Earth

Prejudice, poverty, gender - illustrations show the reality of living with disease

image: Long distances and poor roads hinder many with NTDs from accessing healthcare, especially those with poor mobility.

Image: 
Sightsavers

Illustrations by a local artist in Nigeria are helping health workers and policy makers understand what it's really like to live with a neglected tropical disease (NTD).

The twelve illustrations have been drawn as part of a research project to improve services for those living with long term impacts of conditions such as lymphatic filariasis, buruli ulcer and leprosy. They include depictions of some of the social and mental health impacts of these conditions - including stigmatisation, loneliness and depression - and will be used in new areas later this month.

When the images, created by Nigerian artist, Christian Okwananke, were shown to NTD health professionals including programme implementers, healthcare workers and policy makers in the Nigerian capital Abuja, it was clear that they had an impact.

"The illustrations kickstarted conversations in a sensitive, non-confrontational way. The health professionals clearly related to the images and were able to understand more effectively the challenges faced by their patients," said Martins Imhansoloeva, research coordinator at Sightsavers.

"We rightly spend a lot of time working to eliminate NTDs, but sometimes at the expense of considering the people behind the numbers and providing services which reflect the realities experienced by people living with an NTD," he added.

The illustrations were drawn following a community-based participatory research programme looking into morbidity management and disability prevention (MMDP) services. These services rarely have input from the people who have been directly affected, which is why research like this is critical.

NTDs affect more than a billion people around the world - often in the poorest and most rural communities - and can cause severe and lifelong physical impairments.

Community stigma and discrimination is often based on misinformation, cultural or traditional beliefs, and further pressures come from fear of surgery, difficulties accessing transport to take up services, worry over the cost of treatment and overstretched health workers.

Large scale mass drug administration programmes to combat NTDs are well established, whilst services for those living with an NTD remain generally underfunded and poorly accessed.

Sightsavers works with partners and ministries of health to eliminate and treat five neglected tropical diseases in over 30 countries: The five NTDs it treats are: trachoma, river blindness (onchocerciasis), elephantiasis (lymphatic filariasis), schistosomiasis and intestinal worms (soil transmitted helminths).

Credit: 
Sightsavers

Scientists improve a land surface model to better simulate the carbon-nitrogen flux

image: The nitrogen cycle related to carbon flux in the Atmosphere--Vegetation Interaction Model

Image: 
Li Dan

Along with Europe and North America, East Asia has in the past few decades become one of the three largest nitrogen deposition centers in the world. This can lead to considerable impacts on the structure and function of ecosystems; for instance, excessive nitrogen is thought to be one of the drivers of biodiversity change across the globe; and nitrogen deposition can also cause acidification of soils and water. Consequently, it is important to study the carbon-nitrogen cycle in East Asia.

Professor Li Dan from the Institute of Atmospheric Physics, Chinese Academy of Sciences, and his colleagues, incorporated the full nitrogen cycle--including deposition, mineralization, immobilization, biological fixation, nitrification, denitrification, volatilization, and leaching of nitrogen--into a land surface model (AVIM: Atmosphere-Vegetation Interaction Model), which was designed and developed by Chinese scientists and was one of the earliest models to consider the dynamical process of vegetation. The latest version of AVIM has been run for the China region for the period 1979 to 2015 at a resolution of 10 km, and the results have been recently published in Atmospheric and Oceanic Science Letters (https://doi.org/10.1080/16742834.2020.1819145).

According to this study, gross primary production and net primary production are simulated well by AVIM across China when compared to carbon flux data from MODIS and the ensemble mean data of TRENDY(Trends in Net Land-atmosphere Carbon Exchange) . The nitrogen deposition and biological fixation are also reasonable well simulated at the regional scale. However, the variation in carbon and nitrogen fluxes shows discrepancies in the different datasets and in AVIM, which highlights the complexity and importance of coupling nitrogen with the carbon cycle into land surface models in East Asian monsoon regions.

"The variation by standard deviation and anomaly will be the benchmark to improve the carbon-nitrogen interaction in the future, which can decrease the uncertainty in simulating the carbon-nitrogen flux and improve the land-air interaction at regional scales", concludes Prof. Dan.

Credit: 
Institute of Atmospheric Physics, Chinese Academy of Sciences

New understanding of how proteins operate

image: Professor Philip Hogg (left) and Dr Diego Butera (right)

Image: 
Centenary Institute

A ground-breaking discovery by Centenary Institute scientists has provided new understanding as to the nature of proteins and how they exist and operate in the human body.

The key finding-the changing state of a protein's structural bonds-is likely to have significant implications as to how proteins are targeted by medical researchers, particularly in terms of drug development and the fight against disease.

Proteins are responsible for all of life's processes and had previously been considered to exist in an intact single state when mature. The new study however has found two human proteins involved in blood clotting and immunity existing in different and changing states.

"The most sophisticated molecules made in nature are proteins which consist of unique sequences of amino acids," said Dr Diego Butera from the ACRF Centenary Cancer Research Centre and lead author of the study. "Disulphide bonds link the amino acid chains together and were thought to just stabilise protein structure."

Previously it has been believed that these disulphide bonds were fully formed in the mature and functional protein. In this study however, the researchers found that the proteins are being produced in multiple disulphide-bonded states.

"We were able to precisely measure whether the disulphide bonds in the blood proteins were formed or broken. Remarkably, we saw that the proteins were made in multiple, possibly thousands, of different disulphide-bonded states," said Dr Butera.

Professor Philip Hogg, Head of the ACRF Centenary Cancer Research Centre and senior author of the study believes that their research will change how proteins are viewed and targeted in future drug and medical experiments.

"It's very likely that we will find many other proteins that exist in multiple states. Crucially, a drug may bind more or less preferentially to different states, impacting the effectiveness of the drug."

"In experimental settings, differing states of a protein should now be considered as part of the investigative medical research process," Professor Hogg said.

Credit: 
Centenary Institute

Why protecting the brain against infection takes guts

The brain is uniquely protected against invading bacteria and viruses, but its defence mechanism has long remained a mystery. Now, a study in mice, confirmed in human samples, has shown that the brain has a surprising ally in its protection: the gut.

The brain is arguably the most important organ in the body, as it controls most other body systems and enables reasoning, intelligence, and emotion. Humans have evolved a variety of protective measures to prevent physical damage to the brain: it sits in a solid, bony case - the skull - and is wrapped in three layers of watertight tissue known as the meninges.

What has been less clear is how the body defends the brain from infection. Elsewhere in the body, if bacteria or viruses enter the bloodstream, our immune system kicks in, with immune cells and antibodies that target and eliminate the invader. However, the meninges form an impermeable barrier preventing these immune cells from entering the brain.

In research published today in Nature, a team led by scientists at the University of Cambridge, UK, and the National Institute of Health, USA, have found that the meninges are home to immune cells known as plasma cells, which secrete antibodies. These cells are specifically positioned next to large blood vessels running within the meninges allowing them to secrete their antibody 'guards' to defend the perimeter of the brain. When the researchers looked at the specific type of antibody produced by these cells, they got a surprise - the antibody they observed is normally the type found in the intestine.

Plasma cells are derived from a particular type of immune cell known as a B cell. Every B cell has an antibody on its surface that is unique to that cell. If an antigen (the part of a bacterium or virus that triggers an immune response) binds to that surface antibody, the B cell becomes activated: it will divide to make new offspring that also recognise that same antigen.

During division, the B cell introduces a mutation into the antibody gene so that one amino acid is changed and its binding characteristics are slightly different. Some of these B cells will now produce antibodies that enable better binding to the pathogen - these go on to expand and multiply; B cells whose antibodies are less good at binding die off. This helps ensure the body produces the best antibodies for targeting and destroying particular antigens.

Normally, the antibodies found in the blood are a type known as Immunoglobulin G (IgG), which are produced in the spleen and bone marrow - these antibodies protect the inside of the body. However, the antibodies found in the meninges were Immunoglobulin A (IgA), which are usually made in the gut lining or in the lining of the nose or lungs - these protect mucosal surfaces, the surfaces that interface with the outside environment.

The team were able to sequence the antibody genes in B cells and plasma cells in the gut and meninges and show that they were related. In other words, the cells that end up in the meninges are those that have been selectively expanded in the gut, where they have recognised particular pathogens.

"The exact way in which the brain protects itself from infection, beyond the physical barrier of the meninges, has been something of a mystery, but to find that an important line of defence starts in the gut was quite a surprise," said lead scientist Professor Menna Clatworthy from the Department of Medicine and CITIID at the University of Cambridge and the Wellcome Sanger Institute.

"But actually, it makes perfect sense: even a minor breach of the intestinal barrier will allow bugs to enter the blood stream, with devastating consequences if they're able to spread into the brain. Seeding the meninges with antibody-producing cells that are selected to recognise gut microbes ensures defence against the most likely invaders."

The team made the discovery using mice, which are commonly used to study physiology as they share many characteristics similar to those found in the human body. They showed that when the mice had no bacteria in their gut, the IgA-producing cells in the meninges were absent, showing that these cells actually originate in the intestine where they are selected to recognise gut microbes before taking up residence in the meninges. When the researchers removed the plasma cells in the meninges - and hence no IgA was present to trap bugs - microbes were able to spread from the bloodstream into the brain.

The team confirmed the presence of IgA cells in the human meninges by analysing samples that were removed during surgery, showing that this defence system is likely to play an important role in defending humans from infections of the central nervous system - meningitis and encephalitis.

Credit: 
University of Cambridge

'Monster tumors' could offer new glimpse at human development

image: Histology image of a teratoma

Image: 
Daniella McDonald

Finding just the right model to study human development--from the early embryonic stage onward--has been a challenge for scientists over the last decade. Now, bioengineers at the University of California San Diego have homed in on an unusual candidate: teratomas.

Teratomas-- which mean "monstrous tumors" in Greek--are tumors made up of different tissues such as bone, brain, hair and muscle. They form when a mass of stem cells differentiates uncontrollably, forming all types of tissues found in the body. Teratomas are generally considered an undesired byproduct of stem cell research, but UC San Diego researchers found an opportunity to study them as a model for human development.

Researchers report their work in a paper published Nov. 4 in Cell.

"We've been fascinated with the teratoma for quite a while," said Prashant Mali, a professor of bioengineering at the UC San Diego Jacobs School of Engineering. "Not only is the teratoma an intriguing tumor to look at in terms of the diversity of cell types, but it also has regions of organized tissue-like structures. This prompted us to explore its utility in both cell science and cell engineering contexts."

"There's no other model like it. In just one tumor, you can study all of these different lineages, all of these different organs, at the same time," said Daniella McDonald, an M.D/Ph.D. candidate in Mali's lab and co-first author of the study. "Plus, it's a vascularized model, it has a three-dimensional structure and it's human-specific tissue, making it the ideal model for recreating the context in which human development happens."

The team used teratomas grown from human stem cells injected under the skin of immunodeficient mice. They analyzed the teratomas with a technique called single-cell RNA sequencing, which profiles the gene expression of individual teratoma cells. The researchers were able to map 20 cell types, or "human lineages" (brain, gut, muscle, skin, etc.) that were consistently present in all the teratomas they analyzed.

The researchers then used the gene editing technology CRISPR-Cas9 to screen and knock out 24 genes known to regulate development. They found multiple genes that play roles in the development of multiple lineages.

"What's remarkable about this study is that we could use the teratoma to discover things in a much faster way. We can study all of these genes on all of these human lineages in a single experiment," said co-first author Yan Wu, who worked on this project as a Ph.D. student in the labs of Mali and UC San Diego bioengineering professor Kun Zhang. "With other models, like organoids, that separately model one lineage at a time, we would have had to run many different experiments to come up with the same results as we did here."

"Teratomas are a very unique type of human tissue. When examined through the lens of single-cell sequencing, we can see that they contain most major representative cell types in the human body. With that understanding, we suddenly have an extremely powerful platform to understand, manipulate and engineer human cells and tissues in a far more sophisticated way than what was previously possible," Zhang said.

The researchers also showed that they can "molecularly sculpt" the teratoma to be enriched in one lineage--in this case, neural tissue. They accomplished this feat using a microRNA gene circuit, which acts like a molecular chisel by carving away unwanted tissues--these are selectively killed off using a suicide gene--and leaving behind the lineage of interest. The researchers say this has applications in tissue engineering.

"We envision that this study will set a new foundation in the field. Hopefully, other scientists will be using the teratoma as a model for future discoveries in human development," McDonald said.

Credit: 
University of California - San Diego

Revealing the identity of the last unknown protein of autophagy

image: Isolation membranes expand to form autophagosomes by receiving lipids from endoplasmic reticulum, which is mediated by Atg2. However, Atg2 alone cannot mediate membrane expansion because lipids will accumulate at the cytoplasmic leaflet.

Image: 
Nobuo N. Noda & Kazuaki Matoba

Drs. Nobuo Noda (Director) and Kazuaki Matoba (Senior Researcher) et al. at the Institute of Microbial Chemistry (BIKAKEN, Tokyo, Japan) discovered that Atg9, one of the proteins that function to mediate autophagy, has phospholipid-translocation activity (the lipid scramblase activity (1)) between the two layers of the lipid bilayer (2) and elucidated that the protein's activity brings about autophagosome (3) membrane expansion.

Autophagosome formation is an essential step in determining the target of degradation in autophagy, which is one of the mechanisms of intracellular protein degradation. Although this research group has previously revealed that Atg2, a lipid transfer protein, transfers phospholipids from the endoplasmic reticulum, the manner in which the membrane is expanded using the transported phospholipids remains unknown.

The research group demonstrated that yeast and human Atg9, a membrane protein of unknown function, exhibits lipid scramblase activity through in vitro experiments. Moreover, as a result of examining the three-dimensional structure of yeast Atg9 by cryo-electron microscopy (4), they found that Atg9 has pores connecting the two membrane leaflets of the lipid bilayer. They also found that the mutations to the pore-forming amino acids resulted in losing the lipid scramblase activity of Atg9 in vitro and inhibited the autophagosome formation in yeast. Consequently, they revealed a brand-new mechanism that Atg9 is a novel scramblase (1); in conjunction with Atg2, a lipid transfer protein, these two proteins act to form autophagosomes.

The elucidation of the mechanisms of isolation membrane expansion, which have been a long-standing issue in the field of autophagy holds promise in accelerating research that will contribute to a complete understanding of the molecular mechanisms of autophagosome formation. It is also expected to promote the research and development of treating and preventing various diseases through the artificial control of autophagy due to deepening our understanding of autophagosome formation mechanisms.

Credit: 
Japan Science and Technology Agency

Convection-permitting modelling improves simulated precipitation over the Tibetan Plateau

image: A glance at Himalayas Mountains, the highest mountains of the Tibetan Plateau

Image: 
Qi Zhang (http://photography.zhangqibot.com)

The Tibetan Plateau (TP) is the highest and most extensive highland in the world, and is widely known as "the Roof of the World", "the World Water Tower" and "the Third Pole". The thermal and mechanical forces of the TP play an essential role in influencing the global climate, and precipitation is one of its most important water-cycle components.

However, accurately simulating precipitation over the TP is a long-standing worldwide challenge. Current state-of-the-art climate models tend to overestimate precipitation over the TP. The wet bias over the TP in current numerical models could be a combined outcome of the model's dynamical core, inadequate model physical parameterizations and relative coarse model resolution. The deep convection parameterization has been regarded has the largest source of model uncertainty in simulating precipitation.

Due to the rapid development of high performance computing resources, convection-permitting models (CPMs), which with horizontal-grid spacing of less than 5 km are constructed to partially resolve (rather than parameterize) convective heat and moisture transport, and thereby offer a path towards fundamental advances in our understanding of factors influencing clouds and precipitation, have become important tools for climate research.

Recently, under the Climate Science for Service Partnership China (CSSP China; https://www.metoffice.gov.uk/research/approach/collaboration/newton/cssp-china/index) and Convection-Permitting Third Pole (CPTP, which was endorsed by WCRP-CORDEX as a Flagship Pilot Study; http://rcg.gvc.gu.se/cordex_fps_cptp/), researchers from the Institute of Atmospheric Physics at Chinese Academy of Sciences, the Chinese Academy of Meteorological Sciences at China Meteorological Administration and the UK Met Office, have jointly investigated the added value of a CPM in simulating precipitation characteristics over the TP, and explained the possible reasons for excessive precipitation over the TP in the mesoscale convection-parameterized models.

Their results show that two mesoscale models (MSMs) have notable wet biases over the TP and can overestimate the summer precipitation by more than 4.0 mm per day in some parts of the central and eastern TP. Moreover, both MSMs have more frequent light rainfall, increasing horizontal resolution of the MSMs alone does not reduce the excessive precipitation. Further investigation reveals that the MSMs have a spurious early-afternoon rainfall peak, which can be linked to a strong dependence on convective available potential energy (CAPE) that dominates the wet biases.

"Herein, we highlight that the sensitivity of CAPE to surface temperatures may cause the MSMs to have a spurious hydrological response to surface warming. Users of climate projections should be aware of this potential model uncertainty when investigating future hydrological changes over the TP", said Dr. Puxi Li, the paper's lead author, a researcher from the Chinese Academy of Meteorological Sciences.

By comparison, the CPM removes the spurious afternoon rainfall and thus significantly reduces the wet bias simulated by the MSMs. "The CPM also better depicts the precipitation frequency and intensity, and is therefore a promising tool for dynamic downscaling over the TP", Dr. Kalli Furtado, the second author of the study, added.

Credit: 
Institute of Atmospheric Physics, Chinese Academy of Sciences

Coral larvae movement is paused in reaction to darkness

video: Upon light attenuation (at the 0 sec mark in the movie), the larvae temporarily stopped swimming (from around 20 sec mark). After a certain period of time from the light attenuation, the larvae resume swimming (from around 120 sec mark).

Image: 
NIBB

Light is essential for the growth of reef-building corals. This is because corals grow by using the photosynthetic products of the algae living inside their cells as a source of nutrients. Therefore, the light environment of coral habitats are important for their survival.

A new study published in Scientific Reports shows that coral larvae swimming in seawater behave in such a manner so as to temporarily stop swimming due to reduced light, especially blue light. Researchers think that this behavior may play a role in determining where corals settle.

Corals can only move freely during the larval stage of their lives. Larvae that hatch from eggs are able to swim by moving the cilia on the surface of their bodies. After that, when the larva settles on the seabed and transforms into a sedentary form (called a "polyp"), it becomes immobile.

How the corals, whose growth requires light, select a suitable light environment for survival is a mystery. To solve it, a research team led by Dr. Yusuke Sakai, Professor Naoto Ueno of the National Institute for Basic Biology in Japan thoroughly observed the response of coral larvae to light. They found that coral larvae temporarily stop swimming in response to a decrease in light intensity and then subsequently resumed swimming at their initial speed.

Corals mostly lay eggs once a year. "In collaboration with Andrew Negri, principal investigator at the Australian Institute of Marine Science, and Professor Andrew Baird and his colleagues at James Cook University, we have not only tested corals in Japan, but also in Australia's Great Barrier Reef, where coral spawning occurs at a different time than here. This was performed in order to repeat the experiment and thus validate our findings " said Dr. Sakai.

The research team then conducted a detailed analysis of the wavelengths of light that coral larvae react to. The Okazaki Large Spectrograph, the world's largest spectroscopic irradiator at the National Institute for Basic Biology, was used for this experiment. Experiments with coral larvae exposed to various light wavelengths revealed that coral larvae respond strongly to purple to blue light.

How does pausing behavior in response to light decay affect the destination of coral larvae? To answer this question, researchers conducted mathematical simulations; the results of which show that the pause caused by the attenuation of light and the subsequent resumption of swimming have the effect of resetting the swimming direction of the larva once when it moves into a dark region and turning it in a random direction. As a result, it was suggested that it would lead to the gathering of larvae in a bright space.

Dr. Sakai said "In cnidarians, including corals, the mechanism of light reception is largely unknown. We would like to clarify the molecular mechanism of light reception in coral larvae, which do not have an eye structure".

"In the future, it will be important to elucidate not only this phenomenon but also the mysterious ecology of coral at the molecular and cellular levels, such as the mechanism for controlling the spawning time" Professor Naoto Ueno commented.

Credit: 
National Institutes of Natural Sciences

Recipe for a storm

image: The active grid in the wind tunnel can stir up air flows to generate realistic storm turbulence.

Image: 
University of Oldenburg/Mohssen Assanimoghaddam

Strong storms often seem to leave behind random destruction: While the roof tiles of one house are blown away, the neighboring property may not be damaged at all. What causes these differences are wind gusts - or, as physicists say, local turbulence. It results from large-scale atmospheric flows, but up to now, it is impossible to predict it in great detail.

Experts from the University of Oldenburg and the Université de Lyon have now paved the way for studying small-scale turbulence: The team led by Oldenburg physicist Prof. Dr. Joachim Peinke succeeded in generating turbulent flows in a wind tunnel. The flows resembled those occurring in big gales. The team has found a way to literally cut a slice out of a storm, the researchers report in the journal Physical Review Letters. "Our experimental discovery makes our wind tunnel a model for a new generation of such facilities in which, for example, the effects of turbulence on wind turbines can be realistically investigated," says Peinke.

The most important parameter characterising the turbulence of a flow is the so-called Reynolds number: This physical quantity describes the ratio of kinetic energy to frictional forces in a medium. In simple terms, you can say: The greater the Reynolds number, the more turbulent the flow. One of the greatest mysteries of turbulence is its statistics: Extreme events such as strong, sudden wind gusts occur more frequently if you look at smaller scales.

Unresolved equations

"The turbulent eddies of a flow become more severe on smaller scales," explains Peinke, who heads the research group Turbulence, Wind Energy and Stochastics. In a strong storm - that is, when the Reynolds number is high - a fly is therefore affected by much gustier flow conditions than, say, an airplane. The specific reasons for this are not well known: the physical equations describing fluids are not yet solved when it comes to turbulence. This task is one of the famous millennium problems of mathematics, on whose solution the Clay Mathematics Institute in the U.S. has put up one million dollars each.

In the large wind tunnel of the Center for Wind Energy Research (ForWind), the Oldenburg team has now succeeded in generating more turbulent wind conditions than ever before. Compared to previous experiments, the researchers increased the Reynolds number a hundred times and thus simulated conditions similar to those encountered in a real storm. "We do not yet see an upper limit," says Peinke. "The turbulence generated is already very close to reality."

Experiments in the wind tunnel

The Oldenburg wind tunnel has a 30-meter long test section. Four fans can generate wind speeds of up to 150 kilometers per hour, which corresponds to a category 1 hurricane. To create turbulent air flow, the researchers use a so-called active grid, which was developed for the special requirements in the large Oldenburg wind tunnel. The structure, three by three meters in size, is located at the beginning of the wind tunnel and consists of almost a thousand small, diamond-shaped aluminum wings. The metal plates are movable. They can be rotated in two directions via 80 horizontal and vertical shafts. This allows the wind researchers to selectively block and reopen small areas of the wind tunnel nozzle for a short time, causing air to be swirled. "With the active grid - the largest of its kind in the world - we can generate many different turbulent wind fields in the wind tunnel," explains Lars Neuhaus, who is also a member of the team and played a key role in this study.

For the experiments, the team varied the movement of the grid in a chaotic manner similar to the conditions occurring in turbulent air flow. They also changed the power of the fans irregularly. Thus, in addition to small-scale turbulence, the air flow generated a larger movement in the longitudinal direction of the wind tunnel. "Our main finding is that the wind tunnel flow combines these two components into perfect, realistic storm turbulence," explains co-author Dr. Michael Hölling. The physicist also chairs the international Wind Tunnel Testing Committee of the European Academy of Wind Energy (EAWE). This storm turbulence emerged 10 to 20 meters behind the active grid.

Swirls on a small scale

"By adjusting the grid and the fans of the wind tunnel, we have generated a large-scale turbulence about ten to one hundred metres in size. At the same time, a small-scale turbulence with dimensions of a few meters and less appeared spontaneously. However, we still don't know exactly why," Hölling explains. As he and his colleagues report, this new approach makes it possible to scale down atmospheric turbulence relevant to wind turbines, aircraft or houses to a size of one meter in the wind tunnel. This will allow researchers to conduct realistic experiments with miniaturized models in the future - in which extreme gusts occur just as frequently as in real storms.

Credit: 
University of Oldenburg

Dietary supplement may help in the treatment of fatty liver

image: Academy of Finland Research Fellow Satu Pekkala and her research team are developing treatments for fatty liver disease.

Image: 
Photo: University of Jyväskylä

A recent study by researchers at the University of Jyväskylä was successful in partially preventing fatty liver disease in rats. Rats with fatty liver disease were fed with a dietary supplement that is known to increase the growth of good bacteria in the gut. Simultaneous with the increased abundance of the bacteria, the liver fat content decreased significantly. In addition, preliminary results from a human study seem promising.

It is estimated that quarter of the Finnish population has fatty liver. Fatty liver disease is an important metabolic disease, which without treatment can develop into cirrhosis or even hepatocellular carcinoma, that is, hepatic cancer.

Earlier Academy of Finland Research Fellow Satu Pekkala and her research team were able to treat the fatty liver of mice by administering Faecalibacterium prausnitzii, a member of the gut microbiota with known anti-inflammatory properties. In the most recent study, the research team fed rats with a dietary supplement that partly prevented the fatty liver of rats.

"Unfortunately, this type of health-beneficial gut microbes cannot necessarily be sold at the pharmacies for human use," Pekkala explains, "so we wanted to find out whether we can increase its natural abundance in the gut with a prebiotic fiber."

A prebiotic is defined as a selectively fermented dietary component that cannot be digested in the gut but serves as food for the good gut microbes, such as lactobacilli, thereby conferring beneficial effects for the health of the host. The research team first found that the above-mentioned Faecalibacterium prausnitzii was able to use prebiotic Xylo-oligosaccharides as food, which increased its growth.

After these positive results, the research team performed a dietary intervention in rats, in which fatty liver was induced in rats and at the same time they were fed with a diet supplemented with XOS for 12 weeks. XOS is a dietary supplement that can be found in natural products shops and online stores.

"The results of the research showed that XOS increased the growth of the health-beneficial bacterium, and at the same time, significantly decreased the liver fat content of the rats," says Pekkala, summarizing the main results.

The most important contributing factors to the reduced liver fat were improved hepatic fat and glucose metabolism.

This is the first study to show such effects for XOS. Though the study was made using rats, the research team has already conducted XOS intervention in humans having fatty liver. Pekkala says the human study ended in June and some of the preliminary results seem promising. The research team expects to publish more results next year.

Credit: 
University of Jyväskylä - Jyväskylän yliopisto

Victims of school bullying are more prone to develope violent behavior in the future

image: The Phd student of the University of Cordoba Raquel Espejo, during her stay at the Institute of Criminology at the University of Cambridge

Image: 
Universidad de Córdoba

There is another pandemic that humans have been experiencing for a long time now and for which effective preventive measures have yet to be found: violence. This is shown in various ways in different aspects of life and continues to have serious consequences for society, the economy, our health and human relations. The onset of violent behavior can be observed from childhood and adolescence, so studying what aspects lead to the development of these kinds of behaviors and which curb them has become a necessary step in their prevention.

The University of Cordoba and the University of Cambridge have been collaborating for a long time now on research into aspects related to violence, thus helping decrease its risks and prevent it. In their latest piece of research, they studied possible risk and protection factors for violence and, in this way, they verified whether violent behavior can be predicted months or even years before it develops.

Specifically, the study focused on finding out if morality, victimization, empathy and social and emotional skills predict the expression of different violent behaviors in children and adolescents in different contexts, including at school and in a family setting. "These behaviors refer to, for instance, troubling behavior at home, including physical violence towards parents and siblings, at school, including physical violence towards teaching staff and schoolmates, and other settings, including bad behavior in public", explains Raquel Espejo Siles, doctoral student at the University of Cordoba who carried out this research during her stay at the Institute of Criminology at the University of Cambridge thanks to one of the ELMER grants from the Diputación de Córdoba (Cordoba's county government).

Raquel Espejo worked with Izabela Zych, Professor at the Psychology Department at the University of Cordoba and part of the LAECOVI (Study Laboratory on Coexistence and Violence Prevention) research group, whose line of research is this study's framework. The study also had the participation of David P. Farrington, Emeritus Professor of Criminology at the University of Cambridge, and Vicente J. Llorent, Professor at the Education Department at the University of Cordoba.

871 students between 10 and 17 years of age at different Andalusian educational centers took part in the research. They filled out two questionnaires, one in June 2017 and one in June 2018.

Interesting conclusions were drawn from the results. "We found that violence used directly towards people was related to a tendency to make impulsive decisions and to a blind motivation to accomplish one's aims, without regard for the disadvantages or negative consequences from using violence", reveals Raquel Espejo.

What is more, being a victim of bullying was detected as a risk factor for developing violent behavior at home against their family as well as at school. Likewise, those people who were violent in public or in class were shown to have higher scores in moral disengagement, meaning that they usually made excuses so that these acts would seem less serious than they really were.

At school, it was verified that higher scores for social and emotional competencies such as social awareness, self-management, motivation and decision making are protection factors against violence. Therefore, these results support prevention initiatives based on the potential of learning social and emotional skills at home as well as at school.

The data show that reducing victimization in a school setting could be effective in decreasing violence in different contexts in the future. "It is important to prevent violence, both victimization and bullying, since the data found in this study and others indicate that violence is a vicious cycle. Being the aggressor or the victim entails a high risk of developing the opposite role, reinforcing and increasing violence both at school and outside of school", points out Raquel Espejo.

According to this research study, enabling teenagers to reassess their goals and the consequences of their violent behavior could have an impact on decreasing violence further down the road. In addition, teaching different strategies to resolve issues in a different way could help them to compare and see the high individual and social price to pay for violent behavior.

Credit: 
University of Córdoba

Scientists find Ebola virus antibodies in people before 2018 DRC outbreak

image: Residents walk along a road in Eastern Democratic Republic of Congo.

Image: 
Tracey Goldstein/UC Davis

Scientists found antibodies to Ebola virus in people up to a year before the 2018 Ebola virus disease outbreak began in the Eastern Democratic Republic of Congo, or DRC. This suggests that either early cases may have been missed or that exposure occurs more commonly than previously thought, according to a study led by the University of California, Davis.

The study, published today in the journal One Health Outlook, also documents the first detection of antibodies to Bombali ebolavirus in a person, showing that spillover of that virus from bats to humans has likely occurred. Scientists from the UC Davis One Health Institute and Columbia University discovered Bombali virus -- a sixth ebolavirus species -- in bats in Sierra Leone in 2018.

"This study highlights that, yes, these are lethal diseases, but there's a range of severity -- not everyone who is exposed dies," said lead author Tracey Goldstein, an associate director of the One Health Institute at the UC Davis School of Veterinary Medicine. "Spillover doesn't always cause lethal outbreaks. To prevent outbreaks, we need a better understanding of what's happening between them. If you really are trying to understand how a virus works, you need to study it at all times, not just during an outbreak."

WOMEN AT INCREASED RISK

For the study, scientists collected and tested biological samples from 272 people seeking care in the Rutshuru Health Zone of North Kivu Province over the year before the start of the outbreak that killed nearly 2,300 people. Antibodies, which indicate past exposure to a virus, were found in 10 percent of patients.

Scientists also administered questionnaires to patients to collect demographic and behavioral information, and to better understand their interactions with domestic animals and wildlife.

While people of both sexes and all ages tested positive for antibodies, women had a significantly increased risk of exposure. This is consistent with other studies and may be due to the larger role women play in preparing food and caring for livestock and sick family members.

"These findings are important for those of us who live in eastern Congo, because it shows that people may become exposed to Ebola virus without becoming ill," said Jean-Paul Kabemba Lukusa, the Gorilla Doctors' medical technologist who coordinated human surveillance for this study. "It helps reinforce the work we do to explain to people how important it is to limit direct contact with wild animals and to follow hygiene and safety best practices."

MOVING FORWARD

The study also demonstrates the need to address how humans come into contact with wildlife and the viruses they exchange.

Co-author Kirsten Gilardi directs the UC Davis Karen C. Drayer Wildlife Health Center and the Gorilla Doctors program, which provides veterinary care to wild mountain and eastern lowland gorillas in Rwanda, Uganda and DRC. As the region's country lead for the USAID PREDICT Project, Gorilla Doctors sampled both wildlife and humans for viruses that may be circulating among them.

"These findings suggest there are more spillover events than we realize," Gilardi said. "This may not happen once in a while and then the virus disappears. Preventing spillover means understanding and minimizing high-risk human-to-wildlife interactions."

Credit: 
University of California - Davis

Brain region implicated in predicting the consequences of actions

image: Brain cells switched off in the anterior cingulate cortex (green) prevent mice from learning flexibly.

Image: 
Thomas Akam / Rui Costa / Champalimaud Centre for the Unknown

NEW YORK -- Our minds can help us make decisions by contemplating the future and predicting the consequences of our actions. Imagine, for instance, trying to find your way to a new restaurant near your home. Your brain can build a mental model of your neighborhood and plan the route you should take to get there.

Scientists have now found that a brain structure called the anterior cingulate cortex (ACC), known to be important for decision making, is involved in using such mental models to learn. A new study of mice published today in Neuron highlights sophisticated mental machinery that helps the brain simulate the results of different actions and make the best choice.

"The neurobiology of model-based learning is still poorly understood," said Thomas Akam, PhD, a researcher at Oxford University and lead author on the new paper. "Here, we were able to identify a brain structure that is involved in this behavior and demonstrate that its activity encodes multiple aspects of the decision-making process."

Deciphering how the brain builds mental models is essential to understanding how we adapt to change and make decisions flexibly: what we do when we discover that one of the roads on the way to that new restaurant is closed for construction, for example.

"These results were very exciting," said senior author Rui Costa, DVM, PhD, Director and CEO of Columbia's Zuckerman Institute, who started this research while an investigator at the Champalimaud Centre for the Unknown, where most of the data was collected. "These data identify the anterior cingulate cortex as a key brain region in model-based decision-making, more specifically in predicting what will happen in the world if we choose to do one particular action versus another."

Model or model-free?

A big challenge in studying the neural basis of model-based learning is that it often operates in parallel with another approach called model-free learning. In model-free learning, the brain does not put a lot of effort into creating simulations. It simply relies on actions that have produced good outcomes in the past.

You might use a model-free mental approach when traveling to your favorite restaurant, for example. Because you've been there before, you don't need to invest mental energy in plotting the route. You can simply follow your habitual path and let your mind focus on other things.

To isolate the contributions of these two cognitive schemes - model-based and model-free - the researchers set up a two-step puzzle for mice.

In this task, an animal first chooses one of two centrally located holes to poke its nose into. This action activates one of two other holes to the side, each of which has a certain probability of providing a drink of water.

"Just like in real life, the subject has to perform extended sequences of actions, with uncertain consequences, in order to obtain desired outcomes," said Dr. Akam.

To do the task well, the mice had to figure out two key variables. The first was which hole on the side was more likely to provide a drink of water. The second was which of the holes in the center activated that side hole. Once the mice learned the task, they would opt for the action sequence that offered the best outcome. However, in addition to this model-based way of solving the puzzle, mice could also learn simple model-free predictions, e.g. "top is good," based on which choice had generally led to reward in the past.

The researchers then changed up the experiment in ways that required the animals to be flexible. Every now and then, the side port more likely to provide a drink would switch - or the mapping between central and side ports would reverse.

The animals' choices as things changed revealed what strategies they were using to learn.

"Model-free and model-based learning should generate different patterns of choices," said Dr. Akam. "By looking at the subjects' behavior, we were able to assess the contribution of either approach."

When the team analyzed the results, about 230,000 individual decisions, they learned that the mice were using model-based and model-free approaches in parallel.

"This confirmed that the task was suitable for studying the neural basis of these mechanisms," said Dr. Costa. "We then moved on to the next step: investigating the neural basis of this behavior."

A neural map of model-based learning

The team focused on a brain region called anterior cingulate cortex (ACC).

"Previous studies established that ACC is involved in action selection and provided some evidence that it could be involved in model-based predictions," Dr. Costa explained. "But no one had checked the activity of individual ACC neurons in a task designed to differentiate between these different types of learning."

The researchers discovered a tight connection between the activity of ACC neurons and the behavior of their mice. Simply by the looking at patterns of activity across groups of the cells, the scientists could decode whether the mouse was about chose one hole or another, for example - or whether it was receiving a drink of water.

In addition to representing the animal's current location in the task, ACC neurons also encoded which state was likely to come next.

"This provided direct evidence that ACC is involved in making model-based predictions of the specific consequences of actions, not just whether they are good or bad," said Dr. Akam.

Moreover, ACC neurons also represented whether the outcome of actions was expected or surprising, thereby potentially providing a mechanism for updating predictions when they turn out to be wrong.

The team also turned off ACC neurons while the animals were trying to make decisions. This prevented the animals from responding flexibly as the situation changed, an indicator that they were having trouble using model-based predictions.

Understanding how the brain controls complex behaviors like planning and sequential decision making is a big challenge for contemporary neuroscience.

"Our study is one of the first to demonstrate that it is possible to study these aspects of decision-making in mice," said Dr. Akam. "These results will allow us and others to build mechanistic understanding of flexible decision making."

Credit: 
The Zuckerman Institute at Columbia University

Hydrogen bonds may be key to airborne dicamba

Dicamba has been the subject of lawsuits across the country, with landowners contending the herbicide, when used by neighboring growers, has blown onto their property, killing valuable non-resistant crops.

Dicamba is sprayed in a formulation that contains an amine, a chemical agent that is supposed to keep the herbicide in place, preventing it from going airborne. Ongoing reports of crop damage despite these measures have previously shown, however, that it may not be working as it should, particularly when the dicamba/amine formulation is sprayed with the most commonly used herbicide in the world, glyphosate, the main component of Roundup.

Washington University in St. Louis researchers in the lab of Kimberly Parker, assistant professor in the Department of Energy, Environmental & Chemical Engineering in the McKelvey School of Engineering, have proposed a mechanism that describes how dicamba volatility is controlled by amines.

The finding was published in October in Environmental Science & Technology.

The factors that result in dicamba volatilizing -- becoming airborne -- have been investigated before in scientific studies conducted on fields and in greenhouses where researchers measured how much dicamba transformed into a gas that could be measured in the air or by assessing damage to plants.

But there remained major gaps when it came to understanding the molecular processes at work, so Parker's lab set out to fill them.

"We decided to approach it from a unique direction," said lead author Stephen Sharkey, a PhD student in the Parker Lab. "We wanted to try to get into the chemistry behind the volatility process."

He started with considering the interactions of molecules in the solid phase of the dicamba/amine formulation.

There are three amines that are typically used in commercial dicamba formulations. Sharkey considered those three commonly used amines as well as six others to get a better, more generally applicable understanding of their properties and their impacts on dicamba volatilization. How are the amines interacting with dicamba and can this information be used to discover why dicamba is still volatilizing?

Parker said that there are a couple of common assumptions about what is happening between amines and dicamba: the heavier amine acts like an anchor, thus weighing down the herbicide, or volatilization is determined by pH levels.

Sharkey's research showed something different. In regard to the three most-used amines, he said, "the ones that work best have more hydrogen bonding functioning groups." He went on to find the same results in the six additional amines.

The researchers also looked at how other molecules may impact these interactions. "We found glyphosate increased volatility in two of the three main amines," Sharkey said. "One way dicamba products may be used is alongside glyphosate as a way of killing many different weeds," including those resistant to glyphosate and/or those resistant to dicamba.

The research team believes it may be the case that glyphosate, which has lots of places where it can form hydrogen bonds, may be interfering with dicamba's ability to form bonds with the amines. In essence, glyphosate may be driving a chemical wedge between the two by forming its own bonds to the dicamba or amine molecules.

None of the other potential factors they tested had as reliable or consistent an effect on volatility as the number of hydrogen bonding sites on the amine.

The team tested several different variables, including temperature, reducing the amine concentration relative to dicamba, amine acidity, amine vapor pressure, amine molecular weight, solution pH values and the presence of glyphosate.

"We showed those were not primary determinants," Parker said. "Hydrogen bonding seemed to be the primary factor. If the amine has more hydrogen bonding functional groups, dicamba volatility is decreased compared to other amine formulations."

Going forward, this better understanding of how dicamba and amines interact identifies a specific characteristic that can be modified to improve a formula's ability to remain on a crop and away from surrounding fields. It also points to the benefits of studying herbicides in the lab in addition to the work done by other researchers in the field. That's something Parker and her team have been doing and will continue to do.

As for next steps, Sharkey's latest work is a look at how the introduction of more tolerant crops affect usage of herbicides. Parker said she'd like an expanded understanding of the effects of more complex chemistries on dicamba volatility.

"What about other chemicals on a leaf's surface, for example?" she asked. "How might those further affect volatilization?"

Credit: 
Washington University in St. Louis

Brown carbon 'tarballs' detected in Himalayan atmosphere

Some people refer to the Himalaya-Tibetan Plateau as the "third pole" because the region has the largest reserve of glacial snow and ice outside of the north and south poles. The glaciers, which are extremely sensitive to climate change and human influence, have been retreating over the past decade. Now, researchers reporting in ACS' Environmental Science & Technology Letters have detected light-absorbing "tarballs" in the Himalayan atmosphere, which could contribute to glacial melt.

Burning biomass or fossil fuels releases light-absorbing, carbonaceous particles that can deposit on snow and ice, possibly hastening the melting of glaciers. Previous research has shown that one type of particle, called black carbon, can be transported long distances by wind to the Himalayan atmosphere. But much less is known about the presence of brown carbon, a particle that can form tarballs -- small, viscous spheres consisting of carbon, oxygen and small amounts of nitrogen, sulfur and potassium. Weijun Li and colleagues wanted to see what types of individual aerosol particles were present in air samples taken at a remote, high-altitude research station on the northern slope of the Himalayas.

Using electron microscopy, the researchers unexpectedly found that about 28% of the thousands of particles in the air samples from the Himalayan research station were tarballs, and the percentage increased on days with elevated levels of pollution. Analyzing wind patterns and satellite data revealed that a dense array of active fire spots, corresponding to large-scale wheat-residue burning on the Indo-Gangetic Plain, occurred along the pathways of air masses that reached the Himalayan research station during sampling. Through modeling calculations, the team estimated that tarballs deposited on glacial surfaces could contribute a significant warming effect. As a result, future climate models should consider the long-range transport of tarballs to the Himalayas, the researchers say.

Credit: 
American Chemical Society