Culture

Knowing when to fight and when to flee is a big part of many animal societies, including our own.

University of Cincinnati biologist Elizabeth Hobson says some animals make the call based on a sophisticated understanding of social standing and their place in it.

"We have a phrase: Choose your battles wisely. Animals do that. People do that," said Hobson, an assistant professor in UC's College of Arts and Sciences.

In a new article published in the journal Current Opinion in Psychology, Hobson says animals such as monk parakeets seem to understand where they fit in a dominance hierarchy and pick their fights accordingly. This high-level social information helps animals improve or maintain their status.

Dominance hierarchies are common social organizations in nature. They're found in everything from hermit crabs to human society, Hobson said.

"Understanding how information is perceived, processed and used by individuals in hierarchical systems is critical to understanding how animals make aggression decisions because different types of information can underlie different kinds of aggression strategies," she said in the article.

The most basic understanding comes from firsthand experience. 

"The low-information case is when animals only perceive and remember things that happened to them. A good example of this is if you are beaten in a fight. You remember that you lost but not to whom you lost," she said.

Biologists say these battles can have a lasting impact on the combatants called winner effects and loser effects. Winners are more likely to be aggressive in future conflicts while losers are less likely to meet aggression with aggression or pick a new fight.

"With a strong loser effect, if you got beaten, you're less likely to fight again in the future," Hobson said.

Other animals might remember losing to a particular foe and be less inclined to challenge that foe in the future.

"What if you don't just remember the outcome but you remember who beat you? You can build on that," she said. "Going forward, you'll be less aggressive with the individual who beat you. It's a different social dynamic."

But some animals can make judgments not just through their own direct interactions but by observing other animals and making inferences about where those would-be opponents stand in the hierarchy. 

This ability, known as transitive inference, goes like this: If animal A beats animal B and animal B beats animal C, you know animal A can beat animal C. It's a logical conclusion some animals seem to understand, Hobson said.

"Maybe they never have to fight C or they'll know they can beat C," she said.

Hobson is putting her ideas to the test with captive parakeets.

"This paper is setting up a perspective I want to push in my research program. It will be an exciting time," Hobson said.

"We know that without a vaccine we're going to be dealing with this virus for a while," said Johnese Spisso, president of UCLA Health, in an interview with Johannes Czernin. "We have to learn how to continue to provide health care as a health system with the presence of this emerging infectious disease." The interview is one of 5 new COVID-related articles and commentaries published in the June issue of The Journal of Nuclear Medicine (JNM).

In the interview, a JNM "Discussions with Leaders" column, Spisso discusses how UCLA Health and the UCLA Hospital System have dealt with the pandemic and some of their ongoing initiatives in research, including a convalescent plasma study. The organization has now begun dealing with reintroduction of care that had been postponed at the height of the crisis.

In "Guidance and Best Practices for Nuclear Cardiology Laboratories during the Coronavirus Disease 2019 (COVID-19) Pandemic: An Information Statement from ASNC and SNMMI," Hicham Skali, MD, MSc, and colleagues address the practice of nuclear cardiology in the setting of the pandemic, reflecting perspectives of diverse practices across the United States and worldwide. The statement focuses on how to adapt nuclear cardiology practice to COVID, including steps for protecting healthcare personnel and patients.

In "The Role of Nuclear Medicine for COVID-19 - Time to Act Now," Freimut Juengling and colleagues point out that nuclear medicine has much to offer in COVID research, including substantial experience in detecting inflammatory disease. The authors suggest repurposing established nuclear medicine pharmaceuticals and developing new ones to target different aspects of the virus.

In "Yttrium-90 Radioembolization: Telemedicine during the COVID-19 Outbreak, Opportunity for Prime Time," Lawrence Han Hwee Quek and colleagues discuss the use of telemedicine in Singapore to bridge the gap among physicians with necessary medical expertise and ensure continuity of service. "This outbreak may spark a wider adoption of tele-nuclear medicine in the post-COVID-19 era--not just in diagnosis and therapy but also in education for developing nations with limited access to formal training," the authors said.

In "Who Was the First Doctor to Report the COVID-19 Outbreak in Wuhan, China?" Xixing Li and colleagues tell the story of Dr. Zhang Jixian, who is considered to be the first doctor to report the novel coronavirus before its outbreak.

JNM is fast-tracking COVID-related content and providing free access without subscription.

ANN ARBOR, Mich. - For children and young adults with Crohn's disease, steroid-sparing therapies may help reduce the risk of developing a severe and common complication of the inflammatory bowel condition, a new study suggests.

About one in three people with Crohn's disease develop what's known as a perianal fistula, which can be painful, difficult to treat and may become debilitating - and they're much more common in children.

These fistulas are caused by severe inflammation in the digestive tract that spreads so deep it creates an abnormal opening through the wall of the intestine in the rectum area and connects to other neighboring tissues in the body or to the skin.

But children and young adults with Crohn's disease who used steroid-sparing therapies were nearly 60% less likely to develop perianal fistulas than those who didn't, according to the findings that appear in JAMA Network Open. And if they did develop a fistula, those previously treated with such therapies were 55% less likely to undergo surgery to create an ostomy, a medical device that diverts stool into a pouch or "ostomy bag".

"Perianal fistulas have a devastating effect on quality of life for people with Crohn's disease," says lead author Jeremy Adler, M.D., M.Sc., pediatric gastroenterologist and researcher at Michigan Medicine C.S. Mott Children's Hospital and the Susan B. Meister Child Health Evaluation and Research (CHEAR) Center.

"Most of the research so far has focused on treating fistulas once they occur, but we found that effective therapy ahead of time may significantly reduce the risk of developing them in the first place. Until now, there has been little if any data to guide strategies aimed at preventing perianal fistulas."

Adler and colleagues analyzed national data among 2,214 privately-insured people ages 5-24 with Crohn's disease between 2001-2016. Fifty-six percent of patients, or 1,242, initiated steroid-sparing therapy, such as azathioprine, methotrexate and/or infliximab, before developing perianal fistulas. Overall, 20% of those in the study developed perianal fistulas within two years after diagnosis, less commonly in those treated with steroid-sparing therapies.

Addressing Severe Complications

Crohn's disease affects around 60,000 children in the U.S. and may trigger abdominal pain, severe diarrhea, fatigue, weight loss and malnutrition.

The condition can cause destructive intestinal inflammation, which often tunnels into the layers of affected bowel tissue and may create fistulas that penetrate through the bowel wall.

Fistulas provide a path for stool to invade tissues and cause severe complications, with the most common area for fistula development in the area of the rectum or anus.

About 70% of patients with perianal fistulas eventually undergo surgery while 8-19% of patients ultimately require permanent diverting ostomy. Fistulas can cause extreme discomfort, abnormal mucus drainage and fecal incontinence.

"Despite improvements in medical therapies, these fistulas remain difficult to treat and commonly reoccur. Even after surgery, many patients only experience temporary relief," Adler says.

"Effective treatments could potentially have a significant role in preventing perianal fistulas and improve outcomes for patients."

Fistulas also develop more commonly among children who develop Crohn's disease compared to those who first experience the disease in adulthood.

"For reasons that aren't well understood, Crohn's disease often tends to be more aggressive when it develops during childhood," Adler says. "Children are almost twice as likely to develop perianal fistulas than adults. This can be really hard on families.

"For teens and young adults especially, these complications may increase risk for negative body image."

Steroid-sparing immune suppressive drugs have been used for decades and can be effective in healing fistulas - although they still often reoccur and commonly require surgery. But the study found that these medications were significantly associated with reduced complications and perianal fistula development as well, and they may reduce the severity of fistulas in those who do develop them.

The new research follows another recent study from Adler and colleagues of 248 pediatric patients at Michigan Medicine that showed similar results. The findings, published in Clinical Gastroenterology and Hepatology, also suggest that African Americans and Asians may be at higher risk of developing perianal fistulas.

While guidelines from medical societies recommend steroid-sparing therapy for treating Crohn's, national data shows that nearly half of patients aren't using them. Possible barriers may include cost and insurance coverage, or lack of clarity about medication safety and side effects Adler says.

"We need to advocate for broader use of drugs that are known to be effective in treating and controlling Crohn's disease and that may help prevent lifelong complications for young patients," he says.

"Our research supports efforts to provide the best known therapy as early as possible to improve chances of altering disease course and preventing complications. This can make a huge difference in quality of life for children and young adults diagnosed with this serious chronic condition."

Scientists have expanded our understanding of potentially habitable planets orbiting distant stars by including a critical climate component - the presence of airborne dust.

The researchers suggest that planets with significant airborne dust - similar to the world portrayed in the classic sci-fi Dune - could be habitable over a greater range of distances from their parent star, therefore increasing the window for planets capable of sustaining life.

The team from the University of Exeter, the Met Office and the University of East Anglia (UEA) isolated three primary impacts of dust.

Planets orbiting close to stars smaller and cooler than the Sun, so-called M--dwarfs, are likely to exist in synchronised rotation-orbit states, resulting in permanent day and night sides.

The researchers found that dust cools down the hotter dayside but also warms the night side, effectively widening the planet's `habitable zone', the range of distances from the star where surface water could exist. Detection and characterisation of potentially habitable distant planets is currently most effective for these types of worlds.

The results, published today in Nature Communications, also show that for planets in general, cooling by airborne dust could play a significant role at the inner edge of this habitable zone, where it gets so hot that planets might lose their surface water and become inhabitable - in a scenario thought to have occurred on Venus.

As water is lost from the planet and its oceans shrink, the amount of dust in the atmosphere can increase and, as a result, cool the planet down. This process is a so-called negative climate feedback, postponing the planet's loss of its water.

Crucially, the research also suggests that the presence of dust must be accounted for in the search for key biomarkers indicative of life - such as the presence of methane - as it can obscure their signatures as observed by astronomers.

The experts suggest that these results mean exoplanets must be very carefully considered before being potentially rejected in the search for habitable distant worlds.

Dr Ian Boutle, lead author of the study and jointly from the Met Office and the University of Exeter said:" On Earth and Mars, dust storms have both cooling and warming effects on the surface, with the cooling effect typically winning out. But these 'synchronised orbit' planets are very different. Here, the dark sides of these planets are in perpetual night, and the warming effect wins out, whereas on the dayside, the cooling effect wins out. The effect is to moderate the temperature extremes, thus making the planet more habitable."

The presence of mineral dust is known to play a substantial role in climate, both regionally as found on Earth and globally, as experienced on Mars.

The research team performed a series of simulations of terrestrial or Earth-sized exoplanets, using state-of-the-art climate models, and showed for the first time that naturally occurring mineral dust will have a significant impact on whether exoplanets can support life.

Prof Manoj Joshi from UEA said that this study again shows how the possibility of exoplanets supporting life depends not only on the stellar irradiance - or the amount of light energy from the nearest star - but also on the planet's atmospheric make-up. "Airborne dust is something that might keep planets habitable, but also obscures our ability to find signs of life on these planets. These effects need to be considered in future research."

The research project included part of an undergraduate project by Duncan Lyster, who features on the paper's list of authors. Duncan, who now runs his own business crafting surfboards added: "It's exciting to see the results of the practical research in my final year of study paying off. I was working on a fascinating exoplanet atmosphere simulation project, and was lucky enough to be part of a group who could take it on to the level of world-class research."

The quest to identify habitable planets far beyond our solar system is an integral part of current and future space missions, many focused on answering the question of whether we are alone.

Nathan Mayne, from the University of Exeter, who along with a co-author was able to work on this project thanks to funding from the Science and Technology Facilities Council (STFC) added: "Research such as this is only possible by crossing disciplines and combing the excellent understanding and techniques developed to study our own planet's climate, with cutting edge astrophysics.

"To be able to involve undergraduate physics students in this, and other projects, also provides an excellent opportunity for those studying with us to directly develop the skills needed in such technical and collaborative projects.

"With game-changing facilities such as the JWST and E-ELT, becoming available in the near future, and set to provide a huge leap forward in the study of exoplanets, now is a great time to study Physics!"

Inside our cells, DNA is tightly packed and spooled around proteins called histones. Packaging DNA in this way allows large amounts of genetic material to exist inside the cell in a final form called chromatin. Tiny enzymes modify the histones to make sure the genes that are part of the DNA can be accessed and precisely regulated. The result of this is proper gene expression and the production of proteins important for cell function and human health. When this process goes awry, the result can be diseases such as cancers.

The lab of Brian Strahl, PhD, interim chair of the UNC Department of Biochemistry and Biophysics, has been studying this process for years and has now revealed another piece of an intricate epigenetic puzzle - how one enzyme can lead to slightly different chemical modifications that control distinct biological functions important for gene expression and the repair of DNA.

Published in the journal Cell Reports, this research reinforces the notion that the multiple chemical modifications placed on histones by a single enzyme ensures multiple and distinct functions - an idea that was postulated by Strahl and his former mentor, David Allis, PhD, and was called the Histone Code hypothesis.

The Histone Code is important for genome function, yet the rules that govern the code are not fully deciphered. One of the early findings in the field of epigenetics was that a class of enzymes called histone methyltransferases can add a chemical modification multiple times on a single amino acid residue of a histone.

The process by which a histone methyltransferase adds this chemical modification is called methylation. The methyltransferase adds one carbon atom and three hydrogen atoms - a so-called 'methyl group' to a specific amino acid reside of a histone. This process can occur once, twice, or three times on a single amino acid residue, creating different "flavors" of methylation.

A major question in the field had been: do different "flavors" of methylation have the same or distinct biological functions on, say, gene expression important for the maintenance of healthy cells? While other studies had explored this idea for some histone sites that are methylated, many locations of histone methylation had not been investigated.

To answer this question, first author Julia DiFiore, PhD, a graduate student in the Strahl lab at the time of this research, genetically engineered one such methyltransferase called Set2 so it could perform only select flavors of methylation on its amino acid within histones. By achieving this high degree of specificity, the researchers could finally test if the different degrees of methylation at this site have the same or distinct functions.

"We found there are indeed unique functions, as well as shared functions, in gene expression and in DNA repair," Strahl said. "Our findings help to uncover the potential for different methylation states on histones to regulate diverse chromatin functions."

In addition to understanding fundamental cellular processes, "This work could also explain how dysregulation of enzymes such as Set2 might lead to incorrect 'flavors' of methylation to cause human disease," said Strahl, an Oliver Smithies Investigator at the UNC School of Medicine and member of the UNC Lineberger Cancer Center.

One process they examined was how stress conditions - specifically nutrient stress - affects gene expression. Strahl's group observed that when no methylation on the histone H3K36 was present, gene expression was very different than when normal amounts of methylation were present during nutrient stress. Interestingly, they observed that having only two or only three methyl groups (also called di- and trimethylation) had exactly the same effect as having all three types of methylation that are normally present.

DiFiore explained, "During nutrient stress, the overlapping roles of di- and trimethylation help provide flexibility to dynamic processes and better allow the cell to respond to stress." Being able to quickly respond to stress allows the cells to grow and function properly even under less than ideal conditions.

In future studies, Strahl's lab will examine the functions of the different forms of this methylation event in other important cellular contexts and in other model systems including human cells. They hope to put their findings into a broader context of how histone methylation functions and if the inappropriate changes found with these methylation events in human diseases, such as cancers, are behind how these diseases are formed.

Never before have we experienced social isolation on a massive scale as we have during the evolving COVID-19 pandemic. A new paper published in the journal Trends in Cognitive Sciences explores the wide-ranging, negative consequences that social isolation has on our psychological well-being and physical health, including decreased life span. The paper was co-authored by Associate Professor Danilo Bzdok (McGill University and Mila Quebec Artificial Intelligence Institute) and Emeritus Professor Robin Dunbar (University of Oxford).

Through examining a broad range of studies, a full picture emerged of the severe impact that loneliness can have:

-having strong interpersonal relationships is critical for survival across the entire lifespan;

-social isolation is a significant predictor of the risk of death;

-insufficient social stimulation affects reasoning and memory performances, hormone homeostasis, brain grey/white-matter, connectivity and function, as well as resilience to physical and mental disease;

-feelings of loneliness can spread through a social network, causing negatively skewed social perception, escalating morbidity and mortality, and, in older people, precipitating the onset of dementia such as Alzheimer's disease.

Loneliness directly impairs the immune system, making us less resistant to diseases and infections. Indeed, feeling lonely and having few friends can result in a particularly poor immune defence. People who are more socially integrated, however, have better adjusted biomarkers for physiological function, including lower systolic blood pressure, lower body mass index, and lower levels of C-reactive protein (another molecular response to inflammation).

Humans are intensely social and benefit psychologically and physically from social interaction. The tighter we are embedded in a network of friends, for example, the less likely we are to become ill and the higher our rates of survival. People who belong to more groups, such as sports clubs, church, hobby groups, have been found to reduce their risk of future depression by almost 25%.

Associate Professor Department of Biomedical Engineering at McGill University & Canada CIFAR Artificial Intelligence Chair Danilo Bzdok, said: "We are social creatures. Social interplay and cooperation have fuelled the rapid ascent of human culture and civilization. Yet, social species struggle when forced to live in isolation. From babies to the elderly, psychosocial embedding in interpersonal relationships is critical for survival. It is now more urgent than ever to narrow the knowledge gap of how social isolation impacts the human brain as well as mental and physical well-being."

Emeritus Professor of Evolutionary Psychology Robin Dunbar, said: "Loneliness has accelerated in the past decade. Given the potentially severe consequences this can have on our mental and physical health, there is growing recognition and political will to confront this evolving societal challenge. As one consequence, the United Kingdom has launched the 'Campaign to End Loneliness' - a network of over 600 national, regional and local organizations to create the right conditions for reducing loneliness in later life. Such efforts speak to the growing public recognition and political will to confront this evolving societal challenge. These concerns can only be exacerbated if there are prolonged periods of social isolation imposed by national policy responses to extraordinary crises such as COVID-19."

"The smaller the particle, the bigger the hammer." This rule from particle physics, which looks inside the interior of atomic nuclei using gigantic accelerators, also applies to this research. In order to "X-ray" a two-atom molecule such as oxygen, an extremely powerful and ultra-short X-ray pulse is required. This was provided by the European XFEL which started operations in 2017 and is one of the the strongest X-ray source in the world

In order to expose individual molecules, a new X-ray technique is also needed: with the aid of the extremely powerful laser pulse the molecule is quickly robbed of two firmly bound electrons. This leads to the creation of two positively charged ions that fly apart from each other abruptly due to the electrical repulsion. Simultaneously, the fact that electrons also behave like waves is used to advantage. "You can think of it like a sonar," explains project manager Professor Till Jahnke from the Institute for Nuclear Physics. "The electron wave is scattered by the molecular structure during the explosion, and we recorded the resulting diffraction pattern. We were therefore able to essentially X-ray the molecule from within, and observe it in several steps during its break-up."

For this technique, known as "electron diffraction imaging", physicists at the Institute for Nuclear Physics spent several years further developing the COLTRIMS technique, which was conceived there (and is often referred to as a "reaction microscope"). Under the supervision of Dr Markus Schöffler, a corresponding apparatus was modified for the requirements of the European XFEL in advance, and designed and realised in the course of a doctoral thesis by Gregor Kastirke. No simple task, as Till Jahnke observes: "If I had to design a spaceship in order to safely fly to the moon and back, I would definitely want Gregor in my team. I am very impressed by what he accomplished here."

The result, which was published in the current issue of the renowned Physical Review X, provides the first evidence that this experimental method works. In the future, photochemical reactions of individual molecules can be studied using these images with their high temporal resolution. For example, it should be possible to observe the reaction of a medium-sized molecule to UV rays in real time. In addition, these are the first measurement results to be published since the start of operations of the Small Quantum Systems (SQS) experiment station at the European XFEL at the end of 2018.

Researchers have confirmed that adapting splints in combination with the footwear used by disabled children to help them walk can decrease the energy they use by as much as 33%.

The Clinical Biomechanics team at Staffordshire University and the orthotics specialists from The Royal Wolverhampton NHS Trust examined the effectiveness of tuning the splint – footwear combination, using clinical trials with families in the West Midlands.

Nachi Chockalingam, Professor of Clinical Biomechanics, explained: “Helping children with disabilities to play longer and do the things that other children can do is important for all families. The more children with disabilities can play with their friends and do activities they enjoy, the more included they feel.

“We know that children with cerebral palsy use more energy to walk and our team have found fine-tuning splints to suit the individual needs of a child can make huge difference to their overall mobility.”

Dr Nicola Eddison, Clinical lead for Orthotics Service at The Royal Wolverhampton NHS Trust and a Senior Research Fellow, Centre for Biomechanics and Rehabilitation Technologies, Staffordshire University, said: “Our research shows that the appropriate design and tailoring of splints can reduce the energy used by children with CP while increasing their speed and distance, compared with a splint which is not fine-tuned. This is something which could have a significant impact on their quality of life.”

During the study, the researchers analysed the walking pattern of children with cerebral palsy at Staffordshire University’s specialist gait laboratory and participants were assessed while barefoot and with both non-tuned and tuned splints.

Children wearing the fine-tuned splints showed improvements in several areas including hip and pelvic function and knee extension, while a non-tuned splint potentially showed a decrease in hip function.

Mrs Susan Hayfield, from Wolverhampton, is mother of 15-year-old Robert who suffers with Cerebral Palsy. She said: “Dr Eddison and her team have helped Robert from the age of three with his mobility.

“After having his footwear and splint adapted, my son’s walking improved. This treatment has enabled him to be active for longer and he has felt less fatigued, which have all helped to give him a better quality of life”

Robert added: “Wearing the splint helps me stay off my toes and to help me walk heel to toe instead of toe to heel. The splint keeps my foot at a 90-degree angle which supports my walking. When I first remember wearing a splint, I felt different to other people, but now I just feel like it’s normal for me.”

The researchers recommend fine-tuning splints for all children with cerebral palsy who wear them and hope that their findings will be used to inform future clinical practice. Both Dr Eddison and Professor Chockalingam are calling for standardisation of terminologies used within splints, which are also known as Ankle Foot Orthoses (AFO), to help future research and clinical practice.

Professor Chockalingam added: “There still remains a lack of research on the longer-term effects of using a fine-tuned splints but our studies provide a stepping stone to improving quality of life for many children.”

The full research findings, which were published in the June edition of The Foot Journal, are available below:

Does user perception affect adherence when wearing biomechanically optimised ankle foot orthosis – footwear combinations: A pilot study
The effect of tuning ankle foot orthoses-footwear combinations on gait kinematics of children with cerebral palsy: A case series
Ankle Foot Orthoses: Standardisation of Terminology

Journal

The Foot

DOI

10.1016/j.foot.2019.101660

The oncogenic herpesvirus (HHV8 or KSHV) causes a cancer known as Kaposi's Sarcoma. An international team of scientists led by the University of Helsinki has discovered key factors that control the genome maintenance and replication of a virus responsible for lymphatic vascular cancer.

Kaposi Sarcoma (KS) is the most common cancer among AIDS patients and it is often seen in sub Saharan and Mediterranean populations or after graft transplant. Kaposi Sarcoma is suggested to originate from the endothelium in immunocompromised individuals. This disease is caused by a herpesvirus, Kaposi Sarcoma herpesvirus (KSHV).

KSHV displays two modes of infection, latency and lytic phase, with both phases contributing to the tumorigenesis. Latency represents the default mode of infection in virtually all susceptible cell types. Quite exceptionally, lymphatic endothelial cells (LEC), the suggested KS tumor cells precursors, display a unique viral infection program with spontaneous lytic gene expression as well as high intra- and extracellular viral load.

In the current publication in Cancer Research, a journal of the American Association for Cancer Research, a collaborative team of researchers led by Professor Päivi Ojala decided to address a long-standing question: What is the molecular etiology of the spontaneous lytic phase observed in KSHV-infected primary human lymphatic endothelial cells (KLECs)?

"The research group discovered that two central proteins that directly regulate gene expression on the DNA are key factors, control the genome maintenance and replication of a virus responsible for lymphatic vascular cancer. These two factors support the virus-induced tumor formation and represent new attractive therapeutic targets," Ojala says.

A finding turns around the current dogma

Silvia Gramolelli, an Academy of Finland post-doctoral researcher at the University of Helsinki, investigated the role in Kaposi Sarcoma of PROX1, SOX18 and COUPTF2, the three key transcription factors (TFs) governing the birth of the lymphatic vasculature during embryonic development.

The results of the study demonstrate that all three key factors are expressed in a cohort of KS tumors concomitant with unexpectedly prominent marker of the late lytic phase, the protein K8.1.

"Key transcription factors SOX18 and PROX1 expressions are crucial to support the spontaneous and productive KSHV lytic infection program in LECs, and their expression in tumors correlates with lytic and latent markers of infection," says Gramolelli.

This finding turns around the current dogma that regards the KS tumor cells predominantly latently infected and indicates that lytic gene expression is far more abundant than previously thought.

"To our surprise, SOX18 and PROX1 regulate two different and complementary processes in the virus oncogenic replication cycle independently from each other," says Gramolelli.

"While PROX1 enhances the viral lytic gene expression, SOX18 is involved in the maintenance of a higher number of viral genome copies. Besides revealing an exciting insight on the KSHV infection program in endothelial cells, this study uncovers how the virus mechanistically hijacks PROX1 and SOX18 to its genome to support its own replication and lytic gene expression," Gramolelli continues.

A companion study demonstrating PROX1-Enhanced Productive Lytic Replication of KSHV led by Professor Young Kwon Hong (Keck School of Medicine, University of Southern California) is also published as a back-to-back article in Cancer research.

A new KS therapy?

Despite decades of research, no standard treatment for KS has been established. Clinical outcomes are particularly unfavorable, especially in resource-limited communities.

The research group discovered in collaboration with Associate Professor Mathias Francois (the Centenary Institute, University of Sydney) that both a SOX18 small molecule inhibitor previously developed by Francois and the R-enantiomer of an FDA-approved beta blocker, propranolol, showed a striking reduction in intracellular and extracellular viral loads in vitro.

"These findings suggest a potential, novel therapeutic avenue for KS, but further work is required to see if it will be possible to apply them to design new KS therapeutic strategies targeting SOX18," Ojala says.

A new study from the University of Georgia has shown that exposure to a now-banned flame retardant can alter the genetic code in sperm, leading to major health defects in children of exposed parents.

Published recently in Scientific Reports, the study is the first to investigate how polybrominated biphenyl-153 (PBB153), the primary chemical component of the flame retardant FireMaster, impacts paternal reproduction.

In 1973, an estimated 6.5 million Michigan residents were exposed to PBB153 when FireMaster was accidentally sent to state grain mills where it made its way into the food supply. In the decades since, a range of health problems including skin discoloration, headache, dizziness, joint pain and even some cancers have been linked to the exposure.

More striking, the children of those who were exposed seemed to experience a host of health issues as well, including reports of hernia or buildup in the scrotum for newborn sons and a higher chance of stillbirth or miscarriage among adult daughters.

Yet, little work has been done to understand how the chemical exposure could have impacted genes passed from an exposed father, said study author Katherine Greeson.

"It is still a relatively new idea that a man's exposures prior to conception can impact the health of his children," said Greeson, an environmental health science doctoral student in Charles Easley's lab at UGA's College of Public Health and Regenerative Bioscience Center.

"Most studies where a toxic effect is observed in children look only to the mothers and the same has been true of studies conducted on PBB153," she said.

Greeson and a team of researchers from UGA and Emory University used a unique combination of observational and laboratory approaches to demonstrate how PBB153 acted on sperm cells.

"Typically, scientific studies are either epidemiological in nature and inherently observational or focus on bench science, but in this study, we did both," said Greeson.

This approach allowed the researchers to mimic the known blood exposure levels of PBB153 in a lab environment.

"We were uniquely able to recreate this effect using our previously characterized human stem cell model for spermatogenesis," she said, "which allowed us to study the mechanism that causes this effect in humans."

The team looked at the expression of different genes in their human spermatogenesis model after dosing with PBB153 and found marked alterations in gene expression between dosed and undosed cells, specifically at genes important to development, such as embryonic organ, limb, muscle, and nervous system development.

"PBB153 causes changes to the DNA in sperm in a way that changes how the genes are turned on and off," said Greeson. "PBB153 seems to turn on these genes in sperm which should be turned off," said Greeson, which may explain some of the endocrine-related health issues observed in the children of exposed parents.

Though the study used this model to directly replicate exposure to PBB153, Greeson says this approach could be used to better understand the impact of other environmental exposures on reproduction, including large-scale accidental exposures to toxic chemicals or everyday exposures.

"Hopefully this work will lead to more studies combining epidemiology and bench science in the future, which will tell us more about why we're seeing an effect from an environmental exposure in human populations and encourage experimental studies to more closely mimic human exposures," she said.

Chronic bone and joint diseases, such as osteoporosis and rheumatoid arthritis, affect millions of people worldwide, particularly the elderly, degrading their quality of life. An important factor in both of these diseases is the excessive activity of bone-dissolving cells called osteoclasts. Osteoclasts are formed through differentiation from a certain type of immune cell called macrophage, after which they acquire their new role in the maintenance of bones and joints: breaking down bone tissue to allow osteoblasts-another type of cell-to repair and remodel the skeletal system.

Broadly, two intracellular processes are involved in this differentiation: first, transcription-in which a messenger RNA (mRNA) is created from the genetic information in DNA-and then, translation-in which the information in the mRNA is decoded to produce proteins that perform specific functions in the cell. Since the discovery of the role of a particular protein called RANKL in osteoclast formation, scientists have solved a considerable portion of the puzzle of which cell signaling pathways and transcription networks regulate osteoclast generation. Yet, the post-transcription cellular processes involved remain to be understood.

Now, in a new study published in Biochemical and Biophysical Research Communications, scientists at Tokyo University of Science, Japan, unraveled the role of a protein called Cpeb4 in this complex process. Cpeb4 is part of the "cytoplasmic polyadenylation element binding (CPEB)" family of proteins, which bind to RNA and regulate translational activation and repression, as well as "alternative splicing" mechanisms that produce protein variants. Dr Tadayoshi Hayata, who led the study, explains: "CPEB proteins are implicated in various biological processes and diseases, such as autism, cancer, and red blood cell differentiation. However, their functions in osteoclast differentiation are not clearly known. Therefore, we conducted a series of experiments to characterize a protein from this family, Cpeb4, using cell cultures of mouse macrophages."

In the various cell culture experiments conducted, mouse macrophages were stimulated with RANKL to trigger osteoclast differentiation and the evolution of the culture was monitored. First, the scientists found that Cpeb4 gene expression, and consequently the amount of Cpeb4 protein, increased during osteoclast differentiation. Then, through immunofluorescence microscopy, they visualized the changes in the location of Cpeb4 within the cells. They found that Cpeb4 moves from the cytoplasm into nuclei, while presenting specific shapes (osteoclasts tend to fuse together and form cells with multiple nuclei). This indicates that the function of Cpeb4 associated with osteoclast differentiation is likely carried out inside the nuclei.

To understand how RANKL stimulation causes this Cpeb4 relocalization, the scientists selectively "inhibited" or represses some of the proteins that become involved "downstream" in the intracellular signaling pathways triggered by the stimulation. They identified two pathways as necessary for the process. Nonetheless, further experiments will be required to fully learn about the sequence of events that takes place and all the proteins involved.

Finally, Dr Hayata and his team demonstrated that Cpeb4 is absolutely necessary for osteoclast formation using macrophage cultures in which Cpeb4 was actively depleted. The cells in these cultures did not undergo further differentiation to become osteoclasts.

Taken together, the results are a stepping stone to understanding the cellular mechanisms involved in osteoclast formation. Dr Hayata remarks: "Our study sheds light on the important role of the RNA-binding protein Cpeb4 as a positive "influencer" of osteoclast differentiation. This gives us a better understanding of the pathological conditions of bone and joint diseases and may contribute to the development of therapeutic strategies for major diseases like osteoporosis and rheumatoid arthritis." Hopefully, the deeper level of understanding of osteoclast generation facilitated by this study will ultimately translate into improved quality of life for people living with painful bone and joint diseases.

About The Tokyo University of Science

Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized
private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido.
Established in 1881, the university has continually contributed to Japan's development in science through
inculcating the love for science in researchers, technicians, and educators.

With a mission of "Creating science and technology for the harmonious development of nature, human beings, and
society", TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a
multidisciplinary approach to research and undertaken intensive study in some of today's most vital fields. TUS is a
meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that
has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the
natural sciences field.

Website: https://www.tus.ac.jp/en/mediarelations/

About Associate Professor Tadayoshi Hayata from the Tokyo University of Science

Since 2018, Dr Tadayoshi Hayata has been Associate Professor and Principal Investigator at the Department of Molecular Pharmacology, Faculty of Pharmaceutical Science, at the Tokyo University of Science. His laboratory focuses on bone metabolism, cellular differentiation, molecular pharmacology, and similar fields to understand the nature of bone and joint diseases and find therapeutic targets. Dr Hayata is affiliated with several Japanese Societies and the American Society for Bone and Mineral Research. He has published over 50 original articles and given over 150 presentations at academic conferences. In addition, his research on osteoporosis has made it to Japanese newspapers several times.
https://www.tus.ac.jp/en/fac/p/index.php?7014

Journal

Biochemical and Biophysical Research Communications

DOI

10.1016/j.bbrc.2020.05.089

A group on organic compounds under Professor Ivan Stoikov's guidance has been working on phenothiazine derivatives at Kazan Federal University since 2016.

Probably the most well-known derivative among the general public is methylene blue - a dye with antiseptic properties.

According to co-author Alena Khadieva, recent studies also show its high potential for use as photochemical and photodynamic agent that can be applied in the incision area during surgical operations and for localized therapy of cancerous tumors. The main problem of using compounds similar in structure to methylene blue is their aggregation in aqueous media.

This paper is devoted to the preparation of new phenothiazine derivatives containing phenyl groups instead of alkyl groups, which, according to published data, will provide greater photochemical activity. The presence of phenyl groups should also provide steric hindrances to the dimerization of phenothiazine derivatives. It also leads to high absorption in the near-infrared spectrum. Near-infrared radiation is characterized by high penetration of biological tissues without damaging them. Photoactive antimicrobial, antibacterial and anti-cancer agents based on organic oligoaromatic and polyaromatic compounds are currently attracting increased attention of researchers, since this direction opens up prospects for overcoming antibiotic resistance.

The next objective of the study was to ensure high stability of the dispersions of new phenothiazine derivatives. For this, a binary associate was obtained in which the phenothiazine derivative containing carboxyl groups acts as an acid, and the deprotonated phenothiazine derivative as a base. Due to the presence of complementary groups, stable dispersions were obtained. The stability of the dispersions was confirmed by dynamic light scattering, and the composition of the associate - by ultraviolet spectroscopy. The particle morphology was also studied by scanning electron microscopy, which made it possible to establish that the formation of the associate also changes the shape of the particles.

The synthesis of new phenothiazine derivatives containing, along with phenyl groups, fragments capable of forming intermolecular hydrogen bonds and capable of forming stable dispersions in water, will significantly expand the scope of their application in the composition of materials for photodynamic therapy.

In addition to working to obtain more stable dispersions, as well as water-soluble phenothiazine derivatives for use in medicine, the group also plans to move further to creating phenothiazine-cyclophane associates for use as colorimetric test samples to determine the content of toxic ions. Some of the results were published in Synthesis of Tris-pillar [5] arene and Its Association with Phenothiazine Dye: Colorimetric Recognition of Anions.

Both inquiries under Dr. Vladimir Gorbachuk's supervision were financially supported by the Russian Science Foundation (Project No. 18-73-00293).

Due to the structural similarity of arylamine derivatives of phenothiazine with emeraldine (a popular conductive organic polymer), research for obtaining electrochemically active stable dispersions based on the emeraldine-phenothiazine associate is also seen as promising.

Although social distancing is crucial in thwarting the spread of COVID-19, isolation and the ensuing loneliness may be severely detrimental for older adults. A new study conducted by researchers at Bar-Ilan University and the University of Haifa has linked COVID-19-based loneliness in older adults with elevated psychiatric symptoms of anxiety, depression, and trauma symptoms that immediately follow exposure to trauma. The findings were recently published in the American Journal of Geriatric Psychiatry.

The study focused on older adults, a sector of the population at greater risk for COVID-19 health complications that likely remained in stricter self-isolation than other age groups due to this risk. Notably, the researchers found that the effect of loneliness on psychiatric symptoms was most pronounced among participants who felt subjectively older than their chronological age. On the other hand, participants who felt subjectively younger than their chronological age exhibited no psychiatric symptoms related to loneliness.

"The way older adults perceive old age and their own aging may be more important to their coping and wellbeing than their chronological age," said Prof. Amit Shrira, from the Gerontology Program at the Interdisciplinary Department of Social Sciences at Bar-Ilan University, who conducted the study with Prof. Ehud Bodner and Dr. Yaakov Hoffman, of Bar-Ilan, and Prof. Yuval Palgi from the University of Haifa.

The findings may assist in identifying older adults at high risk for developing psychiatric symptoms due to COVID-19-related loneliness. In addition, they can guide the development of suitable interventions aimed at lowering perception of age in order to mitigate the negative impact of such loneliness and create a protective factor to prevent such a link. The data should also be helpful in advancing preparatory measures for a future pandemic.

What can be done to relieve the emotional burden of isolation among the elderly? Shrira, a clinical psychologist by training, recommends providing ongoing assistance and communication while adhering to relevant health guidelines. Regular conversations with family members, volunteers and even strangers can prevent the onset of deeper loneliness and the sense that no one is willing to hear their pain. Allowing them to share their experience and wisdom helps them feel more valuable. For those coping with feelings of boredom and emptiness during isolation, Shrira suggests that reading, listening to music, solving puzzles, cooking and baking, physical exercise (even the most minimal) and other leisure activities can refresh the normal, monotonous routine.

Correction: The headline on this news release has been changed to, "National calorie menu labeling law could add years of healthy living, save billions" from the original, "Study: National calorie menu labeling law will add years of healthy living, save billions."

BOSTON (June 9, 2020, 9:00 a.m. EDT)--The national law requiring chain restaurants to include calorie labels on menus is estimated to prevent tens of thousands of new heart disease and type 2 diabetes cases--and save thousands of lives--in just five years, according to a new study estimating the law's impact.

The research model also estimated that the law would produce $10-14 billion in healthcare cost savings and another $3-5 billion in societal cost savings, such as from prevented lost productivity, over a lifetime.

The study simulates what would happen if one million hypothetical Americans, aged 35-80, cut their calorie intake moderately while dining out, after making healthier choices based on the labels. The research, published in Circulation: Cardiovascular Quality and Outcomes, was led by researchers at the Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy at Tufts University and the Harvard T.H. Chan School of Public Health.

The analysis estimated that beginning in 2018, when the law was implemented, until 2023, healthier consumer menu choices would:

Prevent 14,698 new cases of heart disease (including 1, 575 deaths)

Prevent 21,522 new type 2 diabetes cases

Add 8,749 years of life (in good health)

When calculated over a lifetime, the analysis estimated better consumer menu choices would:

Prevent 135,781 new heart disease cases (including 27,646 deaths)

Prevent 99,736 type 2 diabetes cases

Add 367,450 years of life (in good health)

"Prior to COVID-19, Americans were relying on restaurants for one in five calories, on average. Most likely, we will come to rely on them again. Our study shows that menu calorie labeling may prevent meaningful disease and save billions of dollars in healthcare costs," said Dariush Mozaffarian, dean of the Friedman School. Mozaffarian is co-first author of the study along with Junxiu Liu, a postdoctoral scholar at the Friedman School.

The simulation estimated, based on prior interventional studies of food labeling, that menu calorie labeling would lead consumers toward lower calorie choices, resulting in a modest 7 percent fewer calories eaten at any average restaurant meal. The researchers conservatively assumed that half of these "saved" calories from each restaurant meal would be offset by additional calories unconsciously consumed by the consumer elsewhere, for example, at home.

"We also found that menu calorie labeling could help reduce health disparities, with larger benefits among Hispanics and Blacks, those with lower income or education, and people with obesity," said Renata Micha, co-last author and associate research professor at the Friedman School.

In addition to consumer responses, the research team estimated the potential health and economic impacts if restaurants respond to the calorie labeling law by reformulating some of their items to reduce calorie contents. They found that the law's health benefits could be twice as large, compared to health effects from changes in consumer choices alone. To estimate the potential effects of restaurant reformulations, the team projected that at the end of five years, there would be an average 5 percent calorie reduction in restaurant meals. Once again, the researchers conservatively assumed that half of the "saved" calories from reformulated restaurant meals would be offset by additional calories consumed elsewhere.

"Our estimates were cautious, based on the idea that both consumers and restaurants would cut calories only modestly. Part of the attraction of eating out is pleasure, and our model assumes people will still treat themselves, but the experience can be healthier overall if both diners and the restaurant industry make changes," said co-last author Thomas Gaziano, of the Harvard Chan School and Brigham and Women's Hospital, who designed the simulation model used in the study.

The federal law and resulting FDA regulation requires restaurants that are part of a chain with 20 or more locations to post calorie information for menu items. The FDA has given covered restaurants temporary flexibility during the COVID-19 crisis, due to the pandemic's impact on the restaurant industry.

"Current flexibility is appropriate when so many Americans are unemployed, and schools are closed. But improving the healthfulness of our food system is crucial, given the pandemic's disproportionate impact on people with diet-related conditions like diabetes and obesity, and further links to health disparities," Mozaffarian said.

"We need to change our food system through equitable, efficient and sustained food and nutrition policies. Food labeling is an effective tool to support informed consumer choice and stimulate industry reformulation," Micha said.

Methodology

The researchers used the Harvard CVD-PREDICT, a validated microsimulation model, and a simulated nationally representative sample of adults from four cycles of the National Health and Nutrition Survey (NHANES 2009-2016). Calorie intake was derived using up to two 24-hour recalls per person, with calorie intake from restaurants estimated by the reported source of food. Each simulated person was followed for 28 years on average, until death or age 100, whichever came first.

The authors caution that modeling results do not provide proof of the menu calorie labeling law's health and cost impacts. In addition, the study was conducted before the emergence of SARS-CoV-2 and does not include the impact of the pandemic on consumer habits and the restaurant industry.

Estonian scientists are developing a DNA-based method of analysis that enables them to identify food components and specify the origin of a foodstuff.

Bioinformatics specialists at the University of Tartu, in cooperation with the Competence Centre on Health Technologies, have published a research paper in the journal Frontiers in Plant Science in which they indicated the possibility to identify components in thermally processed food using DNA analysis even if the quantities were very small. The scientists analysed thermally processed cookies that contained a small amount of lupin flour. The DNA analysis provided reliable identification of lupin even when the lupin flour content in the dough was just 0.02%.

Food always contains the DNA traces of the plants, animals and microorganisms that have been used or that the food or its raw materials have come into contact with in the production process. DNA analysis can provide valuable information on the content, origin, safety and health benefits of food and will make the identification of counterfeit foods and non-compliances in the ingredients specified on the packaging more reliable in the future. For example, certain cases gained attention last year in which the origin of honey and the authenticity of Estonian honey needed verification. The novel DNA analysis would make it possible to solve such issues.

According to Kairi Raime, the lead author of the article, Research Fellow of Bioinformatics at the Institute of Molecular and Cell Biology and a doctoral student at the University of Tartu, their method is a major step forward in the development of DNA-based methods for food analysis. "Our method helps to identify the actual biological contents and origins of food via DNA information and thus ensures the safety and authenticity of the food," she explained. Raime is planning to defend her PhD dissertation on the topic.

The DNA may be significantly degraded in processed food. Scientists extracted DNA from the cookies and analysed it using DNA sequencing technology. For the analysis of a single biscuit, approximately 20 million DNA sequences were obtained. Based on these, and by using bioinformatic analysis, it was possible to specify the DNA of the species found in the sample analysed. The main issue was the preparation of the DNA for sequencing, as the DNA is often degraded in food and even minute amounts of DNA molecules must be identified.

Kaarel Krjutškov, Head of the Precision Medicine Laboratory of the Competence Centre on Health Technologies and Senior Research Fellow of Molecular Medicine at the University of Tartu, whose laboratory was used to prepare the sequencing of the DNA extracted from the biscuits, noted that faking the DNA fingerprint of a food is complicated and expensive, and it is therefore cheaper to offer authentic food. "People can see that in medicine, precise DNA analysis is already a reality, but in food industry and in the field of food safety, the golden age of DNA-based analysis is yet to come," Krjutškov remarked.

The research used a method based on short, unique DNA sequences (k-mers) for analysing genomic DNA data, which enables the scientists to quickly identify plant or bacterial DNA present in a food or an environmental sample. The Chair of Bioinformatics at the Institute of Molecular and Cell Biology at the University of Tartu has been developing competence in the bioinformatics of k-mers and DNA analysis over the last five years. The software developed in the Chair of Bioinformatics has been used both in medicine and for providing food safety.

The article authors' earlier cooperation resulted in the NIPTIFY foetal chromosomal disorder test, which helps to detect, with almost 100% accuracy, the DNA sequences causing foetal Down syndrome in the mother's blood sample as early as the tenth week of pregnancy. The genome analysis method developed in the Chair of Bioinformatics is used to identify pathogenic bacteria, specify their disease-causing capabilities and predict antibiotic resistance. This enabled Maido Remm, Professor of Bioinformatics at the University of Tartu, and his working group to advise the management board of a production company contaminated with a dangerous strain and to help determine the spread of type ST1247 in the company during the listeria outbreak in autumn 2019.

According to Remm, the research article proves that DNA sequencing can also be used for identifying allergenic ingredients in processed food. "DNA sequencing is a promising diagnostic method which makes it possible to quickly obtain precise information about food and the microbes around us," he said. "The use of sequencing and k-mers makes it possible in a very short time to implement a diverse range of diagnostic tests that meet the needs of researchers and companies."