Culture

Scientists from Russia demonstrated a novel approach leveraging the combination of high-resolution mass spectrometry and chemoinformatics to identify biologically active molecular components of humic substances extracted from coal, and discovered substances with antiviral activity against the tick-borne encephalitis virus. The results of their study were published in the Scientific Reports journal.

Natural multicomponent mixtures, such as humic substances found in soil, peat and coal are a very important source of biologically active compounds. Understanding their composition and extracting active components can be a great help in creating new drugs. However, finding a specific compound in these environments is a highly challenging task that requires advanced methods capable of differentiating and separating one substance from another.

A joint study conducted by scientists from the Skolkovo Institute of Science and Technology (Skoltech), M.P. Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of the RAS, and M.V. Lomonosov Moscow State University revealed that humic substances inhibit the reproduction of a dangerous human pathogen, tick-borne encephalitis virus. The authors relied on high-resolution mass spectrometry to study the composition of humic samples and chemoinformatics to analyze their findings. They compared the results against extensive databases of chemical compounds and identified the compounds' structural features which may be responsible for their virucidal activity. The data analysis results clearly attest to the importance of natural central fragments of flavonoids and polyphenols, two classes of natural compounds with wide-ranging biological activity.

"We made an attempt at understanding the structural reasons behind the antiviral activity of the molecular components of humic substances. Aware that standard methods of complex mixture separation do not work for humic substances, we looked at some known structures matching the molecular compositions determinable by mass spectrometry and noticed that some structures correspond to compounds often extracted from natural sources, for example, flavonoids. We undertook further mass spectrometry experiments, which suggest that there can indeed be a match between the types of structures we found in the databases and the molecular components of humic systems," says one of the authors of the study and Research Scientist at Skoltech, Alexander Zherebker, PhD.

The results of the study can serve as a stepping stone towards detailed research into the molecular mechanisms of biological activity exhibited by humic substances and other natural inseparable multicomponent mixtures and assessment of their pharmaceutical potential.

Washington, DC - Some research shows facts are better received when presented on their own. Other studies show facts are more accepted when interwoven with stories; stories can help bridge emotional connections. If someone is trying to persuade or influence others, should they use a story or stick to the facts? According to research from social psychologists at Northwestern University, stories can increase the persuasiveness of weak facts, but actually decrease the persuasiveness of strong facts.

"Stories persuade, at least in part, by disrupting the ability to evaluate facts, rather than just biasing a person to think positively," says Rebecca Krause, who coauthored the paper with Derek Rucker.

The research appears in Personality and Social Psychology Bulletin, a publication of the Society for Personality and Social Psychology.

Prior psychological research on storytelling and persuasion demonstrated that stories led to more persuasion.

However, why stories were more persuasive was less clear. It could be that stories focused people on good aspects of a message and away from the negative ones. Alternatively, stories might have disrupted people's ability to process information in an elaborated manner. This distinction is important because these two accounts imply different predictions for when stories will be more or less persuasive.

To test this interplay between facts, stories, and persuasion, Krause and Rucker had 397 U.S. adults evaluate a set of either all strong or all weak facts about a fictitious brand of cell phone called Moonstone. Half of the people read only facts about the phone, while the other half read a story about the phone that had the facts embedded within it. For a strong fact, they used "The phone can withstand a fall of up to 30 feet." For a weak fact, they used "The phone can withstand a fall of up to 3 feet."

Krause and Rucker found that when facts were weak, a story with the facts embedded within it led to greater persuasion than facts alone. But when facts were strong, the opposite effect occurred: facts alone led to more persuasion than a story with the facts embedded within it. This result suggests that stories don't just direct people away from weak information; they reduce people's general processing of information. As a consequence, stories help persuasion when facts are weak, but they hurt persuasion when facts are strong.

Krause replicated the first study, this time with 389 U.S. adults, and observed similar results.

A third study occurred in a lab setting, and changed the content. In the third experiment, 293 people read about a fictitious flu medicine, either on its own or embedded within a story, and were asked whether they would provide their email to receive more information. While people are generally protective of sharing their email, people's willingness to share that information varied in a manner similar to the first two studies.

Specifically, stories once again undermined the persuasive appeal of strong facts. In the absence of a story, 34% of participants agreed to provide their email address in response to strong facts. However, when these same strong facts were included in a story, only 18% of participants agreed to provide their email address.

Krause notes that avoiding stories isn't the message they are trying to send.

"Knowing that stories may provide the most persuasive benefit to those with the least compelling arguments could be important given concerns about 'fake news.'" suggests Krause. "But this does not mean a story is indicative of weak facts. Rather, when you feel especially compelled by a great story you might want to give more thought and consideration to the facts to determine how good they are."

Prevailing economic research anticipates the burden of climate change falling on hot or poor nations. Some predict that cooler or wealthier economies will be unaffected or even see benefits from higher temperatures.

However, a new study co-authored by researchers from the University of Cambridge suggests that virtually all countries - whether rich or poor, hot or cold - will suffer economically by 2100 if the current trajectory of carbon emissions is maintained.

In fact, the research published today by the National Bureau of Economic Research suggests that - on average - richer, colder countries would lose as much income to climate change as poorer, hotter nations.

Under a "business as usual" emissions scenario, average global temperatures are projected to rise over four degrees Celsius by the end of the century. This would cause the United States to lose 10.5% of its GDP by 2100 - a substantial economic hit, say researchers.

Canada, which some claim will benefit economically from temperature increase, would lose over 13% of its income by 2100. The research shows that keeping to the Paris Agreement limits the losses of both North American nations to under 2% of GDP.

Researchers say that 7% of global GDP is likely to vanish by the end of the century unless "action is taken". Japan, India and New Zealand lose 10% of their income. Switzerland is likely to have an economy that is 12% smaller by 2100. Russia would be shorn of 9% of its GDP, with the UK down by 4%.

The team behind the study argue that it isn't just about the number on the thermometer, but the deviation of temperature from its "historical norm" - the climate conditions to which countries are accustomed - that determines the size of income loss.

"Whether cold snaps or heat waves, droughts, floods or natural disasters, all deviations of climate conditions from their historical norms have adverse economic effects," said Dr Kamiar Mohaddes, a co-author of the study from Cambridge's Faculty of Economics.

"Without mitigation and adaptation policies, many countries are likely to experience sustained temperature increases relative to historical norms and suffer major income losses as a result. This holds for both rich and poor countries as well as hot and cold regions."

"Canada is warming up twice as fast as rest of the world. There are risks to its physical infrastructure, coastal and northern communities, human health and wellness, ecosystems and fisheries - all of which has a cost," he said.

"The UK recently had its hottest day on record. Train tracks buckled, roads melted, and thousands were stranded because it was out of the norm. Such events take an economic toll, and will only become more frequent and severe without policies to address the threats of climate change."

Mohaddes worked on the study with Cambridge PhD candidate Ryan Ng, as well as colleagues from the University of Southern California, USA, Johns Hopkins University, USA, National Tsing Hua University, Taiwan, and the International Monetary Fund.

Using data from 174 countries dating back to 1960, the research team estimated the link between above-the-norm temperatures and income levels. They then modelled the income effects under a continuation of business-as-usual emissions as well as a scenario in which the world "gets its act together" and holds to the Paris Agreement.

Researchers acknowledge that economies will adapt to changing climates, but argue that their modelling work shows adaptation alone will not be enough.

The scientific consensus suggests that adapting to climate change takes an average of 30 years, as everything from infrastructure to cultural practice slowly adjusts. But even if this adjustment speeds up to just 20 years, the United States still loses almost 7% of its economy, with over 4% of global GDP gone by the century's end.

The team also undertook a more focused approach to the U.S. to gauge the strength of their results. "Cross-country studies are important for the big picture, but averaging data at national levels leads to loss of information in geographically-diverse nations, such as Brazil, China or the United States," said Mohaddes.

"By concentrating on the U.S., we were able to compare whether economic activity in hot or wet areas responds to temperature fluctuations around historical norms in the same way as that in cold or dry areas within a single large nation."

They looked at ten sectors ranging from manufacturing and services to retail and wholesale trade across 48 U.S. states, and found each sector in every state suffered economically from at least one aspect of climate change - whether heat, flood, drought or freeze.

When scaled up, these are the effects that will create economic losses at the national and global levels, even in advanced and allegedly resilient economies, say the researchers.

"The economics of climate change stretch far beyond the impact on growing crops," said Mohaddes. "Heavy rainfall prevents mountain access for mining and affects commodity prices. Cold snaps raise heating bills and high street spending drops. Heatwaves cause transport networks to shut down. All these things add up."

"The idea that rich, temperate nations are economically immune to climate change, or could even double and triple their wealth as a result, just seems implausible."

Mohaddes is from Sweden, which some predict will benefit from higher temperatures. "But what about the winter sports depended upon by the Swedish tourism industry?"

"If advanced nations want to avoid major economic damage in the coming decades, the Paris Agreement is a good start."

A new study suggests there may be genetic explanations for why some children with poor language also have poor mental health.

The University of York-led study examined genetic variants in six genes that are thought to contribute to language development in children.

The researchers used Polygenic scoring, a statistical technique which adds up the effect of different genetic variants, to determine whether variants that are associated with children's language are also associated with poor mental health.

They found that nearly half of the genetic variants which contribute to children's language were also associated with poor mental health.

As part of the study, the team analysed genetic data from over 5,000 children, as well as parental responses to questionnaires and clinical assessments on children's language ability.

If future research confirms these findings, it may have important implications for timing of mental health provision for children with language disorders, the researchers say.

Lead author of the study, Dr Umar Toseeb, from the Department of Education at the University of York, said: "This study provides very preliminary evidence that children with language disorders, such as developmental language disorder (DLD), may experience poor mental health due to shared biological mechanisms.

"This means that children with DLD may have poor mental health because the genes that are responsible for building neural systems responsible for language might also be responsible for mental health.

"If our findings are confirmed in future work, it could mean that, rather than wait for children with developmental language disorder to show symptoms of poor mental health before intervening, mental health support is put in place as soon as language difficulties become apparent, as a preventative measure."

The mental health difficulties often experienced my children with a DLD have commonly been thought to be caused by their struggles with language, but this study is the first to suggest that there may also be genetic factors which put children with DLD at risk of poor mental health.

First author of the study, Dr Dianne Newbury, from the Department of Biological and Medical Sciences at Oxford Brookes University, said: "This is the first study to demonstrate these genetic effects but they need to be replicated in larger independent datasets to confirm the findings.

"We looked at genetic variation across six genes, but there are many thousands more in the human genome that we did not investigate, so these results only represent a subset of the relevant networks.

"The study illustrates the complexity of language related genetic networks and shows that this is an area that should be investigated further."

Adding vitamin D to wheat flour would prevent 10 million new cases of vitamin D deficiency in England and Wales over the next 90 years, say researchers at the University of Birmingham.

The researchers say overhauling existing public health policy to introduce the mandatory fortification of vitamin D in wheat flour would not only be cost saving but would significantly reduce the burden on the NHS by preventing 25% of the estimated 40 million new cases of vitamin D deficiency over the coming 90 years.

Furthermore, offering free vitamin D supplements to targeted groups of the population - including children, the elderly and Black and Asian Minority Ethnic (BAME) risk groups - would prevent an additional eight per cent of new cases of vitamin D deficiency over the next 90 years.

Therefore, the combination of wheat flour fortification and targeted supplementation would in total prevent 33% (13.2 million) of cases of vitamin D deficiency, the researchers concluded.

They concluded that fortifying flour with vitamin D alone would save the public purse £65 million by reducing demand for healthcare and treatment for vitamin D deficiency and its complications. Meanwhile, they projected that adding vitamin D to flour would cost just 12 pence per person per year.

The research, published today [Aug 20th] in European Journal of Clinical Nutrition, was led by the University of Birmingham's Institute of Applied Health Research and Institute of Metabolism and Systems Research.

Vitamin D is essential for skeletal growth and bone health, and deficiency can lead to rickets, soft bones, bone pain, and muscle weakness. Previous research (i) led by the University of Birmingham has shown that, in extreme cases, vitamin D deficiency in babies and children can cause seizures or heart failure as a result of a lack of calcium.

Dietary sources of vitamin D are limited. The main natural source is through exposure of skin to sunlight. However, sun screen use, air pollution, indoors lifestyles, and wearing full body clothing can all reduce exposure to sunlight and lead to vitamin D deficiency. Dark skin produces far less vitamin D than white skin, and from October to April in the UK there is insufficient ambient ultraviolet sunlight to produce healthy levels of vitamin D in all ethnicities.

Those particularly at risk of vitamin D deficiency are older adults, and those of BAME origin. However, vitamin D deficiency is common in many populations across the world, regardless of ethnicity.

Most countries have adopted policies to increase their population's intake of vitamin D. In the UK, multivitamin supplements containing vitamin D are recommended to all children aged up to four, pregnant women and breastfeeding mothers and are provided free-of-charge to those in low-income households. In addition, infant formulas and spreadable fats are fortified with vitamin D. Other foods, including breakfast cereals and milk substitutes, are commonly fortified.

In the UK, the average daily vitamin D intake is below the Reference Nutritional (ii) Intake of 400 IU per day, and 20% of adults and 16% of children aged between 11 and 18 years are estimated to be deficient in Vitamin D. (iii)

Dr Magda Aguiar, who carried out the research at the University of Birmingham, said: "While both supplements and fortified foods are important sources of vitamin D for the UK population, evidence (iv) suggests current UK supplementation polices are not working.

"Addressing vitamin D deficiency in the UK requires a multi-disciplinary approach and preventing conditions that are the consequence of deficiency would save the NHS money to the extent that it would more than compensate for the money needed to implement flour fortification at a national level."

Dr Aguiar, now at the University of British Columbia, added: "We now hope that UK policy makers will consider a new national policy to fortify foods such as wheat flour with vitamin D to address this serious health issue. This will lead to significant benefits for the population, particularly the most vulnerable groups."

She said that a similar national food fortification policy in Finland has reduced vitamin D deficiency from 13% to 0.6% in the population. (v)

Meanwhile, the Birmingham researchers' latest analysis showed that the optimal way to prevent vitamin D deficiency would be to combine flour fortification with offering vitamin D supplements to key groups.

They proposed a new UK strategy to add 400IU of vitamin D per 100g of flour, while also offering free vitamin D supplements at a dose of 400IU for children aged up to 18, as well as doses of 800IU for all those aged over 65. This, they estimated, would cost £250 million over 90 years - equivalent to 38p per person.

Professor Emma Frew, of the University of Birmingham's Institute of Applied Health Research, said: "We have provided compelling evidence that a new strategy is not only safe but would also improve vitamin D intake, which in turn would enhance the health of millions in England and Wales.

"Most previous research into strategies to improve population vitamin D intake have focused only on supplementation programmes, which are generally expensive and not sustainable in the long term.

"Our study showed that, even though supplements are still a viable option for those at a higher risk, food fortification strategies should be prioritized as a response to the rising prevalence of vitamin D deficiency, as it is a safe and cost-saving option."

The study is the first to provide evidence on the health and economic impact of preventing vitamin D deficiency as well as being the first to compare a supplementation programme with flour fortification.

BALTIMORE, MD, August 20 - Each year there are more than 200 million cases of malaria worldwide, a mosquito-borne disease caused by a parasite that brings on fever and body aches and, in some cases, more serious conditions such as coma and death. While the vast majority of these cases occur in sub-Saharan Africa and South Asia, the U.S. each year sees more than 1,500 cases, and currently there is limited access to an intravenously-administered (IV) drug needed for the more serious cases, according to a top malaria researcher at the University of Maryland School Medicine (UMSOM).

Treatment for severe malaria cases is an intravenous-administered (IV) form of quinidine gluconate. However, there is no longer a widely available supply of this drug in IV form in the United States, warned Mark Travassos, MD, MSc, Assistant Professor of Pediatrics at UMSOM and scientist at the Center for Vaccine Development and Global Health (CVD), in a commentary published in Annals of Internal Medicine today. Oral doses of quinidine are available, but they are not typically effective in more serious malaria cases, he said.

"Severe malaria is a medical emergency that requires immediate treatment with IV medication to reduce the risk of death," said Dr. Travassos, a pediatric infectious diseases specialist and malaria expert in UMSOM's Malaria Research Program within the CVD. Dr. Travassos cited 2015 Centers for Disease Control and Prevention (CDC) statistics showing more than 1,500 malaria cases in the U.S., of which 259 were serious and needed IV treatment. Now, with increased global interconnectedness, the rate of U.S. malaria cases is indeed rising steadily over the past 40 years, according to the CDC.

Dr. Travassos notes that while oral treatments for malaria are available in the U.S., often times these are not effective in more serious cases. "Severe malaria patients can have brain involvement or repeated vomiting and may not tolerate oral medication, placing them at high risk for complications," said Dr. Travassos.

Since 1991, quinidine has been the only Food and Drug Administration-approved (FDA) treatment for severe malaria. However, since April of 2019, remaining supplies of IV-administered quinidine have expired, leaving U.S. physicians with no readily available treatment.

Without a broad supply of the IV drug, physicians treating serious malaria cases must on a case-by-case basis request IV artesunate, a non-FDA-approved drug for severe malaria that is only available from the CDC at ten different airports in the U.S. The CDC will then ship the drug to the airport closest to a requesting hospital. Delivery times will take on average eight hours, but they could be as long as 24 hours.

"This plan raises serious concerns," said Dr. Travassos, adding that the CDC's recommendation that a physician treat a patient with oral medication while waiting for IV treatment to arrive does not meet the standard of care for severe malaria and will not reduce parasite replication in the blood as rapidly as an effective intravenous medication.

"Malaria is a leading killer worldwide, impacting millions of people each year. While we continue to work on developing vaccines and other treatments, it is critical that patients everywhere have access to the regimens needed to combat this disease," said Kathleen Neuzil, MD, MPH, Professor of Medicine and Pediatrics and Director of the CVD.

Federal agencies and professional societies need to work to remedy this situation, Dr. Travassos recommended in his commentary. The CDC should identify potential pharmaceutical companies for manufacture of IV form of artesunate and evaluate the need for incentives, Dr. Travassos recommended. He added that a priority review of a new drug application for IV artesunate would reduce the time for FDA approval to as little as six months. He further cautioned that given the shortage of IV treatments for the most serious malaria cases, hospitals in the U.S. should develop a preparedness plan.

At the hospital level, a plan should address potential delays in diagnosis and treatment of malaria, with anticipation of different scenarios. At triage, patients should be questioned about recent travel
outside the country. Those who are febrile and have recently traveled to malaria-endemic regions should immediately have a rapid diagnostic test for malaria, and a thick and thin blood smear should be sent for an immediate reading, Dr. Travassos recommended.

"As we become more connected globally in the U.S., it is important to understand the risks and concerns of diseases like malaria. At the University of Maryland School of Medicine, our scientists and physician-scientists are studying the best treatments and approaches for managing and treating the most complex and challenging diseases," said UMSOM Dean E. Albert Reece, MD, PhD, MBA, who is also the Executive Vice President for Medical Affairs, University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor.

Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information.

Case studies suggest that 'red flag' laws play a role in preventing mass shootings
Experts examine 21 cases in which extreme risk protection orders were used in response to threats of mass violence

Abstract: http://annals.org/aim/article/doi/10.7326/M19-2162

URLs go live when the embargo lifts

Case studies of individuals threatening mass violence suggest that extreme risk protection orders (ERPOs), colloquially known as 'red flag' orders, may play a role in preventing mass shootings. An aggregate summary and individual histories for a preliminary series of 21 cases are published in Annals of Internal Medicine.

Nearly 80 percent of perpetrators of mass violence in public places make explicit threats or behave in a manner "indicative of their intent to carry out an attack." For example, the shooters in the infamous Parkland, Aurora, and Tucson events, among others, were known by family members, acquaintances, law enforcement, and in some cases, health care professionals, to be at high risk for violence. ERPOs provide a rapid, focused response when risk of imminent firearm violence is high. Studies suggest that these interventions are effective at preventing suicide, but their efficacy in preventing mass shootings is not known. To date, there have been only two reported cases of ERPO use in efforts to prevent mass shootings. California enacted the nation's first ERPO statue, which took effect in January 2016.

Researchers from the Violence Prevention Research Program at UC Davis School of Medicine sought to evaluate the California statute's implementation and effectiveness by reviewing court cases for persons subject to the orders. Of 414 cases, the authors received 159 and developed an aggregate summary and individual histories for a preliminary series of 21 cases. Their research showed that most subjects were male and non-Hispanic white and the mean age was 35. Most subjects made explicit threats and owned firearms. Four cases arose primarily in relation to medical or mental health conditions, and such conditions were noted in four others. Fifty-two firearms were recovered. The researchers conducted print, broadcast, and Internet media Google searches using the subjects' names and locations to determine if they were the perpetrators of any violent events from the date of the order. As of early August 2019, none of the threatened shootings had occurred, and no other homicides or suicides by persons subject to the orders were identified. According to the authors, these cases suggest that this urgent, individualized intervention has a role to play in efforts to prevent mass shootings, in healthcare settings and elsewhere. They believe that further research would be helpful in determining definitively the effectiveness of such orders.

Scientists have developed a large-scale economical method to extract hydrogen (H2) from oil sands (natural bitumen) and oil fields. This can be used to power hydrogen-powered vehicles, which are already marketed in some countries, as well as to generate electricity; hydrogen is regarded as an efficient transport fuel, similar to petrol and diesel, but with no pollution problems. The process can extract hydrogen from existing oil sands reservoirs, with huge existing supplies found in Canada and Venezuela. Interestingly, this process can be applied to mainstream oil fields, causing them to produce hydrogen instead of oil.

Hydrogen powered vehicles, including cars, buses, and trains, have been in development for many years. These vehicles have been acknowledged to be efficient, but the high price of extracting the Hydrogen from oil reserves has meant that the technology has not been economically viable. Now a group of Canadian engineers have developed a cheap method of extracting H2 from oil sands. They are presenting this work at the Goldschmidt Geochemistry Conference in Barcelona.

"There are vast oil sand reservoirs in several countries, with huge fields in Alberta in Canada, but also in Venezuela and other countries" said Dr Ian Gates, of the Department of Chemical Engineering at the University of Calgary, and of Proton Technologies Inc.).

Oil fields, even abandoned oil fields, still contain significant amounts of oil. The researchers have found that injecting oxygen into the fields raises the temperature and liberates H2, which can them be separated from other gases via specialist filters. Hydrogen is not pre-existing in the reservoirs, but pumping oxygen means that the reaction to form hydrogen can take place.

Grant Strem, CEO of Proton Technologies which is commercialising the process says "This technique can draw up huge quantities of hydrogen while leaving the carbon in the ground. When working at production level, we anticipate we will be able to use the existing infrastructure and distribution chains to produce H2 for between 10 and 50 cents per kilo. This means it potentially costs a fraction of gasoline for equivalent output". This compares with current H2 production costs of around $2/kilo. Around 5% of the H2produced then powers the oxygen production plant, so the system more than pays for itself.

The economics of the process is favourable according to Grant Strem "What comes out of the ground is hydrogen gas, so we don't have the huge above-ground purification costs associated with oil refining: we use the ground as our reaction vessel. Just taking Alberta as an example, we have the potential to supply Canada's entire electricity requirement for 330 years (Canada uses around 2.5% of the world's electricity - around the same amount as Germany, and more than France or the UK). Our initial aim is to scale up the production from Canadian oil sands, but in fact, we anticipate that most of the interest in this process will come from outside Canada, as the economics and the environmental implications make people look very hard at whether they want to continue conventional oil production. The only product of this process is hydrogen, meaning that it the technology is effectively pollution and emission free. All the other gases remain in the ground because they cannot go through the hydrogen filter and up to the surface".

The technology was developed by Ian Gates and Jacky Wang as the result of an agreement between the University of Calgary and Proton Technologies Inc., which now holds the patent.

Professor Brian Horsfield (GFZ German Research Centre for Geosciences, Potsdam) said: "The research is highly innovative and exciting. It's an adaptation of some 1970's fire-flood production concepts, but tuned to a modern day perspective. Declining oil field production infrastructures now stand to get a new lease of life. Extensive field testing will be crucial in assessing how the system works on industrial scales and over time"

A researcher at The University of Texas at Arlington has found that blood vessels within bone marrow may progressively convert into bone with advancing age.

Examination of these vessels by Rhonda Prisby, associate professor of kinesiology in the College of Nursing and Health Innovation, led to the discovery of bone-like particles in the peripheral circulation. Her findings have recently been published in the journal Microcirculation and suggest that ossified particles may contribute to diseases such as vascular calcification, heart attack, stroke and inadequate blood supply to the limbs.

"By examining seemingly unrelated images and linking the details of them together, I was able to posit the presence of bone-like particles in the blood," Prisby said "In fact, some of the ossified particles are large enough to clog the smallest blood vessels in the vascular tree."

Approximately 610,000 people die each year from a heart disease-related event, making it the leading cause of death for both men and women in the United States, according to the Centers for Disease Control and Prevention.

Vascular calcification is a common characteristic and risk factor for morbidity and mortality, Prisby said. These bone-like particles are potentially more dangerous because of their sharp edges.

"Some of the ossified particles have sharp tips and edges that could damage the lining of blood vessels," she said. "This damage could initiate events leading to atherosclerosis (build-up of plaque), which can restrict blood flow over time."

The discovery of these bone-like particles could help physicians detect and treat potentially life-threatening conditions.

"When looking for etiologies related to vascular calcification, heart attack and/or stroke, perhaps we should consider if and how ossified particles contribute to these diseases," Prisby said. "My lab will examine these possibilities."

The effects of more than 60 minutes of moderate daily physical exercise, such as walking, accumulate throughout life and are associated with a 39% reduction in the risk of advanced adenomatous polyps, a precursor of colorectal cancer, the third most frequent type of cancer in Brazil.

This is the main finding of an epidemiological study published in the British Journal of Cancer. The study was conducted by researchers in the Department of Preventive Medicine at the University of São Paulo's Medical School (FM-USP) in Brazil and colleagues elsewhere, specifically Harvard University in the United States. It was supported by a Research Internship Abroad Scholarship (BEPE) from FAPESP.

"The links between physical activity, adenomas and colorectal cancer are well understood, but this is the first study to demonstrate the cumulative effects of physical activity starting in adolescence on the incidence of colorectal adenoma," said Leandro Rezende, a researcher at FM-USP and one of the authors of the study.

The authors analyzed the data of 28,250 women included in the Nurses' Health Study II (NHS II), one of the largest investigations into risk factors for major chronic diseases ever conducted. The sample population included women aged 25-42 years who were employed as nurses and medical residents in the United States. It was one of a series of prospective cohort studies conducted to examine the etiology of chronic diseases and the long-term effects of physical activity, nutrition, hormones and the environment, among other factors, on health and disease development.

The study published this year in the British Journal of Cancer analyzed the association between physical activity during adolescence and risk of adenoma later in life and adjusted for such known risk factors as smoking, diet, alcohol intake, and family history of colorectal cancer.

The results of the analysis showed that physical activity in adolescence (12-22) reduced the risk of adenoma by 7% compared with little or no physical activity (less than 60 minutes per day). Physical activity in only adulthood (23-64) reduced the risk by 9%. Physical activity in both adolescence and adulthood reduced the risk by 24%.

According to Rezende, the small difference between the impact of physical activity in adolescence alone and in adulthood alone reflects the different lengths of the two periods. "The reduction is actually similar in each case," he said. "This tendency suggests that there is a cumulative effect of physical activity as life goes on. Whether it's during adolescence or adulthood, the more physical activity we get, the lower the risk of developing adenoma in adulthood becomes."

The finding that most surprised the researchers, however, was that adequate physical activity in both adolescence and adulthood reduced the risk of advanced adenoma by 39%. "This increased level of risk reduction correlated with villous adenomas, which are aggressive polyps with a diameter of more than 1 cm and are the most likely to evolve into colorectal cancer," Rezende said.

According to the researchers, physical activity may reduce the risk of carcinogenesis by decreasing body fat, inflammation and insulin levels.

Wealth of data

For José Eluf Neto, Full Professor at FM-USP and Rezende's PhD thesis adviser, the results of the study confirm the importance of policies to encourage physical activity as a public health priority.

"Colorectal cancer is one of the most common types of cancer, and the science shows that physical activity alone is a key factor in reducing the risk of adenoma. However, it should be kept in mind that an adenoma is not cancer. In other words, we've shown that physical activity helps prevent the disease from even occurring because it reduces the risk of developing a precursor," Eluf Neto told.

Sedentary behavior in adolescence has been a major concern, especially in connection with colorectal cancer, he added. "Although in most cases the disease appears after the age of 60, the number of patients under 50 is rising. We don't know if this is because more people are being diagnosed or undergoing colonoscopies, or whether early exposure to risk factors such as a sedentary lifestyle may be driving the earlier incidence of colorectal adenoma or cancer," he said.

The Nurses' Health Study II began in the late 1980s, with a target population of nurses between 25 and 42 years of age. Each set of two-year cohort members received a follow-up questionnaire with questions about diseases and health-related topics, including smoking, hormone use, pregnancy history, and menopausal status. The 1997 questionnaire was the first to include items relating to physical activity, diet and obesity during adolescence (when they were between 12 and 22 years of age).

"They answered questions on home-school commute times and methods, and on moderate physical activity such as walking as well as more intense exercise such as gym classes, swimming and other sports. This enabled us to estimate the level of physical activity during their adolescence," Rezende said.

Follow-up continued until 2011, when the questionnaire included further items on lifestyle habits between the ages of 23 and 64 - a period in which the nurses responded the questionnaire every two years. To participate in the study, the nurses had to have undergone at least one sigmoidoscopy or colonoscopy, since polyps and adenomas are asymptomatic.

The brain activity evoked from processing written or heard semantic information is almost identical, according to research in adults published in JNeurosci. These findings add to the understanding of how the brain processes written and oral language.

Language is a complex process that involves many regions of the brain, and it was previously unclear if the brain represented spoken and written semantic information in different ways.

To clarify this, Jack Gallant and colleagues at The University of California, Berkeley used functional magnetic resonance imaging to record the brain activity of healthy adults while they listened to or read a transcription of a radio show. The research team mapped out the specific areas of the brain that responded to each word when it was read or heard.

The brain activity associated with each word was largely consistent across the two senses. The scientists were also able to use data from one sense to predict the brain activity that would occur due to the other sense. These results suggest that the same parts of the brain process information surrounding words, regardless if the word is heard or read.

Over the course of 40 years, biologist Sharon Long has become an expert in symbiotic bacteria that help alfalfa grow. She has published over 150 papers on this one topic but when she realized her lab's decades of highly focused research could contribute to a solution for citrus greening - a disease that devastates citrus crops - she was inspired to go in a new direction.

"I'm only two generations off a farm, and I read about citrus farmers losing their livelihood and land, and thus also losing generations of family tradition," said Long, who is the William C. Steere, Jr. - Pfizer Inc. Professor in Biological Sciences in the School of Humanities and Sciences. "We decided to redirect our efforts to work on this problem because we wanted to make a difference."

That risk paid off with a new way of finding potential treatments for the disease, and a short list of 130 compounds to explore further. Details of the system and their screenings were published Aug. 19 in the Proceedings of the National Academy of Sciences.

"What we've completed is just a small part of what needs to be done," said Melanie Barnett, a senior researcher in the Long lab and lead author of the paper. "It's beyond our expertise to pursue these findings to the level needed for real-world application, but it's a foot in the door for researchers who can take those next steps."

Decades of knowledge

Citrus greening has devastated the citrus industry in Florida and is found in many of the country's citrus growing regions. Even with high surveillance, the disease is spreading, and by the time symptoms of the lethal bacterial infection appear, it's too late - the plants, bearing mottled leaves and ugly fruit with unpalatably bitter juice, must be uprooted and destroyed.

An increasingly common treatment for the infection is spraying whole orchards with antibiotics, which is a risky procedure that could allow drug-resistant bacteria to emerge and spread.

Despite its devastation, citrus greening has been difficult for researchers to study. The bacteria that cause the disease - Liberibacter asiaticus - won't grow in a lab, and studying infected plants is possible only in a few highly protected and sealed locations in the U.S. Some researchers have turned to a close, but less harmful, bacterial relative to find answers. But the Long lab realized they could tackle the problem by focusing on a more distant relative - Sinorhizobium meliloti, which partners with certain plants, allowing them to grow without added nitrogen fertilizer.

"We've been working on this bacterium for 40 years and have developed tools that allow finely detailed genetic studies to be done," Long said. "That provides an experimental platform not possible by working directly on this pathogen or even its close relatives."

The researchers started by introducing genes from the citrus greening bacterium into their familiar S. meliloti cell. Those genes each code for a protein that the scientists think regulates aspects of infection.

Then, they engineered the bacteria so that when those infection-critical proteins were active, the bacteria glowed green in certain light. With this setup, if they exposed the bacteria to a chemical that inhibits the proteins - and perhaps also decreases the bacteria's ability to infect citrus - the cell would become visibly less green.

This visual signal made it possible to screen over 120,000 different compounds with help from the Stanford High-Throughput Bioscience Center. That screen identified 130 compounds that dimmed the cells' green glow without affecting its growth.

"Our system allowed us to find very specific inhibitors that do not harm beneficial bacteria," explained Long. "Such inhibitors would be a big improvement compared to environmental spraying of general antibiotics."

Beyond studying the 130 compounds, the group said other researchers could now test additional chemicals with the system they devised, or examine different genes.

"With this system, any gene from this pathogen or closely related pathogens can be tested in a very controlled way, very efficiently," said Barnett. "The years of research that have gone into studying and working with Sinorhizobium can now save years of time that others would have spent developing such a system from scratch."

Making a difference

For Long and Barnett, this endeavor had personal significance. Long is a Texas native whose grandparents grew up on farms and whose aunt was from a town in the Rio Grande Valley known for its citrus industry. She funded the first few months of this research from her own savings. Two of Barnett's great-grandparents owned a wheat farm in Colfax, Washington before moving to California. Another set moved to California from Arkansas in 1920 and worked as migrant farmworkers throughout the state, often in the citrus industry. Barnett grew up in Southern California, where citrus greening disease was first found in 2012.

"Being able to provide for ourselves is rewarding. It's also important for our well-being and for our national security," said Barnett. "Most of the citrus eaten out of hand comes from California and I feel a lot of pride and gratitude being from a state that feeds the country."

Alongside encouraging further work on their candidate compounds and with their screening system, Long and Barnett finished their paper with a call to action. They urge other researchers to follow their lead and step out of their comfort zones to contribute whatever they can to the citrus greening crisis. The team has donated all information and materials to the public domain to encourage as many researchers as possible to use this system.

A common origin shared by teeth and taste buds in a fish that has regenerative abilities has been identified by a team of researchers from the UK and the States. Regulated by the BMP signalling pathway, the results suggest that the oral organs have surprising regenerative capabilities and can be manipulated to express characteristics of different tissue types.

The collaborative study between King's College London and Georgia Institute of Technology, Atlanta was recently published in the journal PNAS (Proceedings of the National Academy of Sciences of the United States of America). As nearly one-third of all adults over the age of 65 have lost all their teeth, the two teams set out to understand tooth renewal in animals that have replacement and regeneration capabilities.

Using cichlid fishes and mouse models and building on previous studies in regeneration, the researchers found that replacement teeth share a continuous epithelium with developing taste buds and that both organs share very similar stem cell populations. The BMP signalling pathway acts on this shared epithelium to distinguish teeth from taste buds.

At Professor Paul Sharpe's lab at King's College London, mouse genetic models where BMP signalling activity is modified showed that teeth gene expression is ectopically activated in taste buds when BMP signalling is elevated. These findings indicate underappreciated epithelial cell populations with promising potential in bioengineering and dental therapeutics.

Professor Sharpe, Head of the Centre for Craniofacial & Regenerative Biology at King's College London said: "This research is an excellent example of the power of studying multiple species in order gain novel insights that can impact upon human regenerative medicine."

Research also may lay the foundation for understanding group-based biases

Studies build upon prior work showing that attitudes toward racial groups can be influenced by nonverbal signals

Researcher: 'When we see people being less friendly toward one individual relative to another, we often attribute the unfriendliness to the target.'

EVANSTON, Ill. --- If you were to meet two new people, and others seem to be more friendly toward one of those individuals, would that lead you to like that individual more than the other?

A new Northwestern University study examined whether people can acquire attitudes toward other individuals from the nonverbal signals that are directed toward them.

"This is important because often we are not explicitly thinking about the nonverbal signals that people display," said Allison Skinner, formerly a postdoctoral researcher at Northwestern University, and now an assistant professor at the University of Georgia. "So we could be picking up messages from the nonverbal signals in our environment that we are not even aware of."

The researchers found that after people watched a brief silent video of individuals interacting, they acquired attitudes toward the individuals in the video based on the nonverbal signals that were displayed toward them. This was true of the attitudes that people were explicitly aware of, but this also impacted their implicit attitudes.

"This means that people were quicker to pair the individual who received positive nonverbal signals with good things, than the individual who received negative nonverbal signals," said Skinner, lead author of the study. "This was especially interesting because most of our participants did not think that the nonverbal signals that were displayed toward the individuals in the videos influenced their attitudes. Only about 30% of people indicated that how the individuals were treated influenced their attitudes toward them."

Skinner said the fact that people often attributed their attitudes to the behavior of the recipients of nonverbal signals was eye opening.

"Even though we edited the videos so that the targets of nonverbal signals all responded in the same way -- whether they received positive or negative nonverbal signals, and only the nonverbal signals that they received varied, a substantial proportion of participants attributed their attitudes to the targets' behavior," Skinner said.

"This has important implications for how people make sense of the nonverbal messages that they are exposed to in everyday life. These findings suggest that when we see people being less friendly toward one individual relative to another, we often attribute the unfriendliness to the target. Believing that we like them less because they do not seem to be very friendly, when in fact, it is others who were not very friendly to them."

Skinner said it is possible that this research also may lay the foundation for group-based biases.

"These studies build upon prior work showing that attitudes toward racial groups can be influenced by nonverbal signals," Skinner said. "For example, white people in the U.S. who observe white people displaying negative nonverbal signals toward black people tend to go on to show more anti-black bias than those who were exposed to a positive nonverbal signals directed toward a black person."

Co-author Sylvia Perry said their findings suggests that, even in contexts in which people's attitudes toward others are relatively neutral to begin with, the nonverbal signals that they observe can create new attitudes toward unfamiliar others.

"I think this has important implications for our understanding of how we develop biases toward social groups, in general -- even from a young age," said Perry, assistant professor of psychology in the Weinberg College of Arts and Sciences at Northwestern and a faculty fellow with the University's Institute for Policy Research.

TAMPA, Fla. - Lung cancer is the second most common cancer found in both men and women. It is estimated there will be roughly 228,000 new lung cancer cases this year, and nearly 30% of those patients will have mutations in the KRAS pathway. This type of mutation makes the cancer more aggressive and difficult to treat. Researchers at Moffitt Cancer Center are hoping to change that. In a new study published in Cancer Research, the team discovered a new treatment approach that may help this group of patients.

KRAS is a gene that regulates cell signaling in an "on" and "off" manner, leading to normal cell growth and division. Mutations that occur in the KRAS gene cause the protein to ignore any "off" signals that it receives, which results in unchecked cell growth. This is why researchers have been investigating areas in the KRAS pathway as possible therapeutic targets. For example, in melanoma, therapies that target the BRAF mutation, a protein in the KRAS pathway, have led to a positive patient response.

Moffitt researchers believe the MEK kinase, also found in the KRAS pathway, can be a possible target for lung cancer treatment. Through a series of drug screens, cell line and animal model experiments, they found that lung cancer cells treated with the MEK inhibitor trametinib in combination with the cytokines TNFα and IFNγ resulted in substantially more cell death than treating with a MEK inhibitor alone. TNFα was identified in the 1970s as Tumor Necrosis Factor but initial enthusiasm for using it in cancer treatment was quickly dampened by inflammatory response induced following TNFα administration, and the fact that most tumor cells resist killing by TNFα. In this study, the research team found that MEK inhibitors increase the number of receptors on the cell surface for TNFα to bind to, which leads to the delivery of a more potent and sustained cell death signal. IFNγ, a cytokine known to be crucial for anti-tumor immunity, further enhances the anti-tumor activity of MEK inhibitors and TNFα. Importantly, MEK inhibitors also considerably increases expression of TNFα and IFNγ target genes, which can lead to increase in anti-tumor immunity.

"MEK inhibitors alone do not provide strong overall response for this group of patients," said Amer A. Beg, Ph.D., senior member of the Immunology Department and Lung Cancer Center of Excellence at Moffitt and lead author of this study. Beg and his team took their research further by investigating whether MEK inhibitors in combination with therapies known to increase expression of TNFα and IFNγ would provide a better response. They discovered that adding a PD-1 immune checkpoint inhibitor with MEK inhibitors resulted in the strongest tumor regression in mice. The researchers are planning further studies to combine MEK inhibitors with other immune therapies that provide strong expression of these cytokines in the tumor microenvironment, such as CAR T and adoptive T cell therapy approaches.

"These studies will help determine if modulation of the immune microenvironment along with tumor signaling is a viable treatment strategy for lung cancer patients with KRAS mutations and potentially other mutations that rely on MEK signaling," said Mengyu Xie, a cancer biology graduate student studying at Moffitt and a first author of the study.

"Demonstrating that an anti-cancer agent can so effectively modulate the activity of a cytokine signaling pathway crucial for so many biological processes is conceptually novel and can lead to new understanding of oncogenic pathways and strategies for targeting them" said Beg.