Brain

Genetic testing improves the diagnoses of abnormalities in developing babies that are picked up during ultrasound scans, scientists report today (31 January) in The Lancet. Scientists from the Wellcome Sanger Institute, University of Cambridge, University of Birmingham, Great Ormond Street Hospital (GOSH) and their collaborators used genome sequencing to improve the diagnoses of abnormalities detected by ultrasound by around 10 per cent. Without genomic information, these abnormalities may not have been diagnosed until after pregnancy, if at all.

The findings suggest that if the results from genome sequencing can be delivered in the timeframe of a pregnancy, then the additional diagnosis can support the care, counselling and the family's decision-making during pregnancy.

Approximately 3 per cent of pregnancies will have an abnormality in the structure of the developing baby, which is detected by a routine prenatal ultrasound scan. These can include problems with the baby's heart, brain, skeleton or in some cases, multiple organs.

Having detected a problem with the baby's development using prenatal ultrasound, parents will want to know the likely outcome for their child, however there can be many different possible causes of the abnormality.

In the largest study of its kind, researchers at the Wellcome Sanger Institute and their collaborators provided a genetic diagnosis for around 10 per cent of pregnancies with detected abnormalities. Without genetic testing, the genetic changes causing the developmental problem would not have been detected by standard diagnostic testing.

The research supports the mainstream use of more detailed genetic testing alongside other tests in order to provide better information to parents about how their child is likely to be affected.

Dr Matthew Hurles, from the Wellcome Sanger Institute, said: "Genetic testing gets to the root cause of some of the problems seen in ultrasound scans and can give families much clearer answers about a baby's condition. For example, a structural heart defect seen on an ultrasound scan could be caused by a disease that just affects the heart and may be relatively easily corrected, or it could be linked to something more complicated, such as neurological development, which could impact on the child's schooling in the future."

The research fell under the Prenatal Assessment of Genomes and Exomes (PAGE) study, which strives to gain a better understanding of genetic alterations, or variants, that cause developmental problems during pregnancy. The PAGE study aims to improve prenatal diagnostics, allow better genetics-derived prognoses and more informed parental counselling in the future.

Scientists worked with a national network of fetal medicine and genetics clinics around the UK to recruit pregnant mothers with an ultrasound scan anomaly that had been detected, for participation in the study.

The team completed whole-exome sequencing* on 610 developing babies with detected abnormalities and 1206 biological parents. DNA samples from the pregnancies were taken during routine checks for other conditions, such as Down syndrome, through procedures such as amniocentesis and chorionic villous sampling.

Researchers identified new diagnoses of known genetic disorders for 52 of the 610 pregnancies, or 8.5 per cent. The team found that genetic diagnoses were considerably more common in fetuses with heart defects, skeletal abnormalities or multi-organ problems, which could lead to some ultrasound findings being prioritised for genetic testing.

Professor Eamonn Maher, from the University of Cambridge, said: "More genetic diagnoses were made for developing babies with problems surrounding the heart, skeleton or multiple organs, indicating that in the future genetic testing to make diagnoses may be tailored according to the type of problem."

Lyn Chitty, Professor of Genetics and Fetal Medicine at GOSH and the UCL Great Ormond Street Institute of Child Health (ICH), said: "The study shows that genome sequencing improves the diagnosis of genetic conditions in developing babies who have been found to have structural abnormalities during a routine ultrasound. Making these results available during pregnancy means we can offer better counselling to parents and enable access to appropriate care. The next step is to work on implementing this approach nationally so more families can benefit."

Professor Mark Kilby, of the University of Birmingham's Institute of Metabolism and Systems Research and Clinical Lead in Fetal Medicine at Birmingham Women's and Children's NHS Foundation Trust, said: "We hope that our research will aid NHS England's ambition to roll out by next summer the use of invasive and then later non-invasive technology to perform exome sequencing in the generic or targeted screening of babies for congenital abnormalities during pregnancy."

The results from this study were fed back to the families via their genetic counsellors to help them decide on treatment or management for the condition. Most of the diagnoses made were of conditions that have a low risk of recurrence in future pregnancies.

Jane Fisher, Director of the Antenatal Results and Choices charity, said: "When expectant parents are told from a scan that their baby is not developing as expected, it most often comes as a huge shock and they are anxious to know as much as possible about what is ahead. A genetic diagnosis can help provide them with important information about the outlook for their baby and whether they might face a similar situation in future pregnancies."

Restaurants frequently serve oversized meals, not only in the United States but also in many other countries, according to a study conducted by an international team of researchers and supported by FAPESP - São Paulo Research Foundation.

Published in the British Medical Journal, the study weighed and measured the energy content of meals served by restaurants in Brazil, China, Finland, Ghana and India.

The results showed that 94% of the most popular main dishes served in sit-down restaurants and 72% of those purchased over the counter from fast food outlets contained more than 600 kilocalories (kcal), the benchmark recently recommended by the United Kingdom's National Health Service (NHS) to help reduce the global obesity epidemic.

The researchers found a significant correlation between meal weight and energy content. They concluded that some popular meals were both far larger and more caloric than necessary.

Examples include Brazil's traditional rice, beans, chicken, cassava and salad with a bread roll (841 g and 1,656 kcal); Ghana's classic fufu, goat and soup (1,105 g and 1,151 kcal); and India's popular mutton biryani (1,012 g and 1,463 kcal).

"Obesity is a world health problem caused by several factors, such as sedentary living, processed food and sugar intake, and overeating. Many people may confuse food craving with hunger. This study shows that any strategy to combat obesity should also consider these excesses," said Vivian Suen, a professor in the Department of Clinical Medicine at the University of São Paulo's Ribeirão Preto Medical School (FMRP-USP), who is a coauthor of the article.

The World Health Organization (WHO) considers obesity a global epidemic and a major risk factor for heart disease, stroke and diabetes, among other diseases. It estimates that 1.9 billion adults are overweight and 600 million are obese worldwide.

According to the study, the selected restaurant and fast food meals supplied between 70% and 120% of the daily energy required by a sedentary woman - approximately 2,000 kcal - except in China, where the energy content of the most popular meals was significantly lower.

"The study did not take into account the mode of preparation or the nutritional composition of the meals analyzed. The fact is that many people who patronize these restaurants are overeating," Suen said.

The researchers measured the energy content of a representative sample of 223 popular meals purchased from 111 randomly selected sit-down restaurants and fast food outlets located in the following five cities: Ribeirão Preto (Brazil), Beijing (China), Kuopio (Finland), Accra (Ghana) and Bangalore (India).

They compared these findings with data from restaurants in Boston (USA) extracted from previous studies by Tufts University. The restaurants and fast food outlets were located within an area of 25 square kilometers around each participating research center.

"The findings refute two widely held ideas. We're not just eating the wrong foods but also overeating, and in terms of calories, a meal considered healthy may often increase the organism's energy balance and hence add more weight than a fast food meal," Suen said.

The results showed that the energy content of a fast food meals was lower on average (809 kcal) than that of a sit-down restaurant meal (1,317 kcal). However, the study was far from being a defense of fast food outlets.

"It can be taken as a warning that while we're focusing on fast food and campaigns to encourage healthy eating, all of which is positive and necessary, we're overlooking important factors such as the sheer amount of food we eat, which can also have a major impact on global obesity," Suen said.

Compensation

Oversized portions also have an effect on the so-called compensation mechanism, Suen explained.

"When nonobese people have a large midday meal, they normally feel less hungry in the evening and eat less for dinner, for example," she said. "However, obese people appear not to have this perception, as has been found in several studies by the research group at Tufts University. Therefore, this regulation in terms of eating less in the next meal doesn't happen in obese individuals."

Another problem with obesity is the organism's resistance to weight loss.

"There are countless diets - low carb, high protein, low fat, and so on - but which is best for weight loss? No one truly knows. What matters in the long term is total energy content in terms of calories.

Food quality is also important, of course. Eating low-quality carbohydrates such as saturated fat or large amounts of sugar contributes to diseases associated with excessive intake of these products. Weight gain is associated with excessive calorie intake," Suen said.

An international team of researchers has performed molecular analysis on fossil feathers from a small, feathered dinosaur from the Jurassic. Their research could aid scientists in pinpointing when feathers evolved the capacity for flight during the dinosaur-bird transition.

Anchiornis was a small, feathered, four-winged dinosaur that lived in what is now China around 160 million years ago - almost 10 million years before Archaeopteryx, the first recognized bird. A team of researchers from the Nanjing Institute of Geology and Paleontology, North Carolina State University, and the University of South Carolina analyzed Anchiornis feathers to see how they differed at the molecular level from those of younger fossil birds and modern birds.

"Modern bird feathers are composed primarily of beta-keratin (β-keratin), a protein also found in skin, claws, and beaks of reptiles and birds. Feathers differ from these other β-keratin containing tissues, because the feather protein is modified in a way that makes them more flexible," says Mary Schweitzer, professor of biological sciences at NC State with a joint appointment at the North Carolina Museum of Natural Sciences and co-author of a paper describing the research.

"At some point during the evolution of feathers, one of the β-keratin genes underwent a deletion event, making the resultant protein slightly smaller. This deletion changed the biophysics of the feather to something more flexible - a requirement for flight. If we can pinpoint when, and in what organisms, that deletion event occurred, we will have a better grasp on when flight evolved during the transition from dinosaurs to birds."

The researchers, led by Yanhong Pan, a visiting researcher from the Nanjing Institute, examined fossilized feathers from Anchiornis, using high-resolution electron microscopy, as well as multiple chemical and immunological techniques to determine the molecular composition of the feathers. They did the same to other feathers from the Mesozoic and Cenozoic eras, as well as other β-keratin tissues not expected to show this deletion, then compared results with modern bird feathers and tissues.

They found that Anchiornis feathers were comprised of both β-keratins and alpha-keratins (α-keratins), a protein all terrestrial vertebrates have, including mammals. This was surprising because α-keratin is present in only small amounts in modern feathers. In addition to co-expressing both keratin proteins, the Anchiornis feathers had already undergone the deletion event that sets feathers apart from other tissues.

"Molecular clocks, which scientists use as benchmarks for evolutionary and genetic divergence, predict that the deletion, and thus functional flight feathers, evolved around 145 million years ago," Schweitzer says. "Anchiornis is millions of years older, yet has the shortened protein form. This work shows that we can utilize molecular fossil data to root molecular clocks and improve their accuracy - we can start to put timing on genetic events in the dinosaur-bird transition via absence or presence of these two keratins. The data also give us more information about how feathers evolved to enable flight."

The work appears in Proceedings of the National Academy of Sciences. Pan is lead author. Wenxia Zheng and Elena Schroeter of NC State and Roger Sawyer from the University of South Carolina also contributed to the work, which was supported in part by the National Science Foundation and the Packard Foundation.

Anchiornis, one of the earliest feathered dinosaurs ever discovered, was found to have the ability to fly. However, could it fly like birds today? A new study published in the Proceedings of the National Academy of Sciences (PNAS) by researchers from China and the U.S. says no.

The flight feathers of modern birds are mainly composed of β-keratin, which gives them special biomechanical properties (such as flexibility, elasticity and strength) to meet the needs of flight.

Dr. PAN Yanhong from the Nanjing Institute of Geology and Palaeontology of the Chinese Academy of Sciences (NIGPAS) and her colleagues used electron microscopy and chemical analyses to compare flight feathers of Anchiornis with those of a chicken and four other feathered dinosaur and fossil birds.

They found that Anchiornis feathers were predominated by thicker α-keratins rather than thinner β-keratins, and lacked the biomechanical properties needed for flight, although they did contain some of the necessary molecular structures as indicated by the presence of feather β-keratins.

On the other hand, Pan and colleagues also showed that the flight feathers of Chinese Mesozoic birds such as Eoconfuciusornis and Yanornis, as well as a Cenozoic bird, were mainly composed of β-keratins, as in modern birds.

The findings suggest that even though Anchiornis feathers were not suitable for powerful flight, their molecular composition may signify an intermediate stage in the evolution of avian flight feathers.

Researchers from NIGPAS, the Institute of Vertebrate Paleontology and Paleoanthropology of the Chinese Academy of Sciences, Linyi University, North Carolina State University, and South Carolina State University participated in the study. It was supported by the Chinese Academy of Sciences and the National Natural Science Foundation of China.

HOUSTON - Researchers at The University of Texas MD Anderson Cancer Center have discovered an immune regulator that appears to dictate glioblastoma (GBM) progression by shutting down immune surveillance, indicating a potential new area of therapeutic investigation.

Findings from the preclinical study led by Shulin Li, Ph.D., professor of Pediatrics, and Amy Heimberger, M.D., professor of Neurosurgery, were published in the Jan. 25 online issue of Nature Communications.

"Classical wisdom is that brain tumor progression is linked to oncogene activation and tumor suppressor gene inactivation; however genetic and epigenetic mutations are not the only cause of GBM progression," said Li. "Some immune regulators can do the same thing and are key regulators of cancer, especially in certain tissues and environmental contexts."

GBM, unlike melanoma and lung cancers, does not attract robust T cell immune responses, and, so far, immunotherapies have had little success against it. GBM is considered "immunologically cold" or unreactive likely due to tumor elaborated immune suppressive factors.

Findings from the study indicate FGL2 (fibrinogen-like protein 2), which is known for suppressing the immune system, is highly expressed in GBM. Investigators showed that inactivating or "knocking out" FGL2 from the tumor cells can eliminate tumor progression in mice with intact immune systems. Understanding this type of expression is key to discovering causes of GBM progression.

First author Jun Yan, Ph.D., a research scientist, showed the FGL2 present in tumor cells controls a specialized group of dendritic cells which activates T cells. More specifically, FGL2 secreted from tumor cells prevents the differentiation of a special subpopulation of CD103 dendritic cells that are essential for triggering the activation of the tumor killing T cells. The study also showed these dendritic cells must find a way to the tumor microenvironment in the central nervous center (CNS) in order to activate the T cells.

"This study is important because it shows that the immune system must interact in the CNS and in the tumor to be effective. Previously, this interaction was only thought to be necessary in specialized immune organs such as the lymph nodes," said Heimberger. "It also shows a new mechanism of immune suppression that hasn't been described before, and it further supports how important FGL2 is to this disease."

The team also analyzed human GBM from The Cancer Genome Atlas and found that lower levels of FGL2 protein expression coupled with high levels of GM-CSF or IFN, DC differentiation inducer or T cell activator, are associated with longer survival of GBM patients.

Li and Heimberger are actively working on therapeutic strategies to target FGL2.

HOUSTON - (Jan. 24, 2019) - Nearly 1 in 5 fifth-graders has received violent injuries, the majority delivered by guns or knives, according to recently published research by The University of Texas Health Science Center at Houston (UTHealth).

The study, published in the Journal of Adolescent Health, analyzed data from 4,300 children when they were in fifth, seventh, and 10th grades at public schools in districts in and around cities in three U.S. communities: Houston, Los Angeles County, and Birmingham, Alabama. The children were questioned over time to see whether the number and type of injury changed.

The likelihood of injury increased as children became older, with 1 in 3 high school-age children sustaining a gunshot, stabbing wound, or assault-related injury needing medical attention.

According to the U.S. Centers for Disease Control and Prevention (CDC), which funded the research, bullying is common in high schools nationwide. These findings shed new light on the type of injuries occurring among children and who is most affected - bullies or victims of bullying.

"The biggest surprise was the sheer scale of intentional violent injuries children are suffering, even at elementary school age. It was also unexpected to discover how it's not bullying victims, but bullies themselves who are most likely to get seriously hurt," said first author Katelyn Jetelina, PhD, MPH. "This suggests the act of bullying may not necessarily be violent enough for victims to sustain serious injuries, and that bullies may be involved in other harmful behaviors." Jetelina is an assistant professor of epidemiology, human genetics, and environmental sciences at UTHealth School of Public Health in Dallas.

"It's a first-of-its-kind look at how the injuries are sustained among school-age children and whether these are different for repeat bullying victims and repeat perpetrators," Jetelina said. "The interviews were conducted privately to improve reliability, but underreporting is still a potential issue, so the problem could be even worse."

Data were obtained from Healthy Passages, a study of children and their primary caregivers followed from fifth through 10th grade between 2004 and 2011. That study's principal investigators were Susan Tortolero Emery, PhD, of UTHealth School of Public Health; Susan Davies, PhD, of The University of Alabama at Birmingham Center for the Study of Community Health; and Mark Schuster, MD, PhD, of Kaiser Permanente School of Medicine, who is also senior author of this paper.

In fifth grade, 16.7 percent of children sustained at least one violent injury including firearm injuries (12.5 percent), knife injuries (8.4 percent), and medically attended fighting-related injuries (3.6 percent). The volume and type of injury escalated in later years, especially among bullies.

On average, bullies were 41 percent more likely to be violently injured than other children. By 10th grade, more than a quarter of their injuries were from firearms, the research showed.

"The evidence suggests perpetrators are engaging in various risky behaviors in addition to bullying. This builds as they get older, which may indicate involvement in gangs, as well as drug and alcohol use," Jetelina said.

Boys were 22 percent more likely to sustain violent injury than girls, and black children were 30 percent more likely to experience injury than other race/ethnicity groups, according to the results of the study. Children from lower-income families were also more vulnerable. Those whose parents were widowed had a 60 percent higher chance of reporting a violent injury, Jetelina reported.

"Injury is a leading cause of death for schoolchildren and this research reflects the epidemic. It also underlines the importance of early intervention and prevention strategies that target specific groups," Jetelina said. "Future studies examining factors such as weapon access and gang involvement are necessary to understand more about the pathway of bully perpetrators, why they are being injured so much, and what can be done to stop this spiraling problem."

BINGHAMTON, N.Y. - Water splitting, the process of harvesting solar energy to generate energy-dense fuels, could be simplified thanks to new research including faculty at Binghamton University, State University of New York.

"The key idea is to generate a solar fuel: hydrogen gas, which can be burnt to release energy on demand without releasing carbon dioxide," said Binghamton University Associate Professor of Physics Louis Piper. "For water splitting, we use visible light to generate photo-excited negative electrons and positive holes that are then separated in order to catalyze water into oxygen and hydrogen gases. Storing gases is more straightforward (and cheaper) than employing battery set-ups, so this approach has the benefit of clean energy harvesting and storage."

A research team including Piper figured out how "doping" (or adding metal ions) into vanadium pentoxide (M-V2O5) nanowires raises the highest filled energy levels for more efficient hole transfer from the quantum dots to nanowires i.e. separation of the photo-excited electrons and holes.

"If you don't dope, then there is a buildup of positive holes that corrode the quantum dots (referred to as photo-corrosion)," said Piper. "Using computation and chemical intuition, we predicted doping with Sn2+ ions would result in excellent energy alignment and efficient charge separation. We saw a ten-fold increase in the amount of solar-harvested hydrogen we obtained."

The researchers are now working with their collaborators at University of Buffalo and Texas A&M University to enhance the hydrogen gas evolution by decorating the quantum dots with platinum.

"We expect platinum to improve things by acting as a catalytic site for the electrons, but our ultimate goal is to find less costly alternatives to decorate with," said Piper.

Researchers at Diamond Light Source and Brookhaven National Laboratory also contributed to this paper.

The freshwater Hydra is able to regenerate any part of its body to rebuild an entire individual. The small polyp has a development organizer center located at the head level, and another located in the foot. The head organizer performs two opposite activities, one activating, which causes the head to differentiate, and the other inhibiting, which prevents the formation of supernumerary heads. Researchers at the University of Geneva (UNIGE), Switzerland, have discovered the identity of the inhibitor, a protein called Sp5, and deciphered the dialogue between these two antagonistic activities, which helps maintain a single-headed adult body and organize an appropriate regenerative response. Published in the journal Nature Communications, their study points out that this mechanism has been conserved throughout evolution, both in Hydra and in humans. Sp5 could therefore be an excellent candidate to be tested as an inhibitor of human tumors in which the activator pathway is the motor of proliferation.

Often considered immortal, the freshwater Hydra has a prodigious regenerative power, discovered by the Geneva naturalist Abraham Trembley nearly 300 years ago. Any fragment of the body with a few thousands cells can regenerate the entire animal, which measures about one centimeter. "Regeneration of the head relies on the transformation of the stump into a tissue called the head organizing centre, which has developmental properties and, like an architect, directs the construction of the future head", explains Brigitte Galliot, professor at the Department of Genetics and Evolution of the UNIGE Faculty of Science.

How the dialogue between Yin and Yang takes shape

The head organizer carries out two opposite activities, one activating and the other inhibiting. The first induces the differentiation of stem cells into specialized head cells. The activator is a growth factor called Wnt3, whose action allows the initiation of a three-dimensional cell differentiation program that enables the construction of the head. Thus, in the absence of Wnt3, the head regeneration program cannot proceed. The inhibitory activity, produced under the control of the activator activity, prevents the formation of supernumerary heads. "These two antagonistic activities establish a dialogue between them, but we knew neither the identity of the inhibitor nor the nature of this dialogue", says the biologist.

Using the results of a study conducted by a German team on the planarian flatworm, the biologists developed a gene screening strategy to identify this inhibitor. "We started from 124 candidates who met specific criteria to single out a unique winner, who met all of them. It is a gene that codes for a protein called Sp5", says Matthias Vogg, researcher at the Department of Genetics and Evolution of the UNIGE Faculty of Science and first author of the study. The scientists then demonstrated that Sp5 binds to the regulatory region of the gene that codes for Wnt3, blocks its expression and thus the formation of the head.

The seven heads of the freshwater Hydra

How does the dialogue between the activator pathway and the inhibitor work? "We have quantified the expression of the genes encoding Wnt3 and Sp5 in different parts of the body of intact or amputated Hydra, and discovered that a regulatory loop between the two activities is established according to the location and quantity of each gene expressed", notes Brigitte Galliot. Thus, in intact animals, the growth factor Wnt3 will be mainly present at the tip of the head, while Sp5 will be primarily active in the surrounding area, to prevent the appearance of other heads.

When researchers block the expression of Sp5, Hydra polyps, intact or regenerating, develop multiple heads, all perfectly functional, their tentacles apprehending the food to lead it to the mouth. "We also replicated these results from Hydra polyps whose cells had been completely dissociated from each other, then reaggregated and left in culture: multi-headed Hydra re-formed completely in four to five days", explains Matthias Vogg.

In humans, the cell signaling pathway activated by Wnt3 is mainly active during embryonic development, as well as in different types of tumors in adults. If the inhibitory effect of Sp5 is confirmed in our species, this protein could be a candidate treatment targeting cancer cells that use the Wnt3 pathway to proliferate.

In discovering a mutant gene that "turns on" another gene responsible for the red pigments sometimes seen in corn, researchers solved an almost six-decades-old mystery with a finding that may have implications for plant breeding in the future.

The culmination of more than 20 years of work, the effort started when, in 1997, Surinder Chopra, professor of maize genetics at Penn State, received seeds from a mutant line of corn. At the time, Chopra was a postdoctoral scholar at Iowa State University, and he brought the research with him when he joined the Penn State faculty in 2000.

The mystery involved a spontaneous gene mutation that causes red pigments to show up in various corn plant tissues, such as kernels, cobs, tassels, silk and even stalks, for a few generations and then disappear in subsequent progeny. It might seem like a minor concern to the uninitiated, but because corn genetics have long been studied as a model system, the question has significant implications for plant biology.

"In corn, genes involved in pigment biosynthesis have been used in genetic studies for more than a century -- pigmentation in corn is a relatively simple trait, which makes it ideal for use as a marker for genetic research," Chopra said. "The mutant corn plants were identified in 1960 by Dr. Charles Burnham (University of Minnesota), and that seed was given to one of his students, Derek Styles. We received the seed from Styles in 1997, and we were entrusted to continue the research."

Chopra led efforts to introgress the genes from the mutant corn, dubbed Ufo1 -- Unstable factor for orange1 -- into various inbred corn lines to be studied. Since he came to Penn State, Chopra's research group in the College of Agricultural Sciences has grown and backcrossed lines of corn plants at both the Penn State Agronomy Farm and in greenhouses on campus. In the last three years, the researchers, who recently published their findings in The Plant Cell, have grown more than 4,000 of the backcrossed plants to map where the cause of Ufo1 is located in the genome.

Using tissues from those hybrid plants, and employing RNA-sequencing techniques and gene-cloning tools along with next-generation sequencing, genetic mapping, and data-analysis capabilities not available to plant geneticists until relatively recently, researchers unmasked the culprit in the on-again, off-again, red-pigment-in corn mystery. They found Ufo1, which is only present in corn, sorghum, rice and foxtail millet.

But the Ufo1 mutant gene does not actually cause the red pigments to appear in corn -- that is caused by a gene called the pericarp color1, or p1. Researchers found that the Ufo1 gene is actually controlled by a transposon -- "jumping gene" -- that sits close to the Ufo1 gene. Transposons are sequences of DNA that move from one location in the genome to another, and can influence the expression of nearby essential genes.

When this transposon is switched on, the Ufo1 gene is also turned on, which triggers the p1 gene to signal the plant to produce the red pigments. But when the transposon is off, the Ufo1 gene goes silent and so does the p1-controlled pigment pathway. That is the main reason the Ufo1 gene went unidentified for so long and the mystery persisted, according to Chopra.

"We were able to narrow it down to a single gene out of several thousand genes that are aberrantly expressed in the Ufo1 mutant versus the wild-type plant," he said. "It is an incremental discovery, and yet it is a leap in basic science because it is likely to be valuable to plant breeders."

It is still not entirely clear how Ufo1 interacts with the p1 gene. The discovery's future significance likely will be less associated with red pigments than what the Ufo1 mutant gene controls in corn plants. Chopra believes it may be a "master regulator" that, when overexpressed, signals the plant that it is under stress, even in the absence of stress. Interestingly, Chopra pointed out, in Ufo1 plants, sugars over-accumulate in leaves, and the content of maysin, a natural insecticide made by corn plants, sharply increases in the silk.

"Learning about what controls the regulation of the normal or the non-mutant Ufo1gene will bring us much closer to a realistic breeding process in which we can tinker with gene expression to get higher maysin content or increased sugar content, which would be important in crop protection from pests and biofuel production, respectively," Chopra said.

"And, because it has a pronounced effect on the workings of the cellular machinery, we can now understand further the basic molecular pathway that normally happens during a stress to a plant," he said. "Understanding plant stress resulting from extremes of heat, cold and water is important because of climate change."

Electronegativity is one of the most well-known models for explaining why chemical reactions occur. Now, Martin Rahm from Chalmers University of Technology, Sweden, has redefined the concept with a new, more comprehensive scale. His work, undertaken with colleagues including a Nobel Prize-winner, has been published in the Journal of the American Chemical Society.

The theory of electronegativity is used to describe how strongly different atoms attract electrons. By using electronegativity scales, one can predict the approximate charge distribution in different molecules and materials, without needing to resort to complex quantum mechanical calculations or spectroscopic studies. This is vital for understanding all kinds of materials, as well as for designing new ones. Used daily by chemists and materials researchers all over the world, the concept originates from Swedish chemist Jöns Jacob Berzelius' research in the 19th century and is widely taught at high-school level.

Now, Martin Rahm, Assistant Professor in Physical Chemistry at Chalmers University of Technology, has developed a brand-new scale of electronegativity.

"The new definition is the average binding energy of the outermost and weakest bound electrons - commonly known as the valence electrons," he explains.

"We derived these values by combining experimental photoionization data with quantum mechanical calculations. By and large, most elements relate to each other in the same way as in earlier scales. But the new definition has also led to some interesting changes where atoms have switched places in the order of electronegativity. Additionally, for some elements this is the first time their electronegativity has been calculated."

For example, compared to earlier scales, oxygen and chromium have both been moved in the ranking, relative to elements closest to them in the periodic table. The new scale encompasses 96 elements, a marked increase from previous versions. The scale now runs from the first element, hydrogen, to the ninety-sixth, curium.

One motivation for the researchers to develop the new scale was that, although several different definitions of the concept exist, each is only able to cover parts of the periodic table. An additional challenge for chemists is how to explain why electronegativity is sometimes unable to predict chemical reactivity or the polarity of chemical bonds.

A further advantage of the new definition is how it fits into a wider framework that can help explain what happens when chemical reactions are not controlled by electronegativity. In these reactions, which can be hard to understand using conventional chemical models, complex interactions between electrons are at work. What ultimately determines the outcomes of most chemical reactions is the change in total energy. In the new paper, the researchers offer an equation where the total energy of an atom can be described as the sum of two values. One is electronegativity, and the second is the average electron interaction. The magnitude and character of these values as they change over a reaction reveals the relative importance of electronegativity in influencing the chemical process.

There are endless ways to combine the atoms in the periodic table to create new materials. Electronegativity provides a first important indicator of what can be expected from these combinations.

"The scale is extensive, and I hope it will greatly affect research in chemistry and material science. Electronegativity is routinely used in chemical research and with our new scale a number of complicated quantum mechanical calculations can be avoided. The new definition of electronegativity can also be useful for analysing electronic structures calculated through quantum mechanics, by making such results more comprehensible," says Martin Rahm.

Idling in a long highway line of slowed or stopped traffic on a busy highway can be more than an inconvenience for drivers and highway safety officers.

It is one of the most vulnerable times for "secondary accidents," which often can be worse than an original source of the slowdown, according to the U.S. Department of Transportation's Federal Highway Administration. In fact, secondary crashes go up by a factor of almost 24 during the time that highway safety officials are assessing and documenting the crash site.

In 2016, there were more than 7 million police-reported traffic crashes in which 37,461 people were killed and an estimated 3,144,000 were injured, according to the U.S. Department of Transportation National Highway Traffic Safety Administration. Crash assessments could be safer, faster and more accurate through a Purdue-developed drone technology. In 2016, there were more than 7 million police-reported traffic crashes in which 37,461 people were killed and an estimated 3,144,000 were injured, according to the U.S. Department of Transportation National Highway Traffic Safety Administration.

"It's the people at the back of the queue where you have traffic stopped who are most vulnerable and an approaching inattentive driver doesn't recognize that traffic is stopped or moving very slowly until it is too late," said Darcy Bullock, the Lyles Family Professor of Civil Engineering and Joint Transportation Research Program director at Purdue University. "The occurrence of these secondary crashes can be reduced by finding ways to safely expedite the clearance time of the original crash."

Conventional mapping a severe or fatal crash can take two to three hours depending on the severity of the accident, according to Bullock.

"Our procedure for data collection using a drone can map a scene in five to eight minutes, allowing public safety officers to open the roads much quicker after an accident," said Ayman Habib, Purdue's Thomas A. Page Professor of Civil Engineering, who developed the photogrammetric procedures and envisions even more uses for the technology.

The technology is already in use. The Tippecanoe County Sheriff's Office used drones to map crash scenes 20 times in 2018 and another 15 times in the same year to support specialty law enforcement teams throughout Tippecanoe County and in neighboring counties and jurisdictions.

"Overall, it can cut 60 percent off the down time for traffic flow following a crash," said Capt. Robert Hainje of the Tippecanoe County Sheriff's Office.

Bullock, Habib and colleagues from Tippecanoe County Sheriff's Office presented their findings on Jan. 14 at the annual Transportation Research Board meeting in Washington, D.C., in the "Traffic Law Enforcement: Innovative Tools, Policy and Countermeasures for Law Enforcement Safety" session. A video about the technology can be viewed here.

"The collaboration with Purdue faculty and students has been tremendously effective in helping our law enforcement, first responders and special teams," Hainje said. "The drone technology with the thermal imaging capability helps with all types of emergencies such as search and rescue, aerial support over water for diver teams or in wooded areas and for fugitive apprehension."

John Bullock, a sophomore in the School of Mechanical Engineering and research assistant on the project, worked with local public safety colleagues to develop field procedures and post processing of images to create orthorectified images that clearly illustrate the position of vehicles, infrastructure and general terrain adjacent to the crash site. The drones are programmed to use a grid-type path and record about 100 photos in two-second intervals. This post processed data is used to develop an accurate scale map that with photos at the scene provides enough data to create a 3D print of the scene.

"The technology is so much faster than traditional ground-based measurements and provides a much better comprehensive documentation that it opens up all different kinds of research," Habib said. "It can provide high-quality maps, imagery, and models for post-crash investigation by engineers and public safety officials. This technology has many other civil engineering applications beyond crash scene mapping and can be used to estimate the volume of material needed or used for a construction project within a couple of percentage points. data to create a 3D print of the scene.

"The technology is so much faster than traditional ground-based measurements and provides a much better comprehensive documentation that it opens up all different kinds of research," Habib said. "It can provide high-quality maps, imagery, and models for post-crash investigation by engineers and public safety officials. This technology has many other civil engineering applications beyond crash scene mapping and can be used to estimate the volume of material needed or used for a construction project within a couple of percentage points.

"It is very rewarding to see how this technology can be used to improve safety by reducing secondary crashes and exposure of colleagues to the hazards of working adjacent to highway traffic."

A mechanism which drives leukaemia cell growth has been discovered by researchers at the University of Sussex, who believe their findings could help to inform new strategies when it comes to treating the cancer.

Acute myeloid leukaemia (AML) is a devastating blood cancer with around 3,000 new cases annually in the UK.

Despite considerable improvement in patient survival over the last 50 years, the prognosis remains poor for many subsets of adults and children who suffer from the disease.

Current chemotherapies are highly toxic, and often fail to induce a long-term cure resulting in an urgent clinical need for the design of better tolerated and highly targeted therapies that induce durable remissions.

Leukaemia cells are known to have an overactive level of a protein called β-catenin, which can drive cancer development. Once this protein moves into the nucleus of cells, where DNA is stored, it can assist the activation of genes important for leukaemia development. The activity of β-catenin is highly dependent upon the interactions it forms with other proteins in the cell.

Up until now, the movement of β-catenin into the nucleus of leukaemia cells has been a poorly understood process in blood cells.

But researchers from the University of Sussex, Bristol and Cardiff using funding from the Kay Kendall Leukaemia Fund (KKLF) and Bloodwise have now discovered a protein partner that promotes this process and therefore helps leukaemia cells to grow. Their findings could lead to the development of new therapeutic strategies to treat AML.

In a paper published in the journal Haematologica, Dr Rhys Morgan, Lecturer in Biomedical Science, observed that protein LEF-1 can actively control the level of β-catenin in the nucleus of myeloid leukaemia cells. This is the first study to reveal such a mechanism is active in leukaemia cells, and also the first to reveal β-catenin's interaction partners in blood cells.

Dr Rhys Morgan, from the University of Sussex, said: "Whilst scientists have long been aware of the involvement of β-catenin in cancer progression, drugs directly targeting the protein or its partners haven't yet reached the clinic. From our research findings we'd suggest that pharmacological targeting of β-catenin's movement into the nucleus, through a partner like LEF-1, could be a viable treatment strategy in leukaemia."

He explained further: "This research is at a very early stage and targeting the activity of β-catenin won't be a solution for all leukaemia cases and subtypes.

"However data suggests that anywhere between 20-80% of AML cases display elevated levels of this molecule which justifies further investigation in this setting."

Dr Morgan and his team are now working to further understand the biological significance of many of the new interacting proteins discovered in the study, with the belief that others could be worth targeting to inhibit β-catenin level and activity in leukaemia.

CHARLOTTESVILLE, VA (JANUARY 15, 2019). When we think of the recovery period in adolescents with a sports injury, we tend to focus on milestones marking relief from symptoms, restoration of strength, and perhaps return to play. But what about the effects of sports injury on other aspects of the young athlete's life? How is the young athlete's quality of life (QOL) affected following injury and throughout the recovery process?

In a new article in the Journal of Neurosurgery: Pediatrics ("Health-related quality of life following adolescent sports-related concussion or fracture: a prospective cohort study" by Kelly Russell, PhD, Erin Selci, BSc, Brian Black, MD, FRCSC, and Michael J. Ellis, MD, FRCSC), the authors define health-related QOL as "the 'hidden morbidity' or more subtle consequences of medical conditions or injuries on patient functioning that may not be captured by more traditional clinical outcome measures." These researchers from Winnipeg conducted a prospective study of health-related QOL in young athletes who experienced a sports-related concussion or sports-related extremity fracture. The aim was twofold: 1) compare the effects of these sports-related concussions and extremity fractures on health-related QOL in adolescents during the recovery period and 2) identify what clinical variables are associated with worse QOL in adolescent patients with sports-related concussion.

In general, the study period extended from the date of the initial clinical assessment until physician-verified clinical recovery--a median of 26 days in the 135 patients with a concussion (60% male, mean age 14.7 years) and a median of 31 days in the 96 patients with a fractured extremity (59% male, mean age 14.1 years). Only three patients with a concussion did not attain verified clinical recovery during the study period.

At the time of the first clinical assessment, patients with a concussion were asked to rate their symptoms on a standard questionnaire (Post-Concussion Symptom Scale).

To evaluate all of the patients' health-related QOL, the researchers relied on patient responses to self-assessment questionnaires covering cognitive functioning (Pediatric Quality of Life Inventory [PedsQL] Cognitive Functioning Scale) as well as physical, emotional, social, and school functioning, and also overall QOL (PedsQL Generic Core Scale). The questionnaires were completed at the time of the initial clinical assessment and again at each follow-up clinical appointment until physicians documented clinical recovery.

At the time of the initial clinical assessment (about 1 week postinjury), responses to the QOL questionnaires from the adolescents with a concussion demonstrated clinically meaningful impairments in physical, school, and overall health-related QOL when compared to healthy adolescent norms. The responses also demonstrated significantly worse cognitive QOL as well as greater impairments in school and overall health-related QOL when compared to responses from patients with a fractured extremity.

Patients with a concussion who attained clinical recovery within 28 days reported greater weekly improvements in QOL post-injury than those with delayed recovery times (median 51 days in this study). However, there was no evidence of persistent impairments in health-related QOL in the patients with a sports-related concussion or fracture who attained physician-documented clinical recovery during the study period.

In adolescent patients with a sports-related concussion, the authors found greater impairments in the initial health-related QOL in those patients with a history of previous concussion, higher initial symptom score, and/or length of clinical recovery.

To aid in the recovery process, the authors suggest that management of sports-related concussion in adolescents should be supplemented with early interventions to optimize cognitive, physical, and school QOL.

When asked about the study, Dr. Russell stated, "The results of this study indicate that adolescents who report lower health-related QOL after their concussion will likely take longer to recover. Even though adolescents can experience temporary impairments in health-related QOL after a sport-related concussion or fracture, these deficits generally do not persist past clinical recovery."

When we remember a past event, the human brain reconstructs that experience in reverse order, according to a new study at the University of Birmingham.

Understanding more precisely how the brain retrieves information could help us better assess the reliability of eye witness accounts, for example of crime scenes, where people often are able to recall the overall 'gist' of an event, but recall specific visual details less reliably.

The study, published in Nature Communications, was carried out by researchers in the Centre for Human Brain Health, who reconstructed the memory retrieval process, using brain decoding techniques. These techniques make it possible to track when in time a unique memory is being reactivated in the brain.

They found that, when retrieving information about a visual object, the brain focuses first on the core meaning - recovering the 'gist' - and only afterwards recalls more specific details.

This is in sharp contrast to how the brain processes images when it first encounters them. When we initially see a complex object, it's the visual details - patterns and colours - that we perceive first. Abstract, meaningful information that tells us the nature of the object we're looking at, whether it's a dog, a guitar, or a cup, for example, comes later.

"We know that our memories are not exact replicas of the things we originally experienced" says Juan Linde Domingo, lead author of the study. "Memory is a reconstructive process, biased by personal knowledge and world views - sometimes we even remember events that never actually happened. But exactly how memories are reconstructed in the brain, step by step, is currently not well understood."

During the study, participants saw images of specific objects, and then learned to associate each image with a unique reminder word, for example the word 'spin' or 'pull'. The participants were later presented with the reminder word and asked to reconstruct the associated image in as much detail as possible.

Brain activity was recorded throughout the task via 128 electrodes attached to the scalp, allowing the researchers to observe changes in brain patterns with millisecond precision. Finally the researchers trained a computer algorithm to decode what kind of image the participant was retrieving at different points in the task.

"We were able to show that the participants were retrieving higher-level, abstract information, such as whether they were thinking of an animal or an inanimate object, shortly after they heard the reminder word," explains Maria Wimber, senior author of the study.

"It was only later that they retrieved the specific details, for example whether they had been looking at a colour object, or a black and white outline."

"If our memories prioritise conceptual information, this also has consequences for how our memories change when we repeatedly retrieve them," adds Linde Domingo.

"It suggests they will become more abstract and gist-like with each retrieval. Although our memories seem to appear in our 'internal eye' as vivid images, they are not simple snapshots from the past, but reconstructed and biased representations."

Follow-up studies will need to test whether this reversed reconstruction cascade is 'hard-wired' in the brain. If it is, the sequence of reconstruction should remain stable under different conditions, even when a person for example consciously focuses their attention on specific details during learning.

The team is currently also looking in more detail at how and where the brain reconstructs more complex memories. Once the pathway of memory retrieval is established in the healthy brain, researchers can also start looking into how it is altered in healthy ageing, or how this pathway might contribute to the over-generalization of memories in conditions like post-traumatic stress disorder.