Culture

New research on the genetics of Prader-Willi and Angelman syndromes could help in developing personalised therapies for associated mental illness and autism features. Prader-Willi syndrome (PWS) and Angelman syndrome (AS) have few treatments for associated complications including autism spectrum disorder (ASD) and mental health issues such as psychosis.

Murdoch Children's Research Institute (MCRI) and University of Kansas Medical Center (KU Medical Center) experts have found that changes in expression levels of the UBE3A gene in white blood cells were associated with social and communication difficulties in PWS and impairment of fine motor and language skills in AS. The team now plan to investigate whether these changes are also seen in patients' supporting brain cells, called glia.

PWS and AS each affect 1 in 15,000 people and among other things cause intellectual and behavioural challenges. Apart from giving human growth hormone, treatments for Prader-Willi syndrome only address individual symptoms. The only Angelman syndrome treatments involve symptom-related therapies such as anti-seizure medication and physical, communication and behaviour therapy.

Published in Translational Psychiatry, the study investigated three conditions caused by chromosome 15 alterations, and included 27 participants affected with PWS, 21 with AS and 10 with chromosome 15 duplication (Dup15q) syndrome. It identified new links between UBE3A gene activity in white blood cells, autism features and fine motor and language skills. These raise the possibility that inflammatory pathways may be involved in contributing to disease severity in these conditions.

Senior author, MCRI Diagnosis and Development Laboratory head and University of Melbourne Department of Paediatrics Associate Professor David Godler, said immune system changes had been implicated as key contributors to mental health issues in other disorders, including ASD. This study now suggests this may also be the case in chromosome 15-related conditions.

If confirmed in future studies, these findings could lead to new treatments that control the function of immune cells. They could also lead to new ways of predicting the type and severity of symptoms, using easily accessible biological materials, such as blood, which may be helpful for families and in assessing the effectiveness of new treatments as they arise.

"The immune system plays an important role in ensuring that nerve cells in the brain function properly," Associate Professor Godler said. "This is the first study to show that gene expression changes in white blood cells of individuals with PWS and AS are related to these issues too."

Australian study clinical lead Professor David Amor said the new research made meaningful change possible. "For a child that has significant obsessions, behavioural disturbance or autism, even if we can just improve those by 20 per cent, that can potentially translate into a substantial improvement in quality of life both for the child and for the family," he said.

Project psychologist Dr Emma Baker said psychiatric and behavioural issues associated with these conditions were "quite challenging". Those with PWS are prone to emotional outbursts, communication issues, and restrictive and repetitive behaviours that can exacerbate the core features of the disorder, such as overeating.

"This can really interfere with how an individual with Prader-Willi engages with the world," Dr Baker said. "Motor difficulties are big issues for children with Angelman syndrome. We found associations between UBE3A gene expression levels in white blood cells and fine motor skills. Improving motor skills can improve engagement and learning."

The study was conducted in collaboration with University of Kansas Medical Center PWS expert Professor of Psychiatry and Paediatrics Merlin Butler and his group, primarily supported by US-based Foundation for Prader-Willi Research (FPWR), Foundation for Angelman Syndrome Therapeutics (FAST) Australia and the Medical Research Future Fund.

"The study approach was novel," Professor Butler said. "The resultant genetic and clinical findings are preliminary; but if confirmed may revolutionise our understanding of brain-behavioural-gene interactions, opening new research on the role of genetics in human behaviour and treatment."

The principal investigators on this project have now been awarded additional funding from the US-based Foundation for Prader-Willi Research (FPWR) to build upon its findings by examining brain tissues of individuals affected with PWS.

FPWR Director of Research Programs Dr Theresa Strong said, "These novel insights ... lay the groundwork for exploring new treatment approaches for some of the most challenging aspects of PWS. Autism features, behavioural problems and mental illness can have profound impacts on individuals and families."

Ms Sally Hartmanis has a sister, Stephanie, with Angleman syndrome. "It's been extremely difficult to never hear Stephanie speak and to have no way of knowing what she is thinking or experiencing, or how much she understands. Over the years, Stephanie has developed certain repetitive behaviours which can be quite distressing to witness. It's upsetting not knowing what the cause of these behaviours are, or how we can help her.

"I'm comforted by the knowledge that researchers are finding and putting together the puzzle pieces underlying this heartbreaking condition."

Visit the MCRI website or FPWR for more information.

The ability to detect threatening stimuli and initiate an escape response is critical for survival and under stringent evolutionary pressure. To detect predators, fish use a number of sensory systems including olfaction (smell) and vision, which contribute to the activation of arousal systems. Surprisingly, little is known about the neural mechanisms through which ecological perturbation shapes the evolution of escape response. When startled, do all fish respond the same way?

A few fish, like Mexican cavefish, Astyanax mexicanus, have evolved in unique environments without any predators. To determine how this lack of predation impacts escape responses that are highly stereotyped across fish species, researchers from Florida Atlantic University's Charles E. Schmidt College of Science and Harriet L. Wilkes Honors College explored the tiny A. mexicanus to determine if there are evolved difference in the species. A. mexicanus exist as surface fish that inhabit rivers in Mexico and Southern Texas and as more than 30 geographically isolated cave-dwelling populations of the same species.

The ecology of caves differs dramatically from the surface habitat, resulting in distinct morphological and behavioral phenotypes in A. mexicanus. Cave populations live in environments without light, which is thought to contribute to the evolution of albinism, eye-loss, and circadian rhythm. Because they lack predators they might also lack the selective pressure to avoid predators. Dramatic differences in these cavefish populations combined with the robust ecological differences suggest that the startle reflex could indeed differ between populations of A. mexicanus.

To put this theory to the test, researchers elicited "C-start" responses using acoustic stimuli and high-speed videography in multiple cavefish populations and compared responses to eyed surface fish. The C-start escape response represents a primary mechanism for predator avoidance in fish and amphibians. C-start gets its name from the "c-shaped" curve a fish's body forms during the first stage of the escape response, which is followed by a smaller counter-bend and then rapid swimming.

Results of the study, published in a special issue of the Journal of Experimental Zoology: Molecular and Developmental Evolution on the evolution of Mexican cavefish, support the idea that ecological differences between cave and river environments contribute to differences in A. mexicanus escape behaviors. Findings provide a platform for investigating the evolution of neural circuits contributing to sensory-motor integration and support using A. mexicanus as a model to investigate the evolution of escape behavior.

In diverse fish species, acoustic stimuli activate Mauthner neurons, which initiate a C-start escape response. Mauthner cells receive input from multiple sensory modalities including visual, olfactory, and mechanosensory systems. To compare C-start kinematics between surface fish and cavefish, researchers examined and quantified response latency, maximum change in orientation (referred to as "peak bend angle") and angular speed. They used six-day post-fertilization larvae instead of adult surface fish and cavefish to eliminate the confounding variable of learned behavior.

Researchers found that C-start is present in river-dwelling surface fish and multiple populations of cavefish, but response kinematics and probability differed between populations. The Pachon population of cavefish exhibited an increased response probability, a slower response latency and speed, and reduction of the maximum bend angle, revealing evolved differences between surface and cave populations. Analysis of the responses of two other independently evolved populations of cavefish, revealed the repeated evolution of reduced angular speed. Investigation of surface-cave hybrids showed a correlation between angular speed and peak angle, suggesting that these two kinematic characteristics are related at the genetic or functional levels.

"These findings show that even the most highly conserved behaviors have evolved differences in the cave environment," said Alex Keene, Ph.D., lead author and an associate professor of biological sciences, FAU's Charles E. Schmidt College of Science. "It puts us in a position to identify the biological causes that underlie the reduced response probability and other changes we observed between cavefish and surface fish."

Keene notes that perhaps most interesting, is the difference in response probability in which Molino cavefish which diverged from surface fish more recently, were significantly more responsive than any of the other populations, with Pachon larvae, originating from the more ancestral stock, exhibiting the second highest response probability.

"The finding that multiple populations independently evolved similar phenotypes gives us a way to examine how escape circuits can be modified," said Keene.

Despite having no eyes, cavefish could detect light and sense looming stimuli, raising the possibility that light modulates their C-start response. To assess the influence of visual input on the C-start responses of surface fish and cavefish, researchers assayed both populations under light and dark conditions. The presence of light had no detectable effect on response probability, response latency, or angular speed in cavefish or surface fish. It did however, influence peak bend angle. In the dark conditions, surface fish displayed an increase in peak bend angle compared to cavefish. Although they were able to perceive light at this age, the presence or absence of light had no observable effect on the responses of Pachon cavefish.

To assess differences in responsiveness to acoustic stimuli, researchers quantified the probability of C-start initiation in surface fish and Pachon cavefish at multiple vibration intensities. They found that Pachon cavefish were more likely than surface fish to initiate a C-start in response to vibrations of higher intensities (31 and 35 decibels, but not 28 decibels).

"Interestingly, all cave populations analyzed in our study exhibited decreased angular speed. Furthermore, it is likely that a slower latency, such as that of Pachon larvae, decreases the likelihood of successful evasion," said Alexandra Paz, first author, an FAU doctoral student and a research assistant in the Department of Biological Sciences. "These data suggest that the C-start responses of cavefish, especially from the Pachon population, may be less effective for successful predator evasion. Because no predators have been identified in the caves, it is possible that this change is a result of diminished predation in the cave environment."

Since the ruling of the Court of Justice of the EU of 2018, which placed genome-edited crops under the Genetically Modified Organisms (GMO) legislation, the scientific community has passionately debated the future of these new breeding techniques.

The new ALLEA report "Genome Editing for Crop Improvement" presents the state of the art of scientific evidence in the field and explores paths to harmonise EU legislation with recent scientific developments, while particularly considering relevant ethical and societal considerations.

The report summarises the discussions between scientific experts, policy-makers and civil-society organisations at a public symposium Genome Editing for Crop Improvement held in Brussels in November 2019, where ALLEA and the Royal Flemish Academy of Belgium for Science and the Arts KVAB invited relevant stakeholders and the interested public to assess and discuss the impact of the ruling on present research and developments in genome editing for plant breeding.

"Widening public discourse on innovation in genome-editing for crop improvement is a key responsibility of the scientific community, including academies across Europe. While these new techniques offer exciting opportunities, it remains vital to see the bigger picture and to also consider public perceptions and cultural differences. This report summarises these diverse strands of research and aims to provide a comprehensive overview to European policymakers and the public." states Prof. Antonio Loprieno, President of ALLEA.

At the European level, the ruling of the Court of Justice of the EU on case C-528/16 of 2018 has been met largely with bewilderment and disappointment among the scientific community involved in research in this field. Scientists are concerned that this legislation will impede European research and leave the continent lagging behind other world regions where regulation is less restrictive.

The present report provides an overview of the latest scientific evidence with respect to safety of genome-edited crops and their possible potential to provide solutions to current and future agricultural challenges. Issues related to the traceability of genome-edited crops and how this will likely affect international trade of food and feed are also addressed.

In addition to the bioscience aspects of the technology, the report discusses economic and social implications of genome editing for crop improvement, and the legal hurdles in readdressing the court decision by legislative means. The authors underline that "public participation should be incorporated into the policy-making process for genome editing and should include ongoing monitoring of public attitudes, informational deficits, and addressing concerns about certain applications of genome editing".

Key takeaways from the report:

European legislation should follow the features of the plant, rather than the technique used to generate it, to determine its regulatory status.

Targeted genome edits, which do not add foreign DNA, do not present any other health or environmental danger than plants obtained through classical breeding techniques, and are as safe or dangerous as the latter.

Continued legislative and policy restrictions may hamper the selection of more productive, diverse, and climate-resilient crops with a reduced environmental footprint.

The length and cost of the authorisation process makes it, except for major industrial players, hardly possible to bring into culture and commercialise plants developed with new biotechnological breeding techniques.

To enhance sustainability and to reduce the usage of chemicals, access is needed to the most advanced technologies enabling the improvement of existing varietal heritage and increasing the ability to respond to new challenges of changing environments. These new technologies may contribute to a reduction of the environmental footprint of agriculture.

An open, honest dialogue with all stakeholders, including the public, is needed in the decision-making processes for introducing genome-edited products into the market, ensuring that the implications of market introduction are accurately communicated.

The burden of knee osteoarthritis is set to continue to increase around the world. Ageing populations and rising levels of obesity, combined with an absence of a cure for the disease, will lead to an increased strain on health-care systems. Due to this, there is a focus on how to best manage the disease.

Clinical management is difficult and recommended treatment strategies routinely include a combination of non-pharmacological, pharmacological and in some cases surgical interventions. Management can further be categorised by disease severity, joint site and the presence/absence of comorbidities making OA treatment increasingly personalised.

Facing such complexities, health-care providers turn to clinical practice guidelines to help inform the decision-making process. But according to a research team from the Universities of Oxford, Southampton, Liège, Oulu, Maryland, Oslo and Boston, the complexities for clinicians don't end there.

"Leading experts and national and international organisations frequently publish guidelines outlining the best strategies for managing osteoarthritis," said Thomas Perry, joint first author and Postdoctoral Research Fellow in Sport, Exercise and Osteoarthritis at the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford. "There are a number of OA organisations across the world, each publishing new updated algorithms for how to best manage osteoarthritis, which means it can be difficult for clinicians to keep track of the most up-to-date literature, best practice policies, and ultimately provide the best care for their patients."

In 2019, when OARSI (Osteoarthritis Research Society International) and ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis) updated their guidelines for the non-surgical management of knee osteoarthritis, Nigel Arden, Professor of Rheumatic Diseases at NDORMS proposed a review of their new algorithms. Together with members from OARSI and ESCEO, a working group examined the similarities and differences between the two guidelines and created a narrative to help guide health-care providers through the complexities of treatments.

The results are published today in Nature Reviews Rheumatology.

The guidelines are similar in the majority of their recommendations. OARSI and ESCEO both recommend education, structured exercise and weight loss as core treatments for knee OA and advise the use of topical NSAIDs as first-line treatments, and oral NSAIDs and intra-articular injections for persistent pain. Where they differed was in ESCEO's recommendation for the use of low-dose, short-term acetaminophen, pharmaceutical grade glucosamine and chondroitin sulfate, as compared to OARSI which strongly recommends against their use (including all glucosamine and chondroitin formulations).
Thomas said: "It's reassuring that the majority of recommendations from OARSI and ESCEO are in agreement. The working group concluded that the most likely reason for the differences were down to the methodologies of how they each approach the data and the literature. Each organisation uses slightly different procedures which could translate into the few, but important differences observed. It also highlights that there remain contested treatments for which we need better quality data to confirm use or non-use in the management of knee OA. Moving forward, there is also a need to define a standard protocol, outlining a method for making treatment algorithms which can be adopted by all societies."

Professor Arden said: "It was the first time that OARSI and ESCEO had come together to discuss their guidelines and it proved a very positive experience. Our aspiration would be to expand the collaboration to other societies and to harmonise the algorithms in order to present a consistent set of recommendations, providing confidence and clarity for practising clinicians regarding the treatment for their patients."

A global study of ancient dog DNA, led by scientists at the Francis Crick Institute, University of Oxford, University of Vienna and archaeologists from more than 10 countries, presents evidence that there were different types of dogs more than 11,000 years ago in the period immediately following the Ice Age.

In their study, published in Science today (29th October), the research team sequenced ancient DNA from 27 dogs, some of which lived up to nearly 11,000 years ago, across Europe, the Near East and Siberia.* They found that by this point in history, just after the Ice Age and before any other animal had been domesticated, there were already at least five different types of dog with distinct genetic ancestries.

This finding reveals that the diversity observed between dogs in different parts of the world today originated when all humans were still hunters and gatherers.

Pontus Skoglund, author and group leader of the Crick's Ancient Genomics laboratory, says: "Some of the variation you see between dogs walking down the street today originated in the Ice Age. By the end of this period, dogs were already widespread across the northern hemisphere."

This study of ancient genomics involves extracting and analysing DNA from skeletal material. It provides a window into the past, allowing researchers to uncover evolutionary changes that occurred many thousands of years ago.

The team showed that over the last 10,000 years, these early dog lineages mixed and moved to give rise to the dogs we know today. For example, early European dogs were initially diverse, appearing to originate from two highly distinct populations, one related to Near Eastern dogs and another to Siberian dogs. However, at some point this diversity was lost, as it is not present in European dogs today.

Anders Bergström, lead author and post-doctoral researcher in the Ancient Genomics laboratory at the Crick, says: "If we look back more than four or five thousand years ago, we can see that Europe was a very diverse place when it came to dogs. Although the European dogs we see today come in such an extraordinary array of shapes and forms, genetically they derive from only a very narrow subset of the diversity that used to exist."

The researchers also compared the evolution in dog history to changes in human evolution, lifestyles and migrations. In many cases comparable changes took place, likely reflecting how humans would bring their dogs with them as they migrated across the world.

But there are also cases when human and dog histories do not mirror each other. For example, the loss of diversity that existed in dogs in early Europe was caused by the spread of a single dog ancestry that replaced other populations. This dramatic event is not mirrored in human populations, and it remains to be determined what caused this turnover in European dog ancestry.

Greger Larson, author and Director of the Palaeogenomics and Bio-Archaeology Research Network at the University of Oxford, says: "Dogs are our oldest and closest animal partner. Using DNA from ancient dogs is showing us just how far back our shared history goes and will ultimately help us understand when and where this deep relationship began."

Ron Pinhasi, author and group leader at the University of Vienna, says: "Just as ancient DNA has revolutionised the study of our own ancestors, it's now starting to do the same for dogs and other domesticated animals. Studying our animal companions adds another layer to our understanding of human history."

While this study provides major new insights into the early history of dog populations and their relationships with humans and each other, many questions still remain. In particular, research teams are still trying to uncover where and in which human cultural context, dogs were first domesticated.

The shells of crustaceans and wood waste such as branches pruned from trees usually end up in landfills. These waste materials are given a new lease of life to become nutritional supplements and medicine, with the help of a novel process developed by researchers from the National University of Singapore (NUS).

A team led by Associate Professor Yan Ning and Assistant Professor Zhou Kang from the Department of Chemical and Biomolecular Engineering at the NUS Faculty of Engineering devised a method to turn shells from prawns and crabs into L-DOPA, a widely used drug to treat Parkinson's disease. A similar method can be used to convert wood waste to Proline, which is essential for the formation of healthy collagen and cartilage.

The NUS team's conversion approach can potentially play a pivotal role in the chemical industry, as the movement of waste-derived compounds has been gaining momentum in a bid to reduce reliance on the use of non-renewable fossil fuels and energy-consuming processes.

From waste to useful chemicals

The global food processing industry generates as much as eight million tonnes of crustacean shell waste annually. Concurrently, Singapore generated over 438,000 tonnes of wood waste in 2019, among which include branches pruned from trees and saw dust from workshops. Deriving ways to upcycle these food and agricultural waste materials into useful compounds will reap benefits without straining landfills.

Although reusing waste materials has gained traction in recent years, the typical output of chemicals produced from waste recycling is often less diversified than the conventional chemical synthesis pipeline which uses crude oil or gas. To overcome the limitations, the NUS researchers came up with a pathway that marries a chemical approach with a biological process.

They first applied chemical processes to the waste materials and converted them into a substance that can be "digested" by microbes. The second step involves a biological process, akin to the fermentation of grapes into wine, where they engineered special strains of bacteria such as Escherichia coli to convert the substance produced in the chemical process into a higher value product such as amino acids.

The NUS team took four years to derive their method, and applied it to obtain high value chemicals from renewable sources in a sustainable way.

Producing organic chemicals cheaper and faster

Conventionally, L-DOPA is produced from L-tyrosine, a chemical made from fermenting sugars. With the approach developed by the NUS team, crustacean waste is first treated using a simple chemical step, allowing it to be used by microbes to produce L-DOPA. The yield of the NUS method is similar to that achieved in the traditional method using sugars. In addition, compared to glucose, the most common sugar used, which costs between US$400 to US$600 per ton, shrimp waste costs only about US$100 per ton. Given the low cost and abundance of shell waste, the NUS team's process has the potential to provide L-DOPA at a lower cost.

Proline, on the other hand, is conventionally produced through pure biological processes. The NUS team's unique method has now replaced most of the transformations by using chemical processes, which are much faster. As a result, the new integrated process could achieve higher productivity, and potentially lead to reductions in capital investment and operating costs.

The research on producing amino acids such as L-DOPA from crustacean shells was first published online in the Proceedings of the National Academy of Sciences (PNAS) on 25 March 2020, while the work on producing Proline from wood waste was reported in Angewandte Chemie on 27 July 2020.

"Chemical processes are rapid and can utilise a variety of harsh conditions such as extreme heat or pressure to break down a wide variety of waste materials as no living organism are involved, but they can only produce simple substances. On the other hand, biological processes are a lot slower, and require very specific conditions for the microbes to flourish but can produce complex substances which tend to be of higher value. By combining both chemical and biological processes, we can reap the benefits of both to create high value materials," explained Asst Prof Zhou.

Potential to upcycle other types of waste

The NUS team's methodology has the potential to be applied to different types of waste materials, and they can tailor the process, based on the type of waste as well as the target end product.

Moving forward, the team is looking to adapt their unique process to other forms of waste, such as carbon dioxide and wastepaper. Such development would reduce the society's reliance on non-renewable resources for acquiring chemicals which are important constituents of many nutritional supplements and medicine today.

"Our novel chemical-biological integrated workflow offers a general pathway to produce a variety of high-value organonitrogen chemicals. While it may sound simple on paper to just combine two different methodologies, the devil is in the details. Given that these chemicals are found in a vast array of commercially valuable pharmaceuticals, pigments and nutrients, we are excited to expand our research and develop new methodologies to produce value-added chemicals from other abundant, locally available substrates found in Singapore," shared Assoc Prof Yan.

The research team is also planning to scale up the processes currently developed in their laboratories, and to work with industrial partners to commercialise this technology.

Imagine that you are a job consultant. You are sitting across from your client, an unemployed individual.

After locating them in the system, up pops the following text on the computer screen; 'increased risk of long-term unemployment'.

Such assessments are made by an algorithm that, via data on the citizen's gender, age, residence, education, income, ethnicity, history of illness, etc., spits out an estimate of how long the person -- compared to other people from similar backgrounds -- is expected to remain in the system and receive benefits.

But is it reasonable to characterize individual citizens on the basis of what those with similar backgrounds have managed in their job searches? According to a new study from the University of Copenhagen, no.

"You have to understand that people are human. We get older, become ill and experience tragedies and triumphs. So instead of trying to predict risks for individuals, we ought to look at implementing improved and more transparent courses in the job center arena," says Naja Holten Møller, an assistant professor at the Department of Computer Science, and one of the researchers behind the study.

Together with two colleagues from the same department, Professor Thomas Hildebrandt and Professor Irina Shklovski, Møller has explored possible alternatives to using algorithms that predict job readiness for unemployed individuals as well as the ethical aspects that may arise.

"We studied how to develop algorithms in an ethical and responsible manner, where the goals determined for the algorithm make sense to job consultants as well. Here, it is crucial to find a balance, where the unemployed individual's current situation is assessed by a job consultant, while at the same time, one learns from similar trajectories using an algorithm," says Naja Holten Møller.

Job consultants need to help create the algorithm

The use of job search algorithms is not a well-thought scenario. Nevertheless, the Danish Agency for Labour Market and Recruitment has already rolled out this type of algorithm to predict the risk of long-term unemployment among the citizenry -- despite criticism from several data law experts.

"Algorithms used in the public sphere must not harm citizens, obviously. By challenging the scenario and the very assumption that the goal of an unemployed person at a job centre is always to land a job, we are better equipped to understand ethical challenges. Unemployment can have many causes. Thus, the study shows that a quick clarification of time frames for the most vulnerable citizens may be a better goal. By doing so, we can avoid the deployment of algorithms that do great harm," explains Naja Holten Møller.

The job consultants surveyed in the study expressed concern about how the algorithm's assessment would affect their own judgment, specifically in relation to vulnerable citizens.

"A framework must be established in which job consultants can have a real influence on the underlying targets that guide the algorithm. Accomplishing this is difficult and will take time, but is crucial for the outcome. At the same time, it should be kept in mind that algorithms which help make decisions can greatly alter the work of job consultants. Thus, an ethical approach involves considering their advice," explains Naja Holten Møller.

We must consider the ethical aspects

While algorithms can be useful for providing an idea of, for example, how long an individual citizen might expect to be unemployed, this does not mean that it is ethically justifiable to use such predictions in job centers, points out Naja Holten Møller.

"There is a dream that the algorithm can identify patterns that others are oblivious to. Perhaps it can seem that, for those who have experienced a personal tragedy, a particular path through the system is best. For example, the algorithm could determine that because you've been unemployed due to illness or a divorce, your ability to avoid long-term unemployment depends on such and such," she says, concluding:

"But what will we do with this information, and can it be deployed in a sensible way to make better decisions? Job consultants are often able to assess for themselves whether a person is likely to be unemployed for an extended period of time. These assessments are shaped by in-person meetings, professionalism and experience -- and it is here, within these meetings, that an ethical development of new systems for the public can best be spawned."

Ever since the astronomer Edwin Hubble demonstrated that the further apart two galaxies are, the faster they move away from each other, researchers have measured the expansion rate of the Universe (the Hubble constant) and the history of this expansion. Recently, a new puzzle has emerged, as there seems to be a discrepancy between measurements of this expansion using radiation in the early Universe and using nearby objects. Researchers from the Cosmic Dawn Center, at the Niels Bohr Institute, University of Copenhagen, have now contributed to this debate by focusing on velocity measurements. The result has been published in Astrophysical Journal.

The researchers at the Cosmic Dawn Center found that the measurements of velocity used for determining the expansion rate of the Universe may not be reliable. As stated in the publication, this doesn't resolve the discrepancies, but rather hints at an additional inconsistency in the composition of the Universe.

Measuring the expansion rate of the Universe

Currently, astronomers measure the expansion of the Universe using two very different techniques. One is based on measuring the relationship between distance and velocity of nearby galaxies, while the other stems from studying the background radiation from the very early universe. Surprisingly, these two approaches currently find different expansion rates. If this discrepancy is real, a new and rather dramatic reinterpretation of the development of the Universe will be the consequence. However, it is also possible that the difference in the Hubble constant could be from incorrect measurements. It is difficult to measure distances in the Universe, so many studies have focused on improving and recalibrating distance measurements. But in spite of this, over the last 4 years the disagreement has not been resolved.

The velocity of the remote galaxies is easy to measure - or so we thought

In the recent scientific article, the researchers from the Cosmic Dawn Center now attempt to shine light on a related problem: the measurement of velocity. Depending on the velocity with which a remote object moves away from us, its light shifts to redder colors. With this so-called redshift it is possible to measure the velocity from a spectrum of a remote galaxy. Unlike measurements of distance, until now it was assumed that velocities were relatively easy to measure.

However, when the researchers recently examined distance and velocity measurements from more than 1000 supernovae (exploding stars) collected during the last 25 years, they found a surprising discrepancy in their results. Albert Sneppen, Masters student at the Niels Bohr Institute explains: "We've always believed that measuring velocities was fairly straightforward and precise, but it turns out that we are actually dealing with two types of redshifts".

The first type, measuring the velocity with which the host-galaxy moves away from us, is considered the most reliable. The other type of redshift measures instead the velocity of matter ejected from the exploding star inside the galaxy. Or, more precisely, the matter from the supernova moving towards us with a few percent of the velocity of light (illustration 1). After compensating for this extra movement the redshift - and velocity - of the host galaxy can be determined. But this compensation requires a precise model for the explosion. The researchers were able to determine that the results from these two different techniques result in two different expansion histories for the Universe, and therefore two different compositions as well.

Are things "broken in an interesting way?"

So, does this mean that the measurements of the early Universe and newer measurements are ultimately a question of imprecise measurements of velocity? Probably not, says Bidisha Sen, one the authors of the article. "Even if we only use the more reliable redshifts, the supernova measurements not only continue to disagree with the Hubble constant measured from the early Universe - they also hint at a more general discrepancy regarding the composition of the Universe", she says.

Associate professor at the Niels Bohr Institute Charles Steinhardt, is intrigued by these new results. "If we are actually dealing with two disagreements, it means that our current model would be "broken in an interesting way", he says. "In order to solve two problems, one regarding the composition of the Universe and one regarding the expansion rate of the Universe, rather different physical explanations are required than if we only want to explain a single discrepancy in the expansion rate".

The Scientific work continues at the Nordic Optical Telescope

With the Nordic Optical Telescope in Gran Canaria the researchers are now acquiring new redshifts from the host galaxies. When they compare these results with the supernova based redshifts, they will be able to see if the two techniques remain different. "We have learned that these sensitive measurements require precise measurements of velocity, and these will be attainable with fresh observations", Steinhardt explains.

Our brains are wired to protect us from threats. For social animals like humans, threats often come from other members of our own species when there is conflict over food, mates, or territory. Animals with a strong sense of territory will attack anyone who enters their territory, but will flee if caught in the territory of another individual. In such animals, the decision to stand their ground and attack or to run away and escape depends on where the animal is. How is the decision between these two types of defensive responses made? How does our sense of territory drive our instinctive behaviour?

Previous studies from the Gross group at the site of the European Molecular Biology Laboratory in Rome have revealed the crucial function of a specific brain region, the ventromedial hypothalamus (VMH), in social fear. The VMH is a central node in the brain that receives sensory inputs from the amygdala - a region involved in organising sensory information related to emotional behaviour - and sends outputs to motor areas of the brainstem. This position midway between sensory inputs and motor outputs makes the VMH an ideal subject to understand how threats drive behaviour.

To investigate the possibility that the VMH is involved in the decision between attacking and escaping a social threat, scientists in the Gross group measured the activation of neurons while the mice were exposed to a more aggressive mouse. When the mice were in this situation, activity of a large class of neurons increased proportionally with the threat intensity, confirming that the VMH may encode an internal state of threat that is necessary to trigger defensive responses.

Unexpectedly, the scientists also observed activation of the same neurons when the animal returned to explore the place where it had been threatened previously, even though there was no longer any threat present. And, surprisingly, a second set of neurons now became active when the animal returned (via a corridor) to its home cage. Under these circumstances, the researchers could predict precisely where the animal was located - threat cage or home cage - by looking at the firing of neurons in the VMH. This demonstrates that the VMH encodes spatial context - a function that has never before been attributed to the hypothalamus.

Finally, the researchers showed that exposure to a more aggressive mouse dramatically increased the ability of the VMH to promote flight. When the VMH was artificially activated after such a situation, the animal rapidly ran away from a threat, but not when the VMH was activated before this situation. This shows that social experience can change the VMH. The researchers are currently trying to understand what mechanisms might be involved in this transformation, which allows the neural networks in the VMH to be rewired in response to experience - a process known as neural plasticity.

"This finding has important implications for the field, because previous work had argued that the VMH is hardwired to respond to threats," says group leader Cornelius Gross. "Our view holds that the VMH is dedicated to controlling both attack and flight, and that this choice is driven by its encoding of social space. When an animal is in its own territory it favours attack, but when it is in the territory of another animal it favours flight."

"These results can contribute to understanding how emotions like fear and aggression are regulated, especially in the context of territory," says Piotr Krzywkowski, who conducted the research as a PhD student in the Gross group and is now Senior Data Scientist at the company IQVIA. The results also suggest a novel role of the hypothalamus in behaviour. Rather than being viewed as an innate behavioural response region, the hypothalamus should be seen as a region that integrates present and past sensory and contextual information, processing the level of threat and adapting survival behaviours to a changing environment.

The fur of the platypus - an Australian species threatened with extinction - glows green under ultraviolet light, a new study finds. This is the first observation of biofluorescence in an egg-laying mammal (monotreme), suggesting this extraordinary trait may not be as rare as previously thought.

The research article "Biofluorescence in the platypus (Ornithorhynchus anatinus)" was published in De Gruyter's international journal Mammalia.

Two mammals - the opossum and the flying squirrel - are already known to have fur that biofluoresces under under ultraviolet (UV) light.

One of the paper's authors discovered pink biofluorescence in flying squirrels by accident while conducting a night survey for lichens, a finding reported in an earlier paper. While confirming this field observation with preserved museum specimens, the researchers decided to examine the platypuses in the next drawer along too.

They studied three museum platypus specimens: a female and a male from the Field Museum of Natural History in Chicago and another male specimen from the University of Nebraska State Museum.

In visible light, the fur of all three platypus specimens was uniformly brown. But under UV light they appeared green or cyan. The fur of the platypus absorbs UV (wavelengths of 200-400 nanometers) and re-emits visible light (of 500-600 nanometers), making it fluoresce.

Like the marsupial opossum and the placental flying squirrel, platypuses are most active during the night and at dawn and dusk. It may be that these mammals - and possibly others - developed biofluorescence to adapt to low light conditions. The researchers suggest this may be a way for platypuses to see and interact with each other in the dark.

The researchers would now like to work with an Australian team to observe biofluorescence in wild animals. And with colleagues at Northland College and Colorado State University, they are working on a project to further explore the phenomenon across the mammalian family tree.

"It was a mix of serendipity and curiosity that led us to shine a UV light on the platypuses at the Field Museum," said lead author Professor Paula Spaeth Anich, Associate Professor of Biology and Natural Resources at Northland College. "But we were also interested in seeing how deep in the mammalian tree the trait of biofluorescent fur went. It's thought that monotremes branched off the marsupial-placental lineage more than 150 million years ago. So, it was intriguing to see that animals that were such distant relatives also had biofluorescent fur."

600,000 Danes take medicine containing statins. Statins lower the cholesterol level and thus helps prevent cardiovascular disease and blood clots. But there is a different side to the coin.

Treatment with statins may also have negative side effects, some of which are so severe that people suffering from elevated cholesterol choose to stop treatment. One of the main side effects is muscle pain, also called myalgia, which may lead to reduced quality of life, pain and inactivity due to the pain.

Statin inhibits the production of cholesterol in the cell, but it also inhibits an important element in the energy production in the cells' mitochondria. Mitochondria are small, energy-producing organelles found in almost all cells in the body. Statins are suspected of lowering the energy level in the cells, thus causing myalgia in muscle cells.

The researchers therefore wished to determine whether statins also inhibited the energy production in blood cell mitochondria. And research from the Center for Healthy Aging at the Faculty of Health and Medical Sciences now shows that statins do not have the expected effect.

'We can see that long-term treatment with statins at the recommended dose increases the blood cells' ability to produce energy. These are surprising results. We had expected statins to behave the same way that they do in muscle cells, but in fact they do the exact opposite here', says Executive Director and Professor at the Center for Healthy Aging Lene Juel Rasmussen.

Statins Do Both Good and Bad

Even though the surprising results challenge the theory that statins lower the energy level, this does not necessarily mean that statins do not have adverse effects on some organs.

Because the results say nothing about whether the statins are responsible for affecting the energy level or it is the body that does that to compensate for the change caused by the statins.

'Statins are quite mysterious, as they can have both positive and negative consequences depending on the part of the body', says Lene Juel Rasmussen.

'Our results show an increase in the energy level in the blood cells, but whether that is good or bad, we cannot say. It can either mean that the statins improve the blood cells' ability to produce energy, which would be a good thing, or that the statins do damage and that the body consequently raises the energy level to mend that damage', she explains.

Different Effects on Different Parts of the Body

Even though the mechanism behind statins' effect on the blood remains unknown, the new results provide brand new insight into the effect of statins: Contrary to expectation, statins behave differently in different parts of the body.

'Previous studies suggest that statins have a potentially beneficial effect on some forms of cancer and possibly also on some forms of dementia. If we are able to produce new knowledge on the effect of statins on various parts of the body, we can use this knowledge to design drugs based on the beneficial effects. If statins have a positive effect on the brain, for example, we can focus on using them in the design of drugs for dementia', Lene Juel Rasmussen explains.

UNIVERSITY PARK, Pa. -- Your bag of mulch may not be what you think it is. In a new study, researchers at Penn State found that some bags labeled as "cypress" contain only 50% cypress, while other bags contained no cypress at all.

"Many mulch products claim to be composed of cypress," said researcher Judd Michael, Nationwide Insurance Professor of Ag Safety and Health in the College of Agricultural Sciences. "But some of the largest mulch manufacturers have been accused of intentionally misleading consumers about the species mix, and it is difficult if not impossible for consumers to know whether the product is, indeed, the species listed on the packaging."

In response to complaints about misleading packaging and fraudulent behavior by these companies, Michael and his colleagues conducted an investigation and devised a process to determine the wood species included in bags of mulch and their percentages.

According to Michael, cypress wood is generally considered highly resistant to decay, making it a popular and desired species for landscaping mulch. The research is important because homeowners and professionals apply millions of bags of mulch sold at retail, with estimated U.S. sales of $1 billion dollars annually. There are many large, national mulch brands, and the majority of mulch sold at retail is packaged in 2-cubic-foot bags.

Cypress is promoted by the mulch industry as being superior to other wood species, noted researcher Charles Ray, associate professor of ecosystem science and management. Cypress is more expensive to procure than other species, such as southern pines, he added, so manufacturers may have an economic incentive to replace some percentage of the mulch mix with cheaper, more abundant species.

"Cypress is sold at a premium due to its natural color, rot resistance and resistance to insect infestation," Ray said. "If mulch producers are including at least some non-cypress species in all their products, then this deceptive practice would result in greater profits while harming the consumer. Consumers believe they are receiving a superior wood species but don't get the protection and benefits if the product contains significant volumes of pine or other inferior species."

To assess the situation, the researchers initially tested 10 bags of a nationally distributed, branded cypress mulch product, obtained from six different states. They identified the wood species by low-power microscopic analysis in the College of Agricultural Science's Wood Anatomy Lab. Examination of the largest wood pieces suggested that all bags contained at least some non-cypress.

Next, the researchers developed and utilized a new method to sort the mulch by particle size and estimate species mix by weight. The testing procedure consisted of sifting the entire contents of a bag through a series of graduated screens and then identifying and weighing the wood pieces of similar size. With that information, using a mathematical formula, they were able to estimate the ratio of wood species in a bag.

Using the novel testing procedure, in findings published in the current issue of Wood and Fiber Science, the researchers determined the following: One of the bags, purchased in Austin, Texas, contained roughly 50% cypress, with the remainder of the content being lower-valued pine. A bag purchased in Laredo, Texas, contained no cypress, despite being labeled as cypress mulch. The remaining eight bags, researchers estimated, contained cypress percentages ranging from 30% to 60%.

The research results, Michael pointed out, show that regulators charged with protecting environmental or consumer interests need assistance from the wood-science community.

Adequately protecting the interests of consumers who purchase bio-based products, while assisting regulators and ensuring fair competition, is an important service that should be provided by a land-grant university, said Michael.

"The implication of these findings for the industry is that mulch manufacturers should become much better at process management, quality control and perhaps procurement to avoid practices that draw the ire of regulators," Ray said. "Mulch manufacturers need to more accurately meet legal requirements for species as promoted on packaging."

Philadelphia, October 29, 2020--Using sophisticated 3D genomic mapping and integrating with public data resulting from genome-wide association studies (GWAS), researchers at Children's Hospital of Philadelphia (CHOP) have found significant genetic correlations between inflammatory bowel disease (IBD) and stress and depression. The researchers went on to implicate new genes involved in IBD risk that are enriched in both derived hypothalamic neurons, from a part of the brain that has a vital role in controlling stress and depression, and organoids derived from colon cells, a region more commonly studied in the context of IBD.

The findings were published in Cellular and Molecular Gastroenterology and Hepatology.

"Our results implicate a role for the hypothalamus in the genetic susceptibility to IBD," said senior author Struan Grant, PhD, a director of the Center for Spatial and Functional Genomics at CHOP and the Daniel B. Burke Endowed Chair for Diabetes Research. "Epidemiological data has previously shown overlap between IBD and stress and depression, and now we have generated genomics data to support that association. Our results suggest that the hypothalamus warrants further study in the context of IBD pathogenesis."

IBD, which includes both Crohn's disease (CD) and ulcerative colitis (UC), is principally an immune-mediated condition characterized by dysregulated inflammation of the gastrointestinal tract. The disease course ranges from chronically active to intermittent or rare flares. Multiple genetic and environmental factors are known to contribute to the pathogenesis of IBD, including more than 230 loci for the disease that have been reported through GWAS analyses. Many of the genes residing at these loci have been implicated in pathways related to the immune system and the microbiome.

However, there is also increasing evidence for a clinical association of IBD with stress and depression. Given the role of the hypothalamus in stress responses and in the pathogenesis of depression, the researchers decided to explore the genetic role of the hypothalamus in IBD.

To begin, the researchers performed genetic correlation analyses between IBD and depression to assess the degree of genetic commonality between the two conditions, using publicly available data. The research team used depression as a proxy for stress because there are a limited number of GWAS efforts focused on a consistent definition of stress, while in contrast, the genetics of depression has been relatively well-studied, resulting in a large, relatively uniform body of work.

Analyzing eleven autoimmune diseases for correlations with depression, the researchers found IBD was the most statistically significantly trait positively correlated with depression, though asthma and multiple sclerosis were noted as being highly correlated as well.

The research team then performed further analyses in order to validate the correlation between IBD and depression. First, they measured the enrichment of IBD-associated genetic variants in the 3D genomic patterns within hypothalamic-like neurons (HNs) and colonoids from rectal biopsies and found a highly significant four-fold increase in HNs and a seven-fold increase in the better-known colonoid setting. The researchers then used a sophisticated "variant-to-gene mapping" approach devised at CHOP to determine which genes are implicated in the pathogenesis of IBD at these enriched signals. Then, assessing those implicated genes, the researchers looked for pathways potentially influenced by IBD-associated genetic variants.

Through this variant-to-gene mapping effort, the researchers implicated 25 genes in HNs for conferring risk for IBD. Eleven of those genes have known functions in the brain, in particular CREM, CNTF and RHOA, which are genes that encode key regulators of stress. Seven of those genes were also implicated in the colonoids. In terms of pathways, the researchers observed an overall enrichment for hormonal signaling pathways, in addition to the expected enrichment in immune and microbiome signaling pathways.

"We propose that some IBD-associated variants alter the hypothalamus-pituitary-adrenal axis and stress responses, which could in turn play a role in predisposing patients to this disease and exacerbating its presentation," Grant said. "Future studies are warranted to refine our understanding of the role of the hypothalamus in IBD onset."

The gut is an unusually noisy place, where hundreds of species of bacteria live alongside whatever microbes happen to have hitched a ride in on your lunch. Scientists have long suspected that the gut's immune system, in the face of so many stimuli, takes an uncharacteristically blunt approach to population control and protection from foreign invaders--churning out non-specific antibodies with broad mandates to mow the gut's entire microbial lawn without prejudice.

But now, new research published in Nature suggests that the gut's local immune system can be quite precise, creating antibodies that appear to home in on specific microbiota.

"It was thought that the gut immune system worked sort of like a general-purpose antibiotic, controlling every bug and pathogen," says Gabriel D. Victora, an immunologist and head of the Laboratory of Lymphocyte Dynamics . "But our new findings tell us that there might be a bit more specificity to this targeting."

The research suggests that our immune system may play an active part in shaping the composition of our microbiomes, which are tightly linked to health and disease. "A better understanding of this process could one day lead to major implications for conditions where the microbiome is knocked out of balance," says Daniel Mucida, head of the Laboratory of Mucosal Immunology.

Specificity in the mouse gut

When faced with a pathogen, the immune system's B cells enter sites called germinal centers where they "learn" to produce specific antibodies until one B cell emerges, finely-tuned to recognize its target with high efficiency. Dubbed a winner clone, this B cell replicates to generate a mob of cells that produce potent antibodies.

Victora, Mucida, and colleagues set out to study how these B cells interact with the melting pot of bacterial species in the gut--an overabundance of potential targets. Looking at the germinal centers that form in mice intestines, they found that about 1 in 10 of these gut-associated germinal centers had clear winner clones. They then homed in on the winning B cells and found that their antibodies were indeed designed to bind with ever increasing potency to specific species of bacteria living in the gut.

The findings show that even in the gut, where millions of microbes wave their thousands of different antigens and vie for the immune system's attention, germinal centers manage to select specific, consistent winners.

"We can now investigate the winners and look at evolution in germinal centers as an ecological issue involving many different species, as we try to figure out the rules underlying selection in these complex environments," Victora says. "This opens up a whole new area of inquiry."

ITHACA, N.Y. - In the dark of night, ogre-faced spiders with dominating big eyes dangle from a silk frame to cast a web and capture their ground prey. But these spiders also can capture insects flying behind them with precision, and Cornell University scientists have now confirmed how.

In a new study, researchers confirmed these spiders use metatarsal sensitivity - sensors at the tip of the leg - to detect sound cues of various frequencies from up to 6 feet away. These cues trigger a split-second, ninja-like backflip to strike unsuspecting airborne insects, bag them in a web net, and then dine.

"These spiders have finely tuned sensory systems and a fascinating hunting strategy," said lead author Jay Stafstrom, a postdoctoral researcher in the laboratory of Ronald Hoy, professor of neurobiology and behavior at Cornell. "These spiders have massive eyes so they can see at night and catch things off the ground, but they can 'hear' quite well, detecting sounds through their metatarsal organ, as these spiders excel at catching things from the air."

Net-casting, ogre-faced spiders (Deinopis spinosa), are nocturnal creatures found mostly in the southeastern United States. While people are familiar with spiders that create orb webs, this species makes personal, fuzzy webs - like small nets - and uses the strong, sticky silk like a baseball glove, according to Hoy.

Spiders don't have ears, but they can sense a wide range of sounds thanks to the metatarsal organ located near the tip of their legs.

Stafstrom collected these spiders and brought them to Gil Menda, a postdoctoral researcher in Hoy's lab, who recorded neural activity from both their brains and their legs. He played pure tone frequencies to the spiders and noted the spider's neurons became excited for difference tones.

Stafstrom examined frequencies that ranged from 150 Hz (the flute-like sound of blowing over a glass soda bottle) to 750 Hz (the high-pitched drone of a local television nighttime sign-off) to 10 Khz, a piercing, high-pitched sound.

"While the spiders were sensitive to low-frequency tones, as expected, we didn't really expect to see net-casting spiders sensitive to a wide range of frequencies - all the way to 10 kilohertz," he said.