Tech

DNA-based technique allows researchers to determine age of living beluga whales in Alaska

image: A gray beluga whale calf with three adults in Cook Inlet, Alaska. NMFS ESA/MMPA Permit #20465.

Image: 
Paul Wade, NOAA Alaska Fisheries Science Center.

NEWPORT, Ore. - Researchers can now determine the age and sex of living beluga whales in Alaska's Cook Inlet thanks to a new DNA-based technique that uses information from small samples of skin tissue.

Accurate age estimates are vital to conservation efforts for Cook Inlet belugas, which were listed as endangered following a significant population decline in the 1990s. Previously, researchers could only determine the age of beluga whales by studying the teeth of dead animals.

The new aging method uses DNA methylation data and machine learning to develop a model that captures the relationship between methylation and age. This relationship provides an epigenetic clock for beluga whales.

Epigenetics broadly refers to non-heritable molecular modifications of DNA that change the way genes function. Methylation is one form of epigenetics; it is a biological process by which methyl groups are added to the DNA molecule. In mammals, there are places along the genome that become more methylated as an animal ages.

The new method for determining Cook Inlet beluga whales' age represents a significant advance in understanding the life history of the species and will have applications to other whale species. The method also can be used to identify an animal's sex.

"The development of this tool and the use of the epigenetic clock is a major advance in the science of aging," said Eleanor Bors, the study's lead author. Bors worked on the project as a post-doctoral fellow at Oregon State University's Marine Mammal Institute. "We have the technology now to do this easily and it can become a routine part of research on beluga whales."

The researchers' findings were just published in the journal Evolutionary Applications. Co-authors include Scott Baker, associate director of OSU's Marine Mammal Institute; Paul Wade of NOAA's Alaska Fisheries Science Center; and Steve Horvath of the University of California, Los Angeles.

Beluga whales are known for their distinctive white color and rounded heads. They average 13 feet in length and 3,150 pounds, and have a lifespan of up to 80 years. They are found in Alaska and throughout the Arctic.

Cook Inlet beluga whales are a geographically and genetically distinct population that does not migrate. The population had numbered more than 1,000 in 1979 but declined sharply from 653 to 347 between 1994 and 1998, in part due to unregulated hunting.

Hunting regulations were implemented in 2000 but the population has not rebounded. Today there are an estimated 279 beluga whales in the population, and they have been designated one of NOAA's "Species in the Spotlight," an initiative to bring greater attention and resources to species most highly at risk of extinction.

A NOAA species recovery plan issued in 2016 highlighted the need to determine the age structure of the Cook Inlet beluga population to better understand growth, reproduction and survival rates.

In toothed whales and dolphins, age is typically determined by examining teeth, which record age in growth layers similar to tree rings. But that option is only available once an animal has died. Using genomic information, which can be collected with a small biopsy dart, is an important development in the study of living whales and dolphins.

Researchers were able to develop the DNA methylation technique in part because the beluga whale's genome had already been sequenced, Baker said.

Working with tissue samples from 67 dead whales, the researchers measured methylation levels across tens of thousands of sites in the genome and determined that an effective clock model could be built using just 23 sites related to aging.

The researchers used machine learning to develop an epigenetic age profile for the species based on their findings. Finally, researchers calibrated their findings against age information determined by teeth recovered from the same animals.

"With all of that information, we were able to accurately model the relationship between methylation and age," Bors said.

Once the profile was built, researchers analyzed skin samples collected between 2016 and 2018 from 38 living whales. They were able to estimate ages and identify the sex of the animals using DNA methylation.

The new aging method gives researchers an important piece of data to use in their work to understand and, they hope, identify ways to reverse the population decline, Wade said. For example, while belugas in other populations reach sexual maturity at about age 8 or 9, the researchers have found that among the Cook Inlet whales tested so far, just one between ages 10 and 19 was pregnant.

"If reproduction is substantially delayed like that, it's a signal that is surprising. That is an area we can explore further," said Wade. "We want to keep adding data to see what else we can learn. We see this aging technique as something we want to do routinely now."

As additional samples are collected, the age profile for the species should continue to calibrate and refine itself, Baker added.

One question for future research is whether this process for determining age is applicable to other beluga whale populations, or more broadly to other whales, dolphins and porpoises, the researchers said. Genetic information collected in the database also can be mined for other biological changes.

"There is a lot of interest in methylation as an indicator of stress, for example," Baker said. "I'm also interested in kinship relationships within the population, which will now be easier to determine by knowing the age of individuals."

Credit: 
Oregon State University

Surface effect of electrodes revealed by operando surface science methodology

image: Schematic of the Al/HOPG planar model battery

Image: 
@Science China Press

Surface and interface play critical roles in energy storage devices, thus calling for in-situ/operando methods to probe the electrified surface/interface. However, the commonly used in-situ/operando characterization techniques such as X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray spectroscopy and topography, and nuclear magnetic resonance (NMR) are based on the structural, electronic and chemical information in bulk region of the electrodes or electrolytes.

Surface science methodology including electron spectroscopy and scanning probe microscopy can provide rich information about how reactions take place on the solid surfaces. But the applications of the sophisticated surface science methods in complicated electrochemical systems still remain less explored and more challenges. The main reasons are that the surface science methodology is commonly done in ultra-high vacuum (UHV) condition and over model structures with the open and well-defined surfaces.

In a new research article (entitled "Operando Surface Science Methodology Reveals Surface Effect in Charge Storage Electrodes") published in the National Science Review, scientists at Dalian Institute of Chemical Physics (CAS) in Dalian, China propose a new strategy to apply operando surface science methods to explore the electrochemical process in the surface region of electrodes. Chao Wang and Qiang Fu et al. successfully carried out multiple operando surface science characterizations including Raman, XPS, AFM and SKPM over a planar Al/HOPG model battery. Intercalation of super-dense multilayer anions together with cations into the graphite electrode surface region has been directly visualized.

Based on UHV compatible ionic liquid (IL) electrolyte and well-defined electrodes, a planar Al/HOPG model battery which is composed of Al foil, HOPG flake and IL electrolyte in between has been designed for the following operando surface analysis (Figure 1 left). The model battery performs the same electrochemical behaviors as the real one. Furthermore, the diffusion length of the intercalated ions within HOPG model electrode can reach to millimeter. Thus, the electrochemical process can be directly probed on the open and clean electrode surface (Figure 1 right).

Operando Raman spectra have been acquired on the model battery. As displayed in Figure 2(a), a stage-1 graphite intercalation compound (GIC) in the surface region is formed after being charged. In addition to the Raman signals of graphite, the co-intercalation of AlCl4- and EMI+ has also been discovered for the first time through operando Raman measurements. Subsequently, the model battery is further investigated by operando XPS. A set of XPS Al 2p and C 1s core-level signals are displayed in Figure 2 (b) and (c). Co-intercalation of EMI+ has been further proved by operando XPS and its stoichiometric ratio with AlCl4- is 4:5 (Figure 2(d)). The quantitative description of the charging mechanism in AIB has been proposed for the first time.

Notably, the intercalant ion concentrations (Figure 2(e)) in the surface region (Al/C ? 1:1.7) at the fully charged state (2.45 V) deduced from the operando XPS measurements are amazingly one order higher than the theoretical value (Al/C ? 1:24, dash line in Figure 2(e)). Such results demonstrate the super-dense multilayer anions together with cations in the surface region. This distinct electrochemical process in the surface region can be further proved by quasi in-situ Raman, XPS, TOF-SIMS, and in-situ XRD/AFM measurements. The electrochemical behavior in the surface region and surface-dominant nanometer thickness graphite electrode can be described as the intercalation pseudocapacitance in contrast with the battery process in the bulk region (Figure 3). Based on the super-dense anion/cation intercalation mode in the surface region, the capacity can be doubled by using nanometer thickness graphite electrode in real coin-type AIB, which supports the operando characterization results based on the model devices.

Based on the operando surface science analysis over a well-designed Al/HOPG model device, in depth and comprehensive charging mechanisms of AIB has been reached in this work. Particularly, an obvious surface effect has been discovered which can be used to improve the capacity. This work provides a new strategy of using operando surface science methodology to explore the surface/interface process in energy storage systems and highlight the critical role of the surface effect and surface science methodology in energy storage systems.

Credit: 
Science China Press

Imaging technique provides link to innovative products

When we think about the links to the future - the global transition to solar and wind energy, tactile virtual reality or synthetic neurons - there's no shortage of big ideas. It's the materials to execute the big ideas - the ability to manufacture the lithium-ion batteries, opto-electronics and hydrogen fuel cells - that stand between concept and reality.

Enter two-dimensional materials, the latest step in innovation. Consisting of a single layer of atoms, two-dimensional materials like graphene and phosphorene exhibit new properties with far-reaching potential. With a capability to be combined like Lego bricks, these materials offer connections to future products, including new means to convey both power and people, with more-efficient energy transmission, and solar- and wind-powered vehicles on roads and in skies.

A study led by University of Georgia researchers announces the successful use of a new nanoimaging technique that will allow researchers to test and identify these materials in a comprehensive way at the nanoscale for the first time. Now, there's a way to experiment with new materials for our big ideas at a really, really small scale.

"Fundamental science - small-scale electrical conductivity, light emission, structural changes - happen at the nanoscale," said Yohannes Abate, Susan Dasher and Charles Dasher MD Professor of Physics in the Franklin College of Arts and Sciences and lead author on the new paper. "This new tool allows us to visualize all of this combined at unprecedented specificity and resolution."

"Since we cannot see atoms with traditional methods, we needed to invent new tools to visualize them," he said. The hyperspectral imaging technique allows scientists to inspect electrical properties, optical properties, and the mechanical properties at the fundamental length scale, simultaneously.

The hyperspectral imaging research is supported by grants from the United States Air Force and the National Science Foundation. The researchers created a one-atom thick sheet of two kinds of semiconductors stitched together, similar to assembling an atomic Lego, with properties not found in traditional thick materials. With single-atom-thick crystals, each atom is literally exposed on the surface, combining atomic properties that result in new properties.

"At the heart of materials science is the need to understand fundamental properties of new materials, otherwise it is impossible to take advantage of their unique properties," Abate said. "This technique puts us one step closer to being able to use these materials for a number of potential applications."

Those include various forms of electronics or light-emitting systems applications. How to verify the effect of very small changes in atomic composition, conductivity and light response of single-atom-thick materials simultaneously has been the challenge until now, Abate said.

Nobel Prize-winning physicist Richard Feynman, who envisioned nanotechnology as early as the 1960s, predicted that as scientists became able to choose and replace certain kinds of atoms, they would able to fabricate practically any imaginable material.

"More than half a century later, we're not there yet, but where we are, we can visualize them, and at that scale there are new issues that can arise and we have to understand those properties as a part of understanding the large scale material properties, before we can use them," Abate said.

Credit: 
University of Georgia

U.S. Air Force Academy intervention reduces unwanted sexual contact by over 40 percent

image: Dr. Kenneth Griffin led the study that found that this prevention program effectively reduced unwanted sexual contact among Air Force Cadets.

Image: 
George Mason University

Sexual assault and sexual harassment are significant problems in the U.S. military and military service academies in the United States. In 2018, 15.8% of female and 2.4% of male cadets and midshipmen across the military service academies reported unwanted sexual contact in the past year. This unwanted behavior can contribute to a variety of negative mental and behavioral health outcomes.

While the military service academies have implemented multiple sexual assault prevention programs and social marketing campaigns to improve awareness of and response to sexual assault, prevention initiatives have been hindered by an absence of evidence from rigorous research about what works.

Eliminating sexual assault in the military is a key focus of the Biden Administration's newly confirmed Defense Secretary Lloyd Austin. As one of his first actions in office, Austin has ordered a review of military sexual assault prevention programs.

To address the gap in evidence-based interventions, Dr. Kenneth W. Griffin, professor at George Mason University’s College of Health and Human Services, worked with colleagues to rigorously test the effectiveness of the Cadet Healthy Personal Skills (CHiPS) primary prevention program. CHiPS was developed by National Health Promotion Associates (NHPA) and tested in a randomized controlled trial among cadets at the U.S. Air Force Academy (USAFA) by a research team led by Dr. Griffin. The results were published online in the American Journal of Public Health January 21, 2021.

Griffin and colleagues found a more than 40% reduction in unwanted sexual contact among U.S. Air Force cadets who participated in the CHiPS intervention compared to those who did not participate in the intervention.

"CHiPS is a small group preventive intervention, developed by NHPA for the U.S. Air Force Academy. The program is based on Botvin Life Skills Training, an evidence-based program which has proven effective at preventing substance abuse, violence, and sexual risk taking among adolescents," explains Griffin. "The intervention is designed to positively change social norms and bystander intervention behaviors surrounding sexual violence; increase knowledge and skills regarding obtaining consent for sexual activities; address the relationship between sexual violence and alcohol and substance abuse; and build social, self-regulation, and healthy relationship skills through interactive learning and behavioral rehearsal scenarios."

Their randomized control study included 832 participants, and the new program was implemented in the summer of 2018. About half of the incoming class of 2021 cadets were assigned to receive the prevention program and half were assigned to a control group.

The CHiPS intervention has been sustained at USAFA and implemented with the incoming classes of cadets each summer since the conclusion of this study. This suggests that the program is both effective and has high potential for institutionalization.

Credit: 
George Mason University

Switching nanolight on and off

image: An optically excited gas of electronic carriers confined to the planes of the layered van-der Waals semiconductor tungsten diselenide is shown. The consequent hyperbolic response permits passage of nanolight.

Image: 
Ella Maru Studio

A team of researchers led by Columbia University has developed a unique platform to program a layered crystal, producing imaging capabilities beyond common limits on demand.

The discovery is an important step toward control of nanolight, which is light that can access the smallest length scales imaginable. The work also provides insights for the field of optical quantum information processing, which aims to solve difficult problems in computing and communications.  

"We were able to use ultrafast nano-scale microscopy to discover a new way to control our crystals with light, turning elusive photonic properties on and off at will," said Aaron Sternbach, postdoctoral researcher at Columbia who is lead investigator on the study. "The effects are short-lived, only lasting for trillionths of one second, yet we are now able to observe these phenomena clearly." 

The research appears Feb. 4 in the journal Science.

Nature sets a limit on how tightly light can be focused. Even in microscopes, two different objects that are closer than this limit would appear to be one.  But within a special class of layered crystalline materials--known as van de Waals crystals--these rules can, sometimes, be broken. In these special cases, light can be confined without any limit in these materials, making it possible to see even the smallest objects clearly.

In their experiments, the Columbia researchers studied the van der Waals crystal called tungsten diselenide, which is of high interest for its potential integration in electronic and photonic technologies because its unique structure and strong interactions with light. 

When the scientists illuminated the crystal with a pulse of light, they were able to change the crystal's electronic structure. The new structure, created by the optical-switching event, allowed something very uncommon to occur: Super-fine details, on the nanoscale, could be transported through the crystal and imaged on its surface.

The report demonstrates a new method to control the flow of light of nanolight. Optical manipulation on the nanoscale, or nanophotonics, has become a critical area of interest as researchers seek ways to meet the increasing demand for technologies that go well beyond what is possible with conventional photonics and electronics.

Dmitri Basov, Higgins professor of physics at Columbia University, and senior author on the paper, believes the team's findings will spark new areas of research in quantum matter.

"Laser pulses allowed us to create a new electronic state in this prototypical semiconductor, if only for a few pico-seconds," he said. "This discovery puts us on track toward optically programmable quantum phases in new materials. "

Credit: 
Columbia University

Soil bacteria hormone discovery provides fertile ground for new antibiotics

image: The soil-dwelling Streptomyces coelicolor bacteria producing antibiotics in a Petri dish.

Image: 
Christophe Corre

Mechanism for control of antibiotic production in soil bacteria is visualised for the first time by scientists at University of Warwick and Monash University

Research reported in Nature could lead to improved manufacturing of existing antibiotics, and open up opportunities to discover new ones

The majority of clinically used antibiotics are derived from soil bacteria, but can be hard to find because their production is switched off in laboratory cultures

The discovery of how hormone-like molecules turn on antibiotic production in soil bacteria could unlock the untapped opportunities for medicines that are under our very feet.

An international team of scientists working at the University of Warwick, UK, and Monash University, Australia, have determined the molecular basis of a biological mechanism that could enable more efficient and cost-effective production of existing antibiotics, and also allow scientists to uncover new antibiotics in soil bacteria.

It is detailed in a new study published today (3 February) in the journal Nature.

Most clinically used antibiotics are molecules produced by micro-organisms such as bacteria. The majority of these are soil bacteria called Actinobacteria, which are cultivated in the laboratory to allow the molecules they produce to be extracted. However, the production of these molecules is frequently switched off in laboratory cultures, making them difficult to find.

The bacteria tightly control the production of their antibiotics using small molecules akin to hormones. The team at Warwick and Monash investigated a specific class of these bacterial hormones that they had previously discovered, termed 2-akyl-4-hydroxymethylfuran-3-carboxylic acids or AHFCAs, to find out what role they played in controlling the production of an antibiotic in the Actinobacterium Streptomyces coelicolor.

Using x-ray crystallography and single-particle cryo-electron microscopy techniques, they analysed the structure of a protein, known as a transcription factor, bound to a particular region of DNA from the bacterium. This prevents the bacterium from producing the antibiotic.

They then determined the structure of the transcription factor with a synthesized version of one of the AHFCA hormones bound to it, which showed how the DNA is released and antibiotic production is switched on.

Joint lead author Dr Chris Corre, Associate Professor of Synthetic Biology at the University of Warwick Departments of Life Sciences & Chemistry, said: "Antibiotic resistance is becoming a major issue and we urgently need new antibiotics to tackle it.

"We already know that similar processes control the production of a lot of commercially important molecules. If we understand the mechanisms that control the production of these compounds, we can improve the process, to make it more economically viable.

"It turned out that although we were only looking at one particular class of hormones, the mechanism we found appears to be conserved across all of the different hormone classes in Actinobacteria."

Actinobacteria are more complicated than conventional bacteria. They are generally not motile like other forms of bacteria and they have a complex development cycle that the production of the antibiotics is integrated into.

However, when grown in pure culture these bacteria will often switch off antibiotic production, confounding scientists' efforts to study them. By understanding the molecular mechanism for how this process is controlled, scientists can switch on the production of new antibiotics that are not produced in laboratory cultures.

Dr Corre adds: "We can use these strategies to turn on production of new antibiotics in Actinobacteria. Among them, we'd hope to find some that could be useful for tackling infections caused by resistant microbes, as well as other diseases. These compounds would be hard to find via traditional processes."

Key to the discovery was determining the structure of the complex of the transcription factor bound to the DNA, which required the use of single particle cryo-electron microscopy facilities at Monash University to overcome challenges with x-ray crystallography.

Professor Greg Challis, who co-led the study and has a joint appointment at the University of Warwick Department of Chemistry and Monash University, said: "Only a modest number of structures of this type of protein-DNA complex have been determined using x-ray crystallography over the last few decades due to the challenge of obtaining suitable crystals. By using cryo-electron microscopy we have circumvented this challenge, which should make it easier to determine the structures of similar complexes in the future. It wouldn't have been possible to illuminate the molecular basis for control of antibiotic production by these hormones without the combined expertise of colleagues at Warwick and Monash."

Credit: 
University of Warwick

European hibernating bats cope with white-nose syndrome which kills North American bats

image: Mouse-eared bats

Image: 
C Voigt/Leibniz-IZW

What are the reasons for such a contrast in outcomes? A scientist team led by the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) has now analysed the humoral innate immune defence of European greater mouse-eared bats to the fungus. In contrast to North American bats, European bats have sufficient baseline levels of key immune parameters and thus tolerate a certain level of infection throughout hibernation. The results are published in the journal "Developmental and Comparative Immunology".

During infections caused by Pseudogymnoascus destructans (Pd), North American bats arouse frequently from hibernation to trigger a more elaborate immune response, whereas European bats remain dormant, owing, as the new results reveal, to their competent baseline immunity. Not being able to deal with the fungus by baseline immunity causes North American bats to deplete fat stores before the end of winter bnecause of the need for additional and energetically expensive arousals, which ultimately leads to their starvation. European bats may also arouse once in a while when infected but their strong baseline immunity allows them to balance the tight energy budget better during winter hibernation.

For this investigation, the scientists went to hibernation sites in Germany and studied 61 mouse-eared bats (Myotis myotis) with varying levels of natural infections by Pseudogymnoascus destructans. The animals were divided into three groups according to the severity of fungal infections (asymptomatic, mild symptoms, severe infection). Body mass and skeletal body size of bats was measured and blood samples taken from torpid animals. In addition, the team monitored in other conspecifics how often infected animals arose from hibernation. "We could show that there is no link between infection and the frequency of waking up from hibernation in the European greater mouse-eared bat," say Marcus Fritze and Christian C. Voigt, bat experts from the Department Evolutionary Ecology at Leibniz-IZW. "This is consistent with the idea that the fungus does not trigger an immune response in European hibernating bats but is rather kept under control by the bats' baseline immunity."

In contrast, North American bats such as little brown bats (Myotis lucifugus) arouse frequently when infected by the fungus to elicit an immune response. Frequent arousal and the immune response require energy and prematurely deplete the body's fat stores before the winter has ended. The protein haptoglobin seems key in the bats' fight against the fungus. Haptoglobin is an acute phase protein, which can be produced by bats without large metabolic costs. "Our results demonstrated the central role of haptoglobin in the defence against the fungus. Interestingly, baseline levels of this protein are sufficient to protect the European host against the fungus and there is no need to actively synthesise the protein during the torpid phase", adds Gábor Á. Czirják, wildlife immunologist at the Department of Wildlife Diseases of the Leibniz-IZW.

A second key finding of the team's investigation is that heavier European greater mouse-eared bats arouse from hibernation more frequently than lean conspecifics. This seems counterintuitive because each arousal event causes a depletion of fat stores. Well-nourished bats seem to assist their immune system by actively clearing off the external fungal hyphens from their body while being awake for short periods. Thus, heavy bats are in a healthier condition towards the end of hibernation than lean animals. Lean animals cannot afford to arouse as often and thus depend on the efficacy of the baseline immunity to control the fungus. The safety net of a competent immunity keeps European (and Asian) bats alive during infections with P. destructans but proves to be insufficient for North American bats.

These results add further evidence that there are differences in the defence strategies against the causative agent of white-nose syndrome in European and North American bat species. Tolerance strategies aim to limit the impact of the fungal infection on the health of animals. Resistance strategies, on the other hand, try to actively reduce the load of pathogens. "Tolerance strategies are effective, as the immune defences of hibernating European mouse-eared bats show," Voigt summarises. "In North American bats, however, this ability is not present to a sufficient degree, possibly because the Pd fungus originated in Europe, giving European species a head start in developing efficient defence mechanisms."

Credit: 
Leibniz Institute for Zoo and Wildlife Research (IZW)

From waste heat to electrical power: A new generation of thermomagnetic generators

image: The thermomagnetic generators are based on magnetic thin films with highly temperature-dependent properties.

Image: 
Photo: IMT/KIT

Use of waste heat contributes largely to sustainable energy supply. Scientists of Karlsruhe Institute of Technology (KIT) and T?hoku University in Japan have now come much closer to their goal of converting waste heat into electrical power at small temperature differences. As reported in Joule, electrical power per footprint of thermomagnetic generators based on Heusler alloy films has been increased by a factor of 3.4. (DOI: 10.1016/j.joule.2020.10.019)

Many technical processes only use part of the energy consumed. The remaining fraction leaves the system in the form of waste heat. Frequently, this heat is released into the environment unused. However, it can also be used for heat supply or power generation. The higher the temperature of the waste heat is, the easier and cheaper is its reuse. Thermoelectric generators can use waste heat of low temperature for direct conversion into electrical power. Thermoelectric materials used so far, however, have been expensive and sometimes even toxic. Moreover, thermoelectric generators require large temperature differences for reaching efficiencies of just a few percent.

Thermomagnetic generators represent a promising alternative. They are based on alloys, whose magnetic properties are highly temperature-dependent. Alternating magnetization induces an electrical voltage in a coil applied. Researchers presented first concepts of thermomagnetic generators in the 19th century already. Since then, research has covered a variety of materials. Electrical power, however, has left a lot to be desired.

Scientists of KIT's Institute of Microstructure Technology (IMT) and T?hoku University in Japan have now succeeded in largely increasing the electrical power per footprint of thermomagnetic generators. "Based on the results of our work, thermomagnetic generators are now competitive with established thermoelectric generators for the first time. With this, we have come a lot closer to the goal of converting waste heat into electrical power at small temperature differences," says Professor Manfred Kohl, Head of the Smart Materials and Devices Group of IMT. Work of the team is reported in the cover story of the latest issue of Joule.

Vision: Recovery of Waste Heat Close to Room Temperature

So-called Heusler alloys - magnetic intermetallic compounds - are applied in the form of thin films in thermomagnetic generators and provide for a big temperature-dependent change of magnetization and quick heat transfer. This is the basis of the new concept of resonant self-actuation. Even at small temperature differences, resonant vibrations are induced in devices and can be converted efficiently into electrical power. Still, electrical power of single devices is low and upscaling will depend on material development and engineering. The researchers of KIT and T?hoku University used a nickel-manganese-gallium alloy and found that alloy film thickness and the device footprint influence electrical power in opposite directions. Based on this finding, they succeeded in improving electrical power per footprint by a factor of 3.4 by increasing the thickness of the alloy film from five to 40 micrometers. The thermomagnetic generators reached a maximum electrical power of 50 microwatts per square centimeter at a temperature change of just three degrees Celsius. "These results pave the way to the development of customized thermomagnetic generators connected in parallel for potential use of waste heat close to room temperature," Kohl explains. (or)

Credit: 
Karlsruher Institut für Technologie (KIT)

Two studies shed light on how, where body can add new fat cells

image: An image showing a blood vessel in fat tissue, surrounded by fat progenitor cells (in green).

Image: 
UT Southwestern Medical Center

DALLAS - Feb. 3, 2021 - Gaining more fat cells is probably not what most people want, although that might be exactly what they need to fight off diabetes and other diseases. How and where the body can add fat cells has remained a mystery - but two new studies from UT Southwestern provide answers on the way this process works.

The studies, both published online today in Cell Stem Cell, describe two different processes that affect the generation of new fat cells. One reports how fat cell creation is impacted by the level of activity in tiny organelles inside cells called mitochondria. The other outlines a process that prevents new fat cells from developing in one fat storage area in mice - the area that correlates with the healthy subcutaneous fat just under the skin in humans. (Both studies were done in mice.)

In the second study, a commonly used cancer drug was able to jump-start healthy fat cell creation in mice, a finding that raises the possibility of future drug treatments for humans.

While fat isn't popular, as long as people overeat they will need a place to store the excess calories, explains Philipp Scherer, Ph.D., director of the Touchstone Center for Diabetes Research at UT Southwestern and senior author of the first study focusing on mitochondria. There are two options, he says: squeezing more lipids (fat) into existing fat cells and ballooning their size, leading to problems such as inflammation and, eventually, diabetes; or creating new fat cells to help spread the load. Fat stored properly - in fat cell layers under the skin (subcutaneous fat) that aren't overburdened instead of around organs (visceral fat) or even inside organs - is the healthy alternative, he says.

Problems follow if existing fat cells are left on their own to become engorged, adds Rana Gupta, Ph.D., associate professor of internal medicine and senior author of the second study. "When these cells are so overwhelmed that they can't take it anymore, they eventually die or become dysfunctional, spilling lipids into places not intended to store fat."

Those lipids may move into the liver, leading to fatty liver disease; to the pancreas, resulting in diabetes; or even to the heart, causing cardiovascular disease, Gupta says. Visceral, or belly fat, may surround the organs, creating inflammation.

The healthiest place to store fat is in subcutaneous fat, adds Gupta. Ironically, that is where mice in his study were least able to create new fat cells, despite the fact that stem-cell-like progenitor cells primed to become fat cells were present there as well, he says.

Gupta's study identified a process that prevents progenitor cells from developing into fat cells in mouse subcutaneous inguinal fat.

The protein HIF-1a (short for hypoxia-inducible factor-1 alpha) is central to the process. It kicks off a series of cellular actions that ultimately inactivate a second protein called PPARgamma, the key driver of fat cell formation.

These proteins are found in both humans and mice. In fact, in a culture of human subcutaneous fat cell progenitors, HIF-1a also inhibited new fat cells from being created, according to Gupta.

In Gupta's mouse study, researchers used a genetic approach to inhibit HIF-1a and found that the progenitor cells could then make subcutaneous inguinal fat cells and fewer were inflamed or fibrotic.

Next, they tested the cancer drug imatinib (brand name Gleevec) and found it had the same effect. The cancer drug was tried because it was known to have beneficial effects against diabetes in cancer patients with both diseases, Gupta says.

In Scherer's study, researchers manipulated a protein called MitoNEET in the outer membrane of the precursor cells' mitochondria, organelles known as the cells' power plants. The resulting mitochondrial dysfunction and drop in cell metabolism caused precursor cells to lose the ability to become new fat cells and increased inflammation.

"This study shows we can manipulate the precursor cells' willingness to become fat cells," Scherer says. "The ability to recruit new fat cells by tickling these pre-fat cells to become fat cells is very important and has profound beneficial effects on health, particularly in the obesity-prone environment that we all live in."

He says his goal is now to design a drug that could stimulate mitochondrial activity.

"Understanding the mechanism is an important first step," Scherer says, referring to the findings from the two studies. "We will have to learn in the future how to manipulate these processes pharmacologically."

Credit: 
UT Southwestern Medical Center

CABI study updates safer options for fall armyworm control in Africa

image: Fall armyworm on maize

Image: 
CABI

CABI scientists have updated the first major study of potential biological controls that could be used in the fight against the devastating fall armyworm in Africa. The research offers new insight into evidence of their efficacy in the field and increased availability as commercial products.

Indeed, the review, published in the Journal of Applied Entomology, includes many biocontrol products which are now featured in the CABI BioProtection Portal - a free web-based tool that enables users to discover information about registered biocontrol and biopesticide products around the world.

The fall armyworm (Spodoptera frugiperda) attacks around 100 species of plant but favours maize. It has already caused substantial damage to staple crops grown by smallholder farmers in many parts of Africa.

Lead researcher Dr Melanie Bateman, together with other CABI colleagues and scientists from the International Centre of Insect Physiology and Ecology (ICIPE) in Nairobi, Kenya, and Lancaster University, UK, reveal the revised list of biopesticide active ingredients (AI) - which have been registered in one or more of the 30 study countries for fall armyworm management - now stands at 41.

The current paper builds on the first assessment (Bateman et al, 2018) by profiling four additional AI. These are Aspergillus oryzae, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), Spodoptera littoralis nucleopolyhedrovirus
(SpliNPV) and thyme oil.

Dr Bateman said, "Many smallholder farmers continue to resort to pesticides to tackle the fall armyworm but we believe that safe, sustainable and effective interventions such as biopesticides should be a key element of Integrated Pest Management plans.

"This is particularly important when you consider that many farmers are using highly hazardous pesticides without personal protective equipment and the use of broad-spectrum pesticides can negatively impact natural enemies to help manage fall armyworm."

The scientists add that since the first assessment field trials demonstrating the efficacy have been carried out for eight AIs (A. oryzae, azadirachtin, B. thuringiensis subsp. aizawai, maltodextrin, FAW sex pheromones, spinosad, Spodoptera frugiperda multiple nucleopolyhedrovirus and Spodoptera littoralis nucleopolyhedrovirus) which has led to products being registered across some countries in Africa.

Dr Steve Edgington, co-author of the paper and who is responsible for product data on the CABI BioProtection Portal, said, "The findings of this update are encouraging. In the relatively short time since the last assessment, the number of biopesticide AIs registered per country that could potentially be used to manage FAW has more than doubled, and there have been similar increases in the numbers of products registered. But of course, at the farm gate knowledge is still needed of what products are actually available and how to use them correctly."

"I would recommend farmers and extension workers to keep up to date with the latest biopesticide products available in their region to fight the fall armyworm, and a range of other pests for that matter, by using tools such as the CABI BioProtection Portal."

The researchers added that further studies could include, for many AIs, looking at establishing the most cost-effective method of use to fight the fall armyworm.

Credit: 
CABI

"Ghost particle" ML model permits full quantum description of the solvated electron

image: The dynamics run with the resulting ML PES was not only able to recover the stable cavity, but could also trace the correct localization dynamics

Image: 
@Vladimir Rybkin

The behavior of the solvated electron e-aq has fundamental implications for electrochemistry, photochemistry, high-energy chemistry, as well as for biology--its nonequilibrium precursor is responsible for radiation damage to DNA--and it has understandably been the topic of experimental and theoretical investigation for more than 50 years.

Though the hydrated electron appears to be simple--it is the smallest possible anion as well as the simplest reducing agent in chemistry--capturing its physics is...hard. They are short lived and generated in small quantities and so impossible to concentrate and isolate. Their structure is therefore impossible to capture with direct experimental observation such as diffraction methods or NMR. Theoretical modelling has turned out to be as challenging.

Density functional theory (DFT) is the electronic structure method most often used to study the solvated electron and water. Standard density functionals suffer from delocalization error though, making it impossible to model radicals accurately. Pure water complicates DFT approximations considerably, though choosing the right functionals can lead to acceptable results compared to high-level electronic structure benchmarks and values that can be observed through experiment. An accurate description of liquid water can be also achieved with many-body quantum chemistry methods, but they are extremely expensive.

Though a recent picosecond-scale molecular dynamics-based breakthrough unprecedented in complexity and requiring computational resources at the limits of what's possible provided a crucial argument in favor of a cavity structure for e-aq, it did not result in other new insights or in a complete statistical description. Comprehensive characterization of the system's properties requires far longer timescales, but simulating quantum nuclei at this level of electronic structure theory is currently beyond computational reach.

The modern way of working around this problem involves the use of machine learning. Training an ML force field or potential energy surface (PES) based on ab initio data allows for much longer MD simulations because the cost of evaluating such energies and forces is almost negligible compared to that associated with electronic structure calculations. The problem is that the solvated electron is a non-typical species. It doesn't have an atomistic formula, which poses a problem because machine learning PES work with atomistic representations.

In the paper Simulating the Ghost: Quantum Dynamics of the Solvated Electron, University of Zurich researcher Vladimir Rybkin, doctoral student Jinggang Lan and lecturer Marcella Iannuzzi combined their expertise in electronic structure and solvated electrons with the knowledge of EPFL professor Michele Ceriotti and his former PhD students Venkat Kapil, now a researcher at Cambridge University, and Piero Gasparotto, now a researcher at Empa, in machine learning and quantum dynamics. That, with the contributions of other colleagues, resulted in the application of the ML approach to data acquired from a many-body quantum chemistry method known as second-order Møller-Plesset perturbation theory (MP2), a method that gives an accurate description of water, anyway, without any special treatment of the excess electron.

They were surprised to discover that the model was able to learn the presence of the solvated electron as a factor that distorted the structure of the pure liquid water. The dynamics run with the resulting ML PES was not only able to recover the stable cavity, but could also trace the correct localization dynamics, starting from the delocalized excess electron added to the water. In the end, ML simulated the electron as a sort of "ghost particle" that was not explicitly present in the model.

This allowed the researchers to achieve a time scale of several hundred picoseconds and collect reliable statistics by running a lot of computationally cheap classical trajectories and compute vibrational spectra, structures and diffusion. The ML approach also allowed them to simulate the quantum rather than classical nuclei with path-integral molecular dynamics (PIMD). This technique is at least one order of magnitude computationally more expensive than classical MD and cannot be carried out without ML PES at a high level of electronic structure theory.

Taking the nuclear quantum effects into account delivered accurate vibrational spectra, allowing the researchers to quantify the impact of these effects--already shown to be very important in the relaxation dynamics of the excess electron--on the hydrated electron. It also revealed transient diffusion, an unusual, rare event that is not present in the classical regime. While non-transient diffusion of the solvated electron is achieved by solvent exchange followed by gradual displacement of the "electron cloud" or spin density distribution, transient diffusion is rather a jump of the spin density from the stable cavity to the adjacent one.

While the ghost particle approach was applied here to the solvated electron, it could also be applied to excited states and quasiparticles such as polarons, opening up new opportunities for uniting high-level electronic structure theory with machine learning to achieve highly accurate dynamics simulations at a moderate price.

Credit: 
National Centre of Competence in Research (NCCR) MARVEL

Synthetic biology reinvents development

Richard Feynman, one of the most respected physicists of the twentieth century, said "What I cannot create, I do not understand". Not surprisingly, many physicists and mathematicians have observed fundamental biological processes with the aim of precisely identifying the minimum ingredients that could generate them. One such example are the patterns of nature observed by Alan Turing. The brilliant English mathematician demonstrated in 1952 that it was possible to explain how a completely homogeneous tissue could be used to create a complex embryo, and he did so using one of the simplest, most elegant mathematical models ever written. One of the results of such models is that the symmetry shown by a cell or a tissue can "break" under a set of conditions. However, Turing was not able to test his ideas, and it took over 70 years before a breakthrough in biology technique was able to evaluate them decisively. Can Turing's dream be made a reality through Feynman's proposal? Genetic engineering has proved it can.

Now, a research team from the Institute of Evolutionary Biology (IBE), a joint centre of UPF and the Spanish National Research Council (CSIC), has developed a new type of model and its implementation using synthetic biology can reproduce the symmetry breakage observed in embryos with the minimum amount of ingredients possible.
The research team has managed to implement via synthetic biology (by introducing parts of genes of other species into the E. coli bacteria) a mechanism to generate spatial patterns observed in more complex animals, such as Drosophila melanogaster (fruit fly) or humans. In the study, the team observed that the strains of modified E. coli, which normally grow in (symmetrical) circular patterns, do as in the shape of a flower with petals at regular intervals, just as Turing had predicted.

"We wanted to build symmetry breaking that is never seen in colonies of E. coli, but is seen in patterns of animals, and then to discover which are the essential ingredients needed to generate these patterns", says Salva Duran-Nebreda, who conducted this research for his doctorate in the Complex Systems laboratory and is currently a postdoctoral researcher at the IBE Evolution of Technology laboratory.

Using the new synthetic platform, the research team was able to identify the parameters that modulate the emergence of spatial patterns in E. coli . "We have seen that by modulating three ingredients we can induce symmetry breaking. In essence, we have altered cell division, adhesion between cells and long-distance communication capacity (quorum sensing), that is to say, perceive when there is a collective decision", Duran-Nebreda comments.

The observations made in the E. coli model could be applied to more complex animal models or to insect colony design principles. "In the same way that organoids or miniature organs can help us develop therapies without having to resort to animal models, this synthetic system paves the way to understanding as universal a phenomenon as embryonic development in a far simpler in vitro system", says Ricard Solé, ICREA researcher with the Complex Systems group at the IBE, and head of the research.

The model developed in this study, the first of its kind, could be key to understanding some embryonic development events. "We must think of this synthetic system as a platform for learning to design different fundamental biological mechanisms that generate structures, such as the step from a zygote to the formation of a complete organism. Moreover, such knowledge on the frontier between mechanical and biological processes, could be very useful for understanding developmental disorders", Duran-Nebreda concludes.

Credit: 
Universitat Pompeu Fabra - Barcelona

Quantum tunneling in graphene advances the age of terahertz wireless communications

image: Quantum tunneling

Image: 
Daria Sokol/MIPT Press Office

Scientists from MIPT, Moscow Pedagogical State University and the University of Manchester have created a highly sensitive terahertz detector based on the effect of quantum-mechanical tunneling in graphene. The sensitivity of the device is already superior to commercially available analogs based on semiconductors and superconductors, which opens up prospects for applications of the graphene detector in wireless communications, security systems, radio astronomy, and medical diagnostics. The research results are published in a high-rank journal Nature Communications.

Information transfer in wireless networks is based on transformation of a high-frequency continuous electromagnetic wave into a discrete sequence of bits. This technique is known as signal modulation. To transfer the bits faster, one has to increase the modulation frequency. However, this requires synchronous increase in carrier frequency. A common FM-radio transmits at frequencies of hundred megahertz, a Wi-Fi receiver uses signals of roughly five gigahertz frequency, while the 5G mobile networks can transmit up to 20 gigahertz signals. This is far from the limit, and further increase in carrier frequency admits a proportional increase in data transfer rates. Unfortunately, picking up signals with hundred gigahertz frequencies and higher is an increasingly challenging problem.

A typical receiver used in wireless communications consists of a transistor-based amplifier of weak signals and a demodulator that rectifies the sequence of bits from the modulated signal. This scheme originated in the age of radio and television, and becomes inefficient at frequencies of hundreds of gigahertz desirable for mobile systems. The fact is that most of the existing transistors aren't fast enough to recharge at such a high frequency.

An evolutionary way to solve this problem is just to increase the maximum operation frequency of a transistor. Most specialists in the area of nanoelectronics work hard in this direction. A revolutionary way to solve the problem was theoretically proposed in the beginning of 1990's by physicists Michael Dyakonov and Michael Shur, and realized, among others, by the group of authors in 2018. It implies abandoning active amplification by transistor, and abandoning a separate demodulator. What's left in the circuit is a single transistor, but its role is now different. It transforms a modulated signal into bit sequence or voice signal by itself, due to non-linear relation between its current and voltage drop.

In the present work, the authors have proved that the detection of a terahertz signal is very efficient in the so-called tunneling field-effect transistor. To understand its work, one can just recall the principle of an electromechanical relay, where the passage of current through control contacts leads to a mechanical connection between two conductors and, hence, to the emergence of current. In a tunneling transistor, applying voltage to the control contact (termed as ''gate'') leads to alignment of the energy levels of the source and channel. This also leads to the flow of current. A distinctive feature of a tunneling transistor is its very strong sensitivity to control voltage. Even a small "detuning" of energy levels is enough to interrupt the subtle process of quantum mechanical tunneling. Similarly, a small voltage at the control gate is able to "connect" the levels and initiate the tunneling current.

"The idea of ??a strong reaction of a tunneling transistor to low voltages is known for about fifteen years," says Dr. Dmitry Svintsov, one of the authors of the study, head of the laboratory for optoelectronics of two-dimensional materials at the MIPT center for photonics and 2D materials. "But it's been known only in the community of low-power electronics. No one realized before us that the same property of a tunneling transistor can be applied in the technology of terahertz detectors. Georgy Alymov (co-author of the study) and I were lucky to work in both areas. We realized then: if the transistor is opened and closed at a low power of the control signal, then it should also be good in picking up weak signals from the ambient surrounding. "

The created device is based on bilayer graphene, a unique material in which the position of energy levels (more strictly, the band structure) can be controlled using an electric voltage. This allowed the authors to switch between classical transport and quantum tunneling transport within a single device, with just a change in the polarities of the voltage at the control contacts. This possibility is of extreme importance for an accurate comparison of the detecting ability of a classical and quantum tunneling transistor.

The experiment showed that the sensitivity of the device in the tunnelling mode is few orders of magnitude higher than that in the classical transport mode. The minimum signal distinguishable by the detector against the noisy background already competes with that of commercially available superconducting and semiconductor bolometers. However, this is not the limit - the sensitivity of the detector can be further increased in "cleaner" devices with a low concentration of residual impurities. The developed detection theory, tested by the experiment, shows that the sensitivity of the "optimal" detector can be a hundred times higher.

"The current characteristics give rise to great hopes for the creation of fast and sensitive detectors for wireless communications," says the author of the work, Dr. Denis Bandurin. And this area is not limited to graphene and is not limited to tunnel transistors. We expect that, with the same success, a remarkable detector can be created, for example, based on an electrically controlled phase transition. Graphene turned out to be just a good launching pad here, just a door, behind which is a whole world of exciting new research."

The results presented in this paper are an example of a successful collaboration between several research groups. The authors note that it is this format of work that allows them to obtain world-class scientific results. For example, earlier, the same team of scientists demonstrated how waves in the electron sea of ??graphene can contribute to the development of terahertz technology. "In an era of rapidly evolving technology, it is becoming increasingly difficult to achieve competitive results." - comments Dr. Georgy Fedorov, deputy head of the nanocarbon materials laboratory, MIPT, - "Only by combining the efforts and expertise of several groups can we successfully realize the most difficult tasks and achieve the most ambitious goals, which we will continue to do."

Credit: 
Moscow Institute of Physics and Technology

Pioneering technique paves way for fast and cheap fabrication of rapid medical diagnostic tools

image: Example 100-micron wide 3D-printed microchannel scaffolds, shown next to a 20p coin - the cost to print 1000 of these channels.

Image: 
University of Bristol

New technology developed by the University of Bristol has the potential to accelerate uptake and development of on-chip diagnostic techniques in parts of the world where rapid diagnoses are desperately needed to improve public health, mortality and morbidity.

Microfluidic devices underpin lab-on-a-chip (LOC) technologies which are developed to provide the rapid diagnoses at that are needed at point of care (POC) for the swift and effective treatment of many diseases.

Researchers at Bristol have developed a fast, reliable and cost-effective alternative for producing the soft-lithographic moulds used for fabricating microfluidic devices, published in the journal PLOS ONE. This discovery means fabrication of microfluidic devices (with channel dimensions ~width of a human hair) is now both accessible and affordable using simple, low-cost 3D-printing techniques and the open-source resources developed by the team.

"Previously, techniques for producing the soft-lithographic scaffolds/moulds (microfluidic channel patterns) were time-consuming and extremely expensive, while other low-cost alternatives were prone to unfavourable properties. This development could put LOC prototyping into the hands of researchers and clinicians who know the challenges best, in particular those in resource-limited settings, where rapid diagnostics may often have the greatest impact," said lead author of the study, Dr Robert Hughes.

"This technique is so simple, quick & cheap that devices can be fabricated using only everyday domestic or educational appliances and at a negligible cost (~0.05% of cost of materials for a single microfluidic device). This means researchers and clinicians could use our technique and resources to help fabricate rapid medical diagnostic tools, quickly and cheaply, with minimal additional expertise or resources required," said co-author, Mr Harry Felton.

"The simplicity and minimal cost of this technique, as well as the playful click-and-connect approach developed, also makes it suitable for hobbyists and educational use, to teach about microfluidics and the applications of lab-on-a-chip technology," said co-author Ms Andrea Diaz Gaxiola.

"It is our hope that this will democratise microfluidics and lab-on-a-chip technology, help to advance the development of point-of-care diagnostics, and inspire the next generation of researchers and clinicians in the field," said Dr Hughes.

The next step for the team is to identify potential collaborators in both research and education to help demonstrate the impact this technology could have in both settings by developing and supporting outreach activities and applications for on-chip diagnostic testing.

Credit: 
University of Bristol

Scientists believe studies by colleagues are more prone to biases than their own studies

The properties of human mind affect the quality of scientific knowledge through the insertion of unconscious cognitive biases. Scientists from the University of Turku, Finland, have found that the current level of awareness about research biases is generally low among ecology scientists. Underestimation of the risks associated with unconscious cognitive biases prevents avoiding these risks in a scientist's own research. Due to unconscious origin of biases, it is impossible to combat them without external intervention.

When scientists use some device in their research, they always account for characteristics of this device, such as accuracy and precision. The human mind is the most important tool in the scientific research. Nevertheless, its properties are rarely taken into account by the ecologists while conducting their research.

The cognitive biases emerge most frequently due to tendency of humans to search for and interpret information in a way that confirms one's pre-existing beliefs or hypotheses.

- For example, an influential theory predicts that pollution increases asymmetry of plant leaves. When two groups of scientists were asked to measure the same set of leaves, the group which was told that leaves originate from a polluted site reported significantly higher asymmetry than the group which was told that leaves originate from a clean site. Thus, the first group of scientists found non-existing effect only because they believed that it should exist, says Adjunct Professor Elena Zvereva from the Department of Biology of the University of Turku.

- This kind of biases may considerably influence the output of the research, generally leading to overestimation of the effects under study. Development of measures for combating cognitive biases in research requires information on the current level of awareness about biases among scientists, Zvereva adds.

Responses of 308 ecology scientists from 40 countries to a web-based questionnaire revealed that knowledge about biases and attitude towards biases depend on the scientist's career stage, gender and affiliation country. Respondents from high GDP countries have better knowledge about biases than respondents from low GDP countries. Early career scientists were more concerned about biases, know more about measures to avoid biases, and twice more often have learned about biases from their university courses when compared with their senior colleagues. This difference indicates current improvement of education about biases and gives hope that their impact on scientific research will decrease in the future.

Ecological scientists estimate that the risk of biases in their own studies is much lower than in science in general and in studies by other scientists working in the same research field. In other words, they "see the speck that is in their brother's eye, but do not notice the log that is in their own eye". The strength of this "bias blind spot" is two times larger in men than in women and two times larger in senior scientists than in early career scientists. These differences suggest that this bias is more typical for persons with high self-confidence and self-esteem.

- Education about biases is necessary, but not yet sufficient, to avoid biases because the unconscious origin of biases necessitates external intervention to combat them. Obligatory reporting of measures taken against biases in all relevant manuscripts will likely increase the quality of scientific publications and enhance the reproducibility of scientific results, concludes Adjunct Professor Mikhail Kozlov from the University of Turku.

Credit: 
University of Turku