putting those patients at less risk of hospitalization.

The study also identified, for the first time, why this drug is effective for treating heart failure. In heart failure, the heart goes through "adverse remodeling," in which the left ventricle dilates, becomes thicker (hypertrophic) and more spherical, and pumps in a weaker way with a lower ejection fraction. The researchers demonstrated that this drug lessens and reverses this adverse remodeling. It reduces the dilation and hypertrophy of the left ventricle, helps the left ventricle pump more strongly (increasing the ejection fraction), and changes the shape of the left ventricle, making it more elongated and less spherical.

"We were very surprised at how fast the benefits appeared with empagliflozin. The patients were already feeling better in the first few weeks of taking it. Another key issue is how safe this drug is; we saw no severe side effects, despite being an antidiabetic drug, no hypoglycemia was noticed. This shows that empagliflozin is a safe and potent treatment for heart failure with reduced ejection fraction independently of the diabetic status of the patient," explains co-author Juan Badimon, PhD, Professor of Medicine (Cardiology) and Director of the Atherothrombosis Research Unit at the Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai.

A team of researchers has discovered more about the grain-scale fluid connectivity beneath the earth's surface, shedding new light on fluid circulation and seismic velocity anomalies in subduction zones.

Lithospheric plates collide at convergent boundaries. Here, the less dense oceanic lithosphere subducts below the continental plate, and releases an abundance of water due to a progressive metamorphic reaction at high pressure and high temperature. The released water can infiltrate into the mantle wedge which lies between the subducting oceanic lithosphere and the continental crust.

Fluids that circulate in subduction zones have a significant effect on magma genesis, global material exchange between the Earth's interior and surface, and seismicity. The dihedral angle (θ)--the angle between two intersecting planes--holds the key to revealing the fluid connectivity and migration regime for a fluid-bearing, deep-seated rock in the Earth's interior known as pyrolite--a rock mainly composed of olivine.

Although H2O is the predominant composition of subduction-zone fluids, minor components in the fluid can have a dramatic impact on the wetting properties of olivine. This is evidenced in the dihedral angle between olivine and fluid.

Salt (NaCl) and non-polarized gases such as CO2 are two crucial components of subduction-zone fluids that significantly affect the dihedral angle between olivine and fluid. CO2 is known to increase the olivine-fluid θ under conditions in which the olivine does not react with CO2. Whereas, a recent study showed that NaCl can effectively decrease the olivine-fluid θ even with a low NaCl concentration. NaCl and CO2 have opposite effects on the olivine-fluid θ, and this factor has inhibited researchers in their understanding of fluid migration in subduction zones.

Clarifying the competing effects of NaCl and CO2 on θ in an olivine + multicomponent (H2O-CO2-NaCl) fluid system can help researchers understand the connectivity of aqueous fluid with more realistic compositions of the mantle wedge; thus making mapping of fluid distribution easier.

To do this, doctoral student Yongsheng Huang, professor Michihiko Nakamura, and postdoctoral researcher Takayuki Nakatani from Tohoku University worked alongside professor Catherine McCammon from the University of Bayreuth. The research team sought to constrain θ in olivine + H2O-CO2 fluid and olivine + H2O-CO2-NaCl (multicomponent) fluid systems at 1-4 GPa and 800-1100 °C.

The results in the H2O-CO2 system showed that CO2 tends to increase θ at 1 GPa and 800-1100 °C and at 2 GPa and 1100 °C. In contrast, CO2 reduced the θ to below 60° at relatively high-pressure and low-temperature conditions. Here, the olivine partly reacts with CO2 to form magnesite and orthopyroxene (opx).

Additional experiments on olivine-magnesite + H2O and olivine-opx + H2O systems showed magnesite or opx decreased the olivine-fluid θ. This implies that coexisting minerals affect the olivine-fluid interfacial energy by changing fluid chemistry. The multicomponent system results showed that the effect of NaCl on θ is much more significant than CO2. Strikingly, θ was smaller than 60° in all the magnesite- and opx-bearing multicomponent systems.

"Our study has revealed that CO2-bearing multicomponent aqueous fluid can infiltrate the overlying plate through an interconnected network at pressures above 2 GPa, which facilitates significant fore-arc fluid circulation and confirms the origin of the high electrical conductivity anomalies detected in the fore-arc mantle wedge," said Nakamura.

The contrasting effects of aqueous fluid and silicate melt on the seismic wave velocity may allow for mapping partial melt in the mantle wedge.

To date, numerous studies had looked at think tanks and networks involved in the climate change counter movement in the US. Now, for the first time, the most important contrarian climate change think tanks in Europe have been studied systematically. The study whose first author, Núria Almiron, is a researcher with the UPF Department of Communication, covers a 24-year period (1994-2018) and takes account of the messages issued in six European countries, in four languages.

For the first time, an organized climate change counter movement led by conservative groups in Europe has been studied rigorously

"We have studied the messages issued with reference to climate change since this topic first emerged. The discourse we have found is a carbon copy of that used by American denialists. They repeat the same thing, even in some cases where climate change does not exist", says Núria Almiron. "As in the United States, in Europe contrarian think tanks have a neoliberal ideological stance", she adds.

The study, carried out within the framework of the THINKClima project, funded by the Spanish National Research Agency (AEI) and the European Regional Development Fund (ERDF), was published on 9 September in the international journal Climatic Change, and in addition to Almiron it also involved Maxwell Boykoff, a researcher at the University of Colorado Boulder (USA); Marta Narberhaus, a researcher at the International University of Catalonia; and Francisco Heras, an independent researcher.

This study documents for the first time that activities against climate change constitute a global counter movement that is also present in the EU

The authors considered eight European climate change counter movement think tanks, in six countries, studying their messages in four different languages. Their content analysis has shown that the messages issued by European organizations against climate change are very similar to those broadcast in the US. In short, this study documents for the first time that activities against climate change constitute a global counter movement that is also present in the EU.

Therefore, the main conclusion of the research is that although the organized climate change counter movement had been associated with the US, mainly due to the powers that be related to the coal industry and the political and cultural opposition to environmental movements, and although its influence in Europe is more modest, the study highlights that there is an organized counter movement in Europe led by conservative think tanks.

Exposure to an urban environment characterised by high levels of air pollution and noise in areas with a high building density during the foetal period and in early childhood may contribute to higher blood pressure. This was the conclusion of a study led by the Barcelona Institute for Global Health (ISGlobal) published in Environment International. ISGlobal is an institution supported by the "la Caixa" Foundation.

To study the impact of urban exposures on the cardiovascular health of children, the research team analysed data from 4,279 children living in six European cities (Bradford in the United Kingdom, Poitiers and Nancy in France, Sabadell and Valencia in Spain, and Heraklion in Greece). All the children were participants in the European HELIX project.

The team assessed multiple aspects of the children's environment: initially, during the prenatal period, the place of residence of the mothers during their pregnancy, and subsequently the homes of the children themselves. Factors studied included the built environment, natural spaces, traffic, air pollution, noise, climate and level of social and economic privation. Assessing the children's blood pressure when they were between four and five years of age allowed them to study the long-term effect of the exposures analysed.

Analysis of the results showed that exposure to higher levels of air pollution, particularly during the first two terms of pregnancy, was associated with higher blood pressure in childhood. Specifically, a 9.1 μg/m3 increase in NO2 was associated with a 0.9 mmHg increase in diastolic blood pressure. (A healthy diastolic blood pressure in children is around 50-80 mmHg) The limit value established by the World Health Organisation to protect the population from the damaging effects of NO2 is 40 μg/m3, a threshold exceeded on a regular basis in cities like Barcelona and Madrid.

Furthermore, other characteristics of the urban environment during childhood also appear to be important. High building density is associated with higher blood pressure and good urban transport connectivity is linked to lower blood pressure. "It is possible that these associations reflect how people move around in the city and may indicate that greater connectivity promotes physical activity in the population" explains ISGlobal researcher Charline Warembourg, first author of the study. Exposure to noise also appears to be associated with higher blood pressure in children.

Based on their analysis of the results, the authors concluded that one in every five children lives in an urban environment characterised by levels of air pollution, noise, and building density that are associated with blood pressure values higher than those observed in children not exposed to these environmental factors.

The Role of Urbanisation in Cardiovascular Disease

High blood pressure is one of the chief risk factors for cardiovascular disease, a condition which is currently the leading cause of death worldwide. "Numerous studies have shown that children with higher blood pressure are more likely to develop hypertension later in life," says Martine Vrijheid, study leader and director of ISGlobal's Childhood and Environment Programme. "The results of this study show how important it is to identify environmental exposures that contribute to hypertension in early life, from conception onwards."

Given the increasing urbanisation of the world's population, the role that urban design and transport plays in health is a topic of growing concern. This study assessed, for the first time, the effects on the cardiovascular health of children of numerous exposures associated with the urban environment. "Our results show that, from conception onwards, the urban environment can affect blood pressure in preschool children" Warembourg points out. "This means that a commitment to urban design and transport planning designed to reduce damaging environmental exposures has the potential to reduce the risk of cardiovascular disease in adulthood".

A study using extensive nationwide registry data showed that girls born extremely preterm, earlier than 28 weeks gestational age, were three times more likely to be diagnosed with depression than peers born close to the expected date of delivery. Increased risk of depression also applied to girls and boys with poor fetal growth born full-term and post-term. The effects of poor fetal growth were more evident with increasing gestational age.

All the results were adjusted for paternal psychopathology, paternal immigrant status, maternal psychopathology, maternal depression, maternal substance abuse, number of previous births, maternal marital status, maternal socio-economic status, maternal smoking during pregnancy, and the infant's birthplace.

Childhood depression can be addressed preventively

Depression is a common psychiatric disorder that has been reported to affect 1-2 percent of preschool and prepubertal children and 3-8 percent of adolescents. However, childhood depression is a severe disorder and its prevention can be advanced with the identification of at-risk groups.

"The study highlights the need for preventive interventions for high-risk infants and support programmes for parental mental health during pregnancy and neonatal care, especially for extremely preterm infants and growth-retarded full-term infants. Follow-up care practices should include psychosocial screening and developmental testing for children born preterm and their families, with appropriate support for sound mental health," says researcher Subina Upadhyaya from the Research Centre for Child Psychiatry, University of Turku.

"Future studies should examine the risk associated with preterm birth and infant long-term outcomes in the present era of family centered neonatal care practices," she continues.

The study included 37,682 children born in Finland between January 1987 and December 2007 and diagnosed with depression. They were compared with 148,795 matched controls without depression.

The study is part of a larger body of research that investigates the associations between antenatal risk factors and major psychiatric disorders.

"The results are significant both for understanding the risk factors for psychiatric disorders and for prevention, notes the primary investigator," Professor Andre Sourander.

The study belongs to the INVEST Research Flagship funded by the Academy of Finland Flagship Programme. INVEST aims at providing a new model for the welfare states that is more equal, better targeted to at risk groups, more anticipatory as well as economically and socially sustainable.

An associate professor from RUDN University developed a computer model that describes all types of vehicle body damage caused by fatigue failure. According to his computer simulation, low speed on bumpy roads can be more dangerous for a vehicle body than moderate. The results of the study can help measure fatigue resistance in vehicles more accurately. An article about this study was published in the Simulation Modelling Practice and Theory journal.

A car on a bumpy road is subjected to different dynamic loads that causes fatigue failure. Cyclic stress leads to the formation of micro-cracks, and after some time, spot welded joints fail. The vehicle body structure is the main load-bearing part among other parts of the car. A vehicle body with damaged spot welded joints has lower level of vehicle crashworthiness. The level of fatigue resistance can be measured experimentally, but it requires a lot of expendable supplies and a testing site with special equipment. An associate professor from RUDN University created a mathematical model that describes all possible damages of spot welded joints caused by fatigue failure. Using this model, one can assess fatigue resistance of a car without conducting expensive experiments.

To develop this model, scientists used the so-called multibody dynamic method. It describes interactions within a system of details that move relative to one another. Then, the research team created a computer simulation in which the 'car' moved on different types of roads at different speeds. For example, type B was an almost perfectly smooth road with no bumps and the model moved on it at the speed of 50, 70, and 90 km/h. Type E was assigned to the bumpiest of all roads on which the speed was only 5, 10, and 15 km/h. With 4 types of roads and 3 speeds on each of them, the team conducted 12 experiments in total.

"We modeled the movement of a vehicle on different types of roads and at different speeds and measured force and momentum at 12 suspension attachment points, that is, the points at which the suspension transmits the load to the body. Each of these 12 points is affected by six force and momentum components. So, 72 values had to be calculated for each experiment," said Kazem Reza Kasyzadeh, an associate professor at the Department of Mechanical and Instrumental Engineering of the Engineering Academy, RUDN University.

The results of this studyshow that low speeds on bumpy roads can cause more body damage than medium ones. For example, 100 spot weld joints were damaged when the model moved on a type E road at the speed of 5 km/h; 50--at 15 km/h, and only 40--at 10 km/h. Moreover, the front of a vehicle body turned out to be twice more prone to damage than the rear, regardless of the speed and road type. The team also found out that the service life of a vehicle body can be affected by the nugget diameter of spot welding joints (connection points at which two sheets are welded together). With the increase of the nugget diameter, the durability and service life of a body decreases.

Biotechnologists have been attempting to "reprogram" natural cell organelles for other processes for some time - with mixed results, since the "laboratory equipment" is specialised on the function of organelles. Dr Joanna Tripp, early career researcher at the Institute for Molecular Biosciences has now developed a new method to produce artificial organelles in living yeast cells (ACS Synthetic Biology: https://doi.org/10.1021/acssynbio.0c00241).

To this end, she used the ramified system of tubes and bubbles in the endoplasmic reticulum (ER) that surrounds the nucleus. Cells continually tie off bubbles, or vesicles, from this membrane system in order to transport substances to the cell membrane. In plants, these vesicles may also be used for the storage of proteins in seeds. These storage proteins are equipped with an "address label" - the Zera sequence - which guides them to the ER and which ensures that storage proteins are "packaged" there in the vesicle. Joanna Tripp has now used the "address label" Zera to produce targeted vesicles in yeast cells and introduce several enzymes of a biochemical metabolic pathway.

This represents a milestone from a biotechnical perspective. Yeast cells, the "pets" of synthetic biology not only produce numerous useful natural substances, but can also be genetically changed to produce industrially interesting molecules on a grand scale, such as biofuels or anti-malaria medicine.

In addition to the desired products, however, undesirable by-products or toxic intermediates often occur as well. Furthermore, the product can be lost due to leaks in the cell, or reactions can be too slow. Synthetic cell organelles offer remedies, with only the desired enzymes (with "address labels") encountering each other, so that they work together more effectively without disrupting the rest of the cell, or being disrupted themselves.

"We used the Zera sequence to introduce a three-stage, synthetic metabolic pathway into vesicles," Joanna Tripp explains. "We have thus created a reaction space containing exactly what we want. We were able to demonstrate that the metabolic pathway in the vesicles functions in isolation to the rest of the cell."

The biotechnologist selected an industrially relevant molecule for this process: muconic acid, which is further processed industrially to adipic acid. This is an intermediate for nylon and other synthetic materials. Muconic acid is currently won from raw oil. A future large-scale production using yeast cells would be significantly more environment-friendly and sustainable. Although a portion of the intermediate protocatechuic acid is lost because the vesicle membrane is porous, Joanna Tripp views this as a solvable problem.

Professor Eckhard Boles, Head of the Department of Physiology and Genetics of Lower Eukaryotes observes: "This is a revolutionary new method of synthetic biology. With the novel artificial organelles, we now have the option of generating various processes in the cell anew, or to optimise them." The method is not limited to yeast cells, but can be utilised for eukaryotic cells in general. It can also be applied to other issues, e.g. for reactions that have previously not been able to take place in living cells because they may require enzymes that would disrupt the cell metabolic process.

For galaxies, as for people, living in a crowd is different from living alone. Recently, astronomers used the National Science Foundation's Karl G. Jansky Very Large Array (VLA) to learn how a crowded environment affects galaxies in the Perseus Cluster, a collection of thousands of galaxies some 240 million light-years from Earth.

Left: The giant galaxy NGC 1275, at the core of the cluster, is seen in new detail, including a newly-revealed wealth of complex, filamentary structure in its radio lobes.

Center: The galaxy NGC 1265 shows the effects of its motion through the tenuous material between the galaxies. Its radio jets are bent backward by that interaction, then merge into a single, broad "tail." The tail then is further bent, possibly by motions within the intergalactic material.

Right: The jets of the galaxy IC 310 are bent backward, similarly to NGC 1265, but appear closer because of the viewing angle from Earth. That angle also allows astronomers to directly observe energetic gamma rays generated near the supermassive black hole at the galaxy's core.

Such images can help astronomers better understand the complex environment of galaxy clusters, which are the largest gravitationally-bound structures in the universe, and which harbor a variety of still poorly-understood phenomena.

"These images show us previously-unseen structures and details and that helps our effort to determine the nature of these objects," said Marie-Lou Gendron-Marsolais, an ESO/ALMA Fellow in Santiago, Chile. She and a number of international collaborators are announcing their results in the Monthly Notices of the Royal Astronomical Society.

As the COVID-19 pandemic began in the United States, universities were forced to make difficult operational decisions to help slow the spread of the disease and protect their students, faculty, staff, and community members. Guidance from the Centers for Disease Control (CDC) and Prevention, the World Health Organization (WHO), and other agencies informed these decisions about non-pharmaceutical interventions (NPI)--the only interventions available at the early stages of the pandemic.

A new George Mason University College of Health and Human Services (CHHS) study found that most university announcements coincided with the WHO pandemic declaration on March 11, 2020. The study, published in PLOS ONE, was led by Master of Public Health student Kevin Cevasco, with collaboration from fellow Mason students *, CHHS global and community health faculty Drs. Michael von Fricken and Amira Roess, and Mason's Executive Director for Safety and Emergency Management David Farris.

"When the pandemic began, we realized how important it could be to track university decisions on NPIs," explains von Fricken, assistant professor of epidemiology.

For the study, the researchers created an original database of COVID-19-related NPI university policies. They included data from 575 universities that were four-year degree-granting institutions with more than 5,000 students. The researchers included universities from all 50 states and the District of Columbia, using the Department of Education Integrated Postsecondary Education Data System (IPEDS) to select the data so they would have additional variables available for the study such as census information and private/public university status.

Cevasco and colleagues examined when and if universities made four types of decisions between February 25 and March 31, 2020: moving courses online, discouraging campus housing, canceling travel, closing campus, and remote working.

About 75% of universities implemented all five of these recommendations, 93% implemented four, and 98% implemented at least three.

Announcements about canceling university-sponsored international travel (including study abroad) were made earliest, with these announcements beginning February 25 and more than half canceling international travel by March 11. Of those universities who made international travel announcements, all had canceled international travel by March 26.

Announcements to move to remote learning also came quickly, with all universities making announcements between March 4 and March 20. Seventy-three percent of these announcements were made between the day of the WHO pandemic declaration (March 11), and the U.S. national emergency declaration (March 13). Announcements discouraging on-campus housing came soon after and were made by 82% of universities between March 9 and March 20.

"The timing of NPI decisions may have avoided the movement of millions of students back onto campus and ensuing instances of community spread," explains Cevasco. "We can also expect that university return-to-campus plans and management of on-campus cases may vary widely given university differences in spring 2020 closure decisions. Both could be important areas to study in future work."

The data collected for this study have been published by the authors under the article's supporting information and are available for future study purposes. The authors call for researchers to provide feedback to state and federal leaders for more clear and concise guidance that assists universities in making decisions.

URBANA, Ill. - We don't know precisely how hot things will get as climate change marches on, but there's reason to believe animals in the tropics may not fare as well as their temperate relatives. Many scientists think tropical animals, because they're accustomed to a more stable thermal environment, may be pushed beyond their limits quickly as temperatures soar. And that could lead to massive species loss.

Yet, in a first-of-its-kind study, University of Illinois researchers show both temperate and tropical birds can handle acute heat stress much better than expected.

"In terms of their thermal physiology, a lot of these birds, including tropical species, can tolerate temperatures that are a lot higher than what they experience in their daily lives. That was surprising because tropical ectotherms, such as insects, have been shown to be extremely vulnerable to climate warming," says Henry Pollock, postdoctoral researcher at Illinois and first author on the study. "We're just not seeing the same things in birds. It is somewhat encouraging."

Although they observed some promising trends, the researchers caution against celebrating too soon.

"It's not necessarily comforting news. If someone walked away from this thinking tropical birds are going to do fine because they're not going to overheat, that would be a simplistic bottom line to take away from this paper," says Jeff Brawn, professor in the Department of Natural Resources and Environmental Sciences at Illinois and co-author on the study. "Warming is likely to affect tropical birds indirectly, by impacting their resources, the structure of tropical forests. So they may not be flying around panting, suffering from heat exhaustion, but there may be more indirect effects."

To test the assumption that tropical and temperate birds differ in their ability to cope with heat stress, Pollock brought 81 species from Panama and South Carolina into field labs to test their responses to rising temperatures. Using tiny sensors, he was able to detect internal body temperatures, as well as metabolic rates, when he exposed the birds to warmer and warmer environments.

Species from both temperate and tropical zones handled the rising temperatures just fine. Birds from South Carolina had a higher heat tolerance, on average, than Panamanian birds, but both groups exceeded Pollock and Brawn's expectations. And among all the birds, doves and pigeons emerged as thermal superstars. Most birds cool down by panting, but doves and pigeons take advantage of their unique-among-birds ability to "sweat." In fact, Pollock says, they exceeded the limits of his testing equipment.

Although the study provided the first-ever heat tolerance data for many bird species, the results take on more meaning when put into the context of warming projections.

"Both temperate and tropical birds were able to tolerate temperatures into the 40s [in degrees Celsius], but they only experience maximum temperatures of around 30 degrees Celsius in their everyday environments, so they have a substantial buffer," Pollock says.

In other words, even if maximum air temperatures rise 3 to 4 degrees Celsius, as projected by some scientists, that's well within the thermal safety margins of all the birds Pollock measured.

It's important to note the experiment, which measured acute heat stress, doesn't exactly replicate what's projected to happen during much more gradual climate warming. But few studies have examined the effects of chronic heat stress in birds, and having this baseline knowledge of their acute physiological limits is a good start.

"This is the first geographic comparison ever for birds. We need more data from more sites and studies of chronic heat stress over longer periods of time. But I think at the very least, what we can say is that they're able to tolerate higher temperatures than I think anybody expected," Pollock says.

Brawn adds, "We're just starting to scratch the surface of what we need to do to really understand how climate change is going to affect birds. But this is an important first step."

Mars once had oceans but is now bone-dry, leaving many to wonder how the water was lost. University of Arizona researchers have discovered a surprisingly large amount of water in the upper atmosphere of Mars, where it is rapidly destroyed, explaining part of this Martian mystery.

Shane Stone, a graduate student in the UArizona Lunar and Planetary Laboratory and lead author of a new paper published today in Science, describes himself as a planetary chemist. Once a laboratory chemist who helped to develop polymers that could be used to wrap and deliver therapeutic drugs more efficiently, he now studies the chemistry of planetary atmospheres.

Since 2014, he has worked on the NASA MAVEN mission, short for Mars Atmosphere and Volatile EvolutioN. The MAVEN spacecraft began orbiting Mars in 2014 and has been recording the composition of the upper atmosphere of Earth's planetary neighbor ever since.

"We know that billions of years ago, there was liquid water on the surface of Mars," Stone said. "There must have been a thicker atmosphere, so we know that Mars somehow lost the majority of its atmosphere to space. MAVEN is trying to characterize the processes responsible for this loss, and one portion of that is understanding exactly how Mars lost its water."

Co-authors of the study include Roger Yelle, a UArizona planetary sciences professor and Stone's research adviser, as well as researchers from NASA Goddard Space Flight Center and the Center for Research and Exploration in Space Science and Technology in Maryland.

Watching for Water

As MAVEN orbits Mars, it dips into the planet's atmosphere every 4 1/2 hours. The onboard NGIMS instrument, short for Neutral Gas and Ion Mass Spectrometer, has been measuring the abundance of charged water molecules called ions in the upper Martian atmosphere, about 100 miles from the planet's surface. From this information, scientists can infer how much water is present in the atmosphere.

Past observations using MAVEN and the Hubble Space Telescope showed that loss of water from the Martian upper atmosphere varies with the seasons. Compared to Earth, Mars takes a more oval-shaped path around the sun and is closest to it during summer in the Martian southern hemisphere.

Stone and his team found that when Mars is nearest the sun, the planet warms, and more water - found on the surface in the form of ice - moves from the surface to the upper atmosphere where it is lost to space. This happens once every Martian year or about every two Earth years. The regional dust storms that occur on Mars every Martian year and the global dust storms that occur across the planet about once every 10 years lead to further heating of the atmosphere and a surge in the upward movement of water.

The processes that make this cyclical movement possible contradict the classical picture of water escape from Mars, showing it is incomplete, Stone said. According to the classical process, water ice is converted to a gas and is destroyed by the sun's rays in the lower atmosphere. This process, however, would play out as a slow, steady trickle, unaffected by the seasons or dust storms, which doesn't mesh with current observations.

"This is important because we didn't expect to see any water in the upper atmosphere of Mars at all," Stone said. "If we compare Mars to Earth, water on Earth is confined close to the surface because of something called the hygropause. It's just a layer in the atmosphere that's cold enough to condense (and therefore stop) any water vapor traveling upward."

The team argues that water is moving past what should be Mars' hygropause, which is likely too warm to stop the water vapor. Once in the upper atmosphere, water molecules are broken apart by ions very quickly - within four hours, they calculate - and the byproducts are then lost to space.

"The loss of its atmosphere and water to space is a major reason Mars is cold and dry compared to warm and wet Earth. This new data from MAVEN reveals one process by which this loss is still occurring today," Stone said.

A Dry and Dusty World

When the team extrapolated their findings back 1 billion years, they found that this process can account for the loss of a global ocean about 17 inches deep.

"If we took water and spread it evenly over the entire surface of Mars, that ocean of water lost to space due to the new process we describe would be over 17 inches deep," Stone said. "An additional 6.7 inches would be lost due solely to the effects of global dust storms."

During global dust storms, 20 times more water can be transported to the upper atmosphere. For example, one global dust storm lasting 45 days releases the same amount of water to space as Mars would lose during a calm Martian year, or 687 Earth days.

And while Stone and his team can't extrapolate farther back than 1 billion years, he thinks that this process likely didn't work the same before that, because Mars might have had a stronger hygropause long ago.

"Before the process we describe began to operate, there must have been a significant amount of atmospheric escape to space already," Stone said. "We still need to nail down the impact of this process and when it began to operate."

In the future, Stone would like to study the atmosphere of Saturn's moon, Titan.

"Titan has an interesting atmosphere in which organic chemistry plays a significant role," Stone said. "As a former synthetic organic chemist, I'm eager to investigate these processes."

The current dominant variant of SARS-CoV-2, containing a D614G substitution in the spike protein, appears to have evolved to enhance transmissibility, according to a new study in human cells and animal models. Its results address concerns that have been raised about how this emergent mutation could enhance transmissibility, antigenicity, and/or pathogenesis, with implications for therapies under development. Pandemic spread of a virus in naïve populations can select for mutations that alter pathogenesis, virulence and/or transmissibility. Mutations could challenge the development of vaccine and therapeutic antibodies. Today, the ancestral form of SARS-CoV-2 that emerged from China has been largely replaced by strains containing a D614G mutation in the virus spike. While this spike substitution is prevalent in global SARS-CoV-2 strains, its effects on viral pathogenesis and transmissibility remain unclear. To better understand them, Yixuan Hou, Ralph Baric and colleagues engineered a SARS-CoV-2 variant containing this substitution and used it to compare, in a series of experiments in human cells and animal models, the characteristics of the new variant against the ancestral form. Compared to the ancestral virus, the variant showed an enhanced ability to infect upper airway epithelial cells and to replicate, the work in human cells showed. In mice and Syrian hamsters engineered to exhibit human cell features, both viruses resulted in similar viral titers in respiratory tissues; the hamsters displayed some increased weight loss, which suggests a marginal impact on disease outcomes from the variant, the authors say, but overall, the results suggest the D614G substitution doesn't significantly enhance virus pathogenesis. The variant did transmit significantly faster in hamsters, the authors say. Thus, they say, the virus seems to have evolved not for greater pathogenicity, but for greater transmissibility in humans. They also evaluated the neutralization properties of convalescent human serum samples and SARS-CoV-2 neutralizing monoclonal antibodies on the variant and the ancestral form, finding no significant difference. These data suggest that the current vaccine approaches targeted against the ancestral spike protein should be effective against the D614G strains, the authors say. They note several limitations of their study and emphasize:" It is clearly important to monitor and identify the emergence of new variants of SARS-CoV-2."

When it comes to complex life -- that of the multicellular variety -- cell death can be just as important as survival. It allows organisms to clean house and prevent the proliferation of damaged cells that could compromise tissue function.

Several years ago, biologist Denise Montell, a distinguished professor at UC Santa Barbara, found that sometimes cells survive after what was considered the critical step in cellular suicide. Now, she and her lab have identified two key factors involved in this remarkable recovery.

The findings, published in Nature Communications, indicate that this survival mechanism may be critical to normal tissue recovery from extreme stress rather than a fluke occurrence. Understanding its nuances could also provide new strategies for treating cancers.

Apoptosis is the most common way cells commit suicide, and this process is critical in maintaining an organism's wellbeing. Living things need a way to terminate cells when they are badly injured or their DNA is damaged. Apoptosis is also part of natural turnover, especially in blood cells, skin cells and the lining of the gut.

"Before our work, people really thought that apoptosis was an all-or-nothing decision," said Montell, Duggan Professor in the Department of Molecular, Cellular, and Developmental Biology. "You either committed to suicide and went through with it, or you didn't."

Scientists considered the activation of an enzyme appropriately called "executioner caspase" to be the point of no return. This enzyme essentially slices and dices many of the cell's proteins. But it turns out apoptosis is more nuanced than previously known, and sometimes cells survive the executioner caspase via another process -- anastasis.

Back from the brink

This phenomenon first came to Montell's attention around 2010. Generally, scientists studying apoptosis use extreme conditions that cause all the cells in their sample to die. A doctoral student in her lab at the time was curious whether cells could survive the activation of caspase if he removed the substance that induced apoptosis. To everyone's surprise, many of them did.

Since then scientists have observed anastasis in cells from many different organisms, including humans, mice and fruit flies. Montell and her team decided to search for genes that would either enhance or inhibit the ability of cells to undergo this process.

To this end, the researchers applied a technique they developed in 2016. By breeding transgenic fruit flies that express a specific protein that is cut by the executioner caspase, they initiated a series of events that ultimately makes the cells fluoresce green. That permanently identifies any cell that has survived through this phase of apoptosis.

With this tool on hand, the team, led by former postdoctoral fellow Gongping Sun, set out to identify the genes involved in anastasis. Given they couldn't investigate all 13,000 genes in the fruit fly genome, the researchers combed their own data as well as the literature to identify candidate genes, eventually settling on about 200 to investigate further.

Sun and her lab mates took hundreds of fruit flies and knocked out the expression of a different gene in half of the cells of each animal. This enabled them to control for other factors that might influence the results.

In the paper published in 2016, the team found that some cells undergo anastasis during normal development of the fruit fly. In the new paper, they therefore looked for changes in the percentage of cells that went through this process during development. They also tested the genes for their ability to affect anastasis in response to stresses like radiation and heat.

Distinguishing between genes involved in anastasis and those that are simply necessary for basic survival was a challenge. "Because if it's necessary for survival, period, then it's also going to be necessary for recovery from the brink of death," Montell said.

So, the team looked not only at how many cells in a sample fluoresced green after the experiment, but the ratio of green cells to non-green cells. If the gene in question was necessary for basic survival, but not involved in anastasis, it affects all cells equally. This would impact the overall number of fluorescent cells, but leave the ratio unchanged.

The researchers found two proteins, and the genes that coded for them, were instrumental in anastasis. The first, AKT1, is a well-studied and renowned survival protein that is activated in response to growth factors, essentially telling the cell to grow and divide. Scientists were aware that it can block the activation of executioner caspase, but the team discovered it can also make the difference between survival and death after caspase has been triggered.

The other protein, CIZ1, is not as well-studied, and shows up in a number of unrelated papers across the literature. In nearly all these instances it appears that CIZ1 also promotes survival from stress. For instance, a decreased amount of CIZ1 is associated with increased age-dependent neurodegeneration in mice.

The involvement of these two proteins in anastasis indicates that it is probably a very ancient process. "Not just the phenomenon of cells recovering from the brink of death, but even the mechanism -- the molecules involved -- are so deeply conserved in evolution that flies and mice are using the same molecules," Montell said.

Apoptosis and fighting cancer

These findings are a huge step forward in understanding apoptosis on a fundamental level. They also suggest possible applications -- especially in efforts to combat cancer.

Apoptosis serves an important function in maintaining stable equilibrium within complex organisms. Under normal circumstances -- say UV damage to a skin cell -- the body wants the injured cell to die so that it doesn't develop into a condition like melanoma.

"However, if you were subjected to extreme stress you might not want every cell to commit apoptosis," Montell said. "That might result in permanent tissue damage from which it would be very hard to recover."

In response to severe but temporary trauma, it could be beneficial for some of the cells to be able to bounce back. Montell suspects this is the primary reason that organisms evolved a way to circumvent apoptosis.

The temporary nature of the stress seems to be the critical factor both in the role anastasis plays in promoting healing and in the mechanism itself. When a cell is under extreme stress, like radiation or chemical exposure, two things happen simultaneously: The cell activates the apoptosis response -- including executioner caspase-- while also activating pro-survival responses.

"It's like putting on the accelerator and the brake at the same time," Montell said.

The apoptotic factors reinforce themselves, so if the stressful conditions persist, the process crosses a threshold and the cell dies. But if the stress is only transient, the pro-survival pathway is already poised to kick in and help the cell recover. Researchers don't fully understand how the cell turns off the apoptotic pathway, but proteins like AKT1 and CIZ1 are likely involved.

There is, however, a dark side to this survival mechanism. "Anastasis could be a good thing if you're trying to repair a damaged tissue, but it could be a bad thing in that it might promote the growth of tumors," Montell pointed out, "especially in response to chemotherapy and radiation treatments, which are extreme temporary stresses."

This matches the experience of many physicians, Montell explained. A lot of cancer patients initially respond well to treatments; their tumors shrink and their condition improves. But unfortunately, the tumors often grow back. And scientists aren't certain why this is.

Some think the resurgence could be the result of drug-resistant cells that exist in the tumor, which then seed the relapse. This paper provides another hypothesis -- "the idea that the treatment itself could induce the cancer cells to undergo this stress-dependent survival process," Montell said.

This notion could fundamentally change the way doctors think about preventing relapse. There isn't much you can do against drug-resistant cells, Montell said, but if the relapse is due to this survival mechanism, these findings could inform new therapies.

Drugs that inhibit AKT1 are currently in clinical trials. These could be combined with other therapies to increase their effectiveness, potentially enabling doctors and researchers to inhibit anastasis in cancer cells while promoting it normal cells.

What's more, successful cancer cells can actually induce apoptosis in the T cells that the immune system sends to attack them, according to Montell. This presents another target for anastasis therapies.

"There's this ongoing war between the immune system and cancer," Montell said, "and if you can tip the balance even a little bit, you can start to win."

Computational models suggest that melting water originating in the deep interior of Greenland could flow the entire length of a subglacial valley and exit at Petermann Fjord, along the northern coast of the island. Updating ice sheet models with this open valley could provide additional insight for future climate change predictions.

Radar surveys have previously mapped Greenland's bedrock buried beneath two to three thousand meters of ice. Mathematical models were used to fill in the gaps in survey data and infer bedrock depths. The surveys revealed the long valley, but suggested it was segmented, preventing water from flowing freely through it. However, the peaks breaking the valley into segments only show up in areas where the mathematical modelling was used to fill in missing data, so could not be real.

Christopher Chambers and Ralf Greve, scientists at Hokkaido University's Institute of Low Temperature Science, wanted to explore what might happen if the valley is open and melting increases at an area deep in Greenland's interior known for melting. Collaborating with researchers at the University of Oslo, they ran numerous simulations to compare water dynamics in northern Greenland with and without valley segmentation.

The results, recently published in The Cryosphere, show a dramatic change in how water melting at the base of the ice sheet would flow, if the valley is indeed open. A distinct subglacial watercourse runs all the way from the melting site to Petermann Fjord, which is located more than 1,000 kilometers away on the northern coast of Greenland. The watercourse only appears when valley segmentation is removed; there are no other major changes to the landscape or water dynamics.

"The results are consistent with a long subglacial river," Chambers says, "but considerable uncertainty remains. For example, we don't know how much water, if any, is available to flow along the valley, and if it does indeed exit at Petermann Fjord or is refrozen, or escapes the valley, along the way."

If water is flowing, the model suggests it could traverse the whole length of the valley because the valley is relatively flat, similar to a riverbed. This suggests no parts of the ice sheet form a physical blockade. The simulations also suggested that there was more water flow towards the fjord with a level valley base set at 500 meters below sea level than when set at 100 meters below. In addition, when melting is increased only in the deep interior at a known region of basal melting, the simulated discharge is increased down the entire length of the valley only when the valley is unblocked. This suggests that a quite finely tuned relationship between the valley form and overlying ice can allow a very long down-valley water pathway to develop.

"Additional radar surveys are needed to confirm the simulations are accurate," says Greve, who has been developing the model used in the study, called Simulation Code for Polythermal Ice Sheets (SICOPOLIS). "This could introduce a fundamentally different hydrological system for the Greenland ice sheet. The correct simulation of such a long subglacial hydrological system could be important for accurate future ice sheet simulations under a changing climate."