Culture

The three known human trefoil factor family peptides TFF1, TFF2 and TFF3 are mainly produced by the gastrointestinal mucosa. Named after their trefoil-like folded structure, the molecules provide clinically intriguing properties. Studies demonstrated that these peptides are locally produced to combat inflammation and injuries of the gastrointestinal tract by accelerating wound healing. Therefore, they have a considerable therapeutic potential for gastrointestinal and other mucosal disorders such as the dry eye disease and asthma as the researchers state in an additional review article published in ACS Pharmacology & Translational Science.

Local effects

"To date, there are two oral peptide therapeutics against diseases such as irritable bowel syndrome on the market," says the medicinal chemist Muttenthaler. "Due to the relatively large size of the molecules, they are not being absorbed through the gastrointestinal wall into the bloodstream, and therefore can only act locally in the gastrointestinal tract without major side effects."

The trefoil factor family is "an essential starting point for new therapeutic strategies to treat chronic diseases that remain incurable", explains Muttenthaler, who leads research groups at the Department of Biological Chemistry at the University of Vienna and at the University of Queensland in Brisbane. The studies are being conducted in the context of Muttenthaler's ERC Starting Grant project, which aims at disclosing the mechanisms of wound healing in the gastrointestinal tract. "Based on the chemical synthesis of the TFF peptides, we can now find answers to fundamental questions that we were not able to tackle before."

TFF1 acts as homodimer

In their study, the researchers present the chemical synthesis of TFF1 and its homodimer, a molecule that comprises two TFF1 subunits. Only in its homodimeric form was TFF1 able to interact with mucins, main structural constituents of the gastrointestinal tract, which accelerates the closure of the mucosal barrier and its healing process.

With a length of 60 amino acids, conventional approaches were not applicable for the synthesis of TFF1. The scientists developed a new method to synthesise the peptide in two fragments and assemble them subsequently. The second challenge that the scientists had to overcome was to fold TFF1 correctly by selecting from a multitude of possibilities. Correct folding was then confirmed through structural analysis and the TFF1 homodimer was shown to interact with the gastric mucosa. Muttenthaler and his team now work on the chemical synthesis of the other two members of the trefoil factor family, TFF3 and the more challenging TFF2, which is longer and more complex with its 106 amino acids and 7 disulfide bonds.

New possibilities for molecular design

The chemical synthesis of TFF1 is a milestone for the field since it provides more options to modify this peptide class. To date, recombinant expression was the only way to produce these molecules. "Therefore, their design was limited to the 20 natural amino acids. Chemical synthesis now enables us to design advanced TFF1 probes to study their mechanisms of action or to optimise TFF1 towards its therapeutic applications", Muttenthaler explains.

Molecular probes are essential for a better understanding of TFF1 and its mode of action. Certain attachments such as fluorescent molecules or other reporter tags can help to study TFF1 interactions with its target proteins or receptors. Other modifications could be used to further improve the stability of the peptides and their drug-like properties for a more efficient therapeutic application.

BINGHAMTON, NY -- Students tend to be more engaged in activism if the school that they attend emphasizes social and political issues, according to new research featuring faculty at Binghamton University, State University of New York.

A research team including Binghamton University Assistant Professor of Student Affairs Administration John Zilvinskis examined survey responses to an experimental itemset of the National Survey of Student Engagement measuring behaviors related to student activism. The sample included 3,257 seniors from 22 four-year institutions.

The survey items had respondents measure, "How much does your institution emphasize the following?"

- Discussing social or political issues, causes, campaigns or organizations

- Participating in activities focused on social or political issues, causes, campaigns or organizations

- Organizing activities focused on social or political issues, causes, campaigns or organizations

- Being an informed and active citizen focused on social or political issues, causes, campaigns or organizations

For administrators and educators in higher education, the researchers found that institutions with higher averages of emphasized activism had students who were more likely to participate in these behaviors.

"The higher institutional averages could indicate that a culture of emphasizing activism leads to more student engagement in activism; however, there also may be a self-selection effect in that activists choose to attend institutions that hold these values," said Zilvinskis.

The researchers also found that Black students and queer students were significantly more likely than other respondents to participate in activism.

"Our country has a history of marginalizing people from these groups, so I suspect they are more motivated to engage in activism behaviors to create more equitable experiences," said Zilvinskis. "The disappointing counter-finding is that their straight and White peers are not as engaged in activism."

Zilvinskis is now researching student participation in high-impact practices at community colleges and the engagement of students with disabilities at these institutions.

Scientists have engineered natural killer immune cells that not only kill head and neck tumour cells in mice but also reduce the immune-suppressing myeloid cells that allow tumours to evade the immune response, according to a new study in eLife.

The engineered cell therapy could be used as an alternative approach for treating cancer in patients for whom previous immunotherapy based on the activation of T cells has failed. These findings are reported by researchers at the U.S. National Institutes of Health (NIH) in Bethesda, Maryland.

In recent years, treatments called T-cell therapy or CAR-T cell therapy have been approved to treat blood cancers, and many others are now in development for other forms of cancer. However, these T-cell therapies rely on the ability to reprogram a patient's own T cells to express a chimeric antigen receptor (CAR) that targets tumour cells. This process of reprogramming a patient's own T cells is expensive and laborious.

High affinity natural killer cells (haNKs) represent potential 'off-the-shelf' cell therapies that do not rely on reprogramming a patient's own immune cells. The same cells could be produced in mass and potentially given to anyone. But the presence of immune-suppressing myeloid cells in the tumour microenvironment remains a barrier to effective immunotherapy, including haNK cell-based treatment.

To address this barrier, researchers from the NIH's National Institute on Deafness and Other Communication Disorders (NIDCD) and National Cancer Institute have utilised haNKs expressing a CAR that targets a molecule called programmed death ligand 1 (PD-L1). PD-L1 is a well-known culprit that cancer and immunosuppressive myeloid cells produce in high amounts to dampen down the immune system.

Led by senior author Clint Allen, Principal Investigator, Section on Translational Tumor Immunology, NIDCD, the team tested the engineered PD-L1 haNKs versus ordinary haNKs against human and mouse head and neck cancer cells. They found that the haNKs expressing the PD-L1 CAR kill mouse and human tumour cells to a greater degree than haNKs without the CAR, and that this ability was retained even if they had already been exposed to cells carrying PD-L1 before. This is important because natural killer cells are known to become 'exhausted' after killing target cells.

In mice with head and neck tumours, the haNK cell-based therapy cured the mice in 30% of cases and slowed the growth of tumours in the rest of the mice, without causing toxicity. Treatment with haNKs also reduced the numbers of immunosuppressive myeloid cells that carry PD-L1 within the tumour, while having no effect on other immune-boosting white blood cells.

To investigate whether this effect on the immune cells also occurred in patients, the team incubated white blood cells from people with advanced head and neck cancer with the PD-L1 haNK cells. As they saw in the mice, the immunosuppressive myeloid cells that carry PD-L1 were significantly reduced after treatment with the PD-L1 haNK cells. This suggests that this treatment can both directly kill tumour cells and remove the immunosuppressive myeloid cells that prevent conventional immunotherapies from working.

These findings suggest that haNK cells expressing a PD-L1 CAR may overcome some of the limitations of conventional immunotherapy that relies on T-cell activation, and could be used in patients who are predicted to be insensitive to or have failed existing immunotherapy treatments. The researchers say the next steps would be to take this treatment into the clinic to explore the safety of PD-L1 haNKs in people with advanced or recurring cancer, and to see whether combining haNK cell therapy with other immunotherapies that activate T cells can enhance treatment response.

Toddlers who were obese or overweight show concerning signs of cardiovascular disease at 11-12 years of age, according to a new study led by the Murdoch Children's Research Institute (MCRI).

The study, published in Pediatrics, found Australian children who were obese or overweight very early in life already show evidence by age 11-12 years of stiffer arteries, thickened arterial lining and are a high risk of later developing metabolic syndrome. This worsened the longer these young children were overweight or obese.

MCRI Professor Melissa Wake said the study highlighted the silent effects of obesity in childhood and the need to intervene early.

"Public health efforts are needed in the very early years to prevent problems with obesity and being overweight, to avoid the risk of adolescent and adult cardiovascular disease," she said.

"Our findings are in line with the World Health Organization's calls for urgent collaborative action to address the matter through systems-based approaches and policy implementation.

"Such policies include increasing taxes on processed foods high in fat and sugar, safer and improved public transport and walking to school pathways and making community-based sporting activities more affordable and accessible."

MCRI Dr Kate Lycett said until now little was known about when and how early life BMI impacted heart health in childhood and most studies have previously just looked at standard risk factors such as blood pressure alone.

"Previous studies have tended to rely on a single BMI measurement in childhood and then examined subsequent heart health outcomes in adulthood," she said.

"This overlooks the considerable BMI changes as part of normal childhood growth."

The study involved 1811 children from the Longitudinal Study of Australian Children whose weight and height were measured every two years (age 0-1 to 9-10 years) to determine cardiovascular disease risk scores. At age 11-12, the participants underwent further health checks looking at blood pressure, blood vessel health, cholesterol and glucose levels.

Dr Lycett said the obesity epidemic was a major threat to public health.

"This public health crisis threatens the modest decline in cardiovascular deaths in developed countries, which has largely been achieved through preventive efforts focused on cardiovascular risk factors," she said.

"Policy changes to reign in this epidemic require strong support from the clinical community if they are to be realised."

Early infections of influenza A can help predict how the virus will affect people across different ages in the future and could impact the effectiveness of flu vaccines, says a new study published today in eLife.

The findings may help improve estimates of both the age-specific risk of acquiring seasonal influenza infections and vaccine effectiveness in similarly vaccinated populations.

Seasonal influenza is an acute respiratory infection caused by influenza viruses that occur across the world. It causes approximately 100,000-600,000 hospitalisations and 5,000-27,000 deaths per year in the US alone. There are three types of seasonal influenza viruses in humans: A, B and C, although C is much less common. Influenza A viruses are further classified into subtypes, with the A(H1N1) and A(H3N2) subtypes currently circulating in humans. A(H1N1) is also written as A(H1N1)pdm09 as it caused the 2009 pandemic and replaced the A(H1N1) virus which had circulated before that year.*

The rapid evolution of seasonal influenza that allows it to escape preexisting immunity adds to the relatively high incidence of infections, including in previously infected older children and adults. But how susceptibility arises and changes over time in human populations has been difficult to quantify.

"Since the risk of influenza infection in a given age group changes over time, factors other than age may affect our susceptibility to infection," says first author Philip Arevalo, a postdoctoral researcher in senior author Sarah Cobey's lab, Department of Ecology and Evolution, University of Chicago, US. "We wanted to see whether these differences can be explained in part by the protection gained from childhood flu infection, which has lasting impacts on the immune response to future infections and the protection against new influenza A subtypes."

To measure the effect of early exposures to seasonal influenza on risk and vaccine effectiveness, Arevalo and his team applied statistical models to flu cases identified through seasonal studies of vaccine effectiveness from the 2007-2008 to 2017-2018 seasons in the Marshfield Epidemiologic Study Area (MESA) in Marshfield, Wisconsin, US. Each flu season, individuals in a defined community group were recruited and tested for flu when seeking outpatient care for acute respiratory infection. Those eligible for the study were individuals older than six months of age living in MESA and who received routine care from the Marshfield Clinic.

Despite the extensive evolution in influenza A subtypes H1N1 and H3N2 over the study period, the team's model showed that early infection reduces the risk of people needing to seek medical attention for infections with the same subtype later in life. This effect is stronger for H1N1 compared to H3N2. The model also revealed that the effectiveness of flu vaccines varies with both age and birth year, suggesting that this effectiveness also depends on early exposure.

"We hope the findings from our study will improve our understanding of influenza epidemiology and the low and variable effectiveness of the seasonal flu vaccine," concludes senior author Sarah Cobey, Principal Investigator at the Department of Ecology and Evolution, University of Chicago. "This would lead to better forecasting and vaccination strategies to help combat future flu seasons."

CHAMPAIGN, Ill. -- Charitable giving is a nearly half-trillion-dollar sector of the U.S. economy, but what accounts for why some individuals, foundations and corporations give locally while others give to charities on the other side of the globe? According to a new paper co-written by a University of Illinois at Urbana-Champaign expert in consumer behavior and global marketing, the dynamic interplay between the accessibility of local impact versus more global goals can influence charitable behaviors between donors and recipients.

An appeal to morality can persuade people to make donations that benefit recipients halfway around the world - even though those same resources could be allocated to helping those with similar needs who live closer, said Carlos Torelli, a professor of business administration and the James F. Towey Faculty Fellow at Illinois.

"Although past research suggests that people are more likely to donate money to nearby causes to maximize the positive impact on their local community, donations to foreign causes are growing rapidly," he said. "With the rise of globalization, geographic borders are becoming less relevant for making charitable donations, which means nonprofits and charities can make more effective pitches to donors by emphasizing higher-level concepts such as morality and idealistic values."

Torelli and his co-authors conducted five studies to identify the conditions under which donors pledge higher amounts of money to recipients who are located spatially far away versus nearby recipients, and to rule out the possibility that the effect of spatial distance is driven by unequal economic conditions and, thus, differences in need between the two recipients.

"What we found is that people who donate money to causes that aren't local do so to feel more fulfilled, because it's something that's more aligned with their moral identity, which is the extent to which moral traits, goals and behaviors are important to one's self-concept or self-identity," said Torelli, also the executive director of Executive and Professional Education at the Gies College of Business. "We also found that this positive effect was more prevalent among people high in moral self-concept and was attenuated or even reversed among people low in moral self-concept."

The appeal to morality in requesting donations for distant recipients is "an entirely different framework" than for requesting donations to a local cause, which should emphasize the concrete, actionable impact of a monetary donation, Torelli said.

"For local or nearby causes, you really have to push the immediate impact aspect of it - how many people you can help, how much and how quickly your dollar can be put to work for individuals who are members of the community," he said. "The morality appeal, on the other hand, really has to tap into higher-level idealistic goals - clean water for everyone the alleviation of hunger, for example."

The paper's findings can help organizations increase the efficacy of marketing initiatives, Torelli said.

"The same cause can use different appeals depending on who they're targeting and where they are," he said. "If they're far away, then an appeal to morality is going to be more effective than an appeal to sheer numbers and impact."

The research also has implications for for-profit organizations engaging in corporate social-responsibility initiatives.

"Many large organizations are global and choose international charitable organizations to partner with, to align their social impact with their practices and beliefs," Torelli said. "Not only does this type of initiative have a social impact, it can also have a positive impact on employees of the organization. Our findings suggest that companies with corporate social-responsibility initiatives that help recipients in distant locations could benefit by focusing their communications on the higher-level goals that such initiatives are accomplishing instead of just touting their impact.

"Doing so might result in higher employee involvement with the charitable cause and higher employee satisfaction, particularly for employees who place a lot of importance on moral identity."

What The Article Says: A New York hospital's restructuring of general surgery resident teams and educational infrastructure in response to the COVID-19 pandemic is detailed in this article.

Authors: Heather L. Yeo, M.D., M.H.S., M.B.A., M.S., of NewYork-Presbyterian Hospital/Weill Cornell Medicine in New York, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamasurg.2020.3107)

Editor's Note: The article includes conflicts of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

The outermost reaches of our solar system are a strange place--filled with dark and icy bodies with nicknames like Sedna, Biden and The Goblin, each of which span several hundred miles across.

Two new studies by researchers at the University of Colorado Boulder may help to solve one of the biggest mysteries about these far away worlds: why so many of them don't circle the sun the way they should.

The orbits of these planetary oddities, which scientists call "detached objects," tilt and buckle out of the plane of the solar system, among other unusual behaviors.

"This region of space, which is so much closer to us than stars in our galaxy and other things that we can observe just fine, is just so unknown to us," said Ann-Marie Madigan, an assistant professor in the Department of Astrophysical and Planetary Sciences (APS) at CU Boulder.

Some researchers have suggested that something big could be to blame--like an undiscovered planet, dubbed "Planet 9," that scatters objects in its wake.

But Madigan and graduate student Alexander Zderic prefer to think smaller. Drawing on exhaustive computer simulations, the duo makes the case that these detached objects may have disrupted their own orbits--through tiny gravitational nudges that added up over millions of years.

The findings, Madigan said, provide a tantalizing hint to what may be going on in this mysterious region of space.

"We're the first team to be able to reproduce everything, all the weird orbital anomalies that scientists have seen over the years," said Madigan, also a fellow at JILA. "It's crazy to think that there's still so much we need to do."

The team published its results July 2 in the Astronomical Journal and last month in the Astronomical Journal Letters.

Power to the asteroids

The problem with studying the outer solar system, Madigan added, is that it's just so dark.

"Ordinarily, the only way to observe these objects is to have the sun's rays smack off their surface and come back to our telescopes on Earth," she said. "Because it's so difficult to learn anything about it, there was this assumption that it was empty."

She's one of a growing number of scientists who argue that this region of space is far from empty--but that doesn't make it any easier to understand.

Just look at the detached objects. While most bodies in the solar system tend to circle the sun in a flat disk, the orbits of these icy worlds can tilt like a seesaw. Many also tend to cluster in just one slice of the night sky, a bit similar to a compass that only points north.

Madigan and Zderic wanted to find out why. To do that, they turned to supercomputers to recreate, or model, the dynamics of the outer solar system in greater detail than ever before.

"We modeled something that may have once existed in the outer solar system and also added in the gravitational influence of the giant planets like Jupiter," said Zderic, also of APS.

In the process, they discovered something unusual: the icy objects in their simulations started off orbiting the sun like normal. But then, over time, they began to pull and push on each other. As a result, their orbits grew wonkier until they eventually resembled the real thing. What was most remarkable was that they did it all on their own--the asteroids and minor planets didn't need a big planet to throw them for a loop.

"Individually, all of the gravitational interactions between these small bodies are weak," Madigan said. "But if you have enough of them, that becomes important."

Earth times 20

Madigan and Zderic had seen hints of similar patterns in earlier research, but their latest results provide the most exhaustive evidence yet.

The findings also come with a big caveat. In order to make Madigan and Zderic's theory of "collective gravity" work, the outer solar system once needed to contain a huge amount of stuff.

"You needed objects that added up to something on the order of 20 Earth masses," Madigan said. "That's theoretically possible, but it's definitely going to be bumping up against people's beliefs."

One way or another, scientists should find out soon. A new telescope called the Vera C. Rubin Observatory is scheduled to come online in Chile in 2022 and will begin to shine a new light on this unknown stretch of space.

"A lot of the recent fascination with the outer solar system is related to technological advances," Zderic said. "You really need the newest generation of telescopes to observe these bodies."

Researchers at McMaster University who study how the brain processes sound have discovered the common practice of using artificial tones in perception experiments could mean scientists are overlooking important and interesting discoveries in the field of brain research.

The research, published recently in the journal Scientific Reports, is the culmination of a decade of rigorous analysis, in which the team reviewed one thousand auditory experiments published in several leading journals.

They found nearly 90 per cent of sounds used in these experiments have no connection to the natural world.

"Many theories and models derived from the use of artificial tone beeps in research experiments fail to describe the actual listening processes," says Michael Schutz, lead author and associate professor of Music Cognition and Percussion at McMaster.

Schutz's interdisciplinary background plays an important role in this project. A percussionist by training, he directs the McMaster University Percussion Ensemble and is an active performing musician. This regular immersion in professional music-making has tuned his ears to the complexities of sound--and the lack thereof in artificial tones.

His research team in the MAPLE lab team has repeatedly shown crucial differences in the processing of natural versus artificial sounds, raising questions about the degree to which tone beeps can actually properly test the auditory system.

"Although useful in experiments as they are 'controlled,' tone beeps are unnatural. Nothing in the natural world sounds like them," he says.

His team focuses in particular on the property of amplitude envelope, or the shape of the sound, which they have repeatedly shown plays a crucial role in perception. Their survey of auditory experiments found it was often not even considered or even adequately documented in hundreds of experiments.

The implications are not only theoretical, but also practical, says researchers.

For instance, artificial tones figure prominently in assessing the fit of hearing aids and cochlear implants, yet users frequently find listening to be problematic in natural environments. Researchers suggest unnatural sounds in research of this nature can have implications for our understanding of sensory integration in children with Autism Spectrum Disorder.

Although these children often struggle with integration of speech sounds, research using tone beeps has often failed to replicate those deficits. Given his expertise in studying the perception of natural sounds versus tone beeps, autism researchers at the University of Rochester Medical Centre approached Schutz about using his paradigm to close the gap between lab-based findings and real-world listening which is filled with rich, dynamically changing sounds.

In contrast to the complexity of natural sounds, tone beeps are incredibly impoverished, says Schutz.

"Think of the simplistic sounds we hear every day at the checkout counter, the auditory alerts of a truck backing up or the alarm of a medical device. By showing that these flat, artificial sounds are ubiquitous in research it is easier to understand how they have inadvertently become ingrained into design standards," he says.

Schutz is currently working with an international team to improve auditory alarm design of medical devices, which are often poorly designed and draw upon artificial tones which can create numerous problems in the operating of emergency rooms in hospitals, where they go off frequently, are missed altogether, keep patients awake, among other issues.

He suggests the soundscape of a hospital is jarring and there is tremendous room for improvement, which might include alarms that use musical tones.

"We believe we can improve these sounds and reduce overall annoyance, without sacrificing detectability."

ST. LOUIS, MO, July 7, 2020 - Growth and development of all organisms depends on coordinated regulation of gene expression in time and space, and this is largely controlled by non-coding sequences in the genome. A major challenge in genomics-enabled crop improvement is functional annotation of cis-regulatory elements in crop genomes and the ability to harness these sequences, either through breeding or biotechnology, to fine-tune target pathways with minimal disruption to the complex networks in which they reside.

A team of researchers led by Andrea Eveland, Ph.D., assistant member, Donald Danforth Plant Science Center, has mapped out the non-coding, 'functio nal' genome in maize during an early developmental window critical to formation of pollen-bearing tassels and grain-bearing ears.

Integrating information on chromatin structure, transcript profiles, and genome-wide association studies, their analyses provide a comprehensive look into the regulation of inflorescence differentiation in a major cereal crop, which ultimately shapes architecture and influences yield potential. This study by Parvathaneni and Bertolini et al., "The regulatory landscape of early maize inflorescence development", was published on July 6, 2020 in the journal, Genome Biology.

"We have a good idea of the major controllers of inflorescence development in maize from years of classical genetics studies" said Eveland. "But simply removing their function or expressing them constitutively usually does not result in higher-yielding corn. We need to learn how to adjust their expression precisely in space and time to achieve optimal outputs. This study serves as a foundation for doing that."

Over the past century, hybrid-based breeding and improvement in maize has led to selection of smaller tassels that intercept less light and sequester less resources, and larger, more productive ears. Since the tassel and ear develop by a common developmental program, further improvement of ear traits will require decoupling of this program, for example, by tassel- or ear-specific regulatory elements. Understanding how the same genes are regulated differently in tassel and ear, and using this specificity to control one over the other, will enhance breeding efforts in maize.

Eveland's research focuses on the developmental mechanisms that control plant architecture traits in cereal crops. Specifically, she investigates how plant organs are formed from stem cells, and how variation in the underlying gene regulatory networks can precisely modulate plant form. Her team integrates both computational and experimental approaches to explore how perturbations to these gene networks can alter morphology, both within a species and across the grasses, with the ultimate goal of defining targets for improving grain yield in cereals.

In addition to Eveland's team, co-authors include researchers from Florida State University, the University of California at Davis, and the University of Illinois Urbana-Champaign. The collaborative research was funded by the National Science Foundation PGRP in awards to Eveland and co-author Alexander Lipka, Ph.D. (UIUC) to identify regulatory variation for improving maize yield traits, and to Hank Bass, Ph.D. (FSU) to apply techniques in chromatin profiling to important agronomic crop species.

Ribonucleic acid, or RNA, is part of our genetic code and present in every cell of our body. The best known form of RNA is a single linear strand, of which the function is well known and characterized. But there is also another type of RNA, so-called "circular RNA", or circRNA, which forms a continuous loop that makes it more stable and less vulnerable to degradation. CircRNAs accumulate in the brain with age. Still, the biological functions of most circRNAs are not known and are a riddle for the scientific community. Now scientists from the Max Planck Institute for Biology of Ageing have come one step closer to answer the question what these mysterious circRNAs do: one of them contributes to the ageing process in fruit flies.

Carina Weigelt and other researchers in the group led by Linda Partridge, Director at the Max Planck Institute for Biology of Ageing, used fruit flies to investigate the role of the circRNAs in the ageing process. "This is unique, because it is not very well understood what circRNAs do, especially not in an ageing perspective. Nobody has looked at circRNAs in a longevity context before", says Carina Weigelt who conducted the main part of the study. She continues: "Now we have identified a circRNA that can extend lifespan of fruit flies when we increase it, and it is regulated by insulin signaling".

Specific circRNA influences lifespan via insulin signalling

The insulin pathway regulates ageing, metabolism, reproduction and growth in worms, flies and humans. When this pathway is blocked by different methods, for instance by using genetically modified flies that lack insulin, the flies live longer. But it is not known how exactly this happens. The scientists now believe that part of the answer could lie with the circRNAs. They found a specific circRNA, called circSulfateless (circSfl), that behaved differently compared to other circRNAs. CircSfl was expressed at much higher levels in the long-lived fruit flies that lacked insulin as compared to normal flies. Furthermore, when flies were genetically manipulated to have higher level of circSfl, these flies also lived longer. These findings show that not only is circSfl dependent on insulin - circSfl itself can also directly influence the lifespan of fruit flies.

In the cells the necessary proteins that the body needs for all sorts of functions are made from normal linear RNAs, but generally not from circular RNAs. Again, the scientists found another difference between circSfl and other circular RNAs: a protein is indeed made from circSfl. The exact function of this protein is not known, but Carina Weigelt says: " The circSfl protein is similar but not identical to the classical Sfl protein originating from the linear Sfl RNA. We don't know exactly how the circSfl-derived protein influences ageing, but perhaps it interacts with similar proteins as the regular Sfl protein."

What does this mean for ageing research? Carina Weigelt says: "We want to understand how ageing works and why the flies lacking insulin are long-lived. It seems like one of the mechanisms is circSfl. We now want to further investigate the ageing process by looking at other circular RNAs also in other animals." Because circular RNAs also accumulate in the mammalian brain, these findings most likely also have important implications for humans.

Astrophysicists of Far Eastern Federal University (FEFU) with colleagues from Russia and oversea have revealed that large and dense particles with irregular shapes possess a 10-μm silicate feature introduced in lots of comets and protoplanetary discs. The outcome based on 15 examples of olivine silicate studied doesn't meet Mie theory provisions applied for comet particles modelling and capable of helping to reconsider the results of data. A related article appears in Icarus.

A silicate feature of a measured space object unfolds as a series of peaks in a certain region of the infrared spectrum. They are typical for silicates, minerals forming the mass of Earth rocks. The group of peaks lays in the spectrum at wavelengths of 9.2, 10.0, 10.5, 11.2 and 11.9 micrometres. Since they are all close to a wavelength of 10 microns, the phenomenon got a name as "a ten-micron silicate feature".

Studying the spectrum of protoplanetary disks and comets with a silicate feature, many scientists use the Mie theory for modeling. The theory restricts the size and shape of particles, suggesting that particle shall show a silicate feature only if it is spherical and of a size smaller than 1 micrometer, or bigger which comes along with a porous structure or constitution of individual small fragments.

"Yet such a structure of particles does not correspond to what we see in high-precision images took during the study of comet 67P / Churyumov-Gerasimenko, and is not in agreement with a part of the ground-based studies, which allows us to draw up a number of questions to the modeling method." Ekaterina Chornaya said, a Ph.D. student at the FEFU School of Natural Sciences. "We set up an experiment to find out whether it is possible to reproduce the silicate feature in sufficiently large olivine particles, which can be represented as analogues of cosmic dust. The selected particles had a size much more than 1 micron and a dense structure, which already put off the restrictions of the Mie theory. The olivine particles were not porous and did not consist of separate small fragments, but we have proved that they also have a silicate feature."

The outcome of the experiment puts aside the restriction of the mandatory sphericity and size of particles with a ten-micron silicate feature. It can significantly affect our knowledge about comets and deep space.

Young astrophysicists from FEFU University Ekaterina Chornaya and Anton Kochergin have been studying the microphysical properties of cometary dust for several years. They investigate the principles of cosmic dust particles motion considering solar radiation affect and conduct laboratory experiments with comet dust particles analogues. The purpose of the research is to shed light on the evolutionary processes of the solar system. This is the basic research direction that many scientific groups around the world are engaged in.

The practical measurements (polarimetry and photometry of comets) FEFU scientists carry out on the base of the Ussuriysk Astrophysical Observatory of the Institute of Applied Astronomy of the Russian Academy of Sciences.

Olivine particles were investigated using the latest equipment on the base of the research and educational center "Nanocenter" run in FEFU.

In a new study published in the Journal of Child Psychology and Psychiatry, Candice Alfano, University of Houston professor of psychology and director of the Sleep and Anxiety Center of Houston, reports the results from an innovative, experimental study showing inadequate nighttime sleep alters several aspects of children's emotional health.

Although plenty of correlational research links inadequate sleep with poor emotional health, experimental studies in children are rare. Alfano and her team studied 53 children ages 7-11 over more than a week. The children completed an in-lab emotional assessment twice, once after a night of healthy sleep and again after two nights where their sleep was restricted by several hours.

"After sleep restriction, we observed changes in the way children experience, regulate and express their emotions," reports Alfano. "But, somewhat to our surprise, the most significant alterations were found in response to positive rather than negative emotional stimuli."

The multi-method assessment had children view a range of pictures and movie clips eliciting both positive and negative emotions while the researchers recorded how children responded on multiple levels. In addition to subjective ratings of emotion, researchers collected respiratory sinus arrhythmias (a non-invasive index of cardiac-linked emotion regulation) and objective facial expressions. Alfano points out the novelty of these data. "Studies based on subjective reports of emotion are critically important, but they don't tell us much about the specific mechanisms through which insufficient sleep elevates children's psychiatric risk."

Alfano highlights the implications of her findings for understanding how poor sleep might "spill over" into children's everyday social and emotional lives. "The experience and expression of positive emotions are essential for children's friendships, healthy social interactions and effective coping. Our findings might explain why children who sleep less on average have more peer-related problems," she said.

Another important finding from the study is that the impact of sleep loss on emotion was not uniform across all children. Specifically, children with greater pre-existing anxiety symptoms showed the most dramatic alterations in emotional responding after sleep restriction.

According to Alfano, these results emphasize a potential need to assess and prioritize healthy sleep habits in emotionally vulnerable children.

In a new study published in Cell, "RNA sensing by gut Piezo1 is essential for systemic serotonin synthesis", a research team led by Kenta Maruyama M.D., Ph.D. from National Institute for Physiological Sciences (NIPS) explored the role of Piezo1, a mechano-sensing receptor, in the sensing of bacterial RNA. They found that gut Piezo1 stimulated by bacterial RNA was pivotal for the production of serotonin, an important hormone that regulates gut and bone homeostasis.

Serotonin is critical for normal functioning of the central and peripheral nervous system to control emotion, peristalsis and blood pressure. The two production origins of serotonin include brain neurons and the gut enterochromaffin cells. Notably, serotonin does not cross the blood-brain barrier and 90% of the body's total serotonin is secreted by enterochromaffin cells, establishing gut as the major source of peripheral serotonin. Most of the gut-derived serotonin is absorbed by platelets that release it after a various stimulation. This then leads to the activation of several biological phenomena, such as gut peristalsis and bowel inflammation. Interestingly, it has been reported that small fraction of gut-derived serotonin acts as a hormone. For instance, bone forming osteoblasts function is inhibited by serotonin. Notably, gut specific deletion of tryptophan hydroxylase-1 (Tph-1), a synthase that generates serotonin from tryptophan, leads to the high bone mass phenotype. Despite the pleiotropic functions of gut-derived serotonin in various biological phenomena, the molecular mechanisms controlling serotonin production remain largely unexplored.

Sensation of the mechanical forces in the gut is critical for normal peristalsis, but their molecular mechanisms are elusive. The mechanosensitive Piezo1 cation channel was recently identified, which is expressed in various tissues and is critical for mechano-transduction in vascular development, red blood cell volume control and blood pressure homeostasis. Despite the importance of Piezo1 in mechano-sensation, its function in gut remains to be explored.

In this study, NIPS research team demonstrated that microbiome-derived single-stranded RNA (ssRNA) induces serotonin production from the gut enterochromaffin cells via Piezo1 in the absence of mechanical force. The intestinal epithelium-specific deletion of Piezo1 causes impaired gut peristalsis, mild manifestations of experimental colitis, and increases bone mass accompanied by low serum serotonin levels. The researchers further found that mouse fecal extracts contain large amounts of RNA and purified fecal RNA activates Piezo1. Strikingly, RNase A, a ssRNA degrading enzyme, abolishes the ligand activity of fecal RNA and successfully suppresses serum serotonin level and increases bone mass by infusion to the colon. These findings indicate that targeting gut ssRNA can be a good strategy for modulating the gut-derived serotonin associated pathophysiology.

Astronomers can go their whole career without finding a new object in the sky. But for Lina Necib, a postdoctoral scholar in theoretical physics at Caltech, the discovery of a cluster of stars in the Milky Way, but not born of the Milky Way, came early - with a little help from supercomputers, the Gaia space observatory, and new deep learning methods.

Writing in Nature Astronomy this week, Necib and her collaborators describe Nyx, a vast new stellar stream in the vicinity of the Sun, that may provide the first indication that a dwarf galaxy had merged with the Milky Way disk. These stellar streams are thought to be globular clusters or dwarf galaxies that have been stretched out along its orbit by tidal forces before being completely disrupted.

The discovery of Nyx took a circuitous route, but one that reflects the multifaceted way astronomy and astrophysics are studied today.

FIRE in the Cosmos

Necib studies the kinematics -- or motions -- of stars and dark matter in the Milky Way. "If there are any clumps of stars that are moving together in a particular fashion, that usually tells us that there is a reason that they're moving together."

Since 2014, researchers from Caltech, Northwestern University, UC San Diego and UC Berkeley, among other institutions, have been developing highly-detailed simulations of realistic galaxies as part of a project called FIRE (Feedback In Realistic Environments). These simulations include everything scientists know about how galaxies form and evolve. Starting from the virtual equivalent of the beginning of time, the simulations produce galaxies that look and act much like our own.

Mapping the Milky Way

Concurrent to the FIRE project, the Gaia space observatory was launched in 2013 by the European Space Agency. Its goal is to create an extraordinarily precise three-dimensional map of about one billion stars throughout the Milky Way galaxy and beyond.

"It's the largest kinematic study to date. The observatory provides the motions of one billion stars," she explained. "A subset of it, seven million stars, have 3D velocities, which means that we can know exactly where a star is and its motion. We've gone from very small datasets to doing massive analyses that we couldn't do before to understand the structure of the Milky Way."

The discovery of Nyx involved combining these two major astrophysics projects and analyzing them using deep learning methods.

Among the questions that both the simulations and the sky survey address is: How did the Milky Way become what it is today?

"Galaxies form by swallowing other galaxies," Necib said. "We've assumed that the Milky Way had a quiet merger history, and for a while it was concerning how quiet it was because our simulations show a lot of mergers. Now, with access to a lot of smaller structures, we understand it wasn't as quiet as it seemed. It's very powerful to have all these tools, data and simulations. All of them have to be used at once to disentangle this problem. We're at the beginning stages of being able to really understand the formation of the Milky way."

Applying Deep Learning to Gaia

A map of a billion stars is a mixed blessing: so much information, but nearly impossible to parse by human perception.

"Before, astronomers had to do a lot of looking and plotting, and maybe use some clustering algorithms. But that's not really possible anymore," Necib said. "We can't stare at seven million stars and figure out what they're doing. What we did in this series of projects was use the Gaia mock catalogues."

The Gaia mock catalogue, developed by Robyn Sanderson (University of Pennsylvania), essentially asked: 'If the FIRE simulations were real and observed with Gaia, what would we see?'

Necib's collaborator, Bryan Ostdiek (formerly at University of Oregon, and now at Harvard University), who had previously been involved in the Large Hadron Collider (LHC) project, had experience dealing with huge datasets using machine and deep learning. Porting those methods over to astrophysics opened the door to a new way to explore the cosmos.

"At the LHC, we have incredible simulations, but we worry that machines trained on them may learn the simulation and not real physics," Ostdiek said. "In a similar way, the FIRE galaxies provide a wonderful environment to train our models, but they are not the Milky Way. We had to learn not only what could help us identify the interesting stars in simulation, but also how to get this to generalize to our real galaxy."

The team developed a method of tracking the movements of each star in the virtual galaxies and labelling the stars as either born in the host galaxy or accreted as the products of galaxy mergers. The two types of stars have different signatures, though the differences are often subtle. These labels were used to train the deep learning model, which was then tested on other FIRE simulations.

After they built the catalogue, they applied it to the Gaia data. "We asked the neural network, 'Based on what you've learned, can you label if the stars were accreted or not?'" Necib said.

The model ranked how confident it was that a star was born outside the Milky Way on a range from 0 to 1. The team created a cutoff with a tolerance for error and began exploring the results.

This approach of applying a model trained on one dataset and applying it to a different but related one is called transfer learning and can be fraught with challenges. "We needed to make sure that we're not learning artificial things about the simulation, but really what's going on in the data," Necib said. "For that, we had to give it a little bit of help and tell it to reweigh certain known elements to give it a bit of an anchor."

They first checked to see if it could identify known features of the galaxy. These include "the Gaia sausage" -- the remains of a dwarf galaxy that merged with the Milky Way about six to ten billion years ago and that has a distinctive sausage-like orbital shape.

"It has a very specific signature," she explained. "If the neural network worked the way it's supposed to, we should see this huge structure that we already know is there."

The Gaia sausage was there, as was the stellar halo -- background stars that give the Milky Way its tell-tale shape -- and the Helmi stream, another known dwarf galaxy that merged with the Milky Way in the distant past and was discovered in 1999.

First Sighting: Nyx

The model identified another structure in the analysis: a cluster of 250 stars, rotating with the Milky Way's disk, but also going toward the center of the galaxy.

"Your first instinct is that you have a bug," Necib recounted. "And you're like, 'Oh no!' So, I didn't tell any of my collaborators for three weeks. Then I started realizing it's not a bug, it's actually real and it's new."

But what if it had already been discovered? "You start going through the literature, making sure that nobody has seen it and luckily for me, nobody had. So I got to name it, which is the most exciting thing in astrophysics. I called it Nyx, the Greek goddess of the night. This particular structure is very interesting because it would have been very difficult to see without machine learning."

The project required advanced computing at many different stages. The FIRE and updated FIRE-2 simulations are among the largest computer models of galaxies ever attempted. Each of the nine main simulations -- three separate galaxy formations, each with slightly different starting point for the sun -- took months to compute on the largest, fastest supercomputers in the world. These included Blue Waters at the National Center for Supercomputing Applications (NCSA), NASA's High-End Computing facilities, and most recently Stampede2 at the Texas Advanced Computing Center (TACC).

The researchers used clusters at the University of Oregon to train the deep learning model and to apply it to the massive Gaia dataset. They are currently using Frontera, the fastest system at any university in the world, to continue the work.

"Everything about this project is computationally very intensive and would not be able to happen without large-scale computing," Necib said.

Future Steps

Necib and her team plan to explore Nyx further using ground-based telescopes. This will provide information about the chemical makeup of the stream, and other details that will help them date Nyx's arrival into the Milky Way, and possibly provide clues on where it came from.

The next data release of Gaia in 2021 will contain additional information about 100 million stars in the catalogue, making more discoveries of accreted clusters likely.

"When the Gaia mission started, astronomers knew it was one of the largest datasets that they were going to get, with lots to be excited about," Necib said. "But we needed to evolve our techniques to adapt to the dataset. If we didn't change or update our methods, we'd be missing out on physics that are in our dataset."

The successes of the Caltech team's approach may have an even bigger impact. "We're developing computational tools that will be available for many areas of research and for non-research related things, too," she said. "This is how we push the technological frontier in general."