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An international consensus panel led by researchers from The Westmead Institute for Medical Research (WIMR) has highlighted the need to redefine Non-Alcoholic Fatty Liver Disease (NAFLD), and to name it Metabolic Associated Fatty Liver Disease (MAFLD). Researchers highlighted that the new terminology will better reflect its causes, and improve public health initiatives.

MAFLD is a condition characterised by a build-up of fat in the liver and affects over one billion people. Over time, this can lead to complications including cirrhosis, liver failure, liver cancer, and heart health issues. The consensus panel found that both the term 'NAFLD' and its diagnostic criteria must be updated in order to better reflect our current understanding of the disease.

Associate Professor Mohammed Eslam, co-lead author of the paper said, "Since it was first described in 1980, we haven't revisited the appropriateness of the name, or the criteria used to diagnose fatty liver disease.

"By updating terminology and definitions, we can shift towards more precise and personalised treatment pathways, trial design and drug development."

Professor Jacob George, co-lead author of the paper said, "Initially, the disease was defined as fatty liver in the absence of significant alcohol intake. This definition was problematic and has resulted in a 'one-size-fits-all' approach to treatment, despite the significant variation we see in people affected by the disease.

"This may be one of the reasons why we are seeing relatively low response rates in our current trials.

"The proposed name and definition recognises that the disease we are looking at is associated with metabolic dysfunction. It also acknowledges that there are multiple overlapping causes and drivers of the disease."

Researchers are now conducting further studies to characterise the different sub-types and causes of MAFLD to help design new clinical trials, and best practices for patient management.

"Ultimately, we hope that by strengthening the diagnostic criteria and language surrounding MAFLD, we can help reduce the progression of the disease, and reduce the number of people affected worldwide," Professor George concluded.

Unmanned aerial vehicles (UAV), commonly known as drones, are widely used in mapping, aerial photography, rescue operations, shipping, law enforcement, agriculture, among other things. Despite great potential for improving public safety, use of drones can also lead to very undesirable situations, such as privacy and safety violations, or property damage. There is also the highly concerning matter of drones being harnessed to carry out terrorist attacks, which means a threat to public safety and national security.

Radar technology is one of the solutions to monitor the presence of drones and prevent possible threats. Due to their varying sizes, shapes and composite materials, drones can be challenging to detect.

Researchers from Aalto University (Finland), UCLouvain (Belgium), and New York University (USA) have gathered extensive radar measurement data, aiming to improve the detection and identification of drones. Researchers measured various commercially available and custom-built drone models' Radar Cross Section (RCS), which indicates how the target reflects radio signals. The RCS signature can help to identify the size, shape and the material of the drone.

'We measured drones' RCS at multiple 26-40 GHz millimetre-wave frequencies to better understand how drones can be detected, and to investigate the difference between drone models and materials in terms of scattering radio signals. We believe that our results will be a starting point for a future uniform drone database. Therefore, all results are publicly available along with our research paper,' says the author, researcher D. Sc. Vasilii Semkin.

The publicly accessible measurement data can be utilised in the development of radar systems, as well as machine learning algorithms for more complex identification. This would increase the probability of detecting drones and reducing fault detections.

'There is an urgent need to find better ways to monitor drone use. We aim to continue this work and extend the measurement campaign to other frequency bands, as well as for a larger variety of drones and different real-life environments,' Vasilii Semkin says.

Researchers suggest that 5G base stations could made in the future for surveillance.

'We are developing millimetre-wave wireless communication technology, which could also be used in sensing the environment like a radar. With this technology, 5G-base stations could detect drones, among other things,' says professor Ville Viikari from Aalto University.

The results of this work have been published in IEEE Access, a special section on Millimetre-wave and Terahertz Propagation Channel Modeling and Applications (link). The measurement data can be accessed here (https://ieee-dataport.org/open-access/drone-rcs-measurements-26-40-ghz)

Women run more sophisticated campaigns for office than men, says David Niven, a leading political researcher and associate professor of political science at the University of Cincinnati.

In research accepted for publication in the upcoming June issue of Political Research Quarterly, Niven analyzed 1,351 candidate responses to detailed questionnaires provided by the League of Women Voters in races across the nation in 2016. Those races ranged from local school boards and city councils all the way up to the U.S. Senate.

What he and his graduate students found was that women tend to run more sophisticated campaigns even when the odds are against them.

Niven's study reinforces the importance of pursuing research that highlights inclusion and prepares the next generation of leaders, one of the primary goals of Next Lives Here, UC's strategic direction.

According to Niven, "Women tend to take the prospect of a political campaign more seriously, and their campaigns reflect that. Even when a woman is running in a difficult district, she is likely to make a serious effort." By contrast, Niven said, "Men will run for office at the drop of a hat. In long shot circumstances, men's campaigns tend to be very amateurish."

Niven's measure of campaign sophistication is based on how many details candidates provided in their responses. Niven found that more successful candidates tended to answer questions with general, thematic responses, while less successful candidates wallowed in specifics.

As an example, Niven pointed to campaigns in Texas where one of the issues candidates faced was traffic congestion. "One woman who won her race spoke generally about her goals and the shared reality that 'we all sit in traffic together.' One unsuccessful male candidate got himself trapped in the confines of the questions and went into great detail, including discussing his hope for developing moving sidewalks like on the Jetsons."

"Overall, we found that women candidates are less likely to get caught up in details that, quite frankly, can lose votes and get in the way of the candidate's message."

Niven says it's not surprising that pundits who are reviewing Sen. Elizabeth Warren's campaign for president are saying that she ran a very smart campaign, and yet she didn't win any states.

Senator Elizabeth Warren with a group of African-American students on the campaign trail

Sen. Elizabeth Warren on the campaign trail for the 2020 presidential election. Photo: senate.gov/newsroom

"The bottom line here is that women run more sophisticated campaigns in general, but that doesn't mean they are rewarded commensurately by the voters."

Niven is continuing his analysis of the League of Women Voter guides from the 2018 midterm elections and will also analyze the guides and outcomes from the 2020 elections. Working with Niven on this soon-to-be-published research were graduate students Alexis Straka and Anwar Mhajne.

HSE researchers, jointly with colleagues from the RAN Institute of Organoelement Compounds and the RAN Institute of Physical Chemistry and Electrochemistry, have studied the properties of a polyarylene ether ketone-based copolymer (co-PAEK) for potential space applications. Co-PAEK films are highly resistant to electrostatic discharges caused by ionizing radiation and can thus be used as protective coating for spacecraft electronics. The study findings have been published in Polymers.

Spacecraft electronics are continuously exposed to the ambient space plasma. Its ionizing radiation causes electric charge to accumulate in dielectric materials on board space-based vehicles, leading to electrostatic discharges which can result in failures of electronic devices and, ultimately, of the spacecraft itself.

Worldwide, just three research centres are equipped and staffed to study the effects of ionizing radiation on materials used in spacecraft construction in virtually real-life conditions. These facilities are the MIEM HSE Laboratory of Space Vehicles and Systems' Functional Safety (Moscow) , John Robert Dennison's Laboratory at Utah State University (Logan, Utah, USA), and Thierry Paulmier's Laboratory in Toulouse, France.

The researchers investigated the conductive properties of co-PAEK films by first supplying film specimens with very thin aluminium electrodes via vacuum deposition and then placing the specimens inside a vacuum chamber equipped with an electron gun. By bombarding the specimens with charge carriers of 50,000 eV, the researchers measured the film's radiation-induced conductivity associated with electron-hole pairs produced by the radiation. This parameter reflects how effectively materials can remove accumulated charges. In particular, the researchers examined the current-voltage (I-V) characteristics, i.e., the relationship between the electric current passing through the film and the voltage at the electrodes; they found that due to their super-linear I-V characteristics, the films are highly effective in removing electrostatic charges.
The researchers also studied the films' switching effect, i.e., the polymer's ability to make a reversible transition from a high-ohmic to a low-ohmic state in a strong electric field. This latter state increases the polymer's conductivity.

There is still no generally accepted physical model describing the switching effect in thin polymer films. However, the co-PAEK films' low switching thresholds and the reversibility of these effects appear highly promising. Notably, it is possible to modify the co-polymers' resistivity switching ability by varying its phthalide content.

The authors investigated the transport of charge carriers in co-PAEK films with varied phthalide content; for this purpose, they synthesized 20- to 25-micron films with 3, 5 and 50 percent of phthalide-containing units.

The results show that an increase in phthalide-containing units in co-PAEKs from 3 to 50 percent produced virtually no change in radiation-induced conductivity within the studied electric field range. This indicates that charge carriers in these experiments moved in an isolated manner and that the applied electric fields were below the threshold needed for collective interaction of charges and formation of conductive channels triggering the effect of high-to-low resistivity transition.

Unfortunately, at the studied film thicknesses, further increase in electric fields causes an electric breakdown; therefore, it may be too early to plan for their space application. Nevertheless, the researchers believe that this material is highly promising and that further research of the switching effect could produce more conclusive results. This copolymer has already been used to protect prototype models of silicone solar cells in spacecraft.

Fundamental research supported by supercomputers could help lead to new strategies and better technology that combats infectious and genetic diseases.

Viruses such as the dreaded severe acute respiratory syndrome coronavirus 2 rely on the host cell membrane to drastically bend and eventually let loose the replicated viruses trapped inside the cell. Scientists have used supercomputer simulations to help propose a mechanism for this budding off of viruses. What's more, a related study also used simulations to find a mechanism for how the DNA of all life adds a base to its growing strand during replication..

The study on cell membrane remodeling, important for viral reproduction, cell growth and communication, and other biological processes was published online in the Biophysical Journal in February 2020. The study co-author Qiang Cui also was part of a study on DNA base addition, published in the Proceedings of the National Academy of Sciences, December 2019. Qiang Cui is a professor in the Departments of Chemistry, Physics, and Biomedical Engineering, Boston University.

Cui is also the principal investigator on both studies for supercomputer time awarded through XSEDE, the Extreme Science and Engineering Discovery Environment funded by the National Science Foundation. "Supercomputers with massive parallelization are very much required to push the boundary of bimolecular simulations," Cui said.

His science team developed supercomputer simulations of the cell membrane, in particular filaments of the Vps32 protein, a major component of the endosomal sorting required for transport complex (ESCRT-III), which was the prime suspect for the driving force that causes the cell membrane to form buds in a process called membrane invagination. ESCRT proteins function in the cytosol, the liquid inside cells surrounding organelles, the cell subunits. They perform various jobs such as making organelles; sorting recyclable material in the cell and ejecting waste, and more.

Electron microscopy shows the Vps32 protein polymerizes, or assembles itself into a corkscrew shape during membrane invagination. The study authors sought to establish whether the atomistic forces inside Vps32 cause it to bend and twist, ultimately tugging and budding off the membrane. Unfortunately, experimental studies currently lack the resolution to characterize the protein-membrane interactions that lead to the membrane deformations.

The science team employed atomistic molecular dynamics simulations to investigate protein-protein interfaces in one-dimensional filament structures in solution and also to find the residues holding the filament together. They also studied the protein-membrane interface using a Vps32 trimer model.

"I think the most interesting observation is that the ESCRTIII polymer that we studied features a clear intrinsic twist," Cui said. "This suggests that twisting stress that accumulates as the polymer grows on the surface might play a major role in creating the three-dimensional buckling of the membrane. People focused more on the bending of the filament in the past."

"We also showed explicitly that the N-terminal helix does generate explicit curvature," Cui added. "People speculated about this before, since amphipathic helices are known to do so in other systems."

Amphipathic molecules contain both water-loving (hydrophilic) and water-hating (hydrophobic) parts. "Nevertheless, explicitly showing the curvature generated by atomistic forces is important because even more recent studies appear to argue that Vps32 alone is unable to generate membrane curvature," Cui said. The proposed mechanism supported by simulations basically involves initially dimpling and then pushing out of the membrane as the corkscrew Vps32 protein filament grows, eventually causing the neck of the membrane invagination.

Simulations of systems containing up to two million atoms posed a large hurdle for Cui and his colleagues. They applied for and were awarded supercomputing time through XSEDE, and completed their simulations on the Stampede2 system at the Texas Advanced Computing Center of UT Austin.

"Stampede2 has been crucial for us to set up these relatively large-scale membrane simulations," Cui said.

While this study is pure research, the knowledge gained could help benefit society. "Membrane remodeling is an important process that underlies many crucial cellular functions and events, such as synaptic transmission and virus infection. Understanding the mechanism of membrane remodeling will help propose new strategies for battling human diseases due to impaired membrane fusion activities -- or preventing viral infection -- a timely topic these days given the quick spread of the new coronavirus," Cui said.

Cui also co-authored a computational study that used supercomputer simulations to determine a chemical mechanism for the reaction of nucleotide addition, used in the cell to add nucleotide bases to a growing strand of DNA.

"By doing that, computationally, we are also able to determine the role of a catalytic metal ion of magnesium that's in the active site of the enzyme DNA polymerase," said study co-author Daniel Roston, an assistant project scientist in the Department of Chemistry and Biochemistry at UC San Diego. "This metal has been a bit controversial in the literature. Nobody was really sure exactly what it was doing there. We think it's playing an important catalytic role."

DNA polymerase adds the nucleotides guanine, adenine, thymine, cytosine (G-A-T-C) to DNA by removing a proton from the end of the growing strand through reaction with a water molecule. "When we say in the study that a water molecule serves as the base, it serves as a base to remove a proton, an acid base chemistry. What's left there after you remove the proton is much more chemically active to react with a new nucleotide that needs to be added to the DNA," Roston said.

The chemistry needs multiple proton transfers in a complex active site. Experimental probes using X-ray crystallography have been unable to distinguish among the many possible reaction pathways.

"Simulations offer a complement to crystallography because you can model in all the hydrogens and run molecular dynamics simulations, where you allow all the atoms to move around in the simulation and see where they want to go, and what interactions are helping them get where they need to go," Roston said. "Our role was to do these molecular dynamics simulations and test different models for how the atoms are moving around during the reaction and test different interactions that are helping that along."

The number of energy calculations needed to complete the molecular dynamics simulations was huge, on the order of 10e8 to 10e9 for the system with thousands of atoms and many complex interactions. That's because timesteps at the right resolution are on the order of femtoseconds, 10e-15 seconds.

"Chemical reactions, life, doesn't happen that quickly," Roston said. "It happens on a timescale of people talking to each other. Bridging this gap in timescale of many, many orders of magnitude requires many steps in your simulations. It very quickly becomes computationally intractable."

"One of the great things about XSEDE is that we can take advantage of a ton of computational power," Roston added. Through XSEDE, Roston and his colleagues used about 500,000 CPU hours on the Comet system at the San Diego Supercomputer Center. Comet allowed them to simultaneously run many different simulations that all feed off one another.

Said Roston: "DNA replication is what life is about. We're getting at the heart of how that happens, the really fundamental process to life as we know it on Earth. This is so important, we should really understand how it works at a deep level. But then, there are also important aspects of technology, such as CRISPR, that take advantage of this kind of work to develop systems to manipulate DNA. Understanding the details of how life has evolved to manipulate DNA will play a role in feeding our understanding and our ability to harness technologies in the future."

'Molecular simulation of mechanical properties and membrane activities of the ESCRT-III complexes' was published online in the journal Biophysical Journal in February 2020. The study co-authors are Taraknath Mandal and Qiang Cui of Boston University; Wilson Lough, Saverio E. Spagnolie, and Anjon Audhya of the University of Wisconsin-Madison. Study funding came from the National Science Foundation. Computations are also supported in part by the Shared Computing Cluster, which is administered by Boston University's Research Computing Services.

'Extensive free-energy simulations identify water as the base in nucleotide addition by DNA polymerase' was published in the Proceedings of the National Academy of Sciences in December 2019. The study co-authors are Daniel Roston of the University of California San Diego; Darren Demapan of the University of Wisconsin-Madison; and Qiang Cui of Boston University. Study funding came from the National Institutes of Health.

Flexible temporary electronic displays may one day make it possible to sport a glowing tattoo or check a reading, like that of a stopwatch, directly on the skin. In its current form, however, this technology generally depends on plastic. New research in ACS Nano describes a way to make these displays, which would likely be discarded after a single use, more environmentally friendly using a plentiful and biodegradable resource: fish scales.

Within such displays, electricity-conducting and light-emitting components are layered onto a transparent film. To make them flexible enough to withstand the bending required to stay on skin or other soft surfaces, researchers have so far relied on films made of plastic -- a substance derived from fossil fuels, a limited resource and a source of pollution. Hai-Dong Yu, Juqing Liu, Wei Huang and colleagues wanted to find a more sustainable and environmentally friendly material for the film. They settled on gelatin derived from collagen in fish scales, which are usually thrown away.

After preparing a gelatin solution from the fish scales, they poured it into a petri dish that acted as a mold for the film as it dried. In tests, they found the film had the attributes, including flexibility and transparency, needed for use in wearable devices. The film also appeared unlikely to linger in landfills: It dissolved within seconds in hot water and could then be recycled into a new film. When buried in soil, it degraded within 24 days. The team used the film to build a working alternating current electroluminescent device that continued to glow even after being bent and relaxed 1,000 times. Films derived from fish scales are a promising alternative for more sustainable flexible electronics, including wearables and folding displays, the researchers conclude.

March 18, 2020--Once-daily treatment of patients with chronic obstructive pulmonary disease (COPD) with an inhaler combining fluticasone furoate (FF), umeclidinium (UMEC) and vilanterol (VI) reduced all-cause mortality by 42 percent, according to new research published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

In "Reduction in All-Cause Mortality With Fluticasone Furoate/Umeclidinium/Vilanterol in COPD Patients," David A. Lipson, MD, and co-authors report on an expanded post hoc analysis of data from the multicenter, 37-country Phase 3 IMPACT trial, which includes additional vital status data from patients one year after the start of the study.

More than 10,000 IMPACT participants with COPD who were at risk for severe exacerbations (flare-ups) were randomized to be in one of three groups: those receiving once-daily inhalations of FF/UMEC/VI, FF/VI or UMEC/VI combinations. IMPACT participants were followed for one year. Fluticasone furoate is an inhaled corticosteroid, while umeclidinium is a long-acting muscarinic antagonist (a type of bronchodilator) and vilanterol is a long-acting ß2 agonist (another type of bronchodilator).

The initial IMPACT study showed that daily inhalation of FF/UMEC/VI led to more significant reductions in moderate/severe exacerbations and COPD hospitalizations, as well as improved lung function and health-related quality of life than the two dual combination therapies. The study also showed patients on triple therapy had lower death rates than those on VI/UMEC.

Data from 5.5 percent of participants were removed from the one-year analysis, however, because some investigators did not report vital status data for all-cause mortality at the end of the study. This new analysis includes vital status data for 99.6 percent of IMPACT participants.

"Because the number of missing patients exceeded the numbers of deaths in the study we felt caution was warranted in the interpretation of the original published findings," said Dr. Lipson, senior director, clinical sciences, GlaxoSmithKline and adjunct associate professor of medicine, Perelman School of Medicine, University of Pennsylvania. "Given the importance of this finding for patients and physicians we undertook a global collection of the missing data at week 52. These new repeat analyses demonstrate the robustness of the original finding. We have concluded that we can improve survival in symptomatic patients with COPD at risk of exacerbation."

The study focused on patients with a history of exacerbations of their COPD.

Dr. Lipson added, "We believe that the mortality finding with FF/UMEC/VI compared to UMEC/VI was primarily driven by the steroid component and its effect on reducing exacerbations, especially hospitalized exacerbations. Frequently exacerbating patients are at higher risk of hospitalization and death. These are the patients who appear to achieve the greatest survival benefit with once-daily FF/UMEC/VI triple therapy."

No previous study has prospectively demonstrated that drug therapy can reduce all-cause mortality in people with COPD. Major studies done prior to IMPACT suggested mortality reductions, but were not able to prove this with certainty.

A research team from ITMO University, with the help of their colleagues from MIPT (Russia) and Politecnico di Torino (Italy), has predicted a novel type of topological quantum state of two photons. Scientists have also applied a new, affordable experimental method for testing this prediction. The method relies on the analogy: instead of expensive experiments with quantum systems of two or more entangled photons, the researchers have used resonant electric circuits of higher dimensionality described by similar equations. The obtained results can be useful for the engineering of optical chips and quantum computers without the need for expensive experiments. The research was published in Nature Communications.

Light plays a key role in modern information technologies: with its help, information is transmitted over large distances via optical fibers. In the future, scientists anticipate the invention of optical chips and computers that process information with the help of photons - light quanta - instead of electrons, as it is done today. This will decrease energy consumption, while also increasing the capabilities of computers. However, to turn these predictions into reality, fundamental and applied research of light behavior at the micro- and nanoscale is needed.

ITMO University physicists, with the help of their colleagues from the Moscow Institute of Physics and Technology (Russia) and Politecnico di Torino (Italy), have theoretically predicted the formation of a new quantum state of photons: two photons propagating in the array of quantum microresonators (qubits) can form a bound pair and settle down on the edge of the array. A proper experiment demands special nanostructures, as well as special devices to create such quantum state of photons and detect it. Currently, such capabilities are available only to very few research teams worldwide.

If conducting a precise experiment is too expensive, it may be useful to come up with a model, or an analogy, which would allow one to test the theoretical assumptions without spending too many resources. This is exactly what ITMO University physicists managed to do. They have drawn an analogy between a specific class of quantum systems and classical electric circuits of higher dimensionality.

"We connect various points on the board to an external power source and study the system's response using a multimeter and oscilloscope," explains Nikita Olekhno, PhD student at ITMO University. "The result is described by classical equations that in our case coincide with the quantum equations describing two-photon states in the array of qubits. The same equations must have the same solutions, and it doesn't matter whether it's a wave function of a quantum particle or an electric potential."

Of course, the analogy that ITMO University scientists have come up with can not entirely replace experiments with quantum systems. However, the classical structure that was developed by the team allows researchers to conduct many experiments, providing valuable information for the field of quantum photonics. The fact that the scientists from St. Petersburg managed to find such an analogy for quantum systems of many particles for the first time is very promising.

"Theory is always ahead of experimental capabilities. To be at the forefront of theory, we study subtle effects that we will be able to detect experimentally only in several years," says Maxim Gorlach, head of the project and Senior Researcher at ITMO University. "We are currently conducting a series of experiments in this field by researching topological edge states of more exotic quantum systems and developing ways of their emulation. Such experiments are important both for fundamental physics and future practical applications."

Colorectal carcinoma (CRC), the most common form of intestinal cancer, is the second leading cause of cancer related death worldwide. While some patients have a genetic predisposition to the disease, the majority of cases are sporadic and largely influenced by the ever-increasing "Western lifestyle", which includes obesity, poor diet and physical inactivity.

A recently published study now sheds new light on how this disease develops: Through the use of genetically modified mice, an international team of researchers was able to demonstrate that the protein MCL1 is essential for maintaining intestinal homeostasis and thus protecting against intestinal cancer formation. The research project was led by Achim Weber, professor at the Institute of Molecular Cancer Research at the University of Zurich and at the Institute of Pathology and Molecular Pathology of the University Hospital Zurich, in collaboration with researchers from the German Cancer Research Center in Heidelberg and the Beatson Institute in Glasgow, Scotland.

MCL1 protein protects the intestine against cancer

For their study, the researchers modified the genetic makeup of mice so that the animals' intestinal cells would no longer produce the MCL1 protein. This protein normally prevents the death of cells and thus maintains the right balance of dying and new cells in the intestinal mucosa. The loss of MCL1 resulted in irreparable damage to the intestine and the subsequent formation of intestinal tumors. Similar changes can also be observed in the intestine of humans suffering from chronic intestinal inflammation, who also carry an elevated risk of developing intestinal cancer.

Tumors also develop without bacterial-driven inflammation

Microbiota-driven chronic intestinal inflammation has long been considered essential in the development of intestinal cancer. "What's remarkable, however, is that the loss of MCL1 can drive intestinal cancer even without bacteria-driven inflammation," says Weber. This was demonstrated by experiments in which mice without the MCL1 protein were held in a germfree environment. "This means that the loss of certain genes is apparently enough to cause intestinal cancer - even in the absence of inflammation. This groundbreaking finding significantly furthers our understanding of the critical early steps associated with intestinal cancer development," says Weber.

Treating cancer with MCL1 inhibitors is like walking a tightrope

This study also reveals a second surprising result: In some types of tumor - including colorectal carcinoma - there is too much MCL1, rather than too little. Researchers assume that these tumors ramp up the production of MCL1 to gain an advantage for survival and enable them to better resist conventional treatment methods. As a result, a number of new therapies are currently being trialled to interfere with and reduce MCL1 function.

However, the study's findings show that not only the overexpression, but also the loss of MCL1 can be detrimental. It is possible that the loss of MCL1 function - even only temporarily - may trigger a disturbance of the intestinal mucosa and the initial steps of tumor development. "The regulation of this protein is like walking a tightrope," warns Marc Healy, first author of the study. "Our study therefore urges an element of caution when it comes to using MCL1 inhibition in cancer therapy."

A single x-ray can unravel an enormous molecule, physicists report in the March 17 issue of Physical Review Letters. Their findings could lead to safer medical imaging and a more nuanced understanding of the electronics of heavy metals.

Medical imaging techniques such as MRIs use heavy metals from the bottom of the periodic table as "dyes" to make certain tissues easier to see. But these metals, called lanthanides, are toxic. To protect the person getting the MRI, some chemists wrap the lanthanide inside a cage of carbon atoms.

Molecular physicist Razib Obaid and his mentor, Prof. Norah Berrah in the physics department, wanted to know more about how the lanthanides interact with the carbon cages they're wrapped in. The cages, 80 carbon atoms strong, are called fullerenes and are shaped like soccer balls. They don't actually bond to the lanthanide; the metal floats inside the cage. There are many similar situations in nature. Proteins, for example, often have a metal hanging out close to a giant organic (that is, mostly made of carbon) molecule.

So Obaid and his team of collaborators from Kansas State University, Pulse Institute at Stanford, Max Planck Institute at Heidelberg, and the University of Heidelberg studied how three atoms of the lanthanide element holmium inside of an 80-carbon fullerene reacted to x-rays. Their initial guess was that when an x-ray first hit one of the holmium atoms, it would get absorbed by an electron. But that electron would be so energized by the absorbed x-ray that it would fly right out of the atom, leaving a vacant spot. That spot would than get taken by another of the holmium's electrons, which would have to jump down from the outer edge of the atom to fill it. That electron had formerly been partnered with another electron on the outskirts of the atom. When it jumped down, its lonely ex, called an Auger electron, would zoom away from the whole molecule and get detected by the scientists. Its distinctive energy would give it away.

It sounds complicated, but that would have been the simplest (and thus most likely) scenario, the physicists thought. But it's not what they saw.

When Obaid and his colleagues zapped the holmium-fullerene molecule with a soft x-ray (about 160 electron-volts), the number of the Auger electrons detected was too low. And too many of the electrons had energies much less than the Auger electrons should have.

After some calculating, the team figured out there was more going on than they'd guessed.

First, the x-ray would hit the holmium, which would lose an electron. The vacant spot would then be filled by the outer edge electron from the holmium atom. That much was correct. But the energy released by the jumping electron (when it jumps 'down' from the outskirts of the atom to the interior, it also jumps 'down' in energy) would then be absorbed by the carbon fullerene cage or another of the neighboring holmium atoms. In either case, the energy would cause an additional electron to zoom away from whatever absorbed it, the fullerene cage or the holmium atom.

Losing these multiple electrons destabilized the whole molecule, which would then fall apart entirely.

The end result?

"You can induce radiation damage just by striking one atom out of 84," says Obaid. That is, a single x-ray strike is enough to destroy the entire molecule complex through this energy transfer process involving neighboring atoms. It gives some insight into how radiation damage occurs in living systems, Obaid says. It was always thought that radiation damaged tissue by stripping away electrons directly. This experiment shows that interactions between an ionized atom or molecule and its neighbors can cause even more damage and decay than the original irradiation.

The work also gives medical physicists an idea of how to limit patients' exposure to heavy metals used as dyes in medical imaging. Shielding all parts of the body from the radiation except for those to be imaged with heavy metal dyes can potentially restrict the heavy metal exposure as well as the radiation damage, the researchers say. The next step of this work would be to understand exactly how fast this interaction with the neighbors occurs. The researchers expect it to take place in just a few femtoseconds.

Some intriguing physics can be found at the interfaces between fluids, particularly if they are straddled by particles like proteins or dust grains. When placed between un-mixable fluids such as oil and water, a variety of processes, including inter-molecular interactions, will cause the particles to move around. These motions are characterised by the drag force experienced by the particles, which is itself thought to depend on the extent to which they distort fluid interfaces. So far, however, experiments investigating the intriguing effect haven't yet fully confirmed the influence of this distortion. In new research published in EPJ E, a team led by Jean-Christophe Loudet at the University of Bordeaux, France, showed that the drag force experienced by fluid-straddling particles is less affected by interface distortion than previously believed.

Since drag forces are ubiquitous in fluids, the team's discovery could be relevant to the self-assembling properties of a great variety of species which can stick, or 'adsorb' to liquid surfaces, including nano- and microparticles, proteins, and other groups of molecules. For the relatively large particles investigated by Loudet and colleagues, interfacial distortions arise from the buoyant weight of straddling particles. This force produces curved menisci in both fluids, similar to the curves found on the surface of water as it touches a glass.

In their study, the researchers approached this problem numerically using techniques for simulating multi-phase flows, capable of accurately describing how the interfacial dynamics were coupled to flows in the bulk of each fluid. This allowed them to explore how drag forces are affected by interface deformations, which depend on factors including the densities of the two fluids and the particle, and the contact angles between the three substances. Loudet's team revealed that for some values of these parameters, large drag forces don't necessarily correspond to large interfacial distortions, and that lower drag forces can even be reached through non-flat distortions.

Showy peacock feathers, extravagant elk antlers and powerful crayfish claws are just a few examples of the ostentatious animal extremes used to compete for and attract mates, a process called sexual selection.

Now, thanks to Arizona State University researcher Zackary Graham and his colleagues, we can add the "unicorn of the seas," the narwhal, to the list.

"Broadly, I'm interested in sexual selection, which is responsible for creating some of the craziest traits in biology. As an evolutionary biologist, I try to understand why some animals have these bizarre traits, and why some don't," said Graham, a doctoral student at ASU's School of Life Sciences.

"One way we try to understand these traits is by looking at the morphology, or the size and shape of them. I immediately became obsessed with trying to think of some interesting animals to study. I was Googling everything; maybe I can find a dinosaur in a museum. Eventually, I found the narwhal tusk."

Graham is the lead author of a new study which demonstrates the best evidence to date that the narwhal tusk functions as a sexual trait, published in online in the journal Biology Letters DOI: http://dx.doi.org/10.1098/rsbl.2019.0950 or URL
https://royalsocietypublishing.org/doi/10.1098/rsbl.2019.0950

A tusk among us

Like walruses and elephants, male narwhals (Monodon monoceros) grow tusks; these are modified teeth. In narwhals, the left tooth erupts from their head, reaching more than 8-feet-long in some individuals. The tusk grows out in a spiral pattern, giving the appearance of a sea-dwelling unicorn.

Since narwhals spend most of their lives hidden under the Arctic ice, there has been much speculation on what exactly the tusk is used for: hunting, fighting or perhaps something more amorous in nature?

Graham mentions that there have been reports of head scarring, broken tusks and tusks impaled in the sides of males, who may have been on the receiving end of some aggression. Other scattered observations include a behavior of "tusking," where two narwhals cross and rub their tusks together, suggests that the tusk is used for communication during intra- or intersexual interactions.

Graham has studied sexual selection in all sorts of species, including the crayfish he studies for his PhD dissertation. He realized, that to demonstrate that the tusk is sexually selected, he could use the relationship between tusk size with body size to understand this mysterious trait. To do so, his team collected morphology data on 245 adult male narwhals over the course of 35 years.

With colleagues Alexandre V. Palaoro of the LUTA do Departamento de Ecologia e Biologia Evolutiva, UNIFESP, Brazil, and Mads Peter Heide-Jørgensen and Eva Garde, from the Greenland Institute of Natural Resources, they created a large dataset from the carefully curated narwhal field data.

When comparing individuals of the same age, sexually selected traits often exhibit disproportional growth --- that is, for a given body size, sexually selected traits are often larger than expected in the largest individuals. Importantly, they compared the growth (or scaling) of the tusk to the scaling relationship between body size and a trait that is unlikely to have sexual functions. To do so, they used the tail of the narwhals, called the fluke.

"We also predicted that if the narwhal tusk is sexually selected, we expect greater variation in tusk length compared to the variation in fluke width," said Graham. This is because many sexual traits are highly sensitive to nutrient and body condition, such that only the biggest and strongest individuals can afford the energy to produce extremely large traits.

According to Graham, they found that male tusks can have over 4-fold variation in tusk length (the same body size males can have tusks ranging from 1.5-feet to 8.2-feet) long. However, the fluke hardly varies at all, ranging from 1.5-feet to 3-feet long within individuals of the same body size. They also found disproportional growth in the tusk compared to the fluke. Based on the disproportional growth and large variation in tusk length they found, they have provided the best evidence to date that narwhal tusks are indeed sexually selected.

"By combining our results on tusk scaling with known material properties of the tusk, we suggest that the narwhal tusk is a sexually selected signal that is used during the male-male tusking contests," said Graham. "The information that the tusk communicates is simple: "I am bigger than you.""

And if only the highest quality males produce and adorn the largest tusks, then the tusk likely serves as an honest signal of quality to females or males.

Under the Ice

Graham hopes that future researchers will use aerial and aquatic drones to provide concrete evidence of the tusk function in nature and elucidate the tusks exact role as either an aggressive weapon, a sexual signal or both.

Perhaps one day, we can look forward to a "Big Love: Narwhals Under the Ice" nature documentary coming to an IMAX near you.

"Overall, our evidence supports the hypothesis that the tusk functions both as a sexually selected weapon and sexually selected signal during male-male contests," said Graham. "However, further evaluations of the narwhal's ecology are warranted."

An independent investigative agency as well as an international offender database are needed to tackle allegations of abuse in elite youth sport properly, urges an expert, in an editorial published online in the British Journal of Sports Medicine.

Much is being done to protect young athletes, but "there are still significant gaps," contends Dr Margo Mountjoy, of McMaster University, Canada, and member of the International Olympic Committee Working Group on the Prevention of Harassment and Abuse in Sport.

She cites the case of Mary Cain as an exemplar of unhealthy practices in elite youth sport.

Cain was a star performer at the age of 17 when she joined Nike's Oregon Project, a training centre to promote long distance running.

But Cain was constantly harried to lose more and more weight to boost her performance and ended up with major health problems. She went public last year with allegations of physical and psychological abuse at the hands of her coach, Alberto Salazar.

"Mary Cain's story demonstrates a culture where the sport leadership of Nike's Oregon Project failed to protect their female athletes," points out Dr Mountjoy. "Cain reported that there was no qualified sport-specific physician, physiologist, dietician or psychologist available, nor an independent safeguarding officer to hear her concerns."

Salazar has subsequently apologised and Nike has stated that it has investigated the allegations and stepped up support for women athletes.

But abuse in elite youth sport isn't just an issue for Nike leadership, contends Dr Mountjoy. It's an issue for the media, society in general, and women's sport, she says, referring to the widespread sexual abuse of US female gymnasts by Dr Larry Nassar, which came to light in 2018.

"Abuse is nurtured in a sport culture where athletes are commodified in an environment that pursues 'winning at all costs': one in which athletes have no power, and where abuse is either accepted as being normal or is ignored," she writes.

She lists a commendable array of international programmes, initiatives, and policies, designed to protect athletes from abuse. But adds: "While much is being done in the field of athlete safeguarding, there are still significant gaps."

She calls for the establishment of an independent international safeguarding agency for sports, to handle athlete disclosures, investigate and process allegations, and to support victims of abuse. The expertise developed could then be used for preventive efforts, she suggests. But this agency would have to have sufficient cash and clout to be effective, she insists.

An international database of offenders should also be set up, she says. This would stop "perpetrator migration" to new sport organisations, and athletes charged with misconduct from competing elsewhere.

This has happened in the National Collegiate Athletes Association (NCAA), where 33 athletes, charged with sexual offences since 2014, have managed to transfer to other colleges, she explains.

"Together we must act to stop the victimisation of youth elite athletes from abusive coaching practices. From Mary Cain's story, we know what the problem is. We should strive to achieve a safe sporting environment for all," she concludes.

The observed 'gateway' effect of e-cigarette use among teens is "likely to be small," with only a tiny proportion of experimental vapers going on to smoke regular cigarettes, suggests research published online in the journal Tobacco Control.

If anything, young vapers are less likely to go on to smoke regular cigarettes than their peers who try out other tobacco products first, the findings indicate.

The potential 'gateway' impact of e-cigarettes on teen smoking uptake has been hotly contested. And several studies have linked teen vaping to a heightened risk of smoking.

But, importantly, most of these studies have looked only at initial uptake, and not continued use, say the researchers. And for obvious reasons, no clinical trials can actually test whether e-cigarette use inevitably leads to smoking.

To try and produce a more nuanced analysis of the issues, the researchers compared first experimentation with different types of tobacco products among nearly 40,000 US teens, using responses to the National Youth Tobacco Survey for 2014-17.

The teens were asked if they had ever tried a cigarette, even if it was only a puff or two. Those who said yes, were classified as ever smokers; those who had smoked at least one cigarette in the past 30 days were classified as such; while those who had smoked more than 100 cigarettes to date were classified as established smokers.

Teens in each of these groups who had tried e-cigarettes first were compared with those who had first used other combustible tobacco products, such as cigars, cigarillos, hookahs, or pipes, and those who had first used non-combustible tobacco products, such as snuff and chewing tobacco.

The three groups of smokers who had first tried e-cigarettes were then matched with teens with similar social, demographic, and behavioural characteristics, including vulnerability to taking up smoking, but who hadn't tried e-cigarettes first.

This was done, using a statistical technique (PSM), which mimics some of the features of a clinical trial and reduces the influence of other potentially important factors.

The most common 'starter' product was cigarettes, the findings showed, followed by other combustibles, e-cigarettes, and non-combustibles. This is despite e-cigarettes being more frequently used than any other product from 2015 onwards, point out the researchers.

Girls were less likely than boys to have tried any product, but, overall, the likelihood of experimentation rose with increasing age.

Compared with those who first used tobacco alternatives to cigarettes, those who first tried e-cigarettes were less likely to have ever smoked cigarettes.

Less than 1% of teens who tried e-cigarettes became established smokers, a proportion that was significantly smaller than any other category.

The conversion rate from ever to established smoking was much lower for teens who tried e-cigarettes first: 2.7%, which compares with 9% for combustible product first timers and almost 16% for non-combustible product first timers. These findings were backed up by the PSM analysis.

What's more, "the association of subsequent use of e-cigarettes was stronger for adolescents initiating with cigarettes than the association of subsequent cigarette smoking for e-cigarette initiators," write the researchers.

"This underlines the fact that cigarettes act as a much more important gateway for any product use," they explain.

This is an observational study, and as such, can't establish cause, added to which not all factors that might have potentially influenced the findings, such as behaviour and mental health issues, were accounted for.

Nevertheless, the findings of their analysis lead the researchers to conclude: "This suggests that, over the time period considered, e-cigarettes were unlikely to have acted as an important gateway towards cigarette smoking, and may, in fact, have acted as a gateway away from smoking for vulnerable adolescents....The postulated gateway effect is likely to be small."

UNIVERSITY PARK, Pa. -- Pesticide-coated seeds -- such as neonicotinoids, many of which are highly toxic to both pest and beneficial insects -- are increasingly used in the major field crops, but are underreported, in part, because farmers often do not know what pesticides are on their seeds, according to an international team of researchers. The lack of data may complicate efforts to evaluate the value of different pest management strategies, while also protecting human health and the environment.

"We reviewed existing evidence, as well as proprietary and novel government data, on seed treatment usage and found that many farmers either did not know what pesticides were on their seeds or falsely assumed that seed treatments did not include certain pesticides," said Paul Esker, assistant professor of epidemiology and crop pathology, Penn State. "This lack of knowledge could lead to overuse of pesticides, which could harm the environment and farmers' health."

The team analyzed proprietary data from Kynetec, a third-party global marketing and research firm that maintains one of the most comprehensive datasets on pesticide use in the United States, collected from 2004-2014. They found that the use of seed treatments in the U.S. grew over the past decade, particularly in corn and soybean production. In the 2012 to 2014 period, 90 percent of corn acres and 76 percent of soybean acres were grown with treated seeds. Of the insecticides applied to seeds, neonicotinoids accounted for roughly 80%.

Next, the researchers analyzed farmers' responses to questions about pesticide-coated seeds documented in the Agricultural Resource Management Survey (ARMS) -- the U.S. Department of Agriculture's primary source of information on the production practices, resource use and economic well-being of America's farms and ranches. Specifically, they examined farmer responses to the ARMS for cotton in 2015, corn in 2016, wheat in 2017 and soybean in 2018.

They found that around 98% of farmers were able to provide the names of the field-applied pesticides used on their cotton, corn, wheat or soybean crops. By contrast, only 84% of cotton growers, 65% of corn growers, 62% of soybean growers, 57% of winter wheat growers and 43% of spring wheat growers could provide the name of the seed-treatment product on their crops. The rest either did not answer the survey question or specified that they did not know.

The researchers also found that, in 2015, cotton growers reported that 13% of total acreage was not treated with an insecticide and 19% was not treated with a fungicide, while simultaneously reporting the use of products containing those types of pesticides on that acreage.

The results appear today (March 17) in the journal BioScience.

"One of the most important findings of this study is that farmers know less about pesticides applied to their seeds than pesticides applied in other ways," said Margaret Douglas, assistant professor of environmental studies, Dickinson College. "This is likely because seed is often sold with a 'default' treatment that contains a mix of different pesticide active ingredients, and the treated seed is exempt from some labeling requirements. Without knowing what is on their seeds, it is nearly impossible for farmers to tailor pesticide use to production and environmental goals."

According to the study's lead author Claudia Hitaj, research and technology associate, Luxembourg Institute of Science and Technology, the lack of information on the use of pesticidal seed treatments means that a significant portion of pesticide use, particularly for active ingredients that are applied almost exclusively as seed treatments, is not captured in existing pesticide-use datasets.

"Reliable data on pesticide use is needed by regulators, farmers, and researchers to increase agricultural production and profitability and to protect human health and the environment from the adverse effects of pesticides," she said.

By comparing the data Kynetec collected during the 2004-2014 window to that collected in 2015, when Kynetec stopped offering information on seed treatments, the team found a significant drop in pesticide use for a number of pesticides known to be used as seed treatments. The researchers used clothianidin as an example of what can happen as a result of poor tracking of pesticide-treated seed use.

"The removal of data on treated seed makes clothianidin use appear to drop from more than 1.5 million kg/year in 2014 to less than a tenth of a million kg/year in 2015," said Aimee Code, pesticide program director, Xerces Society for Invertebrate Conservation. "Clothianidin is currently undergoing review by the U.S. Environmental Protection Agency, so the lost data makes it difficult to ensure accurate risk assessment."

The team concluded that farmers, researchers and regulators could benefit from improved labelling of pesticide-treated seeds and posting of information about the active ingredients contained in treated seed products on public websites. In addition, information could be collected through sales data from seed retailers and other companies. And information about the planting location of treated seeds could help in assessing pest resistance and the local effects of pesticides on the environment.

"The lack of knowledge by farmers about the pesticides applied to seed is an example of why it is important to maintain a strong university extension system that can provide up-to-date information about different seed treatments, what these treatments do, and what the empirical data shows," said Esker. "This is also an opportunity for further collaboration among different disciplines, like agronomy, plant pathology, entomology, economics and environmental science, to address farm issues from a whole-system perspective."