Earth

When the brain gets injured, star-shaped brain cells called astrocytes come to the rescue. In the case of glioma - the most common type of primary brain tumor - this protective action comes at a price.

A new study published in Neurochemistry International reveals that gliomas alter astrocyte function, which normally prevents the brain from being flooded with excess excitatory chemicals. This could contribute to the seizures experienced by many brain cancer patients.

"Seizures are a serious and debilitating comorbidity that affect most patients with primary brain tumors. Unfortunately, epilepsy dramatically reduces quality of life, and our current anti-epileptic drugs are not effective for all patients," said Stefanie Robel, an assistant professor at the Fralin Biomedical Research Institute at VTC and the study's co-senior author.

"My lab is looking for other cellular and molecular targets that contribute to seizures resulting from gliomas, and so far, what we're finding is that the scar-forming astrocytes that surround the tumor play an important role."

Gliomas are competitive, fast-growing tumors that - just like all other living cells - need an energy source to survive. Composed primarily of glia cells, gliomas take over the brain's microvasculature, syphoning off a fresh supply of nutrients from other healthy cells. The tumors also release toxic levels of glutamate, an excitatory neurotransmitter, which can kill off the brain's densely packed healthy neurons, making space for the cancer to grow. An abundance of glutamate can also cause more neurons to become electrically active, which can result in seizures.

Astrocytes swiftly scar the tumor to protect the brain from further damage - but this comes at a price.

"Under ordinary circumstances, you'd expect astrocytes to buffer any additional glutamate. Part of their job is to maintain balanced, homeostatic conditions for neurons by removing excess glutamate and potassium," said Robel, who is also an assistant professor in Virginia Tech's School of Neuroscience and the Virginia Tech Carilion School of Medicine. "Like micro vacuum cleaners, they tidy up neurotransmitters and ions floating amid brain cells."

But the astrocytes encasing gliomas exhibited different molecular signatures based on their proximity to the cancer. The cells directly touching the tumor were elongated and swollen, mimicking the response to other brain injuries associated with epilepsy, such as stroke or physical trauma.

Electrophysiology and staining experiments revealed the stretched cells also lacked proper localization or function of proteins needed to carry potassium and glutamate inside an astrocyte. The cells had also lost a vital enzymatic process that converts glutamate into glutamine, a molecule that neurons use to suppress activity.

Under these conditions, the brain's delicate balance of excitation and inhibition tips, and problems arise.

Toxic levels of glutamate emitted from the tumor, exacerbated by the astrocytes dysfunctional state, destroy healthy neurons. Previous studies led by Sontheimer showed that the fluid suspended between brain cells reaches harmful levels of excitability - enough to spark a seizure. After the first seizure, the circuits involved are preferentially strengthened, making future episodes even more likely.

"A tumor is a dynamic, living tissue that sends and receives chemical signals to surrounding glial cells and neurons, influencing their behavior," Robel said. "What we're seeing is that these very fine changes in astrocyte function and morphology in glioma response could have a very big impact for the patient."

As more research about astrocytic response to injury, disease, and cancer is published, Robel hopes that larger patterns will emerge.

"If we can understand what astrocytes do in the context of glioma, brain trauma, or even autism, maybe these overarching biological patterns will help us identify new diagnostics, therapies, and treatments to help patients suffering from a wide range of diseases," Robel said.

As rural masses migrate to urban areas, populations grow, and people work toward better living standards, global food system sustainability pays a high price, according to a new analysis spanning low- to high-income countries. The study, which was published April 3 in the scientific journal PLOS ONE, shows that only one major global driver - the increase in international trade flows - appears to have a net positive effect on global food systems sustainability. All other major drivers (population growth, urbanization, lifestyle change, and changes in land use) seem to have negative effects.

"Trade seems to be good for food systems - but only up to a point," said Steven Prager, a study co-author from the Alliance of Bioversity International and CIAT. "Beyond a certain level, the positive effect of trade tends to plateau. High-income countries simply don't continue to benefit."

In the context of the COVID-19 pandemic, the immediate focus of the research community is, correctly, on human health. But global disturbances sparked by the pandemic also reveal how fragile our global food systems are.

In those conditions, "Understanding what drives our food systems and how we can measure or monitor them becomes vital if we want to give policymakers better tools for making food systems more sustainable and more resilient to local or global shocks such as the extreme one we are experiencing today," said Christophe Béné, the study's lead author.

Helping policymakers "understand the dynamic of our food systems"

The study builds on a global map of food system sustainability published in November in Scientific Data, a Nature journal. That study showed that high-income countries tend to have a higher level of food system sustainability (despite all the junk food they consume) than lower-income countries. Those findings were one of the motivations behind the new study. Its authors wanted to understand what drives those different levels of sustainability and what can be done to improve the situation.

"Local and global food systems are simply reflecting the ways the world is evolving," said Jessica Fanzo, a co-author and Associate Professor of Global Food & Agricultural Policy and Ethics at the Johns Hopkins School of Advanced International Studies.

"Some of the key drivers of the global demographic transition that the world is experiencing right now are also heavily impacting our food systems," said Fanzo, who was also the team leader on the 2017 report by the High Level Panel of Experts on Food Security and Nutrition, an initiative of the Food and Agriculture Organization of the United Nations.

The problem is that all these drivers, so far, have had a negative impact on food systems and these drivers are very difficult to control.

"It would be very difficult to prevent people from migrating to cities or from embracing new lifestyles as their income rises," said Fanzo. "We need therefore to find very rapidly the way to reverse or mitigate the consequences of these trends."

Though the results of the study point to some serious challenges ahead, they also offer some initial indications for policymakers about where to direct effort and investment to improve the long-term sustainability of our food systems.

NASA-NOAA's Suomi NPP satellite passed over the Southern Pacific Ocean and provided forecasters with a visible image of newly formed Tropical Cyclone Harold. Harold formed near the Solomon Islands and now threatens Vanuatu, which has already issued some warnings.

The Visible Infrared Imaging Radiometer Suite (VIIRS) instrument aboard Suomi NPP provided a visible image of Tropical Cyclone Harold on April 3, 2020. The VIIRS image showed the center near the Solomon Islands, with bands of thunderstorms wrapping tightly into the low-level center from the southeast and western quadrants. A long band of thunderstorms on the eastern side of the storm stretched from southeast of the center to northeast of the center. Outer fragmented bands of thunderstorms extended southeast to Vanuatu. Microwave satellite imagery has detected an eye forming.

At 1500 UTC, (10 a.m. EDT) Tropical cyclone Harold was located near latitude 13.0 degrees south and longitude 163.2 degrees east, about 429 nautical miles northwest of Port Vila, Vanuatu. Harold was moving to the south-southeast and had maximum sustained winds near 55 knots (62 mph/102 kph).

On April 3 EDT (April 4 local time), the Vanuatu Meteorology and Geo-Hazards Department, Port Vila issued Tropical Cyclone Warning Number 4 on Tropical Cyclone Harold for Torba and Sanma. The warning noted, "damaging gale force winds of 75 kph (40 knots/46 mph), gusting to 105 kph (55 Knots/65 mph) are expected to extend closer to Torba and Sanma today." For updated forecasts, visit: https://www.vmgd.gov.vu/

The Joint Typhoon Warning Center (JTWC) noted that rapid intensification is possible. JTWC expects Harold to move south-southeast and intensify to hurricane strength.  JTWC currently forecasts Harold to cross over Vanuatu on April 6 on its track to the southeast.

Normal speech by individuals who are asymptomatic but infected with coronavirus may produce enough aerosolized particles to transmit the infection, according to aerosol scientists at the University of California, Davis. Although it's not yet known how important this is to the spread of COVID-19, it underscores the need for strict social distancing measures -- and for virologists, epidemiologists and engineers who study aerosols and droplets to work together on this and other respiratory diseases.

Aerosols are particles small enough to travel through the air. Ordinary speech creates significant quantities of aerosols from respiratory particles, said William Ristenpart, professor of chemical engineering at UC Davis. Ristenpart is co-author on an editorial about the problem to be published in the journal Aerosol Science and Technology.

These respiratory particles are about one micron, or one micrometer, in diameter. That's too small to see with the naked eye, but large enough to carry viruses such as influenza or SARS-CoV-2.

Some individuals superemitters

Last year, Ristenpart, graduate student Sima Asadi and colleagues published a paper showing that the louder one speaks, the more particles are emitted and that some individuals are "superemitters" who give off up to 10 times as many particles as others. The reasons for this are not yet clear. In a follow-up study published in January in PLOS One, they investigated which speech sounds are associated with the most particles.

Calculating just how easily a virus like SARS-CoV-2 spreads through droplets requires expertise from different fields. From virology, researchers need to know how many viruses are in lung fluids, how easily they form into droplets and how many viruses are needed to start an infection. Aerosol scientists can study how far droplets travel once expelled, how they are affected by air motion in a room and how fast they settle out due to gravity.

"The aerosol science community needs to step up and tackle the current challenge presented by COVID-19, and also help better prepare us for inevitable future pandemics," Ristenpart and colleagues conclude.

WASHINGTON, April 3, 2020 -- You might have heard that COVID-19 vaccine trials are underway in Seattle. What exactly is being tested? How much longer will these tests take? And when can we expect a vaccine against the novel coronavirus? We chat with Benjamin Neuman, Ph.D., one of the world's experts on coronavirus, and Daniel Wrapp, one of the scientists who mapped the structure of the protein that the coronavirus uses to infect your cells, to help us answer these questions: https://youtu.be/gDY8pH6OWBc.

Public health scientists predict that school closures due to the COVID-19 pandemic will exacerbate the epidemic of childhood obesity in the United States. Andrew Rundle, DrPH, associate professor of epidemiology at Columbia University Mailman School of Public Health, and colleagues expect that COVID-19-related school closures will double out?of?school time this year for many children in the U.S. and will exacerbate risk factors for weight gain associated with summer recess.

The Perspective article appears in Obesity, the journal of the Obesity Society.

In many areas of the U.S., the COVID?19 pandemic has closed schools and some of these school systems are not expected to re?open this school year. The experiences in Hong Kong, Taiwan, and Singapore suggest that social distancing orders if lifted after short periods will have to be periodically re?instated to control COVID?19 flare-ups.

While much has been written about poor food and lack of physical activity in schools, the data show that children experience unhealthy weight gain primarily during the summer months when they are out of school. Unhealthy weight gain over the summer school recess is particularly apparent for Hispanic and African-American youth, and children who are already overweight.

"There could be long-term consequences for weight gained while children are out of school during the COVID-19 pandemic," says Rundle, who specializes in research to prevent childhood obesity. "Research shows that weight gained over the summer months is maintained during the school year and accrues summer to summer. When a child experiences obesity, even at a young age, they are at risk for higher, unhealthy weight, all the way into middle age."

Staying at Home During the Pandemic May Contribute to Obesity

As households stock up on shelf-stable foods, they appear to be purchasing ultra-processed, calorie-dense comfort foods. In regards to physical activity, social distancing and stay at home orders reduce the opportunities for exercise, particularly for children in urban areas living in small apartments. Sedentary activities and screen time are expected to expand under social distancing orders; available data show that online video game usage is already soaring. Screen time is associated with experiencing overweight/obesity in childhood, likely because of the dual issues of sedentary time and the association between screen time and snacking.

How to Prevent Childhood Obesity During the Pandemic

The authors present several interventions for reducing risk factors for unhealthy weight gain during the school closures:

Some school districts are offering students grab-and-go meals at school sites or via buses running along their regular pick-up routes. Research shows that food insecurity is associated with unhealthy weight among children, and addressing food insecurity will likely have long term benefits for child health.

Farmers markets, which often provide specialty and ethnic produce and prepared foods valued by immigrant communities. As such, cities and states should consider them as part of essential food services, but also create social distancing plans for such markets.

As schools build their remote teaching capacity, they should make physical education a priority, with home lesson plans for physical activity and/or streaming exercise classes.

"The COVID?19 pandemic is responsible for widespread sickness and death, straining healthcare systems, shutting down economies, and closing school districts," says Rundle. "While it is a priority to mitigate its immediate impact, it is important to consider ways to prevent its long-term effects, including new risks for childhood obesity."

As Tropical Cyclone Irondro continues to move through the Southern Indian Ocean, NASA's Terra satellite saw the storm developing an eye as it continued to intensify.

On April 3, 2020, the Moderate Resolution Imaging Spectroradiometer or MODIS instrument that flies aboard NASA's Terra satellite provided a visible image of Irondro that showed the storm had taken on a classic appearance of an organized tropical cyclone. Bands of thunderstorms were spiraling into a low-level center and MODIS imagery showed what appeared to be a developing cloud-filled eye.

The Joint Typhoon Warning Center or JTWC issues forecasts for tropical cyclones in various parts of the world, and the Center noted at 5 a.m. EDT (0900 UTC) that Irondro had maximum sustained winds near 55 knots (63 mph/102 kph) and was strengthening. Irondro was located near latitude 17.5 degrees south and longitude 73.3 degrees east, about 626 nautical miles south of Diego Garcia.

The tropical cyclone is expected to intensify to hurricane status with maximum sustained winds near 75 knots (86 mph/139 kph) on April 4. Irondro is later forecast to turn east-southeast and become extra-tropical.

NASA's Terra satellite is one in a fleet of NASA satellites that provide data for hurricane research.

Tropical cyclones/hurricanes are the most powerful weather events on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

A team at the Centro Nacional de Investigaciones Cardiovasculares (CNIC), working in partnership with researchers at Mount Sinai Hospital in New York, has discovered a new molecular mechanism mediated by nuclear receptors that determines the identity and expansion of macrophages--one of the cell types that act as immune sentinels in the body. The newly discovered mechanism specifically affects the macrophages resident in the serous cavities, the membrane-surrounded cavities that enclose and protect many organs. The findings, published today in Nature Communications, could have important implications for the treatment of diseases that affect the serous cavities and the organs they contain, including many cancers and myocardial infarction.

"Macrophages are immune-system cells whose main function is to act as sentinels in the body, defending it against pathogens. Macrophages are also important for maintaining homeostasis--the balanced and stable functioning of the body's systems--by eliminating tissue waste products and debris from tissue repair," explained Dr Mercedes Ricote, study coordinator and head of the Nuclear Receptor Signaling group at the CNIC. "In recent years, work from many groups has changed the understanding of the hemopoietic origin and regulation of macrophages. These studies have revealed enormous heterogeneity among tissue macrophages, depending on their embryonic or hemopoietic origin and on the miroenvironmental signals that modulate their identity and maintenance in adult life."

There are three serous membranes: the peritoneum, which covers the abdominal cavity; the pleura, surrounding the lungs; and the pericardium, which covers the heart. "One of the main functions of the macrophages residing in these cavities is to maintain homeostasis by removing dead cells," explained Dr Ricote. In addition, recent studies have demonstrated that these macrophages can infiltrate adjacent injured organs, "generating an effective rapid repair response that is independent of the recruitment of macrophage precursors via the blood supply."

The Nature Communications study was led by Dr Ricote at the CNIC and Dr Miriam Merad at Mount Sinai Hospital, and the joint first authors are Dr María Casanova (Mount Sinai) and Dr Mª Piedad Menéndez (CNIC). The study demonstrates that the expansion of peritoneal macrophages after birth and their maintenance during adult life are controlled by retinoid X receptor (RXR), a member of the nuclear receptor family.

"RXR exists in the interior of cells," explained Dr Mª Piedad Menéndez, "where it detects the presence of lipids and derivatives of vitamin A. These ligands activate RXR, triggering the expression of specific genes that control development, immunity, homeostasis, and metabolism."

The research team showed that RXR is required to establish a population of macrophages in the serous cavities of newborn mice by controlling their proliferation. The study also shows that RXR is important for the survival of these macrophages in adults. As Dr Menéndez explained, "the absence of RXR from serous-cavity macrophages results in a massive accumulation of toxic lipids that kills the cells through a process called apoptosis."

Using models of ovarian cancer in mice, the study shows that peritoneal macrophages can infiltrate ovarian tumors and act as 'tumor-associated macrophages' that "support tumor growth," explained Dr Ricote.

The findings demonstrate that loss of RXR function leads to a decrease in the number of macrophages in the peritoneal cavity, resulting in a decreased contribution of these macrophages to growing ovarian tumors, slowing the progression of the disease. Dr Ricote emphasized that "Serous cavity macrophages thus represent a possible target for the treatment of cancers that affect organs in the serous cavities."

The researchers are especially interested in the possibility of modulating RXR with drugs, including some that are currently used to treat cutaneous lymphomas. "Our research could have implications for the treatment of diseases in which serous cavity macrophages contribute to disease progression, such as cancer, or to the repair of damaged tissue, as in myocardial infarction.

PULLMAN, Wash. - A research team led by Washington State University has found that while drylands around the world will expand at an accelerated rate because of future climate change, their average productivity will likely be reduced.

The study, published in Nature Communications on April 3, is the first to quantify the impact of accelerated dryland expansion under future climate change on their gross primary production. Drylands, which primarily include savannas, grasslands and shrublands, are important for supporting grazing and non-irrigated croplands around the world. They are also an important player in the global carbon cycle and make up 41% of Earth's land surface and support 38% of its population.

"Our results highlight the vulnerability of drylands to more frequent and severe climate extremes," said Jingyu Yao, a research assistant in WSU's Department of Civil and Environmental Engineering and lead author on the paper.

Using satellite data of vegetation productivity, measurements of carbon cycling from 13 sites and datasets from global models of future climate change, the researchers found that productivity of drylands will increase overall by about 12% by 2100 compared to a baseline from about 10 years ago. However, as drylands replace more productive ecosystems, overall global productivity may not increase. Furthermore, due to expected changes in precipitation and temperatures, the amount of productivity in any one dryland area will decrease.

In addition, the researchers found that expansion among different types of drylands will lead to large changes in regional and subtype contributions to global dryland productivity.

Drylands will experience substantial expansion and degradation in the future due to climate change, wildfire and human activities, including changes to their ecosystem structures as well as to their productivity, said Heping Liu, professor in the Department of Civil and Environmental Engineering and corresponding author on the paper.

Because these regions are already water stressed, they are particularly sensitive to temperature or precipitation changes. Warming temperatures from climate change and more frequent and severe droughts threaten their biodiversity as well as their ability to take in and hold carbon.

Especially in developing countries, the degradation of dryland ecosystems could have strong societal and economic impacts, said Yao.

These changes have already started happening in the last few decades. In the U.S. Southwest, the introduction of invasive species has changed dryland regions from green to brown. Precipitation changes in Australia, which is composed almost entirely of drylands, have meant a dryer continent with dramatic impacts and Mongolia's grasslands have deteriorated because of warmer temperatures, less rainfall and overgrazing.

While the drylands' productivity is important for supporting people, these areas also play a critically important role in annual carbon cycling. They help the planet breathe, absorbing carbon dioxide every spring as plants grow and then breathing it out in the fall as they become dormant. Because the growth of dryland ecosystems is very sensitive to changes in rainfall and temperature, drylands show the most impact of any ecosystem in year-to-year changes in the carbon cycle.

Understanding their role in future carbon cycling can help researchers determine how to best preserve areas of high carbon uptake.

"In our society, we are not paying much attention to what's going on with dryland regions," Liu said. "Given their importance in global carbon cycling and ecosystem services, a global action plan involving stringent management and sustainable utilization of drylands is urgently needed to protect the fragile ecosystems and prevent further desertification for climate change mitigation."

A fossilised seal tooth found on a Victorian beach could hold the key to uncovering the history and geography of earless seals that graced Australia's shores three million years ago.

This prehistoric specimen is only the second earless seal fossil ever discovered in Australia, and proves the country's local fur seals and sea lions were preceded by a group of sea mammals, known as monachines, now long extinct in Australia.

The study also highlights the current dangers of climate change to Earth's existing wildlife, with falling sea levels likely to have played a role in the extinction of these ancient seals.

The history of this rare specimen was published today (Friday 3 April) in the Journal of Vertebrate Paleontology by a team of scientists from Monash University's School of Biological Sciences and Department of Anatomy and Developmental Biology, and Museums Victoria, led by PhD candidate James Rule.

"This tooth, roughly three million years old, tells a story similar to what occurred in South Africa and South America in the past. Earless monachine seals used to dominate southern beaches and waters, and then suddenly disappeared, with eared seals replacing them," Mr Rule said.

"Since seal fossils are rare globally, this discovery makes a vital contribution to our understanding of this iconic group of sea mammals."

An Australian citizen scientist and amateur fossil collector discovered the tooth while strolling along the beach at Portland, western Victoria.

But it wasn't until he donated the fossil to Museums Victoria many years later that it was found to have been a tooth from an extinct group of earless seals.

The research team compared the tooth to other pinnipeds - a group that includes earless seals, fur seals, sea lions and the walrus.

They found the tooth possessed characteristics of monachines and shed light on how these seals lived and what they ate.

"This seal lived in shallow waters close to the shore, likely hunting fish and squid. As monachines cannot use their limbs to walk on land, it would have required flat, sandy beaches when it came ashore to rest," Mr Rule said.

Researchers believe drastic changes in the Earth's climate fundamentally altered Australia's environment by eliminating the beaches used by earless seals to rest.

"These changes in the past have led to the extinction of Australia's ancient earless seals," Dr David Hocking, co-author and Research Fellow in Monash University's School of Biological Sciences, said.

"Our living fur seals and sea lions will likely face similar challenges as the Earth continues to warm, with melting polar ice leading to rising sea levels.

"Over time, this may lead to the eventual loss of islands that these species currently rely upon to rest and raise their young."

A Nordic study sheds new light on the role of northern peatlands in regulating the regional climate. According to the researchers, peatlands will remain carbon sinks until the end of this century, but their sink capacity will be substantially reduced after 2050, if the climate warms significantly.

Peatlands develop in waterlogged conditions which slow down plant decomposition rates, so that layers of dead plant material accumulate over many years as peat. They are a huge storehouse for significant quantities of carbon from the atmosphere. Despite only covering around 3% of the Earth's surface, peatlands contain roughly a fifth of its soil carbon. In Europe, these ecosystems store five times more CO2 than forests.

A Nordic team of researchers used novel arctic modelling tools and previously published data on peatland carbon accumulation rates, vegetation and permafrost characteristics to study the role of northern peatlands in regulating the regional climate. A major concern is whether these ecosystems will continue to remain carbon sinks and help in mitigating climate change under changing climatic conditions. The modelling study, published in Global Change Biology, aims to address these important questions.

The model (LPJ-GUESS Peatland) used in this study captured the broad patterns of long-term peatland carbon dynamics at different spatial and temporal scales. The model successfully simulated reasonable vegetation patterns and permafrost extent across the pan-Arctic. Under contrasting warming scenarios (mild and severe), the study showed that peatlands on average continue to remain carbon sinks until the end of this century. However, their sink capacity would be substantially reduced after 2050 under the high-warming scenario due to an increase in soil mineralization rates. This modelling approach contributes to a better understanding of peatland dynamics and its role in the global climate system at different spatiotemporal scales. A major uncertainty of future predictions is the impact of formation of new peatlands with potential change in the peatland sink capacity owing to permafrost thawing and possible landscape changes.

"With this study our aim is to highlight the importance of peatlands in the global carbon cycle. We adopted an advanced peatland modelling tool to address the issues pertaining to peatland carbon balance in the past and future climate conditions. Now, our plan is to take forward our current research on the role of peatlands in regulating the regional climate by coupling our state-of-the-art peatland model with global and regional climate models in order to quantify the peatland-mediated feedbacks," says Postdoctoral Fellow Nitin Chaudhary, the lead author of the study, from the University of Oslo.

"Arctic carbon balance modelling studies working with coarse spatial resolution (half-grid scale) have often ignored the role of peatlands. This study emphasises the role of natural peatlands in the Arctic carbon balance and regional climate regulation. Such studies are needed so that their role is well defined in the global carbon models," University Researcher Narasinha Shurpali from the University of Eastern Finland says.

An article published in the Journal of Medicinal Chemistry shows a new family of molecules with high affinity to join imidazoline receptors, which are altered in the brain of those patients with neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's. According to the preclinical study, the merge of these specific ligands to I2 receptors improves cognitive skills and some biomarkers which are indicators of brain neurodegenerative processes in murine models.

The new study is coordinated by the lecturer M. Carmen Escolano, from the Faculty of Pharmacy and Food Sciences of the University of Barcelona, and counts on the participation of Mercè Pallàs (UBNeuro), Javier Luque (IBUB-IQTCUB) and Pilar Pérez-Lozano (Unit of Pharmaceutic Technology), among other researchers from the same Faculty.

Other collaborators in this research were Julia García-Fuster and Jesús A. García-Fuster (UIB), Belén Pérez (UAB), Elies Molins (Institute of Materials Sciences of Barcelona, ICMAB-CSIC), Luis F. Callado (UPV), and other experts from the University of Santiago de Compostela, the University of Belgrade (Serbia) and Leuven University (Belgium).

Imidazoline receptors I2: looking for new therapeutic targets

Imidazoline receptors I2 are found in several bodies. Selective ligands from these receptors showed they participate in several physiological processes (analgesia, inflammation, human brain disorders, etc.). These are distributed in the brain and in the case of patients with neurodegenerative processes, or with glioma or mental disorders, these are altered. This is why they can be presented as potential pharmacological targets in the fight against neurodegenerative diseases.

Despite their decisive role in cell physiology, the structure of the receptors in this family has not been described yet in order to make its pharmacological characterization.

"We need new therapeutic targets to cope with therapy for diseases which are currently an uncovered in medicine. The discovery of a receptor or a maker can lead to the unfolding of therapeutic technology and become an important process", notes the lecturer M. Carmen Escolano.

New ligands with high affinity for imidazoline I2 receptors

The new article presents a new molecule structural family (Bicyclic α?Iminophosphonates) with high affinity and selectivity regarding imidazoline I2 receptors. These molecules with an innovative profile are not structurally related to any of the standard ligands used for the pharmacological characterization of these receptors, and open new structural possibilities beyond those offered by the classic ligands.

With an only phase of diastereoselective synthesis, the team created a series of membres of the ligand family of the imidazoline I2 receptors, with several compunds to help shape the structure-activity relation and determine the structural features to get the best ligand-receptor affinity.

Specifically, the synthetized molecules have a phosphonic ester -original functional group- integrated in a α?Iminophosphonate system which is not exploited as a functional group of interest in the field of medical chemistry.

With an innovative perspective, affinity studies of the new study have been carried out with competition binding techniques of radioactive ligands in human brain samples. Other comparative studies of affinity in different animal species (humans, rats, mica) have been conducted with the new compounds and the ligands considered as standard according to scientific literature.

Cognitive improvement in neurodegeneration biomarkers and behaviour

In previous studies, the research team had described for the first time the cognitive improvement of a murine model of neurodegeneration (Neurotherapeutics, 2019), produced by new ligands I2, synthetized by these experts (ACD Chemical Neurosciences, 2017).

The new study states that the specific union between a representative molecule of the new family of ligands and the imidazoline I2 receptors produces an improvement of protein markers related to neuroprotector processes in the treated animal models. Also, there is a cognitive improvement in behaviour studies and in parameters associated with neuroinflammation and oxidative stress in the model 5xFAD (murine model with family Alzheimer's).

A multidisciplinary project with a patent in neurosciences

This multidiscipline line of work, unfolded in the frame of a CaixaImpulse project, led to the patent WO 2019/121853, projected in different scenarios with the support from Bosch i Gimpera Foundation (FBG).

With these references, the experts continue with their research to describe pharmaco-technical processes that take place after the administration of the representative ligand in model animals to define the participating metabolites and shape the most accurate therapeutic dose. Another objective is to describe the processes that result from the interaction of the new molecular compound with the receptors (proteomics, signaling pathways, etc.).

AMES, Iowa - Backed by experimental data from a laboratory machine that simulates the huge forces involved in glacier flow, glaciologists have written an equation that accounts for the motion of ice that rests on the soft, deformable ground underneath unusually fast-moving parts of ice sheets.

That equation - or "slip law" - is a tool that scientists can include in computer models of glacier movement over the deformable beds of mud, sand, pebbles, rocks and boulders under glaciers such as the West Antarctic Ice Sheet, said Neal Iverson, the project leader and a professor of geological and atmospheric sciences at Iowa State University. Models using the new slip law could better predict how quickly glaciers are sliding, how much ice they're sending to oceans and how that would affect sea-level rise.

A paper published online today by the journal Science describes the new slip law and the experiments and data that motivate it. Authors are Lucas Zoet, a postdoctoral research associate at Iowa State from 2012 to 2015 and now an assistant professor of geoscience at the University of Wisconsin-Madison, and Iverson.

Why do glaciologists need a slip law?

"The potential collapse of the West Antarctic Ice Sheet is the single largest source of uncertainty in estimations of future sea-level rise, and this uncertainty results, in part, from imperfectly modeled ice-sheet processes," Zoet and Iverson wrote in their paper.

Glacier-in-a-freezer

Iverson started experiments with the 9-foot-tall ring-shear device inside his laboratory's walk-in freezer in 2009. At the center of the device is a ring of ice about three feet across and eight inches thick. Below the ring is a hydraulic press that can put as much as 100 tons of force on the ice and simulate the weight of a glacier 800 feet thick. Above the ring are motors that can rotate the ice at speeds of 1 to 10,000 feet per year.

The ice is surrounded by a tub of temperature-controlled, circulating fluid that keeps the ice ring right at its melting temperature so it slides on a thin film of water - just like all fast-flowing glaciers.

A $530,000 grant from the National Science Foundation supported development of the device. Iverson worked with three engineers from the U.S. Department of Energy's Ames Laboratory - Terry Herrman, Dan Jones and Jerry Musselman - to turn his ideas into a working machine.

And it has worked for about a decade, providing data on how glaciers move over rigid rock and deformable sediment.

A drag on the ice

For the experiments that led to the new slip law, Zoet drove from Ames to Madison to fill six, 5-gallon buckets with real, glacially deposited sediment called till that had the right mix of mud, sand and larger rock particles.

He'd scoop that into the ring-shear device to make the till bed. He'd then construct an ice ring above it by freezing layers of water seeded with ice crystals. He'd apply force on the ice, heat it until it was melting and turn on the machine.

"We were after the mathematical relationship between the drag holding the ice back at the bottom of the glacier and how fast the glacier would slide," Iverson said. "That included studying the effect of the difference between ice pressure on the bed and water pressure in the pores of the till - a variable called the effective pressure that controls friction."

The data indicated the relationship between "drag, slip velocity and effective pressure that is needed to model glacier flow," Iverson said.

"Glacier ice is a highly viscous fluid that slips over a substrate - in this case a deformable till bed - and friction at the bed provides the drag that holds the ice back," Iverson said. "In the absence of friction, the weight of the ice would cause it to accelerate catastrophically like some landslides."

But it's nearly impossible to get drag data in the field. Zoet said the act of drilling through the ice would change the interface between the glacier and bed, making measurements and data less accurate.

So Iverson built his laboratory device to collect that data, and Zoet has built a slightly smaller version for his Wisconsin laboratory. Zoet's machine features a transparent sample chamber so researchers can see more of what's happening during an experiment.

The resulting experimentally based slip law for glaciers moving over soft beds should make a difference in predictions of glacier movement and sea-level rise:

"Ice sheet models using our new slip relationship," Iverson said, "would tend to predict higher ice discharges to the ocean - and higher rates of sea-level rise - than slip laws currently being used in most ice sheet models."

Low-carbon technologies that are smaller scale, more affordable, and can be mass deployed are more likely to enable a faster transition to net-zero emissions, according to a new study by an international team of researchers.

Innovations ranging from solar panels to electric bikes also have lower investment risks, greater potential for improvement in both cost and performance, and more scope for reducing energy demand - key attributes that will help accelerate progress on decarbonisation.

In order to meet international climate targets, emissions of greenhouse gases need to halve within the next decade and reach net-zero around mid-century. To do this will require an unprecedented and rapid transformation in the way energy is supplied, distributed and used.

Researchers from the Tyndall Centre for Climate Change Research at the University of East Anglia (UEA), the International Institute for Applied Systems Analysis (IIASA) in Austria, and the University Institute of Lisbon, collected data on a wide variety of energy technologies at different scales and then tested how well they performed against nine characteristics of accelerated low-carbon transformation, such as cost, innovation and accessibility.

They then asked: is it better to prioritise large-scale, costly, non-divisible or "lumpy" technologies, such as nuclear power, carbon capture and storage, high-speed transit systems, and whole-building retrofits?

Or is it better to focus on more "granular" options, which are smaller in size, lower in cost, and more modular so they scale not by becoming bigger but by replicating? Examples of these more granular technologies include solar panels, electricity storage batteries, heat pumps, smart thermostats, electric bikes, and shared taxis or 'taxi-buses'.

Publishing their findings in the journal Science, the team finds that subject to certain conditions, more granular alternatives out-perform larger scale technologies in a number of important ways.

Lead researcher Dr Charlie Wilson, at UEA, said: "A rapid proliferation of low-carbon innovations distributed throughout our energy system, cities, and homes can help drive faster and fairer progress towards climate targets.

"We find that big new infrastructure costing billions is not the best way to accelerate decarbonisation. Governments, firms, investors, and citizens should instead prioritise smaller-scale solutions which deploy faster. This means directing funding, policies, incentives, and opportunities for experimentation away from the few big and towards the many small."

As well as being quick to deploy, smaller scale technologies have shorter lifespans and are less complex so innovations and improvements can be brought to market more rapidly. They are also more widely accessible and help create more jobs, giving governments a sound basis for strengthening climate policies.

Co-author Prof Arnulf Grubler, at IIASA, said: "Large 'silver bullet' technologies like nuclear power or carbon and capture storage are politically seductive. But larger scale technologies and infrastructures absorb large shares of available public resources without delivering the rapid decarbonisation we need."

The researchers emphasise that smaller scale technologies are not a universal solution. In some situations, there are no like-for-like alternatives to large-scale technologies and infrastructure such as aircraft flying long-haul or industrial plants producing iron, steel, and cement.

In other situations, large numbers of smaller scale technologies need to integrate within existing infrastructure: widespread deployment of heat pumps and solar panels needs electricity networks, electric vehicles need charging stations, and insulation products need buildings.

"Smaller scale innovations are not a panacea," added co-author Dr Nuno Bento, of the University Institute of Lisbon, "but in many different contexts they outperform larger-scale alternatives as a means of accelerating low-carbon transformation to meet global climate targets."

An unusual skullcap and thousands of clues have created a southern twist to the story of human ancestors, in research published in Science on 3 April.

The rolling hills northwest of Johannesburg are famous for fossils of human-like creatures called hominins. Because of this, the area is known as the Cradle of Humankind.

"During our field school excavations at Drimolen, a student began uncovering a cluster of fragments. We could see that they were parts of a skull. But they weren't immediately identifiable," says Ms Stephanie Baker.

Baker is a researcher and PhD candidate at the Palaeo-Research Institute at the University of Johannesburg. She manages research at the Drimolen fossil site in the Cradle of Humankind where the fragments of DNH 134 were found.

The international team was led by researchers from La Trobe University in Australia and Washington University in St. Louis in the United States.

Fossil forensics

Fossils that are millions of years old often come out of the soil in fragments. The fragments need to be rebuilt before researchers can confidently identify what kind of animal they came from.

"Over the course of the field season more and more fragments were uncovered. We began piecing them together. No one could decide what this skullcap was from, until one night it all came together - and we realised we were looking at a hominin!" she says. They named the skullcap DNH 134.

The next question was - what kind of hominin? The Cradle of Humankind has several different species of human ancestors and the Drimolen site had at least two kinds.

"This find really challenged us. We compared the assembled skullcap to all of the other examples of hominins in the Cradle area. Eventually, its teardrop shape and relatively big brain cavity meant we were looking at Homo erectus," says Baker.

Homo erectus is one of our direct human ancestors and is best known for migrating out of Africa into the rest of the world.

These hominins walked upright and were a more human-like species than the other hominins found in the Cradle. They had shorter arms and longer legs. They could walk and run for longer distances over the African grasslands than the others.

How old?

Once the question of 'which species?' was answered, two other huge questions presented themselves. How long ago was this individual alive? And how old were they when they died?

The researchers knew that no other Homo erectus fossils had ever been found in South Africa before. Even more surprising was the time period suggested by the soil layers the skull fragments were found in.
"Before we found DNH 134, we knew that the oldest Homo erectus in the world was from Dmanisi in Georgia dating to 1.8 million years ago," says Baker.

Building a 3D puzzle over time

Trying to figure out how old fossils are from the caves west of Johannesburg is quite tricky. There were no volcanoes during the time of the hominins, so there are no ash layers to give the researchers quick age estimates, like they use for eastern African sites.

But while they were uncovering the fragments at Drimolen, they kept and recorded every clue they could find. This included fragments of small animals like bats and lizards, but also things like soil samples.

They can also tell exactly where in 3D-space in the Drimolen quarry each little fossil fragment was found.

Then the research team used every possible dating technique available to get the most accurate possible date for the deposit. This included Palaeomagnetic dating, Electron spin resonance, Uranium lead dating, and faunal dating.

Possible shifted, earlier origin

"We collated all of the dates from each of these techniques and together they showed that we had a very precise age. We now know that the Drimolen Main Quarry and all of the fossils in it, are dated from 2.04 to 1.95 million years ago," says Baker.

That means that DNH 134 is much older than the next oldest Homo erectus in Africa; and from Georgia.

"The age of the DNH 134 fossil shows that Homo erectus existed 150,000 to 200,000 years earlier than previously thought," says Professor Andy Herries. Herries is the project co-director with Ms Baker and lead researcher. He is Head of the Department of Archaeology and History, at La Trobe University in Australia and an associate in the Palaeo-Research Institute at UJ.

Because Homo erectus is one of our direct ancestors, the discovery has implications for the origins of modern humans.

"Until this find, we always assumed Homo erectus originated from eastern Africa. But DNH 134 shows that Homo erectus, one of our direct ancestors, possibly comes from southern Africa instead. That would mean that they later moved northwards into East Africa. From there they went through North Africa to populate the rest of the world," says Baker.

The skull is also unusual because it is the skull of a young Homo erectus.

"The Homo erectus skull we found, was likely aged between two and three years old when it died," says Herries.

Sharing a landscape

The age of the DNH 134 skullcap shows something else - that three species of early human ancestor lived in southern Africa at the same time at the Drimolen fossil site.

"We can now say Homo erectus shared the landscape with two other types of humans in South Africa, Paranthropus and Australopithecus," says Herries.

This might mean they needed to use different parts of the landscape to avoid competing with one another. For a start, they looked different.

Paranthropus robustus hominins were shorter than Homo erectus and Australopithecus, says Baker.

"Paranthropus robustus ate things like roots and tubers, which is why their teeth are really big. They used their enormous teeth for grinding down what we call fall-back foods - tough hard plants."

Changing weather

In comparison to the other two species, Homo erectus hominins were tall and slender. They ate things which are easier to digest, like fruits and berries.

"We also know that they were eating meat, but we aren't exactly sure how they were getting it yet. We can say that at least these early Homo erectus weren't hunting with any weaponry yet," says Baker.

"We also know that they were able to cover long distances. Which turned out lucky for them, because during their time, the climate changed in southern Africa.

Paranthropus and Australopithecus evolved in warm and humid climates and were used to that. But then the weather began to shift from warm and humid, to cool and dry," she says.

Gradually the tree-cover diminished, and grasses took their place. Eventually the forests were replaced with the African savannah grasslands of today. The cooler weather suited the more mobile and social Homo erectus better. But it meant that Paranthropus had to rely on less desirable foods.