Tech

New mechanism for stroke treatment shows successful proof-of-concept

Many people who suffer a stroke are permanently disabled. Stroke remains the leading cause of long-term disability in the United States. Paralysis of one side of the body, speech and language problems, vision problems and memory loss are some of the major consequences of stroke injury.

Every year, nearly 800,000 people in the United States have a stroke. Even with recent advances in treatments to reduce damage and enhance recovery after stroke, solutions are significantly lacking.

Recently, UConn School of Medicine researchers published a paper in Experimental Neurology showing how they successfully inhibited an important receptor implicated in post-stroke damage and recovery.

The researchers specifically looked at ischemic stroke, which comprises 87% of strokes. Ischemic stroke occurs when there is a blockage in an artery leading to the brain. This reduces the amount of blood and oxygen getting to the brain, causing damage or death of brain cells.

Damaged or dying brain cells release excessive amounts of stored adenosine triphosphate (ATP), a molecule that carries energy within cells, leading to over-stimulation of its receptor P2X4 (P2X4R). When P2X4R is over-active, it causes a cascade of detrimental effects in brain cells, leading to ischemic brain injury.

In this study, the researchers found inhibition of P2X4R can regulate the activation of a kind of immune cell that plays a large role in post-stroke inflammation.

By partially short-term blocking this receptor, the researchers limited the over-stimulated immune response to improve both acute and chronic stroke recovery.

The method presented in this paper is particularly attractive as it only operates during this period of over-activation and does not inhibit normal functions of P2X4R during long-term recovery.

"Short-term P2X4R inhibition works perfectly to prevent brain damage immediately after stroke as well as during long-term recovery," author Rajkumar Verma, assistant professor of neuroscience at the UConn School of Medicine and the Pat and Jim Calhoun Cardiology Center at UConn Health, says.

Using mouse models, the researchers observed improved balance and coordination, as well as reduced anxiety after their intervention.

The P2X4R inhibitor treatment decreased the total number of infiltrated leukocytes, which are white blood cells that promote ischemic injury when over abundant.

This treatment effectively reduced the cell surface expression and activation of P2X4R without reducing its total protein level in brain tissue after stroke injury.

One challenge many experimental drugs, including commercially available P2X4R inhibitors, face is insolubility, meaning they cannot enter the body in order to deliver the treatment. The researchers are currently working with team members Dr. Bruce Liang, Dean of the UConn School of Medicine, and Kenneth Jacobson from the National Institutes of Health to develop more soluble and potent novel P2X4R inhibitors.

This technology would have a major impact as there is currently no effective drug to target stroke damage on the market aside from a few narrowly applicable treatment to dissolve blood clot or device to remove it.

"From a drug perspective, we don't have anything for neuroprotection," Verma says. "It's a very big and open market."

With this successful demonstration of their proof of concept, the researchers will continue to refine this method to find the most effective inhibitors. The team is currently working with UConn Technology Commercialization Services to license this innovation. For more information, contact Ana Fidantsef, PhD (ana.fidantsef@uconn.edu)

Credit: 
University of Connecticut

Unlocking the cell enhances student learning of the genetic code

image: The Genetic Code Kit transforms the way students learn about the central concepts of life.

Image: 
Javin Oza

An open-source educational biotechnology called the "Genetic Code Kit" has been developed by California Polytechnic State University researchers to allow students to interact with the molecular process inside cells in new ways. Researchers show that adapting state-of-the-art biotechnology for the classroom could transform how biology and biochemistry are taught to high school and undergraduate students.

Often referred to as the "central dogma" of biology, the process by which genetic information is used to create proteins is a notoriously difficult topic to teach. While it is critical to students' understanding of life at the molecular level, it is also one of the first "invisible" processes in biology that students are required to learn. Not only are these processes hard to visualize, but they are also trapped inside of the cell. For students, the cell represents a black-box, limiting direct access to biochemical machinery that would be required for active, inquiry-based learning. As a result, instructors are limited to using laboratory experiments with living cells or model- and analogy-based activities to teach these topics, but evidence suggests that these methods are not fully effective for students' learning outcomes.

Reported in the journal Frontiers in Bioengineering and Biotechnology, researchers have harnessed the cell's genetic code in a test tube to create a kit capable of supporting a variety of learning objectives in the classroom. The cell-free protein synthesis (CFPS) biotechnology allows researchers, and now instructors and students, to isolate and manipulate the important, protein-making machinery of cells, without requiring the cells to be alive. This makes CFPS an accessible and open system because the processes of transcription and translation are no longer constrained within the black box of the cell.

These advantages of CFPS inspired professors Javin Oza and Katharine Watts to bring cell-free techniques into biochemistry classrooms at Cal Poly with a goal of achieving greater student understanding of the genetic code. Toward this end, a team of undergraduate student researchers developed a classroom kit containing an inexpensive, modular CFPS reaction that is easy to use for novice scientists and can help teach transcription and translation in a Learn by Doing fashion. Students can now generate a hypothesis and test it by directly manipulating the biochemical machinery and learn in a hands-on, inquiry-based manner. The Genetic Code Kit is accompanied by an augmented reality activity that allows students to explore structure-function relationships in green fluorescent protein.

In addition to developing the Genetic Code Kit, the research team was the first to evaluate the impact this educational biotechnology can have on student learning. In a study of 60 students in a Survey of Biochemistry course, the team found that the Genetic Code Kit significantly improved student learning gains on transcription and translation content. They also identified increases in student comfort and confidence with common biotechnology lab techniques, which indicates that this activity helps prepare students to pursue graduate programs and careers in the biotechnology workforce.

CFPS is poised to transform the way biochemistry and molecular biology are taught. Educators are able to purchase a variety of commercial kits, and the Genetic Code Kit now provides an open-source, modular kit for instructors to support inquiry-based learning in their classrooms.

Researchers at Cal Poly will continue to develop the Genetic Code Kit to address the many gaps that remain in biochemistry and molecular biology education. In addition to addressing a variety of learning objectives, the Genetic Code Kit will help high school teachers better meet the Next Generation Science Standards, and allow college-level instructors to integrate course-based undergraduate research experiences. Continued assessment efforts will evaluate whether educational biotechnologies such as the Genetic Code Kit are able to help narrow the achievement gaps in science, technology, engineering and math (STEM).

Credit: 
California Polytechnic State University

Migration and dispersal of butterflies have contrasting effect on flight morphology

image: Female Lemon Emigrant feeding on a lantana flower, taking a momentary break on its long flight.

Image: 
Krushnamegh Kunte

Butterflies show several different types of movement. They can seasonally migrate long distances over hundreds of kilometres. Alternatively, butterflies also disperse over relatively short distances for feeding and breeding over several hours or days.

Migration and dispersal are vastly different activities with very different benefits and risks. NCBS Grad student Vaishali Bhaumik and her advisor Dr Krushnamegh Kunte decided to investigate the effects of such activities on the morphology (form and structure) and reproduction of butterflies.

To answer this research question Vaishali and her advisor decided to do field studies on several different butterfly species that displayed different dispersal and migration patterns.

The butterflies studied were: (Photos Below)

Two species of Catopsilia butterflies, which have dispersing and non dispersing populations. (C. pomona and C. pyranthe)

Five close relatives of the above butterflies which do not disperse

Two milkweed butterflies that migrate long distances and reproduce only after migration

In all the butterflies Vaishali and Kunte measured the relative investment into their flight muscles (flight morphology) and abdomen (reproductive tissue), as well as how many ova they kept in their body relative to their weight (egg load).

This was done using various tools and methods such as comparing the weight of different segments of their body and counting the number of ova inside of females. The results were very interesting.

The results indicated that the females of migrating milkweed butterflies undergo reproductive diapause. This means their reproductive system stops producing ova (eggs) and makes their abdomen lighter to ensure more efficient long-distance migration. This finding was in accordance with previous findings of the lab when they studied the same group.

Their results on the non-migrating butterflies (Catopsilia species) pointed towards some remarkable conclusions. Like the milkweed butterflies, the females have a much larger investment in the abdomen than males. This is because the females invest a lot of energy in reproductive tissue which makes the ova. This puts them at a disadvantage while flying by making their abdomen relatively heavier, thus requiring higher energy expenditure during flight.

The results further indicated that despite being non-migrating, the females could regulate the number of eggs in their abdomen in response to the type of movement.

Dispersing females of Catopsilia butterflies have a higher egg load than non-dispersing ones, but among dispersers, the number of ova declines rapidly as the relative size of their thorax increases.

The increase in the size of their thorax ensures that the flight muscles of the butterflies are stronger. Vaishali and Krushnamegh think that could be an adaptive response of the butterflies because they received less food as a larvae. In simple terms, when there is less food around you it makes sense to have the strength to fly longer distances to search for food and thus the give preferential investment of energy for a larger thorax (i.e. bigger flight muscles) rather than the abdomen (making eggs).

So why do the non-migrating Catopsilia butterflies have lower egg loads? Krushnamegh and Vaishali suggest that butterflies that do not disperse and stay in the same place can lay eggs frequently but in smaller batches. This keeps their bodies light and ensures efficiency during flight.

To look at the greater picture, Catopsilia butterflies are reproductively active even while dispersing, and the females carry batches of eggs as they disperse. Dispersal allows them to move from one habitat to another even if the habitats are fragmented.

However, unlike the milkweed butterflies, the Catopsilia butterflies cannot pause their reproductive activity to ensure that they can fly very long distances. With habitat loss and fragmentation becoming an ongoing global crisis, female Catopsilia butterflies carrying eggs are put under greater and greater stress. Vaishali and Krushnamegh point out that this would adversely affect the whole species as these butterflies fly over larger distances to habitats which get poorer and poorer every day.

Credit: 
National Centre for Biological Sciences

Alaska's salmon are getting smaller, affecting people and ecosystems

image: One additional year in the ocean makes a big difference in the size of salmon, as seen in these two female sockeye salmon from Pick Creek, Alaska. The top salmon spent three years at sea, the other two years.

Image: 
Andrew Hendry

The size of salmon returning to rivers in Alaska has declined dramatically over the past 60 years because they are spending fewer years at sea, according to a new study led by researchers at the University of California, Santa Cruz, and the University of Alaska Fairbanks.

Salmon are critically important to both people and ecosystems in Alaska, supporting commercial and subsistence fisheries and transporting nutrients from the ocean to inland areas, fertilizing the ecosystems in and around the rivers where they spawn. Smaller salmon provide less food for people who depend on them, less value for commercial fishers, and less fertilizer for terrestrial ecosystems.

For years, people in Alaska have been noticing that wild salmon were getting smaller, but the reasons have been unclear. In the new study, published August 19 in Nature Communications, researchers compiled and analyzed data collected over six decades (1957 to 2018) from 12.5 million fish by the Alaska Department of Fish and Game. This unprecedented dataset enabled them to see patterns of body size changes for four species of salmon--Chinook, chum, coho, and sockeye--across all regions of Alaska.

The results showed that the decreases in body size are primarily due to salmon returning to their spawning grounds at younger ages than they have in the past. Alaskan salmon can spend up to seven years at sea, although this varies by species. During this time they feed and grow to maturity, migrating great distances in the North Pacific Ocean before returning to fresh water to spawn.

"There are two ways they could be getting smaller--they could be growing less and be the same age but smaller, or they could be younger--and we saw a strong and consistent pattern that the salmon are returning to the rivers younger than they did historically," said corresponding author Eric Palkovacs, professor of ecology and evolutionary biology and associate director of the Fisheries Collaborative Program in the Institute of Marine Sciences at UC Santa Cruz.

The researchers identified a range of factors that appear to be driving this shift, some acting across all regions and others affecting only certain species or populations.

"There's not a single smoking gun," said first author Krista Oke, a postdoctoral scientist initially at UC Santa Cruz and now at University of Alaska Fairbanks. "Small contributions from a lot of factors are adding up to drive these changes."

Two factors--climate change and competition with growing numbers of wild and hatchery salmon in the ocean--have clearly contributed to size declines across all species and regions, Palkovacs said. In contrast, the effect of commercial fishing appears to be important only for some salmon populations. Similarly, the results were mixed for another proposed driver of size declines, the recovering populations of marine mammals that prey on salmon.

"We know that climate drives changes in ocean productivity, and we see a consistent signal of climate factors associated with decreasing salmon size," Palkovacs said. "Another consistent association is with the abundance of salmon in the ocean, especially pink salmon. Their abundance in the North Pacific is at historic highs due in part to hatchery production in Alaska and Asia, and they compete with other salmon for food."

The observation that salmon are returning to freshwater streams at younger ages implies that the ocean is becoming a riskier place for them to be, he said. By staying in the ocean longer and growing larger, salmon can have greater success in spawning and lay more eggs, but each additional year increases the risk of not returning to reproduce at all.

"Natural selection has always pushed in both directions, but the balance between the two is changing, pushing harder against the older, larger salmon," Palkovacs said. "It seems that the ocean is becoming a riskier place to be."

According to Oke, understanding exactly what is going on in the ocean to drive this shift is a difficult challenge that will require further study. "That's the next hard step I hope we can get to soon," she said. "It could be that they're having to spend more time feeding, which is putting them in risky places. Lots of things could be happening to increase the overall risk of mortality in the ocean, but we weren't able to pin that down."

The consequences for people and ecosystems, however, are more clear. Smaller salmon means fewer meals per fish for subsistence fishers, lower profits for commercial fishers, fewer eggs laid to sustain salmon populations, and fewer nutrients to support the productivity and biodiversity of freshwater and riparian ecosystems.

"Smaller fish is a real problem for people who depend on salmon for their food and well being," Oke said. "For commercial fishers, smaller fish tend to fetch lower prices, and below a certain size they can't be made into high-value products and might have to be canned."

On the ecosystem side, the nutrients delivered by salmon runs provide critical support for bears, insects, birds, trees, and juvenile salmon themselves. Palkovacs noted that an extensive body of research has tracked the movement of marine nitrogen from salmon into the terrestrial ecosystems around the streams where they spawn.

"Salmon go up into these small streams, and whether they are caught by predators or die after spawning, their nutrients are transferred into the forests and freshwater ecosystems," he said. "It's a classic salmon ecosystem service, and the amount of nutrients they deliver depends on their body size."

The study had its origins in a working group organized by the National Center for Ecological Analysis and Synthesis (NCEAS) at UC Santa Barbara through its State of Alaska's Salmon and People project. With funding from the Gordon & Betty Moore Foundation, the researchers were able to work with the Alaska Department of Fish and Game to compile data the agency had been collecting for decades, but which was dispersed among different field offices in various smaller databases.

"At NCEAS, we had two data scientists who compiled all the data into one massive database on Alaskan salmon that is now publicly available," Palkovacs said. "It took a lot of time and energy, but that's what enabled us to do this comprehensive analysis."

Oke added that getting the data in the first place was no small task either. "When you think about the fact that we used data from 12.5 million salmon, that's how many times someone from ADF&G measured a salmon. It's an exceptional amount of work to make a dataset like this possible," she said.

Credit: 
University of California - Santa Cruz

Out of sync: Ecologists report climate change affecting bee, plant life cycles

image: Andrena transnigra (black-banded miner bee) on Solidago multiradiata (Rocky Mountain goldenrod) at the Rocky Mountain Biological Laboratory near Gothic, Colorado. Utah State University and North Carolina State University ecologists, along with a multi-institution team, report on a community-wide assessment revealing phenological mismatch between bees and flowering plants, due to climate change, in the August 19, 2020 issue of 'Ecology Letters.'

Image: 
David Inouye, RMBL

LOGAN, UTAH, USA - Bees and flowers seem inseparable harbingers of spring, but what happens when pollinators emerge later than their sources of nectar and pollen? Reporting on the first community-wide assessment of 67 bee species of the Colorado Rockies, ecologists Michael Stemkovski of Utah State University and Rebecca Irwin of North Carolina State University say "phenological mismatch," changing timing of life cycles between bees and flowers, caused by climate change, has the potential to disrupt a mutually beneficial relationship.

"We analyzed time-series abundance data collected at 18 sites around the Rocky Mountain Biological Laboratory (RMBL) in the Elk Mountains of western Colorado during a nine-year, National Science Foundation-funded bee monitoring project," says Stemkovski, doctoral student in USU's Department of Biology and the USU Ecology Center.

He and Irwin, senior author, along with colleagues from RMBL, University of Texas at Austin, Imperial College London, University of Manitoba, USDA-ARS Pollinating Insects Research Unit at USU, Central Texas Melittological Institute, Royal Saskatchewan Museum, Texas A&M University, Florida State University and University of Maryland, published findings in the August 19, 2020 issue of Ecology Letters.

"We find bee emergence timing is advancing with snowmelt timing, but bee phenology - timing of emergence, peak abundance and senescence - is less sensitive than flower phenology," says Irwin, professor of applied ecology at NCSU. "Given global concerns about pollinator declines, the research provides important insight into the potential for reduced synchrony between flowers and their pollinators under climate change."

Previous studies focused primarily on temperature, Stemkovski says, but this study probed the effects of topography and bee species traits, as well.

"Elevation played a large role in when bees start foraging, as well as the bees' functional traits, such as whether bees nested below or above ground, and the life stage in which they overwintered," he says. "We found all of these factors predicted bee emergence, but the most important factor was snowmelt timing."

If bees begin foraging later than spring plants reach their flowering peak, consequences could be reduced abundance of pollinators, from limited sustenance, and reduced abundance of plants, from limited pollination.

"In the short-term, we expect mutualist species to suffer fitness losses," Stemkovski says. "In the long-term, bees and plants may be able to adapt and reestablish some synchrony, unless climate change outpaces the rate of adaptation."

Credit: 
Utah State University

Toward an ultrahigh energy density capacitor

image: To make the new material, the thin film is first deposited via a pulsed-laser deposition process in this chamber. The bright "plume" you see is the laser hitting the target and depositing the material.

Image: 
Martin/UC Berkeley

Capacitors that rapidly store and release electric energy are key components in modern electronics and power systems. However, the most commonly used ones have low energy densities compared to other storage systems like batteries or fuel cells, which in turn cannot discharge and recharge rapidly without sustaining damage.

Now, as reported in the journal Science, researchers have found the best of both worlds. By introducing isolated defects to a type of commercially available thin film in a straightforward post-processing step, a team led by researchers at the Department of Energy's (DOE) Lawrence Berkeley National Laboratory (Berkeley Lab) has demonstrated that a common material can be processed into a top-performing energy storage material.

The research is supported by the Materials Project, an open-access online database that virtually delivers the largest collection of materials properties to scientists around the globe. Today, the Materials Project combines both computational and experimental efforts to, among other goals, accelerate the design of new functional materials. This includes understanding ways to manipulate known materials in ways that improve their performance.

Growing requirements for cost reduction and device miniaturization have driven a push toward development of high energy density capacitors. Capacitors are commonly used in electronic devices to maintain power supply while a battery is being charged. The new material developed at Berkeley Lab could ultimately combine the efficiency, reliability, and robustness of capacitors with the energy storage capabilities of larger-scale batteries. Applications include personal electronic devices, wearable technology, and car audio systems.

The material is based on a so-called "relaxor ferroelectric," which is a ceramic material that undergoes a rapid mechanical or electronic response to an external electric field and is commonly used as a capacitor in applications like ultrasonics, pressure sensors, and voltage generators.

The applied field drives changes in the orientation of the electrons in the material. At the same time, the field drives a change in the energy stored in the materials, making them a good candidate for use beyond a small-scale capacitor. The problem to solve is how to optimize the ferroelectric so that it can be charged to high voltages and discharged very rapidly - billions of times or more - without sustaining damage that would render it unsuitable for long-term use in applications such as computers and vehicles.

Researchers in the lab of Lane Martin, a faculty scientist in the Materials Sciences Division (MSD) at Berkeley Lab and professor of materials science and engineering at the University of California, Berkeley, accomplished this by introducing local defects that allowed it to withstand bigger voltages.

"You've probably experienced relaxor ferroelectrics on a gas grill. The button that lights the grill operates a spring-loaded hammer that smacks a piezoelectric crystal, which is a type of relaxor, and creates a voltage that ignites the gas," explained Martin. "We've demonstrated that they can also be made into some of the best materials for energy-storage applications as well."

Placing a ferroelectric material between two electrodes and increasing the electric field causes charge to build up. During discharge, the amount of energy available depends on how strongly the material's electrons orient, or become polarized, in response to the electric field. However, most such materials typically cannot withstand a large electric field before the material fails. The fundamental challenge, therefore, is to find a way to increase the maximum possible electric field without sacrificing the polarization.

The researchers turned to an approach that they had previously developed to "turn off" conductivity in a material. By bombarding a thin film with high-energy charged particles known as ions, they were able to introduce isolated defects. The defects trap the material's electrons, preventing their motion and decreasing the film's conductivity by orders of magnitude.

"In ferroelectrics, which are supposed to be insulators, having charge that leaks through them is a major issue. By bombarding ferroelectrics with beams of high-energy ions, we knew we could make them better insulators," said Jieun Kim, a doctoral researcher in Martin's group and lead author on the paper. "We then asked, could we use this same approach to make a relaxor ferroelectric withstand bigger voltages and electric fields before it catastrophically fails?"

The answer turned out to be "yes." Kim first fabricated thin films of a prototypical relaxor ferroelectric called lead magnesium niobite-lead titanate. Then, he targeted the films with high-energy helium ions at the Ion-Beam Analysis Facility operated by the Accelerator Technology and Applied Physics (ATAP) Division at Berkeley Lab. The helium ions knocked target ions from their sites to create point defects. Measurements showed that the ion-bombarded film had more than twice the energy storage density of previously reported values and 50 percent higher efficiencies.

"We were originally expecting the effects to be mostly from reducing the leakage with isolated point defects. However, we realized that the shift in the polarization-electric field relationship due to some of those defects was equally important," said Martin. "This shift means that it takes larger and larger applied voltages to create the maximum change in polarization." The result suggests that ion bombardment can help to overcome the trade-off between being highly polarizable and easily breakable.

The same ion beam approach could also improve other dielectric materials to improve energy storage, and provides researchers with a tool to repair problems in already-synthesized materials. "It would be great to see folks use these ion-beam approaches to 'heal' materials in devices after the fact if their synthesis or production process didn't go perfectly," said Kim.

Credit: 
DOE/Lawrence Berkeley National Laboratory

Brain remapping dysfunction causes spatial memory impairment in Alzheimer's disease

Alzheimer's disease is one of the most serious diseases in an aging society, yet the cause is often unclear and there is no appropriate treatment method. Many patients with Alzheimer's disease develop spatial memory impairment which causes symptoms such as wandering, putting a great stress on caregivers. However, the cause of spatial memory impairment has been long unclear.

A research group led by Kei Igarashi, an assistant professor at University of California, Irvine elucidated the brain circuit mechanism that cause of spatial memory impairment in Alzheimer's disease. The research group used Alzheimer's disease model mice developed at RIKEN in 2014 and analyzed the brain activity of mice performing memory behaviors using an electrophysiological technique(1). The results showed that brain function to distinguish different locations called as "remapping"(2), a function of the hippocampus(3) of healthy brain, become impaired. The results also showed that this hippocampal dysfunction was caused by decreased activity in the brain region called the entorhinal cortex(4).

These results indicate that the impairment of remapping causes spatial memory impairment in Alzheimer's disease. In the future, improving brain remapping function may reverse spatial memory impairment in patients with Alzheimer's disease, for example using deep brain stimulation methods.

The study was conducted jointly with Takaomi Saido, a team leader at the RIKEN and Professor Takashi Saito at Nagoya City University, as part of the JST Strategic Basic Research Programs.

Credit: 
Japan Science and Technology Agency

Climate change impact on green energy production

image: Historical (thin black) and model-projected (thick red and blue shades) weather variables and solar/wind power generation for two Australian sites. Left is for all time periods and right is for only a peak period (i.e., afternoons of the five hottest days in a year).

Image: 
Jing Huang

WASHINGTON, August 18, 2020 -- As the climate of the planet is changing, as evidenced by record-setting hot summers and extreme weather events, many researchers are looking to more renewable energy sources, such as solar and wind farms.

In a paper for the Journal of Renewable and Sustainable Energy
, by AIP Publishing, researchers investigate whether the power generated by solar and wind farms would differ between current and future climates.

The researchers focused on Australia, since it is an ideal case study with extreme weather events, such as bush fires and windstorms. The sites selected were near Adelaide in South Australia and in southern New South Wales, where variable renewable generators are located or are likely to be located in the future based on the Australian Energy Market Operator's system plan.

The researchers analyzed key weather variables, such as temperature, surface solar irradiance and wind speed, in 30-minute intervals for the years 1980 to 2060.

"We found that the general temporal trends in annual solar and wind power generation due to climate change are small, being at the order of 0.1% of its average production per decade," said Jing Huang, one of the authors.

During the five hottest days of every year, however, the effect of climate change on renewable energy production was more severe. During these peak temperature days that coincided with peak energy demand and peak prices, solar power production was down 0.5%-1.1%, and wind farm production decreased between 1.6%-3% per decade.

The researchers' findings are geared to inform the electricity sector about the reliability of interconnected power networks in different temperature conditions. Central power operators, for instance, need to plan for all contingencies to avoid power blackouts.

While this study looked at two sites in Australia, quantifying temperature impacts on renewable energy generation can be generalized to other areas beyond Australia.

"For different regions, there are different effects of climate change," said Huang.

He said it will be important to conduct more case studies in other areas and climate regions to examine spatial climate variability and couple the findings with other aspects of energy systems, such as load and transmission infrastructure.

Credit: 
American Institute of Physics

Depression and use of marijuana among US adults

What The Study Did: This study examined the association of depression with cannabis use among U.S. adults and the trends for this association from 2005 to 2016.

Authors: Deborah Hasin, Ph.D., of Columbia University Medical Center in New York, 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/jamanetworkopen.2020.13802)

Editor's Note: The article includes funding/support 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

Constructing odor objects in the brain

image: Scientists succeeded in capturing the odor response of all 2000 cells in the fruit fly mushroom body.

Image: 
RIKEN

A research team led by Hokto Kazama at the RIKEN Center for Brain Science (CBS) in Japan has combined brain imaging and models of brain activity to explain how smells can be generalized into categories. The team examined a region of the fly brain that plays a central role in forming olfactory memories and discovered clustered representations of mixtures and groups of odors that are conserved across individual flies. This study, published in Neuron, explains how varying odors are perceived similarly in different individuals.

Recognition and generalization are essential processes that we often take for granted. Whether it's recognizing a person's accent or being able to categorize a never-before seen combination of foods as a type of pizza, somehow our brains do all the hard work in the background. In the case of smell, animals use their sense of smell to recognize food sources, predators, potential mates, and family. An odor is generally a mixture of multiple volatile molecules, yet animals do not recognize each molecule one by one, but rather the entire mixture as a single smell. Consider the citrus odor. Even though oranges, lemons, grapefruits, and yuzu all have different compositions of odor molecules, they can all be recognized as smelling "citrusy".

To date, how the brain generates representations of unitary odor objects has not been well understood. Luckily, the ability to recognize and generalize odors can be accomplished by the common fruit fly, which has a very well mapped out olfactory system with a set number of neurons. The CBS research team focused on this system, particularly on the differences between two brain regions in the sensory pathway.

In the fly brain, odor information travels from the primary olfactory center, called the antennal lobe, to the secondary center, called the mushroom body. For their experiment to work, the team needed to simultaneously measure responses from many more neurons than has been done in the past. "Characterizing the activity of all 2,000 cells of the mushroom body at once was the biggest technical hurdle," explains Kazama. "Previous studies have only recorded from less than 5% of them, which was not enough for our purposes." They overcame this problem by developing an algorithm that automatically locates and tracks all the cells over an hour of recording.

They presented flies with 15 different odors individually as well as in mixtures and recorded neuronal responses by imaging the calcium released when the neurons were active. They found that clusters of neurons in the mushroom bodies responded selectively to individual odors, mixtures, or groups of odors. In contrast, neurons in the antennal lobe responded much less selectively. This tells that the mushroom bodies integrate input from the antennal lobe in some way and create distinct odor representations.

By using a mathematical model of neural information processing, the team was able to reproduce the results obtained from the real fly brains. Furthermore, they discovered that neural expressions of unitary odors in the mushroom bodies were similar among different individual flies, which can explain why odors are similarly recognized in different individuals. "The most surprising finding was that the same computation in the olfactory circuit can generate unitary representations for individual odors as well as groups and mixtures of odors," says Kazama.

"Because the basic wiring pattern of the olfactory circuit is highly conserved across phyla, we believe that the type of computations we have discovered here may also be found in other more complex animals, such as humans," Kazama says. "We are curious to know if these odor object representations remain stable or flexibly change over time as animals experience various odors in their environment."

Credit: 
RIKEN

Green apple e-cigarette flavorant triggers reward-related behavior in the brain

image: Mice chose the farnesene chamber over the saline chamber. Farnesene also enhanced reward when combined with nicotine.

Image: 
Lead Author Skylar Cooper, PhD candidate, Marshall University

HUNTINGTON, W.Va. - A common green apple vape flavor enhances nicotine reward, which could heighten reward and drug-seeking behavior, according to researchers at Marshall University.

Of the more than 7,000 available flavored vape chemicals, only a handful have been studied. In a new study recently published in eNeuro, an open access journal for the Society of Neuroscience, the team of Marshall University researchers, including Ph.D. candidate Skylar Cooper, research technician Austin Akers and Assistant Professor Brandon Henderson, Ph.D., identified that the flavorant farnesene in green apple e-cigarettes triggers reward-related behavior by promoting high-sensitivity nAChRs in the ventral tegmental area.

"With or without nicotine, flavored vapes pose potential risks for the brain and addiction," Cooper said.

Cooper et al. gave mice either nicotine, the green apple flavorant farnesene or both in one room and a saline solution in another. Farnesene was rewarding by itself, as mice chose the farnesene chamber over the saline chamber. However, farnesene also enhanced reward when combined with nicotine.

The research team next measured how farnesene changed nicotine receptor expression and neuron activation. Alone, farnesene partially activated nicotinic receptors, meaning it may increase nicotine's receptor activation when both substances are present. Farnesene also increased the proportion of high- to low-sensitivity receptors. A greater proportion of high-sensitivity receptors increases the effects of a standard nicotine dose, which could heighten reward and drug-seeking behavior.

"Given a consistent rise in adolescent use of these products and the addiction crisis we are facing throughout this country, it is vital to identify a role that these flavors have in nicotine addiction and how this may impact the developing brain," Cooper said.

Cooper plans to further her research on the impact flavorants have on nicotine addiction, focusing on age-dependent experiments to determine the impacts these flavors have on the adolescent brain.

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Marshall University Joan C. Edwards School of Medicine

New tool improves fairness of online search rankings

ITHACA, N.Y. - When you search for something on the internet, do you scroll through page after page of suggestions - or pick from the first few choices?

Because most people choose from the tops of these lists, they rarely see the vast majority of the options, creating a potential for bias in everything from hiring to media exposure to e-commerce.

In a new paper, Cornell University researchers introduce a tool they've developed to improve the fairness of online rankings without sacrificing their usefulness or relevance.

"If you could examine all your choices equally and then decide what to pick, that may be considered ideal. But since we can't do that, rankings become a crucial interface to navigate these choices," said computer science doctoral student Ashudeep Singh, co-first author of "Controlling Fairness and Bias in Dynamic Learning-to-Rank," which won the Best Paper Award at the Association for Computing Machinery SIGIR Conference on Research and Development in Information Retrieval.

"For example, many YouTubers will post videos of the same recipe, but some of them get seen way more than others, even though they might be very similar," Singh said. "And this happens because of the way search results are presented to us. We generally go down the ranking linearly and our attention drops off fast."

The researchers' method, called FairCo, gives roughly equal exposure to equally relevant choices and avoids preferential treatment for items that are already high on the list. This can correct the unfairness inherent in existing algorithms, which can exacerbate inequality and political polarization, and curtail personal choice.

"What ranking systems do is they allocate exposure. So how do we make sure that everybody receives their fair share of exposure?" said Thorsten Joachims, professor of computer science and information science, and the paper's senior author. "What constitutes fairness is probably very different in, say, an e-commerce system and a system that ranks resumes for a job opening. We came up with computational tools that let you specify fairness criteria, as well as the algorithm that will provably enforce them."

Algorithms seek the most relevant items to searchers, but because the vast majority of people choose one of the first few items in a list, small differences in relevance can lead to huge discrepancies in exposure. For example, if 51% of the readers of a news publication prefer opinion pieces that skew conservative, and 49% prefer essays that are more liberal, all of the top stories highlighted on the home page could conceivably lean conservative, according to the paper.

"When small differences in relevance lead to one side being amplified, that often causes polarization, where some people tend to dominate the conversation and other opinions get dropped without their fair share of attention," Joachims said. "You might want to use it in an e-commerce system to make sure that if you're producing a product that 30% of people like, you're getting a certain amount of exposure based on that. Or if you have a resume database, you could formulate safeguards to make sure it's not discriminating by race or gender."

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Cornell University

Behavioural variability in captive African elephants in the use of the trunk while feeding

The behaviours implied in the manipulation of food items by African elephants were correlated with the shape and size of these items. Despite a common ethogram, all the elephants showed different frequencies in the use of at least one behaviour.

In this recently published study, researchers created a behavioural repertoire in order to describe the use of the trunk in six captive female African elephants of savannah (Loxodonta africana) at the Zooparc of Beauval. The repertoire included 65 behaviours implying the trunk. Focusing on feeding behaviour, 19 behaviours were described. The study revealed the influence of the size and shape of the food on the performed behaviours as well as the variability of the strategy used to manipulate a given type of food.

Manipulative strategies and inter-individual behavioural variability are well described in primates due to their hands and their complex grasping abilities. However, the large degree of freedom in the movements of the Proboscideans' trunk, its high precision and the substantial number of muscles in this organ make a good model out of it to study manipulative strategies.

The results emphasized a correlation between the type of food item and the grasping strategy. Some behaviours were involved in the manipulation of only one or a few types of item. This adaptation of the movement allows precise and efficient manipulation of the food and thus increases the speed of feeding and the quantity of ingested food.

The second part of the study focused on hay grasping and consumption and revealed an inter-individual variability in the use of the five main behaviours. Each elephant differed from the others in the frequency of at least one behaviour, and all the behaviours were used in a different proportion by at least two elephants. The selection of the different strategies did not seem to be related to the trunk morphology but more probably to learning and intrinsic preferences.

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PeerJ

The MOF-based multicolor single-mode microlaser

image: a, the schematic synthesis of hierarchically dye-assembled hybrid ZJU-68 microcrystals. b-i, the optical micrographs of ZJU-68 (b) and hierarchically dye-assembled ZJU-68 microcrystals (c-i), scale bar, 10 μm.

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Huajun He, Yuanjing Cui, Hongjun Li, Kai Shao, Banglin Chen and Guodong Qian

Since different tissues, cells or biochemicals have different (such as optical, thermal and acoustic) responses to different wavelengths of light, a light source with visible to near-infrared (NIR) multi-color output provides the fundamental for multi-modal/multi-dimensional sensing/imaging. On the other hand, the polarization properties of light provide an opportunity for the analysis and processing of scattered light signals and can also help to obtain rich structural information in biological materials. In addition, single-mode micro-nano lasers meet the application requirements of miniaturized photonic devices with high information accuracy, avoiding false signals and overlapping interference of different optical signals, which have the potential to achieve targeted sensing/imaging of various cells and molecules when combined with multi-color output characteristics. If a material can combine the advantages of broadband multi-color output, polarization and single-mode micro-nano lasing, it is very useful for multi-mode miniaturized biochemical sensing or imaging, but there is no report of corresponding materials to date.

In a new paper published in Light Science & Application, a research group led by Professor Guodong Qian from State Key Laboratory of Silicon Materials, Cyrus Tang Center for Sensor Materials and Applications, School of Materials Science and Engineering, Zhejiang University, China have reported the hierarchical assembly of different dye molecules based on homoepitaxy process in a host-guest hybrid metal-organic framework (MOF) micro-resonator to achieve up to three-wavelength single-mode polarized lasing in green, red and NIR. The segmented and oriented assembly of different dye molecules within the MOF microcrystal (named ZJU-68) acting as shortened resonator, help to achieve dynamically controllable multi-color single-mode lasing with a low three-color-lasing threshold of ~1.72 mJ/cm2 and degree of polarization > 99.9%. Furthermore, the resulting three-color single-mode lasing possesses the largest wavelength coverage of ~186 nm (range from ~534 nm to ~720 nm) ever reported. These researchers summarized their ideas:

"It is well known that the spatial confinement effect of the metal-organic framework can greatly reduce the aggregation-caused quenching (ACQ) of organic dye systems. However, when we need to load different dye molecules to broaden the emission band, how should we try to avoid their adverse energy transfer between each other, especially for the lasing system that requires extremely large optical gain? Fortunately, we found one of the solutions, that is the combination of in-situ assembly and epitaxial growth."

"Of course, the size matching between the host framework channels and the dye molecules is also an important factor for the final successful hierarchical assembly. Because we need the prepared dye-loaded crystal segments to not leak the previous dye molecules during the epitaxial growth process." they added.

"These MOF-based hybrid microcrystals can be selectively regionally excited to produce single-mode linearly polarized lasing in green, red, and near-infrared, which will be potential in multi-modal biochemical sensing/imaging and on-chip photon information processing." the researchers forecast.

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Light Publishing Center, Changchun Institute of Optics, Fine Mechanics And Physics, CAS

A bright idea -- Genetically engineered proteins for studying neurons using light

image: Four amino acid mutations were introduced in GtACR2 to engineer a new variant protein. The variant can be controlled to induce and stop inward chloride currents using green and red light, respectively, which would turn the neural silencing effects "on" and "off." A photograph of purified proteins is also shown above.

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2020 Okayama University

In many human endeavors, having good tools for a particular task is an essential requirement to obtain the best results possible, and neuroscience is no different than other scientific fields in this regard. However, neuroscientists tackle the colossal objective of shedding light on the inner workings of neurons and neuronal circuits, and they rely on various methods to observe and control the firing of neurons to gain a better understanding of their functions.

Optogenetics has been regarded as one of the most impactful breakthroughs in neuroscience over the last decades. It involves using light of specific frequencies to control neurons in genetically modified organisms. Neurons, like all cells, have "ion channels"--membrane proteins that can be opened or closed and regulate the flow of charged particles in and out of the cell, thus regulating the electrical behavior of neurons. Now, thanks to optogenetics, they can be altered to be light-sensitive--light essentially can be used to open or close these channels in genetically modified organisms, giving researchers control over which and when neurons fire. Now, a new study by scientists from Okayama, Japan, proposes a promising new tool based on optogenetics for studying neurons. But why is this tool so attractive to neuroscientists? Read on to know more.

While optogenetics has certainly facilitated our understanding of neurons, the technique has some limitations. In particular, the available light-sensitive variants of negatively charged ion, or "anion," channel proteins, which regulate the flow of negatively charged ions, are much less diverse than their positively charged ion, or "cation" channel counterparts (for positively charged ions). Whereas light-sensitive cation channels can be used to "activate" neurons using light, light-sensitive anion channels act as neuron "silencers" that prevent the neuron from firing when illuminated at the right frequency.

This new study by Japanese scientists, published in The Journal of Physical Chemistry Letters, expands the available options for optogenetic neuronal silencing, and explores the potential of GtACR2, a natural light-regulated anion channel from an alga.

The scientists first introduced strategic mutations in GtACR2 amino acids to produce more light-responsive anion channels and tested the results using Escherichia coli bacteria. They found a shift in the frequency that was required to open the channel. The mutant GtACR2 channels also remained open much longer than their normal counterparts. Dr Yuki Sudo, Dr Keiichi Kojima and Ms Natsuki Miyoshi of Okayama University, who led the study, remarks: "Long-time neural inhibition generally requires repetitive long-lasting illumination; however, this invariably heats tissues, causing physiological and behavioral changes and tissue damage. Using the observed prolonged channel opening, GtACR2 mutants would be an effective neural silencer over long-term scales with lower illumination time and fewer heat-dependent effects."

GtACR2 mutants can also be activated and inactivated by illuminating them with different light frequencies. Irradiating the channels with green light opens them, silencing the neuron, but irradiation with red light causes them to quickly close. This "step-functional" property could give future scientists finer control over the state of the channels and the associated neurons, providing a more sophisticated tool for neurological experiments.

Having a highly controllable, long-lasting neural silencing technique is invaluable in all fields of neuroscience, both from basic research and applied science viewpoints. In this regard, Dr Kojima adds: "In humans, neural inhibition plays essential roles in many physiological phenomena, such as sleep, awaking, circadian rhythms and hormone secretion. We expect that our understanding of the above phenomena at the molecular level will be accelerated by optogenetic neural silencing using our engineered proteins, and that this will lead to development of new treatments for sleep disorder, jet lag and lifestyle-related diseases." The tool unveiled in this study will hopefully lead to many advances in medicine and neuroscience, as scientists continue the quest to answer one of the hardest questions ever known: how exactly do neurons and the brain work?

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Okayama University