Culture

The NASA/ESA Hubble Space Telescope's Wide Field Camera 3 observed Saturn on 20 June 2019 as the planet made its closest approach to Earth this year, at approximately 1.36 billion kilometres away.

Since the Hubble Space Telescope was launched, its goal has been to study not only distant astronomical objects, but also the planets within our Solar System. Hubble's high-resolution images of our planetary neighbours can only be surpassed by pictures taken from spacecraft that actually visit these bodies. However, Hubble has one advantage over space probes; it can look at these objects periodically and observe them over much longer periods than any passing probe could.

Saturn hosts many recognisable features, most notably its trademark ring system, which is now tilted towards Earth. This gives us a magnificent view of its bright icy structure. Hubble resolves numerous ringlets and the fainter inner rings. Dutch astronomer Christiaan Huygens first identified the rings in 1655 and thought they were a continuous disk encircling the planet, but we now know them to be composed of orbiting particles of ice and dust. Though all of the gas giants boast rings, Saturn's are the largest and most spectacular.

The age of Saturn's ring system continues to be debated. And, even more perplexingly, it's unknown what cosmic event formed the rings. There is no consensus among planetary astronomers today.

Another intriguing feature is the long-lasting hexagon-shaped structure circling the planet's north pole. It is a mysterious six-sided pattern caused by a high-speed jetstream. The hexagon is so large that four Earths could fit inside its boundaries (there is no similar structure at Saturn's south pole).

Other features, however, are not as long-lasting. A large storm in the north polar region spotted by Hubble last year has disappeared. Smaller, convective storms, such as the one just above the centre of the planet's image, also come and go.

Saturn's amber colours come from summer smog-like hazes, produced in photochemical reactions driven by solar ultraviolet radiation. Below the haze lie clouds of ammonia ice crystals, as well as deeper, unseen lower-level clouds of ammonium hydrosulphide and water. The planet's banded structure is caused by the winds and clouds at different altitudes.

Saturn's appearance changes with its seasons, caused by the planet's 27-degree axial tilt. This image was taken during summer in the planet's northern hemisphere.

Many of North America's migratory birds are declining, but the mysteries about when and how birds migrate must to be solved to effectively protect them. A new paper in The Auk: Ornithological Advances, published by Oxford University Press, identifies a previously overlooked area that is critical for conservation: the region between southern Mexico and Guatemala where songbirds fuel up for a grueling flight across the Gulf of Mexico.

Migration is a dangerous time for birds, especially during flights over large bodies of water. Many birds migrate directly across the Gulf of Mexico, requiring over 600 miles of sustained flight. The details of how the survivors manage this feat of endurance have been murky, especially for species like warblers, whose small size prevented researchers from tracking their full migration routes until recently.

Researchers used light-weight geolocators to identify migration strategies for the vulnerable and declining Golden-winged Warbler, finding 80% of individuals spent a week in southern Mexico and Guatemala to feed and build up reserves for the flight over the Gulf of Mexico in spring migration. The importance of this stopover region was previously unknown for this species, and it needs conservation given the rapid conversion of natural habitats to pasture and farmland.

While most Golden-winged Warblers stopped in this region, not all did. Some that overwintered in northern Central America were able to make the trans-Gulf flight directly from their overwintering grounds without the stopover. "This is an important finding," says Dr. Ruth Bennett of the Smithsonian Migratory Bird Center, "because birds that migrated directly across the Gulf were able to shave a week off their total migration time. These birds may experience a selective advantage in the spring." That is because male Golden-winged Warblers race north in spring migration to establish breeding territories. Results from the study suggest the spring period requires more energy and poses a greater risk of predation and starvation, while fall migration allows for more flexibility to minimize energy costs and avoid risks.

"The variation we describe in migration routes and stopovers is encouraging," says Bennett. "Variation helps buffer a population from local changes in environmental conditions." Now that authors have identified where and when Golden-winged Warblers prepare for migration, they can start identifying the habitats that best allow birds to fuel up and successfully cross the Gulf of Mexico. This study provides a critical piece of the larger puzzle about where, when, and how to best protect the declining Golden-winged Warbler and other North American migratory birds.

September 12, 2019 -- In a Lancet Psychiatry commentary, Drs. Morgan M. Philbin and Pia M. Mauro, assistant professors at Columbia University Mailman School of Public Health, offer their insights on the non-medical use of prescription drugs among U.S. young adults, and specifically on a study published by a team of researchers at the University of Michigan. The Michigan investigators, led by Dr. Sean McCabe, explored patterns and drivers of young adults' non-medical use of prescription drugs-- including prescription sedatives, opioids, or stimulants -- and their association with substance use disorder symptoms at age 35. These trajectories of prescription drug use were based on age of peak use and ranged from "rare misuse", the most prevalent trajectory, to peak use at age 27-28, which was most strongly associated with substance use disorder symptoms at age 35.

Compared to other age groups, young adults in the United States (aged 18-25 years) report the highest prevalence of non-medical use of prescription drugs in the past year (15 percent), binge drinking in the past month (37 percent), or illicit drug use in the past month (24 percent).

"Based on the high rates of polysubstance use that we are seeing across the U.S. there is an urgency to educate youth and young adults about potential consequences associated with the non-medical use of prescription drugs. In addition, it's important to discuss diversion, or the sharing of medications with peers," according to Philbin, PhD, in the Department of Sociomedical Sciences.

"There were differences in peak ages for use of opioids (29-30 years), compared to sedatives (35 years), and stimulants (27-28 years). This means that the aggregated peak of 27-28 years for any non-medical use of prescription drugs is not the absolute peak for all prescription drugs," discussed Mauro, PhD, assistant professor of Epidemiology. "A life course perspective could help disentangle polysubstance use patterns across different developmental periods," added Mauro.

Given the differences in age of peak use across substances - for example, younger ages for stimulants than for opioids and even later for sedatives or tranquilizers -- Philbin and Mauro highlight the need to incorporate polysubstance use screening and care linkage across the life course. "While methods remain challenging for adequately measuring the use of more than one substance, there are approaches one can take to more accurately understand patterns of use," they write.

While interventions play an important role in addressing polysubstance use among youth; language and terminology also matter. "For example, the ways that we, as researchers, describe substance use can directly influence perceptions about people who use drugs, and by extension impact access to screening and treatment, and the quality of medical encounters," said Philbin. "We should strive to disseminate research findings to the public in a way that increases clarity and reduces stigma. For example, using the term "non-medical substance use" instead of "misuse" can make a difference."

Mauro and Philbin's own research indicates that more than a third of young adults who use substances are not asked about illicit substance use by their providers. The measurement of polysubstance use and its consequences should incorporate also alcohol, observed Mauro and Philbin, a point also highlighted by Sean McCabe and colleagues at the University of Michigan.

"In summary, we believe in the importance of a multilevel intervention approach to minimize potential harms related to polysubstance use throughout the life course," said Philbin and Mauro. "At the individual level, health-care providers should screen patients and discuss clinically indicated treatment options. At the structural level, we feel that programs should expand access to medication, medication disposal, and harm reduction services, and ensure affordable and non-stigmatizing treatment."

DAVIS, CALIFORNIA, September 12, 2019--People have very individualized inflammatory responses to eating a high-fat meal.

These were the somewhat unexpected results of a study recently published in the Journal of Nutritional Biochemistry by researchers at the Agricultural Research Service (ARS) and their University of California-Davis colleagues.

"We looked at the inflammatory reactions of 20 volunteers at 0, 3 and 6 hours after eating a standardized meal containing 38 percent fat and their responses were completely unique. Like snowflakes, no two were exactly the same," explained molecular biologist Danielle G. Lemay at the ARS Western Human Nutrition Research Center in Davis, California.

Inflammation--defined as a group of responses by the body telling white blood cells how much to react--is a normal reaction to eating a meal, especially one with high amounts of fat. Inflammatory responses are not the same as the blood sugar reactions that also follow eating.

Inflammation is the defense mechanism in the body as the body attempts self-protection. It also is part of the body's immune response.

Each volunteer in the study had both a unique amount of inflammatory response and a unique amount of time for when the responses peaked, up to 6 hours after eating (8 or more hours is considered fasting by nutritionists).

The researchers used a very sensitive test to look at whether any genes in the human genome were turned off or on in order to define a volunteer's reactions. Responses by more than 13,000 genes differed between subjects.

The test meal was equivalent to someone having a small hamburger, small fries, and a small ice cream shake with fruit, according to the scientists.

"Eating a meal with this amount of fat is OK one or two days a week even considering the effect on inflammation. But in a lifetime of meal choices, eating like this every day could do some damage to a person's body," said Lemay.

Inflammation is associated with a whole host of conditions such as asthma, diabetes, peptic ulcers, rheumatoid arthritis, and many others.

One reason these results are so fascinating is the growing interest in personalized nutrition.

"We need to understand what the variability is between people before we can consider starting to set different requirements in diets," Lemay said.

A prehistoric crocodile that lived around 180 million years ago has been identified - almost 250 years after the discovery of it fossil remains.

A fossil skull found in a Bavarian town in the 1770s has been recognised as the now-extinct species Mystriosaurus laurillardi, which lived in tropical waters during the Jurassic Period.

For the past 60 years, it was thought the animal was part of a similar species, known as Steneosaurus bollensis, which existed around the same time, researchers say.

Palaeontologists identified the animal by analysing fossils unearthed in the UK and Germany.

The team, which included scientists from the University of Edinburgh, also revealed that another skull, discovered in Yorkshire in the 1800s, belongs to Mystriosaurus laurillardi.

The marine predator - which was more than four metres in length - had a long snout and pointed teeth, and preyed on fish, the team says. It lived in warm seas alongside other animals including ammonites and large marine reptiles, called ichthyosaurs.

The discovery of fossils in present-day Germany and the UK shows that the species could easily swim between islands, much like modern saltwater crocodiles, researchers say.

The study, led by Naturkunde-Museum Bielefeld in Germany, is published in the journal Acta Palaeontologica Polonica, It was supported by the Palaeontographical Society, Leverhulme Trust and the Natural Sciences and Engineering Research Council of Canada.

Sven Sachs, of the Naturkunde-Museum Bielefeld, who led the study, said: "Mystriosaurus looked like a gharial but it had a shorter snout with its nasal opening facing forwards, whereas in nearly all other fossil and living crocodiles the nasal opening is placed on top of the snout."

Dr Mark Young, of the University of Edinburgh's School of GeoSciences, who was involved in the study, said: "Unravelling the complex history and anatomy of fossils like Mystriosaurus is necessary if we are to understand the diversification of crocodiles during the Jurassic. Their rapid increase in biodiversity between 200 and 180 million years ago is still poorly understood."

New research led by the University of Kent shows that popular mobile phone games could provide a new tool to help doctors spot early signs of cognitive decline, some of which may indicate the onset of serious conditions like dementia.

Investigating the link between patterns of tap, swipe and rotational gestures during mobile game play and the users' cognitive performance, the research shows that the speed, length and intensity of these motions correlates with brain function. In particular, the performance of these gestures reveals key information about players' visual search abilities, mental flexibility and inhibition of their responses. They all offer clues about the individuals' overall brain health.

The results of the study, 'Exploring the Touch and Motion Features in Game-Based Cognitive Assessments', will be presented on Thursday 12 September at the 2019 ACM International Joint Conference on Pervasive and Ubiquitous Computing (UbiComp). Collaborators Dr Jim Ang, Jittrapol Intarasirisawat and Dr Christos Efsratiou from Kent's School of Engineering and Digital Arts; Luke William Feidham Dickens of University College London; and Rupert A. Page of Poole Hospital NHS Foundation Trust will present their findings.

Their research put 21 healthy participants through standard paper-based cognitive assessment tests, followed by 10-minute sessions of playing Tetris, Candy Crush Saga and Fruit Ninja over two separate periods, a fortnight apart. The three games selected were chosen because they are easy to learn, engaging for most players and involve intensive interactions using multiple gestures.

Using the sensors built into the mobile phones to collect data, the team showed how users interacted with the games and illustrated a clear link between the subjects' touch gestures, or taps and swipes, their rotational gestures and their levels of cognitive performance. The study revealed the participants' ability to perform visuo-spatial and visual search tasks, as well as testing their memory, mental flexibility and attention span.

The research team concluded that off-the-shelf, popular mobile games can provide an effective measure of brain function to spot changes in motor abilities which are commonly seen in patients with Alzheimer's Disease, stroke, traumatic brain injury, schizophrenia and obsessive-compulsive-disorder. Early detection of the signs of cognitive decline is crucial to effective treatment and prevention, as well as identification of individuals at risk of brain disease.

Furthermore, the study provides evidence of the potential to use mobile gameplay to detect changes in cognitive performance among athletes who are exposed to traumatic brain injuries, such as boxers, rugby players and footballers. Using mobile technology is not only quicker than the traditional paper-based format, but makes it easier to carry out regular, repetitive testing and is more engaging for the individuals under assessment. The games are also easily modified to test specific cognitive abilities and place greater demands on users.

Dr Ang, who is a senior lecturer in multimedia/digital systems, said: 'We are very encouraged by the results of our study and have since collected data from patients who showed signs of brain damage. This additional analysis reinforced the conclusions of our original research. We're now working to design an algorithm which can carry out automatic monitoring of individuals' cognitive performance while playing these games.'

A collaboration between the laboratories of Vincent Bonin (NERF, empowered by VIB, imec and KU Leuven) and Matthew Holt (VIB-KU Leuven Center for Brain & Disease Research) reveals that noradrenaline plays a key role in how astrocytes - star-shaped cells in the brain closely associated with neurons - track distinct information during behavior. The researchers found that astrocytes can integrate information on arousal state and sensory experience. The results are published in Current Biology.

Noradrenaline in the brain

When we are aroused the hormone noradrenaline is secreted, which helps us to better remember emotional situations compared to neutral ones. In earlier studies, noradrenaline was shown to directly influence synapses - information exchange points between neurons - in brain regions responsible for processing emotions. However, noradrenaline is released across the entire brain and stimulates a class of non-neuronal cells, astrocytes, which listen and respond to locally active neurons. A question remained: do astrocytes integrate this brain-wide signal with the specific activity of local neuronal networks?

Watching astrocytes

To answer this question, Drs. Michal Slezak (VIB-KU Leuven Center for Brain & Disease Research) and Steffen Kandler (NERF) used a special microscope to monitor the activity of astrocytes in mice. When mice were presented with visual stimuli, in some cases astrocytes faithfully responded. "It was so exciting! We know that if you check neuronal activity in the brain region receiving inputs from the retina that it exactly mirrors the movement of the visual stimulus. But this is the first time we saw this pattern when watching non-neuronal cells", says Dr. Bonin co-lead author of the study.

However, in some cases visual stimuli did not elicit any response from the astrocytes. The mystery was solved when each event of visual stimulation was analyzed independently - it turned out that astrocytes were active only when the mouse was in motion, and they were silent when the mouse was stationary. Slezak and Kandler further tested whether noradrenaline is the molecule responsible for this effect. They used a compound which depletes the brain of noradrenaline and found that astrocytic responses were largely decreased, even when mice were in motion. In other words, noradrenaline is necessary for astrocytes to respond to local stimulation: astrocytes are effectively integrating sensory and behavioral information.

Big impact of little-known cells

"This novel finding opens many additional questions. Previous studies on the action of noradrenaline on brain function focused entirely on neurons. Our data highlights that astrocytes can play a much more substantial role than previously thought", says Dr. Slezak.

"The idea that astrocytes respond to neuronal activity has been floating around for some time, but evidence for such a system has been lacking in vivo. Our work fills this gap. I just don't think anyone really expected that the response would be so heavily influenced by the behavioral state of the animal," adds Dr. Matthew Holt, joint lead author on the study. "We now have to work out how this operates at the molecular level and investigate the function consequences for the brain."

PULLMAN, Wash. - Washington State University researchers have for the first time grown the bacteria in a laboratory that causes Citrus Greening Disease, considered the world's most harmful citrus disease.

Being able to grow the elusive and poorly understood bacterium, Candidatus Liberibacter asiaticus (CLas), will make it easier for researchers to find treatments for the disease that has destroyed millions of acres of orange, grapefruit and lemon groves around the world and has devastated the citrus industry in Florida.

The researchers, including Phuc Ha, postdoctoral research associate, Haluk Beyenal, Paul Hohenschuh Professor in the Gene and Linda Voiland School of Chemical Engineering and Bioengineering, David Gang and Ruifeng He, from WSU's Institute of Biological Chemistry, Anders Omsland, from the Paul G. Allen School for Global Animal Health, and researchers from the University of Florida and University of Arizona, report on their work in the journal, Biofilm.

WSU was selected three years ago for a $2 million U.S. Department of Agriculture grant to study the bacteria, in part, because Washington has no citrus industry. The disease, formally known as Huánglóngbìng, (HLB), is spread by Asian citrus psyllids insects. It attacks the vascular system of citrus trees and causes fruit to become green, misshapen, and bitter-tasting.

A critical step in coming up with weapons to fight the disease is being able to study it in the lab, but the CLas bacterium is notoriously difficult to grow. With a small genome, CLas is thought to depend on very specific nutrient availability and possibly compounds secreted by other nearby bacteria. When researchers used a traditional rich media that they typically use for growing bacteria, they mostly grew bacteria other than CLas.

So, in order to conduct research, scientists have had to get bacterial samples directly from the trees themselves or from the insects that spread it, which is time-consuming and cumbersome. Trying to conduct experiments has also been difficult because, unlike neat lab cultures, bacterial samples gathered from a sick tree vary, depending on where and when the sample is gathered and the level of infection.

Without being able to grow the bacteria in a lab, researchers have been unable to even absolutely confirm that the bacteria, in fact, causes the disease.

In their paper, the researchers for the first time successfully established and maintained CLas bacterial cultures outside of its host.

Using infected citrus tissue as their starting point, the researchers developed a biofilm, a kind of bacterial city that allows a variety of bacteria to thrive. Instead of a rich growth medium that would crowd out the CLas, the researchers severely limited the growth of partner bacteria and created a medium with the specific nutrients, acidity, incubation temperatures, and oxygen levels that are optimal for CLas.

The CLas thrived - an important first step.

"We were really excited," said Beyenal, "but then we wondered if we could re-grow it."

The researchers were able to transfer the orange-colored culture and grow new cultures in their biofilm reactors, which they have maintained for more than two years.

"We can do this for as long as we want," said Beyenal.

Beyenal's group is now working to purify the culture, which will further help researchers to study it.  They are also developing genetic-based methods to understand and mitigate the spread of the disease.

A recent study led by researchers from the National University of Singapore (NUS) revealed that regular tea drinkers have better organised brain regions - and this is associated with healthy cognitive function - compared to non-tea drinkers. The research team made this discovery after examining neuroimaging data of 36 older adults.

"Our results offer the first evidence of positive contribution of tea drinking to brain structure, and suggest that drinking tea regularly has a protective effect against age-related decline in brain organisation," explained team leader Assistant Professor Feng Lei, who is from the Department of Psychological Medicine at the NUS Yong Loo Lin School of Medicine.

The research was carried out together with collaborators from the University of Essex and University of Cambridge, and the findings were published in scientific journal Aging on 14 June 2019.

Benefits of regular intake of tea

Past studies have demonstrated that tea intake is beneficial to human health, and the positive effects include mood improvement and cardiovascular disease prevention. In fact, results of a longitudinal study led by Asst Prof Feng which was published in 2017 showed that daily consumption of tea can reduce the risk of cognitive decline in older persons by 50 per cent.

Following this discovery, Asst Prof Feng and his team further explored the direct effect of tea on brain networks.

The research team recruited 36 adults aged 60 and above, and gathered data about their health, lifestyle, and psychological well-being. The elderly participants also had to undergo neuropsychological tests and magnetic resonance imaging (MRI). The study was carried out from 2015 to 2018.

Upon analysing the participants' cognitive performance and imaging results, the research team found that individuals who consumed either green tea, oolong tea, or black tea at least four times a week for about 25 years had brain regions that were interconnected in a more efficient way.

"Take the analogy of road traffic as an example - consider brain regions as destinations, while the connections between brain regions are roads. When a road system is better organised, the movement of vehicles and passengers is more efficient and uses less resources. Similarly, when the connections between brain regions are more structured, information processing can be performed more efficiently," explained Asst Prof Feng.

He added, "We have shown in our previous studies that tea drinkers had better cognitive function as compared to non-tea drinkers. Our current results relating to brain network indirectly support our previous findings by showing that the positive effects of regular tea drinking are the result of improved brain organisation brought about by preventing disruption to interregional connections."

Next step in research

As cognitive performance and brain organisation are intricately related, more research is needed to better understand how functions like memory emerge from brain circuits, and the possible interventions to better preserve cognition during the ageing process. Asst Prof Feng and his team plan to examine the effects of tea as well as the bioactive compounds in tea can have on cognitive decline.

Soybean is one of the most important crops worldwide. A high-quality reference genome will facilitate its functional analysis and molecular breeding. Previously, biologists from China (Chinese Academy of Science, University of Science and Technology of China, Jiangsu Academy of Agricultural Sciences, Berry Genomics Corporation) de novo assembled a high-quality Chinese soybean genome Gmax_ZH13 (Shen et al., 2018). However, due to technical limitations, a large number of small contigs were not anchored onto chromosomes.

Recently, the leader research group for Gmax_ZH13 genome project from the Institute of Genetics and Developmental Biology, Chinese Academy of Science, updated the Gmax_ZH13 genome to a golden reference genome Gmax_ZH13_v2.0.

Based on the Gmax_ZH13, by adding more sequence data and refresh assembly pipeline (Figure 1A), researchers finally assembled Gmax_ZH13_v2.0 with a length of 1,011,174,350 bp. Its assembly quality was increased dramatically. When compared to Gmax_ZH13, the Contig N50 size of Gmax_ZH13_v2.0 increased 6.5 times (from 3.46 Mb to 22.6 Mb), gap number decreased 1.8 times (from 815 to 448) and gap length decreased 8.8 times (from 20.49 Mb to 2.33Mb). Meanwhile, the un-anchored contig number decreased 17 times (from 549 to 36), resulting in the ratio of sequence that anchored to 20 chromosomes reaching 98%. All these assembly parameters indicated the high completeness of Gmax_ZH13_v2.0. Besides nuclear chromosomes, researchers assembled the circular genomes of chloroplast and mitochondria with a length of 152,220 bp and 513,779 bp respectively.

To improve the accuracy of gene annotation, in addition to Iso-seq reads used for Gmax_ZH13 annotation, researches performed RNA-seq and smRNA-seq for another 27 ZH13 samples, which were collected from different tissues at different developmental stages. They finally annotated 55,443 protein coding genes containing 96,366 mRNAs in the nuclear genome, 81 protein coding genes in the chloroplast genome and 49 protein coding genes in the mitochondrial genome. 97% of the 1,440 single copy Embryophyta genes in BUSCO_v3 were completely assembled, confirming the high quality of protein coding gene annotation. Besides that, non-coding genes were also annotated, including 297 rRNA, 1,112 tRNA, 166 snRNA 1,816 snoRNA and 35926 TE. Especially, 331 MIRNA genes and the mature miRNAs they produced were annotated by smRNA-seq data (Figure 1B).

Researchers also provided a detailed expression profiling for all protein coding genes and miRNAs they annotated (Figure 1C). These expression profiling data will be helpful for soybean fundamental research, for instance, searching expression pattern of individual genes or choosing tissue specific expression genes. Moreover, the data can be used to investigate the relationship of miRNAs and their target genes because they came from the same sample sets.

"We updated the Gmax_ZH13 genome to a more complete and continuous platinum reference genome Gmax_ZH13_ v2.0, did comprehensive annotation and provided detailed expression information for it", said Professor Zhixi Tian, the leader of the Gmax_ZH13 Chinese soybean genome project. "We believe that the new genome will greatly facilitate soybean fundamental research and molecular breeding."

Bottom Line: Patients with metastatic colorectal cancer harboring a subset of non-V600 mutations in the BRAF gene, known as class 3 BRAF mutations, were more likely to respond to anti-EGFR treatment.

Journal in Which the Study was Published: Clinical Cancer Research, a journal of the American Association for Cancer Research

Authors: Senior author Hiromichi Ebi, MD, PhD, chief of the Division of Molecular Therapeutics at the Aichi Cancer Center Research Institute in Nagoya, Japan; and first author Rona Yaeger, MD, medical oncologist at Memorial Sloan Kettering Cancer Center

Background: "Cancer genomic profiling is rapidly transforming the clinical management of cancer patients," said Ebi. "Results from our study indicate that metastatic colorectal cancer patients with certain BRAF mutations should be considered for anti-EGFR treatment, a new indication for this population of patients."

Alterations to the RAS signaling pathway, which controls key functions such as cellular proliferation and survival, is a known driver of oncogenesis. Mutations to BRAF, a kinase that interacts with RAS, can result in activation or amplification of the RAS signaling pathway. Roughly 10 percent of metastatic colorectal cancer tumors harbor mutations in the BRAF gene, noted Ebi.

BRAF mutations belong to one of three functional classes. Class 1 comprises BRAF V600 mutations. Non-V600 BRAF mutations are divided into two classes: class 2 mutations are RAS-independent, and class 3 mutations have enhanced binding to RAS and the kinase CRAF, resulting in increased RAS-dependent signaling.

While tumors with V600 BRAF mutations are often susceptible to RAF inhibitors, this therapeutic strategy is not predicted to be successful in tumors with non-V600 BRAF mutations, explained Yaeger. Prior smaller studies have shown that some patients with non-V600 BRAF-mutant colorectal cancer may respond to anti-EGFR treatment, she noted.

How the Study Was Conducted and Results: To determine if different functional classes of non-V600 BRAF mutations affected responses to anti-EGFR therapy, Ebi and colleagues retrospectively analyzed data from 40 patients with metastatic colorectal cancer whose treatment included an anti-EGFR therapy through an international multicenter collaboration. Using biochemical assays, the researchers classified the patients' tumors as having one of the two classes of non-V600 BRAF mutations: 12 patients had class 2 BRAF mutations and 28 patients had class 3 BRAF mutations. Patients from both groups had comparable clinical characteristics.

Eight percent of patients with tumors harboring class 2 BRAF mutations responded to anti-EGFR treatment regimens, compared with 50 percent of those with class 3 BRAF mutations.

The researchers also analyzed responses to anti-EGFR regimens based on treatment line. In the first- or second-line setting, 17 percent of patients with tumors harboring class 2 BRAF mutations responded to treatment, compared with 78 percent of those with class 3 BRAF mutations. In the third-line setting or later, no patients with class 2 BRAF mutations responded to treatment, compared with 37 percent of those with class 3 BRAF mutations.

Author's Comments: "Through the analysis of colorectal cancer tumors with specific BRAF mutations, we identified a potential new indication for anti-EGFR treatment, highlighting the power of precision oncology," noted Ebi.

Study Limitations: Limitations of the study include the small number of patients with metastatic colorectal cancer harboring class 2 or class 3 BRAF mutations. Additionally, because most of the patients analyzed in this study were also treated with chemotherapy, the researchers could not assess the efficacy of anti-EGFR monotherapy based on the functional class of non-V600 BRAF mutations, Ebi noted.

EAST LANSING, Mich. - Stems, leaves, flowers and fruits make up the biggest chunk of potential living space for microbes in the environment, but ecologists still don't know a lot about how the microorganisms that reside there establish and maintain themselves over the course of a growing season.

In a new study in Nature Communications, Great Lakes Bioenergy Research Center scientists at Michigan State University have focused on understanding more about the plant regions above the soil where these microbes can live, called the "phyllosphere." Ashley Shade, MSU assistant professor of microbiology and molecular genetics, and her lab classified core members of this community in two bioenergy cropping systems: switchgrass and miscanthus. In so doing, the group made important distinctions about how these communities assemble - and how they're connected to microbes in the soil.

Microorganisms that dwell in the phyllosphere are thought to play a role in their host's growth and health. And, like their subterranean kin, the topside microbiome affects how much phosphorus, nitrogen and other nutrients bioenergy crops can keep out of our waterways and atmosphere.

Shade says the first step in determining how to maximize production of these bioenergy crops is figuring out which taxa, or kinds of organisms, are long-term residents and which might just be passing through.

Pillars of the community

Shade and her colleagues wanted to ask two questions: does the phyllosphere microbiome change across seasons; and, if so, what role does the soil play in the yearly dance between plants and microbes? To find out, they tapped miscanthus and switchgrass fields at MSU's Kellogg Biological Station in Hickory Corners, established in 2008 as part of a GLBRC biofuel cropping system experiment.

Shade's lab members sampled microbial communities from bioenergy crop leaves every three weeks for one full growing season for miscanthus and two for switchgrass. They defined core microbes as those that consistently could be detected on leaves at the same time points across their fields, and that persistently appeared over sampling periods.

"If we found a microbe in one field, but not another, it couldn't be called a core member at that specific interval," she said. "We also expect these communities to change with the seasons, so we want to make sure we capture as many of those important taxa as possible."

It turns out that many core microbes on bioenergy plant leaves originate in the soil and are fairly consistent across seasons. This means the phyllosphere microbiome can be targeted for cultivation, just like the crops on which they grow.

The team identified hundreds of leaf microbiome members and compared them to thousands that live in the soil with a deep sequencing technique provided by the Joint Genome Institute, a Department of Energy Office of Science user facility.

"Because of our relationship to JGI, we were able to get some really good coverage of the diversity in our soil communities, something we couldn't have done on our own," Shade said.

Some microbes found at consistent but low levels in the soil turned out to be core members of leaf communities.

"This suggests that the leaf environment is a specific habitat where certain organisms fit," Shade said. "The fact that we find them in the soil means the ground is a possible reservoir for these taxa."

To evaluate the idea further, Shade and her team set up a statistical model to mimic results as if microbes were randomly distributed between a plant's leaves and the nearby soil, then compared the output to their real-life observations.

The models showed that, indeed, the microbial community on miscanthus and switchgrass leaves aren't distributed by chance.

"They're not just randomly blowing onto leaves and sticking, so something in the environment is selecting for these taxa above the soil," Shade said. "Because the patterns on the ground are different than the ones we see on the leaves, there's reason to believe many of these core leaf members are there on purpose."

Whittling down the taxa

The next step will be to home in on which of the core microbiome members have important functions for the plant.

"Now that we have a whole bunch of community data from the microbiome that includes thousands of taxa," Shade said, "we can understand which of these core members are just hanging out on the plant, and which ones have an impact on growth and health."

"If we can understand how that microbial community is changing its interactions with its host over a season, we might be able to leverage that to benefit the plant," she added.

It appears that when our nervous system is developing, only the most viable neurons survive, while immature neurons are weeded out and die. This is shown in a ground-breaking discovery by researchers at Karolinska Institutet in Sweden. The results indicate that the long-standing neurotrophic theory, which states that chance determines which cells will form the nervous system, needs to be revised.

During the early stages of the development of the nervous system, an excess of neurons is generated. At a certain time, a large portion of these cells then die, which is a necessary step for the proper formation of the nervous system. The process takes about 24 hours and in certain parts of the nervous system roughly half of all neurons disappear.

Researchers have previously believed this has been a random process, in which all cells have had an equal chance of survival. However, researchers from Karolinska Institute have now publishing a study in Nature Communications which shows that cell death instead appears to be controlled by a mechanism that weeds out the less fitted cells.

"The cells that survive are more mature and inclined to form synapses with other nerve cells", says Saida Hadjab, who has coordinated the study together with Francois Lallemend. They are both researchers at the Department of Neuroscience at Karolinska Institutet.

Several years ago, Hadjab and Lallemend noted that the early neurons are different. On the surface of them are receivers of growth factors that stimulate their survival. Hadjab and Lallemend discovered that certain neurons had more of these receivers than others. They started to suspect that cell death is somehow controlled, so that only certain selected cells survived.

They have now conducted with their team a detailed study of individual neurons in the early nervous system in mice and have among other things discovered which genes are active. Their mapping has revealed two distinct molecular patterns that determine the fate of these cells. The cells that are the most capable of growing and forming connections to other neurons survive, while the more immature cells die.

The study has been performed in the peripheral sensory nervous system. Whether cell death is controlled in the same way in other parts of the nervous system remains to be discovered.

"This discovery can help us understand the brain and the development of the nervous system on a different level. Earlier studies have mainly studied the environment surrounding the cell, and neuronal population as homogenous cell type. One has not examined the actual neurons individually, their fitness and how different they are", says Francois Lallemend.

This discovery could potentially be significant to the treatment of different neurological diseases. For example, in the case of Parkinson's Disease, doctors have tried to transplant healthy stem cells in patients, but the majority of cells die shortly after the treatment. It is possible that the treatment could become more successful if the less fitted cells were weeded out before the transplant, so that the patient was only given viable neurons.

Sophia Antipolis, 12 September 2019: Heart attack symptoms can be gradual or abrupt and both situations are a medical emergency. That's the main message of research published today in the European Journal of Cardiovascular Nursing, a journal of the European Society of Cardiology (ESC).1

The study found that patients with gradual symptom onset took eight hours to get medical help compared to 2.6 hours for those with abrupt symptoms. A maximum delay of two hours is recommended to get fast treatment and the best outcomes; serious complications and death are more likely beyond this window.2-4

Gradual symptoms begin with mild discomfort that slowly gets worse, while abrupt onset refers to sudden and severe pain from the start. "Both are a medical emergency and require urgent help," said study author Dr Sahereh Mirzaei of the University of Illinois at Chicago, US. "But our study shows that gradual symptoms are not taken seriously."

This was a secondary analysis of a prospective, multicentre study conducted in four US regions. The analysis included 474 patients presenting to the emergency department with acute coronary syndrome (myocardial infarction and unstable angina). Symptom characteristics and time from symptom onset to arrival in the emergency department were assessed using the ACS Patient Information Questionnaire.

Overall, the median gap between symptoms and arrival at the hospital was four hours. Symptoms came on abruptly in 56% of patients and emerged gradually in 44%. Both women and men sought medical help more quickly when they experienced abrupt pain.

"Nearly half of patients had a slow onset, so this is not uncommon," said Dr Mirzaei. "The symptoms of acute coronary syndrome are non-specific, and interpretation is often challenging for patients. Chest pain, chest discomfort, and chest pressure are warning signs that an artery may be blocked, and patients should call the emergency medical services immediately."

Symptoms were triggered by exertion in more than half (54%) of men with abrupt onset and a diagnosis of ST-elevation myocardial infarction (STEMI). This is a particularly serious type of heart attack requiring rapid restoration of blood flow to blocked arteries. Risky activities included climbing stairs, pulling, pushing, shovelling, heavy gardening, running, and jogging.

"Men with ischaemic heart disease or with multiple risk factors such as hypertension, diabetes, high cholesterol, or family history of heart disease should be aware that chest pain or discomfort after physical effort could be a heart attack," said Dr Mirzaei.

Arrival by ambulance was associated with a shorter interval between the start of pain and hospital arrival. Just 45% of patients called an ambulance, while more than half (52%) used their own transport and 3% were transferred from another hospital. Being uninsured was linked with a longer delay.

Dr Mirzaei said: "Chest pain or discomfort, whether severe and sudden or mild and slow, should not be ignored. Symptoms can also include pain in the throat, neck, back, stomach or shoulders, and may be accompanied by nausea, cold sweat, weakness, shortness of breath, or fear. Call an ambulance straight away; the sooner you get help, the better your prognosis."

PHILADELPHIA - From improving outcomes in children with brain cancer to lowering the risk of damage to the brainstem in children with central nervous system tumors, a pair of new studies published today add to the growing body of research showing the potential benefits of proton therapy. The first study, published in Pediatric Blood and Cancer, found that very young children who received proton therapy for medulloblastoma had higher rates of overall survival and recurrence free survival compared to patients who received intense chemotherapy without radiotherapy. The second study, published in Acta Oncologica, showed children with central nervous system tumors who received proton therapy with a newer technique called pencil beam scanning experienced a significantly lower rate of brainstem damage than patients treated with older proton techniques. Both studies were led by Christine Hill-Kayser, MD, an associate professor of Radiation Oncology at the Perelman School of Medicine at the University of Pennsylvania, a member of Penn's Abramson Cancer Center, and a pediatric oncologist in the Cancer Center at Children's Hospital of Philadelphia (CHOP).

Proton therapy has key differences from traditional photon radiation. Photon radiation typically uses multiple x-ray beams to attack a tumor target but unavoidably deposits radiation in the normal tissues beyond the target, potentially damaging those tissues as the beam exits the body. Proton therapy is an FDA-approved treatment that directs positively charged protons at the tumor, where they deposit the bulk of the radiation dose, with minimal residual radiation delivered beyond the target, potentially reducing side effects and damage to surrounding tissue.

The first study focused on children with newly diagnosed medulloblastoma - a cancer at the base of the skull. Older children - between the ages of four and 18 - with the disease generally receive radiation to the entire brain and spine; however, this treatment can be very toxic to the developing brains of very young children - ages four and younger. The youngest children with this disease thus typically receive intense chemotherapy regimens rather than radiation, but they can often relapse, and previous studies have shown the highest risk of relapse is tied to an area called the posterior fossa - the part of the base of the skull where the tumor is primarily located.

Researchers evaluated 14 young children who received proton therapy following surgery and chemotherapy. They found the five-year rate of overall survival was 84 percent, while the rate of recurrence-free survival was 70 percent. Historical data shows both rates are usually only between 30 and 60 percent in very young patients who do not receive radiotherapy.

"Our study, while small, shows promising outcomes when we use proton therapy to target just the area of surgery in these cases as opposed to radiating the whole brain and spinal areas," said the study's lead author Amardeep Grewal, MD, chief resident in Radiation Oncology at Penn.

The authors say further research is needed given the small cohort.

The second study deals with a new proton technique called pencil beam scanning (PBS), which is more effective at sparing healthy tissue than older proton techniques such as double scattered or uniform scanning. This study evaluated 166 patients with pediatric central nervous system tumors and found that at 24 months, the rate of patients experiencing brainstem tissue damage from PBS proton therapy is 0.7 percent. This is much lower than rates of serious brainstem toxicity historically reported in the literature after treatment with double scattered proton therapy.

"The effect of proton therapy on the brainstem has been a subject of much debate, but our data show that pencil beam scanning proton therapy does not increase the risk compared to conventional photon techniques," said the study's lead author Jennifer Hyatt Vogel, MD, who completed this work while she was a resident at Penn.

The authors say these data warrant further study, especially in high-risk patients and patients who have had prior radiation therapy.

"Regardless of technique, expertise in proton therapy planning and strict adherence to safety constraints is essential, particularly in treatment of tumors near the brainstem," Hill-Kayser said.