Tech

Although the knowledge we have about human cells and tissues has steadily increased over recent decades, many things remain unknown. For instance, cells exist in transient, dynamic states and understanding them is fundamental to decipher diseases and find cures. Classic techniques used in the lab to study cell types faced limitations and did not enable a finely detailed profile of cell function.

To overcome this obstacle, a group of scientists at the National Centre for Genomic Analysis (CNAG-CRG) from the Centre for Genomic Regulation (CRG), in Barcelona, Spain, led by Holger Heyn, developed a new computational tool, based on the mathematical Graph theory, to infer global, large-scale regulatory networks, from healthy and pathological organs, such as those affected by diabetes or Alzheimer's disease. The researchers were able to pinpoint genes relevant to organ function and potential drivers of diseases. They are publishing their results in the current issue of the Genome Biology journal.

"Our previously developed single-cell transcriptomic tools were very useful to discover unknown cell types", says Giovanni Iacono, senior postdoc researcher at the CNAG-CRG and first author of the study. "Those tools allowed us to describe new types and subtypes of cells, with their unique biological roles and hierarchical relationships", he adds.

Up to now, single-cell analysis had been used to understand cell types and their function within tissue. "Large-scale consortia like the Human Cell Atlas Project generate single-cell maps of entire organisms and sophisticated analysis strategies are required to transform big data into disruptive biological and clinical insights", says Holger Heyn, team leader of the Single Cell Genomics Group at the CNAG-CRG and senior author of the article.

The tool that this scientific team has now developed will enable them to go one step further, to see how genes interact to form tissues. "Our tool tries to address precisely the regulatory process that controls the morphology and functions of a cell", highlights Iacono.

The tool is based on the Graph theory, an abstract mathematical model in which there are nodes connected by edges. Once you have a graph, a structure, you can measure the importance of each node for the network. In this case, each node was a gene and importance was defined as the function of that gene being key for the biological system under study.

CNAG-CRG researchers processed datasets from ten-thousands of cells to infer the regulatory networks that drive cell phenotype formation and their respective functions. They applied their tool to study type 2 diabetes and Alzheimer's disease and were able to find the functional changes relevant to those diseases. Importantly, this opens the door to finding new drug targets.

"The network analysis we have developed goes beyond currently applied approaches to provide deep insights into how gene activities shape tissues and organs. This is critical to understand diseases in which these networks are disrupted and find their 'Achilles heels' for effective treatments." says Heyn.

Potentially, the tool can be applied to any disease, from Alzheimer's to chronic lymphocytic leukaemia. "We will apply our tool to propose new target genes for many diseases that can then be validated in further studies." Iacono states.

DURHAM, N.C. -- Scientists have discovered a small molecule drug that may stop cancer cells from becoming resistant to chemotherapy. Drug resistance is a major cause of cancer relapse and is responsible for as much as 90% of deaths related to the disease.

The new compound, which was tested in an animal model of melanoma, could make current chemotherapies more powerful. It works by thwarting cancer's ability to survive, evolve, and adapt to the DNA damage created by traditional chemotherapy drugs like cisplatin.

"Chemotherapies are often effective the first time around, but then the cancers mutate and become resistant to that drug, and the next, and the next," said senior study co-author Pei Zhou, Ph.D., a professor of biochemistry at Duke University School of Medicine.

"It reminds me of Boggarts, those shapeshifting creatures from Harry Potter that morph from one scary thing to another. The beauty of this approach is that you essentially freeze the Boggart in its current form, so you can kill it off for good."

The study was published June 6 in Cell.

In their simplest form, cancer cells are normal cells that are growing out of control. Each time these cells divide, the DNA within them must replicate to generate new copies to go inside each new cell. The first chemotherapy drugs were based on the rationale that rapidly growing cancer cells would be more sensitive to damage to their DNA. Drugs like cisplatin are designed to damage DNA, causing the sensitive replication machinery normally tasked with copying each strand to stall. If DNA replication is stalled for too long, cell division halts, and cells die.

The strategy is brutal and effective, even curative in some cases. But long-term, it often fails, as cancer cells figure out a way to proliferate even in the presence of DNA damage.

"The cancer cells often swap out the high fidelity replication machinery, which usually does the copying, with a sloppy replacement that covers up the lesions and moves on," said Zhou. "As a result, the cells survive, but with mutations in their DNA."

Because this process, known as translesion synthesis, is a major cause of cancer drug resistance, it has become a major area of study in cancer research. Scientists have identified a key protein involved, named Rev1, and have even disrupted it through genetic means -- works done in the laboratories of Graham C. Walker and Michael T. Hemann at MIT, both senior co-authors of this study. However, attempts to do the same with small molecules had never succeeded, presumably because the protein lacked an obvious binding pocket that a potential drug could exploit.

In this study, Zhou and his collaborators at Duke, MIT, and the University of Rhode Island decided to try their luck at finding a small molecule to block or inhibit Rev1. They screened 10,000 small molecule compounds, and were surprised to find that one -- a molecule called JH-RE-06 -- appeared to do the trick.

The researchers used a technique called x-ray crystallography to visualize the unexpected interactions between Rev1 and JH-RE-06. They found that when Rev1 interacts with JH-RE-06, it pairs up or dimerizes with another copy of itself, creating a binding pocket where there wasn't one before. When Rev1 is locked up in this dimer, it can no longer help cancer cells survive and attain their shape-shifting powers.

The researchers then tested the new molecule in human cancer cell lines and showed that it enhanced the ability of several forms of chemotherapy to kill cells, while also suppressing their ability to mutate in the presence of DNA-damaging drugs. Finally, they tested it in a mouse model of human melanoma. They found that not only did the tumors stop growing in mice treated with a combination of cisplatin and JH-RE-06, but also that those mice survived longer.

Senior study co-author Jiyong Hong, PhD, a professor of chemistry at Duke, said that they are currently creating versions of JH-RE-06 that have enhanced pharmacologic properties that could make it an even more attractive drug. "This is a great proof of principle that it is possible to target this protein, but we have a lot of work to do to turn this lead compound into a viable candidate that we can take to the clinic."

DALLAS (SMU) - Researchers at SMU's Center for Drug Discovery, Design and Delivery (CD4) have succeeded in lab testing the use of chemotherapy with a specific protein inhibitor so that the chemotherapeutic is better absorbed by drug-resistant cancer cells without harming healthy cells. The approach could pave the way for a more effective way to treat cancers that are resistant to treatment.

A mix of drugs is frequently used to shrink cancer tumors or keep tumor cells from spreading to other parts of the body. But chemotherapy is so toxic that the mix often kills healthy cells, too, causing dreadful side effects for cancer patients. And eventually, many cancers learn how to resist chemotherapy, making it less effective over time.

"When multidrug resistance evolves, this leaves the patient with a very poor prognosis for survival and the oncologist with few, if any, effective tools, such as chemotherapy medicines, to treat what is very likely an aggressive and/or metastatic cancer at this point," said John Wise, associate professor in the SMU Department of Biological Sciences and co-author of a study on the findings published Friday in PLOS ONE.

Much of the research led by CD4 director Pia Vogel and Wise is centered on a class of proteins called ABC transporters, a key factor in why many cancers resist chemotherapy.

"These transporters are defensive proteins and are normally very, very good for us. They protect us from toxic chemicals by literally pumping them out of the cell, almost like a sump pump removes water from one's cellar," Vogel said.

But when someone has cancer, these proteins do more harm than good.

"One protein, P-glycoprotein, can pump nearly all chemotherapeutics out of the cancer cell, thereby making the cancer resistant to many drugs and untreatable," Wise noted.

For this reason, SMU researchers tested the combination of using an inhibitor that temporarily shuts down P-glycoprotein's ability to remove drugs from the cancer cells along with chemotherapeutics on prostate cancer cells grown in the lab, which have been shown to be resistant to multiple chemotherapeutic drugs.

The SMU team was able to show that if inhibitors of P-glycoprotein are used during and after the multidrug resistant cancer cells have been exposed to the chemotherapy drugs, then the cancer cells become much more sensitive to the chemotherapeutics.

The recipe for success was giving cancer cells a dose of both chemotherapy drugs and the P-gp inhibitor for just two hours. Researchers then washed the prostate cancer cells to get rid of any residual chemotherapy drugs before giving the cells another dose of just P-gp inhibitor for 22 hours, lead author and SMU Ph.D. doctoral candidate Amila K. Nanayakkara explained.

Prostate cancer cells that were given this treatment were shown to retain chemotherapy drugs at a much higher level compared to cancer cells not treated with the P-glycoprotein inhibitor. After about 24 hours, much fewer of these cancer cells survived in this treatment compared to the cells which had not seen the inhibitor.

When the same tests were performed on normal noncancerous cells, "there was no sign of extra toxicity to the healthy cells using this method," Wise added.

One issue, though, is how to duplicate this method in a patient's body. "Once you've taken a chemotherapy drug, it's not easy to remove it after just two hours," said co-author Vogel, a professor in the SMU Department of Biological Sciences.

Still, the researchers argued that it is worth further research, because there are currently few options for cancer patients once their disease becomes resistant to multiple chemotherapies.

"Our paper shows these remarkable effects when the inhibitor is present during, and importantly, after exposure to chemotherapeutic," Wise said. "And while 'washing' is not feasible in humans, the kidneys and other organs are in a sense doing the washing step for a patient. These organs are washing the chemotherapy from the bloodstream and therefore, out of cancer cells. So in that way, we think our preliminary cell culture studies may be translatable at least in principle to animals and people."

SAN ANTONIO - Small intestine bacterial overgrowth (SIBO) may be more prevalent among patients with restless legs syndrome (RLS), according to preliminary findings from a small, new study.

Results show that SIBO was found in all seven participants who have RLS. In contrast, the prevalence of SIBO in the general population is estimated to be no more than 15%.

"We've observed extremely high rates of small intestinal bacterial overgrowth in the RLS group," said lead author Daniel Jin Blum, Ph.D., D.B.S.M., an adjunct clinical instructor at Stanford Center for Sleep Sciences and Medicine in Redwood City, California. "Exploring the relationship between RLS and gut microbial health has the potential to open novel avenues for possible detection, prevention and treatment for RLS and other sleep disorders."

SIBO is a condition in which rare gut-residing bacteria are over-represented in the gut. RLS is a sensorimotor disorder characterized by a complaint of a strong, nearly irresistible urge to move the limbs that is often accompanied by other uncomfortable sensations. These symptoms begin or worsen during periods of rest or inactivity such as lying down or sitting, are partially or totally relieved by movement such as walking or stretching, and occur exclusively or predominantly in the evening or at night.

Low iron in the brain is a key risk factor for RLS. According to the authors, this brain iron deficiency may be secondary to dietary iron deficiency or, potentially, gut inflammation.

Study participants completed questionnaires concerning sleep and SIBO symptoms and took home a fecal collection kit and a SIBO breath test kit. Fecal samples were examined by the University of Minnesota Genomics Center, and SIBO breath samples were evaluated by Aerodiagnostics for hydrogen and methane abnormalities.

Additional study participants continue to be recruited at the Stanford Sleep Center. Further analyses will examine fecal microbial composition, subtypes of RLS iron deficiency, and comparisons with insomnia.

Researchers at the National Institute of Standards and Technology (NIST) and collaborators have demonstrated a compact frequency-comb apparatus that rapidly measures the entire infrared band of light to detect biological, chemical and physical properties of matter. Infrared light travels in waves longer than visible light and is most familiar as the radiation associated with heat.

The NIST setup, which occupies just a few square feet of table space, has potential applications such as disease diagnosis, identification of chemicals used in manufacturing, and biomass energy harvesting. The work is described in the June 7 issue of Science Advances.

Optical frequency combs measure exact frequencies, or colors, of light. Various comb designs have enabled the development of next-generation atomic clocks and show promise for environmental applications such as detecting methane leaks. Biological applications have been slower to develop, in part because it's been hard to directly generate and measure the relevant infrared light.

To showcase biological applications, the NIST team used the new apparatus to detect "fingerprints" of NIST's monoclonal antibody reference material, a protein made of more than 20,000 atoms that is used by the biopharmaceutical industry to ensure the quality of treatments.

"For the first time our frequency combs have simultaneous coverage across the entire infrared molecular fingerprint region," project leader Scott Diddams said. "Other key advantages are speed, resolution and dynamic range in acquiring data."

Mid-infrared light is an especially useful research probe because molecules usually rotate and vibrate at these frequencies. But until now it's been difficult to probe this region due to a lack of broadband or tunable light sources and efficient detectors such as those available for visible and near-infrared light, the part of the infrared spectrum closest to visible light.

The new NIST apparatus overcomes these problems. Simple fiber lasers generate light spanning the entire range used to identify molecules--that is, mid-infrared to far-infrared wavelengths of 3-27 micrometers (frequencies of approximately 10-100 terahertz). The amounts of light absorbed at specific frequencies provide a unique signature of a molecule. The new system is innovative in detecting the electric fields of the absorbed light using photodiodes (light detectors) operating in the near-infrared range.

"A unique feature is that we detect signals in real time by rapidly sampling the infrared electric field with a near-infrared laser," Diddams explained. "This has two advantages: It shifts the detection from the infrared to the near-infrared where we can use inexpensive telecommunications photodiodes, and we no longer suffer from the limitations of infrared detectors, which require cryogenic (liquid nitrogen) cooling."

The researchers detected signature vibrations of three bands of amides (chemical groups containing carbon, oxygen, nitrogen and hydrogen) in the monoclonal antibody reference material. Amide bands in proteins are used to determine the folding, unfolding and aggregating mechanisms. Specific features of the detected bands indicated that the protein has a sheet structure, agreeing with previous studies. Sheets connect chemical groups in a flat arrangement.

In addition to biological applications, the new apparatus might be used to detect interactions between infrared light and condensed matter for quantum computing approaches that store data in molecular vibrations or rotations. In addition, when combined with novel imaging techniques, the tabletop system could obtain nanometer-scale images of samples that currently require the use of a much larger synchrotron facility.

Whether Harry Potter's invisibility cloak, which perfectly steers light waves around objects to make them invisible, will ever become reality remains to be seen, but perfecting a more crucial cloak is impossible, a new study says. It would have perfectly steered stress waves in the ground, like those emanating from a blast, around objects like buildings to make them "untouchable."

Despite casting deep doubt on dozens of theoretical papers on "elastodynamic" cloaking, the new study's authors from the Georgia Institute of Technology don't think civil engineers should completely give up on it, just on the idea of an ideal cloak. Limited cloaking could still add a degree of protection to structures, particularly against some stress waves common in earthquakes.

"With cloaking, there is this expectation that if you get any kind of stress wave from any kind of direction, a cloak should be able to hide the object from it. We now see that it is not possible," said principal investigator Arash Yavari, a professor in Georgia Tech's School of Civil and Environmental Engineering and in the George W. Woodruff School of Mechanical Engineering. "But for a large class of disturbances, namely the in-plane disturbances, you could probably design a good cloak."

In an earthquake, in-plane disturbances are seismic waves that track along flat and broad -- or planar -- paths through the surface of the Earth.

Yavari and coauthor Ashkan Golgoon, a graduate research assistant studying with Yavari, published their study in the journal Archive for Rational Mechanics and Analysis, a leading journal on theoretical solid mechanics, on May 16, 2019. The research was funded by the Army Research Office.

The dream cloak

The dream of cloaking to steer stress waves past a structure like it isn't even there has a lot in common with the dream of an invisibility cloak, which would bend light -- electromagnetic waves -- around an object then point it out the other side.

The light waves hitting the viewer's eye would reveal what is behind the object but not the object itself. In elastodynamic cloaking, the waves are not electromagnetic but mechanical, moving through the ground. Hypothetically, cloaking the object would completely isolate it from the waves.

In a scenario to protect, say, a nuclear reactor from any stress waves traveling through the ground, whether from a natural or human-made calamity, ideally, civil engineers might lower the base of the reactor into a hole below the surface of the ground. They would build a protective cylinder or a half-spherical underground bowl around it with special materials to steer the stress waves around the circle.

There are dreams, then there are the study's findings.

"We proved that the shape of the cloak does not matter, whether spherical or cylindrical, you can't completely cloak," Yavari said.

The erroneous analogy

A lot of theory and math from electromagnetic (light) cloaking has been transferred onto elastodynamic cloaking research, and some of the former appears to have thrown a wrench into the latter.

"Many times, analogies from other fields are useful, but elasticity adds multiple physical factors that you don't have in electromagnetism," Yavari said. "For example, the balance of angular momentum is being violated in much of the research literature.

Angular momentum is a property of mass in rotational motion, and it is resistant to changes. Many people have experienced angular momentum by tilting a spinning gyroscope and watching it stubbornly move down an unexpected path.

Although it's a wave, light is photons, which have no mass. Stress waves, on the other hand, travel through matter -- specifically, solid matter as opposed to liquid or gas -- and that adds pivotal real-world dynamics to the equation.

Those dynamics also affect that hole that hides the object. Without it, the stress waves travel pretty uniformly through a medium, but with it, stresses concentrate around the hole and mess up the neat geometry of the wave patterns.

The Roman cloak?

What to do? Cloak anyway. If the ideal solution does not exist, make an imperfect one.

"The math says that cloaking is not possible in the strict sense. When you understand that, you don't waste time," Yavari said. "You formulate problems that optimize with what you do know around targeted stresses or loads you want to protect against."

Engineers could protect against important earthquake stresses if they use materials that have been specifically pre-stressed, have certain elastic properties and distribution of densities that are detailed in the study. A real-life cloak can fall short of an ideal and still be great.

"If instead of 100 percent of the wave energy I only feel 10 or 20 percent, it's a huge deal because engineering is not a pursuit of absolute ideals," Yavari said.

Even the ancient Romans, notoriously math-phobic, appear to have inadvertently built seismic cloaks in their design of amphitheaters, according to a report in MIT Technology Review. Their resemblance to modern experimental cloaking devices may have helped preserve them for 2,000 years in seismically active regions.

The new study also examined a popular idea in civil engineering that building with a family of materials that have a microstructure making them "Cosserat solids" might allow for perfect cloaking. The authors concluded that this also can't work. The study did not consider so-called metamaterials, which have received attention for rerouting in particular light waves.

Veterans Affairs patients with diabetes have similar health outcomes regardless of whether their primary provider is a physician, nurse practitioner (NP), or physician assistant (PA), according to a Durham VA Health Care System study.

The results appear in the June 2019 edition of the Journal of the American Academy of Physician Assistants.

"Our study found that there were not clinically important differences in intermediate diabetes outcomes for patients with physicians, NPs, or PAs in both the usual and supplemental provider roles, providing additional evidence for the role of NPs and PAs as primary care providers," said Dr. George Jackson, senior author on the paper.

Jackson is a research health scientist with the Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT) at the Durham VA Medical Center in North Carolina. He is also an associate professor at Duke University.

Several years ago, VA instituted Patient Aligned Care Teams (PACTs) primary care model. PACTs involve a team of care providers working together with veterans to focus on wellness and disease prevention in addition to treatment.

Each PACT is led by either a physician, NP, or PA, and any one of those disciplines can also serve as a supplemental provider, supporting the main provider in the PACT. Within VA, about one-third of primary care visits are with PAs or NPs, rather than with physicians. While care teams led by PAs or NPs are becoming more and more common, questions remain about whether patients do as well with non-physicians leading their care.

The researchers turned to a large patient population within VA who often have complex health care needs those with diabetes. The researchers looked at the electronic health records of more than 600,000 veterans with diabetes.

A physician was the usual provider for 77% of these patients. The researchers did not find any statistically significant difference in quality of care based on the discipline of either the usual care provider or supplemental care providers. Patients whose usual care provider was a physician had similar health outcomes to those who mostly saw a PA or NP.

Whether supplemental primary care providers were physicians or other providers also did not result in clinically important differences in patient outcomes.

For example, compared to physician-only care, patients who saw only PAs in primary care had a 0.03% decrease in HbA1c (a measure of blood sugar, with lower numbers meaning better diabetes control). Patients who saw NPs only in primary care had a 0.06% decrease in HbA1c compared to those who saw physicians only. The differences were not large enough to be considered significant, meaning the results across those groups of patients were about equal.

While the researchers acknowledge that some patients may still prefer that their care be overseen by a physician, other studies have shown that patients are generally satisfied with care from NPs or PAs. VA has been guided in part by such past findings in expanding the use of PAs and NPs as team leaders.

The fact that PAs and NPs had similar results for quality of care without sharing care with a physician suggests that using these providers in primary care may improve the efficiency of health care, say the researchers.

Researchers from the Institute of Process Engineering (IPE) of the Chinese Academy of Sciences and Tsinghua University (THU) proved a sandwiched superstructure for graphene oxide (GO) that transport inside cell membranes for the first time.

The discovery, published in Science Advances, opens up a membrane-specific drug delivery mode, which could significantly improve cytotoxicity effects over traditional drug carriers.

The transport of nanoparticles at bio-nano interfaces is essential for cellular responses and biomedical applications. How two-dimensional nanomaterials interact or diffuse inside the cell membrane is unknown, thus hindering their applications in the biomedical area.

"The sandwiched graphene membrane is a long-simulated superstructure but an unproved issue in vitro. We are excited to provide substantial experimental evidence and open an avenue for novel membrane-specific drug delivery," said WEI Wei, a professor from the State Key Laboratory of Biochemical Engineering of IPE.

The formation process of sandwiched GO was visualized in a fully hydrated/native state, and the significant influence on cell roughness, cell fluidity and membrane rigidity was also revealed.

Furthermore, the sandwiched GO induced greater drug entry and quicker diffusion time inside the membrane lipid layer, thus outperforming a typical liposome carrier in anti-cancer efficacy. This feature is also extremely beneficial when delivering vaccine adjuvants (e.g., membrane receptor ligands) for enhanced immune effect, according to WEI.

All the cell interactions, diffusion dynamics and the enhanced efficiency of membrane-specific drug delivery of sandwiched GO were simulated by Prof. YAN Litang from THU.

"It is a very nice study of graphene-membrane superstructures. It discloses different transport regimes, the presence of pores and a number of other potentially interesting features related to these systems," said peer reviewers from Science Advances. "Moreover, they demonstrate the applicability of GOs for drug delivery. Overall, the paper is very timely and tells a good story."

The GO-based sandwiched superstructure offers immense design capabilities that may enable a considerable number of applications for these emerging nanomaterials in the cutting-edge fields of biological and medical science.

Picture the future, where driving is a thing of the past. You can hop in your car or one from a ride-share, buckle up and tell the car where you want to go. During your ride, you can check your email and look up a few things online through your dashboard. Meanwhile, your whereabouts and other details are being tracked remotely by companies. As self-driving cars develop further, autonomous vehicles will play a much larger role in the digital economy as car companies and others harness personalized customer information through geospatial and navigation technologies, combining it with existing financial consumer profiles, according to a study in Surveillance and Society.

"Self-driving cars will represent a new mode for surveillance. Through a self-driving car's global positioning, system, navigational tools, and other data collection mechanisms, companies will be able to gain access to highly contextual data about passengers' habits, routines, movements, and preferences," explained Luis F. Alvarez León, an assistant professor of geography at Dartmouth. "This trove of personal, locational, and financial data can be leveraged and monetized by companies, by providing a data-stream for companies to target customers through personalized advertising and marketing," he added.

Today's cars are already spatial multimedia environments that are highly computerized but self-driving cars will take this to a whole new level. They will also enable passengers to spend more time engaging with media in a vehicle. As the study point outs, this new economy may challenge notions of traditional car ownership, transforming "the car into a bundle of services rather than just a product." Automobile manufacturers may essentially become digital platforms for media companies, search engines, retailers, vendors, and other companies, aiming to offer services to passengers through a car's infotainment system.

The growth of self-driving cars will require more extensive communication networks, which will benefit ride-sharing companies, automobile manufacturers and other companies entering this new information-centric space. "Through autonomous cars, the automotive and technology industries are likely to become more integrated with synergies across geospatial, navigation, artificial intelligence, ride-hailing, automotive and other industries and technologies," said Alvarez Léon.

As self-driving car technologies develop, privacy and security concerns loom as to how companies will use personal data, an area for which the limits and specific governance mechanisms have yet to be defined by federal regulations.

UPTON, NY--Scientists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory and the University of Arkansas have developed a highly efficient catalyst for extracting electrical energy from ethanol, an easy-to-store liquid fuel that can be generated from renewable resources. The catalyst, described in the Journal of the American Chemical Society, steers the electro-oxidation of ethanol down an ideal chemical pathway that releases the liquid fuel's full potential of stored energy.

"This catalyst is a game changer that will enable the use of ethanol fuel cells as a promising high-energy-density source of 'off-the-grid' electrical power," said Jia Wang, the Brookhaven Lab chemist who led the work. One particularly promising application: liquid fuel-cell-powered drones.

"Ethanol fuel cells are lightweight compared to batteries. They would provide sufficient power for operating drones using a liquid fuel that's easy to refill between flights--even in remote locations," Wang noted.

Much of ethanol's potential power is locked up in the carbon-carbon bonds that form the backbone of the molecule. The catalyst developed by Wang's group reveals that breaking those bonds at the right time is the key to unlocking that stored energy.

"Electro-oxidation of ethanol can produce 12 electrons per molecule," Wang said. "But the reaction can progress by following many different pathways."

Most of these pathways result in incomplete oxidation: The catalysts leave carbon-carbon bonds intact, releasing fewer electrons. They also strip off hydrogen atoms early in the process, exposing carbon atoms to the formation of carbon monoxide, which "poisons" the catalysts' ability to function over time.

"The 12-electron full oxidation of ethanol requires breaking the carbon-carbon bond at the beginning of the process, while hydrogen atoms are still attached, because the hydrogen protects the carbon and prevents the formation of carbon monoxide," Wang said. Then, multiple steps of dehydrogenation and oxidation are needed to complete the process.

The new catalyst--which combines reactive elements in a unique core-shell structure that Brookhaven scientists have been exploring for a range of catalytic reactions--speeds up all of these steps.

To make the catalyst, Jingyi Chen of the University of Arkansas, who was a visiting scientist at Brookhaven during part of this project, developed a synthesis method to co-deposit platinum and iridium on gold nanoparticles. The platinum and iridium form "monoatomic islands" across the surface of the gold nanoparticles. That arrangement, Chen noted, is the key that accounts for the catalyst's outstanding performance.

"The gold nanoparticle cores induce tensile strain in the platinum-iridium monoatomic islands, which increases those elements' ability to cleave the carbon-carbon bonds, and then strip away its hydrogen atoms," she said.

Zhixiu Liang, a Stony Brook University graduate student and the first author of the paper, performed studies in Wang's lab to understand how the catalyst achieves its record-high energy conversion efficiency. He used "in situ infrared reflection-absorption spectroscopy" to identify the reaction intermediates and products, comparing those produced by the new catalyst with reactions using a gold-core/platinum-shell catalyst and also a platinum-iridium alloy catalyst.

"By measuring the spectra produced when the infrared light is absorbed at different steps in the reaction, this method allows us to track, at each step, what species have been formed and how much of each product," Liang said. "The spectra revealed that the new catalyst steers ethanol toward the 12-electron full oxidation pathway, releasing the fuel's full potential of stored energy."

The next step, Wang noted, is to engineer devices that incorporate the new catalyst.

The mechanistic details revealed by this study may also help guide the rational design of future multicomponent catalysts for other applications.

A collaborative investigation has revealed new insight into how room temperature ionic liquids (RTILs) conduct electricity, which may have a great potential impact for the future of energy storage.

The research focuses on the debate surrounding the physical mechanism of the electrical conductivity of RTILs. Their charged positive and negative organic ions lead them to be good conductors, but the conductivity seems paradoxical. Their high conductivity arises from their high density of charged ions within the liquid, but this density should also mean that the positive and negative ions are close enough to neutralise one another, creating new, neutral particles which cannot support an electrical current. The modelling attempts to identify how conductivity is maintained in RTILs in light of these contradictory factors.

The research involved an international group of researchers, including Professor Nikolai Brilliantov of the University of Leicester and led by Professor Alexei Kornyshev of Imperial College London and Professor Guang Feng of the Huazhong University of Science and Technology.

Researchers elaborated special numerical methods and theoretical approaches to trace the dynamics of particles in RTILs. They discovered that, most of the time, positive and negative ions reside together in neutral pairs or clusters, forming a neutral substance which cannot conduct electricity. From time to time however, positive and negative ions emerge by pairs as charged particles in different parts of the liquid, making the liquid conductive.

The emergence of these ions is caused by thermal fluctuations. Suddenly and randomly the ions receive a portion of energy from the surrounding fluid, which helps them to release themselves from the 'paired' neutral state and become free charged particles. This state is only temporary, however: after some time, they will return back to their paired neutral state as they join with another ion of opposite charge.

As this happens, another ionic pair elsewhere in the liquid is splitting into free charged particles, thereby sustaining the conductivity of the liquid and its electrical current in a kind of ongoing 'relay race' of charges. This is similar to the behaviour observed in crystalline semiconductors, where the positive and negative charge carriers also emerge in pairs due to thermal fluctuations. It is therefore expected that a rich variety of physical phenomena observed in semiconductors might also be revealed in RTILs in the future.

Just as these phenomena in semiconductors are exploited for many applications, this research reveals that there may be potential too for RTILs to be exploited in new and innovative ways, with possible uses ranging from supercapacitors, fuel cells and batteries to various power devices.

Professor Brilliantov, Chair in Applied Mathematics and the University of Leicester's lead on the project, said: "Understanding of the conductivity mechanism of RTILs seems to open new horizons in designing ionic liquids with the desired electrical properties."

International group of scientists in the joint study of the laboratory of the Wistar Institute, University of Pittsburgh and I.M. Sechenov First Moscow State Medical University discovered the change in activity of one of the immune cells types called neutrophils during the cancer development: they begin to prevent other immune cells from fighting tumor and thus decelerate treatment. The scientists found protein causing such changes and demonstrated that suppressing its activity in the cells allows to delay cancer development. The research details are published in Nature.

The study is focused on myeloid-derived suppressor cells (MDSCs) developing from neutrophils. In some cases (e.g. in cancer, during inflammation or autoimmune diseases), these immune cells start to fight against other immune cells instead of bacteria and fungi. Thus they weaken the body reaction against the tumor and decrease cancer treatment efficiency.

"If you need a simple comparison - remember a very well-known fairy-tale by Hans Christian Andersen "The Snow Queen" where the little Sister traveled to the North Pole to waken-up her Brother whose heart was frozen by the Queen. The sincere, bitter and warm tears of the little Sister melted the frozen Brother's heart and reminded him about his past happy life at home. Well, that's approximately what we do: we recall the memories of neutrophils to work as good immune cells against the tumor not for it," commented Valerian Kagan, one of the study leaders, the head of research laboratories of University of Pittsburgh and Sechenov University.

Despite the fact that the activity of MDSCs complicates the treatment, the mechanisms responsible for its change are still poorly studied. Earlier research showed that during oncological disease polyunsaturated fats (lipids) accumulate in some types of immune cells, so the scientists decided to check whether the dysfunction of lipid metabolism in neutrophils is linked to changes in their activity. They compared the fat content in the cells of healthy mice and animals with different types of cancer, and the latter group had much higher amount of fat.

After that scientists led by professor Dmitry Gabrilovich at the Wistar Institute looked at the difference between the activity (expression) of genes in suppressor cells in healthy and sick mice. They were especially interested in genes that encode proteins carrying fatty acids through the cell wall. A great difference was observed in the activity of the Slc27a2 gene encoding one of these proteins, FATP2, the activity of other genes did not differ. Increased FATP2 content in cancer was present in people as well. These were patients with different types of cancer.

Then the researchers checked whether FATP2 is able to somehow affect the activity of neutrophils. They compared the rate of tumor growth in mice with "deactivated" and activated Slc27a2 and found that in the former group the disease developed more slowly. The scientists also checked whether the efficiency of such therapy depends on other diseases. Experiments showed that if the animal has immunity dysfunction, the treatment gave much smaller results. Besides, the combination of this type of therapy with the suppression of the production of immune checkpoints - molecules that weaken the immune response - showed good efficiency. The activity of checkpoints is useful during autoimmune diseases, but undesirable in cancer.

"One of the contemporary trends in anticancer therapy is immune therapy. This is a type of treatment when pharmaceuticals do not kill tumor cells directly but instead stimulate the body's natural defenses to fight the cancer. Among treatments of this kind, elimination of the modified immune cells in the tumor microenvironment that are reprogrammed to suppress the normal immune surveillance is a very promising approach. Our study published in Nature describes research of this type that attempts to encourage neutrophils to "recall their important immune functions." Based on the conducted research and deciphered mechanisms, the successful treatment has been proposed and achieved using experimental models of tumor-bearing animals," added Valerian Kagan.

The authors of the articles also highlighted the mechanism by which FATP2 can affect the activity of neutrophils: it facilitates the accumulation of some fatty acids, particularly arachidonic acid, and one of its derivatives, prostaglandin E2 (PGE2) in the cells. The last substance, as shown earlier, causes changes in cell activity.

Thus, the authors managed to show that FATP2 protein plays a crucial role in changing of neutrophil activity and accelerating the development of cancer. The fact that FATP2 is synthesized in large quantities near the tumor allows to influence selectively on suppressor cells and to avoid strong side effects.

Scientists since Darwin have been intrigued by the simultaneous alteration of multiple morphological, physiological and behavioural traits across a wide range of domesticated animals, such as horses, pigs and dogs. For instance, reduced brain size, floppy ears, increased docility and hormonal changes are commonly seen in domesticated animals but not their wild ancestors. This phenomenon is known as the domestication syndrome, and the traits within this syndrome are assumed to change together in a correlated fashion during domestication. But surprisingly, whether or not any of these traits are in fact correlated has never been formally tested.

A new study published in Nature Communications by a team of researchers from Stockholm University used behavioural data from more than 76,000 dogs, to test the hypothesis that key behaviours in the domestication syndrome are correlated. Domesticated animals are more social and playful, and less aggressive and fearful than their wild counterparts. Because domestication drives behavioural change in which aggression and fearfulness decrease while sociability and playfulness increase, there is an expectation that behavioural alterations during domestication are correlated in a direction-specific manner. For instance, we should expect sociability to be positively correlated with playfulness, but negative correlated with aggression and so forth. These assumed correlational patterns were exactly what the researchers tested in dogs.

The dataset of 76,158 dogs came from the Swedish Kennel Clubs database and consisted of dogs that had completed the Dog Mental Assessment, a behavioural test that thousands of Swedish dogs go through every year. In this test, behavioural responses to varying kinds of stimuli are assessed under standardized conditions, and among these responses are the behaviours in the domestication syndrome; aggression, fearfulness, sociability and playfulness. With this dataset the researchers had a unique opportunity to test the domestication syndrome hypothesis on an extraordinary large sample size of dogs.

The 78 dog breeds in the study, which ranged from Akitas to Chihuahuas to Mastiffs, were divided into ancient and modern breeds. Ancient breeds belong to a small group of dogs in which wolf genes can still be detected, and this breed group is believed to have an origin approximately 500 years ago. Modern breeds, which make up the majority of present-day dog breeds, have no detectable wolf component and an origin less than 200 years ago. This division of breeds representing early and late stages of dog domestication allowed the researchers to test the domestication syndrome hypothesis on a temporal evolutionary scale.

"Surprisingly, we found that the correlations among behaviours varied between dog breeds representing early and late stages of domestication. The expected correlations among our measured behaviours are generally strong in ancient breeds, such as Siberian Huskies and Alaskan Malamutes, but several of these correlations are weak or gone in the modern breeds, such as Golden Retrievers and Dalmatians", says Christina Hansen Wheat from Stockholm University. This difference between ancient and modern breeds suggests that the behaviours of the domestication syndrome have been decoupled during dog domestication. This decoupling could be caused by a recent shift in selection pressures in modern dog breeds for highly breed-specific traits, such as colour, coat structure or specific behaviours. Importantly, this means that domestication-related behaviours can be selected upon independently in modern dog breeds. With the recent increased focus on animal domestication, and the domestication syndrome in particular, this study provides new insight that invites for a re-evaluation of our expectations to how domestication affects behaviour.

The tides are turning in a quest to solve an earthquake mystery.

Years ago, scientists realized that earthquakes along mid-ocean ridges -- those underwater mountain ranges at the edges of the tectonic plates -- are linked with the tides. But nobody could figure out why there's an uptick in tremors during low tides.

"Everyone was sort of stumped, because according to conventional theory, those earthquakes should occur at high tides," explained Christopher Scholz, a seismologist at Columbia University's Lamont-Doherty Earth Observatory.

In a study published today in Nature Communications, he and his colleagues have uncovered the mechanism for this seeming paradox, and it comes down to the magma below the mid-ocean ridges.

"It's the magma chamber breathing, expanding and contracting due to the tides, that's making the faults move," said Scholz, who co-led the study along with Lamont-Doherty graduate student Yen Joe Tan.

Going against the tide

The low tide correlation is surprising because of the way the mid-ocean fault moves. Scholz described the fault as a tilted plane that separates two blocks of earth. During movement, the upper block slides down with respect to the lower one. So, scientists expected that at high tides, when there is more water sitting on top of the fault, it would push the upper block down and cause the earthquakes. But that's not what happens. Instead, the fault slips down during low tide, when forces are actually pulling upwards -- "which is the opposite of what you'd expect," said Scholz.

To get to the bottom the mystery, he, Tan, and Fabien Albino from the University of Bristol studied the Axial Volcano along the Juan de Fuca Ridge in the Pacific Ocean. Because the volcano erupts every ten years or so, scientists have set up dense networks of ocean bottom instruments to monitor it. The team used the data from those instruments to model and explore different ways the low tides could be causing the tremors.

In the end, it came down to a component that no one else had considered before: the volcano's magma chamber, a soft, pressurized pocket below the surface. The team realized that when the tide is low, there is less water sitting on top of the chamber, so it expands. As it puffs up, it strains the rocks around it, forcing the lower block to slide up the fault, and causing earthquakes in the process.

Furthermore, said Scholz, the tidal earthquakes in this region are "so sensitive that we can see details in the response that nobody could ever see before." When the team charted the earthquake rate versus the stress on the fault, they realized that even the tiniest stress could trigger an earthquake. The tidal data helped to calibrate this effect, but the triggering stress could be caused by anything -- such as the seismic waves from another earthquake, or fracking wastewater pumped into the ground.

"People in the hydrofracking business want to know, is there some safe pressure you can pump and make sure you don't produce any earthquakes?" said Scholz. "And the answer that we find is that there isn't any -- it can happen at any level of stress."

Of course, a small stress over a small area isn't going to cause a devastating earthquake, and the exact amount of stress needed varies from place to place. "Our point is there's no intrinsic stress that has to be exceeded to cause an earthquake," says Scholz. "There isn't any rule of thumb."

PITTSBURGH, June 7, 2019 - The death rate from drug- and alcohol-related causes in people who've had Roux-en-Y gastric bypass surgery is nearly triple that of the general public, according to University of Pittsburgh research published today in Surgery for Obesity and Related Diseases, the journal of the American Society for Metabolic and Bariatric Surgery.

The study also found that fewer than half of those who died had triggered a safety protocol for problematic substance use. Only one of those who died was known to have received treatment for substance use disorder.

"Increasingly with bariatric surgery patients, we're finding that the tools that clinicians traditionally use to screen for drug or alcohol problems don't work well to identify those at risk," said lead author Gretchen White, Ph.D., epidemiologist in the Pitt School of Medicine's Department of Surgery. "These deaths are an extreme and sad example of a problem that needs to be addressed."

For seven years, White and her colleagues followed 2,458 adults who underwent bariatric surgery. The participants were enrolled in the National Institutes of Health-funded Longitudinal Assessment of Bariatric Surgery-2 (LABS-2), a prospective, observational study of patients undergoing weight-loss surgery at one of 10 hospitals across the United States.

Reflecting typical bariatric surgery patients, the majority of study participants were female (79%) and white (86%). At time of surgery, the median age was 46 years old. During the seven-year follow-up, 10 of the participants died of causes directly related to drug- and alcohol-use, with six unintentional drug overdoses, one intentional overdose, one overdose where the intent was unknown and two deaths from alcoholic liver disease. All 10 participants had undergone Roux-en-Y gastric bypass surgery, which reduces the size of the stomach and shortens the intestine, and accounted for 72% of the bariatric procedures in the study sample.

The team looked at the deaths in terms of "person-years," a scientific measure that takes into account both the number of people in a study and the amount of time each person spends in the study. The drug- and alcohol-related death rate was 89 deaths per 100,000 person-years for the Roux-en-Y gastric bypass surgery patients, compared to 30.5 deaths per 100,000 person-years for the general population matched on age, sex, race and calendar year. On average, the deaths occurred nearly five years post-surgery.

"While drug- and alcohol-related deaths were too rare to identify risk factors, it is noteworthy that the demographics of those who died were similar to the full sample. Based on demographics, bariatric surgery patients should be a low-risk group for substance-related death," said senior author Wendy King, Ph.D., associate professor in the Pitt Graduate School of Public Health's Department of Epidemiology. "Laboratory studies indicate that Roux-en-Y gastric bypass changes the way the body reacts to alcohol and drugs, and our previous work demonstrates an increased risk of self-reported problematic alcohol use and illicit drug use following this surgery. This study indicates such problems can lead to loss of life."

In addition to research to better understand the reasons for the high death rate, the scientists suggest that new clinical screening tools, tailored specifically to bariatric surgery patients, are needed so clinicians can better detect patients at high risk for substance use problems.

For example, White says, current questionnaires ask people about the number and frequency of alcoholic beverages they consume. Because bariatric surgery patients tend to experience the effects of alcohol faster and with fewer drinks than the average person, it might be better to ask about how alcohol makes them feel, if it is interfering with daily activities and whether they or their families and friends think they may have a problem.

Because the deaths occurred many years after surgery, co-author Anita Courcoulas, M.D., chief of minimally invasive bariatric surgery at UPMC, said that it is especially important that primary care physicians be aware of the particular risks that bariatric surgery patients face in terms of substance use.

"This is an important issue to recognize in all bariatric surgery patients as there is a clear signal of risk for substance use-related deaths," said Courcoulas. "Further study is required to understand the precise mechanisms, and prospective tracking of patients is very important to be able to offer more timely intervention."