Earth

Study in mice shows genes may be altered through drug repurposing

image: A representative eye of a PAX6 deficient mouse after treatment (right) showing a better-developed eye and clear cornea compared to a control treated PAX6 deficient mouse eye (left) showing a smaller eye with scarring and blood vessel growth.

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University of Illinois Chicago

Researchers at the University of Illinois Chicago have published a study showing a promising approach to using drug repurposing to treat genetic diseases.

A team from the UIC Department of Ophthalmology and Visual Sciences published the article, "Gene dosage manipulation alleviates manifestations of hereditary PAX6 haploinsufficiency in mice" in the journal Science Translational Medicine.

Nearly all the genes in human DNA have two copies, one inherited from the mother and one from the father. There are some genetic diseases where only one copy is normal and the other one is non-functional due to a mistake in the DNA. The idea behind this study was to see if the normal copy can be enhanced to make up for the non-functional copy, said Ali Djalilian, UIC professor of ophthalmology and corresponding author of the paper.

Researchers used a mouse model of the human disease aniridia, an eye disorder that affects the iris and causes substantial visual impairment and can also be associated with systemic abnormalities. In aniridia, one copy of the gene PAX6 is normal and the other copy is non-functional. The PAX6 gene is important in eye development and patients with aniridia and PAX6 deficiency are born with eye problems, which limit their vision and can progress throughout life, Djalilian said.

The investigators screened drugs that can enhance PAX6 and found a particular class of drugs known as MEK inhibitors can stimulate PAX6 expression in the eye. They tested this drug in newborn PAX6 deficient mice and found that either topical or oral administration of the drug enhanced PAX6 and partially normalized their eye development. Mice treated with topical MEK inhibitor had clearer corneas (less scarring) and could see better.

"Patients with aniridia can develop progressive loss of their corneal stem cells which is a challenging clinical problem. Our research in the Corneal Regenerative Medicine Laboratory is aimed at regenerating healthy corneal cells, which we hope can help these and similar patients," said Mark Rosenblatt, dean of the UIC College of Medicine and a co-author on the study.

"More studies are certainly needed before this approach can be tested in human patients, nonetheless, the study opens the possibility of using approved medications in some genetic diseases to enhance the function of a normal copy of a gene to compensate for the non-functional copy," said Djalilian.

Credit: 
University of Illinois Chicago

How climate change is disrupting ecosystems

image: Roesel's bush-cricket is one of the many grasshoppers that might migrate to higher elevations once the climate in lower elevations has become unsuitable.

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Photograph: Christian Roesti

The world is getting warmer and warmer - and many organisms native to lower latitudes or elevations are moving higher.

However, novel organisms moving into a new habitat could disturb the ecological balance which has been established over a long period. Plants and herbivores are characterised by long-term co-evolution, shaping both their geographic distribution and the characteristics that they display in their occupied sites.

At higher elevations, this is seen in insect herbivores being generally less abundant and plants in turn being less well defended against herbivores, as a result of lower energy and shorter growing seasons. In contrast, low-elevation plant species defend themselves against more abundant and diverse herbivores, whether by means of spikes, thorns or hair, or by toxic substances. Climate change could disturb this ecological organisation.

Grasshoppers translocated to high elevations

In an experiment, researchers from ETH Zurich, the Swiss Federal Institute for Forest, Snow and Landscape Research (WSL) and the University of Neuchâtel investigated what could happen if herbivores - in this case various grasshoppers from middle elevations - settled in alpine meadows at higher elevations and encountered new plant communities there. The study has just been published in the journal Science.

The researchers translocated various grasshopper species from medium altitudes (1,400 metres above sea level) to three alpine grassland sites at elevations of 1,800, 2,070 and 2,270 metres above sea level, where the ecologists placed the grasshoppers in cages. The local grasshoppers had previously been removed from the experimental areas. The experiment was carried out in the Anzeindaz region in the Vaud Alps, Switzerland.

In their study, the researchers measured things like how the biomass, structure and composition of the alpine plant communities changed under the influence of the herbivorous insects. The researchers also investigated whether some plant species were more susceptible to herbivory, for instance plants with tougher leaves, or those containing more silica or other constituents such as phenols or tannins.

Lowland grasshoppers influence alpine community

The ecologists discovered that the grasshoppers' feeding behaviour had a clear influence on the vegetation structure and composition of the alpine flora. Alpine communities display clear structure in the organisation of the canopy, with plants with tough leaves at the top, and more shade-tolerant plants with softer leaves at the bottom. But this natural organisation was disturbed, because the translocated grasshoppers preferred to feed on taller and tough alpine plants, which exhibited functional characteristics such as leaf structure, nutrient content, chemical defence, or growth form similar to those of their previous, lower-elevation food plants. As a result, the insects reduced the biomass of dominant tough alpine plants, which in turn favoured the growth of small-stature plant species that herbivores avoid. The overall plant diversity thus increased in the short term.

"Immigrant herbivores consume specific plants in their new location and this changes and reorganises the competitive interaction between those alpine plant species," says the study's first author, Patrice Descombes. Global warming, for example, could disrupt the ecological balance because mobile animals, including many herbivorous insects, can expand their habitat to higher elevations more rapidly than sedentary plants. Herbivorous insects from lower altitudes could therefore have an easy time in alpine habitats with resident plants that are insufficiently or not at all prepared to defend themselves against those new herbivores. This could change the current structure and functioning of alpine plant communities as a whole. Climate change would thus have an indirect impact on ecosystems, in addition to the direct consequences of rising temperatures.

Important drivers of changed ecosystems

For Loïc Pellisier, Professor of Landscape Ecology at ETH Zurich and WSL, this indirect effect of climate change on ecosystems is one of the most important things to emerge from the study: "Climate impact research has largely investigated the direct effects of temperature on ecosystems, but these novel interactions that arise between species moving into new habitats could generate important structural modifications. They are important drivers of changed ecosystems in an increasingly warm climate."

With their results, the researchers also want to improve models that have so far only inadequately integrated such processes. They also hope that this will improve the prognosis of how climate change will influence the functioning of ecosystems and the services they provide.

Credit: 
ETH Zurich

Oceans without oxygen

With no dissolved oxygen to sustain animals or plants, ocean anoxic zones are areas where only microbes suited to the environment can live.

"You don't get big fish," said UC Santa Barbara biogeochemist Morgan Raven. "You don't even get charismatic zooplankton." But although anoxic oceans may seem alien to organisms like ourselves that breathe oxygen, they're full of life, she said.

These strange ecosystems are expanding, thanks to climate change -- a development that is of concern for fisheries and anyone who relies on oxygen-rich oceans. But what piques Raven's interest is the changing chemistry of the oceans -- the Earth's largest carbon sink -- and how it could move carbon from the atmosphere to long-term reservoirs like rocks.

"What happens to our carbon cycle as we get these large areas of the ocean that are oxygen-free?" she said. This question was central to research conducted by Raven and colleagues Rick Keil (University of Washington) and Samuel Webb (Stanford Linear Accelerator Laboratory) in a paper published in the journal Science.

'A spinning wheel'

In oxygen-rich oceans, carbon is moved around largely by food web processes that begin with carbon dioxide-fixing phytoplankton that photosynthesize at the water's surface.

"Most of the time they just get eaten by zooplankton," Raven said. But if they aren't eaten by larger animals, they head to the depths where they respire carbon dioxide and excrete organic carbon.

"It's like a spinning wheel -- CO2 goes to plankton, goes to CO2," Raven said.

In the absence of zooplankton and fish, however, more of the sinking organic carbon can survive and be deposited at depth, she said. In fact, sediments under these anoxic zones generally have more organic carbon deposits than their oxygen-rich counterparts. But, according to the researchers, we lack a "full mechanistic understanding" of how this occurs.

"It's been a bit of a mystery," Raven said.

The team did have a clue in the form of a hypothesis formed about a decade ago by University of Southern Denmark geologist Don Canfield and colleagues.

"They put out this idea that maybe inside of these zones, microbes are still eating organic carbon, but respiring sulfate," Raven said. Called "cryptic sulfur cycling," the idea was somewhat difficult to accept largely because the products of this microbial sulfate reduction (MSR) were difficult to detect, and because other compounds in the area, such as nitrates, were more energetically favorable to metabolize.

However, according to the study, "there is emerging molecular and geochemical evidence that suggests MSR may occur in (oxygen-deficient zones) despite plentiful dissolved nitrate."

The researchers tested whether this enigmatic process might be hiding inside of large (>1mm), fast-sinking organic particles by collecting particles from the Eastern Tropical North Pacific oxygen-deficient zone, roughly located off the northwestern coast of Mexico.

"It really is just this polymeric, sticky stuff," Raven said of the aggregations of mostly dead phytoplankton, fecal matter, other small organisms and bits of sand and clay that get glued together in a "fluffy" matrix. Collection of these particles is itself an accomplishment for researchers combing the vast oceans for relatively small, diffuse particles.

"My colleagues from the University of Washington had this collection device that was really the thing that made it possible to do this," she said. The collected particles were sent to the Stanford Synchotron Radiation Lightsource for analysis.

Pickled phytoplankton

Results of the analysis, such as evidence of the production of organic sulfur within the samples, demonstrate what Raven calls a "pickling" of the dead phytoplankton, as they sink through the anoxic area.

"Phytoplankton grow in the surface ocean, but due to gravity, they sink," she said. As they fall through the anoxic region, these organic aggregates undergo sulfurization, which has the effect of shielding the carbon at their core from enzymes or other substances that would otherwise wear them away.

"Even when it gets to the sediment, bacteria there can't eat these organic particles," noted Raven. And just like the pickles we know and love, the preservation process makes the organic particle resistant to bacteria, she said, which could explain why more organic carbon is found in the sediments below anoxic ocean zones.

Sulfurization of organic carbon particles in anoxic ocean zones, while newly confirmed in modern-day oceans, is actually an ancient process, Raven explained.

"It's the same process that can also make petroleum," she said, pointing out that where oilbeds are found, so, too, is sulfur. This process may have been widespread during the Cretaceous period (145.5 to 65.5 million years ago), when the Earth was consistently tropical and the ocean was subject to geologic and mass extinction events that resulted in the burial of massive amounts of carbon, and anoxic waters throughout the Atlantic.

"What we didn't know is whether this was also going on in these less extreme modern environments," Raven said.

What remains to be seen is how these growing oxygen depleted zones will interact with climate change.

"Potentially as these zones expand, there could be a negative feedback -- more CO2 in the atmosphere makes higher temperatures, which makes these zones bigger," Raven said. "These bigger zones then trap more CO2 and put it in the sediment and rocks." This feedback might help the Earth balance its carbon cycle over time, she said, "but we need to know how this connects to everything else."

Credit: 
University of California - Santa Barbara

SARS-CoV-2-like particles very sensitive to temperature

image: A group of SARS-CoV-2 virus-like particles are shown in panel (A) on a glass surface in room temparture. The color scale describes the height of each particle--red is the tallest and dark blue is the flattest. (B) Virus-like particles imaged at about 93 degrees F (34 degrees C) under dry conditions. There is no discernable features of the particles in panel A, indicating the particle structure degraded. (C) The virus-like particles that were incubated at about 93 degrees F (34 degrees C) in a buffer solution, and imaged at room temperature. The particles are more consistent with A, but still reveal widespread structural degradation.

Image: 
Sharma et. al. (2020) Biochem Biophys Res Comms

Winter is coming in the northern hemisphere and public health officials are asking how the seasonal shift will impact the spread of SARS-CoV-2, the virus that causes COVID-19?

A new study tested how temperatures and humidity affect the structure of individual SARS-Cov-2 virus-like particles on surfaces. They found that just moderate temperature increases broke down the virus' structure, while humidity had very little impact. In order to remain infectious, the SARS-Cov-2 membrane needs a specific web of proteins arranged in a particular order. When that structure falls apart, it becomes less infectious. The findings suggest that as temperatures begin to drop, particles on surfaces will remain infectious longer.

This is the first study to analyze the mechanics of the virus on an individual particle level, but the findings agree with large-scale observations of other coronaviruses that appear to infect more people during the winter months.

"You would expect that temperature makes a huge difference, and that's what we saw. To the point where the packaging of the virus was completely destroyed by even moderate temperature increases," said Michael Vershinin, assistant professor at the University of Utah and co-senior author of the paper. "What's surprising is how little heat was needed to break them down--surfaces that are warm to the touch, but not hot. The packaging of this virus is very sensitive to temperature."

The paper published online on Nov. 28, 2020, in the journal Biochemical Biophysical Research Communications. The team also published a separate paper Dec. 14, 2020 in Scientific Reports describing their method for making the individual particle packaging. The virus-like particles are empty shells made from the same lipids and three types of proteins as are on an active SARS-Cov-2 viruses, but without the RNA that causes infections. This new method allows scientists to experiment with the virus without risking an outbreak.

The SARS-CoV-2 is commonly spread by exhaling sharply, (e.g. sneezing or coughing), which ejects droplets of tiny aerosols from the lungs. These mucus-y droplets have a high surface to volume ratio and dry out quickly, so both wet and dry virus particles come into contact with a surface or travel directly into a new host. The researchers mimicked these conditions in their experiments.

They tested the virus-like particles on glass surfaces under both dry and humid conditions. Using atomic force microscopy they observed how, if at all, the structures changed. The scientists exposed samples to various temperatures under two conditions: with the particles inside a liquid buffer solution, and with the particles dried out in the open. In both liquid and bare conditions, elevating the temperature to about 93 degrees F for 30 minutes degraded the outer structure. The effect was stronger on the dry particles than on the liquid-protected ones. In contrast, surfaces at about 71 degrees F caused little to no damage, suggesting that particles in room temperature conditions or outside in cooler weather will remain infectious longer.

They saw very little difference under levels of humidity on surfaces, however the scientists stress that humidity likely does matter when the particles are in the air by affecting how fast the aerosols dry out. The research team is continuing to study the molecular details of virus-like particle degradation.

"When it comes to fighting the spread of this virus, you kind of have to fight every particle individually. And so you need to understand what makes each individual particle degrade," Vershinin said. "People are also working on vaccines and are trying to understand how the virus is recognized? All of these questions are single particle questions. And if you understand that, then that enables you to fight a hoard of them."

Credit: 
University of Utah

All-cause excess mortality, COVID-19-related mortality among us adults

What The Study Did: Researchers used publicly available data to examine all-cause excess mortality (the gap between observed and expected deaths) and COVID-19-related mortality during the early period of the pandemic among adults ages 25 to 44.

Authors: Jeremy Samuel Faust, M.D., M.S., of Brigham and Women's Hospital in Boston, is the corresponding author.

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

(doi:10.1001/jama.2020.24243)

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

Credit: 
JAMA Network

When dinosaurs disappeared, forests thrived

image: Researcher overlooking one of the two field sites for the study, the Frenchman Valley in Chambery Coulee Saskatchewan in July 2017.

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McGill University

It's known that the primary cause of the mass extinction of dinosaurs, about 66 million years ago, was a meteorite impact. But the exact mechanisms that linked the meteorite impact to mass extinction remain unclear, though climactic changes are thought to have played a part.

To understand how the mass extinction and associated climate changes affected specific ecosystems, a team of McGill scientists has analyzed the microscopic remains of plants from this period, found in the sediment of rivers in southern Saskatchewan. In a recent article in Palaeogeography, Palaeoclimatology, Palaeoecology they show that in this area, local plant communities and ecosystems experienced a long-term shift towards fewer aquatic plants and an increase in terrestrial plants, including trees such as birches and elms. The researchers speculate that this increase was due to the extinction of large plant-eating dinosaurs. They also found, unexpectedly, that changes in rainfall patterns during the extinction event were relatively minor and short-lived.

"This could be important as we look to the future of global warming, where many scientists have predicted that changes in precipitation could have big impacts on humans and ecosystems," says Peter Douglas from McGill's Department of Earth and Planetary Scientists and senior author on the paper. "At other times of major climate change in Earth's history we typically do see evidence for such changes. The absence of such a signal during the most recent mass extinction event is intriguing."

Douglas adds, "Surprisingly, scientists know more about what happened in the oceans at the end-Cretaceous extinction than on land. By clarifying the environmental changes occurring during this period, we narrowed down the factors that are likely to have caused the disappearance of dinosaurs. The research also provides an important analogue for environmental changes humans are causing to the planet, and the potential for future mass extinction."

Credit: 
McGill University

New theranostic approach reduces tumor volume and increases survival in NET study

image: Representative maximum intensity projection PET/CT images of AR42J tumor-bearing female Balb/c nude mice following injection of 64Cu-CuSarTATE (3 MBq, 0.24 nmol of peptide) at 1 and 4 hours post injection.

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Images created by associate professor Carleen Cullinane (Peter MaCallum Cancer Centre).

Reston, Virginia--A pair of copper radionuclides that target the somatostatin receptor overexpressed in neuroendocrine tumors has proven successful in identifying tumors and improving survival. According to new research published in the December issue of The Journal of Nuclear Medicine, the imaging agent 64Cu-CuSarTate produced high-quality positron emission tomography (PET) images in a mouse model of neuroendocrine tumors, while its therapeutic counterpart, 67Cu-CuSarTate, was highly effective in reducing tumor volume and extending lifespan. The research also demonstrated the advantages of delivering the radionuclide therapy as two fractionated doses, as opposed to one.

Neuroendocrine tumors typically are diagnosed with 68Ga-DOTA-octreotate and treated with 177Lu-LuTATE peptide receptor radionuclide therapy. However, using two different chemical elements (Ga and Lu) can lead to inconsistent tissue biodistribution, as they do not have the same binding and internalizations interactions. "Ideally, a chemically identical 'imaging-therapeutic' pair of radionuclides bound to the same targeting agent should be used for diagnosis and treatment," said Paul S. Donnelly, BSc(Hons), PhD, professor in the School of Chemistry at the University of Melbourne in Melbourne, Victoria, Australia.

In the study, researchers utilized a preclinical mouse model to explore the chemically identical radionuclide pair 64Cu-CuSarTate and 67Cu-CuSarTate. To assess the ability of 64Cu-CuSarTate to positively identify tumors, PET imaging occurred at one hour and four hours after injection of the radiotracer. On completion of the four-hour imaging, mice were euthanized and biodistribution studies were performed.

Multiple therapy experiments were also performed to evaluate the efficacy of 67Cu-CuSarTate. In the first, mice were injected with five MBq of 177Lu-LuTATE, five MBq of 67Cu-CuSarTate or saline and monitored for tumor growth. In the second experiment, mice were injected with a total of 30 MBq of 177Lu-LuTATE, 67Cu-CuSarTate or saline either as a single intravenous injection or as two 15 MBq fractions, two weeks apart; tumor growth was then monitored.

64Cu-CuSarTate PET images acquired at both one hour and four hours post-injection revealed very high tumor uptake and excellent tumor-to-background ratios. The high tumor uptake was confirmed with the ex vivo biodistribution analysis. Tumor growth was inhibited by 75 percent with 67Cu-CuSarTate treatment and by 89 percent with 177Lu-LuTATE, and survival was extended from 12 days in the control group to 21 days following treatment with both therapies. Treatment of tumors with two fractions of either 177Lu-LuTATE or 67Cu-CuSarTate significantly improved survival when compared to delivery as a single fraction. Equivalent efficacy was observed between the two therapies following treatment on both the single and fractionated schedules.

"Copper radionuclides are beneficial for several reasons," said Rodney J. Hicks, MBBS, MD, FRACP, FAHMS, professor in the Sir Peter MacCallum department of oncology at the University of Melbourne, in Melbourne, Victoria, Australia. "The strong binding of copper within the tumor allows for increased detection of disease, which can serve to limit radiation exposure to normal tissues during therapy. The ability to image at multiple time points with 64Cu-CuSarTate supports prospective dosimetry for therapeutic treatment planning with 67Cu-CuSarTATE, which could potentially offer shorter cycling of treatment, particularly for more aggressively growing tumors."

In terms of potential translation of the copper-64/67 theranostic pair to clinical studies, it is pertinent that copper-64 is produced in a cyclotron. The longer half-life of 64Cu-CuSarTATE as compared to 68Ga-DOTA-octreotate means that the tracer can be easily produced under good manufacturing practice conditions and transported regionally. 67Cu-CuSarTATE can be produced with linear-accelerators in high specific activity and radionuclide purity, so it is not reliant on nuclear reactors.

"Looking to the future of molecular imaging and nuclear medicine, the chemistry and general concepts presented in this study could be expanded to other peptides that target different receptors, as well as antibodies and engineered antibody fragments. This offers the potential to provide diagnostic imaging using copper-64 to plan individualized treatments with copper-67 agents for a wide range of cancer patients," noted Donnelly.

Credit: 
Society of Nuclear Medicine and Molecular Imaging

A well-rooted study

Spend time in any of the world's great forests and you'll start seeing the trees as immense pillars holding the heavens aloft while firmly anchored in the earth. It's as much fact as sentiment. Trees really do link the ground to the sky by exchanging energy and matter between the soil and the atmosphere. Researchers believe that understanding this connection could provide both a wealth of scientific insight into ecosystems and practical applications that address challenges such as water resource conservation and management.

A recent study led by UC Santa Barbara's Marc Mayes investigates how patterns in tree water loss to the atmosphere, tracked with satellite imagery, relates to groundwater supplies. The results validate at landscape-wide scales ideas that scientists have proposed based on decades of research in labs and greenhouses. What's more, the techniques lend themselves to an accurate, efficient way of monitoring groundwater resources over large areas. The findings appear in the journal Hydrological Processes.

For all their diversity, most plants have a very simple game plan. Using energy from sunlight, they combine water from the ground with carbon dioxide from the air to produce sugars and oxygen. During photosynthesis, plants open small pores in their leaves to take in CO2, which also allows water to escape. This process of water loss is called evapotranspiration -- short for soil evaporation and plant transpiration -- and it's essentially a transaction cost of transporting the ingredients for photosynthesis to the leaves where the process occurs.

Just like evaporating sweat cools down our own bodies, the evapotranspiration from the trees cools down the forest. With the proper understanding and technology, scientists can use thermal image data from satellites as well as manned and unmanned aircraft to understand the relationship between plants and groundwater: cooler temperatures correlate with more evapotranspiration.

"The core hypothesis of this paper is that you can use relationships between plant water use [as] measured by [satellite] image data, and climate data including air temperature and rainfall, to gauge the availability of, and changes in, groundwater resources," said Mayes, an Earth scientist and remote sensing expert based at the university's Earth Research Institute (ERI).

Mayes and his colleagues focused on the flora of dryland rivers -- those in deserts and Mediterranean climates. Throughout these regions, many plants have evolved adaptations that minimize water loss, like slow growth, water retention or boom-bust lifecycles. However, plants that dominate river channels -- species like sycamore, cottonwood and willows -- evolved to take advantage of the surplus groundwater the habitat offers relative to the surrounding landscape.

"Rather than slowing down its water use when water becomes scarce, this vegetation will basically drink itself to death," Mayes said. This makes it a good window into conditions below the surface.

The team used satellite-based thermal imaging to look at temperatures across the San Pedro River corridor in southern Arizona. On cloud-free days the satellites can gather data on surface temperatures at high resolution over large areas of land. By comparing the temperatures along the river to those in nearby, more sparsely vegetated areas, the researchers were able to determine the extent of evapotranspiration along different parts of the river at different times. They found that it correlated with air temperature in water-rich environments and with rainfall in water-scarce environments.

The findings support recent advances in our understanding of plant water use. The hotter and drier the air, the stronger it pulls water from the leaves, and the more water the plant uses. Consequently, Mayes and his colleagues expected to see evapotranspiration vary with air temperature as long as the stream has abundant groundwater for the plants to draw on.

On the other hand, where groundwater is scarce, plants will close the openings on their leaves to avoid water loss; it's more important to avoid drying out than to take advantage of the extra sunshine on a warm day. As a result, evapotranspiration will correlate much more strongly with rainfall and streamflow, which increases the supply of water to trees through their roots.

Scientists had demonstrated the predictable effect of evapotranspiration in lowering surface temperatures in lab and small field experiments. However, this is the first study to demonstrate its impact over large areas. The technology that made this possible has matured only within the past five years.

"This remote sensing method shows great promise for identifying the relevant climatic versus other controls on tree growth and health, even within narrow bands of vegetation along rivers," said coauthor Michael Singer, a researcher at ERI and lead investigator on the project that funded Mayes' work.

In fact, these ecosystems are vitally important to the southwestern U.S. "Despite taking up about 2% of the landscape, over 90% of the biodiversity in the Southwest relies on these ecosystems," said coauthor Pamela Nagler, a research scientist at the U.S. Geological Survey's Southwest Biological Science Center.

The same techniques used in the paper could be applied to the perennial challenge of groundwater monitoring. In fact, this idea helped motivate the study in the first place. "It's very hard to monitor groundwater availability and change[s] in groundwater resources at the really local scales that matter," Mayes said. "We're talking about farmers' fields or river corridors downstream of new housing developments."

Monitoring wells are effective, but provide information only for one point on the map. What's more, they are expensive to drill and maintain. Flux towers can measure the exchange of gasses between the surface and the atmosphere, including water vapor. But they have similar drawbacks to wells in terms of cost and scale. Scientists and stakeholders want reliable, cost-effective methods to monitor aquifers that provide wide coverage at the same time as high resolution. It's a tall order.

While it may not be quite as precise as a well, remote thermal imaging from aircraft and satellites can check off all of these boxes. It offers wide coverage and high resolution using existing infrastructure. And although it works only along stream corridors, "an inordinate amount of agricultural land and human settlements in dry places ends up being where the water is, along stream paths," Mayes said.

The idea is to look for shifts in the relationships of evapotranspiration to climate variables over time. These changes will signal a switch between water-rich and water-poor conditions. "Detecting that signal over large areas could be a valuable early warning sign of depleting groundwater resources," Mayes said. The technique could inform monitoring and pragmatic decision-making on groundwater use.

This study is part of a larger Department of Defense (DOD) project aimed at understanding how vulnerable riverine habitats are to droughts on DOD bases in dryland regions of the U.S. "We are using multiple methods to understand when and why these plants become stressed due to lack of water," said Singer, the project's lead scientist. "[We hope] this new knowledge can support the management of these sensitive ecological biomes, particularly on military bases in dryland regions, where these pristine habitats support numerous threatened and endangered species."

Mayes added, "What's coming down the pipe is a whole ensemble of work looking at ecosystem responses to water scarcity and water stress across space and time that informs ways we both understand ecosystem response and also improve the monitoring."

Credit: 
University of California - Santa Barbara

Aging journal fills knowledge gaps on race, mental health

A new special issue of the journal Innovation in Aging, titled "Race and Mental Health Among Older Adults: Within- and Between-Group Comparisons," is expressly devoted to much-needed research on aging and mental health within racial and ethnic minority populations (e.g., African Americans, Latinx, and Asian Americans, as well as subgroups within these larger pan-ethnic categories).

"The lack of quality research on mental health for older members of racial and ethnic population groups has been a serious impediment to amassing a solid understanding of aging processes and contextual factors that are consequential for mental well-being in later life," wrote Robert Joseph Taylor, PhD, MSW, who served as the guest editor for this special issue. "This gap in the literature on aging is long-standing and particularly problematic given projected increases in the numbers of older adults from racial and ethnic minority population groups."

The articles contained within address several psychosocial issues in relation to mental health status -- including loneliness and hopelessness, risk factors for poor mental health such as obesity and stress, as well as protective factors such as religion and social support.

"Knowledge of the factors associated with mental health and aging for racial and ethnic minority adults is imperative for ensuring the personal well-being of older adults, their families, and communities," Taylor said. "Further, this information is critical for the education and training of mental health practitioners who work with older adults in various settings (e.g., outpatient clinics, hospitals, nursing homes) and the development of mental health interventions and services that are culturally informed and congruent with the life experiences of racial and ethnic older adults."

Credit: 
The Gerontological Society of America

UC Study: Suicide watch more important now than ever

image: Yockey is lead author on the study "Trends in Suicidal Behaviors Among US Adults 2015-2018" - published in Crisis: The Journal of Crisis Intervention and Suicide Prevention.

Image: 
University of Cincinnati

A recent study by a team of University of Cincinnati researchers shows that suicide planning, attempts and completions were already on the rise pre-COVID-19. Add a pandemic to a holiday season, when depression and suicide are typically higher among both adolescents and adults, and the last couple of weeks of 2020 may be a time to be on even higher alert.

According to health data, nearly 1.5 million Americans attempt suicide each year.

"It's just unbelievable to me how we are not talking loudly about mental health; especially now," says Andrew Yockey, a researcher and doctoral student in UC's College of Education, Criminal Justice and Human Services.

Yockey is lead author on the study "Trends in Suicidal Behaviors Among US Adults 2015-2018" - published in Crisis: The Journal of Crisis Intervention and Suicide Prevention.

The study, conducted at UC's Center for Prevention Science, found that between 2015 to 2018, there was a 16% increase in suicide ideation, an 18.6% increase in suicide planning, and an 11.6% increase in suicide attempts. Additionally, significant increases in each behavior were found in African Americans, younger adults, sexual minorities, and individuals who reported past-year drug use. Among these higher-risk groups, the largest increases in suicidal behaviors were African Americans.

The researchers looked at sample data, the most recent available at the time of the study, collected from the National Survey Drug Use and Health Survey.

"The numbers are there," Yockey says. "We have treatment options from a behavioral health and medication standpoint, but we are neglecting the primary prevention aspect ... the development of coping skills."

And preliminary data from 2019-2020 indicates it's getting worse, say the study's co-authors: Keith King, the center's research director, and co-director Rebecca Vidourek, both professors at UC's School of Human Services.

"Suicide is currently among the top ten leading causes of death among adults, and in teenagers it's in the top three," says King, noting that depression, loneliness, and disconnectedness, such as what is occurring now on a national level with the pandemic, are strong contributing factors.

He also points to stress, citing job loss, home schooling, eldercare concerns among the many new stressors the public now faces.

"For the past two decades, the center has been examining and identifying the risk factors to suicide as a means to prevent suicidal thoughts and attempts. We believe our findings can inform harm reduction efforts and health messages surrounding suicide prevention," says Vidourek. Yockey says There needs to be more recognition such as statewide funding for classes, workshops and education for students, educators and families "because the problem will not go away if you don't talk about it."

While the team utilizes research to identify the risk factors, their efforts also concentrate on education, preferably at an early age.

"The most effective way to prevent teen suicide is to ensure that adolescents are positively connected to their family, school, and peers. Positive connections are key, especially this holiday season," says King. "We need to remember that suicide is preventable. Openly talk about suicide and mental health, identify individuals at risk and ensure that those at risk get the help they need."

Five tips from UC experts to help prevent suicide:

1) Build positive connections.

2) Know the warning signs to suicide.

3) Help individuals who are suicidal to seek help from a mental health professional.

4) Develop effective coping skills.

5) Build community awareness of suicide prevention.

Credit: 
University of Cincinnati

New in the <i>Hastings Center Report</i>, November-December 2020

Prescription Requirements and Patient Autonomy: Considering an Over-the-Counter Default
Madison Kilbride, Steven Joffe, and Holly Fernandez Lynch

When new drugs are approved by the Food and Drug Administration, the default assumption is that they will be available by prescription only, safe for use exclusively under clinical supervision. The paternalism underlying this default must be interrogated in order to ensure appropriate respect for patient autonomy. Upon closer inspection, prescription requirements are justified when nonprescription status would risk harm to third parties and when a large segment of the population would struggle to exercise their autonomy in using a drug safely and effectively on their own. Although these justifications can support prescription status for many drugs, this article proposes that reversing the FDA's current default to instead begin with a presumption in favor of over?the?counter status is the best way to avoid interference with valid claims of patient autonomy. Under this approach, a range of drug products, including oral contraceptives, statins, and HIV?prevention drugs, could be considered for an OTC switch. The authors are at the Perelman School of Medicine at the University of Pennsylvania.

Also in this issue:

The Social Risks of Science
Jonathan Herington, Scott Tanona

Another Voice: Health Research and Social Justice Philosophy
Sridhar Venkatapuram

Case Study: A Small-Town Heart
Tim Lahey, Jennifer L. Herbst, Marielle S. Gross, Brandi Braud Scully

Perspective: OK, Boomer, MD: The Rights of Aging Physicians and the Health of Our Communities
Tia Powell

Credit: 
The Hastings Center

SwRI models point to a potentially diverse metabolic menu at Enceladus

image: This figure illustrates a cross-section of Enceladus, showing a summary of the processes SwRI scientists modeled in the Saturn moon. Oxidants produced in the surface ice when water molecules are broken apart by radiation can combine with reductants produced by hydrothermal activity and other water-rock reactions, creating an energy source for potential life in the ocean.

Image: 
SwRI

SAN ANTONIO -- Dec. 16, 2020 -- Using data from NASA's Cassini spacecraft, scientists at Southwest Research Institute (SwRI) modeled chemical processes in the subsurface ocean of Saturn's moon Enceladus. The studies indicate the possibility that a varied metabolic menu could support a potentially diverse microbial community in the liquid water ocean beneath the moon's icy facade.

Prior to its deorbit in September of 2017, Cassini sampled the plume of ice grains and water vapor erupting from cracks on the icy surface of Enceladus, discovering molecular hydrogen, a potential food source for microbes. A new paper published in the planetary science journal Icarus explores other potential energy sources.

"The detection of molecular hydrogen (H2) in the plume indicated that there is free energy available in the ocean of Enceladus," said lead author Christine Ray, who works part time at SwRI as she pursues a Ph.D. in physics from The University of Texas at San Antonio. "On Earth, aerobic, or oxygen-breathing, creatures consume energy in organic matter such as glucose and oxygen to create carbon dioxide and water. Anaerobic microbes can metabolize hydrogen to create methane. All life can be distilled to similar chemical reactions associated with a disequilibrium between oxidant and reductant compounds."

This disequilibrium creates a potential energy gradient, where redox chemistry transfers electrons between chemical species, most often with one species undergoing oxidation while another species undergoes reduction. These processes are vital to many basic functions of life, including photosynthesis and respiration. For example, hydrogen is a source of chemical energy supporting anaerobic microbes that live in the Earth's oceans near hydrothermal vents. At Earth's ocean floor, hydrothermal vents emit hot, energy-rich, mineral-laden fluids that allow unique ecosystems teeming with unusual creatures to thrive. Previous research found growing evidence of hydrothermal vents and chemical disequilibrium on Enceladus, which hints at habitable conditions in its subsurface ocean.

"We wondered if other types of metabolic pathways could also provide sources of energy in Enceladus' ocean," Ray said. "Because that would require a different set of oxidants that we have not yet detected in the plume of Enceladus, we performed chemical modeling to determine if the conditions in the ocean and the rocky core could support these chemical processes."

For example, the authors looked at how ionizing radiation from space could create the oxidants O2 and H2O2, and how abiotic geochemistry in the ocean and rocky core could contribute to chemical disequilibria that might support metabolic processes. The team considered whether these oxidants could accumulate over time if reductants are not present in appreciable amounts. They also considered how aqueous reductants or seafloor minerals could convert these oxidants into sulfates and iron oxides.

"We compared our free energy estimates to ecosystems on Earth and determined that, overall, our values for both aerobic and anaerobic metabolisms meet or exceed minimum requirements," Ray said. "These results indicate that oxidant production and oxidation chemistry could contribute to supporting possible life and a metabolically diverse microbial community on Enceladus."

"Now that we've identified potential food sources for microbes, the next question to ask is 'what is the nature of the complex organics that are coming out of the ocean?'" said SwRI Program Director Dr. Hunter Waite, a coauthor of the new paper, referencing an online Nature paper authored by Postberg et al. in 2018. "This new paper is another step in understanding how a small moon can sustain life in ways that completely exceed our expectations!"

The paper's findings also have great significance for the next generation of exploration.

"A future spacecraft could fly through the plume of Enceladus to test this paper's predictions on the abundances of oxidized compounds in the ocean," said SwRI Senior Research Scientist Dr. Christopher Glein, another coauthor. "We must be cautious, but I find it exhilarating to ponder whether there might be strange forms of life that take advantage of these sources of energy that appear to be fundamental to the workings of Enceladus."

Credit: 
Southwest Research Institute

Unique prediction of 'modified gravity' challenges dark matter

image: The best example is represented by the Sunflower galaxy (NGC 5055) with the strongest external field
among SPARC galaxies, whose well-measured rotation curve shows a mildly declining behavior at large
radial distance and can be accurately modeled only with an external field effect.

Image: 
Creative Commons

An international group of scientists, including Case Western Reserve University Astronomy Chair Stacy McGaugh, has published research contending that a rival idea to the popular dark matter hypothesis more accurately predicts a galactic phenomenon that appears to defy the classic rules of gravity.

This is significant, the astrophysicists say, because it further establishes the hypothesis--called modified Newtonian dynamics (MOND), or "modified gravity"--as a viable explanation for a cosmological dilemma: that galaxies appear to buck the long-accepted rules of gravity traced to Sir Isaac Newton in the late 1600's.

The mystery: For decades, we've measured more gravitational pull in space than we think we should have--that there's not enough visible or known matter to account for it all.

So, dark matter proponents theorize that most of the known universe is actually made of material that doesn't interact with light, making it invisible and undetectable-- but that this material accounts for much of the gravitational pull among galaxies. It has been the prevailing theory for nearly 50 years.

MOND theory, a counter explanation introduced by physicist Mordehai Milgrom from Weizmann Institute (Israel) in the early 1980s, says this gravitational pull exists because the rules of gravity are slightly altered.

Instead of attributing the excess gravitational pull to an unseen, undetectable dark matter, MOND suggests that gravity at low accelerations is stronger than would be predicted by a pure Newtonian understanding.

In addition, MOND made a bold prediction: the internal motions of an object in the cosmos should not only depend on the mass of the object itself, but also the gravitational pull from all other masses in the universe--called "the external field effect" (EFE).

Milgrom said the findings, if robustly confirmed, would be "the smoking gun proving that galaxies are governed by modified dynamics rather than obeying the laws of Newton and of general relativity."

150 galaxies tested for EFE

McGaugh and his collaborators, led by Kyu-Hyun Chae, from Sejong University in South Korea, say they detected this EFE in more than 150 galaxies studied.

Their findings were published recently in The Astrophysical Journal.

"The external field effect is a unique signature of MOND that does not occur in Newton-Einstein gravity," McGaugh said. "This has no analogy in conventional theory with dark matter. Detection of this effect is a real head-scratcher."

The team of six astrophysicists and astronomers includes lead author Chae and other contributors from the United Kingdom, Italy and the United States.

"I have been working under the hypothesis that dark matter exists, so this result really surprised me," Chae said. "Initially, I was reluctant to interpret our own results in favor of MOND. But now I cannot deny the fact that the results as they stand clearly support MOND rather than the dark matter hypothesis."

Analyzing rotating galaxies

The group analyzed 153 rotation curves of disk galaxies as part of their study. The galaxies were selected from the Spitzer Photometry and Accurate Rotation Curves (SPARC) database, created by another collaborator, Federico Lelli, during his postdoctoral studies at Case Western Reserve, McGaugh and co-author James Schombert, of the University of Oregon.

In addition to Chae, McGaugh, Lelli and Schombert, the authors of the research were Pengfei Li from Case Western Reserve and Harry Desmond from the University of Oxford.

The scientists said they deduced the EFE by observing that galaxies in strong external fields slowed (or exhibited declining rotation curves) more frequently than galaxies in weaker external fields--as predicted by MOND alone.

Lelli said he was skeptical by the results at first "because the external field effect on rotation curves is expected to be very tiny. We spent months checking various systematics. In the end, it became clear we had a real, solid detection."

McGaugh said that skepticism is part of the scientific process and understands the reluctance of many scientists to consider MOND as a possibility.

"I came from the same place as those in dark matter community," he said. "It hurts to think that we could be so wrong. But Milgrom predicted this over 30 years ago with MOND. No other theory anticipated the observed behavior."

Credit: 
Case Western Reserve University

Plant diversity in Germany on the decline

image: The study shows that even species that are considered widespread, such as the corn poppy (Papaver rhoeas), are steadily declining in Germany.

Image: 
Sebastian Lakner

In an area covering the whole of Germany, in every grid field of approximately 5 by 5 kilometres - the decline in species diversity averages around two percent per decade. Especially vulnerable are the archaeophytes; species brought to Germany by humans but before the discovery of America. Among others, these include a large proportion of accompanying field flora, such as the corn marigold and the large Venus's looking glass, but also species such as the narrow-leaved rattle and the perennial goosefoot. On the other hand, many neophytes - those species that reached Germany after 1492, were also able to spread, such as the Himalayan balsam or the narrow-leaved ragwort. The results of this study make it clear that even this increase could not compensate for the loss in the number of species per unit of area.

Study shows gradual biodiversity decline in Germany

For this study, the necessarily large and heterogeneous data sets were brought together, for the first time in Germany, and reliably statistically evaluated. Distribution data from 2136 of the over 4300 plant species established in Germany were included in the calculations. Species with very low reporting frequencies were not included. The foundation for this was the FlorKart database, in which the Federal Agency for Nature Conservation has collated data on the distribution of flora in Germany. This data is predominantly the result of intensive mapping work by volunteers; an endeavour which is indispensable for nature conservation. The data was supplemented by further data sets from universities and other scientific institutions, but also by information on the presence of plants from private individuals. Information gaps were filled by calculating the probability of plant occurrence.

BfN President Prof Dr Beate Jessel concludes: "This clearly shows, once again, that we have to rethink our approach to nature and landscape; after all, the population declines proven by the study extend over the whole of Germany. This leaves no doubt; we need a broad-based approach to agriculture and forestry, which together occupy 80 percent of the area of Germany. This demonstrates that there's an urgent need for more nature-compatible forms of land use."

Plant species brought in by humans (neophytes) are gaining ground

"The degree of clarity in these results really surprised us. They paint a very dismal picture of the state of plant diversity in Germany," says first author Dr David Eichenberg of iDiv. "This study has confirmed that the declines are not limited to already rare or particularly endangered species, but that a gradual reduction of biodiversity in the majority of plant species in Germany has obviously been happening for a long time."

The authors consider it likely that the observed decline in plant diversity has a major impact on biodiversity and ecosystem services. Due to the often very complex relationships between, for example, food webs and the cascade effect, such losses can have very serious consequences. It is evident that the intricate interrelationships between insects are affected, leading to decreases in both insect diversity and abundance.

However, the study also shows that data availability must continue to be improved in order to identify even subtle biodiversity losses as early as possible. In order to achieve this, the Federal Agency for Nature Conservation is currently setting out the basis for monitoring semi-frequent plant species in Germany. In contrast to rare species, whose populations and occurrence are often well surveyed, with current recording methods, declines in semi-frequent and common species are only noticed late, or not at all.

Credit: 
German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig

Scientists publish the first human psychological aging clock using artificial intelligence

image: Scientists at Deep Longevity published the first set of psychomarkers of aging developed using deep learning to track the changes in human psychology and assess the effectiveness of interventions, life events, and external events. The new PsychoAge and SubjAge aging clocks were linked to mortality risk.

Image: 
Mary Mitina

Today, Deep Longevity, a company developing artificial intelligence to track human aging and extend productive longevity, released the first AI-powered psychological aging clocks to analyze and interpret psychosocial factors in the context of aging. Deep Longevity researchers, joined by Dr. Peter Diamandis, the visionary physician, engineer, and entrepreneur, the founder of the XPRIZE Foundation and Singularity University published their study titled "PsychoAge and SubjAge: Development of Deep Markers of Psychological and Subjective Age Using Artificial Intelligence" in Aging.

Like other species following the classical evolutionary paradigm, humans are born, develop, reproduce, take care of their young, and then gradually decline and die. However, humans are conscious intelligent species and change their behavior, priorities, beliefs, and attitude, during life. Prior works on Socioemotional Selectivity Theory (SST) demonstrated that human life horizons can be manipulated and affect their behavior. To better understand the features that affect psychological age, and perceived age, and the mind-body connection in the context of aging, scientists at Deep Longevity decided to apply their skills in the development of deep biomarkers of aging to human psychology.

Biomarkers of aging that can accurately quantify the human aging process using various biological data types, commonly referred to as the "aging clocks", are among the most important recent advances in the field of longevity research. For example, in November, Deep Longevity scientists published one such aging clock based on DNA methylation, which showed superior performance to all other comparable solutions.

Despite massive progress in aging clock technology, the psychological aspect of aging has been severely understudied. However, the new study on deep psychomarkers of aging is expected to substantially accelerate the progress in the psychology of aging. The recently published study aims to fill this gap by demonstrating two AI-based age predictors: PsychoAge (which predicts chronological age) and SubjAge (which describes personal aging rate perception). These models were trained on a collection of >10,000 questionnaires completed by people aged 25-75 years as a part of the MacArthur Foundation's "Midlife in the United States (MIDUS)" study. The models presented in the publication were reworked into 15-question long surveys available at Young.AI to enable people to find out estimates of their psychological and subjective age.

The authors of the study verified the SubjAge on large independent datasets to discover that higher SubjAge is very predictive of all-cause mortality. More specifically, a person whose SubjAge is five years greater than the chronological age he or she reported is twice as likely to die as a person with normal age perception.

The authors also point out how SubjAge can be manipulated therapeutically to make patients feel younger and thus reduce their mortality risk. For example, developing openness to new experiences can reduce SubjAge prediction by seven years. Keeping the bar high, being productive and not backing away from difficult-to-reach goals will take another four years off of a person's psychological aging clock.

"For the first time, AI can predict human psychological and subjective age and help identify the possible interventions that can be applied in order to help people feel and behave younger" said Alex Zhavoronkov, PhD, founder and CLO of Deep Longevity and co-author of the study. "One's mindset may determine the decisions that ultimately affect their overall health. By identifying the psychosocial variables that underpin particular mindsets and behaviors, deep psychological clocks can serve as a powerful tool in promoting personal improvement, mental health, wellness, and a wide range of other health and therapeutic applications."

In follow-up studies of psychological aging, Deep Longevity plans to explore differences in the perception of aging between men and women, examine psychosocial markers connected to mental health, and build an integrated model of mental-physical health crosstalk.

About Young.AI: Young.AI is an AI-powered longevity web platform & iOS app created by the product of Deep Longevity. Young.AI users can access a variety of aging analysis tools, including psychological and subjective age estimation, to reach productive longevity.

Credit: 
Deep Longevity Ltd