Culture

Sugar changes the chemistry of your brain

The idea of food addiction is a very controversial topic among scientists. Researchers from Aarhus University have delved into this topic and examined what happens in the brains of pigs when they drink sugar water. The conclusion is clear: sugar influences brain reward circuitry in ways similar to those observed when addictive drugs are consumed. The results have just been published in the journal Scientific Reports.

Anyone who has desperately searched their kitchen cabinets for a piece of forgotten chocolate knows that the desire for palatable food can be hard to control. But is it really addiction?

"There is no doubt that sugar has several physiological effects, and there are many reasons why it is not healthy. But I have been in doubt of the effects sugar has on our brain and behaviour, I had hoped to be able to kill a myth. " says Michael Winterdahl, Associate Professor at the Department of Clinical Medicine at Aarhus University and one of the main authors of the work.

The publication is based on experiments done using seven pigs receiving two liters of sugar water daily over a 12-day period. To map the consequences of the sugar intake, the researchers imaged the brains of the pigs at the beginning of the experiment, after the first day, and after the 12th day of sugar.

"After just 12 days of sugar intake, we could see major changes in the brain's dopamine and opioid systems. In fact, the opioid system, which is that part of the brain's chemistry that is associated with well-being and pleasure, was already activated after the very first intake," says Winterdahl.

When we experience something meaningful, the brain rewards us with a sense of enjoyment, happiness and well-being. It can happen as a result of natural stimuli, such as sex or socializing, or from learning something new. Both "natural" and "artificial" stimuli, like drugs, activate the brain's reward system, where neurotransmitters like dopamine and opioids are released, Winterdahl explains.

We chase the rush

"If sugar can change the brain's reward system after only twelve days, as we saw in the case of the pigs, you can imagine that natural stimuli such as learning or social interaction are pushed into the background and replaced by sugar and/or other 'artificial' stimuli. We're all looking for the rush from dopamine, and if something gives us a better or bigger kick, then that's what we choose" explains the researcher.

When examining whether a substance like sugar is addictive, one typically studies the effects on the rodent brain. ¨It would, of course, be ideal if the studies could be done in humans themselves, but humans are hard to control and dopamine levels can be modulated by a number of different factors. They are influenced by what we eat, whether we play games on our phones or if we enter a new romantic relationship in the middle of the trial, with potential for great variation in the data. The pig is a good alternative because its brain is more complex than a rodent and gyrated like human and large enough for imaging deep brain structures using human brain scanners. The current study in minipigs introduced a well-controlled set-up with the only variable being the absence or presence of sugar in the diet.

Credit: 
Aarhus University

No need to dig too deep to find gold!

image: This is a sampling of volcanic gases in Vulcano Crater (Aeolian Islands).

Image: 
© UNIGE

Why are some porphyry deposits - formed by magmatic fluids in volcanic arcs - rich in copper while others primarily contain gold? In an attempt to answer this question, a researcher from the University of Geneva (UNIGE) investigated how the metals are accumulated over the time duration of a mineralizing event, looking for a correlation between the amounts of copper and gold extracted from the deposits. Not only did the researcher discover that the depth of the deposits influences the quantity of metals produced but also that over 95% of the gold is lost to the atmosphere through volcanic emissions. In short, the deeper a deposit is, the more copper there will be, while gold-rich deposits are closer to the surface. These findings, which are published in the journal Nature Communications, will provide valuable assistance to companies that mine these metals.

Geological processes produce different kinds of deposits. Porphyry-type deposits are formed underneath volcanoes by an accumulation of magma that releases fluids on cooling and precipitates metals in the form of ore. "Precipitation is the extraction of metals from the magmatic fluid and their fixation in an ore", explains Massimo Chiaradia, a researcher in the Department of Earth Sciences in UNIGE's Science Faculty. These porphyry deposits, which are found mainly around the Pacific Ring of Fire, produce three-quarters of the natural copper and a quarter of the natural gold mined. "A copper deposit can contain from one to 150 million tonnes, while the quantity of gold varies from ten tonnes to 2,500 tonnes per deposit," continues Chiaradia. But will a copper-rich deposit automatically be rich in gold? And how can we tell where the largest deposits are located?

The depth of the deposit is crucial

The Geneva-based geologist used a range of statistical models to analyse two hypotheses: either the magmatic fluids have varying amounts of metal from the outset or the fluids are identical but it is the effectiveness of the precipitation of the metals that influences the quantity of copper and gold. "I quickly saw that the first hypothesis wasn't right, and that the answer lays with precipitation but with differences for gold and copper related to the duration of mineralisation," explains Chiaradia. "The longer the mineralisation time, the richer the deposit will be in copper. And for the mineralisation to be as long as possible, the deposit must be deep - 3 km from the surface - to guarantee a certain degree of insulation and a long magma life."

Chiaradia observed that less than 1% of the gold is captured in the ores in the deep copper-rich deposits. On the other hand, in deposits located at a depth of up to 3 km, the rate climbs to 5%, "which is still very small, because over 95% of gold always escapes into the atmosphere». In fact, although gold escapes extremely easily in volcanic emissions, "it is retained more in shallow deposits where a separation takes place between the liquid and the vapor, which helps its precipitation," points out Chiaradia. "In the deeper deposits, however, liquid and vapor form only a single fluid phase, which precipitates the copper quickly and makes the gold leak into the atmosphere as the fluid rises to the surface."

Gold is found on the surface, while copper is found at depth

Recent studies have shown that the demand for copper is increasing to such a degree that it will outstrip its availability in natural and recyclable reserves within a few decades. This means that new exploration methods are needed to help find new deposits. And for the first time, these results clearly distinguish two types of porphyry deposits and explain the different ways they are formed. The first, which are very deep, promote the mineralisation of the copper over a long period, while the latter, which are closer to the surface, produce more gold. "It's a valuable indication for the mineral exploration industry, which now knows at what depth it will find large deposits of copper, or conversely large gold deposits, irrespective of the volcano," concludes Chiaradia.

Credit: 
Université de Genève

X-rays and gravitational waves will combine to illuminate massive black hole collisions

A new study by a group of researchers at the University of Birmingham has found that collisions of supermassive black holes may be simultaneously observable in both gravitational waves and X-rays at the beginning of the next decade.

The European Space Agency (ESA) has recently announced that its two major space observatories of the 2030s will have their launches timed for simultaneous use. These missions, Athena, the next generation X-ray space telescope and LISA, the first space-based gravitational wave observatory, will be coordinated to begin observing within a year of each other and are likely to have at least four years of overlapping science operations.

According to the new study, published this week in Nature Astronomy, ESA's decision will give astronomers an unprecedented opportunity to produce multi-messenger maps of some of the most violent cosmic events in the Universe, which have not been observed so far and which lie at the heart of long-standing mysteries surrounding the evolution of the Universe.

They include the collision of supermassive black holes in the core of galaxies in the distant universe and the "swallowing up" of stellar compact objects such as neutron stars and black holes by massive black holes harboured in the centres of most galaxies.

The gravitational waves measured by LISA will pinpoint the ripples of space time that the mergers cause while the X-rays observed with Athena reveal the hot and highly energetic physical processes in that environment. Combining these two messengers to observe the same phenomenon in these systems would bring a huge leap in our understanding of how massive black holes and galaxies co-evolve, how massive black holes grow their mass and accrete, and the role of gas around these black holes.

These are some of the big unanswered questions in astrophysics that have puzzled scientists for decades.

Dr Sean McGee, Lecturer in Astrophysics at the University of Birmingham and a member of both the Athena and LISA consortiums, led the study. He said, "The prospect of simultaneous observations of these events is uncharted territory, and could lead to huge advances. This promises to be a revolution in our understanding of supermassive black holes and how they growth within galaxies."

Professor Alberto Vecchio, Director of the Institute for Gravitational Wave Astronomy, University of Birmingham, and a co-author on the study, said: "I have worked on LISA for twenty years and the prospect of combining forces with the most powerful X-ray eyes ever designed to look right at the centre of galaxies promises to make this long haul even more rewarding. It is difficult to predict exactly what we're going to discover: we should just buckle up, because it is going to be quite a ride".

During the life of the missions, there may be as many as 10 mergers of black holes with masses of 100,000 to 10,000,000 times the mass of the sun that have signals strong enough to be observed by both observatories. Although due to our current lack of understanding of the physics occurring during these mergers and how frequently they occur, the observatories could observe many more or many fewer of these events. Indeed, these are questions which will be answered by the observations.

In addition, LISA will detect the early stages of stellar mass black holes mergers which will conclude with the detection in ground based gravitational wave observatories. This early detection will allow Athena to be observing the binary location at the precise moment the merger will occur.

Credit: 
University of Birmingham

Plant genomes reveal the basis for adaptation to contrasting climates

image: The researchers studied the plant Lotus japonicus, which -- with relatively limited genomic changes -- has been able to adapt to diverse Japanese climates ranging from subtropical to temperate.

Image: 
Niels Sandal, Aarhus University

It is an open question how we can ensure that our crop plants remain productive in a changing climate. Plants are confronted with similar climate adaptation challenges when colonising new regions, as climate conditions can change quickly across latitudes and landscapes. Despite the relevance of the question, there is very limited basic scientific insight into how plants tackle this challenge and adapt to local climate conditions. Researchers from Denmark, Japan, Austria and Germany have now published the results of their research on this very subject.

The researchers studied the plant Lotus japonicus, which - with relatively limited genomic changes - has been able to adapt to diverse Japanese climates ranging from subtropical to temperate. Using a combination of field experiments and genome sequencing, the researchers were able to infer the colonisation history of L. japonicus in Japan and identify areas in the genome where plant populations adapted to warm and cold climates, respectively, showed extreme genetic differentiation. At the same time, they showed that some of these genomic regions were strongly associated with plant winter survival and flowering.

This is the first time researchers have identified specific genomic regions that have changed in response to natural selection to allow the plant species to adapt to new climatic conditions.

Professor Mikkel Heide Schierup states: "One of the great questions of evolutionary biology is how natural selection can lead to genetic adaptation to new environments, and here we directly observed an example of this in Lotus japonicus."

And Associate Professor Stig Uggerhøj Andersen adds: "Yes, and it is fascinating that we have identified specific traits, including winter survival, that have been under selection during plant local adaptation to contrasting climates. At the same time, we observed extreme genetic signatures of selection in specific genomic regions. This link between selection signatures and specific traits is critical for understanding the process of local adaptation."

"The rapid adaptation of L. japonicus to widely different climates indicates that genetic variation underlying the adaptations was already present before plant colonisation. This is promising for other plant species on a planet with rapid climate change, since it will allow more rapid adaptation," adds Professor Schierup.

"In this case, the different climates have resulted in distinct plant populations adapted to their own local environments. These populations appear to be preserved because certain genotypes are an advantage in warm climates, but a disadvantage in cold climates and vice versa," concludes Dr. Andersen.

Credit: 
Aarhus University

Brain blood flow sensor discovery could aid treatments for high blood pressure & dementia

A study led by researchers at UCL has discovered the mechanism that allows the brain to monitor its own blood supply, a finding in rats which may help to find new treatments for human conditions including hypertension (high blood pressure) and dementia.

For decades, scientists have suspected that the brain had a way of monitoring and regulating its own blood flow separate from the body-wide blood pressure control system, but until now no one had proven this.

The brain needs more blood than any other organ to satisfy neurons' relentless, high demand for oxygen, so it makes sense that it would have a way of buffering itself from blood flow fluctuations in the wider body. Disturbances to brain blood flow are a known cause in many diseases - for example, sustained reduction in brain blood flow is a likely cause of cognitive decline, dementia, and neurodegenerative disease such as Alzheimer's disease.

In a study published in Nature Communications, researchers from UCL, the University of Auckland and Bristol University, found a new function for the star-shaped brain glial cells, known as astrocytes. These cells function as specialised brain blood flow sensors that operate to self-protect the brain from potentially damaging reductions in blood supply.

Astrocytes are strategically positioned between the brain blood vessels and important nerve cells, which control the heart and peripheral circulation, ultimately determining the arterial blood pressure.

In the laboratory-based study in rats, the researchers found that decreases in brain blood flow caused astrocytes to release a chemical signal, which stimulated the specialised nerve cells to increase blood pressure and restore/maintain blood flow (and oxygen supply) to the brain.

Professor Alexander Gourine (UCL Division of Biosciences), who led the study, said: "We are very excited about this observation: there has never been a formal description of a blood flow or blood pressure sensor within the brain before.

"Our new data identify astrocytes as brain blood flow sensors that are critically important for setting the level of systemic (arterial) blood pressure and in doing so ensure that the brain receives a sufficient amount of oxygen and nutrients to support the uninterrupted operation of the information processing machinery."

Co-author Professor Julian Paton, (University of Auckland), said: "These astrocyte cells are exquisitely sensitive to reductions in brain blood flow. When blood supply is reduced, they release a chemical signal to nearby nerve cells that raise blood pressure, restoring blood flow to the brain. What we have discovered is that the brain has an automatic way to make sure that brain blood flow is preserved.

"Unfortunately, in pathological conditions this is happening at the expense of generating higher blood pressure in the rest of the body. This suggests that increasing brain blood flow by reducing activity in these blood flow sensing astrocytes may be a way to lower blood pressure in people with hypertension. It may also be a way to combat migraines and strokes. On the other hand, sensitising these cells may help in conditions of dementia to improve brain blood flow."

Corresponding author, Dr Nephtali Marina-Gonzalez, (UCL Division of Medicine), said: "In disease situations where blood supply to the brain is reduced, the mechanisms we describe can over-react causing migraines, high blood pressure and strokes. The identity of the brain blood flow sensor will make it possible to search for novel targeted treatment strategies to alleviate these diseases".

Credit: 
University College London

Scientists hope to defeat infections after discovering bacterial espionage

image: Arvi Jõers is Senior Research Fellow in Molecular Microbiology, University of Tartu.
Copyright: Kristjan Teedema/Postimees/Scanpix

Image: 
Copyright: Kristjan Teedema/Postimees/Scanpix

University of Tartu scientists hope create a solution for chronic infections that do not respond to antibiotic treatment after having discovered mechanisms for listening in on sleeping bacteria.

Having recently published a research article on the topic in Scientific Reports with his team, Senior Research Fellow in Molecular Microbiology Arvi Jõers writes about the ability of bacteria to listen in on one other and what this discovery means for medicine.

The life of bacteria is not easy. If there is sufficient food, they multiply rapidly, but they do not tend to store it. Once bacteria are out of food, it is over for them: their metabolism slows down and they enter a sleep-like state. In such a state, bacteria are quite resilient to environmental conditions and can even live through difficult times. In this, they are similar to a bear in hibernation - minimal energy is spent while waiting for better times ahead.

These arrive with new food.

Once there is enough food again, all bacteria wake up and start multiplying rapidly. However, bacteria can be more hesitant if there is little food and it is not of the best quality. Is it even worth leaving a secure state for such a lousy meal? Perhaps it is not even real food, but some sort of trick? Naturally, bacteria do not follow this line of thought. Instead, they have developed mechanisms in the course of evolution that offer solutions to such dilemmas.

One particular sign of the environment being sufficiently good for bacteria to grow and multiply is the growth of other bacteria. University of Tartu scientists discovered that sleeping bacteria can learn about the growth of other bacteria by spying on them.

Namely, as bacteria grow, they expel material from their cell walls into the environment. The cell wall is quite a rigid structure that surrounds each bacterial cell and protects it from the external environment. For a bacterium to grow bigger, the cell wall must become softer and give in to a certain degree. As a result of changes like this, part of the cell wall material enters the environment, sending sleeping bacteria a message that conditions have improved and others have enough food to grow.

Once sleeping bacteria identify material originating from the cell walls of other bacteria in the environment, they wake up quickly and in great numbers in order to get their share of the newly arrived nutrients.

Sleeping bacteria unwilling to wake up pose a serious problem in medicine. Antibiotics are, above all, known to kill actively growing bacteria and they do not often work on sleeping bacterial cells. Thus, sleeping bacteria can survive a course of antibiotics in the human body and start to grow again later when the person has finished the treatment. These cells are called persister cells and they can cause long-term chronic infections that do not respond to antibiotic treatment.

If scientists could now use this new knowledge to trick sleeping bacteria and lure them into waking up with some substance similar to a cell wall, there would be hope of killing them with antibiotics on the first try. This would allow bacterial infections to be treated with one course of treatment.

Credit: 
Estonian Research Council

Conversational difficulties with father affect adolescent health

image: Eivind Meland.

Image: 
UiB

"This demonstrates that contact with both parents after a divorce is important," says Professor Eivind Meland at the Department of Global Public Health and Care, University of Bergen.

According to numbers from the Norwegian Institute of Public Health around 40 per cent of all teenagers have experienced a divorce.

"We wanted to explore what happens to the communication between parents and children after a divorce and how this impact the children's future health," Meland explains.

The study included 1225 youths from the former region of Sogn of Fjordane. They were asked if they found it easy or difficult to talk with their parents. The answers were graded from "very easy" to "very hard or lost contact".

The researchers also asked the children about their health complaints and self-esteem. The health complaints included various physical and psychological symptoms, such as headaches, dizziness, stomach aches, anxiety, depression and trouble sleeping.

They asked the children in 2011 and in 2013. In 2011 213 of these children had divorced parents. Two years later the number had increased to 270.

"The divorce did not seem to affect how they communicate with their mother, but are strongly connected to conversational difficulties with father," Meland says.

"We also see that closeness to both father and mother impacts the children's health two year after the divorce."

More health complaints when the children had lost contact with their father

The researchers observed a clear connection between how easy the children found to talk with their father after divorce and health complaints later in life:

"Those children that reported having lost contact or who find it difficult to talk with their father after divorce also had most health complaints," says Meland.

They also saw a clear connection between the divorce and conversational difficulties between children and fathers:

"It seems like conversational difficulties between children and father was present also before the divorce, but we also see that the divorce weakens the relationship between the children and their fathers," Meland states.

If the children reported having a good relationship with both parents after the divorce, the divorce did not seem to affect the self-esteem or health to the children in any negative manner.

Daughters find it hardest to talk with their father

The study also shows that the girls have more difficulties talking with their fathers than the boys. Daughters also reported having more health complaints, but the consequence of conversational difficulties seemed to be the same for both sexes:

"In the data we can see the tendency that girls suffer more from having lost contact with their fathers, but the difference is not significant," the researcher says.

A neglected subject

The data included information on which parent was the child's main caregiver and where the children lived, but it was not considered reliable enough to be included in the article. It suggested that three times as many children reported having lost contact with their fathers than with their mothers:

"If the divorce is taken to court, it is the mother that most often ends up with the status as the main caregiver," says Meland, but adds that he sees a tendency towards that the parents decide to share the custody.

Meland strongly believes that the importance of maintaining a close relationship between father and child after a divorce is a neglected subject:

"Our research clearly shows that a strong relationship with both parents is important for the children's health. This should impact the family policy," says Meland.

Credit: 
The University of Bergen

Neither fishing tales nor sailor's yarn

image: Collectively, environmental stakeholders are just as smart as scientific experts.

Image: 
Photo: Florian Moellers

How can the complex relationships between wildlife, natural ecosystems and humans in a large number of habitats be captured with reasonable effort? Researchers need sound data over long periods of time and complex mathematical models. Can environmental stakeholders produce a similar result? An international team led by Professor Robert Arlinghaus from the Leibniz Institute of Freshwater Ecology and Inland Fisheries (IGB) and the Humboldt-Universität zu Berlin have developed a method for combining the empirical knowledge of fishery stakeholders in such a way that the result corresponds to the best scientific understanding. This is of particular interest when human and financial resources are insufficient to achieve a profound scientific understanding or when, for example, fish stock data cannot be retroactively recorded.

The study published in Nature Sustainability shows that the collective of users of fish stocks is able to identify the ecological cause-effect relationships of the population biology of the top predatory fish species pike in a way that corresponds exactly to the best scientific knowledge. The study by the international team of fisheries biologists, computer scientists and social scientists is the first evidence that the collective intelligence of nature users is able to accurately capture complex human-environment relationships.

In the study, around 220 anglers, fisheries managers and angling club managers identified factors that alone or in interaction with each other determine the development of pike populations, for example nutrients, aquatic plants, cormorants, fishing and angling or water temperature. The individual ideas on pike biology - the so-called mental models - were mathematically combined into a collective understanding of the ecological relationships. The knowledge of 17 fisheries biologists served as a reference.

The result is astonishing: if the anglers' ecological ideas are brought together, the result corresponds almost exactly to the best scientific knowledge on pike biology. "And the result is better the more actors are involved in the collective solution," explains study leader Professor Robert Arlinghaus from IGB.

Many are not necessarily better, they must also be diverse

Sounds like a primal democratic solution. "It's not quite that simple. It is important that the ideas of different types of stakeholders - anglers; fisheries managers and angling club managers - are given due consideration," notes lead author Payam Aminpour, PhD student at Michigan State University. Using only the knowledge of one type of stakeholder can lead to the accumulation of misconceptions and myths that arise from exchanges within this subgroup. "If only one stakeholder group is considered, the collective outcome deteriorates the more people are involved in the solution," Robert Arlinghaus notes.

The wisdom of the crowd (WOC) comes into play when a multi-level analytical approach is chosen. First, the collective knowledge within a user subgroup is determined and then the results are summarized across groups. "Our study shows that it makes sense to take into account the knowledge of as many different types of nature users or interest groups as possible, such as anglers, hunters, foresters, administrators and conservationists. And if as many opinions as possible are then incorporated within each group, the overall result will be particularly good," summarizes Robert Arlinghaus.

The researchers argue that the WOC-principle of resource users should be applied more systematically than today in the investigation and subsequent management of nature and the environment. This is especially true when human and financial resources are not sufficient to achieve a deep scientific understanding. For example, it is difficult to scientifically assess the state of fish stocks in thousands of lakes or to retrospectively estimate the development in a fishing area for which there are no accompanying scientific studies. A concrete example of application, on which Robert Arlinghaus and his team are currently researching, are the pike populations in the inner coastal waters, the so-called Bodden waters, around Rügen. Here, too, the team relies on the wisdom of anglers and fishers, for the hopeful benefit of all.

Credit: 
Forschungsverbund Berlin

Large study of genetic differences reveals several new targets for variety of diseases

Philadelphia, January 14, 2020 - While subtle differences in the number of genes copied from one individual and passed down to the next can be found in many healthy people, their role in disease may be much greater than previously thought.

A large, multicenter study led by researchers at Children's Hospital of Philadelphia (CHOP) compared the genomic data of more than 100,000 people of European ancestry and discovered how relatively rare, albeit recurrent, genetic variations can influence a variety of common diseases.

In addition, existing drugs could be repurposed to target these conditions - ranging from autoimmune diseases to neuropsychological diseases and even cancer - now that the genetic underpinnings of these conditions are known. The findings were published online on January 14, 2019 in the journal Nature Communications.

A copy number variation (CNV) is either a gain or loss of genomic information and occurs when the number of copies of a particular gene or genomic region varies from one individual to the next. Rare CNVs are events that often predispose people to medical conditions, whereas more common CNVs are usually well-tolerated and are common in healthy people. However, there are previously established examples in which CNVs can negatively impact a person's health. In fact, prior studies suggest they could have a widespread impact on human health, but most of those studies were based on limited sample sizes, thereby not providing researchers with a complete picture of their true significance.

"This analysis provides us with a dense map of the impact of rare recurrent copy number variations, which represent an important source of genetic variation in our genome, often predisposing us to, and sometimes causing, complex diseases," said senior author Hakon Hakonarson, MD, PhD, Director of the Center for Applied Genomics at CHOP. "Our study showed that previous methods are likely not capturing the accurate incidence or prevalence of rare copy number variation regions that directly impact human health."

The study team genotyped 100,028 individuals from populations of European ancestry using either genome-wide SNP arrays or array comparative genomic hybridization platforms. The vast majority (more than 99%) of the CNV regions uncovered, while individually rare, were recurrent, meaning that they occurred in at least two individuals.

Among these regions that are most clinically relevant are those with homozygous deletions, or the loss of both alleles or both copies of a gene from the same chromosomal pair. The study team identified 375 previously unreported regions like this. In addition to confirming disease-associated CNV regions from previous studies, the researchers discovered several previously unreported regions that match genes that are already of clinical interest, in some cases because drugs that target relevant pathways may already exist.

Some specific regions of interest identified in this study include the chr7p15.3 deletion associated with autoimmune diseases, since it overlaps with the gene that encodes for ITGB8a, a well-established drug target for ovarian cancer; a homozygous deletion region associated with autoimmunity at chr2q34 that that interrupts the coding region of the gene ERBB4, a key oncogene that can be targeted by multiple FDA-approved small molecule inhibitors; and the locus chr19p13.3, which encodes the gene HCN2 and could be a potential target for therapies to treat both epilepsy and pain.

"The number of gene candidates found in our study that warrant further studies establishes the strong correlation between regions of copy number variations and what we already know about the genome," Hakonarson said. "While ongoing, large scale studies focusing on new discoveriers are important, we believe that further investigating these newly identified regions in parallel will continue to yield even more clinically relevant information and accelerate precision medicine."

Credit: 
Children's Hospital of Philadelphia

New parasitoid wasp species discovered in the Amazon -- can manipulate host's behavior

image: The tropical parasitoid Acrotaphus wasps manipulate the behaviour of their host spiders in a complex way. The species of the genus are large and colorful.

Image: 
Kari Kaunisto

A research group from the Biodiversity Unit of the University of Turku studies the diversity of parasitoid insects around the world. Parasitoid wasps (Hymenoptera) are one of the most species rich animal taxa on Earth, but their tropical diversity is still poorly known. In the latest study, the group discovered 15 new, sizeable species that parasitise spiders in the lowland rainforests of the Amazon and the cloud forests of the Andes.

The researchers from the Biodiversity Unit of the University of Turku have studied the diversity of tropical parasitoid insects for almost 20 years already. During their research, they have discovered large numbers of new species from different parts of the world. In the newest study, the research group sampled parasitoid wasps of the genus Acrotaphus, which parasitise spiders. The diversity of the insects was studied in e.g. the tropical Andes and the lowland rainforest areas of the Amazon. The research was conducted in cooperation with the Brazilian INPA (Instituto Nacional de Pesquisas da Amazônia) research unit.

- Acrotaphus wasps are fascinating because they are very sizeable parasitoids. The largest species can grow multiple centimetres in length and are also very colourful. Previously, only 11 species of the genus were known, so this new research gives significant new information on the diversity of insects in rain forests, tells postdoctoral researcher and lead author of the new study Diego Pádua, who has worked both for the INPA and the Biodiversity Unit of the University of Turku.

The parasitoid Acrotaphus wasps parasitise on spiders. A female Acrotaphus attacks a spider in its web and temporarily paralyses it with a venomous sting. After this, the wasp lays a single egg on the spider, and a larva hatches from the egg. The larva gradually consumes the spider and eventually pupates.

- The Acrotaphus wasps we studied are very interesting as they are able to manipulate the behaviour of the host spider in a complex way. During the time period preceding the host spider's death, it does not spin a normal web for catching prey. Instead, the parasitoid wasp manipulates it into spinning a special web which protects the developing pupa from predators. Host manipulation is a rare phenomenon in the nature, which makes these parasitoid wasps very exciting in terms of their evolution, tells Ilari E. Sääksjärvi, Professor of Biodiversity research from the University of Turku.

The University of Turku and INPA continue to study the diversity of the parasitoid wasps in collaboration in the west Amazon area and in the Andes. On each research trip, the researchers discover many new species with unknown habits.

Credit: 
University of Turku

Chronic inflammation may turn skin-protecting antibody into a tumor promoter

One of the skin's defences against environmental assault can help tumours to grow when skin is exposed to chronic inflammation, finds a study in mice published today in eLife.

The IgE antibody is most commonly known for its inadvertent involvement in allergic reactions, but it is commonly found in healthy skin and believed to protect against harmful substances or parasitic infections. However, this study shows that chronic inflammation caused by repeated exposure to skin-irritating chemicals may turn this helpful defence into a harmful one. Learning more about this process may help scientists develop ways to prevent or treat skin cancer.

"Chronic inflammation has been linked to many types of cancers, and may cause these by enabling the growth and survival of cells with cancer-causing mutations," explains lead author Mark Hayes, who was a postdoctoral scientist at the Department of Immunology and Inflammation, Imperial College London, UK, at the time the study was carried out. "But the exact steps in this process and the role of IgE were not previously clear."

To learn more, Hayes and his colleagues looked at what happened after inflammation-causing substances were applied to the skin. They saw an increase in the amount of IgE produced and that immune cells called basophils were attracted to the skin. When the basophils were activated by IgE, they stimulated skin cells to divide and grow.

"IgE fortifies the skin barrier defences by promoting cell growth to thicken the surface of the skin in response to noxious stimuli," Hayes notes. "However, this response should be temporary. If it persists in the long term, it may lead to tumour growth."

The team found that in mice with cancer-causing mutations, chronic activation of IgE caused by inflammation subverts its protective effects and supports the growth of precancerous skin cells into tumours. On the other hand, mice lacking IgE were protected from developing these tumours in response to inflammation.

Surprisingly, the results of a previous study by the team showed that IgE protects mice against cancer-causing substances that damage DNA. This suggests that the mechanism of tumour growth, and the role of IgE in this process, may depend on different kinds of environmental exposure.

"Our previous and current findings reveal a strong link between IgE and cancer," says senior author Jessica Strid, Reader in Cellular Immunology at the Department of Immunology and Inflammation, Imperial College London. "But the biological consequences of IgE engagement in the skin clearly depends on the nature of the antibodies and the microenvironment in which the tumour grows."

Credit: 
eLife

Intestine-chip populated with organoids demonstrates superior function vs. organoids alone

image: SEM image of the Intestine-Chip showing the presence of a well-developed continuous brush border consisting of densely packed microvilli, as well as mature specialized cell types such as mucus producing goblet cells.

Image: 
Emulate, Inc.

BOSTON, Mass., January 14, 2020 -- Emulate, Inc. announced today a published study in collaboration with Johns Hopkins University School of Medicine, that demonstrated superior functionality of the Duodenum Intestine-Chip populated with organoids, compared to organoids alone. The study, published in the peer-reviewed journal, eLife, showed that the Intestine-Chip produced a nearly identical global transcriptomic profile compared to human intestine duodenum tissue, whereas the signature from the organoids alone had significant differences from the human intestine tissue. The authors further showed that the similarities at the transcriptomic level also resulted in significantly more accurate physiological function of the Intestine-Chip compared to organoids alone. These results demonstrate the potential of the Intestine-Chip to provide a robust system to accurately recreate human intestine tissues for highly predictive and human-relevant preclinical drug assessment, including drug transport, metabolism, and drug-drug interactions.

In this research, Emulate scientists in collaboration with scientist at Johns Hopkins University School of Medicine established the Duodenum Intestine-Chip from organoids derived from endoscopic biopsies of healthy adult human donors and primary human intestinal microvascular endothelial cells derived from human small intestine. The Intestine-Chip recreated the barrier function and multilineage differentiation of adult human intestinal tissue. Global gene expression was assessed by RNA-sequencing analysis and showed that the profile of the Intestine-Chip and freshly isolated human adult duodenum tissue were remarkably similar; in contrast, the organoids alone from the same donor showed significant differences in RNA-sequencing analysis. Additionally, the biology for drug transporters and drug metabolizing enzymes of the intestine remained intact in the Duodenum Intestine-chip, which is not effectively modeled with current animal testing due to the species-specific nature of these drug transporters, drug metabolizing enzymes, and the factors regulating them.

"Using our Intestine-Chip, we are able to accurately recreate key functions of the human duodenum. These findings show a path forward to using a more human-relevant and robust system to better predict pharmacokinetics and drug-drug interaction," said Geraldine A. Hamilton, President and Chief Scientific Officer of Emulate. "Today, we see the value of using our Intestine-Chip product with organoids as a leading-edge preclinical testing method. Further in the future, we envision exciting potential applications for our Intestine-Chip to utilize cells isolated from individual patients to be used for personalized medicine."

Findings from the published functional testing demonstrated that the Duodenum Intestine-Chip more accurately recreated several aspects of the human intestine, compared to organoids or Caco-2 models, including:

Expression of drug transporters. Expression levels of several important transporters for efflux (MDR1, CVRP, MRP2, and MRP3) and uptake (PEPT1, OATP2B1, OCT1, and SLC40A1) were similar for the Duodenum Intestine-Chip and freshly isolated duodenal tissue, but not in the previously described Caco-2 Intestine-Chip which showed significant variation in expression of OATPB1 and OCT1.

Localization and function of drug transporters. In vivo-relevant localization of the luminal efflux pumps, MDR1 and BCRP, and the uptake pump PEPT1 were shown to co-distribute together with villin, a marker specific for apical cell membrane, at the intestinal cell brush border in Duodenum Intestine-Chip. The MDR1 activity was confirmed by measuring the intracellular accumulation of rhodamine 123 in the presence and absence of specific MDR1 inhibitor, vinblastine, across the Duodenum Intestine-Chip.

Drug-mediated CYP3A4 expression and induction potential. The Duodenum Intestine-Chip expressed CYP3A4 gene and protein levels at significantly higher levels than the Caco 2 Intestine-Chip, reaching levels similar to that observed in the adult human duodenum. Expected CYP3A4 induction was observed in the Duodenum Intestine-Chip when exposed to rifampicin and vitamin D3, two prototypical CYP3A4 inducers. The Caco 2 Intestine-Chip showed induction when exposed to vitamin D3 but not rifampicin.

Study results were derived from testing of the Duodenum Intestine-Chip established from individual donors of biopsy-derived organoids. The ability to establish the Duodenum Intestine-Chip composed of the cells isolated from individual patients opens the possibility of personalized medicine. Applications include personalized preclinical testing and personalized clinical pharmacology to assess a range of measures, including: inter-individual differences in drug disposition and responses, studies of the effect of genetic polymorphisms on pharmacokinetics and pharmacodynamics, as well as decoupling of the effect of various factors such as age, sex, disease state, and diet on metabolism, clearance, and bioavailability of drugs.

Credit: 
The Yates Network

Researchers develop tool to identify molecular receptors in worms

image: WPI researcher Jagan Srinivasan (left) and Douglas K. Reilly.

Image: 
Worcester Polytechnic Institute

Worcester, Mass. - January 14, 2020 - Researchers at Worcester Polytechnic Institute (WPI) have developed a tool to identify molecular receptors in worms that are involved in sensing pheromones related to mating, an advance that could speed up neuroscience research into pheromones by eliminating months of work.

Associate professor of biology and biotechnology Jagan Srinivasan, doctoral candidate in biology Douglas K. Reilly, and researchers at Cornell University published their findings in Organic & Biomolecular Chemistry, a journal of the Royal Society of Chemistry in the United Kingdom.

Pheromones are chemicals produced by animals that send signals to other animals and trigger social responses, such as mating. Srinivasan and Reilly study pheromones in microscopic worms known as Caenorhabditis elegans, or C. elegans, to better understand how the sense of smell works. Their research could have implications for human research because C. elegans has a nervous system that mimics the basic mechanisms of smell in humans, and loss of the sense of smell is associated with neurodegenerative disorders such as Alzheimer's disease.

Srinivasan and Reilly developed a process that more quickly isolates pheromone receptors in C. elegans. Receptors are specialized proteins that act as docking stations for molecules. When worms are exposed to pheromones, the pheromones latch onto the molecular receptors in the worms.

Isolating a specific molecular receptor traditionally has been a long, laborious process because the worms possess more than 1,000 molecular receptors. Srinivasan described the traditional process--which takes three or four months--as hunting for a needle in a haystack. The new method he and Reilly developed takes about a month.

"Here we are saving months of work, we're streamlining the process, and we're getting a targeted approach," Srinivasan said.

In their study, Srinivasan and Reilly attached a chemical known as an alkyne to an ascaroside, a pheromone produced by C. elegans to attract male worms for mating.

"We wanted to find a way that we could take a pheromone and link it to a probe, yet it would still be biologically active so a male would sense it and respond to it with the right receptor," Reilly said. "Then we wouldn't have to screen 1,200 receptors that are in the genome."

For this study, the researchers focused on the process rather than the resulting receptor, which they said could be a subject of further research. Their probe methods could also be applied to other pheromones and to other research organisms, such as flies, to better understand how receptors function, they said.

"We're looking at this mate attractant pheromone, but there are people looking at pheromones involved in foraging for food and other actions," Reilly said. "For those, we can start to ask what receptors are sensing the pheromone we're using."

In addition, Srinivasan said, "Applications of this new technology could help identify receptors in parasitic nematodes that cause damage to agricultural crops."

Credit: 
Worcester Polytechnic Institute

'Coolsculpting' inventors develop new non-surgical method for targeting fat

BOSTON - How cool is this: the Massachusetts General Hospital (MGH) laboratory that invented cryolipolisis or "Coolsculpting," a popular non-surgical method for reducing fat under the skin, is developing a new form of the technology that can selectively reduce fat almost anywhere in the body using a safe, injectable ice solution or "slurry."

The technology, not yet approved for use in humans, is designed for removal of fat in the abdomen or other parts of the body - virtually anywhere that can be reached with a hypodermic needle. Fat is a normal part of our bodies, but in excess or with some diseases can be life-threatening.

The new technique is described in a paper published online ahead of print in the journal Plastic and Reconstructive Surgery. As one of the reviewers of the paper said, "this treatment has the potential to become one of the most performed cosmetic procedures in plastic surgery practice."

"The appeal of this technique is that it's easy and convenient to do," says lead author Lilit Garibyan, MD, PhD, investigator in the Wellman Center for Photomedicine at MGH and the Department of Dermatology at Harvard Medical School. "With Coolsculpting, which is a topical cooling technique, the patient has to sit there for almost an hour for enough heat to diffuse from the fat underneath the skin. With this new technique the doctor can do a simple injection that takes just less than a minute, the patient can go home, and then the fat gradually disappears."

Cryolipolysis is currently the leading non-invasive fat removal technology because of its minor side effects and non-invasive nature. The Coolsculpting method is limited, however, by the amount of fat that can be removed per treatment, and is not practical for reaching more deeply seated fat surrounding organs or other body structures.

The MGH team's innovative spin on the technique involves the use of an injectable ice "slurry," a sterile solution of normal saline and glycerol (a common food ingredient) containing approximately 20% to 40% small ice particles, similar in texture to slush. The solution can be injected directly into fat deposits, causing the fat cells (adipocytes) to crystallize and die and fat deposits to shrink. The killed adipocytes are gradually eliminated by the body over a period of weeks. "One of the cool things about this is how the injected slurry causes selective effects on fat," said Rox Anderson, MD, a co-author and leader of the Wellman Center. "Even if the slurry is injected into other tissue such as muscle, there is no significant injury."

As the investigators report, injection of the ice solution into pigs resulted in a 55% reduction in fat thickness compared to that of pigs injected with the same but melted ice solution. There was no damage to skin or muscle at the injection site, and no systemic side effects or abnormalities seen.

Unlike topical cooling, slurry injection can target and remove fat tissue at essentially any depth and any site that can be accessed by a needle or catheter. Injection of physiological ice slurry could be a transformative method for nonsurgical body contouring.

Credit: 
Massachusetts General Hospital

Final images from Cassini spacecraft

image: Composite of a true colour image of Saturn, observed by Cassini in 2016, overlaid with a false colour representation of the ultraviolet aurora in the northern hemisphere as observed on 20 August 2017.

Image: 
NASA/JPL-Caltech/Space Science Institute/A. Bader (Lancaster University).

Researchers are busy analysing some of the final data sent back from the Cassini spacecraft which has been in orbit around Saturn for more than 13 years until the end of its mission in September 2017.

For the last leg of its journey, Cassini was put on a particularly daring orbit passing between Saturn and its rings which brought it closer to Saturn than ever before. This allowed scientists to obtain images of Saturn's ultraviolet auroras in unprecedented resolution.

The new observations are detailed in two new studies published in Geophysical Research Letters and JGR: Space Physics.

Saturn's auroras are generated by the interaction of the solar wind, a stream of energetic particles emitted by the Sun, with Saturn's rapidly rotating magnetic field. They are located in the planet's polar regions and known to be highly dynamic, often pulsating and flashing as different dynamic processes occur in the planet's plasma environment.

Lancaster University PhD student and lead author of the research Alexander Bader said: "Surprisingly many questions revolving around Saturn's auroras remain unanswered, even after the outstanding success of the Cassini mission.

"This last set of close-up images gives us unique highly detailed views of the small-scale structures which couldn't be discerned in previous observations by Cassini or the Hubble Space Telescope. We have some ideas about what their origin could be, but there is still a lot of analysis to be done."

Satellite imagery alone will hardly be enough to unravel the aurora's mysteries - the energetic particles causing the bright lightshows around Saturn's poles originate far away from the planet's surface where magnetic field lines twist and clouds of plasma interact with one another. When located in the right region, Cassini was sometimes embedded in the particle stream connecting the auroras to the magnetosphere.

First analysis of the spacecraft's particle measurements recorded during these times showed that Saturn's auroras, like Jupiter's, are generated by much more energetic particles than Earth's. However, the underlying physical mechanisms appear to show similarities between all the three.

Even though Cassini's mission is over, the data it provided remains full of surprises and will continue to help researchers understand the workings of giant planet auroras, especially in combination with Juno observations of Jupiter's magnetosphere.

Credit: 
Lancaster University