Culture

'White matter lesion' mapping tool identifies early signs of dementia

image: Caption: MRI image of human brain shows multiple bright spots (white matter hyperintensities) in center
Courtesy of Elsevier/Academic Radiology

Image: 
Courtesy of Elsevier/Academic Radiology

A new tool for analyzing tissue damage seen on MRI brain scans can detect with more than 70 percent accuracy early signs of cognitive decline, new research shows.

The findings by imaging specialists at NYU Grossman School of Medicine center on small bright spots on scans called white matter hyperintensities. Increased numbers and size of the intense-white spots seen on the mostly gray images of the brain have long been linked to memory loss and emotional problems, especially as people age.

More spots on MRI and their occurrence in the center of the brain have also been shown to correlate with the worsening of dementia and other brain-damaging conditions, such as stroke and depression, say the study authors. The spots represent fluid-filled holes in the brain, lesions that are believed to develop from the breakdown of blood vessels that nourish nerve cells.

Current methods for grading white matter lesions rely on little more than the "trained eye," researchers say, using an imprecise three-point scale, with a score of 1 meaning minimal white spots, while grades of 2 or 3 suggest more significant disease. The new tool was developed, researchers say, in an effort to provide a uniform, objective method for calculating the spots' volume and location in the brain.

In the new study, publishing in the journal Academic Radiology online Oct. 27, the NYU Langone team randomly selected 72 MRI scans from a national database of elderly people, the Alzheimer's Disease Neuroimaging Initiative. Equal numbers were from elderly men and women, mostly white and over age 70, with normal brain function, or showing some mild cognitive decline, or suffering from severe dementia.

Using the latest MRI techniques for accurate mapping of the brain's surface, the team then used computer software to calculate the precise position and volume measurements for all observed white matter lesions. Specifically, they tabulated volumes, which are three-dimensional measurements in liters, based on each lesion's distance from both side surfaces of the brain, with normal ranges between 0 milliliters (no lesions seen) and 60 milliliters (some lesions). Volumes greater than 100 milliliters indicated severe disease. When researchers cross-checked their measurements, they found that seven out of 10 calculations correctly matched the patient's actual diagnosis.

"Amounts of white matter lesions above the normal range should serve as an early warning sign for patients and physicians," says study lead researcher Jingyun "Josh" Chen, PhD, a research assistant professor in the Department of Neurology at NYU Langone Health.

Chen cautions that the white matter brain measures alone are not sufficient to certify a finding of early dementia, but should be considered along with other factors, including a history of brain injury, memory loss, and hypertension, as clear features of cognitive decline and/or other brain and blood vessel diseases.

"Our new calculator for properly sizing white matter hyperintensities, which we call bilateral distancing, offers radiologists and other clinicians an additional standardized test for assessing these lesions in the brain, well before severe dementia or stroke damage," says study senior investigator Yulin Ge, MD, a professor in the Department of Radiology at NYU Langone.

With a standardized tracking and measuring tool, says Chen, it is now possible to monitor the growth of white matter lesions relative to that of other tau and beta-amyloid proteins also believed to be potential causes of dementia and Alzheimer's disease. The buildup of either substance could also prove or disprove one or more of the theories about what biological processes actually lead to various forms of dementia.

Chen says the team plans to broaden and test their measuring tool on an additional 1,495 brain scans to include a more diverse group from the same database.

Physicians can access the tool, which is available without cost online at github.com/jingyunc/wmhs.

Credit: 
NYU Langone Health / NYU Grossman School of Medicine

Vampire bats social distance when they get sick

image: A new paper in Behavioral Ecology finds that wild vampire bats that are sick spend less time near others from their community, which slows how quickly a disease will spread. The research team had previously seen this behavior in the lab, and used a field experiment to confirm it in the wild.

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Sherri and Brock Fenton/Behavioral Ecology

A new paper in Behavioral Ecology, published by Oxford University Press, finds that wild vampire bats that are sick spend less time near others from their community, which slows how quickly a disease will spread. The research team had previously seen this behavior in the lab, and used a field experiment to confirm it in the wild.

As a pathogen spreads across a population, changes in social behavior can alter how the disease spreads. Transmission rates can increase when parasites change host behavior or decrease when healthy individuals avoid sick ones. In certain social insects, sick ones might self-isolate voluntarily or be excluded by their colony mates. A simpler mechanism causing reduced transmission is that infected animals often show sickness behavior, which includes increased lethargy and sleep, and reduced movement and sociality. This sickness-induced social distancing does not require cooperation from others and is probably common across species.

Researchers here conducted a field experiment to investigate how sickness behavior affects relationships over time using a dynamic social network created from high-resolution proximity data. After capturing 31 adult female vampire bats from a roost inside a hollow tree at Lamanai, Belize, researchers simulated "sick" bats by injecting a random half of bats with the immune-challenging substance, lipopolysaccharide, while the control group received saline injections.

Over the next three days, the researchers glued proximity sensors to the bats, released them back into their hollow tree, and tracked changes over time in the associations among all 16 "sick" bats and 15 control bats under natural conditions.

Compared to control bats, "sick" bats associated with fewer groupmates, spent less time with others, and were less socially connected to healthy groupmates when considering both direct and indirect connections. During the six hours of the treatment period, a 'sick' bat associated on average with four fewer associates than a control bat. A control bat had, on average, a 49% chance of associating with each control bat, but only a 35% chance of associating with each "sick" bat. During the treatment period, "sick" bats spent 25 fewer minutes associating per partner. These differences declined after the treatment period and when the bats were sleeping or foraging outside the roost.

"The sensors gave us an amazing new window into how the social behavior of these bats changed from hour to hour and even minute to minute during the course of the day and night, even while they are hidden in the darkness of a hollow tree," said the study's lead author, Simon Ripperger. "We've gone from collecting data every day to every few seconds."

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Oxford University Press USA

Cerebrospinal fluid as liquid biopsy for characterizing & policing of medulloblastoma

image: Joan Seoane, Director of Translational Research, Vall d'Hebron Institute of Oncology (VHIO).

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VHIO

Cerebrospinal fluid as liquid biopsy for the precise characterization and policing of medulloblastoma

Results from a proof-of-concept study led by Joan Seoane show the promise of
cerebrospinal fluid as liquid biopsy for the more precise characterization and real time tracking of medulloblastoma.

Circulating tumor DNA from cerebrospinal fluid reveals genomic alterations during disease evolution -even prior to surgery- to more precisely guide treatment decision making.

Cerebrospinal fluid as liquid biopsy against medulloblastoma translates in less invasive sampling, better identification and characterization of disease relapse.

Building on previous research 1 - 3 led by Joan Seoane, Director of Translational Research at the Vall d'Hebron Institute of Oncology (VHIO) and ICREA Research Professor, latest findings from a proof-of-concept study published in Nature Communications, show that the analysis of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA), allows for the more precise characterization, molecular diagnosis (including subtyping and risk stratification), and real time tracking of medulloblastoma (MB) - the most prevalent malignant brain tumor in childhood.

Carried out in multidisciplinary collaboration across the Vall d'Hebron Barcelona Hospital Campus, results also evidence that this novel and less invasive approach can also provide precious insights into minimal residual disease, tumor evolution, and identify disease at relapse.

While the genomic characterization of medulloblastoma promises a more precise molecular diagnosis, accessing tumor tissue -due to the very nature of its location- is complex and can suppose high-risk surgical procedures and stereotactic biopsies, neither of which can guarantee access to a truly representative part of the tumor. The classification of this tumor type is also particularly challenging due to its ever changing intra-tumor heterogeneity which demands an in-depth and serial analysis of the evolving genomic landscapes in response to treatment or during disease recurrence. Establishing the molecular make-up of medulloblastoma is particularly critical since this tumor type is the most common of all paediatric brain cancers.

"Results from this present study represent a potentially practice-changing approach in more precisely steering the surgical and clinical management of these young patients. By evidencing the promise of cerebrospinal fluid as liquid biopsy for the personalized treatment of this extremely aggressive disease, our findings could ultimately spur the development of more effective and tailored therapeutic strategies. As importantly, they could also reduce excessive treatment to prevent long-term secondary effects," observes corresponding author Joan Seoane, who also leads VHIO's Gene Expression and Cancer Group.

"Medulloblastoma is highly a complex, heterogenous tumor type that evolves over time. Currently, acquiring further samples to monitor and track changes in the tumor to more precisely match the most effective therapy in real time represents a major challenge. By liquid biopsy of cerebrospinal fluid, we aim to respond to the critical need of rendering the molecular characterization and monitoring of this disease more precise," adds Laura Escudero, first author of the study and a Post-Doctoral Fellow of Joan's group at VHIO.

Hydrocephalus is an abnormal accumulation of cerebrospinal fluid and is very common in paediatric patients whose tumors are growing in the area of the posterior fossa, including medulloblastoma. In these cases, cerebrospinal fluid drainage must be performed prior to surgery to reduce increased intracranial pressure (ICP). Since the fluid is routinely collected for cytologic evaluation, this facilitates easy access to samples for research in the laboratory.

This latest research -supported through funding received from the Spanish Association against Cancer (AECC) and the Fero Foundation- demonstrates that the evaluation of cerebrospinal fluid can not only identify genomic alterations during tumor progression even before surgery, but also detect disease recurrence and track cancer progression to better inform treatment decision making in real time. Data derived from the liquid biopsy is therefore fundamental in disease prognosis as well as gauging tumor aggressiveness. This information is crucial for both the surgeon and the oncologist when balancing the risks and benefits of each intervention and therapeutic strategy.

The study investigators also show that CSF ctDNA facilitates the subgrouping and risk stratification of patients suffering from medulloblastoma, which provides valuable insights for the diagnosis and prognosis of disease towards more effectively matching therapies to the unique specificities of each individual patient. Specifically, certain genetic mutations are critical in treatment selection, such as mutations in the PTCH1 gene which encodes a protein called patched-1. In this case, inhibitors of the Hedgehog signaling pathway could be a more effective treatment option.

"Our research represents an important forward step towards better characterizing medulloblastoma, providing an earlier and more accurate molecular diagnosis, more closely monitoring our patients, and providing crucial data on minimal residual disease tumor evolution and disease at relapse. Larger cohort studies are now warranted to bring cerebrospinal fluid as liquid biopsy closer to the clinic and deliver on the promise of precision medicine for the treatment of this disease," concludes Joan Seoane.

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Vall d'Hebron Institute of Oncology

Postpartum depression may persist three years after giving birth

A National Institutes of Health study of 5,000 women has found that approximately 1 in 4 experienced high levels of depressive symptoms at some point in the three years after giving birth. The rest of the women experienced low levels of depression throughout the three-year span. The study was conducted by researchers at NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). It appears in the journal Pediatrics.

The American Academy of Pediatrics recommends that pediatricians screen mothers for postpartum depression at well-child visits at one, two, four and six months after childbirth. Researchers identified four trajectories of postpartum depressive symptoms and the factors that may increase a woman's risk for elevated symptoms. The findings suggest that extending screening for postpartum depressive symptoms for at least two years after childbirth may be beneficial, the authors write.

"Our study indicates that six months may not be long enough to gauge depressive symptoms," said Diane Putnick, Ph.D., the primary author and a staff scientist in the NICHD Epidemiology Branch. "These long-term data are key to improving our understanding of mom's mental health, which we know is critical to her child's well-being and development."

The researchers analyzed data from the Upstate KIDS study, which included babies born between 2008 and 2010 from 57 counties in New York State. The study followed 5,000 women for three years after their children were born.

Researchers assessed women's symptoms through a brief, five-item depression screening questionnaire, but the study did not clinically diagnose depression in the women. Women with underlying conditions, such as mood disorders and/or gestational diabetes, were more likely to have higher levels of depressive symptoms that persisted throughout the study period.

The researchers noted that the study participants were primarily white, non-Hispanic women. Future studies should include a more diverse, broad population to provide more inclusive data on postpartum depression, Dr. Putnick said.

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NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development

Computer vision helps find binding sites in drug targets

Scientists from the iMolecule group at Skoltech Center for Computational and Data-Intensive Science and Engineering (CDISE) developed BiteNet, a machine learning (ML) algorithm that helps find drug binding sites, i.e. potential drug targets, in proteins. BiteNet can analyze 1,000 protein structures in 1.5 minutes and find optimal spots for drug molecules to attach. The research was published in the Communications Biology journal.

Proteins, the molecules that control most biological processes, are typically the common targets for drugs. To produce a therapeutic effect, drugs should attach to proteins at specific sites called binding sites. The protein's ability to bind to a drug is determined by the site's amino acid sequence and spatial structure. Binding sites are real "hot spots" in pharmacology. The more binding sites are known, the more opportunities there are for creating more effective and safer drugs.

Skoltech CDISE assistant professor Petr Popov and PhD student Igor Kozlovskii developed a new computational approach for spatio-temporal detection of binding sites in proteins by applying deep learning algorithms and computer vision to protein structures treated as 3D images. With this new technology, one can detect even elusive sites: for instance, scientists managed to detect binding sites concealed in experimental atomic structures or formed by several protein molecules for the ion channel, G protein-coupled receptor, and the epithelial growth factor, one of the most important drug targets.

Petr Popov, the study lead and assistant professor at Skoltech, comments: "The human genome consists of nearly 20,000 proteins, and very few among them get associated with a pharmacological target. Our approach allows searching the protein for binding sites for drug-like compounds, thus expanding the array of possible pharmacological targets. Besides, initial structure-based drug discovery strongly depends on the choice of the protein's atomic structure. Working on a structure with the binding site barred for the drug or missing altogether can fail. Our method enables analyzing a large number of structures in a protein and finding the most suitable one for a specific stage."

According to Igor Kozlovskii, the first author of the paper, BiteNet outperforms its counterparts both in speed and accuracy: "BiteNet is based on the computer vision, we treat protein structures as images, and binding sites as objects to detect on this images. It takes about 0.1 seconds to analyze one spatial structure and 1.5 minutes to evaluate 1,000 protein structures of about 2,000 atoms."

Credit: 
Skolkovo Institute of Science and Technology (Skoltech)

How do basal ganglia neurons convey information for the control of voluntary movements?

image: Summary of findings. Activity of multiple neurons located in the arm regions of the basal ganglia was recorded while monkeys performed a motor task that required their arm movements. Most neurons in the basal ganglia exhibited non-correlated activity, although they showed firing rate changes during the task.

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Atsushi Nambu

Okazaki, Japan - It is common that neurons transmit information to another group of neurons by increasing or decreasing their activity, i.e. "firing rate changes". In addition to firing rate changes, synchronized activity of a certain group of neurons, i.e. "correlated activity", has been suggested to play an important role in conveying information. This study revealed that, in the basal ganglia, information for the movement control is conveyed primarily by firing rate changes and correlated activity play only minor role in healthy conditions (Figure).

The research team consists of Dr. Woranan Wongmassang, Professor Atsushi Nambu, and their colleagues recorded neuronal activity of multiple neurons simultaneously in the basal ganglia while monkeys performed a motor task that required their arm movements. They found that most neurons located in the arm regions of the basal ganglia showed firing rate changes in relation to arm movements. On the other hand, the percentage of neurons that showed correlated activity during the task was very small.

Professor Nambu claims, "Unlike in healthy conditions, a large proportion of neurons in the basal ganglia show strong synchronized activity in Parkinson's disease. So, it is possible that symptoms could be improved by decreasing abnormally increased correlated activity in the basal ganglia. The findings provide important clues to develop effective treatment for Parkinson's disease."

Credit: 
National Institutes of Natural Sciences

Small mussels in the Baltic are getting even smaller

image: Blue mussels in the Baltic Sea are getting smaller with time but bigger in numbers, according to a new study from Stockholm University. Analyzing data from the last 24 years, the main reason for this appears to be changes in food quality. The type of phytoplankton that is available for blue mussels to eat can in turn be linked to our changing climate.

Image: 
Thomas Tranåker

Blue mussels in the Baltic Sea are getting smaller with time but bigger in numbers, according to a new study from Stockholm University. Analyzing data from the last 24 years, the main reason for this appears to be changes in food quality. The type of phytoplankton that is available for blue mussels to eat can in turn be linked to our changing climate.

Blue mussels in the Baltic Sea are already small in their nature - the length of the mussels is about the length of a nail to the mere eye. In this study, the researchers discovered that blue mussels are now weighing around half of what they used to weigh in the 90's, despite the mean length difference just being a few millimeters. But on the other hand there are now more mussels that are really tiny, sometimes as many as 1000 in one square meter compared to about 500 per square meter before.

Mussels compose the largest biomass of animals without a backbone in the Baltic, providing food to eider ducks and fish, for example. But because they are getting 'smaller' it means less food for the species feeding on them. It is also estimated that all blue mussels in the Baltic, together filter the entire waters of Baltic sea every year - and this is essential for cleaning the water from particles and helping to combat eutrophication - one of the Baltics biggest threats. Since the mussel size is affected it might therefore have effects on filtration rates, although this was not tested in this particular study:

"Even though an increase in the number of mussels to some extent may compensate for the smaller size, it is likely that important functions like filtration of the water has been reduced, which could lead to more turbid water" says Agnes Karlsson, Assistant Professor at Department of Ecology, Environment and Plant Sciences (DEEP) at Stockholm University.

The reason for the mussels getting smaller is likely altered mix of phytoplankton, now with greater quantities of cyanobacteria and particles from land. Warmer waters favour cyanobacteria, in turn causing increased summer blooms. Yet, the study found no direct role of increasing temperature for the decrease in mussel size. This means that indirect effects of climate change might be more important for mussels. The study is based on continuously monitored and collected samples of both mussels and phytoplankton from 1993 to 2016:

"We want to call attention to the benefits of long-term monitoring. If not for monitoring, we wouldn't have known that this key species for the Baltic is on a slippery slope", says Agnes Karlsson, Assistant Professor at Department of Ecology, Environment and Plant Sciences (DEEP) at Stockholm University.

The study highlights the importance of keeping an eagle eye perspective when considering how environmental changes affect key-organism in the long-run:

"There is often multiple and interacting factors responsible for changes in an organisms' condition or population and all of this likely affects the entire ecosystem functioning" says Camilla Liénart, postdoc at Department of Ecology, Environment and Plant Sciences (DEEP) at Stockholm University.

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Stockholm University

Precaution: Lessons from COVID-19

Which is more important in the initial phase of a pandemic: taking precautionary actions or responding to its severity? That is the question that researchers from the Singapore University of Technology and Design (SUTD) set out to address in an article published in BioEssays.

The authors explored and reported the various strategies taken by the United States of America, European group of nations (comprising nations in the European Union, the Schengen area and the United Kingdom), People's Republic of China, Japan and South Korea. By looking at how the number of new cases changed with the adoption or relaxing of strategies, the data collated suggest that the following three strategies should have been considered for implementation during the COVID-19 pandemic: (1) controlled movement by implementing some form of coordinated social distancing, stay-at-home order or extreme lockdown; (2) early and sustained implementation of containment through internal and external border controls; and (3) efficient and early testing to identify symptomatic and asymptomatic transmitters.

These are not new strategies, but were learnt from previous pandemics. However, at a time when these strategies should have been implemented in some form as a precaution to contain COVID-19 in the early days, many countries chose to "wait".

The article explained how a collective strategy is needed, not just country-wide, but globally. If the effort to contain COVID-19 is not implemented in unison, a community that opens up out of phase to the others might see new infections. The researchers observed that incoherent strategy allows waves in each territory to superposition and form a sustain wave for the virus to ride on as it hops from territory to territory, country to country, continent to continent. In particular, because these known strategies were not adopted early with sustained implementation, the US continues to account for a fifth of the world's total COVID-19 cases and is facing the start of a third wave. Another example cited was the post-summer resurgence of COVID-19 cases in Europe when measures were significantly relaxed.

"As the world moves forward and prepares itself for future pandemics of such scale, the lessons learnt from COVID-19 should be part of every country's pandemic response. When another virus of such protean nature hits us again, we will not be caught off-guard by successive wavelets constructively interfering to give a sustained wave," said Joel Lai, the lead author of the study from SUTD.

"This article identifies the effectiveness of various strategies adopted by the governments of key hotspots for COVID-19. We noticed that the strategies were not new, yet, somehow, they were not implemented as swiftly and with authority as expected. These were effective in the past, proven to be effective to tackle COVID-19 and will continue to be effective for future pandemics," Lai added.

COVID-19 has significantly changed the way of life for everyone. In the initial response to the growing number of cases, governments across the spectrum of affected countries have adopted different strategies in implementing control measures, in a hope to reduce the number of new cases. Despite not having any precedence on the nature of this coronavirus, many of the strategies to tackle infectious diseases like COVID-19 is known. The precautions that we could have taken were not implemented as a precautionary preparation, but as a reaction after COVID-19 became widespread.

"Hindsight is always 20/20, but we do not need to be deep in a crisis only to acknowledge that certain precautionary measures should have been executed earlier. This time, with hindsight, precaution was indeed better than the cure," observed Assistant Professor Kang Hao Cheong, the principal investigator for this study from SUTD. "The successes and failures of COVID-19 management thus far have set a precedent for how countries should approach future outbreaks. These should form lessons for mankind to deal with future pandemics as a precaution, not a reaction."

Credit: 
Singapore University of Technology and Design

Detect with PKAchu

video: These two mice are seemingly the same, but under blue light, one mouse glows green. This green mouse is a transgenic PKAchu mouse that changes color when the protein PKA is activated. Taking a sheet of retinal cells from PKAchu, you can see that PKA is activated by darkness only in the stimulated area

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Kyoto University/Matsuda Lab

Kyoto, Japan -- Publishing in PNAS, biologists at Kyoto University report on a previously unknown mechanism in the retina that will perhaps lead to a better understanding of how our eyes see at night. The finding was made possible thanks to mice engineered to change fluorescence when a specific molecule -- protein kinase A, or PKA -- is activated.

These 'PKAchu' mice were developed to provide researchers with a way of visualizing the activation of one of the body's most essential and widely studied proteins.

"PKA is found in many cells and is involved in a wide variety of biological processes. It's natural that researchers would find a way to observe its activities," explains first author Shinya Sato of the Graduate School of Biostudies.

"PKAchu mice were developed in 2012 -- 'chu' being Japanese for 'squeak'-- to allow us to closely monitor how PKA acts during specific biological processes. I decided to apply this to my work in retina biology."

The team first developed a method for recording high resolution, microscopic images of living retinal tissue. They then observed how PKA reacts to light stimulation. Knowing the pathways involved, the team hypothesized that light would deactivate PKA.

But to their surprise, the exact opposite happened.

"We started with a six-second illumination of the tissue. Incredibly, this activated PKA in the selected area for nearly 15 minutes," continues Sato. "We then did a ten-minute illumination, during which PKA was inactive. But when the lights were turned off, PKA kicked into gear. It was as if the darkness had activated it."

Single-cell level analysis revealed that this lights-off PKA activation occurred only in rod cells, which are indispensable for our night vision.

Sato hypothesizes that this previously unknown mechanism of rod-specific PKA activation may be a key in boosting light sensitivity in our eyes, contributing to our night vision. Rod-type photoreceptor cells are thought to have evolved from color-sensing cone cells. PKA activation, it now appears, is rod-specific.

Michiyuki Matsuda, the study's senior author, concludes: "We have not only uncovered many interesting aspects of retinal cells, but the further utility of PKAchu mice as well. We are excited to uncover the mechanisms and purpose behind these new findings, and perhaps illuminate our understanding of conditions such as night blindness."

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Kyoto University

Langerhans cells are up to the job, they just need a chance

image: Figure

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University of Tsukuba

Tsukuba, Japan - Blood stem cell transplants are an important part of treatment for a variety of serious conditions. However, adverse reactions of the host to donor cells present a significant risk. Now, researchers from the University of Tsukuba have pinpointed cell level behavior that could be used to help the host fight back, their findings are published in Journal of Investigative Dermatology.

A significant proportion of patients who receive blood stem cells develop acute graft-versus-host disease (aGVHD), which is a fatal immune disorder in which the white blood cells of the stem cell donor attack the organs of the recipient. This attack leads to damage to the skin, liver, and gastrointestinal tract.

One of the types of skin cell that is attacked is Langerhans cells (LCs). LCs are known to negatively or positively regulate various types of immune responses--that is, to induce, or prevent them. However, these antigen-presenting cells are known to be killed by T cells in the early phase of aGVHD. Therefore, working out their roles in the disease is difficult.

The researchers carried out two experiments using mice with mucocutaneous aGVHD lesions to assess different aspects of the roles played by LCs.

"We investigated mice with normal and depleted amounts of LCs and found that when LCs were depleted at the outset, the lesions became more severe," study corresponding author Professor Naoko Okiyama explains. "In another experiment we found that the exacerbated disease resulted from a lack of death of OT-I cells that infiltrate the skin."

It was also found that the ability of LCs to cause the programmed death of OT-I cells and stop them from multiplying is partly the result of their expression of proteins in the B7 family.

"Having determined the proteins that contribute to LCs inducing the death of OT-I cells, we can explore the possibility that enhancing the expression of B7 proteins on LCs could provide an opportunity to prevent aGVHD development," says Professor Okiyama. "This could significantly improve treatments and have a positive effect on patient quality of life."

It is hoped that future work to enhance the expression of specific proteins on LCs will lead to more successful blood stem cell transplants.

Credit: 
University of Tsukuba

Saving the climate from the ground up

image: Increased carbon inputs into the soil could slow down climate change and at the same time increase crop yields, the international research team emphasizes.

Image: 
Frank Luerweg / University of Bonn

Soil has the capacity to bind large quantities of carbon in the long term. An international team of researchers, including from the University of Bonn, is now advocating effective use of this potential. Experts estimate that this could reduce the increase of the greenhouse gas carbon dioxide in the atmosphere by a third. At the same time, agricultural yields in many regions would also increase significantly. In a recent publication they present a strategy to achieve these goals. The study is published in the journal Nature Communications.

The climate summit in Paris in 2015 was also the birth of the so-called "4 per 1,000" initiative. Its name stands for a link that has not received enough attention in climate research and politics for a long time: Every year the amount of carbon in the atmosphere increases by more than four billion tons due to the man-made greenhouse gas CO2. If these four billion tons were instead sequestered in the earth's soils (thus completely halting the greenhouse effect), the amount of carbon contained in the soil would grow by only 0.4 per cent annually (i.e. 4 out of 1,000). In other words: Soils are already a gigantic carbon store. So why not simply dump the excess CO2 in it as an additional minuscule amount?

Experts are indeed confident today that this strategy could significantly slow down climate change. "0.4 percent additional carbon input is somewhat too optimistic," explains Prof. Wulf Amelung, who heads the Division of Soil Science at the University of Bonn. "However, a third of this is probably achievable." Nevertheless, little has changed since 2015. Together with colleagues from Europe, the USA, Australia and China, Amelung and colleagues therefore want to put the issue back on the agenda. In the current issue of the journal Nature Communications, they outline a strategy to effectively use the potential of soils in the fight against climate change. Amelung, together with his French colleague Prof. Abad Chabbi, is in charge of the initiative; in Germany, the TU Munich and Forschungszentrum Jülich were also involved.

There are a number of simple measures to increase the amount of carbon in the soil, such as mulching (i.e. covering the soil with crop residues) or adding plant-based coal. The most important method, however, is to increase plant growth (and thus crop yields): by liming acidic soils, by fertilizing as needed, by using smart irrigation. "The more grows on the soil, the better is it rooted," explains Amelung. "And roots with their widely branching networks of organic material store lots of carbon." Conversely, the organic matter contains essential nutrients for plant growth and thus promotes crop yield. "Our strategy therefore ultimately addresses two important goals: climate protection and food security."

Measures must be adapted locally

However, the global implementation of this ambitious plan is not quite so simple: The quality and characteristics of soils in different locations are too different, and the available management technologies are too dissimilar. "Increasing the carbon input therefore requires locally adapted measures; we need completely different strategies in the rice-growing regions of Asia than, for example, on a cereal field in northern Germany," Amelung emphasizes. In addition, many carbon sequestration measures are particularly effective when soils are partially degraded by long-term overuse and have lost a lot of carbon. "From a cost-benefit perspective, it certainly makes the most sense to start on such areas, not least because the yield increases are likely to be greatest there," explains the soil expert.

Unfortunately, however, knowledge about the condition of soil is very patchy. The researchers therefore recommend the establishment of databases that record the condition of land around the globe on a very small scale, as well as an equally small-scale modeling of possible yield gains and the necessary use of fertilizers. It must furthermore be ensured that there is no mere redistribution of carbon inputs: for example, organic material is moved from one farm to another at great expense and is now missing at its place of origin.

Credit: 
University of Bonn

Cauliflower coral genome sequenced

image: KAUST researchers compared populations of cauliflower corals to identify sites in the genome linked with adaptations.

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© 2020 KAUST; Hagan Gegner

The sequencing of the genome of the cauliflower coral, Pocillopora verrucosa, by an international team, provides a resource that scientists can use to study how corals have adapted to different environmental conditions.

The cauliflower coral, also known as brush or lace coral, is one of the most popular corals in research because it is found throughout the Red Sea, the Indian Ocean and the Pacific Ocean. "Having the genome will help us understand the genetic basis underlying the species' adaptation to different environmental conditions," says Carol Buitrago-López, a Ph.D. student supervised by Christian R. Voolstra, "which might shine light on how corals could respond to global warming."

Buitrago-López was seeking a sequenced cauliflower coral genome for use in population genomics studies of corals throughout the Red Sea. The habitat gradient in the Red Sea waters means corals have adapted or acclimated to different conditions, such as variation in temperature, salinity and nutrients. After researchers compared populations to identify sites in the genome linked with these adaptations, the next step was to determine what those differences meant. A reference genome is invaluable in this process. "It's very helpful to know where specific genes are or to be able figure out which genes are under selection," says Buitrago-López.

The team's analysis predicted about 27,500 genes based on information from about 50,000 transcripts used for subsequent gene modeling, which is comparable to genomes from closely related corals. However, the cauliflower coral genome has a higher percentage of repetitive elements--in particular, more transposable elements--than closely related corals. This might be indicative of a radiation of the genus, which is consistent with the species' broad distribution in geography and depth.

The researchers also looked at the proportion of genes without introns, a typical signature of genes that were acquired through horizontal gene transfer. The proportion was similar to that in another Pocillopora coral and significantly greater than in a coral of a different genus. It is currently not known what these genes are for.

With the genome revealed, researchers can now investigate these and other patterns and work to understand the evolutionary history of these corals. Figuring out how they have adapted to conditions in the Red Sea may point toward ways to support corals to cope with the pressures of climate change. "With a sequenced genome, you're not working blindly," says Buitrago-López. "It will help to figure out where we should focus our attention."

Credit: 
King Abdullah University of Science & Technology (KAUST)

Can individual differences be detected in same-shaped pottery vessels by unknown craftsmen?

image: Cross recurrence plots of hand position sequences

A. Two trials by the same potter.?B. Two trials by different potters.

The light blue regions show when similar hand positions occurred in the two sequences.

Image: 
©2020 Gandon et al.

An interdisciplinary research team has investigated whether there are quantitative differences that can be used to identify individual potters who make traditional, fixed-shape vessels that have been made in the same way for generations. Consequently, they discovered that there are clear variations between individuals in the formation process and hand movements used.

Members of the research team included Dr. Enora Gandon (Institute of Archaeology, University College London), Professor NONAKA Tetsushi (Graduate School of Human Development and Environment, Kobe University), and Professor Emeritus John A. Endler (Deakin University).

Up until now, the transmission of cultural traditions has been viewed in terms of 'imitation' and 'transmitted information'. However, the results quantitatively show that other factors beyond imitation, such as the individual's corresponding ability and exploratory learning process, play a role. In addition, it is hoped that these results will serve as a basis for determining whether unattributed archaeological artefacts were produced by one or multiple artisans.

These research results were published in the scientific journal 'PloS ONE' as two separate papers on September 22 and October 1 respectively.

Main Points

There were quantitative differences distinct to individual potters, even when standard traditionally-shaped vessels were produced.

There was greater diversity between potters during the formation process compared with the finished product.

Multiple hand movement patterns that could be used to distinguish individual craftsmen were found.

Research Methodology and Findings

Humans pass down various skills to their communities and the next generation. One of these skills that has been transmitted since ancient times is pottery. This study investigated how the individuality of each craftsman stands out during the formation process of traditional pottery pieces, in particular the standardized, unsigned pottery produced for the mass-market.

First of all, the research team recorded video footage of potters making traditionally shaped pottery in the workshops of two different communities located in the Indian state of Uttar Pradesh (a Hindu community which uses a hand-operated stick-wheel, and a Muslim community which uses a foot-operated kick-wheel). The researchers performed an elliptical Fourier analysis on the recorded images in order to investigate the shape formation process during pottery throwing (Figure 1).

The results revealed that:

1. There were quantitatively distinguishable differences between the pottery produced by individual craftsmen, even among standard traditionally-shaped vessels produced for the consumer market.

2. There was greater variation between potters during the formation process than in the finished form.

Next, the researchers recorded video footage of traditional pottery shapes being made by craftsmen in a workshop in Bhaktapur, Nepal. The research team used this footage to analyze the hand movement patterns and transitions during the vessel formation processes, comparing them with those from the Indian communities.

Out of the 31 identified patterns of hand movements; similarities could be seen between different communities in approximately half of this number (cross-cultural), ten were particular to the Nepalese community (cultural), and five were identified as unique to the particular individual. The remaining movements were only observed once in one individual.

Cross Recurrence Quantification Analysis (CRQA) is a method used to quantify the dynamics of shared activity between two time series. CRQA was conducted on hand position sequences from different trials resulting in plots showing the temporal relationship between all possible combinations of hand positions in one trial with hand positions in another trial during the fashioning. These analyses revealed that there were hand position sequences that were unique to individual craftsmen (Figure 3).

The significance of this research

This research revealed that there is actually much variation in the formation process and the hand movements of the individual craftsmen, even when producing traditionally-shaped pottery in a manner that has been passed down for generations. From these results it can be surmised that each potter has been searching for their own distinct way of forming the shape of the vessel within the constraints of the tools used, such as the type of wheel, and differences in material.

Various theoretical models that have been proposed on the cultural transmission of handicrafts have viewed the inheritance of such skills as 'imitation' and 'transmitted information'. Conversely, this study provides quantitative evidence that traditional 'inherited' craftsmanship is more than mere imitation, shedding light on how individuals' ability is flexibly adopted from exploratory activities channeled by the social environment (e. g. of the pottery workshop) and the processes behind these factors. These aspects have been overlooked by existing theoretical models. The impact of these results will bring about the revision of existing theories that have reduced the transmission of traditional handicraft skills to 'imitation' and 'transmitted information'.

Furthermore, it is also hoped that this study's methodology and data could be used to determine whether unattributed archaeological artefacts were produced by an individual or several craftspeople.

Credit: 
Kobe University

A new playbook: COVID-19, athletes' hearts and return to play

BOSTON - Reports have indicated that COVID-19 may cause heart damage in hospitalized patients with severe cases of the disease, but it's unclear whether cardiac injury also occurs in infected patients who are asymptomatic or experience only mild symptoms. This question is of particular concern for athletes because myocarditis--inflammation in the heart usually caused by a viral infection--can cause sudden cardiac death during exercise. In a special report published in JAMA Cardiology, a group led by sports cardiologists at Massachusetts General Hospital (MGH) and Emory University School of Medicine offers guidance for athletes' return to play after they have recovered from COVID-19.

The article addresses the most common questions posed by the media, in clinics and athletic training rooms, and during discussions among cardiologists who care for athletes. With a consideration of evolving data, it represents a reassessment of a previous consensus statement by the American College of Cardiology that was published in May.

"This new set of recommendations is based on my and my fellow authors' clinical experience treating athletes with COVID-19 over the past few months. Our primary objective was to outline an approach that reduced unnecessary testing while simultaneously ensuring we use resources responsibly to detect athletes at increased risk of adverse cardiac events attributable to the virus during their return to sports," said senior author Aaron Baggish, MD, director of the Cardiovascular Performance Program at MGH.

Baggish and his colleagues have observed that athletes infected with COVID-19 who experienced no or mild symptoms did not exhibit signs of heart injury. For such athletes, they do not recommend detailed cardiac screening. The prevalence of cardiac injury in athletes who were infected with COVID-19 is still unknown, however, and the team believes it's prudent to screen for heart damage in athletes with moderate to severe symptoms. The experts also note that despite recent small studies showing that cardiac magnetic resonance imaging has detected potential cardiac abnormalities in individuals who have recovered from COVID-19, they feel that current evidence doesn't justify its use as a universal screening tool for athletes' return to play.

"We hope the recommendations put forth in the document will assist practitioners in sports medicine, sports cardiology and general cardiology in the evaluation of athletes for return to play after COVID-19 infection," said lead author Jonathan Kim, MD, MSc, chief of Cardiology Sports at Emory University School of Medicine. "These recommendations are intended to guide the process of determining who requires more detailed cardiac screening and ensure that all athletes post-COVID-19 infection should have a slow and gradual return to training with close monitoring of persistent symptoms, regardless of the severity of infection."

The paper's other authors were Benjamin D. Levine, MD, of the Institute for Exercise and Environmental Medicine at Texas Health Presbyterian Dallas and The University of Texas Southwestern Medical Center; Dermot Phelan, MD, PhD, of the Sanger Heart and Vascular Institute, Atrium Health, Charlotte, North Carolina; Michael S. Emery, MD, MS, of the Sports Cardiology Center, Department of Cardiovascular Medicine, Cleveland Clinic; Mathew W. Martinez, MD, of Morristown Medical Center, Atlantic Health System, Morristown, New Jersey; Eugene H. Chung, MD, MSc, of Michigan Medicine at the University of Michigan, Ann Arbor; and Paul D. Thompson, MD of Hartford Hospital in Connecticut.

Credit: 
Massachusetts General Hospital

Renewable energy targets can undermine sustainable intentions

image: Expanding renewables can also cause problems, especially if poorly planned.

Image: 
The University of Queensland

Renewable energy targets (RETs) may be too blunt a tool for ensuring a sustainable future, according to University of Queensland-led research.

PhD candidate Scott Spillias, from UQ's School of Earth and Environmental Sciences, said that, while RETs are a go-to for policymakers, more nuanced approaches were more effective at actually achieving holistic, sustainable outcomes.

"Many jurisdictions around the world including the European Union, Australia, India and several states in the USA have set specific quantitative targets for renewable energy development," Mr Spillias said.

"While it's encouraging to see action being taken to move us away from fossil fuels, unless there's rigorous analysis and stakeholder engagement that goes into their formulation, these targets could exacerbate many sustainability issues we face.

"For example, California is currently suffering extensive rolling energy blackouts that some attribute to an overzealous pursuit of state-wide targets for renewables.

"They've done this without solving the associated problem of what to do when energy demands are high and there is no sun or wind, and affordable battery storage is not yet a reality.

"Setting a target - a quantitative threshold to be attained, such as 80 per cent wind energy - rather than an objective - a qualitative direction in which to go, such as working to maximise wind energy - can blind us to trade-offs when evaluating different policy actions.

"They can also create psychological incentives to act quickly to implement them, causing decision-makers to lose sight of the more fundamental objectives that motivated the target in the first place.

"Europe's Renewable Energy Directive, for example, instead of reducing carbon emissions and protecting the environment, threatens to increase net carbon emissions and deforestation."

The researchers believe that setting such targets are a simple, easy policy instrument, but lack the nuance of more considered mechanisms for energy development.

"Targets may or may not be appropriate tools to use for renewable energy development," Mr Spillias said.

"We argue that, instead, a rigorous decision-making process should be undertaken to evaluate the trade-offs between different sustainability objectives with respect to a variety of possible targets and/or other policy instruments.

"For example, the Sustainable Development Goals have an energy-related objective, but it refers to clean energy not renewable energy.

"Renewable energy is likely going to be the best way to generate clean energy in the future, but importantly it should be recognised as merely the means to achieving that objective, rather than the ends in of itself.

"The energy-related goals and targets we set for ourselves in the years ahead will guide the course of renewable energy development and will flow through to every sector of our society.

"If, for whatever reason, we make mistakes in setting those goals, no matter how well-intentioned they might be, there will be real and enduring consequences for biodiversity, communities, and economies."

Credit: 
University of Queensland