Tech

New cellular player involved in obesity discover

image: Researcher and paper author.

Image: 
Ana Morais

The prevalence of obesity, a disease considered a serious public health problem, is increasing globally. In Portugal, almost half of the population is overweight and close to one million adults suffer from obesity. Known as a risk factor for the development of cardiovascular disease and diabetes, obesity is associated with chronic inflammation in fat tissues. New strategies to fight this disease are needed. Therefore, a deeper understanding of the mechanisms involved in metabolic deregulation are critical to approach the obesity problem.

To Colin Adrain, principal investigator of the research group, "it is important to understand the fundamental mechanisms underlying how metabolic dysregulation occurs." Adrain added that during the research they found that "iRhom2 protein is strongly present in metabolic tissues and organs, which made us decide to study the role of iRhom2 in obesity in more detail."

The paper, now published in the Molecular Metabolism journal, demonstrates how the researchers reached these results: they used an animal model, comparing groups with iRhom2 deletion to controls, and feeding them with normal diet versus a high fat diet.

Surprisingly, they found that during obesity, iRhom2 protein levels increase specifically in brown adipose tissue in obese animals compared to controls. Following up on this, they found that, on a high fat diet, the animals lacking iRhom2 protein were metabolically more healthy than their wild type counterparts.

Marina Badenes, a researcher and the main author of the paper, explains that "the deletion of iRhom2 led to enhanced energy consumption in adipose tissue, which protected animals from fat accumulation and inflammation, fatty liver and insulin resistance when the animals were placed on a diet that predisposed them to obesity". Furthermore, the researchers found that "at the cellular level deletion of iRhom2 leads to an increase in thermogenesis (heat production) in brown adipose tissue. Thermogenesis in brown adipose tissue is an important physiological mechanism to consume excess body energy".

Interestingly no deleterious side effects were found in the animals with iRhom2 deletion, indicating that blocking iRhom2 may potentially be beneficial in the treatment of obesity and associated complications. Researchers intend to continue the project to further understand the mechanisms and cell types involved in the iRhom2 control of obesity. They also want to find out the specific targets involved in the protection against obesity associated with loss of iRhom2.

Credit: 
Instituto Gulbenkian de Ciencia

Trace Metals in Leatherback Turtle Eggs May Harm Consumers

image: Turtle eggs sale in Panama.

Image: 
Argelis Ruíz

Leatherback turtle (Dermochelys coriacea) eggs laid in Bocas del Toro nesting beaches in the Panamanian Caribbean may be harmful to consumers. According to a study by the Smithsonian Tropical Research Institute (STRI) and collaborating institutions, they contain high concentrations of trace metals and their ingestion could pose health risks to local communities. Decreasing the consumption of leatherback turtle eggs would benefit the well-being of consumers and the conservation of this endangered species.

Leatherback turtle eggs are not inherently harmful. The accumulation of trace metals in them reflects the contamination in the environment that nesting females are exposed to throughout their migratory routes. Because of their longevity and relatively late maturity, marine turtles can accumulate significant amounts of trace metals as they grow. For leatherback turtles nesting in Bocas del Toro, the Gulf of Mexico is a potential risk zone for contamination. This gulf is an important feeding area for the species, but it is also strongly polluted from agriculture, industry and oil facilities, as other areas in the Caribbean and Atlantic.

This was reflected on the measurements taken by scientists on freshly laid eggs in Panama. They revealed higher concentrations of iron, zinc, arsenic, selenium and strontium than previously reported for this species, with arsenic values being the highest ever measured for eggs of any sea turtle species, while mercury and zinc levels were above international standards for children. These results demonstrate that the ingestion of leatherback turtle eggs poses health risks to local communities, including an increased life-time carcinogenic risk for adults and children.

These potential health hazards are not exclusive to the eggs of this turtle species. A 2016 study by STRI researchers analyzed Green turtle (Chelonia mydas) and Olive Ridley turtle (Lepidochelys olivacea) eggs from the Panamanian Pacific and also found high concentrations of toxic metals in them, including manganese, iron, copper, zinc, arsenic, cadmium and mercury.

Meanwhile, efforts to halt or reduce marine turtle egg poaching have failed in many countries. At Changuinola beaches in Bocas del Toro, a high percentage of sea turtle clutches may be exploited during the nesting season. For many locals, this represents an important food source and a way to generate income. At the same time, it remains a major threat to the survival of turtle populations.

"The conservation of sea turtles has been compromised for decades from regional and local exploitation, with few successful protection measures," said Hector M. Guzman, STRI researcher and principal author of the study. "Populations, instead of recovering, continue to be affected by bycatch and egg poaching."

Leatherback turtle populations in this area (northwest Atlantic) are already considered vulnerable and under evaluation, but in other oceanic regions the situation is more serious. The harvesting of eggs and the destruction of nesting habitats has severely affected the eastern Pacific populations, which are categorized as critically endangered. That is, they face an extremely high risk of extinction.

"Our study demonstrated that there is a severe risk coming from eating turtle eggs due to the accumulation of certain metals with unknown long-term impacts," said Stefanie Kaiser, a biologist at Universität Hamburg and co-author of the study. "Clearly, turtle eggs are not made for human consumption, and both local residents and sea turtle populations will benefit from putting a stop to the exploitation and consumption of eggs."

The researchers recommend that conservationists focus their attention on the human health effects of consuming turtle eggs as an alternative approach to discourage egg poaching. They further suggest health education initiatives that increase awareness among local doctors, health workers and the public about these risks.

"We must open our eyes to the potential toxic effects of egg consumption on human health," Guzman said. "It is best to raise public awareness country-by-country, but we also need the support of our health and environmental institutions to communicate the message."

Credit: 
Smithsonian Tropical Research Institute

Molecular 'doormen' open the way to potential obesity treatment

Fat cells are filled with droplets coated by molecules that act like hotel doormen: These "doormen" control cellular access for nutrients as well as for the exit of energy-supplying molecules called lipids. In healthy individuals, outgoing and incoming traffic in fat cells is finely balanced, supplying energy while preventing excessive spread of undesirable fat in the belly.

But in obese individuals, these cellular doormen have opened the gates far too wide in certain key fat cells, known as visceral fat cells, letting in too many carbohydrates without first burning off lipids. This leads to a ballooning of the size of visceral fat cells in the belly.

Obesity is linked to increased risk of heart disease, diabetes, and chronic liver disease, as well as other disorders.

Yale researchers report Jan. 10 in the journal Nature Communications that they have found the molecular regulator of this fat droplet doorman, and potential new treatments for obesity based on restoring healthy balance found in lean individuals.

The regulator, or commander, of these fat droplet sentinels is an enzyme called O-GlcNAc transferase (OGT), according to the research team. Mice lacking the enzyme are lean, exhibit a dramatic reduction in the size of fat cells and tend to burn off lipids first rather than taking in more carbohydrate fuel.

Conversely, the overexpression of OGT in mice triggers obesity by increasing intake of carbohydrates without burning off excess lipids.

"The commander of this doorman makes it easier for nutrients to get in, but harder for lipids to get out," said senior author Xiaoyong Yang, associate professor of comparative medicine and of cellular and molecular physiology at Yale University School of Medicine.

In previous studies, Yang's team found that overexpression of OGT in fat cells has another side effect -- it signals the brain to consume more calories (essentially asking the brain to order another pizza).

"This makes OGT a very attractive target to pharmaceutically treat obesity," Yang said.

Credit: 
Yale University

Cracks in Arctic sea ice turn low clouds on and off

In the wintertime Arctic, cracks in the ice called "leads" expose the warm ocean directly to the cold air, with some leads only a few meters wide and some kilometers wide. They play a critical role in the Arctic surface energy balance. If we want to know how much the ice is going to grow in winter, we need to understand the impacts of leads.

The extreme contrast in temperature between the warm ocean and the cold air creates a flow of heat and moisture from the ocean to the atmosphere. This flow provides a lead with its own weather system which creates low-level clouds. The prevailing view has been that more leads are associated with more low-level clouds during winter. But University of Utah atmospheric scientists noticed something strange in their study of these leads: when lead occurrence was greater, there were fewer, not more clouds.

In a paper published in Nature Communications, they explain why: wintertime leads rapidly freeze after opening, so most leads have newly frozen ice that shuts off the moisture supply but only some of the heat flow from the ocean, thus causing any low-level clouds to dissipate and accelerating the freezing of sea ice compared to unfrozen leads. Understanding this dynamic, the authors say, will help more accurately represent the impact of winter-time leads on low-level clouds and on the surface energy budget in the Arctic - especially as the Arctic sea ice is declining.

Credit: 
University of Utah

Pearls of wisdom

image: Population structure of the pearl oyster, Pinctada fucata, in the western Pacific. (A) Sampling localities. JPN: mainland Japan including Honshu, Shikoku, and Kyushu. NAN: Nansei Islands. CHN: China. KHM: Cambodia. MMR: Myanmar. (B) PCA (principal component analysis) using genome-wide SNP data revealed that the northern population (mainland Japan) genetically diverged from southern population (Cambodia, China, and Nansei Islands). Individuals from Myanmar in the Indian Ocean are distinguishable from others in the Pacific because of a geographical barrier. In addition, the population in Kamikoshiki Island, Japan is genetically unique because they live in a local lagoon isolated from ocean by a sand bank.

Image: 
OIST

Since the late 19th century, pearl aquaculture has been a revered industry in Japan, enabling widespread cultivation and commercialization of beautiful pearls. From a genetic and evolutionary perspective, scientists have known little about the source of these pearls - the Japanese pearl oyster, Pinctada fucata - until now.

Researchers in the Marine Genomics Unit at the Okinawa Institute of Science and Technology Graduate University (OIST), in collaboration with scientists from Mie Prefecture, Japan, have, using genome-wide genetic data from specimens collected across the western Pacific, elucidated how pearl oyster populations vary genetically and geographically. Their analyses provide insight into how these pearl oysters have adapted to environmental changes over time. Understanding the genetic structure of these populations will be crucial for developing effective and targeted conservation strategies for the species in light of climate change, the researchers said.

"In particular we wanted to understand the population structure of P. fucata and how these pearl oysters moved from the southwestern Pacific (of which Okinawa is a part), north, to mainland Japan," said Dr. Takeshi Takeuchi, the first author of the new study, published in Evolutionary Applications. "P. fucata is a good model for understanding genetic differentiation because the species is so widespread across the western Pacific."

Cracking the pearl oyster genome

After a century of success, Japanese pearl production plummeted during the 1990s due to detrimental algal blooms and an outbreak of bacterial disease, both of which damaged pearl oyster populations. Additionally, during this time, pearl farmers introduced Chinese pearl oysters into Japanese waters, threatening the genetic diversity of the P. fucata population.

To better understand and conserve these animals, the scientists analyzed about 200 individual P. fucata specimens from across mainland Japan, the southern Nansei Archipelago, including sites near Okinawa, along with China, Myanmar, and Cambodia. In order to minimize the effect of recent intermingling between Japanese and Chinese populations, they used frozen specimens collected between 2000 and 2003. They sequenced the genomes of the specimens and analyzed 36,203 single nucleotide polymorphism (SNP) sites. SNPs are tiny differences in DNA's building blocks that help scientists study genetic variation.

Takeuchi and his colleagues found that pearl oysters in mainland Japan (the northern population) are genetically distant from the southern population in the Nansei Islands, China, and Cambodia.

However, the researchers could not understand why pearl oysters in the Japanese mainland and Nansei Islands were genetically distinct, since they weren't separated by a land barrier. Due to the strong Kuroshio Current, the oysters could easily be propelled from Nansei to the mainland, mixing the populations.

To solve this mystery, the scientists looked at environmental factors that might influence genetic diversification, including sea surface temperature, oxygen, carbon dioxide, phosphate, and nitrate levels in the water, as well as ocean salinity.

Through statistical analyses, they found that sea surface temperature and oxygen concentration strongly correlated with genetic variation. The mainland and Nansei populations are likely distinct because they adapted to local environmental conditions, the researchers said.

Traveling back in time

These findings then helped the researchers piece together P. fucata's history. During the Last Glacial Maximum (about 20,000 years ago), ocean surface temperatures were much lower than present day, and P. fucata populations were absent in the Japanese mainland. After the last glacial period, however, temperatures in Japan increased and peaked 6,000 years ago at two to three degrees higher than present, and the pearl oyster populations moved north to mainland Japan.

Moving forward, the researchers hope to continue studying the pearl oysters' genes, since climate change and increasing ocean temperatures may affect P. fucata's distribution.

"Using genome-wide data, we revealed population structure of the pearl oyster in the western Pacific," said Takeuchi. "We are now developing DNA markers to distinguish the Japanese population from others. This will be useful for conserving the unique genetic resources of the Japanese pearl oysters," said Takeuchi.

Credit: 
Okinawa Institute of Science and Technology (OIST) Graduate University

Antibiotics could be promising treatment for form of dementia

image: University of Kentucky researchers (from left) Matthew Gentry, Haining Zhu and Lisha Kuang co-authored a study that shows a class of antibiotics could be a promising therapy for frontotemporal dementia.

Image: 
Mark Cornelison | UK Photo

LEXINGTON, Ky. (Jan. 10, 2020) -- Researchers at the University of Kentucky's College of Medicine have found that a class of antibiotics called aminoglycosides could be a promising treatment for frontotemporal dementia.

Results of their proof of concept study, which was a collaborative effort between UK's Department of Molecular and Cellular Biochemistry and the University of California San Francisco's Department of Pathology, were recently published in the journal, Human Molecular Genetics.

Frontotemporal dementia is the most common type of early onset dementia. It typically begins between ages 40 and 65 and affects the frontal and temporal lobes of the brain, which leads to behavior changes, difficulty speaking and writing, and memory deterioration.

A subgroup of patients with frontotemporal dementia have a specific genetic mutation that prevents brain cells from making a protein called progranulin. Although progranulin is not widely understood, its absence is linked to the disease.

A group led by Haining Zhu, a professor in UK's Department of Molecular and Cellular Biochemistry, discovered that after aminoglycoside antibiotics were added to neuronal cells with this mutation, the cells started making the full-length progranulin protein by skipping the mutation.

"These patients' brain cells have a mutation that prevents progranulin from being made. The team found that by adding a small antibiotic molecule to the cells, they could 'trick' the cellular machinery into making it," said Matthew Gentry, a co-author of the study and the Antonio S. Turco Endowed Professor in the Department of Molecular and Cellular Biochemistry.

The researchers found two specific aminoglycoside antibiotics - Gentamicin and G418 - were both effective in fixing the mutation and making the functional progranulin protein. After adding Gentamicin or G418 molecules to the affected cells, the progranulin protein level was recovered up to about 50 to 60%.

These results could be promising to drug development. Currently, there are no effective therapies for any type of dementia.

After this preclinical proof of concept study, the next step is to study the antibiotics' effects on mice with the mutation that causes frontotemporal dementia, Zhu says. Another focus is to possibly develop new compounds from Gentamicin and G418 that could be safer and more effective. Although Gentamicin is an FDA-approved medication, its clinical usage is limited as it is associated with a number of adverse side effects.

"If we can get the right resources and physician to work with, we could potentially repurpose this drug. This is an early stage of the study, but it provides an important proof of concept that these aminoglycoside antibiotics or their derivatives can be a therapeutic avenue for frontotemporal dementia," said Zhu.

Credit: 
University of Kentucky

How do fruit flies see in color? Columbia study uncovers human-like brain circuit at work

image: Fly retina showing all R8 photoreceptors in green and yR8 receptors in red.

Image: 
Sarah Heath/Behnia lab/Columbia University's Zuckerman Institute

NEW YORK -- Columbia scientists have identified a brain circuit that drives fruit flies' ability to see in color -- and found that it bears a striking resemblance to the circuitry behind our own capacity for color vision. These findings shed light on the fundamental, yet mysterious, process by which information about light waves is transmitted from the eye to the brain. This research will not only fuel new investigations into how color vision works in flies and humans, but could also spur efforts to develop algorithms that help computers see in color.

This study was published today in Current Biology.

"The brain can recognize over a million different colors, an astounding power that we are only just beginning to understand," said Rudy Behnia, PhD, a principal investigator at Columbia's Mortimer B. Zuckerman Mind Brain Behavior Institute and the paper's senior author. "With today's study, we pinpointed a circuit of nerve cells that act as a color synthesizer for the fly's brain. This discovery is so exciting because such a similar system appears to be at work in the human brain. As we delve deeper into the fruit fly brain, we are discovering more about our own ability to see and process color."

In both flies and humans, color vision starts with the eye, which contains specialized nerve cells called photoreceptors. These color-sensitive cells line the retina on the back of the eye. Most people (except, for example, those with color blindness) have three types of photoreceptors for color vision. Fruit flies have four. In all animals, each photoreceptor type is sensitive to a particular range of wavelengths of light. Light hitting the photoreceptors triggers a series of electrical signals that are sent into the brain.

"We know that the brain compares these electrical signals from the different photoreceptors, ultimately translating them into color, but precisely how this happens has remained elusive," said Dr. Behnia, who is also an assistant professor of neuroscience at Columbia's Vagelos College of Physicians and Surgeons. "Thanks to recent advances in molecular and imaging technology, we can now view nerve cells across different areas of the fly's brain in exquisite detail."

The small size and relative simplicity of the fruit fly brain make it an ideal organism to investigate color vision. The organization and structure of its brain are also well documented, thanks to initiatives like the Fly Connectome Project at Janelia Research Campus, which has mapped the location and connections of every cell in the fly brain.

For today's Zuckerman Institute study, Sarah Heath, a doctoral candidate in the Behnia lab and the paper's co-first author, recorded the activity of the fruit fly's photoreceptors, one at a time, while the fly looked at different colored LED sources.

Each photoreceptor had long branches, called axons, that extended into the fly's optic lobe, the brain area responsible for vision. These axons communicated with each other, sending information back and forth about the signals they were transmitting. As the researchers traced each signal's path, they found that these paths led to a type of nerve cell called Dm9.

"We think Dm9 serves as a synthesizer, a place for each photoreceptor signal to be compared to each other," said Dr. Behnia.

This comparison is important. Decades of experiments have shown that signals from just one photoreceptor are not enough for the brain to identify a color. This is why people lacking one or more type of photoreceptor have varying degrees of color blindness.

"Each photoreceptor signal must be quantitively compared and analyzed by the brain for the correct color to be identified," Dr. Behnia continued. "And our work has shown that Dm9 may in fact serve that role."

Using this newly collected data as well as data from the Fly Connectome Project, Matthias Christenson, a co-first author on this paper and doctoral candidate in the Behnia lab, developed a computational model of the fly's color circuit. This model could help scientists predict how flies behave in response to different colors -- filling in the many holes in our understanding of the visual system.

Christenson hopes that a better understanding of how the brain perceives color could also lead to new computer-based technologies for those with vision impairments.

"Today's systems struggle to sort out the panoply of hues that we experience every day," said Christenson. "As we continue to uncover the mechanisms behind color processing, one could foresee vision algorithms that improve the way computers recognize different colors."

This research also revealed an unexpected connection to people. For example, the team found that photoreceptors in the fly actually behave similarly to those in humans.

"Dm9 cells bear a striking resemblance in structure, organization and function to nerve cells in the human visual system called horizontal cells," said Heath. "This likeness could be the result of convergent evolution, a phenomenon in which two evolutionary distinct species -- in this case, flies and people -- evolve the same solution to a common problem."

These and future insights the team uncovers in flies could be used to as a starting point to better understand the human visual system.

"The more we learn about how flies experience the world around them, the more commonality we find to ourselves," Dr. Behnia said. "This makes the fly incredibly informative for answering some of biology's oldest questions."

Credit: 
The Zuckerman Institute at Columbia University

Martian water vapor varies with the seasons

The potential for Mars' water to be lost into space is greater during the planet's warm and stormy seasons, according to a new study. This seasonal variation likely regulated the rate at which the red planet lost its once-abundant quantities of liquid water, the authors suggest. Ancient alluvial fans, dry lake beds and winding river valleys clearly demonstrate that the surface of Mars was once a far wetter place. The vast majority of the liquid water that once flowed freely across the Martian surface was later lost to space, leaving behind a dusty, desert-like landscape. Still, water persists on Mars. Today, almost all of the water that remains on Mars is frozen and locked up in the planet's polar ice caps; however, small amounts of water vapor and clouds of water ice crystals are still present in the atmosphere. Although atmospheric water vapor represents a minute fraction of Mars' remaining water, it can potentially dissipate into space if it rises high enough into the upper atmosphere, which controls the rate of the planet's continued desiccation. Anna Fedorova, Franck Montmessin, Oleg Korabley and colleagues used measurements from the ExoMars Trace Gas Orbiter spacecraft to investigate the vertical distribution of water throughout the Martian atmosphere. They found that while the planet's massive dust storms impacted water vapor distributions, seasonal changes were the most dominant regulator of atmospheric water. During the warmest parts of Mars' orbit, large portions of the Martian atmosphere became supersaturated, allowing water to continue to reach the upper atmosphere. The authors conclude that the higher-than-expected amount of water in the upper atmosphere during this season likely dominated the loss of water into interplanetary space.

Credit: 
American Association for the Advancement of Science (AAAS)

Researchers decipher a new way that immune cells detect infections and cancers

image: Picture shows part of a melanoma tumor with expression of butyrophilin 2A1 highlighted in green and cell
nuclei in blue.

Image: 
Image supplied

Published today in Science, the research team from the Peter Doherty Institute for Infection and Immunity (Doherty Institute), the Olivia Newton-John Cancer Research Institute and CSL Limited say this breakthrough of discovering how gamma-delta T cells become activated addresses a question that has baffled scientists for 25 years.

The study by University of Melbourne's Marc Rigau, PhD student at the Doherty Institute, was co-led by Dr Adam Uldrich, a Senior Research Fellow at the Doherty Institute, Professor Dale Godfrey a laboratory head at the Doherty Institute, and Dr Andreas Behren, a Laboratory Head from the Olivia Newton-John Cancer Research Institute.

Dr Uldrich explained that gamma-delta T cells are known to respond to the presence of small molecules, known as phosphoantigens, that are produced by bacteria and cancer cells.

"This leads to the activation of these gamma-delta T cells and often eradication of the diseased cells."

Professor Godfrey said "Up until now, scientists have struggled to understand the fundamental question of how phosphoantigens are detected by gamma-delta T cells."

"We found that molecules on the surface of the gamma-delta T cells, called T cell receptors, bind to another molecule called butyrophilin 2A1 that is present on many different cell types throughout the body, including cancer cells."1

Dr Behren said "These findings represent a key advance in our understanding of how gamma-delta T cells function to protect us from disease."

"The research team believes that this breakthrough could ultimately lead to the development of new and improved immunotherapy treatments for millions of people worldwide impacted by cancer and infection."

The research is the result of a collaboration between the Doherty Institute, the Olivia Newton-John Cancer Research Institute, and CSL Limited.

"This research project demonstrates the power of collaboration between academia and industry. Nearly a decade ago, we identified Butyrophilin 2A1 as a potential therapeutic target but its precise biological function remained elusive," said Dr Con Panousis, Senior Director Molecular Biology, CSL Limited and an author on the paper.

"This discovery makes a significant contribution to our understanding of how gamma-delta T cells work and in doing so, paves the way for translating this research into new immunotherapies for the treatment of serious human disease."

The collaborators have filed patents surrounding their discovery.

Credit: 
University of Melbourne

Peering into the genome of brain tumor

image: MR images of gliomas were fed into a pre-trained deep neural network that can classify natural images. The activities of neurons in each layer of the network were used to characterize the textures of the MR images. These texture features were used to infer three key molecular subtypes of gliomas. The obtained algorithm was able to predict these molecular subtypes with an accuracy of 63.1%.

Image: 
Osaka University

Osaka, Japan - Researchers at Osaka University have developed a computer method that uses magnetic resonance imaging (MRI) and machine learning to rapidly forecast genetic mutations in glioma tumors, which occur in the brain or spine. The work may help glioma patients to receive more suitable treatment faster, giving better outcomes. The research was recently published in Scientific Reports.

Cancer treatment has undergone a revolution in recent years. Spurred by recognition that each cancer case is unique, the specific genetic mutations tumor cells carry are now sequenced to discover which chemotherapy drugs will work best. However, certain types of cancer, especially brain tumors, are less accessible for genetic testing. The tumor's genotype can't be found until a sample is taken during surgery, and this can significantly delay treatment.

Glioma is a type of cancer that originates in the brain's supporting cells. Two types of mutations are especially important; these are changes in the gene for the enzyme isocitrate dehydrogenase (IDH) or the promoter region of telomerase (TERT). Identifying these mutations can help direct the proper course of treatment. The researchers produced a machine-learning algorithm that can predict which mutations are present using only the MR images of the tumors.

"Machine learning is increasingly used to diagnose medical images. But our work is one of the first to even attempt to classify something as hidden as the genotype based on image data alone," study first author Ryohei Fukuma explains. The algorithm was found to be significantly better at predicting the mutations compared with conventionally used radiomic features of the MR images, such as size, shape, and intensity.

To construct the algorithm, the researchers used a convolutional neural network to extract features from the MR images. Then, using a machine-learning method called support vector machines, they classified the patients into groups based on the presence or absence of mutations. "We hope to expand this approach to other types of cancer, so we can take advantage of the large cancer gene databases already collected" senior author Haruhiko Kishima says.

The end result could remove the need for surgical tissue sampling. Even more, it could lead to better clinical outcomes for patients as the process of delivering personalized medicine becomes easier and faster.

Credit: 
Osaka University

Scientists observe ultrafast chemistry in water caused by ionizing radiation

image: Associate Professor Loh Zhi-Heng (left) with his Ph.D. student Muhammad Shafiq Bin Mohd Yusof (right) working on tabletop laser experiments involving chemistry reaction in water at NTU.

Image: 
NTU Singapore

An international research team jointly led by Nanyang Technological University, Singapore (NTU Singapore), the U.S. Department of Energy's (DOE) Argonne National Laboratory and Germany's Deutsches Elektronen-Synchrotron (DESY) has for the first time observed the ultrafast formation and then breakdown of the water ion that is created when water is exposed to ionising radiation.

The water ion plays a crucial role in many chemical reactions, but has never been directly observed due to its extremely short lifetime.

When ionising radiation with enough energy hits water molecules (H2O), it forcefully strips an electron away from them, creating the water ion known as a radical cation (H2O+), which is missing an electron and is therefore highly unstable.

The H2O+ radical then gives up a proton to a neighbouring water molecule, creating both hydronium (H3O+) and a hydroxyl radical (OH), in a step known as 'proton transfer'. All of this occurs in just 50 femtoseconds (50 quadrillionths of a second, or 0.000 000 000 000 05 of a second.)

Scientists believe that the H2O+ radical is the first chemical species in a long cascade of chain reactions that can eventually lead to radiation damage in biological tissue. Highly reactive radicals, such as the OH radical, have been reported by other studies to strip electrons from stable compounds that are rich in electrons, such as DNA.

This eventually leads to a cascade reaction where DNA strands become damaged and fall apart. Most of the time the cell's machinery corrects this damage, but if it does not it can lead to the first steps in changes to the DNA which become mutations and may eventually cause serious problems, including cancer.

The proton transfer reaction is significant in a wide range of fields, including nuclear engineering, space travel and environmental remediation. It also helps scientists better understand how radiation interacts with water in aqueous environments, such as in biological systems and water-cooled nuclear reactors.

Published today in Science, the clocking of this chemical reaction in ionised water was the result of an international collaboration between NTU Singapore, Argonne National Laboratory and the German research centre DESY, with the experiments conducted at SLAC National Accelerator Laboratory, USA. The study also included contributions from other institutions in the US and Germany, including those from Sweden, France and Denmark.

The publication marks the latest discovery by lead author, NTU Associate Professor Loh Zhi-Heng, whose group has studied the ultrafast dynamics of ionising molecules using ultrafast lasers for the past nine years. His team included PhD student Mr Muhammad Shafiq Bin Mohd Yusof and Dr Tushar Debnath, a former postdoctoral researcher who is currently a Humboldt Research Fellow at LMU Munich.

The chemical reactions involving the water ion are among the fastest known to mankind and to capture its existence the team used a state-of-the-art X-ray free-electron laser.

"While we had observed a glimpse of the possible lifetime of the H2O+ radical in earlier experiments using femtosecond lasers at NTU, its direct spectroscopic observation lies beyond the capability of most tabletop equipment," said Assoc Prof Loh, who is also the Assistant Chair (Academic) at NTU's School of Physical and Mathematical Sciences.

"However, using the ultrafast x-ray laser at SLAC enabled us to not only observe the proton transfer, but will also potentially allow us to precisely determine what happens before, during and after the reaction."

"What we are observing is like the prequel to radiation damage - the very first chemical reaction which leads to subsequent chemical reactions that lead to what scientists have classified as radiation damage. If we can fully understand how this chemical reaction happens, then finding a way to stop or reverse this reaction could pave the way towards stopping or reducing radiation damage in biological cells."

Scientists have long studied the ionisation of water, with a first sighting in the 1960s by scientists at Argonne of the hydrated electron that is produced by the radiolysis of water. However, without a sufficiently fast X-ray probe like that provided by the Linac Coherent Light Source (LCLS) at SLAC, a DOE Office of Science User Facility, researchers had no way to observe the residual positively charged ion, the other half of the reaction pair.

"The truly exciting thing is that we've witnessed the fastest chemical reaction in ionised water, which leads to the birth of the hydroxyl radical," said Argonne Distinguished Fellow and Professor of Physics at The University of Chicago, Prof Linda Young, the senior corresponding author of the study.

"The hydroxyl radical is itself of considerable importance, as it can diffuse through an organism, including our bodies, and damage virtually any macromolecule including DNA, RNA, and proteins."

By understanding the time scale for the formation of the chemically aggressive hydroxyl radical and, thereby, gaining a deeper mechanistic understanding of the radiolysis of water, it may become possible to develop strategies to suppress this key step that can lead to radiation damage.

The development of the theory behind the experiment was led by Prof Robin Santra of the Center for Free-Electron Laser Science at DESY in Germany. Santra showed that using the technique of ultrafast X-ray absorption, scientists could detect the structural dynamics--both in terms of electron and nuclear motion--near the ionization and proton transfer site.

"We could show that the X-ray data actually contain information on the dynamics of the water molecules that enable the proton transfer," said Santra, who is a lead scientist at DESY and principal investigator at the Hamburg Centre for Ultrafast Imaging, a cluster of excellence at the University of Hamburg and DESY.

"In just 50 quadrillionths of a second, the surrounding water molecules literally move in on the ionized H2O+ until one of them comes close enough to grab one of its protons in a sort of handshake, turning into hydronium H3O+ and leaving behind the hydroxyl radical OH."

Understanding the formation of the hydroxyl radical could be of interest in aqueous environments containing salts or other minerals that might in turn react with ionised water or its byproducts. Such environments could include nuclear waste repositories or other places in need of environmental remediation.

Credit: 
Nanyang Technological University

The Vikings erected a runestone out of fear of a climate catastrophe

image: Rök runes.

Image: 
Helge Andersson

Several passages on the Rök stone - the world's most famous Viking Age runic monument - suggest that the inscription is about battles and for over a hundred years, researchers have been trying to connect the inscription with heroic deeds in war. Now, thanks to an interdisciplinary research project, a new interpretation of the inscription is being presented. The study shows that the inscription deals with an entirely different kind of battle: the conflict between light and darkness, warmth and cold, life and death.

The Rök runestone, erected in Östergötland around 800 CE, is the world's most famous runestone from the Viking Age, but has also proven to be one of the most difficult to interpret. This new interpretation is based on a collaboration between researchers from several disciplines and universities.

"The key to unlocking the inscription was the interdisciplinary approach. Without these collaborations between textual analysis, archaeology, history of religions and runology, it would have been impossible to solve the riddles of the Rök runestone," says Per Holmberg, professor in Swedish at the University of Gothenburg, who led the study.

A previous climate catastrophe

The study is based on new archaeological research describing how badly Scandinavia suffered from a previous climate catastrophe with lower average temperatures, crop failures, hunger and mass extinctions. Bo Gräslund, professor in Archaeology at Uppsala University, points to several reasons why people may have feared a new catastrophe of this kind:

"Before the Rök runestone was erected, a number of events occurred which must have seemed extremely ominous: a powerful solar storm coloured the sky in dramatic shades of red, crop yields suffered from an extremely cold summer, and later a solar eclipse occurred just after sunrise. Even one of these events would have been enough to raise fears of another Fimbulwinter," says Bo Gräslund.

Nine riddles

According to the researchers' new interpretation now being published, the inscription consists of nine riddles. The answer to five of these riddles is "the Sun". One is a riddle asking who was dead but now lives again. The remaining four riddles are about Odin and his warriors.

Olof Sundqvist, professor in History of Religions at Stockholm University, explains the connection:

"The powerful elite of the Viking Age saw themselves as guarantors for good harvests. They were the leaders of the cult that held together the fragile balance between light and darkness. And finally at Ragnarök, they would fight alongside Odin in the final battle for the light."

Parallels with other Old Norse texts

According to the researchers, several points in the inscription have clear parallels with other Old Norse texts that no one has previously noted.

"For me, it's been almost like discovering a new literary source from the Viking Age. Sweden's answer to the Icelandic Poetic Edda!" says Henrik Williams, professor in Scandinavian Languages with a specialty in Runology at Uppsala University.

Credit: 
University of Gothenburg

Earlier falls predict subsequent fractures in postmenopausal women

image: X-ray image of a fractured ankle.

Image: 
Heikki Kröger

The risk of fracture in postmenopausal women can be predicted by history of falls, according to new findings from the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) at the University of Eastern Finland. Published in Osteoporosis International, the study is the first to follow up on the association between history of falls and subsequent fractures.

Falls in the elderly are common, resulting in fractures and other serious health consequences. In people aged 65 years or over, falls are the leading cause of injury-related death and hospitalisation. Fall-induced injuries cause a substantial economic burden worldwide.

Conducted at the University of Eastern Finland and Kuopio University Hospital, the study comprised 8,744 women whose mean age at the beginning of the study was approximately 62 years. The study started in 1999 with an enquiry asking the study participants about their history of falls in the preceding 12 months. The researchers wanted to know how many times the study participants had fallen, what had caused the falls and how severe the falls had been; i.e., did they lead to injuries that required treatment. A follow-up enquiry was conducted in 2004, asking the study participants about any fractures they had suffered during the five-year follow-up. The self-reported fractures were confirmed from medical records.

Nearly one in five women reported a fall during the preceding 12 months. The risk of fracture was 41% greater in women who had reported a fall in comparison to those who hadn't. Slip falls were associated with a greater risk of subsequent fracture than falls caused by other reasons. Furthermore, injurious falls predicted future fractures: the risk of fracture was 64% higher in women who had experienced an injurious fall. In particular, earlier injurious falls predicted other fractures than those typically associated with osteoporosis.

Credit: 
University of Eastern Finland

Kangaroo mother care reduces infant mortality

image: Professor Halvor Sommerfelt is the leader of CISMAC at the University of Bergen.

Image: 
Eivind Senneset.

Researchers at Centre for Intervention Science in Maternal and Child Health (CISMAC) at the University of Bergen (UiB) followed 8400 low birth weight infants, from 2015 to 2018.

The research team wanted to measure the effect of the so-called kangaroo mother caremethod on these children, both those born at home those who returned home only few hours after birth.

The method is based on holding the newborn tightly into the body with the help of a scarf or harness, during the first month, preferably more than 12 hours a day.

"We discovered that the chance of survival increased as much as 30 per cent within the first month and by 25 per cent within the first six months," says Professor Halvor Sommerfelt, leader of CISMAC, UiB.

"There are few health interventions that reduce mortality with as much as 30 per cent. The only ones are vaccination programmes," Sommerfelt says.

Important contribution against child mortality

India is one of the countries in the world with the highest frequency of low birth weight babies. As many as one in four newborns is underweight.

"We know that the underweight infants are more vulnerable for disease and death than other infants. Half of the ones that don't survive, die during the first month of their life," Sommerfelt points out.

Home confinements have become less frequent in India, but it is still considered normal for mothers return home only six hours after giving birth, even if the infant is premature. Similar to other low- and middle-income countries, hospitals and health centres in India have little access to incubators and other modern technology.

"Most of the deaths occur among infants with low birth weight. Kangaroo mother care shows remarkable results in increasing survival. We hope that as many as possible will start to use the method," says Sommerfelt.

New guidelines

Earlier studies have shown that the use of Kangaroo Mother Care in hospital settings increased survival of low birth weight babies by 40 per cent. The new study documents this positive effect in community-based kangaroo mother care as well.

Sommerfelt believes that the World Health Organisation (WHO) will develop guidelines supporting this intervention within a year, recommending Kangaroo Mother Care at home, in addition to the recommendation for hospital use.

"It is, however, important to say that our study does not include children under 1,8 kilograms. Such small infants and very sick infants must be treated at a hospital until their health situation is stable," underlines Sommerfelt.

Easy and inexpensive treatment

The researchers do not know if the good effect from kangaroo mother care is caused by better access to breast feeding, or better temperature regulation or whether it is other factors such as the experience of safety when the child hears the mother´s heartbeats.

"Kangaroo mother care is an easy and inexpensive initiative. I am convinced that it will be recommended, not only by WHO, but also by Indian health authorities," says Halvor Sommerfelt.

Facts:

The Kangaroo Mother Care Study:

Researchers at Centre for Intervention Science in Maternal and Child Health (CISMAC) and their Indian partners at Society for Applied Studies in India, followed 45 000 pregnant woman and their 8 400 infants born with low birthweight, from 2015-2018.

150 researchers and health workers were recruited through CISMAC.

Half of the infants were randomized into one group with Kangaroo Mother Care and another group with ordinary care. The two groups were compared.

The infants in the intervention group had on average, four weeks and 11 hours per day with Kangaroo Mother Care.

The study was conducted in close collaboration with WHO

Low birth weight:

Every year 20 million low birth weight infants are born globally.

80 per cent of infant deaths occur among those with low birth weight. 50 percent of these are pre-born.

Nearly 97 per cent of low birth weight infants are born in low- and middle-income countries, 40 per cent of these in India.

Credit: 
The University of Bergen

New study shows dominance of local air pollution sources in Delhi

The University of Surrey has revealed results from a new, comprehensive study that suggests that activities such as construction and vehicle traffic contribute significantly to the Delhi National Capital Region's high concentrations of harmful air pollutants and gases.

According to the World Health Organisation, air pollution was estimated to cause nearly 4.2 million premature deaths worldwide in 2016. In India, around 600,000 deaths annually are attributed to air pollution, and some of the world's highest levels can be found in Delhi city.

In a study published in Sustainable Cities and Society, a team led by Surrey's Global Centre for Clean Air Research (GCARE) gathered and analysed four years of pollution data from 12 sites across Delhi, Haryana and Uttar Pradesh, with the aim of understanding how particulate matter (PM2.5 and PM10) and gases (oxides of nitrogen, sulphur dioxide, carbon monoxide and ozone) impact this area of India.

Despite the long-term nature of the study, the GCARE results show a clear trend with significantly higher levels of air pollutants in winter months than in summer or monsoon periods, with the exception of ozone levels. The high levels of fine and coarse particulate matter (PM2.5 and PM2.5-10) in winter months were attributed to fumes from crop burning upwind of Delhi and a likely increase in biomass burning for residential heating because most parts of the region do not have central heating systems.

The weather during winter months - particularly reduced precipitation and low wind speeds - is also thought to play a significant role in raising pollutant levels.

Crucially, the GCARE team also obtained meteorological data from each station for the duration of the study, allowing the examination of wind speeds and the direction of particulate matter using the Bivariate polar plot and k-mean clustering. The results of the team's analysis suggest that local sources of pollution, such as traffic, construction and domestic heating, influenced pollutant levels more than regional sources (air pollution from long-range traffic).

Professor Prashant Kumar, Founding Director of GCARE at the University of Surrey, said: "It is heartening to see the world come to terms with the fact that the climate change emergency should be at the top of every nation's agenda - not least India. Our analysis of Delhi's air pollution data over a significant period of time confirms that local sources of pollution - such as traffic and the heating of homes - are having a tremendous impact on air quality in the Delhi region. Moreover, the surrounding regions of Delhi are suffering substantial impacts during winter periods."

"The currently configured network of air pollution monitors does not permit the evaluation of long-range transport between Delhi and the NCR (and vice versa), highlighting a need for well-thought-out planning to expand the current network in the future. It is fair to hypothesise that on the one hand, solutions on a local level can go a long way towards improving air quality in one of the most heavily populated areas of India; on the other hand, there is a need for coordination with surrounding regions for effective control of air pollution sources. Moreover, given the dominance of local sources, efforts to control pollution are needed across the whole year, not just during winters, when the problem reaches its peak."

Credit: 
University of Surrey