Culture

More than a decade before people with Huntington's disease show symptoms, they can exhibit abnormally high levels of an immune-system molecule called interleukin-6 (IL-6), which has led many researchers to suspect IL-6 of promoting the eventual neurological devastation associated with the genetic condition. A new investigation by MIT neuroscientists shows that the story likely isn't so simple. In a new study they found that Huntington's model mice bred to lack IL-6 showed exacerbated symptoms compared to HD mice that still had it.

"If one looks back in the literature of the Huntington's disease field many people have postulated that reductions to IL-6 would be therapeutic in HD," said Myriam Heiman, associate professor in MIT's Department of Brain and Cognitive Sciences and a member of The Picower Institute for Learning and Memory and the Broad Institute of MIT and Harvard. She is senior author of the paper in Molecular Neurodegeneration. Former postdoc Mary Wertz is the lead author.

To test the hypothesis that knocking out IL-6 would help HD mice, the researchers crossbred mice engineered to model HD with mice engineered to lack IL-6. They then compared the performance of offspring on a variety of standard movement tasks to that of healthy mice, mice just lacking IL-6, and mice just modeling HD but still having IL-6. The HD mice lacking IL-6 performed significantly worse than the other mouse lines, including the HD mice that still had IL-6.

The result was as surprise not only because of the record in prior studies, but also because in a paper published earlier this year, Wertz and Heiman conducted a sweeping analysis of genes that promoted neuron survival in Huntington's disease and some of the hits they turned up were ones that are associated with interleukin signaling.

Gene expression differences

Struck by the findings in the new study, the team sought to understand why they occurred. To do that, they measured gene expression in all the major cell types in the striatum, the brain region most affected in HD, by sequencing RNA in thousands of individual cells in each mouse line. When they looked at the differences in gene expression in neurons between the two HD mouse lines - the ones that had IL-6 and the ones that didn't - they saw that many genes important for synapses, the connections that link neurons into circuits, were significantly less expressed in the HD mice without IL-6.

"Perhaps this worsening of the phenotype is due to perturbation of those synaptic signaling pathways," Heiman said.

While the study shows there is definitely not a therapeutic benefit to completely knocking out IL-6, it may still be possible to find a level between overexpression and complete knockout that is therapeutic, Heiman said. It may also be possible that timing is crucial. For instance, in this study mice lacked IL-6 right from birth, but potentially intervening to modulate IL-6 levels is more beneficial at some stage of adulthood, she said. The lab plans to continue to pursue that investigation.

"What these results show us is that we really have to understand which parts of innate immune signaling are activated when and what the order of events is," she said.

Researchers at the National Institute of Standards and Technology (NIST) have developed a mathematical formula that, computer simulations suggest, could help 5G and other wireless networks select and share communications frequencies about 5,000 times more efficiently than trial-and-error methods.

The novel formula is a form of machine learning that selects a wireless frequency range, known as a channel, based on prior experience in a specific network environment. Described at a conference this week, the formula could be programmed into software on transmitters in many types of real-world networks.

The NIST formula is a way to help meet growing demand for wireless systems, including 5G, through the sharing of frequency ranges, also known as bands, that are unlicensed. Wi-Fi, for example, uses unlicensed bands -- those not assigned by the Federal Communications Commission to specific users. The NIST study focuses on a scenario in which Wi-Fi competes with cellular systems for specific frequencies, or subchannels. What makes this scenario challenging is that these cellular systems are raising their data-transmission rates by using a method called License Assisted Access (LAA), which combines both unlicensed and licensed bands.

"This work explores the use of machine learning in making decisions about which frequency channel to transmit on," NIST engineer Jason Coder said. "This could potentially make communications in the unlicensed bands much more efficient."

The NIST formula enables transmitters to rapidly select the best subchannels for successful and simultaneous operation of Wi-Fi and LAA networks in unlicensed bands. The transmitters each learn to maximize the total network data rate without communicating with each other. The scheme rapidly achieves overall performance that is close to the result based on exhaustive trial-and-error channel searches.

The NIST research differs from previous studies of machine learning in communications by taking into account multiple network "layers," the physical equipment and the channel access rules between base stations and receivers.

The formula is a "Q-learning" technique, meaning it maps environmental conditions -- such as the types of networks and numbers of transmitters and channels present -- onto actions that maximize a value, known as Q, that returns the best reward. By interacting with the environment and trying different actions, the algorithm learns which channel provides the best outcome. Each transmitter learns to select the channel that yields the best data rate under specific environmental conditions.

If both networks select channels appropriately, the ef?ciency of the combined overall network environment improves. The method boosts data rates in two ways. Speci?cally, if a transmitter selects a channel that is not occupied, then the probability of a successful transmission rises, leading to a higher data rate. And if a transmitter selects a channel such that interference is minimized, then the signal is stronger, leading to a higher received data rate.

In the computer simulations, the optimum allocation method assigns channels to transmitters by searching all possible combinations to find a way to maximize the total network data rate. The NIST formula produces results that are close to the optimum one but in a much simpler process. The study found that an exhaustive effort to identify the best solution would require about 45,600 trials, whereas the formula could select a similar solution by trying only 10 channels, just 0.02 percent of the effort.

The study addressed indoor scenarios, such as a building with multiple Wi-Fi access points and cellphone operations in unlicensed bands. Researchers now plan to model the method in larger-scale outdoor scenarios and conduct physical experiments to demonstrate the effect.

RESEARCH TRIANGLE PARK, N.C. -- As 5G hits the market, new U.S. Army-funded research has developed a radio-frequency switch that is more than 50 times more energy efficient than what is used today.

With funding from the Army Research Office, an element of the U.S. Army Combat Capabilities Development Command's Army Research Laboratory, researchers at The University of Texas at Austin and the University of Lille in France, have built a new component that will more efficiently allow access to the highest 5G frequencies, in a way that increases devices' battery life and speeds up how quickly users can do things like stream HD media.

Smartphones are loaded with switches that perform a number of duties. One major task is jumping back and forth between different networks and spectrum frequencies: 4G, WiFi, LTE, Bluetooth, etc. The current radio-frequency switches that perform this task are always running, consuming precious processing power and battery life.

"Radio-frequency switches are pervasive in military communication, connectivity and radar systems," said Dr. Pani Varanasi, division chief, materials science program at ARO. "These new switches could provide large performance advantage compared to existing components and can enable longer battery life for mobile communication, and advanced reconfigurable systems."

The journal Nature Electronics published the research team's findings.

"It has become clear that the existing switches consume significant amounts of power, and that power consumed is useless power," said Dr. Deji Akinwande, a professor in the Cockrell School of Engineering's Department of Electrical and Computer Engineering who led the research. "The switch we have developed can transmit an HDTV stream at a 100GHz frequency, and that is an achievement in broadband switch technology."

The new switches stay off, saving battery life for other processes, unless they are actively helping a device jump between networks. They have also shown the ability to transmit data well above the baseline for 5G-level speeds.

Prior researchers have found success on the low end of the 5G spectrum - where speeds are slower but data can travel longer distances. This is the first switch that can function across the spectrum from the low-end gigahertz frequencies to high-end terahertz frequencies that could someday be key to the development of 6G.

The team's switches use the nanomaterial hexagonal boron nitride, a rapidly emerging nanomaterial from the same family as graphene. The structure of the switch involves a single layer of boron and nitrogen atoms in a honeycomb pattern sandwiched between a pair of gold electrodes. Hexagonal boron nitride is the thinnest known insulator with a thickness of 0.33 nanometers.

The impact of these switches extends beyond smartphones. Satellite systems, smart radios, reconfigurable communications, and Internet of Things, are all examples of potential uses for the switches. In addition, these switches can be realized on flexible substrates making them suitable for Soldier wearable radios and communication systems that can benefit from the improved energy efficiency for longer battery life with faster data speeds as well as other defense technologies.

"This will be very useful for radio and radar technology," Akinwande said.

This research spun out of a previous project that created the thinnest memory device, also using hBN. Akinwande said sponsors encouraged the researchers to find other uses for the material, and that led them to pivot to RF switches.

PHILADELPHIA - The lens of the eye is an unusual organ. Unlike most of the body's organs, blood vessels don't reach the lens. If they did, they'd obscure our vision and we wouldn't be able to see. The lack of vasculature led scientists to believe immune cells, which travel via the bloodstream, couldn't get to this part of the body either. But a few years ago, Jefferson researchers challenged this long held assumption by demonstrating that immune cells populate the lens in response to degeneration. Now the Jefferson team finds the eye also launches an immune response in the lens after injury. The discovery adds to a growing body of evidence that is working to overturn the accepted dogma of the field.

"Why would we evolve a tissue that is so central to our being able to see without ways to ensure its protection, its ability to repair itself?" says, Sue Menko, PhD, Professor in the Department of Pathology, Anatomy and Cell Biology at Thomas Jefferson University, who led the research. "Immune cells are central to that protection and repair."

The lens of the eye works like a camera lens. Its main purpose is to focus images coming in through the cornea - the transparent front layer of the eye - onto the retina at the back of the eye. The images are detected by the retina and then translated in the brain as what we see. That lens must be crystal clear. As a result, scientists have always described the lens as a tissue without vasculature and therefore no source of immune cells either.

"At some point, you think about it and you wonder how that's possible," Dr. Menko says. "It doesn't really make a lot of sense."

The puzzle led Dr. Menko and her team to investigate whether immune cells are present in the eye. In a previous study, they discovered that when the lens is in a diseased state, immune cells are not only recruited there, but they also show up in the cornea, retina, and vitreous body - all parts of the eye that don't normally have immune cells. Dr. Menko's work suggested that the immune cells come from the ciliary body, a sort of muscle that helps squeeze and pull the lens, changing its shape, and helping it focus.

"The ciliary body is also a place that is vascular rich so it seemed like the most obvious place to look," Dr. Menko says.

Now, in the latest work, Dr. Menko and colleagues show that after injury to the cornea, immune cells travel from the ciliary body to the lens along fibers known as ciliary zonules. The researchers used fluorescent markers and high-powered microscopes to observe structures of mouse eyes one day after receiving a scratch on the cornea. The high-tech imaging analysis Dr. Menko's team used revealed that following injury to the cornea, the immune system launches a response to protect the lens. Immune cells are recruited to the lens via the ciliary zonules, and crawl along the surface of the lens to surveille and protect from adverse impacts of the corneal wound.

"This is really the first demonstration that surveillance by immune cells of the lens in response to injury somewhere else in the eye," Dr. Menko says.

The researchers also found that some immune cells were able to cross the lens capsule, a membranous structure that helps to keep the lens under tension. The results could point to a role for immune cells in cataract formation.

Together, the findings indicate that in response to damage or disease, the eye utilizes alternative mechanisms - rather than direct contact with the bloodstream like non-transparent tissues do - to ensure that immune cells get to sites to provide healing and protection.

"We're excited to go from thinking this doesn't make sense to proving that the body is amazing and can adapt to anything. You just have to go in and look for it," Dr. Menko says.

"We should be willing to challenge dogma because that's where discovery is," she adds. "It can enlighten what we know if we always keep our mind open to what doesn't make sense and what maybe should be challenged to understand things better."

Five years after NASA's MAVEN spacecraft entered into orbit around Mars, data from the mission has led to the creation of a map of electric current systems in the Martian atmosphere.

"These currents play a fundamental role in the atmospheric loss that transformed Mars from a world that could have supported life into an inhospitable desert," said experimental physicist Robin Ramstad of the University of Colorado, Boulder. "We are now currently working on using the currents to determine the precise amount of energy that is drawn from the solar wind and powers atmospheric escape." Ramstad is lead author of a paper on this research published May 25 in Nature Astronomy.

Earth has such current systems, too: we can even see them in the form of colorful displays of light in the night sky near the polar regions known as the aurora, or northern and southern lights. Earth's aurora are strongly linked to currents, generated by the interaction of the Earth's magnetic field with the solar wind, that flow along vertical magnetic field lines into the atmosphere, concentrating in the polar regions. Studying the flow of electricity thousands of miles above our heads, though, only tells part of the story about the situation on Mars. The difference lies in the planets' respective magnetic fields, because while Earth's magnetism comes from within, Mars' does not.

Planetary magnetic fields

Earth's magnetism comes from its core, where molten, electrically conducting iron flows beneath the crust. Its magnetic field is global, meaning it surrounds the entire planet. Since Mars is a rocky, terrestrial planet like Earth, one might assume that the same kind of magnetic paradigm functions there, too. However, Mars does not generate a magnetic field on its own, outside of relatively small patches of magnetized crust. Something different from what we observe on Earth must be happening on the Red Planet.

What's going on above Mars?

The solar wind, made up largely of electrically charged electrons and protons, blows constantly from the Sun at around a million miles per hour. It flows around and interacts with the objects in our solar system. The solar wind is also magnetized and this magnetic field cannot easily penetrate the upper atmosphere of non-magnetized planets like Mars. Instead, currents that it induces in the planet's ionosphere cause a pile-up and strengthening of the magnetic field, creating a so-called induced magnetosphere. How the solar wind powers this induced magnetosphere at Mars has not been well understood until now.

As solar wind ions and electrons smash into this stronger induced magnetic field near Mars, they are forced to flow apart due to their opposite electric charge. Some ions flow in one direction, some electrons in the other direction, forming electric currents that drape around from the dayside to the nightside of the planet. At the same time, solar x-rays and ultraviolet radiation constantly ionize some of the upper atmosphere on Mars, turning it into a combination of electrons and electrically charged ions that can conduct electricity.

"Mars' atmosphere behaves a bit like a metal sphere closing an electric circuit," Ramstad said. "The currents flow in the upper atmosphere, with the strongest current layers persisting at 120-200 kilometers (about 75-125 miles) above the planet's surface." Both MAVEN and previous missions have seen localized hints of these current layers before, but they have never before been able to map the complete circuit, from its generation in the solar wind, to where the electrical energy is deposited in the upper atmosphere.

Directly detecting these currents in space is infamously difficult. Fortunately, the currents distort the magnetic fields in the solar wind, detectable by MAVEN's sensitive magnetometer. The team used MAVEN to map out the average magnetic field structure around Mars in three dimensions and calculated the currents directly from their distortions of the magnetic field structure.

"With a single elegant operation, the strength and paths of the currents pop out of this map of the magnetic field," Ramstad said.

The Red Planet's destiny

Without a global magnetic field surrounding Mars, the currents induced in the solar wind can form a direct electrical connection to the Martian upper atmosphere. The currents transform the energy of the solar wind into magnetic and electric fields that accelerate charged atmospheric particles into space, driving atmospheric escape to space. The new results reveal several unexpected features particular to MAVEN's goal to understand atmospheric escape: the energy that drives escape appears to be drawn from a much larger volume than was often assumed.

Solar-wind-driven atmospheric loss has been active for billions of years and contributed to the transformation of Mars from a warm and wet planet that could have harbored life into a global cold desert. MAVEN is continuing to explore how this process works and how much of the planet's atmosphere has been lost.

This research was funded by the MAVEN mission. MAVEN's principal investigator is based at the University of Colorado's Laboratory for Atmospheric and Space Physics, Boulder, and NASA Goddard manages the MAVEN project. NASA is exploring our Solar System and beyond, uncovering worlds, stars, and cosmic mysteries near and far with our powerful fleet of space and ground-based missions.

Enzymes: they are the central drivers for biochemical metabolic processes in every living cell, enabling reactions to take place efficiently. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics. A topic that is currently being widely discussed is photoinduced catalysis, in which researchers harness the ability of nature to start biochemical reactions with the aid of light. What they need for this purpose is enzymes which can be activated by means of light. It is not, however, a simple matter to incorporate the few naturally occurring light-activatable enzymes into biotechnological processes, as they are highly specialised and difficult to manipulate.

Researchers at the Universities of Münster (Germany) and Pavia (Italy) have now identified an enzyme which becomes catalytically active when exposed to blue light and which immediately triggers a reaction hitherto unknown in enzymology. The reaction in question is a special monooxygenase reaction, in which an oxygen atom is transferred to the substrate. The reaction is supported by a "helper molecule" which stepwise delivers two electrons. Up to now, it had been assumed that such a light-dependent reaction cannot occur in enzymes.

"The enzyme we have identified belongs to a very large family of enzymes, and it is realistic to assume that other enzymes can be produced, by means of genetic manipulations, which can be activated by light too and which can be used in a very wide range of applications," says Dr. Steffen L. Drees, who headed the study and works at the Institute of Molecular Microbiology and Biotechnology at Münster University. One possible application, for example, is in the field of medicine, where pharmaceuticals could be activated by means of light. The study has been published in the journal "Nature Communications".

Background and method:

In their study, the researchers investigated the enzyme PqsL, which is found in the opportunistic pathogen Pseudomonas aeruginosa and, originally, is not light-dependent. The researchers stimulated the enzyme with blue light and analysed the reaction using, for example, a combination of time-resolved spectroscopic and crystallographic techniques.

The enzyme examined belongs to the family of flavoproteins and - typically for this family of proteins - uses a derivative of vitamin B2 as a so-called cofactor for catalysing the incorporation of oxygen into organic molecules. The cosubstrate NADH (reduced nicotinamide adenine dinucleotide) is needed as a "helper molecule" for the enzymatic reaction, providing the necessary electrons. The reaction mechanism the researchers observed in their study is new, however, and so far, unique. Activated by the exposure to light in the flavin-NADH complex, NADH transfers a single electron to the protein-bound flavin. In this way, a flavin radical is created - a highly reactive molecule which is characterised by an unpaired electron. Using time-resolved spectroscopy, the researchers were able to observe how the molecule formed and changed its state.

The flavin radical has a very negative redox potential, which means that it has a large capacity for transferring electrons to reaction partners. "Because of this property, we assume that the flavin radical can also enable additional reactions to take place which would expand the catalytic potential of this enzyme - as well as of other enzymes too, perhaps," says group leader Prof. Susanne Fetzner.

The enzyme identified is the only one so far which is not naturally photoactive, and carries out a light-independent reaction in the bacterial cell. "The three-dimensional structure of the enzyme shows that the outward-facing flavin co-factor might be the key to photoactivation," says Simon Ernst, first author of the study.

Photoactive enzymes enable a large number of applications - for example, multi-step catalysis in a one-vessel reaction or spatially resolved catalysis, for example to functionalise surfaces in certain patterns. They can also be useful for so-called prodrug activation in the body or on the skin - a process in which a pharmacological substance becomes active only after metabolization in the organism.

Traffic congestion is a serious problem in the United States, but a new analysis shows that interactive technology - ranging from 511 traffic information systems and roadside cameras to traffic apps like Waze and Google Maps - is helping in cities that use it.

Potentially, the researchers said, technology could limit the need to widen and expand roadways while saving commuters time and money and lessening environmental damage.

"Technology has the potential to help society, and one way is to help us make better infrastructure decisions and put less pressure on roads," said Paul A. Pavlou, dean of the C.T. Bauer College of Business at the University of Houston and corresponding author for the report, published by the journal Information Systems Research.

Pavlou and colleagues Aaron Cheng of the London School of Economics and Min-Seok Pang of Temple University found that U.S. cities using Intelligent Transportation Systems (ITS) saved money, time and other resources, including:

More than $4.7 billion a year in lost work or productivity

175 million hours a year in travel time

53 million gallons a year in fossil fuel consumption and

10 billion pounds less CO2 emitted each year.

The researchers analyzed longitudinal data from ITS technologies deployed in 99 urban areas in the United States from 1994 to 2014. That included the metropolitan areas of Chicago, Los Angeles, Atlanta, New York-Newark, Houston, Dallas-Fort Worth and Washington D.C., among others.

Pavlou noted that technology has advanced - and traffic has continued to grow - since 2014, the latest year in the dataset used for the research, making it likely that today's savings would be greater.

The U.S. Department of Transportation describes ITS as "an integrated system of advanced communications technologies embedded in the transportation infrastructure and in vehicles to improve transportation safety and mobility," and has awarded grants to cities to invest in the technologies. Technologies included in the research include both those developed by DOT and commercial technologies designed to improve traffic safety and mobility.

The researchers found that the technology is most effective at reducing traffic congestion when two things happen: commuters use more online services for traffic information, including such apps as Waze, and when state governments incorporate more advanced functions into their 511 traveler information systems.

But each city is different. Pavlou noted that while Houston has not adopted the 511 system, it does collaborate with private companies to design and build intelligent transportation systems, including messaging signs, roadside cameras and solar-powered radar detection sites.

Pavlou said the study suggests alternatives to simply building more and bigger roads to keep up with population and traffic growth. Using large-scale technology systems in conjunction with real-time traffic apps at the individual level is less expensive and more effective than only spending funds to expand and maintain roadways, he said
.
Houston traffic and its freeway system, for example, have grown significantly since he was a student here in the 1990s, he said. "Traffic is even worse than before since people move where the roads are built and drive more. The city is growing, but there are alternative ways that do not impose some much demand on roads with the intelligent use of technology in parallel."

May 26, 2020 - (BRONX, NY) Montefiore Health System Albert Einstein College of Medicine have begun the next stage of the Adaptive COVID-19 Treatment Trial (ACTT), to evaluate treatment options for people hospitalized with severe COVID-19 infection. The new iteration of the trial, known as ACTT 2, is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

In March, Montefiore was the first New York location to join the multicenter trial, which evaluated remdesivir, a broad-spectrum antiviral drug given intravenously. Preliminary results from the trial, announced last month and published on Friday in the New England Journal of Medicine, show that patients with COVID-19 who received remdesivir recovered in 11 days on average compared to 15 days for patients in the placebo group--a statistically significant improvement. Of the 1,063 clinical trial participants, 91 of them, nearly 10%, were from Montefiore and Einstein.

Following up on remdesivir's promising results, the trial is now studying remdesivir in combination with baricitinib or placebo in a double-blind, randomized trial. Baricitinib is marketed for reducing inflammation associated with rheumatoid arthritis. Researchers want to know if baricitinib combined with remdesivir can prevent or reduce the hyper-inflammatory "cytokine storm" that can fatally overwhelm the lungs and other parts of the body in people with COVID-19 when their immune system reacts to coronavirus infection.

"What concerns us is that in some people the immune response to coronavirus can be more deadly than the infection itself, and there is no known treatment for this yet," said Barry Zingman, M.D., professor of medicine at Einstein and clinical director, infectious diseases, at the Moses division of Montefiore Health System. "Including baricitinib in our trial may reduce COVID-19-related inflammation and combining baricitinib with remdesivir may yield an even more effective treatment option for people most severely affected by this illness." Dr. Zingman oversaw the original remdesivir study at Montefiore and is directing ACTT 2.

Patients enrolled in ACTT 2 are hospitalized with a laboratory-confirmed coronavirus infection and lung complications, including rattling sounds when breathing, a need for supplemental oxygen, abnormal chest X-rays showing pneumonia, or the need for a mechanical ventilator. All patients will receive remdesivir intravenously for up to 10 days. Half of the patients will also be given baricitinib by mouth, with the remaining half receiving an identical placebo, both for up to 14 days.

Remdesivir was developed by Gilead Sciences, Inc. Baricitinib was developed by Eli Lilly and Company.

In cells, protein is synthesized based on the genetic code. Each protein is coded by the triplet combination of chemicals called "nucleotides," and a continuous "reading" of any set of triplet codes will, after a multi-step process, result in the creation of a chain of amino acids, a protein. The genetic code is matched with the correct amino acid by a special functional RNA aptly named transfer RNA or tRNA (which, incidentally, is itself composed of its own type of "codes"). An enzyme called "aminoacyl-tRNA synthetase" or aaRS accurately assigns a specific amino acid to the correct "code" through a tRNA by recognizing unique structural components called 'identity elements' on the tRNA. In the case of the amino acid alanine, the identity element for recognition by the enzyme alanyl-tRNA synthetase (AlaRS) is an unlikely base pair "G3:U70," present in the minihelix structure (amino acid-accepting upper half region) of tRNA. Considering its importance in the recognition of the code, the base pair is popularly known as the "operational RNA code."

The evolution of this complex tRNA-aaRS system is a fascinating enigma, as the existing evolutionary evidence suggests that the upper half of the tRNA containing this operational code appeared earlier in evolutionary history than the lower half part that binds to the triplet code of mRNA. Interestingly, in a primitive microorganism, Nanoarchaeum equitans, the genes coding for each AlaRS subunit α and β are split, with the two genes being separated by half the length of the chromosome.

This interesting fact inspired a team of scientists at Tokyo University of Science, led by Prof. Koji Tamura, to hypothesize that these split forms of AlaRS in N. equitans might be connected with the evolutionary history of aaRS enzyme activity.

Prof. Tamura emphasizes the significance of their study, published in Journal of Molecular Evolution, in the evolutionary context, "AlaRS-α shows the G3:U70-independent addition of alanine to RNA minihelix regions. Our data indicate the existence of a simplified process of alanine addition to tRNA by AlaRS early in the evolutionary process, before the appearance of the G3:U70 base pair."

The aforementioned minihelix parts of tRNAs were previously known to function as the region of occurrence of addition of amino acids by many aaRSs. To understand the interaction process of the minihelix (minihelixAla) of alanine-specific tRNA (tRNAAla) and AlaRS subunits, the researchers cloned the coding sequences of α and β subunits of N. equitans and then purified the synthesized proteins.

The researchers noticed that, at a relatively high concentration, AlaRS-α alone was capable of adding alanine to both tRNAAla and minihelixAla. Then also observed that AlaRS-α alone interacts with the end of the alanine-accepting region of tRNAAla, but not with the G3:U70 base pair. This was in stark contrast to prior knowledge regarding tRNAAla and AlaRS system. In brief, when both AlaRS-α and AlaRS-β were present, AlaRS behaved in a G3:U70-dependent manner, but working alone, AlaRS-α could add alanine to tRNAAla and minihelixAla in a G3:U70-independent manner. The researchers deduced that "the G3:U70 may be a late-arriving 'operational RNA code,' relevant to later alanylation systems incorporating further specificity through the evolution of the AlaRS-β subunit."

So, what makes the findings of this study so important? Prof. Tamura explains the significance of the striking results of their research, "our findings reveal for the first time that a G3:U70-independent mechanism of alanine addition exists. Furthermore, using 'RNA minihelix' molecules, which are considered to be the primitive form of tRNA, we could also illuminate the 'morphology' of tRNA before the evolutionary appearance of the G3:U70 base pair.''

While discussing the broader implication of their study, Prof. Tamura comments thoughtfully "The breakthroughs in science almost always came from the curiosity-driven research, and the results of our study approach the mystery of the origin of life. It has the potential to transform many areas". His team is now focusing on an extensive structural analysis using the mutants of N. equitans AlaRS-α, but their current findings, published in August issue in printing and selected as the cover of the August issue, are enough to give cause to rethink chapters scientists that have believed to be fundamental in evolutionary history!

The evolutionary processes underlying metastasis-the development of secondary malignant growths away from the primary tumor site-in human patients are still incompletely understood.

Metastases can form in locoregional lymph nodes draining the primary tumor-a form of progression that portends a worse prognosis but can still be curable-or they can develop in distant organs. The latter case defines stage IV disease and treatments for it are typically considered palliative.

It is unknown whether lymph node and distant metastases are only distinguished by their different prognostic implications, or whether the biology underlying their formation is also distinct.

In a new study, published in Nature Genetics, Kamila Naxerova, PhD, of the Center for Systems Biology at Massachusetts General Hospital, Johannes Reiter, PhD, of the Canary Center for Cancer Early Detection at Stanford and colleagues now show that lymph node and distant metastases develop through different evolutionary mechanisms.

Reconstructing the evolutionary histories of dozens of primary colorectal cancers and their metastases, the team showed that lymph node metastases are a genetically highly diverse group. Their pronounced heterogeneity indicates that they can be seeded by many different primary tumor sub-lineages.

In contrast, distant metastases are homogeneous. They typically resemble each other and have a recent common ancestor, suggesting that fewer primary tumor cells possess the ability to form lesions in distant organs. Moreover, the genetic diversity within individual lymph node metastases is also higher than the genetic diversity within individual distant lesions.

These results show that the selective pressures shaping metastasis development in different anatomical sites differ substantially. Lymph node metastasis formation is comparatively "easy" and can be achieved by many cells. Dissemination to and outgrowth in distant organs, on the other hand, appears to be much more challenging and represents a major bottleneck in tumor progression. A significantly smaller fraction of genetic lineages within a primary tumor appears to be capable of this feat. Perhaps these differences can explain why diagnosis of lymph node metastases generally is a less ominous sign than the presence of distant metastases.

In future studies, it will be important to study the molecular and cell biological mechanisms underlying differential selection in lymph nodes and distant sites.

For example, it is possible that distant metastasis is more difficult to achieve because target organs like the liver are located further away from the primary tumor than locoregional lymph nodes, requiring cells to travel farther distances.

Or perhaps, the microenvironment of the lymph node is for some reason a more hospitable milieu for disseminating tumor cells than the parenchyma of distant organs. Understanding the molecular factors that are rate-limiting for metastasis formation in different sites could lead to novel preventative treatments.

COVID-19 pandemic is proving to be havoc for the whole world and an unending challenge for the healthcare systems, hospitals, medics and paramedics. The most vivid example is the shortage of equipment and preventive kits, including the n95 masks. Indeed, there has been high demand of the n95 masks in the hospitals but the shortage of it has forced many local hospitals to use the ordinary masks also. The bigger problem for the healthcare professionals and others in the hospitals is, how best to sterilize (clean) the masks for use and, if need arises, reuse.

Dr. Craig G Burkhart, from the Department of Medicine, University of Toledo College of Medicine, Toledo, Ohio, USA, in his Editorial published in the journal, The Open Dermatology Journal, defines a suitable way for sterilizing the protective masks. According to him, the best cleansing solution for protective masks is treating them with chemical sterilizing agents. The sterilizing agents following the chemistry that the oxidative processes with low molecular weight molecules, used with tested methodologies, can kill all bacteria, mold, and viruses. Ozone sterilization is one very effective method.

Ozone or activated oxygen (O3) is a sterilizing agent that has proved successful in destroying bacteria, fungi, viruses, and protozoa. Combatting viruses, ozone diffuses into their protein coat, all the way to the nucleic acid, damaging and killing the organism. The activated oxygen destroys the unsaturated lipid envelope of the virus by breaking the existing multiple bond configuration. As the nuclear content of the virus cannot live without an intact lipid envelope, thus the virus gets killed. COVID-19 virus is one such virus that has an unsaturated lipid envelope enclosing the nuclear content. Other viruses that cannot withstand the activated oxygen include poliovirus 1 and 2, human rotavirus, Norwalk virus, Parvoviruses, and Hepatitis A, B, and non-A non-B.1.

SoClean is one of the sanitizers that use this very method for sterilizing cloths, masks and such items. It comes with the Continuous Positive Airway Pressure (CPAP) machines and, both can be used to sterilize the n95 and other masks for reusing in the hospitals and elsewhere.

This editorial is open access and can be read from the following link: https://benthamopen.com/ABSTRACT/TODJ-14-14

Light and foraging ants seem totally unrelated, but they have one thing in common: they travel along time-reducing paths. According to Fermat's principle about the refraction of a ray of light, the light bends when it meets a matter with different refractive indices and travels through time-minimizing paths. Recently, similar behavior was reported in foraging ants in a lab setting: ants 'bend' their travel paths when they enter a substrate that slows them down. But would the ants behave similarly as the light passing through convex or concave lenses when they travel through impediments with lens-like shapes? A multidisciplinary team of researchers from Seoul National University (SNU) and DGIST in Korea, composed of ecologists and an engineer conducted experiments in the field to find out if the ants indeed behave similarly to the light.

The study has started with the following reasoning. Laws of optics predict that light rays reach the target on the other side of a convex lens by crossing the convex lens nearly everywhere; the crossing points can be quite far from the center of the lens (Fig. 1b). On the other hand, light rays cross the concave lens can reach the target only when it pass through the points near the center of the lens (Fig. 1e)

The researchers asked whether ants also show similar trends when they cross lens-shaped impediments, made of Velcro tape, during their foraging trips. On the Velcro "lens", the ants cannot walk as fast as they can on normal, flat surface. The researchers put these "lenses" between the nest entrance and the food source near several colonies of the Japanese carpenter ants and observed what happened. It turned out that the trails of ants crossing the "convex lens" diverged away from the center more than they did on the "concave lens". This means that more ants avoided the central thick part of convex impediment, and more ants walked through the central narrow part of concave impediment. This suggests that ants tend to avoid the parts of impediments that considerably slow them down.

This general similarity to the behavior of light crossing through convex and concave lenses is consistent with the idea that foraging ants, like light rays, use time-reducing paths. "I studied math and physics as an undergraduate, and this has helped me to come up with this research idea after I was exposed to the wonders of the behavior of ants by my Lab mate, Dr. Woncheol Song" says Ph.D. candidate Jibeom Choi, who conducted the experiments and created a mathematical model of ant behavior. Collaboration between a behavioral ecologist, Prof. Piotr Jablonski (Laboratory of Behavioral Ecology and Evolution, SNU) and a theoretical engineer, Prof. Hoyoung Kim (Microfluids & Soft Matter Laboratory, SNU), additionally highlights the multidisciplinary merit of this study. "This is an example of synergistic effect of multidisciplinary collaboration; by crossing the boundaries between disciplines, we have a fuller understanding of the natural world.", remarks the integrative ecologist in the study, Prof. Sang-im Lee (Laboratory of Integrative Animal Ecology, DGIST), who has been actively pursuing multidisciplinary research at SNU and DGIST, and has been involved in research on ants for years.

There are, however, remaining questions to be solved. As pointed out by authors themselves, the behavior of individual ants on the Velcro impediment and its borders has not been thoroughly investigated and it may contribute to the observed pattern. Therefore, further studies should focus on the behavior of individual ants at the edges between different substrates.

Consumers often struggle to achieve self-set life improvement goals, but what if deliberately emulating the successful strategies used by their friends could help them?

A new paper published in the Journal of the Association for Consumer Research shows that encouraging people to find and mimic exercise strategies used by their friends increases the amount of time people spent exercising relative to receiving an exercise strategy passively. In the study, Katie S. Mehr, Amanda E. Geiser, Katherine L. Milkman, and Angela L. Duckworth introduce the "copy-paste prompt," a nudge that encourages consumers to seek out and mimic a goal-achievement strategy used by an acquaintance.

Copy-paste prompts "are easy to implement, virtually costless, and widely applicable with the potential to improve outcomes ranging from healthy eating to academic success," the authors write in "Copy-Paste-Prompts: A New Nudge to Promote Goal Achievement."

Copy-paste prompts may be more effective than other methods for bolstering goal achievement for several reasons: behaviors are more appealing when learned from observation, plus learning from models increases both a person's expectations of their own abilities and their likelihood of using information. However, consumers may not take full advantage of opportunities to observe and emulate others in their social network. In this case, copy-paste prompts may add value by helping consumers better take advantage of this resource. Plus, the information is more customized and goal relevant, since consumers select peers whose behavior they want to emulate.

In the authors' longitudinal study, over 1,000 participants were asked how many hours they spent exercising in the last week and were randomly assigned to one of three conditions: the copy-paste prompt condition, a quasi-yoked control condition, or a simple control condition.

In the copy-paste prompt condition, participants read the following:

"In this study, we want to help you learn about an effective hack or strategy that someone you know uses as motivation to exercise. Over the next two days, we'd like you to pay attention to how people you know get themselves to work out. If you want, you can ask them directly for their motivational tips and strategies."

In the quasi-yoked control condition, participants read the following:

"In this study, we're hoping to help you learn about an effective hack or strategy that motivates people to exercise. Over the next two days, we'd like you to get ready to learn a new strategy to motivate you to exercise."

The participants who received the copy-paste prompt spent more time exercising the following week than participants assigned to either a quasi-yoked or simple control condition. "The benefits of copy-paste prompts are mediated by the usefulness of the adopted exercise strategy, commitment to using it, effort put into finding it, and the frequency of social interaction with people who exercise regularly," the authors write.

Looking ahead, the authors write, "It may be that once a consumer learns to copy-paste in one domain (e.g., exercise), she will be able to apply this technique in a way that improves many other outcomes (e.g., retirement savings)."

Threats to self-esteem and negative feedback are pervasive in today's society. Social media researchers, for example, have shown a link between frequent usage of social media websites and upward social comparison and negative affect.

How does this influence consumer behavior? A new paper published in the Journal of the Association for Consumer Research examines how single and repeated exposure to negative feedback in one domain influences goal-directed consumer behaviors.

In "The Motivating And Demotivating Effects Of Negative Feedback On Cross-Domain Goal Pursuit Behaviors," authors Alison Jing Xu, Shirley Y. Y. Cheng, and Tiffany Barnett White hypothesize that receiving negative feedback induces a general motive to boost one's self-view, which motivates people to pursue proving goals (i.e., those that allow them to demonstrate their competence), even in areas that are unrelated to the feedback. The authors propose that negative feedback also demotivates the pursuit of enjoyment goals (i.e., those that focus on the pursuit of pleasure and therefore have no self-restorative characteristics).

These motivational consequences not only influence consumers' goal pursuit behaviors when a single goal (either a proving goal ["Playing this game can prove my intellectual abilities"] or an enjoyment goal ["I would have a lot of fun playing this game"] is activated, but also affect consumers' choice between a proving goal and an enjoyment goal.

Although receiving negative feedback may give rise to negative affect, the motivational consequences of negative feedback on goal pursuit behaviors were not driven by negative affect, per se. Instead, the motivation to boost one's self-view mediates the motivational influence of negative feedback on goal pursuit behaviors in other unrelated domains.

The authors conducted four experiments to support their hypothesis: manipulating negative feedback by providing performance feedback on a creativity test or an emotional intelligence test, and demonstrating its influence on consumers' motivation to pursue either a proving or an enjoyment goal, as well as on consumers' choice between a proving goal and an enjoyment goal.

"We showed that receiving negative feedback in an unrelated domain motivated consumers to spend more effort searching for product information if their search behavior was driven by the goal to identify the best option and prove their ability to make wise decisions (i.e., a proving goal)," the authors write. However, when consumers' search behavior was driven by the goal of having fun (i.e., an enjoyment goal), receiving negative feedback reduced search efforts.

Study participants who received negative performance feedback on a creativity task in one study responded by searching for information about options in an ostensibly unrelated study when this search behavior was framed as a proving goal. Similarly, receiving negative feedback on an emotional intelligence quiz increased participants' later likelihood of choosing to play a game that could demonstrate and improve their intellectual abilities (Clash of Clans) versus one they would enjoy more and have more fun playing (Fruit Ninja).

The findings also suggest that while consumers may be eager to self-improve when they receive initial negative feedback, repeated negative feedback exposure may undermine their confidence in their ability to self-repair, resulting in their being less motivated to pursue proving goals. This finding has important implications not only for the dynamic effects of self-repair motives on consumer behavior, but also for how to give negative feedback. "Specifically, it suggests that although people generally strive to self-improve after negative feedback, too much negative feedback can lead them to seek enjoyment rather than self-improvement, even in areas that have nothing to do with what they failed on previously," the authors write.

The findings may offer a path through which firms can have a positive impact on consumers' well-being. The findings suggest that, independent of potential effects of mood, receiving feedback that causes consumers to experience a threat to their self-concept (e.g., unflattering social comparison on a social media website) can influence not only their preferences for a given brand, but also the depth of their engagement with that brand. For example, the consumers in the first experiment were not only interested in trying the items in the assortment following negative (versus positive) feedback, they also literally searched more options for a longer period of time.

The drop of self-esteem as a result of upward social comparison may facilitate the marketing of goods, services, and activities that are associated with proving (but not enjoyment) goals (e.g., via Facebook ads) in the short run but not in the long run.

Renewable technologies are a promising solution for addressing global energy needs in a sustainable way.

However, widespread adoption of renewable energy resources from solar, wind, biomass and more have lagged, in part because they are difficult to store and transport.

As the search for materials to efficiently address these storage and transport needs continues, University of Delaware researchers from the Catalysis Center for Energy Innovation (CCEI) report new techniques for characterizing complex materials with the potential to overcome these challenges.

The researchers recently reported their technique in Nature Communications.

Seeing the parts, as well as the whole

Currently technologies exist for characterizing highly ordered surfaces with specific repeating patterns, such as crystals. Describing surfaces with no repeating pattern is a harder problem.

UD doctoral candidate and 2019-2020 Blue Waters Graduate Fellow Josh Lansford and Dion Vlachos, who directs both CCEI and the Delaware Energy Institute and is the Allan and Myra Ferguson Professor of Chemical and Biomolecular Engineering, have developed a method to observe the local surface structure of atomic-scale particles in detail while simultaneously keeping the entire system in view.

The approach, which leverages machine learning, data science techniques and models grounded in physics, enables the researchers to visualize the actual three-dimensional structure of a material they are interested in up close, but also in context. This means they can study specific particles on the material's surface, but also watch how the particle's structure evolves -- over time -- in the presence of other molecules and under different conditions, such as temperature and pressure.

Put to use, the research team's technique will help engineers and scientists identify materials that can improve storage technologies, such as fuel cells and batteries, which power our lives. Such improvements are necessary to help these important technologies reach their full potential and become more widespread.

"In order to optimize electrochemical storage technologies, such as fuel cells and batteries, we must understand how they work and what they look like," said Lansford, the paper's lead author, who is advised at UD by Vlachos, the project's principal investigator.

"We need to understand the structure of the materials we are generating, in detail, so that we can recreate them efficiently at a large scale or modify them to alter their stability."

Computational modeling

Lansford concedes that it is too costly and time-consuming to model complex structures directly. Instead, they take data, generated from a single spot on the surface of a material, and scale it to be representative for a variety of catalysts on many surfaces of many different materials.

Imagine a cube made up of many atoms. The atoms located on the corners of the cube will have different properties than, say, the atoms located on one side of the cube. This is because on the corners, fewer atoms will be connected to each other and atoms may be spaced closer together. While on the side of the cube, more atoms will be connected even though they may be spaced farther apart from each other.

The same is true for catalyst materials. Even if we can't see them with the naked eye, the particles that make up a catalyst are adsorbed onto many different sites on the material -- and these sites have different edges, bumps and other variations that affect how materials located there will behave. Because of these differences, scientists can't just use a single number to try to quantify what's happening across a material's entire surface, so they have to estimate what these surfaces look like.

According to Lansford, this is where computational modeling can help.

The research team used experimental measurements of different wavelengths of infrared light and machine learning to predict and describe the chemical and physical properties of different surfaces of materials. The models were trained entirely on mathematically generated data, allowing them to visualize many different options under many different conditions.

They developed special open-source software to apply the technique on different metals, materials and adsorbates. The methodology is flexible enough to be used with other spectroscopic techniques beyond infrared light, so that other scientists and engineers can modify the software to advance their own work.

"This work introduces an entirely new way of thinking on how to bridge the gap between real-world materials and well-defined model systems, with contributions to surface science and machine learning that stand on their own," said Lansford.