Tech

Not just Chinese medicine,Traditional Tibetan Medicine also exposes people and environment to high mercury levels

Many people view the Tibetan Plateau, or "Roof of the World," as a pristine alpine environment, largely untouched by pollution. But researchers, reporting in ACS' journal Environmental Science & Technology, have now shown that traditional Tibetan medicine (TTM) exposes people and the environment to high levels of mercury and methylmercury.

Used by Tibetans for more than 1,000 years, TTM is a complex concoction of herbs and minerals in pill form. Pharmacists often add minerals to TTM that might contain mercury and other heavy metals in the belief that they have therapeutic effects. High levels of total mercury have been reported in TTM, but until now nobody has analyzed the amount of methylmercury - one of the most toxic forms of the element. Xuejun Wang and coworkers wanted to understand the life cycle of mercury and methylmercury from their ingestion in TTM to their release into the environment.

The researchers began by measuring total mercury and methylmercury concentrations in seven commonly used types of TTM. With this information, they estimated that the average probable daily intake of total mercury by Tibetans was 34-fold higher than in a region of China specializing in mercury mining and 200¬-3,000-fold higher than in Japan, Norway and the U.S. Probable intake of methylmercury was also higher in Tibet than in the other regions, except for in Japan, where high amounts of marine fish (another source of methylmercury) are consumed. In 2015, Tibetans excreted about 1,900 pounds of total mercury, mostly from TTM, into municipal sewage treatment plants and released about 7,900 pounds directly into the environment, the researchers estimated. Only about 3.2 ounces of methylmercury likely entered municipal sewage. However, actual methylmercury levels could be much higher because bacteria in sewage might convert inorganic mercury into the more toxic form, the researchers say.

Credit: 
American Chemical Society

New target protein for colon cancer identified

(Boston)--Researchers at Boston University School of Medicine (BUSM) have identified a new potential target protein (c-Cbl) they believe can help further the understanding of colon cancer and ultimately survival of patients with the disease.

They found colon cancer patients with high levels of c-Cbl lived longer than those with low c-Cbl. Even though scientists have studied this protein in other cancers, it has not been explored in colon cancer until now.

The researchers examined the level of c-Cbl in tumors that were removed from people with colon cancer. Based on the level of this protein, c-Cbl, patients were split into two groups, high c-Cbl and low c-Cbl.

The researchers then wanted to find out what happens to cells when this protein was turned off. They did this by using two types of colon cancer cells split into three groups each. One group consisted of un-manipulated colon cancer cells, one group had increased expression of normal c-Cbl and the other group had increased expression of the "off" version of c-Cbl. This off version of c-Cbl lacked an essential function of c-Cbl called ubiquitin ligase activity. Cells that were given the "off" version of c-Cbl grew more tumors than those that were given the "on" version.

For tumors to grow and metastasize they need blood vessels. The next step was to look at how c-Cbl affected blood vessel growth by using three experimental models, (one group was normal, one group was given the c-Cbl protein and the third group was given the "off" version of the protein). The model that was given the "off" version of c-Cbl grew more blood vessels. "This helps us to understand the role of the ubiquitin ligase activity of c-Cbl in preventing tumors from growing and reducing tumor's ability to grow blood vessels," explained corresponding author Vipul Chitalia, MD, PhD, associate professor of medicine at BUSM.

According to the researchers, this study suggests that c-Cbl might improve the survival of patients with colon cancer. "This information will help cancer researchers understand colon cancer better and possibly design new treatments to better cure colon cancer and help patients live longer."

Credit: 
Boston University School of Medicine

Scientists uncover mechanism that stabilizes fusion plasmas

image: This is Physicist Isabel Krebs.

Image: 
Elle Starkman/PPPL Office of Communications

Sawtooth swings -- up-and-down ripples found in everything from stock prices on Wall Street to ocean waves -- occur periodically in the temperature and density of the plasma that fuels fusion reactions in doughnut-shaped facilities called tokamaks. These swings can sometimes combine with other instabilities in the plasma to produce a perfect storm that halts the reactions. However, some plasmas are free of sawtooth gyrations thanks to a mechanism that has long puzzled physicists.

Researchers at the U.S. Department of Energy's (DOE) Princeton Plasma Physics Laboratory (PPPL) have recently produced complex simulations of the process that may show the physics behind this mechanism, which is called "magnetic flux pumping." Unraveling the process could advance the development of fusion energy.

Fusion drives the sun and stars

Fusion, the power that drives the sun and stars, is the fusing of light elements in the form of plasma -- the hot, charged state of matter composed of free electrons and atomic nuclei -- that generates massive amounts of energy. Scientists are seeking to replicate fusion on Earth for a virtually inexhaustible supply of power to generate electricity.

The flux pumping mechanism limits the current in the core of the plasma that completes the magnetic field that confines the hot, charged gas that produces the reactions. This development, found in some fusion plasmas, keeps the current from becoming strong enough to trigger the sawtooth instability.

Spearheading the research that uncovered the process was physicist Isabel Krebs, lead author of a Physics of Plasmas paper describing the mechanism that was published last September and made into a DOE Office of Science highlight in June that summarizes the findings. Krebs, a post-doctoral associate, used the PPPL-developed M3D-C1 code to simulate the process on the high-performance computer cluster at PPPL, working closely with theoretical physicists Stephen Jardin and Nate Ferraro, developers of the code. "The mechanism behind magnetic flux pumping had not been understood," Jardin said. "Isabel's paper describes the process."

Hybrid scenarios

In the PPPL simulations, magnetic flux pumping develops in "hybrid scenarios" that exist between standard regimes -- which include high-confinement (H-mode) and low-confinement (L-mode) plasmas -- and advanced scenarios in which the plasma operates in a steady state. In hybrid scenarios, the current remains flat in the core of the plasma while the pressure of the plasma stays sufficiently high.

This combination creates what is called "a quasi-interchange mode" that acts like a mixer that stirs up the plasma while deforming the magnetic field. The mixer produces a powerful effect that maintains the flatness of the current and prevents the sawtooth instability from forming. A similar process maintains the magnetic field that protects the Earth from cosmic rays, with the molten liquid in the iron core of the planet serving as mixer.

The mechanism also regulates itself, as the simulations show. If the flux pumping grows too strong, the current in the core of the plasma stays "just below the threshold for the sawtooth instability," according to Krebs. By remaining below the threshold, the current keeps the plasma temperature and density from zigzagging up and down.

The simulations could lead to measures to avoid the troublesome swings. "This mechanism may be of considerable interest for future large-scale fusion experiments such as ITER," Krebs said. For ITER, the major international fusion experiment under construction in France, creation of a hybrid scenario could produce flux pumping and deter sawtooth instabilities

One way to develop the hybrid scenario will be for operators of ITER to experiment with the timing of the neutral beam power that will heat the ITER plasma to fusion temperatures. Such experiments could lead to the combination of plasma current and pressure that produces sawtooth-free operation.

Credit: 
DOE/Princeton Plasma Physics Laboratory

Solutions to water challenges reside at the interface

image: Seth Darling's research at Argonne National Laboratory blends chemistry, physics, materials science and engineering to address the central global challenge of clean water accessibility.

Image: 
Institute for Molecular Engineering at Argonne National Laboratory

WASHINGTON, D.C., July 17, 2018 -- In response to rising water scarcity, leading Argonne National Laboratory researcher Seth Darling describes the most advanced research innovations that could address global clean water accessibility. His comprehensive paper focuses on understanding and controlling the interfaces between materials and water.

Interfaces determine the performance of technologies like water quality sensors, filtration membranes and even pipes. Darling's own labs are working on adsorbents to advance water treatment. He presented his findings this week in the Journal of Applied Physics, from AIP Publishing.

Adsorbents

Adsorption is one of the best mechanisms for cleaning water. In this process, contaminants adhere to the surface of porous materials to maximize surface-to-volume ratio.

Highly porous activated carbon is the most extensively used because it is abundant and inexpensive. Zeolites can trap whole molecules in their 3D crystalline cage structures, enabling them to selectively bind particular compounds from water-based solutions. Polymer-based sorbents have nearly limitless flexibility in their design.

"We will continue to rely [on] these proven technologies," Darling said. "But there is also a pressing need for sorbents that are more effective and energy-efficient."

Reusability

Reusability is a critical metric for sorbent materials, which can markedly reduce costs and increase the sustainability of a treatment process. Polymeric foam sponges are promising candidates for this approach.

Darling is heading a group that created the Oleo Sponge, which can soak up 90 times its weight in oil throughout the entire water column. To create the Oleo Sponge, the researchers implemented a technique called sequential infiltration synthesis (SIS). Using SIS, they grew metal oxide within the foam fibers to transform common polyurethane foam, found in seat cushions, into an oil adsorbent.

The oxide serves as the "glue" to which the oil-loving (oleophilic) molecules attach. Reusable oil is extracted from the sponge, so it can be used repeatedly.

Targeting Individual Pollutants

Researchers are also designing next-generation sorbents that have higher specificity --more binding power to target individual pollutants. Ideally, researchers could tailor interfacial properties to adsorb specific molecules to capture challenging water contaminants like nutrients and heavy metals.

Researchers are now investigating how to repurpose metal-organic frameworks (MOFs), a material already used in gas sorption, for this purpose. Related to zeolites, MOFs consist of metal ions or clusters bound by organic ligands. MOFs have a high surface area, controllable structures and tunable pores.

"We have a water crisis, which is based on increasing population, urbanization and climate disruption. And there's unsustainable use of our water," Darling said. "Part of addressing this is through policy solutions, but we also need new, more energy-efficient and cost-effective technologies."

Credit: 
American Institute of Physics

Researchers identify brain area linked to motivational disruptions in binge eating

Scientists at Rutgers Brain Health Institute have discovered that a small group of brain cells in the hypothalamus called 'orexin' neurons could be a promising target for medications for controlling binge eating episodes in individuals with obesity. These neurons, named for the chemical messenger they use to communicate with other brain cells, have previously been shown to be important for addiction to several drugs, including cocaine.

"Several key symptoms of eating disorders, such as the sense of losing control, overlap with what we know about the driven nature of drug addiction," said Dr. Gary Aston-Jones, director of the Brain Health Institute at Rutgers, The State University of New Jersey, and one of the senior authors of the study. "Since the orexin system has been implicated in addiction to drugs of abuse, we targeted it to understand the change in food motivation caused by repeated episodes of binge eating."

The researchers studied female rats fed a control diet or a sugary, high-fat diet that causes weight gain and binge eating patterns. Then they set up a task where rats could work to earn sweet treats. As the work required increased, persistent motivation to earn the treat was seen only in the binge-eaters who had previously gained weight on a high-fat diet. Notably, this enhanced motivation was reversed by treatment with a compound that blocks orexin signals in the brain.

"This study was really a proof-of concept for using orexin blockers to reduce binge-like eating in rodents," said the lead study author Dr. Morgan James, post-doctoral research fellow at the Rutgers Brain Health Institute. "Currently there are several orexin-targeting medications in clinical trials or already FDA-approved, so we have begun testing whether these compounds would produce similar results in our rodent model of binge eating." The study team reported their findings this week at the annual meeting of the Society for the Study of Ingestive Behavior (SSIB), an international group of scientific experts on eating behavior.

The researchers also found that the orexin blocker reduced the amount of food consumed during the binge eating episodes, where rats were given unrestricted access to a sweetened fat mixture over a 30 minute period.

"Pharmacological treatments are currently limited for patients with eating disorders, so it is really exciting if a novel therapy could expand treatment options for obese individuals with binge eating disorder," said Dr. Nicholas Bello, associate professor of animal sciences in the School of Environmental and Biological Sciences at Rutgers University and a senior author of the study.

The authors will continue their research by investigating how the size and number of orexin neurons in the brain might be altered following changes to dietary habits or weight or their combination. Funding for this research was provided the Rutgers One Nutrition Pilot Grant program and Rutgers Brain Health Institute.

Credit: 
Society for the Study of Ingestive Behavior

Research on British teeth unlocks potential for new insights into ancient diets

image: This is a skeleton sampled for the study, dating to the post-medieval period in Britain. The analysis suggests the Victorians were partial to a bowl of porridge, while in modern diets potatoes, soybeans and peanuts are flavour of the day.

Image: 
Camilla Speller, University of York.

Goofy, yellow and crooked: British smiles have sometimes had a less-than-flattering international image, but a new study has put tartar from our infamously bad teeth to good use.

Researchers analysing the teeth of Britons from the Iron Age to the modern day have unlocked the potential for using proteins in tooth tartar to reveal what our ancestors ate.

Dental plaque accumulates on the surface of teeth during life and is mineralised by components of saliva to form tartar or "dental calculus", entombing proteins from the food we eat in the process.

Identifying evidence of many foods, particularly plant crops, in diets of the past is a challenge as they often leave no trace in the archaeological record. But proteins are robust molecules that can survive in tartar for thousands of years.

Archaeological tooth tartar has previously been shown to preserve milk proteins, but the international study, led by researchers at the University of York and the Max Planck Institute for the Science of Human History, has proved for the first time that it can also reveal more precise information about a wider range of food proteins, including those from plants.

The discovery could provide new insights into the diets and lifestyles of our ancestors, adding to the value of dental remains in our understanding of human evolution.

The team plans to use the results of this study to help refine their protein-detection methods, and to explore particular problem areas of ancient diet research.

Senior author, Dr Camilla Speller, from the Department of Archaeology at the University of York, said: "This approach may be particularly useful in the detection of understudied vegetative crops, especially in regions where macrobotantical remains are not preserved.

"It may offer a more precise way of identifying foodstuffs compared to other methods such as ancient DNA and isotope analysis as it can distinguish between different crops and indicate whether people were consuming dairy products, like milk or cheese."

Analysing 100 archaeological samples from across Britain, as well as 14 samples from living dental patients and recently deceased individuals, the research team found that potential dietary proteins could be found in about one third of the analysed samples.

Dr Speller added: "In the teeth we look at from individuals who lived around the Victorian era we identified proteins related to plant foods, including oats, peas and vegetables in the cabbage family. Occasionally, we find evidence of milk and oats in the same mouth - I like to think it's from eating porridge!"

In the modern samples, the researchers found proteins that reflected a global British diet, such as those related to potatoes, soybeans and peanuts, as well as milk proteins.

First author Dr Jessica Hendy from the Department of Archaeology at the Max Planck Institute in Germany, said: "While there is still a lot we don't know, this is exciting because it shows that archaeological dental calculus harbours dietary information, including food products that ordinarily do not survive in archaeological sites."

Credit: 
University of York

GPM satellite sees Tropical Cyclone Son-Tinh dropping rain in the Philippines

video: The GPM core observatory satellite passed over on July 16, 2018 at 4:51 a.m. EDT (0851 UTC), GPM's radar (DPR Ku Band) also showed extremely heavy precipitation in the Philippine Sea near the northeastern tip of Luzon where rain was coming down at a rate of greater than 165 mm (6.5 inches) per hour. The satellite's radar showed that a small cluster of powerful storms were reaching heights above 15.2 km (9.4 miles).

Image: 
Credits: NASA/JAXA, Hal Pierce

As Tropical Depression 11W was strengthening into Tropical Storm Son-tinh near the northern Philippines, the Global Precipitation Measurement mission or GPM core satellite analyzed its rainfall.

TD11W or Son-Tinh, is the first tropical cyclone of 2018 for the northern Philippines, where the storm is known locally as "Tropical Cyclone Henry."

At the time GPM passed overhead, Son-Tinh was still a tropical depression. It was close to the northern Philippines on July 16, 2018 at 4:51 a.m. EDT (0851 UTC). GPM is a joint mission between NASA and the Japan Aerospace Exploration Agency, JAXA.

Data collected by GPM's Microwave Imager (GMI) and Dual-Frequency Precipitation Radar (DPR) instruments showed that the tropical cyclone was relatively small but was dropping moderate to heavy rain over much of the northern Philippine island of Luzon.

GPM's radar (DPR Ku Band) also showed that convective storms within the tropical cyclone were producing extremely heavy precipitation in the Philippine Sea near the northeastern tip of Luzon. GPM's radar (DPR Ku Band) scans of these powerful storm showed that rain there was coming down at a rate of greater than 165 mm (6.5 inches) per hour.

GPM's radar data (DPR Ku Band) were used to create a 3-D cross-section image through TD11W's precipitation. The images showed that extremely intense downpours were returning radar reflectivity values exceeding 59 dBZ to the GPM satellite. These probes of TD11W's precipitation by the satellite's radar showed that a small cluster of powerful storms were reaching heights above 15.2 km (9.4 miles).

At 11 a.m. EDT (1500 UTC) the Joint Typhoon Warning Center or JTWC noted that Son-Tinh was located near 19.1 degrees north latitude and 112.4 degrees east longitude. That's about 197 nautical miles south-southwest of Hong Kong. Son-Tinh has tracked westward at 22 knots (25 mph/40 kph). Maximum sustained winds were near 40 knots (46 mph/74 kph).

The Joint Typhoon Warning Center (JTWC) predicts that TD11W will move west-northwestward and become a tropical storm over the South China Sea. The JTWC expects it to approach Hainan in the western South China Sea.

Credit: 
NASA/Goddard Space Flight Center

Close-ups of grain boundaries reveal how sulfur impurities make nickel brittle

image: This is a faceted grain boundary in intergranularly-fractured sulfur-doped nickel.

Image: 
Jian Luo et al.

Engineers at the University of California San Diego have shed new light on a scientific mystery regarding the atomic-level mechanism of the sulfur embrittlement of nickel, a classic problem that has puzzled the scientific community for nearly a century. The discovery also enriches fundamental understanding of general grain boundaries that often control the mechanical and physical properties of polycrystalline materials.

The study was led by Jian Luo, a professor of nanoengineering and materials science and engineering at the UC San Diego Jacobs School of Engineering. The work is published July 17 in Nature Communications.

Since the early 1900s, engineers and scientists have recognized that sulfur impurities cause nickel and other ductile metals, such as iron and steel, to fail at low stress levels. Sulfur embrittlement of metals is of general technological importance because many engineered alloys are used in sulfur-bearing environments, such as the nickel-based high-temperature alloys used in next-generation coal-fired power plants for increasing energy efficiency.

Researchers have known that this embrittlement is related to the grain boundary segregation of sulfur, but the underlying atomic mechanisms have remained elusive.

UC San Diego engineers have shed new light on these mechanisms by examining general grain boundaries in nickel polycrystals doped by sulfur. They used a combination of aberration-corrected scanning transmission electron microscopy and semi-grand-canonical ensemble atomistic simulations.

Luo's team found that competition between interfacial ordering and disordering leads to the alternating formation of amorphous-like and bilayer-like facets at general grain boundaries. They also found that bipolar interfacial structures cause brittle intergranular fractures between polar sulfur-nickel structures that are disorderly aligned in two opposite directions.

"Similar mechanisms may cause grain boundary embrittlement in other metal-nonmetal systems. Examples include oxygen, sulfur, phosphorus and hydrogen embrittlement of other metals and alloys. These are of broad technological importance," said Luo.

This work further advances previous research by Luo's group on the bismuth embrittlement of nickel, which was done in collaboration with Lehigh University and published in two subsequent reports in Science in 2011 and 2017. Researchers discovered that highly-ordered interfacial structures form at general grain boundaries in bismuth-doped nickel. In the new Nature Communications study, Luo's group found that disordered bipolar interfacial structures form in sulfur-doped nickel.

"Bismuth and sulfur are two well-known embrittling impurities for nickel. Interestingly, we found that these represent two extreme cases of interfacial structures--ordered versus disordered, respectively. Thus, they may be considered as two classic examples of grain boundary embrittlement with different underlying atomistic structures," Luo said.

Aside from embrittlement mechanisms, researchers say this study sheds new light on the mysterious abnormal grain growth phenomena in sulfur-doped nickel, and enriches fundamental understanding of disordered interfaces. This study also challenges a traditional view by showing that the orientation of the grain boundary facet, instead of the misorientation, dictates the interfacial structure.

"This work broadens our fundamental knowledge of materials interfaces beyond the well-characterized ordered interfaces and special symmetric boundaries in artificial bicrystals that have been the focus of most prior studies. Now, we have new insight into the disordered interfaces and general grain boundaries in real-world polycrystals, which often limit the performance of most engineered materials," said Luo.

Credit: 
University of California - San Diego

In borophene, boundaries are no barrier

image: Scanning tunneling electron microscope images of line defects in 1-to-6 and 1-to-5 borophene, indicated by blue and red arrowheads, respectively, show how the defects align in a way that preserves the synthetic material's metallic nature. Scientists at Rice and Northwestern universities made the first detailed analysis of ordered defect structures in borophene.

Image: 
Hersam Research Group/Northwestern University

Borophene, the atomically flat form of boron with unique properties, is even more interesting when different forms of the material mix and mingle, according to scientists at Rice and Northwestern universities.

Scientists at the institutions made and analyzed borophene with different lattice arrangements and discovered how amenable the varied structures are to combining into new crystal-like forms. These, they indicated, have properties electronics manufacturers may wish to explore.

The research led by Rice materials theorist Boris Yakobson and Northwestern materials scientist Mark Hersam appears in Nature Materials.

Borophene differs from graphene and other 2D materials in an important way: It doesn't appear in nature. When graphene was discovered, it was famously yanked from a piece of graphite with Scotch tape. But semiconducting bulk boron doesn't have layers, so all borophene is synthetic.

Also unlike graphene, in which atoms connect to form chicken wire-like hexagons, borophene forms as linked triangles. Periodically, atoms go missing from the grid and leave hexagonal vacancies. The labs investigated forms of borophene with "hollow hexagon" concentrations of one per every five triangles and one per every six in the lattice.

These are the most common phases the Northwestern lab observed when it created borophene on a silver substrate through atomic boron deposition in an ultrahigh vacuum, according to the researchers, but "perfect" borophene arrays weren't the target of the study.

The lab found that at temperatures between 440 and 470 degrees Celsius (824-878 degrees Fahrenheit), both 1-to-5 and 1-to-6 phases grew simultaneously on the silver substrate, which acts as a template that guides the deposition of atoms into aligned phases. The labs' interest was heightened by what happened where these domains met. Unlike what they had observed in graphene, the atoms easily accommodated each other at the boundaries and adopted the structures of their neighbors.

These boundary adjustments gave rise to more exotic - but still metallic - forms of borophene, with ratios such as 4-to-21 and 7-to-36 appearing among the parallel phases.

"In graphene, these boundaries would be disordered structures, but in borophene the line defects, in effect, are a perfect structure for each other," said Rice graduate student Luqing Wang, who led a theoretical analysis of atom-level energies to explain the observations. "The intermixing between the phases is very different from what we see in other 2D materials."

"While we did expect some intermixing between the 1-to-5 and 1-to-6 phases, the seamless alignment and ordering into periodic structures was surprising," Hersam said. "In the two-dimensional limit, boron has proven to be an exceptionally rich and interesting materials system."

Wang's density functional theory calculations revealed the metallic nature of the line defects; this implied that unlike insulating defects in otherwise metallic graphene, they have minimal impact on the material's electronic properties at room temperature. At low temperature, the material shows evidence of a charge density wave, a highly ordered flow of electrons.

Theoretical calculations also suggested subtle differences in stiffness, thermal conductivity and electrochemical properties among borophene phases, which also suggested the material can be tuned for applications.

"The unique polymorphisms of borophene are on full display in this study," Yakobson said. "This suggests intriguing interplay in the material's electronic structure through charge density waves, which may lead to tantalizing switchable electronics."

"As an atomically thin material, borophene has properties that should be a function of the substrate, neighboring materials and surface chemistry," Hersam said. "We hope to gain further control over its properties through chemical functionalization and/or integration with other materials into heterostructures."

Yakobson and Hersam also co-authored a recent Nature Nanotechnology perspective about "the lightest 2D metal." In that piece, the authors suggested borophene may be ideal for flexible and transparent electronic interconnects, electrodes and displays. It could also be suitable for superconducting quantum interference devices and, when stacked, for hydrogen storage and battery applications.

Credit: 
Rice University

Researchers engineer bacteria to create fertilizer out of thin air

image: Himadri Pakrasi (left), led a team of researchers that has created a bacteria that uses photosynthesis to create oxygen during the day, and at night, uses nitrogen to create chlorophyll for photosynthesis. The team included Michelle Liberton (second from left), Deng Liu and Maitrayee Bhattacharyya-Pakrasi.

Image: 
Photo: Joe Angeles/Washington University

In the future, plants will be able to create their own fertilizer. Farmers will no longer need to buy and spread fertilizer for their crops, and increased food production will benefit billions of people around the world, who might otherwise go hungry.

These statements may sound like something out of a science fiction novel, but new research by Washington University in St. Louis scientists show that it might soon be possible to engineer plants to develop their own fertilizer. This discovery could have a revolutionary effect on agriculture and the health of the planet.

The research, led by Himadri Pakrasi, the Glassberg-Greensfelder Distinguished University Professor in the Department of Biology in Arts & Sciences and director of the International Center for Energy, Environment and Sustainability (InCEES); and Maitrayee Bhattacharyya-Pakrasi, senior research associate in biology, was published in the May/June issue of mBio.

Creating fertilizer is energy intensive, and the process produces greenhouse gases that are a major driver of climate change. And it's inefficient. Fertilizing is a delivery system for nitrogen, which plants use to create chlorophyll for photosynthesis, but less than 40 percent of the nitrogen in commercial fertilizer makes it to the plant.

After a plant has been fertilized, there is another problem: runoff. Fertilizer washed away by rain winds up in streams, rivers, bays and lakes, feeding algae that can grow out of control, blocking sunlight and killing plant and animal life below.

However, there is another abundant source of nitrogen all around us. The Earth's atmosphere is about 78 percent nitrogen, and the Pakrasi lab in the Department of Biology just engineered a bacterium that can make use of that atmospheric gas -- a process known as "fixing" nitrogen -- in a significant step toward engineering plants that can do the same.

The research was rooted in the fact that, although there are no plants that can fix nitrogen from the air, there is a subset of cyanobacteria (bacteria that photosynthesize like plants) that is able to do so. Cyanobacteria can do this even though oxygen, a byproduct of photosynthesis, interferes with the process of nitrogen fixation.

The bacteria used in this research, Cyanothece, is able to fix nitrogen because of something it has in common with people.

"Cyanobacteria are the only bacteria that have a circadian rhythm," Pakrasi said. Interestingly, Cyanothece photosynthesize during the day, converting sunlight to the chemical energy they use as fuel, and fix nitrogen at night, after removing most of the oxygen created during photosynthesis through respiration.

The research team wanted to take the genes from Cyanothece, responsible for this day-night mechanism, and put them into another type of cyanobacteria, Synechocystis, to coax this bug into fixing nitrogen from the air, too.

To find the right sequence of genes, the team looked for the telltale circadian rhythm. "We saw a contiguous set of 35 genes that were doing things only at night," Pakrasi said, "and they were basically silent during the day."

The team, which also included research associate Michelle Liberton, former research associate Jingjie Yu, and Deng Liu manually removed the oxygen from Synechocystis and added the genes from Cyanothece. Researchers found Synechocystis was able to fix nitrogen at 2 percent of Cyanothece. Things got really interesting, however, when Liu, a postdoctoral researcher who has been the mainstay of the project, began to remove some of those genes; with just 24 of the Cyanothece genes, Synechocystis was able to fix nitrogen at a rate of more than 30 percent of Cyanothece.

Nitrogen fixation rates dropped markedly with the addition of a little oxygen (up to 1 percent), but rose again with the addition of a different group of genes from Cyanothece, although it did not reach rates as high as without the presence of oxygen.

"This means that the engineering plan is feasible," Pakrasi said. "I must say, this achievement was beyond my expectation."

The next steps for the team are to dig deeper into the details of the process, perhaps narrow down even further the subset of genes necessary for nitrogen fixation, and collaborate with other plant scientists to apply the lessons learned from this study to the next level: nitrogen-fixing plants.

Crops that can make use of nitrogen from the air will be most effective for subsistence farmers -- about 800 million people worldwide, according to the World Bank -- raising yields on a scale that is beneficial to a family or a town and freeing up time that was once spent manually spreading fertilizer.

"If it's a success," Bhattacharyya-Pakrasi said, "it will be a significant change in agriculture."

Credit: 
Washington University in St. Louis

New platform discovered at City of Hope poised to be next generation of genetic medicines

image: City of Hope's Saswati Chatterjee (left), Ph.D., discovered a gene-editing technology that could efficiently and accurately correct the genetic defects that underlie certain diseases.

Image: 
City of Hope

DUARTE, Calif. -- A City of Hope scientist has discovered a gene-editing technology that could efficiently and accurately correct the genetic defects that underlie certain diseases, positioning the new tool as the basis for the next generation of genetic therapies.

This editing platform, discovered by City of Hope's Saswati Chatterjee, Ph.D., eventually may be used to cure inherited and acquired diseases.

"Our editing platform provides a new tool for the precise correction of genetic mutations in this rapidly growing field," said Chatterjee, senior author of the new study and a professor in the Department of Surgery at City of Hope. "Think of it as swapping out a mutated gene for a healthy gene to correct genetic mutations."

The proof-of-concept study, published in the journal Proceedings of the National Academy of Sciences on July 16, spotlights a promising new gene-editing platform that may eventually be used to treat diseases such as sickle cell disease, hemophilia (a condition that reduces the ability of blood to clot) and other genetic disorders, Chatterjee said.

This genome-editing platform, tested using human blood and tissue as well as in preclinical models, is based on a family of nondisease-causing viruses known as adeno-associated viruses (AAV).

"Although injecting viruses into humans may sound alarming, a large portion of the population already has been exposed to AAV with no harmful consequences in their normal life," Chatterjee said.

Chatterjee's research group isolated a subgroup of AAV known as AAVHSCs, which originate from human blood stem cells. The team discovered that AAVHSCs have the ability to efficiently deliver corrective DNA sequences to the nuclei of targeted cells in the body. Through a process called homologous recombination, these corrective sequences replace disease-causing genetic mutations in the genome. Since the therapeutic correction is at the genome level, it should lead to lifelong correction.

"We found that AAVHSC-based editing vectors can efficiently edit the genome following a single administration," Chatterjee said. "We hope to use these properties to develop widespread and accessible genome editing used to treat genetic diseases around the world."

The editing platform works efficiently in stem cells and mature cells, including adult liver and muscle cells. Successful utilization of AAV has the potential to change the world of gene editing, said Yuman Fong, M.D., co-author of the study and the Sangiacomo Family Chair in Surgical Oncology at City of Hope.

"We at City of Hope are attempting to build the foundation for another landmark treatment, like we did for synthetic human insulin," Fong said. "The potential of altering the course of genetic diseases is immense. Pairing the right AAV with blood stem cells is going to be an instrumental technique for precision medicine, the next frontier of medical treatment."

Chatterjee and her colleagues still have much work to do to characterize how this platform works and to develop it into therapeutics. They will address these questions in future studies.

This year, Chatterjee received a $2 million grant from the California Institute of Regenerative Medicine to develop a permanent cure for hemophilia A.

City of Hope licensed the pioneering AAV gene editing technology exclusively to Homology Medicines Inc. in May 2016. Chatterjee is the scientific co-founder of Homology Medicines and the chair of the company's scientific advisory board. The genetic medicines company went public in March 2018. Homology Medicines has entered into a research and development collaboration with Novartis.

Credit: 
City of Hope

New development in 3D super-resolution imaging gives insight on Alzheimer's disease

video: Researchers discuss how a new imaging technique could reveal why Alzheimer's disease starts.

Image: 
Purdue University/Erin Easterling

WEST LAFAYETTE, Ind. -- Recent studies show that 40 percent of Americans over the age of 85 have Alzheimer's disease, and that the disease begins 10 to 20 years before people show up at the doctor's office with memory problems.

One major problem with understanding Alzheimer's is not being able to clearly see why the disease starts. A super-resolution "nanoscope" developed by Purdue University researchers now provides a 3D view of brain molecules with 10 times greater detail. This imaging technique could help reveal how the disease progresses and where new treatments could intervene.

The instrument helped Indiana University researchers better understand the structure of plaques that form in the brain of Alzheimer's patients, pinpointing the characteristics that are possibly responsible for damage. Published findings appear in the journal Nature Methods.

Long before Alzheimer's develops in an individual, waxy deposits called amyloid plaques accumulate in the brain. These clusters interact with surrounding cells, causing inflammation that destroys neurons and creates memory problems.

The deposition of these plaques is currently the earliest detectable evidence of pathological change leading to Alzheimer's disease.

"While strictly a research tool for the foreseeable future, this technology has allowed us to see how the plaques are assembled and remodeled during the disease process," said Gary Landreth, professor of anatomy and cell biology at the Indiana University School of Medicine's Stark Neurosciences Research Institute. "It gives insight into the biological causes of the disease, so that we can see if we can stop the formation of these damaging structures in the brain."

The limited resolution in conventional light microscopes and the natural thickness of brain tissue have prevented researchers from clearly observing 3D morphology of amyloid plaques and their interactions with other cells.

"Brain tissue is particularly challenging for single molecule super-resolution imaging because it is highly packed with extracellular and intracellular constituents, which distort and scatter light - our source of molecular information," said Fang Huang, Purdue assistant professor of biomedical engineering. "You can image deep into the tissue, but the image is blurry."

The super-resolution nanoscopes, which Huang's research team has already developed to visualize cells, bacteria and viruses in fine detail, uses "adaptable optics" - deformable mirrors that change shape to compensate for light distortion, called "aberration," that happens when light signals from single molecules travel through different parts of cell or tissue structures at different speeds.

To tackle the challenge of brain tissue, Huang's research team developed new techniques that adjust the mirrors in response to sample depths to compensate for aberration introduced by the tissue. At the same time, these techniques intentionally introduce extra aberration to maintain the position information carried by a single molecule.

The nanoscope reconstructs the whole tissue, its cells, and cell constituents at a resolution six to 10 times higher than conventional microscopes, allowing a clear view through 30-micron thick brain sections of a mouse's frontal cortex.

The researchers used mice that were genetically engineered to develop the characteristic plaques that typify Alzheimer's disease. (A YouTube video is available at https://youtu.be/YNmM_gkwNDY.)

Landreth's lab found through these 3D reconstructions that amyloid plaques are like hairballs, entangling surrounding tissue via their small fibers that branch off waxy deposits.

"We can see now that this is where the damage to the brain occurs. The mouse gives us validation that we can apply this imaging technique to human tissue," Landreth said.

The collaboration has already begun work on using the nanoscope to observe amyloid plaques in samples of human brains, as well as a closer look at how the plaques interact with other cells and get remodeled over time.

"This development is particularly important for us as it had been quite challenging to achieve high-resolution in tissues. We hope this technique will help further our understanding of other disease-related questions, such as those for Parkinson's disease, multiple sclerosis and other neurological diseases," Huang said.

Credit: 
Purdue University

Microscopic trampoline may help create networks of quantum computers

image: This chip, designed by researchers at JILA and measuring less than a half-inch across, converts microwave energy into laser light.

Image: 
Peter Burns and Dan Schmidt

A microscopic trampoline could help engineers to overcome a major hurdle for quantum computers, researchers from the University of Colorado Boulder and the National Institute of Standards and Technology (NIST) report in a new study.

Scientists at JILA, a joint institute of CU Boulder and NIST, have developed a device that uses a small plate to absorb microwave energy and bounce it into laser light--a crucial step for sending quantum signals over long distances.

Graduate student Peter Burns said that his team's research could one day help engineers to link together huge networks of quantum computers.

"We're anticipating a growth in quantum computing and are trying to create a link that will be usable for these networks," said Burns, one of two lead authors of the new study.

Over the last decade, several tech firms have made inroads into designing prototype quantum chips, which have the potential to be much more powerful than traditional computers. But getting the information out of such chips is a difficult feat.

One big challenge lies in translation. Top-of-the-line quantum chips like Google's Bristlecone or Intel's Tangle Lake send out data in the form of photons, or tiny packets of light, that wobble at microwave frequencies. Much of modern communications, however, relies on fiberoptic cables that can only send visible light.

In research published today in Nature Physics, the team reports that zapping a small plate made of silicon-nitride with a beam of microwave photons causes it to vibrate and eject photons from its other end. But those photons now quiver at optical frequencies.

The researchers were able to achieve that hop, skip and a jump at an efficiency of 47 percent, meaning that for every two microwave photons that hit the plate, close to one optical photon came out. That's a much better performance than other methods for converting microwaves into light, such as by using crystals or magnets, Burns said.

He added that what's really impressive about the device is its quietness. Even in the ultra-cold lab facilities where quantum chips are stored, trace amounts of heat can cause the team's trampoline to shake. That, in turn, sends out excess photons that contaminate the signal. To get rid of the clutter, the researchers invented a new way to measure that noise and subtract it from their light beams.

"What we do is measure that noise on the microwave side of the device, and that allows us to distinguish on the optical side etween the signal and the noise," Burns said.

The team will need to bring down the noise even more for the trampoline to become a practical tool. But the potential benefits are huge, said Konrad Lehnert of JILA and a co-author of the new research.

"It's clear that we are moving toward a future where we will have little prototype quantum computers," he said. "It will be a huge benefit if we can network them together."

Credit: 
University of Colorado at Boulder

Electric car batteries souped-up with fluorinated electrolytes for longer-range driving

video: The success of electric car batteries depends on the miles that can be driven on a single charge, but the current crop of lithium-ion batteries are reaching their natural limit of how much charge can be packed into any given space, keeping drivers on a short tether. Now, researchers at the University of Maryland (UMD), the U.S. Army Research Laboratory (ARL), and Argonne National Laboratory (ANL) have figured out how to increase a rechargeable battery's capacity by using aggressive electrodes and then stabilizing these potentially dangerous electrode materials with a highly-fluorinated electrolyte.

Image: 
University of Maryland

College Park, Md. -- The success of electric car batteries depends on the miles that can be driven on a single charge, but the current crop of lithium-ion batteries are reaching their natural limit of how much charge can be packed into any given space, keeping drivers on a short tether. Now, researchers at the University of Maryland (UMD), the U.S. Army Research Laboratory (ARL), and Argonne National Laboratory (ANL) have figured out how to increase a rechargeable battery's capacity by using aggressive electrodes and then stabilizing these potentially dangerous electrode materials with a highly-fluorinated electrolyte.

A peer-reviewed paper based on the research was published July 16 in the journal Nature Nanotechnology.

"We have created a fluorine-based electrolyte to enable a lithium-metal anode, which is known to be notoriously unstable, and demonstrated a battery that lasts up to a thousand cycles with high capacity," said co-first authors Xiulin Fan and Long Chen, postdoctoral researchers at UMD's A. James Clark School of Engineering.

The new batteries can thus charge and discharge many times over without losing the ability to provide a reliable and high quality stream of energy. Even after a thousand charge cycles, the fluorine enhanced electrolytes ensured 93% of battery capacity, which the authors call "unprecedented." This means that a car running on this technology would reliably drive the same number of miles for many years.

"The cycle lives they achieved with the given electrode materials and operation voltage windows sound 'unprecedented.' This work is a [sic] great progress forward in the battery field in the direction of increasing the energy density, although further tuning might be needed to meet various standards for commercialization," said Jang Wook Choi, an associate professor in chemical and biological engineering at Seoul National University in South Korea. Choi was not involved with the research.

The team demonstrated the batteries in coin-cell shape like a watch battery for testing and is working with industry partners to use the electrolytes for a high voltage battery.

These aggressive materials, such as the lithium-metal anode and nickel and high-voltage cathode materials, are called such because they react strongly with other material, meaning that they can hold a lot of energy but also tend to "eat up" any other elements they're partnered with, rendering them unusable.

Chunsheng Wang, professor in the Clark School's Department of Chemical and Biochemical Engineering, has collaborated with Kang Xu at ARL and Khalil Amine at ANL on these new electrolyte materials for batteries. Since each element on the periodic table has a different arrangement of electrons, Wang studies how each permutation of chemical structure can be an advantage or disadvantage in a battery. He and Xu also head up an industry-university-government collaborative effort called the Center for Research in Extreme Batteries, which aims to unite companies that need batteries for unusual uses with the researchers who can invent them.

"The aim of the research was to overcome the capacity limitation that lithium-ion batteries experience. We identified that fluorine is the key ingredient that ensures these aggressive chemistries behave reversibly to yield long battery life. An additional merit of fluorine is that it makes the usually combustible electrolytes completely unable to catch on fire," said Wang.

The team captured video of several battery cells catching on fire in instants, but the fluorine battery was impervious.

The high population of fluorine-containing species in the interphases is the key to making the material work, even though results have varied for different researchers in the past regarding the fluorination.

"You can find evidences from literature that either support or disapprove fluorine as good ingredient in interphases," said Xu, laboratory fellow and team leader of the research at ARL. "What we learned in this work is that, in most cases it is not just what chemical ingredients you have in the interphase, but how they are arranged and distributed."

Credit: 
University of Maryland

The love lives of fruit flies

Two fruit flies meet in an acrylic mating chamber and check each other out. It's the insect version of speed dating for science.

The male taps the female with his leg, which is studded with pheromone-sensing receptors. He then might doggedly follow her around and serenade her with a song by sticking out a wing and vibrating it. But before the male engages in this courtship ritual, he needs to make an important decision: Should he put the moves on this female or not?

In a study published online July 5 in Neuron, scientists at Harvard Medical School show that what tips the balance in favor or against is the convergence of motivation, perception and chance. The combination, the researchers found, powerfully influences the balance of excitatory and inhibitory inputs to a small region of the brain.

It's Not About Sex

Understanding the mechanisms of insect choice, the research team said, could help scientists glean insights into and develop strategies for the treatment of human disorders where motivation goes awry, such as such as addiction and depression.

For study authors Dragana Rogulja, assistant professor of neurobiology at Harvard Medical School, and Michael Crickmore, assistant professor of neurology at Harvard Medical School and the F.M. Kirby Neurobiology Center at Boston Children's Hospital, helping unravel the neurobiology behind such abnormalities in human motivation is the ultimate quest.

However, their explorations take place in the insect brain's motivation circuitry--the interconnected sets of neurons that fruit flies use to choose whether to do things like eating, sleeping or mating.

Fruit fly courtship is an ideal model to study this fascinating circuitry, explains Rogulja, because the anatomy that governs this phenomenon is relatively simple and sexually dimorphic in these insects, which makes it easy to locate and manipulate. A group of about 20 neurons, called P1, functions as the male fly's courtship command center.

The team's research shows that when male fruit flies give females a leg tap, the likelihood of initiating courtship is based on two factors: The males' internal state--their libido or how amorous they feel--and on external stimuli, such as the "quality" of their mating target.

For example, males who haven't mated in a while will initiate courtship about 44 percent of the time following each leg tap of a female that is sexually mature and also hasn't mated in a while. That number drops to about 7 percent if presented with a female who has recently mated, and to about 6.5 percent if the male has engaged in a lot of recent mating himself.

Based on previous work in their laboratories, Rogulja and Crickmore knew that dopamine--a brain chemical that guides desire and motivation in flies and humans alike--is a catalyst in fly mating, and that dopamine levels are high in sex-starved male flies. But the neural mechanisms by which this chemical signal directs courtship behavior were unknown.

Inside the Male (Fruit Fly) Mind

To better understand what motivates courtship in male flies, the researchers used a combination of different methods, including a technique that makes neurons light up under the microscope, deleting particular receptors from the surfaces of other neurons, and using light to stimulate or inhibit populations of neurons.

Together, their results paint a picture of what's happening inside the male fly brain.

After that initial leg tap, the researchers explain, a flood of both excitatory--"Go for it!"--and inhibitory--"Don't bother!"--signals flow into the courtship command center, the P1. If the male's target is perceived as "low quality"--not sexually mature, too young, too old, or if his pheromone receptors detect a low level of sexual desire in her--the P1 center will receive more inhibitory signals than excitatory ones.

However, according to Rogulja, if the male fly's P1 neurons receive a lot of dopamine, they become less sensitive to the inhibitory signals, giving the male fly the go-ahead to court, sometimes even under circumstances that aren't ideal.

After the initial decision to court, dopamine is also responsible for maintaining courtship behavior all the way until mating, she explains. Flies with low levels of dopamine might make a half-hearted attempt at courting but quickly give up.

However, those with high levels of dopamine were more likely to persistently pursue their love interests.

"Dopamine tells the command center how to respond initially and when to give up," Rogulja said. "The decision to court is a function of these neurons."

It's Complicated

However, noted Crickmore, the male flies didn't act reflexively--even highly motivated males paired with ideal females didn't court after every tap. They do so only 44 percent of the time. Similarly, males with low motivation because of recent mating or a less than ideal target still courted occasionally. This binary decision to court or not court, he explained, has an element of chance like a coin toss, weighted by factors including the male's motivation and the sensory information he receives from the female.

That element of chance is a key part of what makes the brain's motivation circuitry different from the circuitry responsible for processing sensory or motor signals.

"When you cross the street, you want to be able to see a car coming toward you with 100 percent certainty," said Crickmore. "When you're walking, you want your right leg to follow your left leg 100 percent of the time. You don't want things left up to chance."

The circuits underlying the decision to pursue someone or something, however, may incorporate an element of chance, rendering these generally logical behaviors occasionally quirky and even irrational.

In future studies, Crickmore and Rogulja want to understand better how chance is integrated into motivational circuits by identifying the responsible genes and circuit principles.

Importantly, the scientists say, the neurobiology and neurochemistry of fruit fly motivation might bring about valuable insights into what goes awry in addiction-- in which individuals are propelled toward substances or activities that can be harmful, or in depression, where it's hard for people to summon up motivation even for the normal activities of daily life.

"When you think about it this way, these conditions lock individuals on the wrong end of the probability distribution," Crickmore said. "Doing productive things too rarely or engaging in destructive behaviors too often."

Historically, the researchers said, discoveries made in the fruit fly model have translated well into insights about humans--evidenced most recently in last year's Nobel Prize for elucidating the molecular mechanisms of circadian rhythms.

Credit: 
Harvard Medical School