Culture

Only about five per cent of the babies born to mothers with hepatitis C are themselves infected by the disease. A possible reason for this low figure is that the baby's immune system has already destroyed the virus before birth. A new study from researchers at Karolinska Institutet published in the journal Gut reveals clear adaptations of the uninfected babies' immune system that can lead the way to new treatment methods.

Unlike other diseases spread via the blood, such as HIV and hepatitis B, the risk of infection during pregnancy is low for hepatitis C, and only five per cent of the babies born to mothers with chronic hepatitis C contract the disease. Researchers at KI now have a possible explanation for the low infection risk.

"The immune system of the healthy babies shows similar changes to that in babies infected with hepatitis C," says Niklas Björkström, doctor and researcher at the Department of Medicine, Huddinge at Karolinska Institutet. "This could suggest that the immune cells have encountered the virus in the womb and managed to eliminate it before birth."

The study was conducted with Maternity Hospital No 16 in Saint Petersburg, Russia. Of the 55 pregnant women participating, 40 had an active hepatitis C infection, while the others had antibodies after a previous infection.

The babies born to women with an active infection were all considered exposed to the virus; despite this, only three of these 40 babies developed hepatitis C.

All the infants were monitored up to the age of 18 months through regular testing, and to increase the volume of comparable data, samples were added from 18 infants who had been infected with hepatitis C at birth.

The study showed that both the babies born with an infection and the babies who had been exposed to the virus by an infected mother had similar changes in their adaptive immune system, with clear adaptations of the B lymphocytes, the role of which is to produce antibodies able to discover and identify alien microbes, such as viruses, bacteria and parasites.

"A possible explanation is that most babies exposed to the virus in utero manage to deal with it, which we can later see by the B lymphocytes," says Dr Björkström. "One interesting hypothesis is that these cells can contain novel information that we can use to protect ourselves against hepatises C in the future."

Some 70 million people around the world live with hepatitis C, a disease that if left untreated leads to liver cirrhosis and liver cancer. Thanks to the recent development of efficacious drugs, the WHO hopes to see the disease eliminated globally by 2030. However, drugs cure only an ongoing infection and there is currently no vaccine.

"Which is why we need to continue researching hepatitis C," Dr Björkström says. "We need to understand what it'll take to obtain lasting protection against the virus. Only then can we attain the WHO goal."

The researchers will now be investigating whether more immune cells in the infants have changed in a similar way.

Until now, scientists had assumed that there are about 80 so-called open reading frames (ORFs) in the genome of herpes simplex virus 1 (HSV-1). These are the locations in the genome where the information in the DNA is read and translated into proteins. It is now clear that there are a lot more - namely 284 ORFs. These are translated from hundreds of novel viral transcripts, which have now also been identified.

This is what research groups from Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, and other institutions report in the journal Nature Communications.

"The new findings now make it possible to study the individual genes of the virus much more precisely than before," says Professor Lars Dölken, head of the JMU Chair of Virology. He was in charge of this project together with Florian Erhard, JMU junior professor of systems virology.

Several institutions involved

The research team used a broad spectrum of the latest systems biology methods for the study. In addition to JMU, the Max Delbrück Center for Molecular Medicine in Berlin, the University of Cambridge in England and Ludwig-Maximilians-Universität of Munich were involved.

The data are not only important for a better understanding of the virus itself. They also have concrete implications, for example for the development of HSV-1-based oncolytic viruses. These are viruses that are used in immunological therapies of certain tumor diseases, such as malignant melanoma.

Facts about herpes simplex virus 1

Herpes simplex viruses of type 1 (HSV-1) are known to many people as the cause of unpleasant itching cold sores. An infection with this virus type can also have serious consequences. For example, HSV-1 can cause life-threatening pneumonia in patients in intensive care units. And in healthy people, it can cause encephalitis, which often leads to permanent brain damage.

Once infected with the virus, a person will retain it for the rest of his or her life: herpes viruses permanently nestle in body cells. There they usually remain inconspicuous for a long time. Only under special circumstances, such as a weakened immune system, they become active again.

Money from the European Research Council

Lars Dölken researches herpes viruses very intensively. For his successes in this field he was awarded a Consolidator Grant by the European Research Council in 2016. The prize was endowed with around two million euros; the money will go towards studies on herpes viruses.

Biologists classify all living organisms into three major groups they call 'domains'. Two of these domains--the Bacteria and the Archaebacteria--consist of single-celled organisms, while the third--the Eukaryota--includes most of the larger, multicellular organisms we are all familiar with: fungi, plants and animals including ourselves. Of the three domains, the Eukaryota almost certainly evolved the most recently, but questions remain about which of the two single-celled domains arose first in the history of life. Over forty years ago, American biologists Carl Woese and George Fox suggested that these two domains both emerged from a more primitive organism or group of organisms scientists now call LUCA, or the Last Universal Common Ancestor. Scientists would love to be able to say something concrete about what LUCA was like, what types of environment it lived in, and how it made its living. For example was it a heterotroph--an organism which eats environmentally supplied organic food--like ourselves, or an autotroph--an organism which is able to make its own food from inorganic compounds--like a photosynthesiser or the 'rock-eating' microbes that scientists call lithoautotrophs? If scientists could nail down some of these questions about LUCA, which they potentially could do by knowing which genes LUCA possessed, this might provide even deeper insights as to how and where life originated on Earth in the first place. New research from Tokyo Tech and the Max Planck Institute suggests understanding early life may be trickier than previously thought.

Scientists can now easily sequence and compare the DNA of microorganisms, which allows them to determine how closely related organisms are. Just as we have our own family trees, organismal DNA comparisons are likewise a measure of which organisms shared common ancestors. Organisms with very similar DNA likely have recent common ancestors; the DNA from monkeys is similar to that from humans, and both monkeys and humans have DNA that is more similar to that of each other than that from octopuses, and so on. Those with less similar DNA sequences are likely more distantly related, and thus must have differentiated earlier. This sort of comparison allows scientists to reconstruct evolutionary relationships among organisms, and construct 'family trees' which relate them in time. DNA sequence comparison has revealed that all organisms on Earth are related to one another, and this allows scientists to build a 'tree of life', which shows how they are related evolutionarily.

There is, however, a major complication to this. Besides the normal parent-to-offspring inheritance of DNA which dominates in higher organisms such as ourselves, in microorganisms snippets of DNA can also 'jump' between organisms. This can occur by various means; for example, sometimes viral infections can move genes from one organism to another. It has been hypothesised that the earliest organisms may have undergone more rapid evolutionary change, partly because they were not able to copy information as accurately as modern ones can, but also due to more widespread 'gene jumping'. If most ancient cells could not copy information as accurately as modern ones, and if their DNA moved more easily between lineages than today, using modern DNA to understand ancient evolution may be extremely misleading.

This is where new research carried out by Sarah Berkemer, based at the Max Planck Institute for Mathematics in the Sciences in Leipzig, Germany, and Shawn McGlynn from the Earth-Life Science Institute at the Tokyo Institute of Technology in Japan comes in. Their analyses confirm other work which suggested that only a limited understanding of the lifestyle of the most ancient cells can be derived from DNA comparison. Although this is a disappointing result for evolutionary biologists, it is important to understand what can and cannot be known from the data that scientists are able to gather from modern organisms. Berkemer and McGlynn's work does supply one silver lining however; while it is clear that we don't know what the first organisms metabolised or where they lived, their work provides insight into how quickly they may have evolved billions of years ago.

Berkemer and McGlynn analysed thousands of phylogenetic trees derived from the comparison of DNA similarity data from thousands of microorganisms to try to identify the oldest genes and when they might have evolved, and to understand how genes move between organisms to shed light on the nature of LUCA. Their careful analysis showed that early in life's history, different gene types changed at different rates. This suggests that early mutation rates were much higher than at present and there has been a significant contribution of 'gene jumping' over time which makes a simple interpretation of the early 'family tree' of life misleading. They concluded that previous studies sometimes vastly under-sampled the available data and that the data cannot resolve these questions, but that it does show that early evolution was wildly different from what it is at present.

Professor McGlynn explains, 'A fundamental question in biology is what were the first life forms on Earth. There are two basic ways to try and address this. First, we can use the comparison of gene sequences to try and understand which ones seem most ancient. Second, we can look for evidence biology may have left in the geological record.' McGlynn says this work shows that although it is clear there is a fuzzy yet remarkable general outline of a family tree of life in the available DNA sequence data, there has been so much evolutionary change that it is still as of yet impossible to say how the earliest organisms made their living or in what types of environments they lived. This is because the signal is simply too noisy due to this early genetic scrambling. As a result, we are still a long way from understanding what the most primitive organisms on Earth were like or the sorts of environments they lived in.

Importantly, however, this study marks the first time scientists have been able to say something about the pace of early evolution. This work shows there is a detectable signal of very rapid early evolution, thus, while we may not know exactly what early organisms were like, it seems likely life was mutating and evolving very quickly early on. Nevertheless, McGlynn believes it is still amazing that this limited information can be understood at all, that it still tells us important things about the evolution of life on Earth, and suggests we need to develop new ways of looking at available DNA data to find novel techniques of learning what Earth's earliest life was like.

A Korean research team has developed a high-performance ceramic fuel cell that can operate on butane fuels. Since butane can be liquified and thus can be stored and carried easily, the new technology is expected to expand the application range of ceramic fuel cells to portable and mobile applications such as electric cars, robots and drones. Previously, ceramic fuel cells had only been considered for application to large-capacity power generation systems due to their high-temperature operation.

The Korea Institute of Science and Technology (KIST) announced that Dr. Son Ji-Won's research team at KIST's Center for Energy Materials Research had developed a high-performance, thin-film-based ceramic fuel cell that could operate at mid-to-low temperatures below 600 °C using butane fuels.

Ceramic fuel cells are a type of high-temperature fuel cell that operates over 800 ?. This high temperature allows the use of inexpensive catalysts, such as nickel, in contrast to low-temperature fuel cells, such as polymer electrolyte fuel cells, which use high-priced platinum catalysts to supplement their low catalytic activity. Another major advantage of high-temperature fuel cells is that they can various fuels other than pure hydrogen, such as LPG and LNG with low emission due to high efficiency. However, ironically, even though high-temperature fuel cells use inexpensive catalysts, their operation requires expensive refractory materials and manufacturing technologies. Another limiting factor is that their system on-off process takes a long time due to the characteristics of high-temperature operation, which restrict their application to large-scale stationary power generation systems.

Many research teams around the world have worked on thin-film-based ceramic fuel cells, which can operate at low temperatures without performance loss. Unfortunately, the problem is that lower-temperature operation causes ceramic fuel cells to lose one of their important advantages, that is, their ability to use various fuels. When the nickel catalyst of ceramic fuel cells is used with hydrocarbon fuels, such as methane, propane, and butane, the carbon generated during fuel conversion is deposited on the surface of nickel. This worsens seriously as the temperature lowers, leading to the failure of the cell operation.

Dr. Son Ji-Won's research team solved this problem by incorporating high-performance secondary catalysts, which can convert fuels more easily, by thin-film technology. Using alternating deposition of the secondary catalyst and the main catalyst layers, the team was able to effectively distribute the secondary catalyst at the nearliest parts of the fuel electrodes to the electrolyte. By this way, controlled incorporation of small amount but effectively positioned secondary catalysts was possible.

Using this procedure, the KIST research team was able to successfully apply secondary catalysts known for their high catalytic activity at low temperatures, such as palladium (Pd), ruthenium (Ru), and copper (Cu), to the nano-structure fuel electrodes. They confirmed the high-performance operation of the newly developed thin-film-based ceramic fuel cells at mid and low operation temperatures (500-600 ?), using butane fuel, which is a very affordable fuel.

"This research systematically examined the possible uses of hydrocarbon fuels in ceramic fuel cells operating at low temperatures," said Dr. Son Ji-won. "The use of the portable fuels like butane at lower operating temperatures would enable the development of smaller and integrated ceramic fuel cell systems, which can be applied to portable and mobile power sources."

At this alarming time, when the COVID-19 pandemic is on everyone's mind, a new special issue in the open-access peer-reviewed journal Population and Economics by Lomonosov Moscow State University (Faculty of Economics) provides a platform for discussion on the impact of the pandemic on the population and economics, both in Russia and worldwide by opening a special issue. An introductory overview for the issue is provided by its Editor-in-Chief, Irina E. Kalabikhina of the Faculty of Economics at Lomonosov Moscow State University.

Today is still too early to draw any final conclusions, with too many things yet to happen. Nevertheless, the time is right to start a discussion on how to soften the possible consequences of the pandemic.

In the first published papers, united by the special issue, various teams of economists assess the uneasy dilemma - saving lives now or saving the economy to preserve lives in the future; demographers draw parallels with previous pandemics and its impact on demographic development; and sociologists analyse the state of various strata throughout the crisis.

The coronavirus pandemic came to Russia in mid-March - two months after China, two weeks after Spain, Italy, France, and about the same time as the United States.

As of 24th April, according to the data available at the Center for System Science and Engineering at John Hopkins University, Russia is amongst the top 10 countries by number of recorded cases. International comparability of national data on COVID-19 is a separate issue; it will be addressed in one of the special issue articles.

"Now I just want to state that Russia is affected by the pandemic, and it disturbs population and society. Moreover, a number of anti-epidemic measures taken in the country can bite the economy. In this context, the search for specific Russian consequences of the pandemic initiated by our authors along with the global consequences is particularly interesting", shares Editor-in-Chief of Population and Economics, Prof. Irina E. Kalabikhina.

All economists, demographers and sociologists are invited to consider the impact of the pandemic and its attendant recession on the population and economy in Russia and the global world. Research papers are welcome to the special issue, which will remain open for submissions until the end of June 2020.

What could the pandemic cost to globalisation, what could be the consequences of the crisis? In his paper, Dean of the Faculty of Economics of Lomonosov Moscow State University, Prof. Alexander Auzan calls to take it as a chance to change the path dependency and proposes a tax system revision. He also suggests that the reform is to be made by the law enforcement agencies.

The possible consequences of the crisis, including a technological shift and a change in the direction and volumes of trade flows, are discussed in the paper by Dr. Oleg Buklemishev from Lomonosov Moscow State University. He also examines the likelihood of the role of the State to strengthen in line with the expected deglobalisation in the face of epidemiological uncertainty.

Meanwhile, the pandemic remains "a global social drama" for the global society, as the world faces a step back to the basic needs as outlined in the Maslow pyramid. Income and wealth inequality appears to be increasing in the future, and when it all ends - we will have no choice but to establish the International Victory Day over Coronavirus, suggested in his paper Prof. Leonid Grigoryev of the Higher School of Economics (Moscow).

Every second Russian worker can be considered as a vulnerable employee, suggests the latest analysis by researchers from the Russian Academy of National Economy and Public Administration (RANEPA). The highest risks are faced by young people, workers with a low level of education and the residents of the regional centers in Russia.

The most important directions of the current COVID-related crisis research are determined in Prof. Andrey Shastitko's (Lomonosov Moscow State University and Russian Academy of National Economy and Public Administration) research. He addresses such questions as how to collect, process and report information on the pandemic relevant with regards to the phenomenon of individual cognitive errors, as well as how this information is perceived by the mass consumer and the voter. Current situation can be considered as force majeure, but life does not stop because of force majeure, which requires micro- and meso-institutions also to find the options for a way out.

Another paper by Dr. Alexander Kurdin (Lomonosov Moscow State University and Russian Academy of National Economy and Public Administration) reveals that the pandemic has provoked the development of "intermediate" regulatory solutions in Russia and has led to the formation of a short-term "institutional continuum", which assumes the possibility of new combinations of norms. At the same time, there is some institutional uncertainty, which stems not only from the lack of legal rules that meet the new "hybrid" regimes, but also from the lack of accompanying informal rules, which often determine human behaviour. However, it is possible that extraordinary circumstances may also increase the flexibility of informal rules.

Still, one of the most vulnerable social groups in the current crisis remain migrants and refugees, who are facing economic, socio-psychological and political challenges, as described in the paper by Dr. Irina Ivakhnyuk (Global Migration Policy Associates).

Within the circumstances of the pandemic, there are many messages across the media about its positive effect on the environment. Though, Prof. Sergey Bobylev (Lomonosov Moscow State University) shares in his research, that despite the short-term reduction in the environmental impact, over the upcoming years we can expect weakened attention from the state, business and the population to environmental issues, a decrease in environmentally oriented costs, redirection of cash flows to maintain or prevent a significant drop in the material standard of living.

Other papers still remain in the press, but we already can get some insights into the future works.

The last pandemics can teach us valuable lessons, point out Dr. Natalia Gavrilova and Dr. Leonid Gavrilov (University of Chicago, Federal Research Institute for Health Organization and Informatics of Ministry of Health of the Russian Federation, Institute of Socio-Political Research at the Federal Center of Theoretical and Applied Sociology of the Russian Academy of Science), who use the Spanish flu of 1918 with its peculiarities regarding mortality as an example.

Another lesson we could learn is the one from the more recent outbreak of Ebola and the following crisis in Sierra Leone, suggests Dr. Ana Androsik (the New School for Social Research, New York and Feminist Data and Research Inc.) in her research paper. Back then, the population also had to assume extra caretaking responsibilities, while the imposed by the government restrictions negatively made it harder for the people to earn their incomes, which, in turn, hit the travel and local market industries. According to Dr. Androsik, we should use this type of evidence, taken from previous public health crises, to learn the mistakes of the past and design the most efficient program interventions.

Russian families also face new issues in the conditions of self-isolation, while "dachas" (countryside family houses) play an important role during the pandemic.

Effective mechanisms to support the population in a period of temporary, yet large-scale
economic decline, which could be a solution for the Russian labour market, are suggested in the paper by Dr. Irina Denisova (University of Manchester and New Economic School, Moscow).

Population and Economics' Editor-in-Chief Irina Kalabikhina addresses in her paper the demographic and social issues of the pandemic.

"We are going through difficult times, and it is hardly possible to overestimate the role of science in the quickest passing through the crisis with the least human and economic losses.
We hope that our Journal will contribute to the crucially important discussion on the impact
of the pandemic on the economy and population", concludes Editor-in-Chief of Population and Economics, Irina E. Kalabikhina.

April 27, 2020 - Intensivists caution against the use of premature novel therapies in lieu of traditional critical care principles in patients with COVID-19 in a recent correspondence letter in the American Journal of Respiratory Cell and Molecular Biology.

In "A Call for Rational Intensive Care in the Era of COVID-19", Benjamin Singer, MD, Assistant Professor of Medicine and Biochemistry & Molecular Genetics, Division of Pulmonary and Critical Care Medicine, Department of Medicine, at Northwestern University Feinberg School of Medicine, and co-authors write that "the intensive care unit is already optimized for the care of COVID-19 patients and that departures from standard of care require evidence..."

The COVID-19 pandemic is unprecedented, resulting in a surge of critically ill patients that have tested the resources of medical centers around the country. The overwhelming patient demand and dwindling resources combined to trigger a cascade of emotions, stress, and fatigue. As hospital staff mobilize to meet the growing demand of COVID-19 patients, some clinicians are making note of a pattern that has emerged where proven interventions are neglected or even rejected.

Dr. Singer, who is also associate editor of the American Journal of Respiratory Cell and Molecular Biology, argues that this is not the time to abandon reason. Instead, he calls for "a rational approach to translating science to the bedside as we care for patients with severe COVID-19. We want to come out of the COVID-19 pandemic knowing what works and what doesn't work for severe viral pneumonia patients."

He added that physicians continuously learn from their patients by making observations and so far what they've learned is that the most effective treatment for COVID-19 patients is supportive therapy. Until there are clinical trials that offer clear direction on a different treatment approach, state-of-the-art supportive care is the best option.

"Off-label and off-study use of novel or repurposed therapeutics prevents potential benefits or harms from being clearly defined and puts some of our most vulnerable people at risk," cautioned Dr. Singer.

Bethesda, MD - In a new animal study examining Alzheimer's disease, researchers found that disease progression could be slowed by decreasing neuroinflammation in the brain before memory problems and cognitive impairment were apparent. The new findings point to the importance of developing therapies that target very early stages of the disease.

In 2011, the National Institute on Aging updated the diagnostic criteria for Alzheimer's disease to reflect its progressive nature. The criteria added a preclinical stage during which brain changes are taking place, but the person is still asymptomatic and, therefore, unaware of his condition. Biomarker profiles could eventually be used to identify people in the disease's early stages who might benefit from early treatments.

"Starting an intervention at the earliest stage of the disease, when cellular and molecular alterations have already been triggered but major damage to the brain has not yet occurred, could offer a way to reduce the number of people who go on to develop full Alzheimer's dementia," said research team leader Caterina Scuderi, PhD, assistant professor of pharmacology and toxicology from Sapienza, University of Rome. "However, there have been few studies in animals examining therapeutic strategies that target timepoints before symptoms can be seen."

Scuderi was scheduled to present this research at the American Association for Anatomy annual meeting in San Diego this month. Though the meeting, to be held in conjunction with the 2020 Experimental Biology conference, was canceled in response to the COVID-19 outbreak, the research team's abstract was published in this month's issue of The FASEB Journal.

The researchers designed an animal study to gain a deeper understanding of neuroinflammation's role in Alzheimer's disease during the pre-symptomatic stage of the disease, which might represent the best time for therapeutic intervention. The study results suggest that rebalancing neuroinflammation in animals that show altered neuroinflammatory parameters could be beneficial.

"Our results help demonstrate that neuroinflammation in Alzheimer's disease is an extremely complex phenomenon that can change over the disease's progression and varies based on factors such as affected brain area," said Scuderi. "We hope that these findings will prompt scientists to further investigate neuroinflammation at the earliest stages of the disease, which may represent an important pharmacological target."

Bethesda, MD - The drug buprenorphine reduces relapse in patients with opioid addiction, and some emerging evidence indicates it may also help treat cocaine addiction. However, the treatment itself comes with a risk of addiction and, thus, is not FDA approved to treat cocaine addiction. New research performed in mice suggests that chemical modifications to buprenorphine can improve its effectiveness to treat cocaine addiction while minimizing abuse potential.

"Our research aims to balance the many different biological activities of buprenorphine to make it better at treating cocaine addiction," said researcher Keith Olson, PhD, a postdoctoral fellow at the University of Michigan in Ann Arbor. "We hope this work can eventually help treat addiction without the abuse potential of buprenorphine."

Dr. Olson was scheduled to present this research at the American Society for Pharmacology and Experimental Therapeutics annual meeting in San Diego this month. Though the meeting, to be held in conjunction with the 2020 Experimental Biology conference, was canceled in response to the COVID-19 outbreak, the research team's abstract was published in this month's issue of The FASEB Journal.

Buprenorphine has several biological targets, including the nociceptin receptors, which have been shown to be involved in reward and addiction to multiple drugs in animal models. The benefits of nociceptin activity are counteracted by buprenorphine's activity at mu opioid receptors involved in addiction to classical opiates. However, for buprenorphine the addiction effects are weaker than stronger opioids like heroin and methadone.

In the new work, the researchers used a mouse model of cocaine relapse to compare the effectiveness of buprenorphine and a related analog known as BU10119. They found that the new compound is better at activating the same nociceptin receptors as buprenorphine and worse at activating mu opioid receptors. These two differences corresponded to modest improvements in preventing cocaine relapse in the mouse model and minimized addiction potential, respectively.

"Our studies show that BU10119 is a promising lead for treating cocaine addiction," said Dr. Olson. "The new compound has better effectiveness and lower abuse potential compared to buprenorphine."

Next, the researchers plan to characterize BU10119 in more sophisticated animal models to better test its potential to treat addiction with reduced abuse potential.

Bethesda, MD - When threatened, the marine parchment tube worm secretes a sticky slime that emits a unique long-lasting blue light. New research into how the worm creates and sustains this light suggests that the process is self-powered.

"The light, or bioluminescence, produced by this worm does not appear as flashes, like in most luminous organisms, but as a long-lasting glow," said Evelien De Meulenaere, PhD, a researcher in Dimitri Deheyn's lab at the Scripps Institution of Oceanography. "Understanding the mechanisms of this bioluminescence process could inform the design of a light stick that works for several days or, with further optimization, environmentally friendly garden and street lighting."

De Meulenaere was scheduled to present this research at the American Society for Biochemistry and Molecular Biology annual meeting in San Diego this month. Though the meeting, to be held in conjunction with the 2020 Experimental Biology conference, was canceled in response to the COVID-19 outbreak, the research team's abstract was published in this month's issue of The FASEB Journal.

After discovering that light production was not linked with any of the organism's metabolic pathways, the researchers realized that sustaining light production for more than a few milliseconds would require the slime to contain its own energy source.

Further work revealed that the worm's slime contains an iron storage protein called ferritin. Artificially adding iron to the mucus increased light production, which led the researchers to believe that ferritin acts as like a molecular battery that stores energy. More recently, they found that exposing ferritin to blue light makes more iron available and that exposing the slime to blue light induces bursts of light lasting several minutes.

"A light source based on this mechanism could be remotely triggered using blue light to initiate and amplify the process," said De Meulenaere. "Once we understand exactly how light production happens in the natural system, that information could potentially be used to develop a long-lasting light that is also biodegradable and rechargeable."

The tube worm's bioluminescence could also be used to create biomedical reporter systems. Because it is sensitive to iron such a system could be used to test for iron deficiencies or toxicities. It could also be used as a light-emitting reporter that works for several days. This would allow experiments where various proteins or cells are tracked for much longer periods of time than possible with today's fluorescent reporters.

Bethesda, MD - The surge in cannabidiol (CBD) popularity means more farmers are growing non-intoxicating strains of cannabis, or hemp, for CBD production. This new market has led to commercial genetic tests for early determination of hemp plant sex. However, a new study has found that these tests may not all produce accurate results.

CBD is used as an alternative treatment for pain and anxiety and various medical conditions. Unfertilized female cannabis plants produce high amounts of the CBD precursor in their flowers, making it important to identify and eliminate male plants at the seedling stage.

"The results from our undergraduate-led project can help hemp growers make accurate sex determination of seedlings," said Allison Nalesnik, senior undergraduate student at Salisbury University. "This could help increase the yield of CBD, which should reduce prices for the public."

Nalesnik was scheduled to present this research at the American Society for Biochemistry and Molecular Biology annual meeting in San Diego this month. Though the meeting, to be held in conjunction with the 2020 Experimental Biology conference, was canceled in response to the COVID-19 outbreak, the research team's abstract was published in this month's issue of The FASEB Journal.

Commercially available genetic tests use DNA markers known as primer pairs to identify male plants weeks before this could be determined visually. This helps farmers avoid spending time and money on growing plants that don't produce flowers and that could potentially lower CBD production by fertilizing female plants.

The new study was conducted through a molecular genetics course offered at Salisbury University. Over the course of a semester, students in the course followed identical protocols to determine the sex of 13 hemp plants. They collectively assessed the effectiveness of three commercially available primer pairs using modern genetics equipment and techniques.

"Two of the primer pairs -- SCAR119 and MADC2 -- were effective for determining the sex of cannabis seedlings," said Nalesnik. "The ineffective primer set would need to be tested further to more confidently say whether or not it is actually scientifically useful."

Next steps for this research include investigating DNA markers that are only found on the male chromosome to see if these offer a more efficient way to determine the sex of hemp seedlings.

Bethesda, MD - While both sexes have the capacity for phenomenal athletic achievements, women on average must work harder to breathe during strenuous exercise compared to men, according to new research. The study suggests one possible way sex could affect exercise dynamics and potentially also contribute to differences in how men and women experience airway disorders such as asthma and chronic obstructive pulmonary disease (COPD).

"The amount of work the respiratory muscles have to do to breathe a given volume is greater in women," said Paolo Dominelli, PhD, assistant professor at the University of Waterloo in Canada. "It is thought that this is due to women having smaller airways than men, which causes the airflow resistance to be higher."

Dominelli was scheduled to present the research at the American Physiological Society annual meeting in San Diego this month. Though the meeting, to be held in conjunction with the 2020 Experimental Biology conference, was canceled in response to the COVID-19 outbreak, the research team's abstract was published in this month's issue of The FASEB Journal.

The research team recruited six men and five women to perform two maximal exercise tests, in which participants gradually increased their level of exertion on a stationary cycle until they were exercising as hard as they could. Participants breathed through a mouthpiece attached to a large bag. During one session, the bag was filled with normal room air. During the other, the bag was filled with a mixture of oxygen and helium. Each bag contained the same amount of oxygen, and participants were not told which mixture they were breathing on which day.

A small tube was inserted into participants' nose and throat during the tests to monitor the pressure inside the esophagus. This procedure allowsthe researchers to measure the amount of work required to breathe. When the bag contained the helium mixture, the results showed no differences in the work of breathing between men and women. When it contained room air, breathing required significantly more work for women than men.

The experiment was designed to mimic how men's larger airways reduce breathing resistance. The helium mixture is much less dense than room air and, as a result, flows in a more laminar manner. In a laminar flow, air molecules are all flowing in the same direction, like water in a smooth river. In a turbulent flow, air molecules swirl in different directions, akin to the eddies that form around a boulder in the middle of a river. Turbulent flow in the airways causes more resistance, which requires more work to overcome.

"Two big factors that determine whether flow is laminar or turbulent is the size of the airway and the flow," Dominelli explained. "At rest, the rate of air flow is very low, so even though women have smaller airways than men, air flow is still laminar. As exercise intensity increases, you breathe faster, and at some point the airflow goes from laminar to turbulent. Air flow in men's airways will also eventually turn from laminar to turbulent, but this requires a higher rate of air flow than is required in women."

Dominelli cautioned that the differences observed in the study relate to size and sex, and that there is great variability in airway size among different individuals. Although men on average have larger airways, a man and woman of the same height could have similar-sized airways. Nonetheless, the research provides useful insights on basic physiology at a population level and could also help researchers better understand how airway diseases affect the transition from laminar to turbulent flow in women and men.

Bethesda, MD - People with post-traumatic stress disorder (PTSD) face a higher risk of heart disease at an earlier age than people without PTSD. A new study helps explain why.

The research was scheduled to be presented at the American Physiological Society annual meeting in San Diego this month. Though the meeting, to be held in conjunction with the 2020 Experimental Biology conference, was canceled in response to the COVID-19 outbreak, the research team's abstract was published in this month's issue of The FASEB Journal.

Scientists found evidence of dysfunction in small blood vessels that appears to be driven by the sympathetic nervous system--the system behind the fight-or-flight response--along with oxidative stress, an imbalance between free radicals and antioxidants in the bloodstream.

Problems in the small blood vessels are often a precursor to stiffening or narrowing of the larger arteries, which can lead to a heart attack, stroke or other forms of heart disease.

"We have found that blood vessel dysfunction is more prevalent in young adults with PTSD than those without," said lead study author Jennifer Weggen, a PhD student at Virginia Commonwealth University. "We hypothesize that both oxidative stress and overactivity of the sympathetic nervous system, independently and cooperatively, may ultimately lead to an increased risk of cardiovascular disease."

In any given year about 8 million adults in the U.S. suffer from PTSD, a mental health problem caused by witnessing or experiencing a traumatic event. Previous studies have shown that PTSD increases a person's likelihood of having heart disease by as much as 50%.

To trace the connections between PTSD and heart disease, the research team conducted a series of cardiovascular assessments in 16 patients with PTSD and 24 healthy volunteers with similar demographics. The average age in both groups was 24 years old. Participants with PTSD underwent two assessments and consumed either an antioxidant supplement containing vitamin C, vitamin E and alpha lipoic acid or a placebo beforehand.

Healthy arteries respond to changes in blood flow by constricting and relaxing. The researchers found that all participants had normal responses in the brachial artery, an artery in the arm. However, those with PTSD showed a significantly lower amount of blood flowing through a given portion of the brachial artery during testing, which reflects abnormal responses in the smaller vessels further downstream. These participants also had a lower variation in the time intervals between heart beats, a marker of increased sympathetic nervous system activation.

Those differences virtually disappeared when volunteers consumed an antioxidant supplement, suggesting oxidative stress plays a role in both the small vessel dysfunction and the sympathetic nervous system activity. Free radicals naturally occur in the body as a result of normal physiological processes, but the body makes its own antioxidants to keep them in check. Oxidative stress occurs when the free radicals overwhelm the body's antioxidant defenses.

"Supplementing with an antioxidant cocktail tipped the balance back to equilibrium, reducing oxidative stress," said Weggen. However, she cautioned that antioxidants were used in the study only to understand the potential role of oxidative stress, not to test the supplements as a potential treatment. "The suggestion of regular use of antioxidants specifically for treatment of PTSD would be premature, as no studies have confirmed its efficacy or safety and appropriate dosage is unknown. Everyone responds differently to antioxidant supplements, and not everyone may reap benefits. Seeking medical guidance would be prudent before taking nutritional supplements."

Oxidative stress can also be reduced by fortifying the body's own antioxidant defense systems through lifestyle changes such as exercise, diet, stress reduction and meditation. Further research could help illuminate whether these methods are effective for mediating the oxidant-antioxidant balance in people with PTSD, Weggen noted.

Bethesda, MD - A new study calls into question the reliance on disease-free laboratory mice for testing new influenza (flu) vaccines. Instead, studying mice that have been exposed to other illnesses could help make vaccine development processes more reflective of real-world conditions and lead to better vaccines, researchers say.

Scientists commonly use "clean" mice--which are raised in conditions that are free of certain bacteria and viruses--in order to study how the immune system responds to certain diseases and vaccines without worrying that the results will be muddied by other diseases. However, the immune response of a clean mouse may not translate well to humans, whose immune systems are constantly exposed to various illnesses.

"While studies on clean mice are a standard scientific method, studies on dirty mice--with their multifaceted immune challenges--might better replicate the immune challenges seen in humans," said lead study author David Meyerholz, DVM, PhD, professor of pathology at the University of Iowa Carver College of Medicine. "In the context of vaccine studies, dirty mice might better predict vaccine efficacy and offer a model to develop more effective human vaccines."

Meyerholz was scheduled to present the research at the American Society for Investigative Pathology annual meeting in San Diego this month. Though the meeting, to be held in conjunction with the 2020 Experimental Biology conference, was canceled in response to the COVID-19 outbreak, the research team's abstract was published in this month's issue of The FASEB Journal.

The flu vaccine is proven to prevent flu infections and reduce the severity of the illness in infected individuals, but the efficacy of the flu vaccine varies greatly year to year. The vaccine for the 2018-2019 flu season, for example, was only 29% effective, according to the U.S. Centers for Disease Control and Prevention (CDC). Researchers say this mixed track record underscores the need for more effective vaccines.

Meyerholz and colleagues studied two groups of laboratory mice: one raised in standard clean conditions, and one that shared a cage with pet-store mice. Half of the mice in each group were given a flu vaccine. The researchers then exposed all the mice to influenza A virus and compared how their bodies handled the illness.

On average, the dirty mice showed more extensive lung damage from their illness than the clean mice, suggesting they were hit harder by the infection. Among mice that had been vaccinated, dirty mice also showed an impaired ability to clear the influenza virus from their systems, indicating the vaccine was less effective in these mice than in clean ones.

"These results suggest that clean mice, when exposed to either a pathogen or vaccine, can often mount an efficient immune response," said Meyerholz. "In dirty mice, much like humans where the immune system is regularly challenged by environmental and seasonal pathogens, the ability to mount an immune response appears to be less efficient. We want to better understand the reason why this happens, which could help us generate more effective vaccines."

CDC recommends all people age 6 months and older receive a flu vaccine each year.

Bethesda, MD - Zika virus is capable of replicating and spreading infectious particles within the outermost cells lining the vaginal tract, according to new research. The findings provide the first molecular-level insights into how the virus can move from person to person through sexual contact.

While Zika is primarily spread by mosquitoes, researchers have been aware of its potential for sexual transmission based on cases in which people became infected after having sex with a partner who had visited a Zika-affected area. Previous studies have also found Zika particles present in semen and vaginal fluid from infected individuals.

Having a more detailed understanding of how Zika infiltrates the body through sexual contact could help scientists identify new ways to prevent or treat Zika infections. The new study examined how Zika particles behaved in cultures of human vaginal epithelial cells and identified the virus's likely entry point as a protein on the surface of the cells called tyrosine-protein kinase receptor UFO, which is encoded by the AXL gene.

"The outcome of this research highlights how local replication of Zika in the vaginal epithelium plays an important role in mediating sexual transmission and subsequent systemic infection in the human host," said lead study author James Mungin Jr., a doctoral candidate at Meharry Medical College. "Additionally, our research findings confirming that the receptor UFO (AXL) promotes viral entry can be very instrumental in developing drugs and antibody-based therapies that target and block this receptor, therefore eliminating the pathology caused by this virus."

Mungin was scheduled to present the research at the American Society for Investigative Pathology annual meeting in San Diego this month. Though the meeting, to be held in conjunction with the 2020 Experimental Biology conference, was canceled in response to the COVID-19 outbreak, the research team's abstract was published in this month's issue of The FASEB Journal.

Zika spread rapidly around the world during a major 2015-2016 outbreak, causing about 42,000 infections in the United States and its territories. While the number of cases has since dropped precipitously, the virus is still considered a health threat in many places around the world. Babies born to mothers infected with Zika have a high risk of birth defects.

Mungin and colleagues found that Zika virus particles were able to successfully enter vaginal epithelial cells through the UFO receptor, replicate their RNA genome and steadily release infectious viral particles inside the cells. The research team plans to further study the factors that contribute to Zika replication for insights on how those factors might be interrupted.

Like Zika, many other viruses in the flavivirus family are spread by insects. However, research on those other viruses, such as dengue and yellow fever, does not always translate well to Zika because they are not sexually transmitted.

"Interestingly, sexual transmission among flaviviruses is in fact unique in nature," said Mungin. "As of now, Hepatitis C and Zika virus have been identified as the [only] two flaviviruses known to establish infection via sexual contact with an infected partner."

According to the U.S. Centers for Disease Control and Prevention, using condoms can prevent sexual transmission of Zika.

(New York) April 27, 2020 - Stand Up To Cancer® (SU2C)-supported research will be presented during the American Association for Cancer Research Annual (AACR) Virtual Meeting 10 from April 27th to 28th.

Work presented by SU2C-funded investigators highlights continued support for developing effective immunotherapy approaches to pediatric and young adult ALL and lung cancer as well as progress in the emerging field of Cancer Interception. Cancer Interception seeks approaches to intervene and stop the formation or progression of early or pre-cancerous conditions.

"Stand Up To Cancer has invested significantly and has made notable contributions in advancing the field of immunotherapy and has pioneered new approaches to cancer diagnostics and treatment, notably through Cancer Interception," stated SU2C CEO Sung Poblete, PhD, RN. "Not only are we excited about the continuing impact SU2C is making in new immunotherapy approaches to treat refractory ALL in children and young adults and to treat non-small cell lung cancer, but we are making measurable strides in moving cancer interception forward toward clinical practice so we can identify and treat patients at earlier stages to optimize outcomes."

Tuesday, April 28, VMS.PR01.01. Translational Prevention Studies

10:50-11:00 a.m. (1098) - Mediators of early immune response in bronchial premalignant lesions

Members of the SU2C-LUNGevity Foundation-American Lung Association Lung Cancer Interception Dream Team used gene expression profiling to identify genes that may be responsible for immune suppression or activation in Bronchial premalignant lesions (PMLs) which are precursors to lung squamous cell carcinoma. Of 15 candidate genes identified, the GSTP1 gene was found to be upregulated in progressing lesions and negatively correlated with several immune activation pathways. Ultimately, GSTP1 represents a promising new target for immunotherapy of squamous cell lung cancer and may allow for novel early intervention treatments.

Tuesday, April 28, VCTPL05. Adoptive Cell Transfer Therapy

11:05-11:15 a.m. (CT051): Safety and efficacy of CD19/CD22 CAR T cells in children and young adults with relapsed/refractory ALL

Haneen Shalabi, DO, investigator on the St. Baldrick's Foundation - Stand Up To Cancer Pediatric Cancer Dream Team reports that the team, which has been pioneering dual antigen targeting strategies for CAR T cell therapy, tested a novel humanized bispecific CD19/CD22 CAR T cell construct in patients with relapsed/refractory B ALL seeking to prevent antigen negative escape. In this phase 1 study, CD19/22 CAR was well tolerated and effective in CAR naïve patients, with four of six patients achieving minimal residual disease, negative complete remission. Future plans include exploring an additional dose level, intensifying lymphodepletion for prior CAR patients, and evaluating CAR T-cell product characteristics with outcomes.

1:00-1:10 p.m. (CT056): Durable complete responses to adoptive cell transfer using tumor infiltrating lymphocytes (TIL) in non-small cell lung cancer (NSCLC): a phase I trial.

Ben Creelan, MD, clinical lead on the SU2C Catalyst® Lung Cancer Immunotherapy Research Team, led by Scott J. Antonia, MD, PhD, H. Lee Moffitt Cancer Center & Research Institute, will be presenting data on durable complete responses in metastatic non-small cell lung cancer (NSCLC) with manageable toxicity, potentially extending the benefits of adoptive cell transfer seen in melanoma to NSCLC.

Tuesday, April 28, VCTPL02. Early Detection and ctDNA

2:30-2:40 p.m. (CT023): Phylogenetic tracking and minimal residual disease detection using ctDNA in early-stage NSCLC: A lung TRACERx study

Christopher Abbosh, MB, young investigator on the SU2C-LUNGeivity-American Lung Association Lung Cancer Interception Dream Team reports that circulating tumor DNA is an adjuvant biomarker capable of both detecting minimal residual disease following surgery and defining the clonality of relapsing disease. These data pave the way for clinical trials predicated on escalation of adjuvant standard of care in patients who exhibit minimal residual disease following surgery.

Tuesday, April 28, VMS.CL11.01 - Predictive Biomarkers for Immunotherapeutics

3:55-4:05 p.m. (5666) - A noninvasive approach for early prediction of therapeutic benefit from immune checkpoint inhibition for lung cancer.

Maximilian Diehn, MD, PhD, co-leader and Ash Alizadeh, MD, investigator on the SU2C-LUNGevity Foundation-American Lung Association Lung Cancer Interception Research Team, and other team members report on the use of circulating tumor DNA to predict which non-small cell lung cancer (NSCLC) patients will achieve durable clinical benefit after treatment with immune checkpoint inhibitors. Currently, conventional imaging is often not able to identify which patients will achieve durable clinical benefit. The team was able to demonstrate that pre-treatment circulating tumor DNA and circulating immune profiles can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving immune checkpoint inhibitor therapy.