Earth

Performance-enhancing substance use: A link to criminal offending

Toronto, ON - Despite research showing associations between anabolic steroid use and criminal offending, the possibility of a similar association between legal performance-enhancing substance use, such as creatine, and criminal offending remained unknown. A new study published online in the journal Drug and Alcohol Dependence now shows that both forms of performance-enhancing substance use is longitudinally associated with criminal offending among U.S. adults.

The study, which analyzed a sample of over 9,000 U.S. participants from the National Longitudinal Study of Adolescent Health (Add Health), highlights the need for more research on performance-enhancing substances to understand the complex social problems associated with their use.

"This is the first study to identify relationships between legal performance-enhancing substance use and criminal offending," says lead author Kyle T. Ganson, PhD, MSW, assistant professor at the University of Toronto's Factor-Inwentash Faculty of Social Work. "This finding is acutely salient because these substances are easily accessible and commonly used, particularly among young people."

The study highlights the importance of clinical professionals screening for performance-enhancing substance use and assessing patterns of criminal offending among young people.

"We need more research to identify effective prevention and intervention techniques to ensure that we reduce the use of these substances, as well as curtail any connection with criminal offending," says co-author Jason M. Nagata, MD, MSc, assistant professor at the University of California, San Francisco's Department of Pediatrics.

"The associations found in this study are likely explained by an intersection of behavioral, psychological, and sociocultural influences," says Ganson. "We therefore need to target this problem from a multitude of angles, including clinically and via public health and policy interventions."

Credit: 
University of Toronto

One "Ring" to rule them all: curious interlocked molecules show dual response

image: Displaying (a) force-free state, (b) reversible, and (c) irreversible responses. ?Scientists explored a curious interlocked molecular architecture called "rotaxane" and reported a new type of mechanophores response that is both reversible and irreversible depending on the magnitude of applied force without scission of chemical bonds.

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Journal of the American Chemical Society

Scientists at Tokyo Institute of Technology design polymers infused with a stress-sensitive molecular unit that respond to external forces by switching on their fluorescence. The researchers demonstrate the fluorescence to be dependent on the magnitude of force and show that it is possible to detect both, reversible and irreversible polymer deformations, opening the door to the exploration of new force regimes in polymers.

Besides causing physical motion, mechanical forces can drive chemical changes in controlled and productive ways, allowing for desirable material properties. One way to go about this is by introducing a so-called mechanophore into the material, molecular units that are sensitive to stress or strain. Specifically, mechanochromic mechanophores, which alter their optical properties in response to mechanical stimuli, are quite useful in quantifying their local mechanical environment.

However, the response mechanism at play in most mechanophores involves severing of chemical bonds. Consequently, they require relatively large mechanical forces to be activated and their response is usually not reversible. To address these issues, researchers led by Prof. Yoshimitsu Sagara from Tokyo Institute of Technology (Tokyo Tech) had previously developed supramolecular mechanophores that show instantly reversible on/off switching of fluorescence without any scission of covalent bonds. The team's next challenge was to determine if both reversible and irreversible mechanoresponses can be elicited from the same molecular motif.

In a new Journal of the American Chemical Society study, the team explores this question using an unusual molecular architecture called "rotaxane" in which a dumbbell-shaped molecule is threaded through a "ring" such that they are mechanically interlocked, i.e. the "ring" cannot be normally pulled out. By attaching a quencher-emitter pair to the rotaxane and selecting appropriate sizes of ring and stopper moieties, the team demonstrates a new type of mechanophore response that can be either reversible or irreversible, depending on the magnitude of the applied force (Figure 1).

"When there is no force applied, the attractive interaction keeps the emitter-containing ring near the quencher fixed on the rotaxane's axle, so that the emission is quenched," explains Sagara. "Upon applying a weak force, the emitter is moved away from the quencher, and its fluorescence is turned on. This effect is reversible, unless the force is sufficiently high to push the ring past the stopper so that irreversible dethreading occurs."

By investigating a carefully designed set of different rotaxanes, the team demonstrated that the combination of appropriately selected ring and stopper moieties having the right sized is crucial to obtain interlocked structures that display such dual response. Tokyo Tech researchers collaborated with Swiss partners from the University of Fribourg's Adolphe Merkle Institute to incorporate the new mechanophores into elastic polyurethane rubbers. These materials which exhibit reversible fluorescence changes over many stretch-and-release cycles to low strains, due to the shuttling function, whereas permanent changes were observed when the rubbers were subjected to repeated deformations to high strains due to dethreading of the ring from the axle. "This mechanism allows one, at least conceptually, to monitor the actual deformation of polymer materials and examine mechanical damage that were inflicted in the past on the basis of an optical signal" says Sagara.

Speculating the possible implications of their results, an elated Sagara comments, "Extending the current library of mechanophores with our rotaxane-based candidates would be useful for studying the mechanical properties of not only polymers but also cells and tissues, as our mechanophores can respond to much smaller forces compared to those involving chemical bond scission."

Simply put, rotaxanes could pervade all of natural science!

Credit: 
Tokyo Institute of Technology

Just mix it up: New synthetic method for making amphiphilic molecules without additives

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Image: 
Dr. Masahiro Yamashina

Amphiphilic molecules, which aggregate and encapsulate molecules in water, find use in several fields of chemistry. The simple, additive-free connection of hydrophilic and hydrophobic molecules would be an efficient method for amphiphilic molecule synthesis. However, such connections, or bonds, are often fragile in water. Now, scientists at Tokyo Institute of Technology have developed an easy way to prepare water-stable amphiphiles by simple mixing. Their new catalyst- and reagent-free method will help create further functional materials.

Soaps and detergents are used to clean things like clothes and dishes. But how do they actually work? It turns out that they are made of long molecules containing a "hydrophilic" or water-loving part and a "hydrophobic" or water-hating part. When added to water, these molecules self-assemble to form giant, spherical "supramolecules" called micelles that get the cleaning up done by using the hydrophobic part to trap the grease.

Known as "amphiphiles" to chemists, these molecules have garnered much attention due to their utility in developing supramolecular materials. The synthesis of amphiphiles usually requires several reactions and purifications. In contrast, if hydrophilic and hydrophobic molecules could be simply connected without chemicals, it would be a very powerful synthetic method. In fact, some reactions that do not require any catalysts or reagents are known today. However, they have a fatal flaw: their chemical bonds are unstable in water, the very medium necessary for micelle formation!

Addressing this issue in a recent study published in Angewandte Chemie, scientists at Tokyo Institute of Technology (Tokyo Tech), Japan, led by Dr. Masahiro Yamashina and Prof. Shinji Toyota, have now come up with a solution using a chemical reaction known as the "Staudinger reaction", in which an azide (hydrophilic part) and a phosphine (hydrophobic part) combine to form an "azaylide".

"Although a typical Staudinger reaction proceeds rapidly and quantitatively at room temperature, the formed azaylide readily hydrolyses into a primary amine and phosphine oxide in water. In contrast, a 'non-hydrolysis' version of this reaction was recently found, in which a halogen atom, such as chlorine, added to an azide compound significantly improves the hydrostability of azaylide," explains Yamashina.

Accordingly, the team of scientists prepared a chlorinated azide subcomponent and mixed it with tris(p-tolyl)phosphine (PTol3), triphenylphosphine (PPh3), and tris(p-anisyl)phosphine (PAni3) to obtain the azaylide-based amphiphiles NPTol3, NPPh3, and NPAni3, respectively. They then dissolved the amphiphiles in water to observe their self-assembling behavior and found spontaneous aggregation in each case. Further measurements revealed that the aggregates were in the shape of spheres roughly 2 nm in size.

The team also prepared the corresponding non-chlorinated azaylide-based amphiphiles--nNPTol3, nNPPh3, and nNPAni3--and investigated the water stability of both the chlorinated and non-chlorinated azaylides. The non-chlorinated azaylides quickly disintegrated in water while their chlorinated counterparts remained stable. While the difference was clearly due to the presence of the chlorine atom, the underlying mechanism was unclear. To figure this out, the scientists performed density functional theory calculations that helped them understand the structures of the azaylides.

Finally, when tested with hydrophobic organic dyes like Nile Red and BODIPY, the team saw that the dye molecules became encapsulated by the spherical azaylide aggregates, exhibiting desirable amphiphile behavior. "The azaylide formation presented in our study serves as a viable technique for on-site preparation of water-stable amphiphiles without catalysts and reagent, which can help create more such functional materials in future," comments an excited Yamashina.

The team's discovery will certainly help usher in significant advancements in the development of highly versatile functional materials, even in aqueous media.

Credit: 
Tokyo Institute of Technology

Scientists use NASA satellite data to track ocean microplastics from space

image: An assortment of microplastic fragments, filaments, and fibers from the North Atlantic Subtropical Gyre displayed in a disposable water bottle.

Image: 
Courtesy of Nicole Trenholm / Ocean Research Project

Scientists from the University of Michigan have developed an innovative way to use NASA satellite data to track the movement of tiny pieces of plastic in the ocean.

Microplastics form when plastic trash in the ocean breaks down from the sun's rays and the motion of ocean waves. These small flecks of plastic are harmful to marine organisms and ecosystems. Microplastics can be carried hundreds or thousands of miles away from the source by ocean currents, making it difficult to track and remove them. Currently, the main source of information about the location of microplastics comes from fisher boat trawlers that use nets to catch plankton - and, unintentionally, microplastics.

The new technique relies on data from NASA's Cyclone Global Navigation Satellite System (CYGNSS), a constellation of eight small satellites that measures wind speeds above Earth's oceans and provides information about the strength of hurricanes. CYGNSS also uses radar to measure ocean roughness, which is affected by several factors including wind speed and debris floating in the water.

Working backward, the team looked for places where the ocean was smoother than expected given the wind speed, which they thought could indicate the presence of microplastics. Then they compared those areas to observations and model predictions of where microplastics congregate in the ocean. The scientists found that microplastics tended to be present in smoother waters, demonstrating that CYGNSS data can be used as a tool to track ocean microplastic from space.

Credit: 
NASA/Goddard Space Flight Center

Controversies and consensus in thyroid cancer care

image: Publishes original articles and timely reviews that reflect the rapidly advancing changes in our understanding of thyroid physiology and pathology, from the molecular biology of the cell to clinical management of thyroid disorders.

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Mary Ann Liebert, Inc., publishers

New Rochelle, NY, June 24, 2021—The American Thyroid Association, the European Association of Nuclear Medicine, the European Thyroid Association, and the Society of Nuclear Medicine and Molecular Imaging released a joint statement on three key topics addressing controversies in thyroid cancer care. The joint statement is published in the peer-reviewed journal Thyroid®, the official journal of the American Thyroid Association® (ATA®).Click here to read the statement now.

An inter-societal working group addressed the current controversies and evolving concepts in three main areas: peri-operative risk stratification; the role of diagnostic radioactive iodine (RAI) imaging in initial staging; and indicators of response to RAI therapy. They reached several conclusions that are detailed in the joint statement, led by Seza Gulec, MD, Florida International University Herbert Wertheim College of Medicine, and coauthors. For peri-operative risk stratification, the working group concluded that this should include “judicious incorporation of molecular theranostics to further refine management recommendations.”

“The article provides a useful update on thyroid cancer management issues through a truly collaborative effort from leading societies across the globe,” says Electron Kebebew, MD, FACS, Editor-in-Chief of Thyroid, Professor of Surgery, Chief, Division of General Surgery, Harry A. Oberhelman and Mark L. Welton Professor, Stanford University School of Medicine (Stanford, CA).

Credit: 
Mary Ann Liebert, Inc./Genetic Engineering News

More intense predation in the tropics can limit marine invasions

video: To better understand the role of predators in shaping marine communities, researchers positioned under?water video cameras to record predator visits to panels colonized by marine invertebrates. They discovered that predators closer to the equator were larger and more diverse and that predation rates were higher than in temperate areas. Predation reduced the abundance of a non-native prey species, especially in the Pacific where this panel was located, leading researchers to conclude that protecting predator species may be a good way to prevent marine invasions in some environments. This video shows a pufferfish and triggerfish, common predators in the Pacific, consuming invertebrates from the panels.

Image: 
Michele Repetto

Night and day, oil tankers, yachts and cargo ships stacked with shipping containers ply the 80-kilometer (50-mile) waterway through the jungles of Panama between the Atlantic and the Pacific Ocean: about 40 ships every 24 hours. But even though the Canal is fed by freshwater rivers that empty through the locks on each end, a system that generally prevents fish and smaller marine invertebrates from hopping from ocean to ocean, some still manage to get through, clinging to the hulls of ships. Other invading species arrive from far-flung ports, dumped with ballast water as ships prepare for transit.

"Panama is a major shipping hub that provides amazing opportunities to test key ideas about marine invasions by studying two very different oceans at the same latitude," said Mark Torchin, staff scientist at the Smithsonian Tropical Research Institute (STRI), "I can check sites in the ocean in front of my lab at the Pacific entrance to the Canal and then drive to the Atlantic coast in an hour to check sites there. Where else in the world can you do that?"

Since the Canal opened in 1914, the human population of the world has catapulted from 2 billion to almost 8 billion. And as people move around the globe, other organisms move as well. Fish breeders in the United States imported carp from Asia to clean their ponds; now Asian Carp have worked their way up the Mississippi River system to Canada, destroying natural bird and fish habitat along the way. Likewise, cane toads were introduced in Australia to control beetles, but because they have no natural predators there, toad numbers exploded. But most invasions are inadvertent, as animals (or viruses, for that matter) hitch rides on boats or planes.

"We have very practical reasons to test ideas about the success of invaders in different locations as we learn how to predict and manage invasions," said Amy Freestone, associate professor at Temple University and research associate at both STRI in Panama and the Smithsonian Environmental Research Center (SERC) in Maryland. "With these paired experimental studies, we wanted to know if marine invaders are equally successful in all environments and how important predators are to keep them in check."

First the team asked whether marine invaders are more successful in one ocean basin compared to the other. Is the proportion of non-native species higher in the less-diverse Pacific compared to the more-diverse Atlantic as theory predicts? And is there asymmetrical exchange between oceans in Panama, with more species introduced from the Atlantic to Pacific than in the opposite direction?

To find out, they suspended PVC panels as habitat patches for colonization. About the size of patio tiles, panels were placed in the water at 10 different sites near each end of the Panama Canal. They waited for 3 months for marine invertebrates to colonize the panels. Then they removed these standard collectors, photographed the results and identified the species on the panels, classifying them as either native, non-native or species of unknown origin.

They found more non-native species in the less-diverse Pacific where there were 18 non-native species, 30% of all Pacific species, than in the more-diverse Atlantic where there were 11 non-native species, 13% of all Atlantic species. And there was a higher influx of invaders from the Atlantic to the Pacific than vice versa.

Along the way they reported 9 new non-native sessile invertebrates in the Pacific and 7 in the Atlantic that were previously unknown from these areas. One of the important contributions of this project was a collaboration with the Panama Canal Authority (Autoridad del Canal de Panama, ACP) and the Panama Maritime Authority (Autoridad Maritima de Panama, AMP), with support from Panama's Secretariat for Science and Technology (SENACYT) to create an online database called Pan-NEMO of non-native species as part of the National Estuarine and Marine Exotic Species Information System (NEMESIS).

The team also combed through previous scientific papers, pulling together the cumulative record of all non-native marine species reported to date in Panama. They found the same thing: eight times more non-native species were reported from the Pacific than from the Atlantic in this area.

Next they looked for evidence of a concept called biotic resistance, the idea that, in biodiverse environments, it is harder for invaders to gain a foothold because they have to compete with the natives and survive alongside native predators. To test effects of predators, they compared caged and uncaged panels in two companion studies. They suspended uncovered panels, panels with mesh cages to keep predators out, and panels with mesh along the sides but open at one end at 3 sites per ocean, waited three months, and then identified the invertebrates and weighed them.

Predation substantially reduced biomass and changed non-native species composition in the Pacific, but not on the Atlantic coast. Some of the dominant non-native species were particularly susceptible to predation in the Pacific, supporting the hypothesis that predation reduces the abundance of certain non-native species.

Based on the results of the Panama experiments the research team secured funding from the US National Science Foundation to also test the idea that predation is stronger the closer you get to the equator and to find out how it impacts communities of marine invertebrates. To do this, they put out PVC panels, with and without cages at 12 sites in 4 regions: subarctic, Ketchikan, Alaska; temperate, San Francisco, California; subtropical La Paz, Mexico and tropical Panama City, Panama.

"These projects not only provide interesting data," said Carmen Schloeder, research manager in the Torchin lab and co-author of both studies, "but also a great experience working for extended periods of time in different environments with collaborators from many different cultural backgrounds. I'm proud to be part of a diverse core team which includes many women: to be able to work with and learn from inspiring colleagues is an essential part of science. "

Results of the second experiment showed that indeed, predators closer to the equator were more diverse, predation rates were higher, predators were larger and they spent more time interacting with their prey. Predation is a much more important force in the tropics than further north. In the tropics, the effects of predators were obvious: they reduced the biomass on the plates and changed the composition of the organisms. In the North, this didn't happen. Communities of marine invertebrates are hit harder by predators in the tropics.

"We show that predators are a critical component of these marine ecosystems, particularly in the tropics, and can limit the abundance of introduced species," Freestone said. "Protect the predators--that is, protect these diverse environments--and you are protecting the world's oceans from invasions by species that may radically alter the balance of marine ecosystems."

"Healthy ecosystems resist invasions," said Gregory Ruiz from the Smithsonian Environmental Research Center (SERC). "Along with global efforts to reduce organism transfers by ships, conservation of native predator populations plays a critical role in biosecurity to prevent new invasions."

Credit: 
Smithsonian Tropical Research Institute

Sleeper cells: Newly discovered stem cell resting phase could put brain tumors to sleep

image: By analyzing brain stem cell data, Assistant Professor Christopher Plaisier and biomedical engineering doctoral student Samantha O'Connor saw the phases of the cell cycle mapped out in more detail than previously possible -- the G0 resting phases, including a new, separate phase they called Neural G0, in addition to growth phases G1 and G2, copying phase S and splitting phase M.

Image: 
Christopher Plaisier/ASU

Christopher Plaisier, an assistant professor of biomedical engineering in the Ira A. Fulton Schools of Engineering at Arizona State University, and Samantha O'Connor, a biomedical engineering doctoral student in the Plaisier Lab, are leading research into a new stage of the stem cell life cycle that could be the key to unlocking new methods of brain cancer treatment. Their work was recently published in the research journal Molecular Systems Biology.

"The cell cycle is such a well-studied thing and yet here we are looking at it again for the umpteenth time and a new phase pops out at us," Plaisier says. "Biology always has new insights to show us, you just have to look."

The spark for this discovery came through a collaboration with Patrick Paddison, an associate professor at the Fred Hutchinson Cancer Research Center in Seattle, and Dr. Anoop Patel, an assistant professor of neurological surgery at the University of Washington who is also involved in the Fred Hutchinson Cancer Research Center.

Paddison's team called upon Plaisier to help analyze their brain stem cell data characterized through a process called single-cell RNA sequencing.

"That data turned out to be pretty amazing," Plaisier says. "It mapped out into this beautiful circular pattern that we identified as all of the different phases of the cell cycle."

O'Connor developed a new cell cycle classifier tool -- called ccAF, or cell cycle ASU/Fred Hutchinson to represent the collaboration between the two institutions -- that takes a closer, "high-resolution" look at what's happening within the growth cycles of stem cells and identifies genes that can be used to track progress through the cell cycle.

"Our classifier gets deeper into the cell cycle because there could be pieces we're capturing that have important implications for disease," O'Connor says.

When Plaisier and O'Connor used the ccAF tool to analyze cell data for glioma tumors, they found the tumor cells were often either in the Neural G0 or G1 growth state. And as tumors become more aggressive, fewer and fewer cells remain in the resting Neural G0 state. This means more and more cells are proliferating and growing the tumor.

They correlated this data with the prognosis for patients with glioblastoma, a particularly aggressive type of brain tumor. Those with higher Neural G0 levels in tumor cells had less aggressive tumors.

They also found that the quiescent Neural G0 state is independent of a tumor's proliferation rate, or how fast its cells divide and create new cells.

"That was an interesting finding from our results, that quiescence itself could be a different biological process," Plaisier says. "It's also a potential point where we could look for new drug treatments. If we could push more cells into that quiescent state, the tumors would become less aggressive."

Current cancer drug treatments focus on killing cancer cells. However, when the cancer cells are killed, they release cell debris into the surrounding area of the tumor, which can cause the remaining cells to become more resistant to the drugs.

"So, instead of killing the cells, if we put them to sleep it could potentially be a much better situation," Plaisier says.

With their ccAF tool, they were also able to find new states at the beginning and end of the cell cycle that exist between the commonly known states. These are among the topics for their next phase of research.

"We're starting to think about ways to dig into those and learn more about the biology of the entry and exit from the cell cycle because those are potentially really important points where the cells will either go into the G1 state or G0," Plaisier says.

Figuring out what triggers a cell to enter the division cycle or remain in a G0 resting state could help understand the processes behind tumor growth.

"The primary feature of any cancer is that the cells are proliferating," Plaisier says. "If we could get in there and figure out what the mechanisms are, that might be a place to slow them down."

Plaisier and O'Connor are making the ccAF classifier tool open source and available in a variety of formats for anyone studying single-cell RNA sequencing data to ease into the process of studying cell cycles.

Credit: 
Arizona State University

Loss of circadian regulation allows for increase in glucose production during lung cancer

image: During lung cancer progression and the corresponding development of cachexia, circadian control of glucose production is disrupted, resulting in increased levels of glucose from the liver. These findings illustrate a tissue-tissue crosstalk whereby a lung tumor can disrupt the circadian metabolism of a distal tissue, potentially for its own growth advantage.

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UCI School of Medicine

Irvine, CA - June 25, 2021 - New research from the University of California, Irvine reveals how the circadian regulation of glucose production in the liver is lost during lung cancer progression, and how the resulting increase in glucose production may fuel cancer cell growth.

The new study titled, "Glucagon regulates the stability of REV-ERBα to modulate hepatic glucose production in a model of lung cancer-associated cachexia," published today in Science Advances, illustrates how the circadian clock is regulated under conditions of stress such as during lung cancer progression and cancer-associated tissue wasting disease called cachexia.

"Our research shows that a critical circadian protein, REV-ERB?, controls glucose production in the liver. During lung cancer progression and specifically under conditions of cachexia, this circadian regulation is lost, resulting in increased glucose production from the liver," said senior author Selma Masri, PhD, assistant professor in the Department of Biological Chemistry at UCI School of Medicine. "Based on our findings, we identified that lung tumors are able to provide instructive cues to the liver to increase glucose production, a major fuel source for cancer cells."

This research places the circadian clock as a central regulator of glucose production during lung cancer progression and provides important insight toward the development of novel therapeutics to target REV-ERB? to suppress cancer cell growth.

"We are continuing to investigate the consequence of increased glucose production during lung cancer progression by tracing the metabolic fate of this newly generated glucose to determine if this fuel source can drive the heightened metabolic demand of lung cancer cells," said Amandine Verlande, PhD, and Sung Kook Chun, PhD, postdoctoral scholars in the Masri Laboratory.

The circadian clock is our intrinsic biological pacemaker that maintains physiological homeostasis in all tissues of the body. Under conditions of stress, the biological clock is rewired as an adaptive mechanism to maintain synchrony and equilibrium throughout the body.

Credit: 
University of California - Irvine

Differences in human, mouse brain cells have important implications for disease research

image: Microscope image of human astrocytes, star-shaped brain cells that play a substantial role in neurological disorders.

Image: 
UCLA Broad Stem Cell Research Center/Nature Communications

FINDINGS

A UCLA-led study comparing brain cells known as astrocytes in humans and mice found that mouse astrocytes are more resilient to oxidative stress, a damaging imbalance that is a mechanism behind many neurological disorders. A lack of oxygen triggers molecular repair mechanisms in these mouse astrocytes but not in human astrocytes. In contrast, inflammation activates immune-response genes in human astrocytes but not mouse astrocytes.

BACKGROUND

Although the mouse is a ubiquitous laboratory model used in research for neurological diseases, results from studies in mice are not always applicable to humans. In fact, more than 90% of drug candidates that show preclinical promise for neurological disorders ultimately fail when tested in humans, in part due to a dearth of knowledge about the differences in astrocytes and other brain cells between the two species.

Astrocytes are crucial to the development and function of the brain, and they play a substantial role in neurological disorders that, nonetheless, is not fully understood. Injury or infection causes astrocytes to go from a resting to reactive state in which they can aid in repairing the brain but can also increase detrimental inflammation.

METHOD

The scientists studied developing cells purified from mouse and human brain tissue, as well as cells grown in serum-free cultures from astrocytes selected using an antibody-based method developed by the study's corresponding author.

This technique was necessary because the conventional method of selecting astrocytes by growing them in serum -- a mixture of proteins, hormones, fats and minerals -- throws them into a reactive state similar to that caused by infection or injury. With the researchers' strategy, they were able to examine the astrocytes in a healthy state and in controlled conditions of oxidative stress, lack of oxygen and excessive inflammation.

IMPACT

The findings have implications for basic and translational research into neurological disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis -- conditions whose underlying mechanisms include oxidative stress, lack of oxygen and excessive inflammation.

Because mouse astrocytes stand up to oxidative stress better, the authors suggest that laboratory models for neurodegeneration could be engineered to lessen that resistance, rendering them more human-like. In addition, the mouse astrocyte's facility for repair in response to lack of oxygen may suggest a new avenue of stroke research. And neuroscientists can take a more informed approach to preclinical studies by accounting for differences in response to inflammation between mouse and human astrocytes, as well as metabolic differences identified in the study.

Credit: 
University of California - Los Angeles Health Sciences

AI used to predict unknown links between viruses and mammals

image: Networks of observed and predicted associations between wild and semi-domesticated mammalian hosts and known virus species.

Image: 
Dr Maya Wardeh

A new University of Liverpool study could help scientists mitigate the future spread of zoonotic and livestock diseases caused by existing viruses.

Researchers have used a form or artificial intelligence (AI) called machine-learning to predict more than 20,000 unknown associations between known viruses and susceptible mammalian species. The findings, which are published in Nature Communications, could be used to help target disease surveillance programmes.

Thousands of viruses are known to affect mammals, with recent estimates indicating that less than 1% of mammalian viral diversity has been discovered to date. Some of these viruses such as human and feline immunodeficiency viruses have a very narrow host range, whereas others such as rabies and West Nile viruses have very wide host ranges.

"Host range is an important predictor of whether a virus is zoonotic and therefore poses a risk to humans. Most recently, SARS-CoV-2 has been found to have a relatively broad host range which may have facilitated its spill-over to humans. However, our knowledge of the host range of most viruses remains limited," explains lead researcher Dr Maya Wardeh from the University's Institute of Infection, Veterinary and Ecological Sciences.

To address this knowledge gap, the researchers developed a novel machine learning framework to predict unknown associations between known viruses and susceptible mammalian species by consolidating three distinct perspectives - that of each virus, each mammal, and the network connecting them, respectively.

Their results suggests that there are more than five times as many associations between known zoonotic viruses and wild and semi-domesticated mammals than previously thought. In particular, bats and rodents, which have been associated with recent outbreaks of emerging viruses such as coronaviruses and hantaviruses, were linked with increased risk of zoonotic viruses.

The model also predicts a five-fold increase in associations between wild and semi-domesticated mammals and viruses of economically important domestic species such as livestock and pets.

Dr Wardeh said: "As viruses continue to move across the globe, our model provides a powerful way to assess potential hosts they have yet to encounter. Having this foresight could help to identify and mitigate zoonotic and animal-disease risks, such as spill-over from animal reservoirs into human populations."

Dr Wardeh is currently expanding the approach to predict the ability of ticks and insects to transmit viruses to birds and mammals, which will enable prioritisation of laboratory-based vector-competence studies worldwide to help mitigate future outbreaks of vector-borne diseases.

Credit: 
University of Liverpool

UC San Diego scientists develop the first CRISPR/Cas9-based gene drive in plants

image: Arabidopsis plants were used to develop the first CRISPR-Cas9-based gene drive in plants.

Image: 
Zhao Lab, UC San Diego

With a goal of breeding resilient crops that are better able to withstand drought and disease, University of California San Diego scientists have developed the first CRISPR-Cas9-based gene drive in plants.

While gene drive technology has been developed in insects to help stop the spread of vector-borne diseases such as malaria, researchers in Professor Yunde Zhao's lab, along with colleagues at the Salk Institute for Biological Studies, demonstrated the successful design of a CRISPR-Cas9-based gene drive that cuts and copies genetic elements in Arabidopsis plants.

Breaking from the traditional inheritance rules that dictate that offspring acquire genetic materials equally from each parent (Mendelian genetics), the new research uses CRISPR-Cas9 editing to transmit specific, targeted traits from a single parent in subsequent generations. Such genetic engineering could be used in agriculture to help plants defend against diseases to grow more productive crops. The technology also could help fortify plants against the impacts of climate change such as increased drought conditions in a warming world.

The research, led by postdoctoral scholar Tao Zhang and graduate student Michael Mudgett in Zhao's lab, is published in the journal Nature Communications.

"This work defies the genetic constraints of sexual reproduction that an offspring inherits 50% of their genetic materials from each parent," said Zhao, a member of the Division of Biological Sciences' Section of Cell and Developmental Biology. "This work enables inheritance of both copies of the desired genes from only a single parent. The findings can greatly reduce the generations needed for plant breeding."

The study is the latest development by researchers in the Tata Institute for Genetics and Society (TIGS) at UC San Diego, which was built upon the foundation of a new technology called "active genetics" with potential to influence population inheritance in a variety of applications.

Developing superior crops through traditional genetic inheritance can be expensive and time consuming as genes are passed through multiple generations. Using the new active genetics technology based on CRISPR-Cas9, such genetic bias can be achieved much more quickly, the researchers say.

"I am delighted that this gene drive success, now achieved by scientists affiliated with TIGS in plants, extends the generality of this work previously demonstrated at UC San Diego, to be applicable in insects and mammals," said TIGS Global Director Suresh Subramani. "This advance will revolutionize plant and crop breeding and help address the global food security problem."

Credit: 
University of California - San Diego

Pushing the boundaries of colloidal quantum dots by making their sizes equal

image: Younghoon kim, Ph.D. (Left) and Prof. Jongmin Choi(Right), DGIST.

Image: 
DGIST

Quantum dots (QDs) are semiconductor particles only a few nanometers across that, thanks to their small size, exhibit peculiar optical and electronic properties due to quantum mechanics. With existing and foreseen applications in screens, lighting, lasers, and energy harvesting, research in quantum dots has been steadily progressing. In particular, colloidal QDs (CQDs) have been in the nanotechnology spotlight for over a decade.

CQDs are semiconductor nanocrystals that can be produced easily from solution-based processes, which make them suitable for mass production. However, for CQD-based devices to operate at their best, the quantum dots should be monodisperse--that is, they should all have the same size. If their sizes are not equal (polydisperse), the energetic disorder within the optoelectronic device increases, which in turn hinders its performance. While some strategies exist to combat polydispersity in CQDs, the problem is trickier to avoid in perovskite-based CQDs (Pe-CQDs), which require a purification step with an antisolvent. This step invariably leads to nanoparticle agglomeration, and ultimately, large variations in size between quantum dots.

Although producing well-purified monodisperse Pe-CQDs might be necessary to produce highly efficient solar cells, no one has carefully explored the relationship between polydispersity and photovoltaic (conversion) performance. To fill in this knowledge gap, Dr Younghoon Kim and Assistant Professor Jongmin Choi from Daegu Gyeongbuk Institute of Science and Technology, Korea, recently led a team of scientists in a study that published in ACS Energy Letters. The researchers used a technique called gel permeation chromatography to 'filter' and group nanoparticles based on their size, as confirmed by several measurements of their optical properties as well as transmission electron microscopy. With this approach, they managed to obtain suspensions of Pe-CQDs with different degrees of polydispersity.

Afterwards, they used these suspensions to fabricate solar cells and demonstrate the link between polydispersity and performance. As expected, the monodisperse suspension resulted in a better solar cell thanks to its homogeneous energy landscape, which led to higher light absorption within the optimal frequency band. "With the monodisperse Pe-CQDs, our solar cells reached a power conversion efficiency of 15.3% and an open-circuit voltage of 1.27 V. These values are the highest ever reported for Pe-CQDs based on CsPbI3, the perovskite we used," highlights Dr Kim.

Overall, this study is a steppingstone in the field of solar cells based on Pe-CQDs, which still need to outperform their silicon-based counterparts to warrant commercialization. "Research on Pe-CQD solar cells began about four years ago, so further studies are needed to improve device performance and stability. Still, our approach for minimizing energetic disorder using monodisperse Pe-CQDs paves the way to further develop their potential in optoelectronic applications," concludes Dr Choi. Let us hope they eventually manage to join up all the (quantum) dots!

Credit: 
DGIST (Daegu Gyeongbuk Institute of Science and Technology)

Water vole genome will help boost conservation of one of UK's most endangered mammals

A new tool to help conserve one of the UK's most threatened mammals has been released today, with the publication of the first high-quality reference genome for the European water vole. The genome was generated by scientists at the Wellcome Sanger Institute, in collaboration with animal conservation charity the Wildwood Trust, as part of the Darwin Tree of Life Project.

The genome, published today (24 June 2021) through Wellcome Open Research, is openly available as a reference for researchers seeking to assess water vole population genetics, better understand how the species has evolved and to manage reintroduction efforts.

The European water vole (Arvicola amphibius) is a small semi-aquatic mammal that lives on the banks of freshwater habitats and in wetlands. The species is native to Europe, west Asia, Russia and Kazakhstan. While the water vole's conservation status is 'least concern' worldwide*, populations in the United Kingdom have declined to such an extent that the species is considered nationally endangered. Habitat loss and predation by the American mink, an invasive alien species, have reduced the UK population from 7.3 million in 1990 to an estimated 132,000 in 2018**.

Water voles gained full legal protection in the UK in 2008. There have been a number of conservation projects in the UK aimed at supporting water vole populations, including efforts at habitat restoration and to control the population of American mink. There are also efforts to reintroduce the water vole in a number of restored urban and wild habitats, as well as mitigate the impact of new development***.

European water voles returned to Britain from ice-free refuges in Iberia and Eastern Europe after the last ice age, with these two clades contributing to genetic diversity in UK populations. This diversity may be apparent in certain traits, such as the black fur of Scottish water voles, which is distinct from those in England that tend to have brown fur. But the full wealth of genetic diversity cannot be estimated by appearance alone. It is also unknown how much diversity has been lost as a result of the recent population crash.

Hazel Ryan, Senior Conservation Officer at the Wildwood Trust, said: "Water voles are amazing animals and we don't fully understand what ecosystems lose without them. They are industrious habitat managers, almost like miniature beavers in the way they fell stems, make burrows and alter the landscape. We suspect that some water vole populations have become inbred in recent decades owing to shrinking numbers and the fragmentation of populations through habitat loss. The reference genome offers us a way to better understand genetic diversity for reintroductions and consider mixing individuals to ensure populations have the best chance to thrive."

To sequence the European water vole reference genome, a blood sample was taken from a live male A. amphibius individual that was part of the captive breeding population of the Wildwood Trust in Kent, UK. DNA was extracted from this sample and sequenced by scientists at the Wellcome Sanger Institute on Pacific Biosciences SEQUEL I and Illumina HiSeq X instruments.

Professor Rob Ogden, Director of Conservation Science at the University of Edinburgh, said: "Understanding the genetic diversity and structure of water vole populations is an important aspect of their conservation in the UK, and is central to international guidelines on the movement of wildlife for conservation management. The release of the water vole genome provides a comprehensive set of genetic tools to support the future sustainability of the species in the UK."

The water vole genome is published as part of the Darwin Tree of Life Project, which will see partner organisations sequence and assemble the genomes of 70,000 animal, plant, fungal and protist species across Britain and Ireland.

Professor Mark Blaxter, Programme Lead for the Darwin Tree of Life project at the Wellcome Sanger Institute, said: "The European water vole is a prime example of a British species whose genetic diversity we're in danger of losing before we've had chance to fully record it. This high-quality Arvicola amphibius reference genome will allow us to do that, as well as support ongoing conservation efforts to preserve existing populations and reintroduce new ones in a way that ensures these populations are genetically robust."

Credit: 
Wellcome Trust Sanger Institute

Antarctic Circumpolar Current flows more rapidly in warm phases

Our planet's strongest ocean current, which circulates around Antarctica, plays a major role in determining the transport of heat, salt and nutrients in the ocean. An international research team led by the Alfred Wegener Institute has now evaluated sediment samples from the Drake Passage. Their findings: during the last interglacial period, the water flowed more rapidly than it does today. This could be a blueprint for the future and have global consequences. For example, the Southern Ocean's capacity to absorb CO2 could decrease, which would in turn intensify climate change. The study has now been published in the journal Nature Communications.

The Antarctic Circumpolar Current (ACC) is the world's strongest ocean current. Since there are no landmasses blocking its way, the West Wind Drift drives the water unhindered eastwards around the Antarctic in a clockwise direction. As a result, a gigantic ring-shaped current forms, linking together the Pacific, Atlantic and Indian Oceans in the south. The ACC is the central distribution point in global ocean circulation - also known as the 'global conveyor belt' - and as such influences oceanic heat transport and marine material cycles around the planet. Major changes in the ACC therefore have global consequences.

"Although the ACC plays an important role in tomorrow's climate, our understanding of its behaviour is still extremely limited," says Dr Shuzhuang Wu, a researcher at the Marine Geosciences Section of the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) and first author of the study released in Nature Communications. "In order to remove the related uncertainties in the climate models and to improve future forecasts, we urgently need paleo-data, which we can use to reconstruct the conditions and behaviour of the ACC in the past."

The only constriction on the ACC's circular route is the Drake Passage between the southern tip of South America and the Northern tip of the Antarctic Peninsula. Here, no less than 150 million cubic metres of ocean water per second force their way through the Passage - more than 150 times the amount of water flowing in all of Earth's rivers. This bottleneck is an ideal place to observe changes in the overall current. Accordingly, in 2016, AWI researchers travelled to the Drake Passage on board the research icebreaker Polarstern to investigate the sediment deposits from past millennia. "The bottom current here is so strong that in many places the sediment is simply washed away," explains the leader of the expedition and co-author of the study, Dr Frank Lamy. "Nevertheless, using the Polarstern's sediment echo sounder, we were able to detect the pockets of sediment and collect samples, including a core from a depth of 3,100 meters, measuring more than 14 metres in length. This was a significant achievement, since the last comparable cores from the Drake Passage dated back to the 1960s."

The sediments from the new core accumulated over the last 140,000 years. As such, they cover an entire glacial-interglacial cycle, and contain information from the last glacial period, which began 115,000 years ago and ended 11,700 years ago, as well as from the preceding Eemian interglacial period, which began 126,000 years ago.

By analysing the particle size in the deposited sediments, the research team was able to reconstruct the flow speed and the volume of water transported by the ACC in the Drake Passage. Based on the high percentage of small particles at the height of the last glacial period, the researchers calculated that the speed was slower compared to today, and there was a significantly smaller volume of water. This was due to the weaker westerlies and the more extensive sea ice in the Passage. This means that during the glacial period, the ACC's main driver blew more weakly, and the area of exposed water was smaller. In contrast, the extremely large particles at the height of the interglacial period indicated a high flow speed and a flow rate 10-15 percent higher than today.

"At the height of the last interglacial period from 115,000 to 130,000 years before today, the global temperature was on average 1.5° to 2° C warmer than it is today. Accordingly, the Circumpolar Current could accelerate as global warming progresses," says Lamy. "That would have far-reaching effects on the climate. On the one hand, the ACC shapes other ocean currents like the Gulf Stream, which in turn plays a role in determining the weather in Northwest Europe. On the other, the oceans absorb roughly a third of the surplus CO2 from the atmosphere. However, a more rapid ACC would promote the transport of CO2-rich deep water to the surface. Accordingly, the ocean's capacity to absorb atmospheric CO2 could decline significantly, and the concentration in the air could rise more quickly. In the long term, large parts of the Southern Ocean could even become sources of CO2."

Credit: 
Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research

Throwing shade: Measuring how much trees, buildings cool cities

COLUMBUS, Ohio - When the summer sun blazes on a hot city street, our first reaction is to flee to a shady spot protected by a building or tree.

A new study is the first to calculate exactly how much these shaded areas help lower the temperature and reduce the "urban heat island" effect.

Researchers created an intricate 3D digital model of a section of Columbus and determined what effect the shade of the buildings and trees in the area had on land surface temperatures over the course of one hour on one summer day.

"We can use the information from our model to formulate guidelines for community greening and tree planting efforts, and even where to locate buildings to maximize shading on other buildings and roadways," said Jean-Michel Guldmann, co-author of the study and professor emeritus of city and regional planning at The Ohio State University.

"This could have significant effects on temperatures at the street and neighborhood level."

For example, a simulation run by the researchers in one Columbus neighborhood found on a day with a high of 93.33 degrees Fahrenheit, the temperature could have been 4.87 degrees lower if the young trees already in that area were fully grown and 20 more fully grown trees had been planted.

Guldmann conducted the study with Yujin Park, who did the work as a doctoral student at Ohio State and is now an assistant professor of city and regional planning at Chung-Ang University in South Korea, and Desheng Liu, a professor of geography at Ohio State.

Their work was published online recently in the journal Computers, Environment and Urban Systems.

Researchers have long known about the urban heat island effect, in which buildings and roadways absorb more heat from the sun than rural landscapes, releasing it and increasing temperatures in cities.

One recent study found that in 60 U.S. cities, urban summer temperatures were 2.4 degrees F higher than rural temperatures - and Columbus was one of the top 10 cities with the most intense summer urban heat islands.

For this new study, Guldmann and his colleagues selected a nearly 14-square-mile area of northern Columbus that had a wide range of land uses, including single-family homes, apartment buildings, commercial and business complexes, industrial areas, recreational parks and natural areas. More than 25,000 buildings were in the study area.

The researchers created a 3D model of the study area using 2D land cover maps of Columbus, as well as LiDAR data collected by the city of Columbus from an airplane. LiDAR is a laser sensor that detects the shape of objects. Combining this data resulted in a 3D model showing the exact heights and widths of buildings and trees.

They then turned to computer software that calculated the shadows cast by each of the buildings and trees in the study area over the course of a one-hour period - 11 a.m. to noon - on Sept. 14, 2015.

In addition, the researchers had data on land surface temperatures in the study area for the same date and time. That data came from a NASA satellite that uses Thermal Infrared Sensors to measure land surface temperatures at a resolution of 30 by 30 meters (about 98 by 98 feet). That resulted in surface temperatures for 39,715 points in the study area.

With that data in hand, the researchers conducted a statistical analysis to determine precisely how the shade cast by buildings and trees affected surface temperatures on that September day.

Results showed that, as expected, buildings turned up the heat in the area, but that the shadows cast by them also had a significant cooling effect on temperatures, particularly if they shaded the rooftops of adjacent buildings.

The statistical model could precisely calculate those effects, both positive and negative. For example, a 1% increase in the area of a building led to surface temperature increases between 2.6% and 3% on average.

But an increase of 1% in the area of a shaded rooftop led to temperature decreases between 0.13% and 0.31% on average.

Shade on roadways and parking lots also significantly decreased temperatures.

"We learned that greater heat-mitigation effects can be obtained by maximizing the shade on building rooftops and roadways," Guldmann said.

Results also showed the importance of green spaces and water for lowering temperatures. Grassy areas, both shaded and exposed, showed significant heat-reducing effects. However, the impact of shaded grass was stronger than that of grass exposed to direct sunlight.

The volume of tree canopies and the area of water bodies also had significant cooling effects.

In the simulation run in the Columbus neighborhood, the researchers calculated that if the current trees there were fully grown, the temperature on a 93.33-degree F day would be 3.48 degrees lower (89.85 degrees).

But that's not all. The simulation showed that if the neighborhood had 20 more full-grown trees, the temperature would be another 1.39 degrees lower.

"We've long known that the shade of trees and buildings can provide cooling," Guldmann said.

"But now we can more precisely measure exactly what that effect will be in specific instances, which can help us make better design choices and greening strategies to mitigate the urban heat island effect."

Credit: 
Ohio State University