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Tuesday, 12 May 2020

Stem cells shown to delay their own death to aid healing


Already known for their shape-shifting abilities, stem cells can now add "death-defying" to their list of remarkable qualities.

A new study shows how stem cells - which can contribute to creating many parts of the body, not just one organ or body part - are able to postpone their own death in order to respond to an injury that needs their attention. The study was done in planarians, which are tiny worms used as model organisms to study regeneration because of their ability to recover from any injury using stem cells.

"Planarian stem cells, even when challenged and under a lot of duress, will still respond to an injury by delaying death," said Divya Shiroor, first author and a graduate student in Dr. Carolyn Adler's lab, in the College of Veterinary Medicine.



The study, published May 7 in Current Biology, is the first to demonstrate this reaction in planarians.

The research team exposed planarians to radiation, then subjected half of them to injury. Radiated worms that had not been injured experienced predicted levels of stem cell death. Stem cells of the injured worms, however, survived, gathering around the site of the wound and postponing their deaths to mount a response.

"We show that this inevitable radiation-induced cell death can be significantly delayed if animals are injured soon after radiation exposure," said Shiroor.

This could have important implications for cancer research and therapies, particularly when examining chemotherapy and surgery options for patients.

"By understanding how injury prompts planarian stem cells to withstand radiation," Shiroor said, "we hope to identify genes that, if shared with mammals, could perhaps help hone existing therapies."

Planarians are commonly used in basic research because of their similarities to humans. Like humans, planarians have stem cells, similar organs and similar genes, but are much more adept at responding to injury, thanks to their higher volume of stem cells and lack of a developed immune system, which in humans complicates the healing process.

"This really simplifies the process of understanding the effects of both injury and radiation on stem cells, and allows us to study it directly without being hampered by parallel processes integral to wound healing, such as inflammation, that get simultaneously triggered in mammals," Shiroor said.

By uncovering the mechanisms that govern stem cells after wounding in a system like planarians, researchers could also apply this knowledge when engineering stem cells to respond similarly in the human body.



Labs have many ways to understand how planarians use stem cells to successfully recover and regenerate, but the Adler lab's combination of radiation and injury to identify a novel stem cell response is unique. The researchers plan on digging deeper to understand how the stressed stem cells know that there is an injury and what role other cells may play in their response.

"We have identified a key gene that is required for stem cell persistence after radiation and injury," Shiroor said, "and we plan on using this as a stepping stone for further exploration."


Bibliography:

Shiroor, D. A., Bohr, T. E., & Adler, C. E. (2020).

Injury Delays Stem Cell Apoptosis after Radiation in Planarians.

Current Biology.

doi: 10.1016/j.cub.2020.03.054

Monday, 11 May 2020

Chemistry breakthrough could speed up drug development



Scientists have successfully developed a new technique to reliably grow crystals of organic soluble molecules from nanoscale droplets, unlocking the potential of accelerated new drug development.

Chemistry experts from Newcastle and Durham universities, working in collaboration with SPT Labtech, have grown the small crystals from nanoscale encapsulated droplets. Their innovative method, involving the use of inert oils to control evaporative solvent loss, has the potential to enhance the drug development pipeline.

Whilst crystallization of organic soluble molecules is a technique used by scientists all over the world, the ability to do so with such small quantities of analyte is ground-breaking.




Through the use of this new method, called Encapsulated Nanodroplet Crystallisation (ENaCt), the researchers have shown that hundreds of crystallisation experiments can be set up within a few minutes. Each experiment involves a few micrograms of molecular analyte dissolved in a few nanolitres of organic solvent and is automated, allowing for rapid set up of hundreds of unique experiments with ease. Concentration of these nanodroplet experiments results in the growth of the desired high quality single crystals that are suitable for modern X-ray diffraction analysis.

Publishing their findings in the journal Chem, the team, led by Drs Hall and Probert, of Newcastle University, UK, successfully developed a new approach to molecular crystallisation which allows access, within a few days, to high quality single crystals, whilst requiring only few milligrams of analyte.

Dr Hall, Senior Lecturer in Chemistry, Newcastle University, said: "We have developed a nanoscale crystallisation technique for organic-soluble small molecules, using high-throughput liquid-handling robotics to undertake multiple crystallisation experiments simultaneously with minimal sample requirements and high success rates.

"This new method has the potential to have far-reaching impact within the molecular sciences and beyond. Fundamental research will benefit from highly detailed characterisation of new molecules, such as natural products or complex synthetic molecules, by X-ray crystallography, whilst the development of new drugs by the pharmaceutical industry will be accelerated, through rapid access to characterised crystalline forms of new active pharmaceutical ingredients."

Understanding these new crystalline forms, known as polymorphs, is essential to the successful generation of new pharmaceutical agents and drugs. The ability to investigate these forms quickly and on a vast scale, whilst minimising the amount of analyte required, could be a key

Breakthrough enabled by the new ENaCT protocol.

Dr Paul Thaw from SPT Labtech, added: "Enabling this work to develop a novel high-throughput method for single crystal X-ray diffraction on mosquito® with the Newcastle team has been a pleasure. Having the ability to quickly screen organic soluble small molecules on the microgram scale will deliver valuable insight for both academic research and pharmaceutical drug design and validation."



Dr Probert, Senior Lecturer in Inorganic Chemistry and Head of Crystallography, Newcastle University, commented ." ..this new approach to crystallisation has the ability to transform the scientific landscape for the analysis of small molecules, not only in the drug discovery and delivery areas but also in the more general understanding of the crystalline solid state ..."

The whole team believe that the ENaCt methodology has the potential rewrite some of the preconceptions within the molecular sciences and beyond.


Bibliography:

Andrew R. Tyler, Ronnie Ragbirsingh, Charles J. McMonagle, Paul G. Waddell, Sarah E. Heaps, Jonathan W. Steed, Paul Thaw, Michael J. Hall, Michael R. Probert.

Encapsulated Nanodroplet Crystallization of Organic-Soluble Small Molecules. 

Chem, 2020;

DOI: 10.1016/j.chempr.2020.04.009

Sunday, 10 May 2020

Study: Could Dark Matter Be Hiding in Existing Data?



Dark matter has so far defied every type of detector designed to find it. Because of its huge gravitational footprint in space, we know dark matter must make up about 85 percent of the total mass of the universe, but we don’t yet know what it’s made of.

Several large experiments that hunt for dark matter have searched for signs of dark matter particles knocking into atomic nuclei via a process known as scattering, which can produce tiny flashes of light and other signals in these interactions.

Now a new study, led by researchers at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) and UC Berkeley, suggests new paths for catching the signals of dark matter particles that have their energy absorbed by these nuclei.



The absorption process could give an affected atom a kick that causes it to eject a lighter, energized particle such as an electron, and it might produce other types of signals, too, depending on the nature of the dark matter particle.

The study focuses mostly on those cases where an electron or neutrino is ejected as the dark matter particle strikes an atom’s nucleus.

Published May 4 in Physical Review Letters, the study proposes that some existing experiments, including ones that search for dark matter particles and processes related to neutrinos – ghostly, detectable particles that can pass through most matter and have the ability to change into different forms – can easily be broadened to also look for these absorption-related types of telltale dark matter signals.

Also, the researchers propose that new searches in previously collected particle detector data could possibly turn up these overlooked dark matter signals.

“In this field, we’ve had a certain idea in mind about well-motivated candidates for dark matter, such as the WIMP,” or weakly interacting massive particle, said Jeff Dror, the lead author of the study who is a postdoctoral researcher in Berkeley Lab’s Theory Group and UC Berkeley’s Berkeley Center for Theoretical Physics.

Photomultiplier tube arrays are prepared for the WIMP-hunting LUX-ZEPLIN experiment during assembly at the Sanford Underground Research Facility in Lead, South Dakota. (Credit: Matt Kapust/SURF)

Dark matter pushes at the boundaries of the known fundamental laws of physics, encapsulated in the Standard Model of particle physics, and “The WIMP paradigm is very easy to build into the Standard Model, but we haven’t found it for a long time,” Dror noted.

So, physicists are now considering other places that dark matter particles may be hiding, and other particle possibilities such as theorized “sterile neutrinos” that could also be brought into the family of particles known as fermions – which includes electrons, protons, and neutrinos.

“It’s easy, with small modifications to the WIMP paradigm, to accommodate a whole different type of signal,” Dror said. “You can make a huge amount of progress with very little cost if you step back a little bit in the way we’ve been thinking about dark matter.”

Robert McGehee, a UC Berkeley graduate student, and Gilly Elor of the University of Washington were study co-authors.

The researchers note that the range of new signals they are focusing on opens up an “ocean” of dark matter particle possibilities: namely as-yet-undiscovered fermions with masses lighter than the typical range considered for WIMPs. They could be close cousins of sterile neutrinos, for example.

The study team considered absorption processes known as “neutral current,” in which nuclei in the detector material recoil, or get jolted by their collision with dark matter particles, producing distinct energy signatures that can be picked up by the detector; and also those known as “charged current,” which can produce multiple signals as a dark matter particle strikes a nucleus, causing a recoil and the ejection of an electron.

The charge current process can also involve nuclear decay, in which other particles are ejected from a nucleus as a sort of domino effect triggered by the dark matter absorption.

This chart shows the sensitivity range to charged current signals by a variety of experiments. (Credit: Jeff A. Dror, Gilly Elor, and Robert McGehee)

Looking for the study’s suggested signatures of both the neutral current and charge current processes could open up “orders of magnitude of unexplored parameter space,” the researchers note. They focus on energy signals in the MeV, which means millions of electron volts. An electron volt is a measure of energy that physicists use to describe the masses of particles. Meanwhile, typical WIMP searches are now sensitive to particle interactions with energies in the keV range, or thousands of electron volts.

For the various particle interactions the researchers explored in the study, “You can predict what is the energy spectrum of the particle coming out or the nucleon that’s getting the ‘kick,'” Dror said. Nucleon refers to the positively charged proton or uncharged neutron that resides in an atom’s nucleus and that could absorb energy when struck by a dark matter particle. These absorption signals could possibly be more common than the other types of signals that dark matter detectors are typically designed to find, he added – we just don’t know yet.

Experiments that have large volumes of detector material, with high sensitivity and very low background “noise,” or unwanted interference from other types of particle signals, are particularly suited for this expanded search for different types of dark matter signals, Dror said.

LUX-ZEPLIN (LZ), for example, an ultrasensitive Berkeley Lab-led dark matter search project under construction in a former South Dakota mine, is a possible candidate as it will use about 10 metric tons of liquid xenon as its detector medium and is designed to be heavily shielded from other types of particle noise.

The EXO-200 time projection chamber during assembly. (Credit: EXO-200 collaboration)

Already, the team of researchers participating in the study has worked with the team operating the Enriched Xenon Observatory (EXO), an underground experiment searching for a theorized process known as neutrino-less double beta decay using liquid xenon, to open up its search to these other types of dark matter signals.

And for similar types of experiments that are up and running, “The data is already basically sitting there. It’s just a matter of looking at it,” Dror said.

The researchers name a laundry list of candidate experiments around the world that could have relevant data and search capabilities that could be used to find their target signals, including: CUORE, LZ predecessor LUX, PandaX-II, XENON1T, KamLAND-Zen, SuperKamiokande, CDMS-II, DarkSide-50, and Borexino among them.



As a next step, the research team is hoping to work with experiment collaborations to analyze existing data, and to find out whether search parameters of active experiments can be adjusted to search for other signals.

“I think the community is starting to become fairly aware of this,” Dror said, adding, “One of the biggest questions in the field is the nature of dark matter. We don’t know what it is made out of, but answering these questions could be within our reach in the near future. For me, that’s a huge motivation to keep pushing – there is new physics out there.”


Bibliography:

Jeff A. Dror, Gilly Elor, Robert McGehee.

Directly Detecting Signals from Absorption of Fermionic Dark Matter.

Physical Review Letters, 2020; 124 (18)

DOI: 10.1103/PhysRevLett.124.181301

Saturday, 9 May 2020

Vitamin D levels appear to play role in COVID-19 mortality rates


After studying global data from the novel coronavirus (COVID-19) pandemic, researchers have discovered a strong correlation between severe vitamin D deficiency and mortality rates.

Led by Northwestern University, the research team conducted a statistical analysis of data from hospitals and clinics across China, France, Germany, Italy, Iran, South Korea, Spain, Switzerland, the United Kingdom (UK) and the United States.

The researchers noted that patients from countries with high COVID-19 mortality rates, such as Italy, Spain and the UK, had lower levels of vitamin D compared to patients in countries that were not as severely affected.

This does not mean that everyone -- especially those without a known deficiency -- needs to start hoarding supplements, the researchers caution.

"While I think it is important for people to know that vitamin D deficiency might play a role in mortality, we don't need to push vitamin D on everybody," said Northwestern's Vadim Backman, who led the research. "This needs further study, and I hope our work will stimulate interest in this area. The data also may illuminate the mechanism of mortality, which, if proven, could lead to new therapeutic targets."

The research is available on medRxiv, a preprint server for health sciences.



Backman is the Walter Dill Scott Professor of Biomedical Engineering at Northwestern's McCormick School of Engineering. Ali Daneshkhah, a postdoctoral research associate in Backman's laboratory, is the paper's first author.

Backman and his team were inspired to examine vitamin D levels after noticing unexplained differences in COVID-19 mortality rates from country to country. Some people hypothesized that differences in healthcare quality, age distributions in population, testing rates or different strains of the coronavirus might be responsible. But Backman remained skeptical.

"None of these factors appears to play a significant role," Backman said. "The healthcare system in northern Italy is one of the best in the world. Differences in mortality exist even if one looks across the same age group. And, while the restrictions on testing do indeed vary, the disparities in mortality still exist even when we looked at countries or populations for which similar testing rates apply.

"Instead, we saw a significant correlation with vitamin D deficiency," he said.

By analyzing publicly available patient data from around the globe, Backman and his team discovered a strong correlation between vitamin D levels and cytokine storm -- a hyperinflammatory condition caused by an overactive immune system -- as well as a correlation between vitamin D deficiency and mortality.

"Cytokine storm can severely damage lungs and lead to acute respiratory distress syndrome and death in patients," Daneshkhah said. "This is what seems to kill a majority of COVID-19 patients, not the destruction of the lungs by the virus itself. It is the complications from the misdirected fire from the immune system."

This is exactly where Backman believes vitamin D plays a major role. Not only does vitamin D enhance our innate immune systems, it also prevents our immune systems from becoming dangerously overactive. This means that having healthy levels of vitamin D could protect patients against severe complications, including death, from COVID-19.



"Our analysis shows that it might be as high as cutting the mortality rate in half," Backman said. "It will not prevent a patient from contracting the virus, but it may reduce complications and prevent death in those who are infected."

Backman said this correlation might help explain the many mysteries surrounding COVID-19, such as why children are less likely to die. Children do not yet have a fully developed acquired immune system, which is the immune system's second line of defense and more likely to overreact.

"Children primarily rely on their innate immune system," Backman said. "This may explain why their mortality rate is lower."

Backman is careful to note that people should not take excessive doses of vitamin D, which might come with negative side effects. He said the subject needs much more research to know how vitamin D could be used most effectively to protect against COVID-19 complications.

"It is hard to say which dose is most beneficial for COVID-19," Backman said. "However, it is clear that vitamin D deficiency is harmful, and it can be easily addressed with appropriate supplementation. This might be another key to helping protect vulnerable populations, such as African-American and elderly patients, who have a prevalence of vitamin D deficiency."


Bibliography:

Ali Daneshkhah, Vasundhara Agrawal, Adam Eshein, Hariharan Subramanian, Hemant Kumar Roy, Vadim Backman. The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients. medRxiv, Posted April 30, 2020; [link]

Friday, 8 May 2020

Coronavirus found in patients' semen in small Chinese study


The virus that causes COVID-19 can be found in semen, Chinese researchers report in a small study that doesn't address whether sexual transmission is possible.

Doctors detected the virus in semen from six of 38 men hospitalized with laboratory-confirmed COVID-19. Four were still very sick with the disease while two were recovering.

The report from Shangqiu Municipal Hospital in China was published Thursday in JAMA Network Open.

There was no long-term follow-up so it is not known how long the virus may remain in semen or if men can spread it to their partners during sex.



The results contrast with a study of 34 Chinese men with COVID-19 published last month in the journal Fertility and Sterility. U.S. and Chinese researchers found no evidence of virus in semen tested between eight days and almost three months after diagnosis.

Dr. John Hotaling of the University of Utah, co-author of that report, said the new study involved much sicker men, most with active disease.

Authorities believe the coronavirus mainly spreads from droplets produced when infected people cough, which are inhaled by people nearby.

Some studies have reported finding the virus in blood, feces and tears or other fluid from COVID-19 patients with inflammation in their eyes.

Evidence suggesting that other infectious viruses including Zika and Ebola may be sexually transmitted has prompted questions about the coronavirus.

Hotaling said it's an important public health concern but that more research is needed to provide a definitive answer.

The American Society for Reproductive Medicine said the new study shouldn't be cause for alarm. To be safe, though, "it may be wise to avoid sexual contact with men until they are 14 days without symptoms," Dr. Peter Schlegel, the group's immediate past president, said in a statement.


Bibliography:

Diangeng Li et al. Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease 2019, 

JAMA Network Open (2020).

DOI: 10.1001/jamanetworkopen.2020.8292

A closer look at superconductors


A new measuring method helps understand the physics of high-temperature superconductivity

From sustainable energy to quantum computers: high-temperature superconductors have the potential to revolutionize today's technologies. Despite intensive research, however, we still lack the necessary basic understanding to develop these complex materials for widespread application. "Higgs spectroscopy" could bring about a watershed as it reveals the dynamics of paired electrons in superconductors.

An international research consortium centered around the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and the Max Planck Institute for Solid State Research (MPI-FKF) is now presenting the new measuring method in the journal Nature Communications. Remarkably, the dynamics also reveal typical precursors of superconductivity even above the critical temperature at which the materials investigated attain superconductivity.

Superconductors transport electric current without a loss of energy. Utilizing them could dramatically reduce our energy requirements -- if it weren't for the fact that superconductivity requires temperatures of -140 degrees Celsius and below. Materials only 'turn on' their superconductivity below this point. All known superconductors require elaborate cooling methods, which makes them impractical for everyday purposes. There is promise of progress in high temperature superconductors such as cuprates -- innovative materials based on copper oxide. The problem is that despite many years of research efforts, their exact mode of operation remains unclear. Higgs spectroscopy might change that.



Higgs spectroscopy allows new insights into high-temperature superconductivity

"Higgs spectroscopy offers us a whole new 'magnifying glass' to examine the physical processes," Dr. Jan-Christoph Deinert reports. The researcher at the HZDR Institute of Radiation Physics is working on the new method alongside colleagues from the MPI-FKF, the Universities of Stuttgart and Tokyo, and other international research institutions. What the scientists are most keen to find out is how electrons form pairs in high-temperature superconductors.

In superconductivity, electrons combine to create "Cooper pairs", which enables them to move through the material in pairs without any interaction with their environment. But what makes two electrons pair up when their charge actually makes them repel each other? For conventional superconductors, there is a physical explanation: "The electrons pair up because of crystal lattice vibrations," explains Prof. Stefan Kaiser, one of the main authors of the study, who is researching the dynamics in superconductors at MPI-FKF and the University of Stuttgart. One electron distorts the crystal lattice, which then attracts the second electron. For cuprates, however, it has so far been unclear which mechanism acts in the place of lattice vibrations. "One hypothesis is that the pairing is due to fluctuating spins, i.e. magnetic interaction," Kaiser explains. "But the key question is: Can their influence on superconductivity and in particular on the properties of the Cooper pairs be measured directly?"

At this point "Higgs oscillations" enter the stage: In high-energy physics, they explain why elementary particles have mass. But they also occur in superconductors, where they can be excited by strong laser pulses. They represent the oscillations of the order parameter – the measure of a material’s superconductive state, in other words, the density of the Cooper pairs. So much for the theory. A first experimental proof succeeded a few years ago when researchers at the University of Tokyo used an ultrashort light pulse to excite Higgs oscillations in conventional superconductors – like setting a pendulum in motion. For high-temperature superconductors, however, such a one-off pulse is not enough, as the system is damped too much by interactions between the superconducting and non-superconducting electrons and the complicated symmetry of the ordering parameter.



Terahertz light source keeps the system oscillating

Thanks to Higgs spectroscopy, the research consortium around MPI-FKF and HZDR has now achieved the experimental breakthrough for high-temperature superconductors. Their trick was to use a multi-cyclic, extremely strong terahertz pulse that is optimally tuned to Higgs oscillation and can maintain it despite the damping factors – continuously prodding the metaphorical pendulum. With the high-performance terahertz light source TELBE at HZDR, the researchers are able to send 100,000 such pulses through the samples per second. "Our source is unique in the world due to its high intensity in the terahertz range combined with a very high repetition rate," Deinert explains. "We can now selectively drive Higgs oscillations and measure them very precisely."

This success is owed to close cooperation between theoretical and experimental scientists. The idea was hatched at MPI-FKF; the experiment was conducted by the TELBE team, led by Dr. Jan-Christoph Deinert and Dr. Sergey Kovalev at HZDR under then group leader Prof. Michael Gensch, who is now researching at the German Aerospace Center and TU Berlin: "The experiments are of particular importance for the scientific application of large-scale research facilities in general. They demonstrate that a high-power terahertz source such as TELBE can handle a complex investigation using nonlinear terahertz spectroscopy on a complicated series of samples, such as cuprates."

That is why the research team expects to see high demand in the future: "Higgs spectroscopy as a methodological approach opens up entirely new potentials," explains Dr. Hao Chu, primary author of the study and postdoc at the Max Planck-UBC-UTokyo Center for Quantum Materials. "It is the starting point for a series of experiments that will provide new insights into these complex materials. We can now take a very systematic approach."



Just above the critical temperature: Where does superconductivity start?

Conducting several series of measurements, the researchers first proved that their method works for typical cuprates. Below the critical temperature, the research team was not only able to excite Higgs oscillations, but also proved that a new, previously unobserved excitation interacts with the Cooper pairs’ Higgs oscillations. Further experiments will have to reveal whether these interactions are magnetic interactions, as is fiercely debated in expert circles. Furthermore, the researchers saw indications that Cooper pairs can also form above the critical temperature, albeit without oscillating together. Other measuring methods have previously suggested the possibility of such early pair formation. Higgs spectroscopy could support this hypothesis and clarify when and how the pairs form and what causes them to oscillate together in the superconductor.


Bibliography:

H. Chu, M.-J. Kim, K. Katsumi, S. Kovalev, R. D. Dawson, L. Schwarz, N. Yoshikawa, G. Kim, D. Putzky, Z. Z. Li, H. Raffy, S. Germanskiy, J.-C. Deinert, N. Awari, I. Ilyakov, B. Green, M. Chen, M. Bawatna, G. Cristiani, G. Logvenov, Y. Gallais, A. V. Boris, B. Keimer, A. P. Schnyder, D. Manske, M. Gensch, Z. Wang, R. Shimano, S. Kaiser:

Phase-resolved Higgs response in superconducting cuprates.

Nature Communications, 2020

DOI: 10.1038/s41467-020-15613-1

Wednesday, 6 May 2020

Abnormally Small Red Blood Cells Could Indicate Cancer


Having abnormally small red blood cells - a condition known as microcytosis - could indicate cancer, according to new research led by a University of Exeter student working with a world-leading team.

Medical Sciences student Rhain Hopkins was lead author of the study of more than 12,000 UK patients aged over 40, which found that the cancer risk in males was 6.2 per cent, compared to 2.7 per cent in those without microcytosis.



The research, funded by Cancer Research UK and NIHR and published in BJGP, found that in females, the risk of cancer was 2.7 per cent in those with microcytosis, compared to 1.4 per cent without.

Of more than 108,000 followed within the Clinical Practice Research Datalink records, 12,289 patients with microcytosis were followed up. Of those, 497 developed cancer within a year.

Microcytosis is related to iron deficiency and with genetic conditions which affect haemaglobn in the blood. Similarly, iron deficiency has been identified as a feature of some cancers, particularly colorectal. Microcytosis is easily identified in a routine blood test.

Rhian Hopkins was working with Exeter's cancer diagnosis team as part of her Professional Training Year, which gives Medical Sciences students practical experience of research. As lead author of the paper, she said: "Research targeted at diagnosing cancer earlier is so important in reducing the burden of this devastating disease. The identification of risk markers, such as microcytosis, that are relevant to a range of cancers, can have a real impact in primary care. Being part of this research has been a very rewarding experience and getting my first paper published is such a massive achievement."

Professor Willie Hamilton, at the University of Exeter Medical School, who oversaw the research, said: "Overall, the risk of cancer in patients with microcytosis was still low, however our research indicates a need to investigate cancer. In two patients with cancer out of three the possibility of cancer is fairly easy to identify. For the other third, symptoms are often vague, and don't clearly point to cancer. For these patients GPs have to use more subtle clues to recognise that cancer may be present. Small red cells have long been recognised with colon cancer, but this study shows that they are a much broader clue, alerting the doctor to the small possibility of one of several possible cancers."



Dr Elizabeth Shephard, who supervised Rhian, said: "Rhian was a dedicated, proactive and enthusiastic student and an absolute pleasure to work with. As part of her Professional Training Year (PTY), Rhian undertook this standalone project of investigating the role of microcytosis as a possible early marker of cancer. She taught herself to use Stata statistical analysis software, and with guidance learned how to build the database from which to run the analyses. She also analysed the data and wrote up the paper for publication, making a meaningful contribution to the potentially life-saving area of cancer diagnosis.

"The PTY placement is a fantastic opportunity for undergraduates to gain valuable research work experience - and for academics to work with bright students. I wouldn't hesitate to recommend the programme."


Bibliography:

Hopkins, R., Bailey, S. E., Hamilton, W. T., & Shephard, E. A. (2020).

Microcytosis as a risk marker of cancer in primary care: A cohort study using electronic patient records.

 British Journal of General Practice.

doi: 10.3399/bjgp20x709577

Tuesday, 5 May 2020

Exoplanets: How we’ll search for signs of life


Whether there is life elsewhere in the universe is a question people have pondered for millennia; and within the last few decades, great strides have been made in our search for signs of life outside of our solar system.

NASA missions like the space telescope Kepler have helped us document thousands of exoplanets -- planets that orbit around other stars. And current NASA missions like Transiting Exoplanet Survey Satellite (TESS) are expected to vastly increase the current number of known exoplanets. It is expected that dozens will be Earth-sized rocky planets orbiting in their stars' habitable zones, at distances where water could exist as a liquid on their surfaces. These are promising places to look for life.

This will be accomplished by missions like the soon-to-be-launched James Webb Space Telescope, which will complement and extend the discoveries of the Hubble Space Telescope by observing at infrared wavelengths. It is expected to launch in 2021, and will allow scientists to determine if rocky exoplanets have oxygen in their atmospheres. Oxygen in Earth's atmosphere is due to photosynthesis by microbes and plants. To the extent that exoplanets resemble Earth, oxygen in their atmospheres may also be a sign of life.

Not all exoplanets will be Earth-like, though. Some will be, but others will differ from Earth enough that oxygen doesn't necessarily come from life. So with all of these current and future exoplanets to study, how do scientists narrow down the field to those for which oxygen is most indicative of life?



To answer this question, an interdisciplinary team of researchers, led by Arizona State University (ASU), has provided a framework, called a "detectability index" which may help prioritize exoplanets that require additional study. The details of this index have recently been published in the Astrophysical Journal of the American Astronomical Society.

"The goal of the index is to provide scientists with a tool to select the very best targets for observation and to maximize the chances of detecting life," says lead author Donald Glaser of ASU's School of Molecular Sciences.

The oxygen detectability index for a planet like Earth is high, meaning that oxygen in Earth's atmosphere is definitely due to life and nothing else. Seeing oxygen means life. A surprising finding by the team is that the detectability index plummets for exoplanets not-too-different from Earth.

Although Earth's surface is largely covered in water, Earth's oceans are only a small percentage (0.025%) of Earth's mass. By comparison, moons in the outer solar system are typically close to 50% water ice.

"It's easy to imagine that in another solar system like ours, an Earth-like planet could be just 0.2% water," says co-author Steven Desch of ASU's School of Earth and Space Exploration. "And that would be enough to change the detectability index. Oxygen would not be indicative of life on such planets, even if it were observed. That's because an Earth-like planet that was 0.2% water -- about eight times what Earth has -- would have no exposed continents or land."

Without land, rain would not weather rock and release important nutrients like phosphorus. Photosynthetic life could not produce oxygen at rates comparable to other non-biological sources.

"The detectability index tells us it's not enough to observe oxygen in an exoplanet's atmosphere. We must also observe oceans and land," says Desch. "That changes how we approach the search for life on exoplanets. It helps us interpret observations we've made of exoplanets. It helps us pick the best target exoplanets to look for life on. And it helps us design the next generation of space telescopes so that we get all the information we need to make a positive identification of life."

Scientists from diverse fields were brought together to create this index. The formation of the team was facilitated by NASA's Nexus for Exoplanetary System Science (NExSS) program, which funds interdisciplinary research to develop strategies for looking for life on exoplanets. Their disciplines include theoretical and observational astrophysics, geophysics, geochemistry, astrobiology, oceanography, and ecology.

"This kind of research needs diverse teams, we can't do it as individual scientists" says co-author Hilairy Hartnett who holds joint appointments at ASU's School of Earth and Space Exploration and School of Molecular Sciences.



In addition to lead author Glaser and co-authors Harnett and Desch, the team includes co-authors Cayman Unterborn, Ariel Anbar, Steffen Buessecker, Theresa Fisher, Steven Glaser, Susanne Neuer, Camerian Millsaps, Joseph O'Rourke, Sara Imari Walker, and Mikhail Zolotov who collectively represent ASU's School of Molecular Sciences, School of Earth and Space Exploration, and School of Life Sciences. Additional scientists on the team include researchers from the University of California Riverside, Johns Hopkins University and the University of Porto (Portugal).

It is the hope of this team that this detectability index framework will be employed in the search for life. "The detection of life on a planet outside our solar system would change our entire understanding of our place in the universe," says Glaser. "NASA is deeply invested in searching for life, and it is our hope that this work will be used to maximize the chance of detecting life when we look for it."


Bibliography:

Donald M Glaser, Hilairy Ellen Hartnett, Steven J Desch, Cayman T Unterborn, Ariel Anbar, Steffen Buessecker, Theresa Fisher, Steven Glaser, Stephen R Kane, Carey M Lisse, Camerian Millsaps, Susanne Neuer, Joseph G O’Rourke, Nuno Santos, Sara Imari Walker, Mikhail Zolotov.

Detectability of Life Using Oxygen on Pelagic Planets and Water Worlds.

The Astrophysical Journal, 2020; 893 (2): 163

DOI: 10.3847/1538-4357/ab822d

New Test Detects Glaucoma Progression Earlier


A new test can detect glaucoma progression 18 months earlier than the current gold standard method, according to results from a UCL-sponsored clinical trial.

The technology, supported by an artificial intelligence (AI) algorithm, could help accelerate clinical trials, and eventually may be used in detection and diagnostics, according to the Wellcome-funded study published in Expert Review of Molecular Diagnostics.

Lead researcher Professor Francesca Cordeiro (UCL Institute of Ophthalmology, Imperial College London, and Western Eye Hospital Imperial College Healthcare NHS Trust) said: "We have developed a quick, automated and highly sensitive way to identify which people with glaucoma are at risk of rapid progression to blindness."

Glaucoma, the leading global cause of irreversible blindness, affects over 60 million people, which is predicted to double by 2040 as the global population ages. Loss of sight in glaucoma is caused by the death of cells in the retina, at the back of the eye.



The test, called DARC (Detection of Apoptosing Retinal Cells), involves injecting into the bloodstream (via the arm) a fluorescent dye that attaches to retinal cells, and illuminates those that are in the process of apoptosis, a form of programmed cell death. The damaged cells appear bright white when viewed in eye examinations - the more damaged cells detected, the higher the DARC count.

One challenge with evaluating eye diseases is that specialists often disagree when viewing the same scans, so the researchers have incorporated an AI algorithm into their method.

In the Phase II clinical trial of DARC, the AI was used to assess 60 of the study participants (20 with glaucoma and 40 healthy control subjects). The AI was initially trained by analysing the retinal scans (after injection of the dye) of the healthy control subjects. The AI was then tested on the glaucoma patients.

Those taking part in the AI study were followed up 18 months after the main trial period to see whether their eye health had deteriorated.

The researchers were able to accurately predict progressive glaucomatous damage 18 months before that seen with the current gold standard OCT retinal imaging technology, as every patient with a DARC count over a certain threshold was found to have progressive glaucoma at follow-up.

"These results are very promising as they show DARC could be used as a biomarker when combined with the AI-aided algorithm," said Professor Cordeiro, adding that biomarkers - measurable biological indicators of disease state or severity - are urgently needed for glaucoma, to speed up clinical trials as the disease progresses slowly so it can take years for symptoms to change.

"What is really exciting, and actually unusual when looking at biological markers, is that there was a clear DARC count threshold above which all glaucoma eyes went on to progress," she added.

First author Dr Eduardo Normando (Imperial College London and Western Eye Hospital Imperial College Healthcare NHS Trust) said: "Being able to diagnose glaucoma at an earlier stage, and predict its course of progression, could help people to maintain their sight, as treatment is most successful if provided at an early stage of the disease. After further research in longitudinal studies, we hope that our test could have widespread clinical applications for glaucoma and other conditions."



The team is also applying the test to rapidly detect cell damage caused by numerous conditions other than glaucoma, such as other neurodegenerative conditions that involve the loss of nerve cells, including age-related macular degeneration, multiple sclerosis, and dementia.

The AI-supported technology has recently been approved by both the UK's Medicines and Healthcare products Regulatory Agency and the USA's Food and Drug Administration as an exploratory endpoint for testing a new glaucoma drug in a clinical trial.

The researchers are also assessing the DARC test in people with lung disease, and hope that by the end of this year, the test may help to assess people with breathing difficulties from Covid-19.


Bibliography:

Normando, E. M., Yap, T. E., Maddison, J., Miodragovic, S., Bonetti, P., Almonte, M., . . . Cordeiro, M. F. (2020).

A CNN-aided method to predict glaucoma progression using DARC (Detection of Apoptosing Retinal Cells).

Expert Review of Molecular Diagnostics, 1-12.

doi: 10.1080/14737159.2020.1758067

Billions projected to suffer nearly unlivable heat in 2070


In just 50 years, 2 billion to 3.5 billion people, mostly the poor who can’t afford air conditioning, will be living in a climate that historically has been too hot to handle, a new study said.

With every 1.8 degree (1 degree Celsius) increase in global average annual temperature from man-made climate change, about a billion or so people will end up in areas too warm day-in, day-out to be habitable without cooling technology, according to ecologist Marten Scheffer of Wageningen University in the Netherlands, co-author of the study.

How many people will end up at risk depends on how much heat-trapping carbon dioxide emissions are reduced and how fast the world population grows.



Under the worst-case scenarios for population growth and for carbon pollution — which many climate scientists say is looking less likely these days — the study in Monday’s journal Proceedings of the National Academy of Sciences predicts about 3.5 billion people will live in extremely hot areas. That’s a third of the projected 2070 population.

But even scenarios considered more likely and less severe project that in 50 years a couple of billion people will be living in places too hot without air conditioning, the study said.

“It’s a huge amount and it’s a short-time. This is why we’re worried,” said Cornell University climate scientist Natalie Mahowald, who wasn’t part of the study. She and other outside scientists said the new study makes sense and conveys the urgency of the man-made climate change differently than past research.

In an unusual way to look at climate change, a team of international scientists studied humans like they do bears, birds and bees to find the “climate niche” where people and civilizations flourish. They looked back 6,000 years to come up with a sweet spot of temperatures for humanity: Average annual temperatures between 52 and 59 degrees (11 to 15 degrees Celsius).

We can — and do — live in warmer and colder places than that, but the farther from the sweet spot, the harder it gets.

The scientists looked at places projected to get uncomfortably and considerably hotter than the sweet spot and calculated at least 2 billion people will be living in those conditions by 2070.

Currently about 20 million people live in places with an annual average temperature greater than 84 degrees (29 degrees Celsius) — far beyond the temperature sweet spot. That area is less than 1% of the Earth’s land, and it is mostly near the Sahara Desert and includes Mecca, Saudi Arabia.

But as the world gets more crowded and warmer, the study concluded large swaths of Africa, Asia, South America and Australia will likely be in this same temperature range. Well over 1 billion people, and up to 3.5 billion people, will be affected depending on the climate altering choices humanity makes over the next half century, according to lead author Chi Xu of Nanjing University in China.



With enough money, “you can actually live on the moon,” Scheffer said. But these projections are “unlivable for the ordinary, for poor people, for the average world citizen.”

Places like impoverished Nigeria — with a population expected to triple by the end of he century — would be less able to cope, said study co-author Tim Lenton, a climate scientist and director of the Global Systems Institute at the University of Exeter in England.


Bibliography:

Future of the human climate niche

 Chi Xu, Timothy A. Kohler,  Timothy M. Lenton,  Jens-Christian Svenning, and Marten Scheffer

PNAS first published May 4, 2020

https://doi.org/10.1073/pnas.1910114117

New Players Involved in Programmed Cell Death Identified


Skoltech researchers have identified a set of proteins that are important in the process of apoptosis, or programmed cell death. These newly identified proteins can become targets in the development of drugs against cancer or other diseases.

Apoptosis is a form 'cell suicide', in which a series of programmed molecular steps in a cell lead to its death. "When a cell senses that something is wrong, it can commit 'suicide', or apoptosis, to prevent itself from dividing and spreading the problem. This is a normal mechanism present in all cells of the body and one way by which the body gets rid of unneeded or abnormal cells.

"Most cancers block this process, so that they can proliferate forever. So, understanding the process and knowing the actors that are involved is important in order to identify new targets that can be used to develop therapy for cancer, for instance", explains Dominique Leboeuf, Skoltech Center for Life Sciences PhD student and one of the authors of the study.



Apoptosis is an essential process for proper organ development, immune system functioning, and defense against viral infections and cancerous transformation. Once the apoptotic program is initiated in a cell, special enzymes, called caspases, are activated and cleave a very specific set of proteins.

"The goal of the study was to sort out this set and identify the proteins that are important in the apoptotic program. To do this, we looked at the evolutionary conservation of caspase substrates and additional characteristics of these proteins, based on sequence, structure and biochemical properties. We believed that the proteins that were the most preserved, and met our selection criteria, would be critical in the apoptotic process," stated Skoltech Neurobiology and Brain Restoration Center professor Konstantin Piatkov.

The steps involved in the identification of the final list of proteins:


This work is an important step in the understanding of the apoptotic program, and can be used to further investigate the therapeutic potential of the identified proteins.


Bibliography:

Gubina, N., Leboeuf, D., Piatkov, K., & Pyatkov, M. (2020).

Novel Apoptotic Mediators Identified by Conservation of Vertebrate Caspase Targets.

Biomolecules, 10(4), 612.

DOI: 10.3390/biom10040612

Monday, 4 May 2020

Parkinson’s Dyskinesia Mechanism Identified


Many people with Parkinson’s disease eventually develop debilitating movements called dyskinesia, a side effect of their much-needed dopamine replacement medication. The mechanism underlying this unwanted side effect has been unknown, until now. An international collaboration led by Scripps Research, Florida has found a key cause, and with it, potentially, a new route to providing relief.

Dopamine replacement therapy makes Parkinson’s symptoms much better at first, but eventually treatment gives way to uncontrollable, jerky body movements. But why? New research shows that underlying this development is the therapy’s unintended boost of a protein with the unwieldy name Ras-guanine nucleotide-releasing factor 1, or RasGRP1 for short. This boost in RasGRP1 produces a cascade of effects which lead to abnormal, involuntary movements known as LID, or L-DOPA-induced dyskinesia, says co-lead author Srinivasa Subramaniam, PhD, associate professor of neuroscience at Scripps Research, Florida.

Encouragingly, the collaboration found that in dopamine-depleted mice and other animal models, inhibiting production of RasGRP1 in the brain during dopamine replacement diminished the involuntary movements without negating the useful effects of the dopamine therapy.



Taken together, the research offers a new path to easing Parkinson’s dyskinesia while allowing maintenance of dopamine replacement therapy, Subramaniam says.

Subramaniam’s group has long been interested in cellular signaling in the brain underlying motor movements, and how it is affected by brain diseases, including Huntington’s and Parkinson’s.

“Parkinson’s patients describe treatment-induced dyskinesia as one of the most debilitating features of their illness,” Subramaniam says. “These studies show that if we can down-regulate RasGRP1 signaling before dopamine replacement, we have an opportunity to greatly improve their quality of life.”

The study was published in the journal Science Advances. In addition to Subramaniam, the co-lead author is Alessandro Usiello, PhD, of the University of Campania Luigi Vanvitelli, Caserta, Italy, and the Behavioural Neuroscience Laboratory at Ceinge Biotecnologie Avanzate, Naples, Italy.

Dopamine is a neurotransmitter and hormone that plays a key role in movement, learning, memory, motivation, and emotion. Parkinson’s develops when dopamine-producing neurons in a region of the mid-brain called the substantia nigra stop working or die. It’s a brain region associated with both movement initiation and reward, so its impairment causes a wide variety of symptoms, including stiffness, balance problems, walking difficulty, tremor, depression and memory issues.

Doctors treat Parkinson’s with dopamine replacement therapy, often a medicine called levodopa. The brain converts levodopa into dopamine, and at proper doses, this leads to resolution of symptoms. But as dose and duration grow, a side effect called dyskinesia can develop. After a decade, about 95 percent of Parkinson’s patients will experience some degree of involuntary dyskinesia, Subramaniam says.

Dyskinesia is different than tremor, according to the Michael J. Fox Foundation.

“It can look like fidgeting, writhing, wriggling, head bobbing or body swaying,” the foundation explains. “Many people say they prefer dyskinesia to stiffness or decreased mobility. Others, though, have painful dyskinesia or movements that interfere with exercise or social or daily activities.”

The reason for its development has eluded scientists. Subramaniam and his team had studied the problem over the past decade, leading them eventually to the discovery that RasGRP1 signaling was a main culprit.

“There is an immediate need for new therapeutic targets to stop LID, or L-DOPA-induced dyskinesia in Parkinson’s disease,” Subramaniam says. “The treatments now available work poorly and have many additional unwanted side effects. We believe this represents an important step toward better options for people with Parkinson’s.”



The next steps in the research will be discovering the best route to selectively reducing expression of RasGRP1 in the striatum while not affecting its expression in other areas of the body, Subramaniam says.

“The good news is that in mice, a total lack of RasGRP1 is not lethal, so we think that blocking RasGRP1 with drugs, or even with gene therapy, may have very little or no major side effects,” Subramaniam says.

“It’s rare for a nonprofit institution to possess the medicinal chemistry and drug development expertise needed to identify and develop such a therapy, but we have that at Scripps Research,” Subramaniam says. “Our next task is to develop suitable compounds capable of blocking RasGRP1 in the striatum.”


Bibliography:

Eshraghi et al. (2020).

RasGRP1 is a causal factor in the development of l-DOPA–induced dyskinesia in Parkinson’s disease.

Science Advances.

DOI: https://doi.org/10.1126/sciadv.aaz7001

Sunday, 3 May 2020

Scientists Regenerate Neurons in Mice with Spinal Cord Injury and Optic Nerve Damage


Like power lines in an electrical grid, long wiry projections that grow outward from neurons -- structures known as axons -- form interconnected communication networks that run from the brain to all parts of the body. But unlike an outage in a power line, which can be fixed, a break in an axon is permanent. Each year thousands of patients confront this reality, facing life-long losses in sensation and motor function from spinal cord injury and related conditions in which axons are badly damaged or severed.

New research by scientists at the Lewis Katz School of Medicine Temple University (LKSOM) shows, however, that gains in functional recovery from these injuries may be possible, thanks to a molecule known as Lin28, which regulates cell growth. In a study published online in the journal Molecular Therapy, the Temple researchers describe the ability of Lin28 -- when expressed above its usual levels -- to fuel axon regrowth in mice with spinal cord injury or optic nerve injury, enabling repair of the body's communication grid.



"Our findings show that Lin28 is a major regulator of axon regeneration and a promising therapeutic target for central nervous system injuries," explained Shuxin Li, MD, PhD, Professor of Anatomy and Cell Biology and in the Shriners Hospitals Pediatric Research Center at the Lewis Katz School of Medicine at Temple University and senior investigator on the new study. The research is the first to demonstrate the regenerative ability of Lin28 upregulation in the injured spinal cord of animals.

"We became interested in Lin28 as a target for neuron regeneration because it acts as a gatekeeper of stem cell activity," said Dr. Li. "It controls the switch that maintains stem cells or allows them to differentiate and potentially contribute to activities such as axon regeneration."

To explore the effects of Lin28 on axon regrowth, Dr. Li and colleagues developed a mouse model in which animals expressed extra Lin28 in some of their tissues. When full-grown, the animals were divided into groups that sustained spinal cord injury or injury to the optic nerve tracts that connect to the retina in the eye.

Injured CNS axons fail to regenerate in adult mammals and there are no effective regenerative strategies to treat patients with CNS injuries. Dr. Li’s group demonstrates that upregulating Lin28 gene in mature neurons induces significant long distance regeneration of both spinal cord axons and optic nerve in adult mice.


Another set of adult mice, with normal Lin28 expression and similar injuries, were given injections of a viral vector (a type of carrier) for Lin28 to examine the molecule's direct effects on tissue repair.

Extra Lin28 stimulated long-distance axon regeneration in all instances, though the most dramatic effects were observed following post-injury injection of Lin28. In mice with spinal cord injury, Lin28 injection resulted in the growth of axons to more than three millimeters beyond the area of axon damage, while in animals with optic nerve injury, axons regrew the entire length of the optic nerve tract. Evaluation of walking and sensory abilities after Lin28 treatment revealed significant improvements in coordination and sensation.

"We observed a lot of axon regrowth, which could be very significant clinically, since there currently are no regenerative treatments for spinal cord injury or optic nerve injury," Dr. Li explained.

One of his goals in the near-term is to identify a safe and effective means of getting Lin28 to injured tissues in human patients. To do so, his team of researchers will need to develop a vector, or carrier system for Lin28, that can be injected systemically and then hone in on injured axons to deliver the therapy directly to multiple populations of damaged neurons.



Dr. Li further wants to decipher the molecular details of the Lin28 signaling pathway. "Lin28 associates closely with other growth signaling molecules, and we suspect it uses multiple pathways to regulate cell growth," he explained. These other molecules could potentially be packaged along with Lin28 to aid neuron repair.


Bibliography:

Fatima M. Nathan, Yosuke Ohtake, Shuo Wang, Xinpei Jiang, Armin Sami, Hua Guo, Feng-Quan Zhou, Shuxin Li.

Upregulating Lin28a Promotes Axon Regeneration in Adult Mice with Optic Nerve and Spinal Cord Injury.

Molecular Therapy, 2020;

DOI: 10.1016/j.ymthe.2020.04.010

Saturday, 2 May 2020

Researchers New study takes superconductivity to the edge


A discovery that long eluded physicists has been detected in a laboratory at Princeton. A team of physicists detected superconducting currents -- the flow of electrons without wasting energy -- along the exterior edge of a superconducting material. The finding was published in the May 1 issue of the journal Science.

The superconductor that the researchers studied is also a topological semi-metal, a material that comes with its own unusual electronic properties. The finding suggests ways to unlock a new era of “topological superconductivity” that could have value for quantum computing.

“To our knowledge, this is the first observation of an edge supercurrent in any superconductor,” said Nai Phuan Ong, Princeton’s Eugene Higgins Professor of Physics and the senior author on the study. Learn more about topological materials in this essay by Ong.

“Our motivating question was, what happens when the interior of the material is not an insulator but a superconductor?” Ong said. “What novel features arise when superconductivity occurs in a topological material?”



Although conventional superconductors already enjoy widespread usage in magnetic resonance imaging (MRI) and long-distance transmission lines, new types of superconductivity could unleash the ability to move beyond the limitations of our familiar technologies.

Researchers at Princeton and elsewhere have been exploring the connections between superconductivity and topological insulators — materials whose non-conformist electronic behaviors were the subject of the 2016 Nobel Prize in Physics for F. Duncan Haldane, Princeton’s Sherman Fairchild University Professor of Physics.

Topological insulators are crystals that have an insulating interior and a conducting surface, like a brownie wrapped in tin foil. In conducting materials, electrons can hop from atom to atom, allowing electric current to flow. Insulators are materials in which the electrons are stuck and cannot move. Yet curiously, topological insulators allow the movement of electrons on their surface but not in their interior.

To explore superconductivity in topological materials, the researchers turned to a crystalline material called molybdenum ditelluride, which has topological properties and is also a superconductor once the temperature dips below a frigid 100 milliKelvin, which is -459 degrees Fahrenheit.

“Most of the experiments done so far have involved trying to ‘inject’ superconductivity into topological materials by putting the one material in close proximity to the other,” said Stephan Kim, a graduate student in electrical engineering, who conducted many of the experiments. “What is different about our measurement is we did not inject superconductivity and yet we were able to show the signatures of edge states.”

Stephan Kim, a graduate student in the Department of Electrical Engineering, conducted experiments demonstrating supercurrents in a topological material.

The team first grew crystals in the laboratory and then cooled them down to a temperature where superconductivity occurs. They then applied a weak magnetic field while measuring the current flow through the crystal. They observed that a quantity called the critical current displays oscillations, which appear as a saw-tooth pattern, as the magnetic field is increased.

Both the height of the oscillations and the frequency of the oscillations fit with predictions of how these fluctuations arise from the quantum behavior of electrons confined to the edges of the materials.

“When we finished the data analysis for the first sample, I looked at my computer screen and could not believe my eyes, the oscillations we observed were just so beautiful and yet so mysterious,” said Wudi Wang, who as first author led the study and earned his Ph.D. in physics from Princeton in 2019. “It’s like a puzzle that started to reveal itself and is waiting to be solved. Later, as we collected more data from different samples, I was surprised at how perfectly the data fit together.”

Researchers have long known that superconductivity arises when electrons, which normally move about randomly, bind into twos to form Cooper pairs, which in a sense dance to the same beat. “A rough analogy is a billion couples executing the same tightly scripted dance choreography,” Ong said.

The script the electrons are following is called the superconductor’s wave function, which may be regarded roughly as a ribbon stretched along the length of the superconducting wire, Ong said. A slight twist of the wave function compels all Cooper pairs in a long wire to move with the same velocity as a “superfluid” — in other words acting like a single collection rather than like individual particles — that flows without producing heating.

If there are no twists along the ribbon, Ong said, the Cooper pairs are stationary and no current flows. If the researchers expose the superconductor to a weak magnetic field, this adds an additional contribution to the twisting that the researchers call the magnetic flux, which, for very small particles such as electrons, follows the rules of quantum mechanics.

The researchers anticipated that these two contributors to the number of twists, the superfluid velocity and the magnetic flux, work together to maintain the number of twists as an exact integer, a whole number such as 2, 3 or 4 rather than a 3.2 or a 3.7. They predicted that as the magnetic flux increases smoothly, the superfluid velocity would increase in a saw-tooth pattern as the superfluid velocity adjusts to cancel the extra .2 or add .3 to get an exact number of twists.

The team measured the superfluid current as they varied the magnetic flux and found that indeed the saw-tooth pattern was visible.



In molybdenum ditelluride and other so-called Weyl semimetals, this Cooper-pairing of electrons in the bulk appears to induce a similar pairing on the edges.

The researchers noted that the reason why the edge supercurrent remains independent of the bulk supercurrent is currently not well understood. Ong compared the electrons moving collectively, also called condensates, to puddles of liquid.

“From classical expectations, one would expect two fluid puddles that are in direct contact to merge into one,” Ong said. “Yet the experiment shows that the edge condensates remain distinct from that in the bulk of the crystal.”

The research team speculates that the mechanism that keeps the two condensates from mixing is the topological protection inherited from the protected edge states in molybdenum ditelluride. The group hopes to apply the same experimental technique to search for edge supercurrents in other unconventional superconductors.

“There are probably scores of them out there,” Ong said.


Bibliography:

Wudi Wang, Stephan Kim, Minhao Liu, F. A. Cevallos, R. J. Cava, N. P. Ong.

Evidence for an edge supercurrent in the Weyl superconductor MoTe2.

Science, 2020; 368 (6490): 534

DOI: 10.1126/science.aaw9270

Friday, 1 May 2020

Scientists explore the power of radio waves to help control fusion reactions


A key challenge to capturing and controlling fusion energy on Earth is maintaining the stability of plasma — the electrically charged gas that fuels fusion reactions — and keeping it millions of degrees hot to launch and maintain fusion reactions. This challenge requires controlling magnetic islands, bubble-like structures that form in the plasma in doughnut-shaped tokamak fusion facilities. These islands can grow, cool the plasma and trigger disruptions — the sudden release of energy stored in the plasma — that can halt fusion reactions and seriously damage the fusion facilities that house them.

Improved island control

Research by scientists at Princeton University and at the U.S. Department of Energy’s (DOE) Princeton Plasma Physics Laboratory (PPPL) points toward improved control of the troublesome magnetic islands in ITER, the international tokamak under construction in France, and other future fusion facilities that cannot allow large disruptions.  “This research could open the door to improved control schemes previously deemed unobtainable,” said Eduardo Rodriguez, a graduate student in the Princeton Program in Plasma Physics and first author of a paper(link is external) in Physics of Plasmas that reports the findings.



The research follows up on previous work by Allan Reiman and Nat Fisch, which identified a new effect called “RF [radio frequency] current condensation” that can greatly facilitate the stabilization of magnetic islands. The new Physics of Plasmas paper shows how to make optimal use of the effect. Reiman is a Distinguished Research Fellow at PPPL and Fisch is a Princeton University professor and Director of the Princeton Program in Plasma Physics and Associate Director of Academic Affairs at PPPL.

Fusion reactions combine light elements in the form of plasma — the state of matter composed of free electrons and atomic nuclei — to generate massive amounts of energy in the sun and stars. Scientists throughout the world are seeking to reproduce the process on Earth for a virtually inexhaustible supply of safe and clean power to generate electricity for all humanity.

The new paper, based on a simplified analytical model, focuses on use of RF waves to heat the islands and drive electric current that causes them to shrink and disappear. When the temperature gets sufficiently high, complicated interactions can occur that lead to the RF current condensation effect, which concentrates the current in the center of the island and can greatly enhance the stabilization. But as the temperature increases, and the gradient of the temperature between the colder edge and the hot interior of the island grows larger, the gradient can drive instabilities that make it more difficult to increase the temperature further.

Point-counterpoint

This point-counterpoint is an important indicator of whether the RF waves will accomplish their stabilizing goal. “We analyze the interaction between the current condensation and the increased turbulence from the gradient the heating creates to determine whether the system is stabilized or not,” Rodriguez says. “We want the islands not to grow.”  The new paper shows how to control the power and aiming of the waves to make optimal use of the RF current condensation effect, taking account of the instabilities. Focusing on this can lead to improved stabilization of fusion reactors,” Rodriguez said.



The researchers now plan to introduce new aspects into the model to develop a more detailed investigation. Such steps include work being done towards including the condensation effect in computer codes to model the behavior of launched RF waves and their true effect. The technique would ultimately be used in designing optimal island stabilization schemes.


Bibliography:

E. Rodríguez, A. H. Reiman, N. J. Fisch.

RF current condensation in the presence of turbulent enhanced transport.

Physics of Plasmas, 2020; 27 (4): 042306

DOI: 10.1063/5.0001881

The ova of obese women have lower levels of omega-3 fatty acids


A study conducted by researchers from the UPV/EHU, Cruces Hospital, the IVI Clinic Bilbao and Biocruces Bizkaia shows that the oocytes of obese or overweight women have a different composition of fatty acids. This difference in levels could be linked to poor IVF outcomes and could suggest that the offspring of overweight women have an unfavourable environment even before conception.

Researchers from the UPV/EHU, Cruces Hospital, the IVI Clinic Bilbao and Biocruces Bizkaia have discovered that the oocytes –immature ova- from obese and overweight women have lower concentrations of omega-3 fatty acids. A study of the lipid composition of 922 ova obtained during IVF treatment from 205 women of normal build and who were overweight or obese has found that the oocytes of both obese and overweight women have a very different lipid composition; the study was led by Roberto Matorras-Weinig, lecturer at the UPV/EHU’s Faculty of Medicine and Nursing, and was published in the journal Fertility and Sterility.

Omega-3 fatty acids are essential in the human diet, in other words, they have to be ingested because the body cannot synthesise them.  The intake of them tends to be low in the western diet. Moreover, as Dr Matorras of the Department of Medical and Surgical Specialties at the UPV/EHU points out, “omega-3 fatty acids compete metabolically with omega-6 ones, and the intake of the latter tends to be too high in the western diet. So the high intake of omega-6 fatty acids contributes towards low levels of omega-3 ones. Presumably this is the mechanism responsible for their low levels in the ova”.



Childhood obesity could kick in before conception

Obesity is a well-known public health problem with numerous repercussions on different organs. “One of its implications in pregnancy is the birth of macrosomic babies (with a high weight), and the subsequent risk of childhood and adult obesity. Until now, this had been attributed to the effect of maternal obesity during pregnancy as well as to unsuitable diets during childhood. But these findings raise the possibility that the problems of these children may start even before conception, due to the poorer lipid composition of the ova which have generated them,” said Matorras.

On another front, the researcher added that “obese patients tend to have poorer IVF outcomes, which have been attributed to a whole range of motives. This discovery highlights another possible cause of these poorer outcomes”.


Bibliography:

Roberto Matorras, Antonia Exposito, Marcos Ferrando, Rosario Mendoza, Zaloa Larreategui, Lucía Laínz, Larraitz Aranburu, Fernando Andrade, Luis Aldámiz-Echevarria, Maria Begoña Ruiz-Larrea, Jose Ignacio Ruiz-Sanz

Oocytes of women who are obese or overweight have lower levels of n-3 polyunsaturated fatty acids compared with oocytes of women with normal weight

Fertility and Sterility

DOI: 10.1016/j.fertnstert.2019.08.059

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