Culture

Globally, pneumonia and diarrhea together led to nearly one of every four deaths that occurred in children under five years of age in 2016. The 2018 Pneumonia and Diarrhea Progress Report--released ahead of the 10th annual World Pneumonia Day, on November 12, by the International Vaccine Access Center (IVAC) at the Johns Hopkins Bloomberg School of Public Health--describes efforts to fight pneumonia and diarrhea in 15 countries with the greatest number of deaths from these illnesses.

This report analyzes how effectively countries are delivering or ensuring the use of 10 key interventions, which include exclusive breastfeeding, vaccination, access to care and use of antibiotics, oral rehydration solution, and zinc supplementation to help prevent and treat pneumonia and diarrhea. These measures are known to help protect children from death due to these illnesses and could help achieve the UN's Sustainable Development Goal target of reducing under-five mortality to at least as low as 25 per 1,000 live births by 2030.

The Pneumonia and Diarrhea Progress Report, issued annually by IVAC for nearly a decade, finds that although countries are making progress toward improved vaccine coverage, they seriously lag in efforts to treat childhood illnesses--especially among populations that are remote, impoverished, or otherwise left behind.

"Progress to stop child deaths is being hampered by persistent inequities in countries around the world," said Kate O'Brien, MD, MPH, a professor in the Bloomberg School's Department of International Health and IVAC's executive director. "Addressing these inequities will demand greater levels of funding, strong political commitment, accountability supported by better data, and a coordinated global effort that prioritizes the most vulnerable."

Eight out of 15 countries assessed failed to meet the targets for any of 10 interventions to protect against and treat pneumonia and diarrhea, as outlined in the World Health Organization and UNICEF's Integrated Global Action Plan for the Prevention and Control of Pneumonia and Diarrhea (GAPPD). Two of the countries met the 90% target coverage rate for at least four vaccines. On treatment measures, none of the 15 countries were able to attain the 90% targeted level of coverage.

For the first time, the annual report reviewed stratified national data, revealing inequities in how well countries were providing life-saving interventions to children based on gender, location of residence (i.e., urban or rural), maternal education, and wealth.

The authors conclude that in order to accelerate progress, governments must collect better data on a regular basis. The global community must prioritize improving access to prevention and treatment interventions for children who are now not being reached. Funders must continue or increase support for proven solutions--or risk having progress slip away. Finally, integrating strategies related to health systems, poverty, and education may yield opportunities to improve equity in many countries.

UNIVERSITY PARK, Pa. -- Mosquitoes of the genus Anopheles are well known as primary vectors of malaria. But a new study suggests that Anopheles species, including some found in the United States, also are capable of carrying and transmitting an emerging pathogen, Mayaro virus, which has caused outbreaks of disease in South America and the Caribbean.

Mayaro virus -- which can cause fever, joint aches, muscle pains, headache, eye pain, rash, nausea, vomiting and diarrhea -- first was isolated from the blood of five symptomatic workers in Mayaro County, Trinidad, in 1954. Since then, it has caused sporadic outbreaks and small epidemics in several South and Central American countries.

In addition, imported cases may be on the rise, with several reported recently in the Netherlands, Germany, France and Switzerland, according to researchers.

"Because the symptoms of Mayaro infection are similar to those caused by other arboviruses [arthropod-borne virus] such as dengue and chikungunya, its prevalence in areas where these other viruses circulate may be higher than reported," said the study's senior author, Jason Rasgon, professor of entomology and disease epidemiology, College of Agricultural Sciences, Penn State.

Rasgon explained that Mayaro virus is thought to be transmitted primarily by canopy-dwelling mosquitoes of the genus Haemagogus. Human infections are sporadic, he said, because Haemagogus species tend to live in rural areas in proximity to forests -- where they cycle the virus among nonhuman primates and birds -- and do not typically prefer to feed on people. However, when the virus is introduced into urban areas, other mosquito species potentially could trigger epidemics in human populations.

"With the recent increase in imported cases, there are invasion concerns similar to those associated with Zika and chikungunya viruses," Rasgon said. "But little is known about the range of mosquito species that are capable vectors of Mayaro, so our aim was to address that knowledge gap."

In this study, the researchers tested six mosquito species -- Aedes aegypti, Anopheles freeborni, An. gambiae, An. quadrimaculatus, An. stephensi and Culex quinquefasciatus -- for their ability to transmit two strains of the Mayaro virus. The four Anopheles species were selected to cover different geographical regions: North America (An. freeborni and An. quadrimaculatus), Africa (An. gambiae) and Southeast Asia (An. stephensi).

Mosquitoes were allowed to feed on human blood spiked with the virus via a glass feeder. Researchers then assessed each species at seven and 14 days after infection to determine infection rate (rate of mosquitoes with infected bodies among those analyzed), dissemination rate (rate of mosquitoes with infected legs among those with positive bodies), transmission rate (rate of mosquitoes with infectious saliva among those with positive legs), and transmission efficiency (rate of mosquitoes with infectious saliva among the total number analyzed).

They found that Aedes aegypti and Culex quinquefasciatus were poor vectors of Mayaro virus, with either poor or null infection and transmission rates. However, the results, reported today (Nov. 7) in PLoS Neglected Tropical Diseases, demonstrated that all four Anopheles species were competent laboratory vectors of the virus.

"The capacity of the two North American species of Anopheles to transmit Mayaro is particularly relevant to the United States, because the estimated geographic distribution of these species covers the entire country," Rasgon said.

"The transmission cycle of Mayaro involves mostly nonhuman primates and birds, although there is some evidence of circulation in rodents and marsupials," he said. "We don't know about the capacity of North American mammal species to act as vertebrate reservoirs, but it's possible that Mayaro virus could be maintained in a human-mosquito-human urban cycle similar to what we've seen with chikungunya."

In addition, the researchers noted, Anopheles mosquitoes tend to take multiple blood meals between egg-laying events, and this bite frequency increases their capacity to transmit viruses.

"Despite the fact that Anopheles mosquitoes are widely dispersed worldwide, they currently are neglected as potential vectors of arboviruses," Rasgon said. "Our results suggest that Anopheles species may be important vectors driving the emergence and invasion of Mayaro virus across geographically diverse regions of the world, and more research is needed on their epidemiological role in virus invasions."

AMHERST, Mass. - A new predictive model developed by an ecologist at the University of Massachusetts Amherst and a climate scientist at the University of Washington suggests that climate change may allow common ragweed to extend its growing range northward and into major northeast metro areas, worsening conditions for millions of people with hay fever and asthma.

Plant ecologist Kristina Stinson at UMass Amherst, who leads a research team that has been studying this plant for over a decade - particularly how it responds to elevated CO2 levels - worked with climate modeler and corresponding author Michael Case at UW on this project. Details appear online in the journal PLOS One.

They point out that though the weed is expected to expand its range, this could be moderated by the plant's own sensitivity to climate variability. For example, they note that in their analysis, ragweed is negatively correlated to very low or very high annual precipitation variability, "indicating a general sensitivity to precipitation extremes" as well as temperature extremes, the authors note. Stinson adds that this could turn out to be an important uncertainty; "if the Northeast turns more wet and cool, it would be less hospitable to ragweed," she says.

"One reason we chose to study ragweed is because of its human health implications. Ragweed pollen is the primary allergen culprit for hay fever symptoms in summer and fall in North America, so it affects a lot of people," the plant ecologist notes.

To better understand how climate change may affect the distribution of common ragweed, Stinson and Case built a maximum entropy, Maxent, predictive model using climate and bioclimatic data and observations across the eastern U.S. They used data from the Denmark-based Global Biodiversity Information Facility, a project that provides hundreds of millions of species occurrence records worldwide, plus plant data from herbarium records like those housed at UMass Amherst.

Stinson says, "We zoomed in on 700 data points for ragweed from all across its range in North America, and paired that information with another database that specifies climate in each of those exact locations. We then used climate change models to project forward in time what might be expected to occur."

The authors also point out, "After building and testing our model, we then projected potential future common ragweed distribution using a suite of 13 global climate models under two future greenhouse gas scenarios for mid- and late-century. In addition to providing geo-referenced hot spots of potential future expansion, we also provide a metric of confidence by evaluating the number of global climate models that agree."

The model suggests a "substantial contraction" of common ragweed may loom in central Florida, the southern Appalachian Mountains and northeast Virginia, along with areas of potential expansion at the northern margins of its current distribution, in particular in the northeast U.S.

Stinson adds, "What I found quite interesting is not so much that ragweed's range is going to expand, because that's what one might expect for a weedy species, but I was interested in seeing where it is most likely to spread and where we might see range contractions. It looks like maybe there will be a temporary burst followed by a contraction in the 2070s."

The researchers point out, "Although other factors and modeling approaches should be explored, we offer preliminary insight into where common ragweed might be a new concern in the future. Due to the health impacts of ragweed, local weed control boards may be well advised to monitor areas of expansion and potentially increase eradication efforts."

Stinson points out, "We don't have a lot of models like this that tell us where individual species may go under different scenarios. Ecologists are working on doing this type of study for more species, but there are not always enough data points from around the world; individual species data are rare. But ragweed happens to be quite abundant, which made this study feasible."

AMHERST, Mass. - A major factor holding back development of wearable biosensors for health monitoring is the lack of a lightweight, long-lasting power supply. Now scientists at the University of Massachusetts Amherst led by materials chemist Trisha L. Andrew report that they have developed a method for making a charge-storing system that is easily integrated into clothing for "embroidering a charge-storing pattern onto any garment."

As Andrew explains, "Batteries or other kinds of charge storage are still the limiting components for most portable, wearable, ingestible or flexible technologies. The devices tend to be some combination of too large, too heavy and not flexible."

Their new method uses a micro-supercapacitor and combines vapor-coated conductive threads with a polymer film, plus a special sewing technique to create a flexible mesh of aligned electrodes on a textile backing. The resulting solid-state device has a high ability to store charge for its size, and other characteristics that allow it to power wearable biosensors.

Andrew adds that while researchers have remarkably miniaturized many different electronic circuit components, until now the same could not be said for charge-storing devices. "With this paper, we show that we can literally embroider a charge-storing pattern onto any garment using the vapor-coated threads that our lab makes. This opens the door for simply sewing circuits on self-powered smart garments." Details appear online in ACS Applied Materials & Interfaces.

Andrew and postdoctoral researcher and first author Lushuai Zhang, plus chemical engineering graduate student Wesley Viola, point out that supercapacitors are ideal candidates for wearable charge storage circuits because they have inherently higher power densities compared to batteries.

But "incorporating electrochemically active materials with high electrical conductivities and rapid ion transport into textiles is challenging," they add. Andrew and colleagues show that their vapor coating process creates porous conducting polymer films on densely-twisted yarns, which can be easily swelled with electrolyte ions and maintain high charge storage capacity per unit length as compared to prior work with dyed or extruded fibers.

Andrew, who directs the Wearable Electronics Lab at UMass Amherst, notes that textile scientists have tended not to use vapor deposition because of technical difficulties and high costs, but more recently, research has shown that the technology can be scaled up and remain cost-effective.

She and her team are currently working with others at the UMass Amherst Institute for Applied Life Sciences' Personalized Health Monitoring Center on incorporating the new embroidered charge-storage arrays with e-textile sensors and low-power microprocessors to build smart garments that can monitor a person's gait and joint movements throughout a normal day.

Because of their antimicrobial and antifungal properties, silver nanoparticles measuring between one and 100 nanometers (billionth of a meter) in size, are being incorporated outside the United States into a variety of kitchen products known as food contact materials (FCMs). Among the nanosilver-infused FCMs now on the market overseas are spatulas, baby mugs, storage containers and cutting boards. However, the use of these items raises concerns that the nanoparticles in them will migrate into foods and the environment, and in turn, whether this poses risks to human health.

To address these issues, government bodies around the world have published guidance documents, set policies and considered regulations. These have been largely based on research that examined nanosilver release from new, unused consumer products or laboratory surrogates, but not actual FCMs during and after use. In a new paper, scientists from the U.S. Food and Drug Administration (FDA), the National Institute of Standards and Technology (NIST) and the U.S. Consumer Product Safety Commission (CPSC) describe how they simulated knife motion, washing and scratching on nanosilver-containing cutting boards to see if consumer use practices affect nanoparticle release.

Using a test method developed at NIST, five different "use scenarios"--each simulating a different type and level of wear commonly seen with human use--were conducted by moving three abrasive surfaces back and forth across samples of nanosilver-enabled cutting board material.

The researchers hope their test method will help regulatory bodies identify if any safety or health risks exist from silver nanoparticles in food contact materials, and if so, find ways to deal with them appropriately before they are approved for sale in the United States.

"A custom-designed razor blade replicated knife cuts, a piece of scrubbing pad mimicked normal dishwashing conditions and a tungsten carbide burr imitated scratching by metal utensils," said NIST physical scientist Keana C.K. Scott, one of the authors on the paper published in the journal Food Additives and Contaminants: Part A. "The washing and scratching scenarios were done at one or two levels of abrasion; for example, 500 and 5,000 cycles for the scratching simulation."

After the abrasion runs, the NIST researchers used sticky tape to see if loose silver nanoparticles were present and could be removed from the worn cutting-board samples. Scanning electron microscopy (SEM) at NIST and inductively coupled plasma mass spectrometry (an incredibly sensitive method for detecting metal ions) at the FDA showed that bits of cutting board polymer were released by abrasion and that some of these contained embedded silver. However, free silver nanoparticles were not found on the SEM-examined tape.

FDA scientists also determined how much, if any, silver ions and intact silver nanoparticles would migrate away from cutting boards when exposed to water and acetic acid. They found that the concentrations of ionic and particulate silver found in both solutions were very low. In fact, there was no discernable difference in the silver migration observed from the new and unused nanosilver-enabled cutting boards compared with the ones that were cut, washed or scratched.

Based on their findings, the NIST and FDA researchers suggested that future studies should examine whether a combination of use scenarios would increase the amount of silver ions or nanoparticles released. For example, they said, perhaps washing the cutting board after scratching would have a different impact.

"Now that we've shown that the migration evaluation method works, it can be used to help answer this and other questions about what happens when people use FCMs with nanoparticles," said NIST research chemist David Goodwin, another author on the paper. "In turn, those findings should be valuable for the bodies that must determine any health or safety risks."

A geology professor at the University of Nevada, Las Vegas, has discovered that a set of 28 footprints left behind by a reptile-like creature 310 million years ago, are the oldest ever to be found in Grand Canyon National Park.

The fossil trackway covers a fallen boulder that now rests along the Bright Angel Trail in the national park. Rowland presented his findings at the recent annual meeting of the Society of Vertebrate Paleontology.

"It's the oldest trackway ever discovered in the Grand Canyon in an interval of rocks that nobody thought would have trackways in it, and they're among the earliest reptile tracks on earth," said Rowland.

Rowland said he's not prepared to say that they're the oldest tracks of their kind ever discovered, but it's a possibility, as he's still researching the discovery.

"In terms of reptile tracks, this is really old," he said, adding that the tracks were created as the supercontinent Pangaea was beginning to form.

Rowland was first alerted to the tracks in spring 2016 by a colleague who was hiking the trail with a group of students. The boulder ended up along the trail after the collapse of a cliff.

A year later, Rowland studied the footprints up close.

"My first impression was that it looked very bizarre because of the sideways motion," Rowland said. "It appeared that two animals were walking side-by-side. But you wouldn't expect two lizard-like animals to be walking side-by-side. It didn't make any sense."

When he arrived home, he made detailed drawings, and began hypothesizing about the "peculiar, line-dancing gait" left behind by the creature.

"One reason I've proposed is that the animal was walking in a very strong wind, and the wind was blowing it sideways," he said.

Another possibility is that the slope was too steep, and the animal sidestepped as it climbed the sand dune. Or, Rowland said, the animal was fighting with another creature, or engaged in a mating ritual.

"I don't know if we'll be able to rigorously choose between those possibilities," he said.

He plans to publish his findings along with geologist Mario Caputo of San Diego State University in January. Rowland also hopes that the boulder is soon placed in the geology museum at the Grand Canyon National Park for both scientific and interpretive purposes.

Meanwhile, Rowland said that the footprints could belong to a reptile species that has never yet been discovered.

"It absolutely could be that whoever was the trackmaker, his or her bones have never been recorded," Rowland said.

Young men who are overly preoccupied with building muscle have a significantly higher risk of depression, weekend binge drinking, and dieting that is not connected to obesity.

They also have four times the probability of using legal and illegal supplements, and anabolic steroids, a new study from the Norwegian University of Science and Technology (NTNU) and Harvard University has shown.

The study also shows that ten per cent of men have what is thought of as the more common type of body image disorder. That is, they think they are too fat and want to be thinner.

According to the study, more than one in three young men have been on a diet in the past year. Their dieting was unrelated to obesity.

The study brings to light many alarming findings. It is the first of its kind in Norway and internationally to investigate men and their relationship to their body and muscles.

The study makes clear that boys and young men struggle much more with body image disorders than we have been aware of.

Want the same body as Ronaldo

"I'm thinking of taking anabolic steroids."

"I don't think my chest is muscular enough."

"I feel guilty if I miss a workout."

These and similar statement were made by 2460 men aged 18-32 years who participated in Trine Tetlie Eik-Nes' study.

She is an associate professor in NTNU's Department of Neuromedicine and Movement Science. The study was recently published in the International Journal of Eating Disorders, and suggests that many young men are preoccupied with a drive for muscularity.

"The problem arises when the bodies of professional athletes like Ronaldo become the ideal for regular young men who have jobs, studies and family. Training has to be your full-time job if you want to look like Ronaldo. He belongs to one in a thousand of the world's population who make their living from sports. Some people train as if they were on the national team, but they're only exercisers. This is the difference we need be concerned about," says Eik-Nes.

She adds, "Girls are supposed to be thin and have small waistlines. Boys should have wide shoulders and big muscles. Those are the narrow ideals that young people grow up with today. It turns out that this unrealistic body image is as challenging for men as for women."

Boys asked questions more appropriate for girls

She believes that the body image challenges facing men have flown under the radar of researchers, parents and health professionals.

"We've been aware of young girls and eating disorders for a long time, and how unfortunate it is to grow up with role models that are so skinny. Studies have been carried out on young men too, but they were asked the same questions as girls. Boys aren't looking to be thin. They want to have big muscles. So the questions given to girls are totally wrong if we want find out how young men see themselves and their own bodies," says Eik-Nes.

Muscles work like cosmetics

Previous studies have shown that boys who are overweight, or thin and lanky, are at greatest risk of developing body image disorders as young men. The study confirmed this idea, since the men's desire for a muscular body was unrelated to their weight.

According to Eik-Nes, muscles become a form of cosmetics for muscle-obsessed men. They're not building their strength to ski faster, or to get better at football or to improve their health.

"They're only exercising to build their muscles, without the training having anything to do with muscle function. That's a big difference," she says.

The challenge of being satisfied with your own body is the same across all education levels. People who are highly educated are no more satisfied with their bodies than anyone else, the study indicates.

Should set off alarm bells

"This drive for muscularity could be a sign that young men don't have mastery over their lives, but they may feel that they're mastering how to work out. In this context, in simple terms, you could say that girls vomit, while boys are much more preoccupied with exercising than normal," says Eik-Nes.

She emphasizes that exercise in itself promotes health. It's when training takes over life that it can be problematic.

"Parents' alarm bells should go off if they have a youngster who's at the gym everyday, who just wants to eat chicken and broccoli and who consumes protein shakes or supplements all the time. If their whole world is about their workouts, parents should take the time to talk with them - for example, by asking questions about what they're actually training for," Eik-Nes says.

Young American men were the respondents for the study, which was conducted in the United States.

"The culture and the role models in the Western world are largely the same. I don't think Norwegian men would answer much differently than the American men did. This is the first study ever that shows the relationships between the desire for muscles among men and the risks this may entail. Now we have to go ahead and investigate the extent of the problem, the risk factors and treatment options," says Eik-Nes.

A study published in The Lancet HIV shows that HIV-2 is more pathogenic than previously demonstrated. The new findings indicate that early treatment should be applied to all patients with HIV, not only to those with HIV-1.

"The study is unique in that we have followed cohort of study participants frequently over a long period, which enabled us to determine when the patients became infected by HIV, as well as to follow the development of the disease. Our data indicates that the majority of those infected with HIV-2 will develop and die of AIDS, something previous studies have not been able to determine", says Joakim Esbjörnsson, associate senior lecturer and researcher in medical microbiology at Lund University in Sweden.

The virus types HIV-1 and HIV-2 are closely related, but vary in their dissemination over the world. HIV-1 has spread globally whereas HIV-2, which is considered to be a milder variant of HIV, is mainly prevalent in West Africa.

The study is the first ever to present reliable estimates of the time between HIV infection and AIDS or HIV-related death for HIV-2. The researchers followed up on 4 900 individuals in a cohort study in Guinea-Bissau over 23 years, between 1990 and 2013, which involved annual examinations including blood tests. The study also compared individuals infected with HIV-1 with HIV-negative individuals in the same cohort. Data from the study shows that people with HIV-2 develop HIV-related infections and AIDS in an almost identical manner to those with HIV-1, although the process is slower over time.

Previous studies have indicated that a large proportion of those with HIV-2, even without antiretroviral treatment, would have a normal life expectancy without any HIV-related complications, unlike those with HIV-1 for whom the absence of treatment led to the development of AIDS in more than 98 per cent of cases. Not even the WHO's treatment recommendations explicitly state that treatment should be offered to patients with HIV-2.

"There is a commonly held belief within research as well as in public healthcare about the various types of HIV: that HIV-2 does not lead to disease in the same way as HIV-1. We want to dismantle this belief and change the views on the international treatment recommendations", says Joakim Esbjörnsson.

A similar study has not been done previously, as the course of HIV disease is long, and it is unlikely that it will be possible to do something similar again. Joakim Esbjörnsson believes that the difficulty in studying HIV-2 over time is one of the reasons for the general uncertainty about how aggressive HIV-2 is, and also for the prevailing view of when treatment should be started.

Another specific problem with HIV-2 is that the majority of HIV-2-infected people do not have measurable virus levels in the blood, which has increased uncertainty as to when and whether treatment should be introduced, according to Hans Norrgren, associate professor of infectious diseases at Lund University and consultant physician at the infection clinic at Skåne University Hospital in Lund.

"Furthermore, HIV-2 mainly occurs in West Africa, which is the world's poorest region, characterised by low investment levels and frequent political instability. This not only makes research and development more difficult in the region, but has also contributed to the fact that commercial interest in the development of diagnostics and treatment of HIV-2 has not been equally strong", says Fredrik Månsson, researcher in clinical infectious diseases at Lund University and specialist physician at the infection clinic at Skåne University Hospital in Malmö.

The researchers would like to see more research in the field and on treatment for HIV, to better understand the differences between the two types. Among other things, a treatment study over time is needed to verify the usefulness of early treatment for patients with HIV-2.

A pioneering technique designed to spot differences between immune cells in tumours could speed the development of cancer treatments, research suggests.

Scientists say the approach could be used to help doctors choose the best treatments for individual patients and predict which tumours are likely to respond to a particular therapy.

It could help target the use of immunotherapy - a new form of treatment that uses the body's own defences to tackle cancer. This therapy has shown great promise in recent years, but identifying which patients will respond best is a challenge for doctors.

The new approach - based on gene analysis - makes it easier to spot the range of immune cells present in a tumour. These cells could help the body detect and kill cancer when activated by certain drugs, scientists say.

Traditional treatments such as radiology do not discriminate between cell types and attack both cancerous and healthy cells, often leading to side-effects.

Researchers at the University of Edinburgh analysed genes from anonymised medical databases of thousands of tumours to identify genes associated with immune cells.

This allowed them to quickly detect immune cells in a tumour based on their genetic code even when they were mixed in with harmful cancerous cells and normal cells.

They say that this resource - called ImSig - paints the best picture of tumours to date and will allow scientists to study how certain immune cell types affect cancer growth.

In future, this could help doctors decide which patients were most likely to respond to immunotherapy, experts say.

Osaka, Japan - Technological advances have enabled scientists to obtain massive amounts of data on different information-carrying molecules in cells and tissues, such as DNA, proteins and various forms of RNA. However, to date, it has been difficult to perform integrated analyses of such information to further our knowledge on the molecules and processes involved in the development of particular diseases.

Researchers from an Osaka University-led collaboration have made a major contribution to our understanding of the complex relationships among the components of cells and tissues. They have established a new analytical approach called MIGWAS that integrates information from two different sources. One of these is associations between genetic variants and diseases and other traits, while the other is data about networks formed between small regulatory molecules called miRNAs and the genes that they target. The team showed that this in silico screening approach provides improved power to reveal novel cellular components associated with diseases and other traits, tissue-specifically.

The use of miRNA data in this way was prompted by accumulating findings on the importance of miRNAs in various physiological functions and diseases. miRNAs are small products of DNA that do not themselves encode proteins, but instead bind to mRNAs to regulate gene expression. In this latest study, the researchers employed previously obtained data on the expression of around 1,800 miRNAs in different cells. They searched for overlaps between these miRNAs and the genes they target on the one hand, and genes identified elsewhere as being linked to diseases and other traits by studies focusing directly on the genetic code on the other.

"It has been difficult to obtain convincing data about the effects of miRNAs as their short length means that they are encoded by only a very small part of the genome," lead author Saori Sakaue says. "Our MIGWAS approach linking findings from genome-wide association studies and miRNA-target networks helps to overcome this. It successfully obtained significant results for miRNA/target gene enrichment for traits such as height and type 2 diabetes across different ethnic groups."

The team attempted to validate this approach by focusing on the disease rheumatoid arthritis (RA), using data on single-nucleotide polymorphisms from nearly 20,000 RA cases and over 60,000 corresponding controls. This revealed four miRNAs linked to RA that were also identified by the MIGWAS pipeline, one of which was significantly highly expressed in RA patients.

"The analytical power of our approach shows its potential for finding new networks of miRNAs and their target genes linked to traits and diseases, in a tissue-specific way," corresponding author Yukinori Okada says. "This should make it easier to find new targets that we can focus on for developing therapeutic strategies for a wide range of diseases."

Overall, men are at greater risk of heart attack than women, but several studies have suggested that certain risk factors have more of an impact on the risk in women than in men.

To look more closely at this association, researchers looked at data on almost half a million people enrolled in the UK Biobank - a database of biological information from British adults.

The 471,998 people had no history of cardiovascular disease, were aged 40 to 69 years and 56% of them were women.

Over an average of seven years, 5,081 people (29% of whom were women) had their first heart attack, meaning that the incidence of heart attack was 7.76 per 10,000 person years in women compared with 24.35 per 10,000 person years in men.

High blood pressure, diabetes and smoking increased the risk of a heart attack in both sexes but their impact was far greater in women.

Smoking increased a woman's risk of a heart attack by 55% more than it increased the risk in a man, while high blood pressure increased a woman's risk of heart attack by an extra 83% relative to its effect in a man.

Type II diabetes, which is usually associated with poor diet and other lifestyle factors, had a 47% greater impact on the heart attack risk of a woman relative to a man, while type I diabetes had an almost three times greater impact in a woman.

The authors believe that theirs is the first study to analyse both absolute and relative differences in heart attack risk between the sexes across a range of risk factors in a general population, but they emphasise that it is an observational study, so no firm conclusions can be drawn about cause and effect.

"The presence of hypertension, smoking, and diabetes were associated with an increased risk of myocardial infarction in both women and men, but with an excess relative risk among women," the authors say.

"Women should, at least, receive the same access to guideline-based treatments for diabetes and hypertension, and to resources to help lose weight and stop smoking as do men."

In the UK, women with diabetes are 15% less likely than men with diabetes to receive all recommended care processes, and may be less likely to achieve target values when treated for cardiovascular risk factors.

While the overall impact of smoking, high blood pressure and diabetes on heart attack risk decreased in both sexes with age, the greater risk these factors had on the risk of heart attack in women relative to their impact in men persisted.

"Rising prevalence of lifestyle-associated risk factors, coupled with the ageing population, is likely to result in women having a more similar overall rate of myocardial infarction to men than is the case at present, with a subsequent significant additional burden on society and health resources," the authors warn.

Menlo Park, Calif. -- Despite its role in shaping life as we know it, many aspects of photosynthesis remain a mystery. An international collaboration between scientists at SLAC National Accelerator Laboratory, Lawrence Berkeley National Laboratory and several other institutions is working to change that. The researchers used SLAC's Linac Coherent Light Source (LCLS) X-ray laser to capture the most complete and highest resolution picture to date of Photosystem II, a key protein complex in plants, algae and cyanobacteria responsible for splitting water and producing the oxygen we breathe. The results were published in Nature today.

Explosion of life

When Earth formed about 4.5 billion years ago, the planet's landscape was almost nothing like what it is today. Junko Yano, one of the authors of the study and a senior scientist at Lawrence Berkeley National Laboratory, describes it as "hellish." Meteors sizzled through a carbon dioxide-rich atmosphere and volcanoes flooded the surface with magmatic seas.

Over the next 2.5 billion years, water vapor accumulating in the air started to rain down and form oceans where the very first life appeared in the form of single-celled organisms. But it wasn't until one of those specks of life mutated and developed the ability to harness light from the sun and turn it into energy, releasing oxygen molecules from water in the process, that Earth started to evolve into the planet it is today. This process, oxygenic photosynthesis, is considered one of nature's crown jewels and has remained relatively unchanged in the more than 2 billion years since it emerged.

"This one reaction made us as we are, as the world. Molecule by molecule, the planet was slowly enriched until, about 540 million years ago, it exploded with life," said co-author Uwe Bergmann, a distinguished staff scientist at SLAC. "When it comes to questions about where we come from, this is one of the biggest."

A greener future

Photosystem II is the workhorse responsible for using sunlight to break water down into its atomic components, unlocking hydrogen and oxygen. Until recently, it had only been possible to measure pieces of this process at extremely low temperatures. In a previous paper, the researchers used a new method to observe two steps of this water-splitting cycle at the temperature at which it occurs in nature.

Now the team has imaged all four intermediate states of the process at natural temperature and the finest level of detail yet. They also captured, for the first time, transitional moments between two of the states, giving them a sequence of six images of the process.

The goal of the project, said co-author Jan Kern, a scientist at Berkeley Lab, is to piece together an atomic movie using many frames from the entire process, including the elusive transient state at the end that bonds oxygen atoms from two water molecules to produce oxygen molecules.

"Studying this system gives us an opportunity to see how metals and proteins work together and how light controls such kinds of reactions," said Vittal Yachandra, one of the authors of the study and a senior scientist at Lawrence Berkeley National Laboratory who has been working on Photosystem II for more than 35 years. "In addition to opening a window on the past, a better understanding of Photosystem II could unlock the door to a greener future, providing us with inspiration for artificial photosynthetic systems that produce clean and renewable energy from sunlight and water."

Sample assembly line

For their experiments, the researchers grow what Kern described as a "thick green slush" of cyanobacteria -- the very same ancient organisms that first developed the ability to photosynthesize -- in a large vat that is constantly illuminated. They then harvest the cells for their samples.

At LCLS, the samples are zapped with ultrafast pulses of X-rays to collect both X-ray crystallography and spectroscopy data to map how electrons flow in the oxygen-evolving complex of photosystem II. In crystallography, researchers use the way a crystal sample scatters X-rays to map its structure; in spectroscopy, they excite the atoms in a material to uncover information about its chemistry. This approach, combined with a new assembly-line sample transportation system, allowed the researchers to narrow down the proposed mechanisms put forward by the research community over the years.

Mapping the process

Previously, the researchers were able to determine the room temperature structure of two of the states at a resolution of 2.25 angstroms; one angstrom is about the diameter of a hydrogen atom. This allowed them to see the position of the heavy metal atoms, but left some questions about the exact positions of the lighter atoms, like oxygen. In this paper, they were able to improve the resolution even further, to 2 angstroms, which enabled them to start seeing the position of lighter atoms more clearly, as well as draw a more detailed map of the chemical structure of the metal catalytic center in the complex where water is split.

This center, called the oxygen-evolving complex, is a cluster of four manganese atoms and one calcium atom bridged with oxygen atoms. It cycles through the four stable oxidation states, S0-S3, when exposed to sunlight. On a baseball field, S0 would be the start of the game when a player on home base is ready to go to bat. S1-S3 would be players on first, second, and third. Every time a batter connects with a ball, or the complex absorbs a photon of sunlight, the player on the field advances one base. When the fourth ball is hit, the player slides into home, scoring a run or, in the case of Photosystem II, releasing breathable oxygen.

The researchers were able to snap action shots of how the structure of the complex transformed at every base, which would not have been possible without their technique. A second set of data allowed them to map the exact position of the system in each image, confirming that they had in fact imaged the states they were aiming for.

Sliding into home

But there are many other things going on throughout this process, as well as moments between states when the player is making a break for the next base, that are a bit harder to catch. One of the most significant aspects of this paper, Yano said, is that they were able to image two moments in between S2 and S3. In upcoming experiments, the researchers hope to use the same technique to image more of these in-between states, including the mad dash for home -- the transient state, or S4, where two atoms of oxygen bond together -- providing information about the chemistry of the reaction that is vital to mimicking this process in artificial systems.

"The entire cycle takes nearly two milliseconds to complete," Kern said. "Our dream is to capture 50 microsecond steps throughout the full cycle, each of them with the highest resolution possible, to create this atomic movie of the entire process."

Although they still have a way to go, the researchers said that these results provide a path forward, both in unveiling the mysteries of how photosynthesis works, and in offering a blueprint for artificial sources of renewable energy.

"It's been a learning process," said SLAC scientist and co-author Roberto Alonso-Mori. "Over the last seven years we've worked with our collaborators to reinvent key aspects of our techniques. We've been slowly chipping away at this question and these results are a big step forward."

For the first time, a team of astronomers has observed several pairs of galaxies in the final stages of merging together into single, larger galaxies. Peering through thick walls of gas and dust surrounding the merging galaxies' messy cores, the research team captured pairs of supermassive black holes--each of which once occupied the center of one of the two original smaller galaxies--drawing closer together before they coalescence into one giant black hole.

Led by University of Maryland alumnus Michael Koss (M.S. '07, Ph.D. '11, astronomy), a research scientist at Eureka Scientific, Inc., with contributions from UMD astronomers, the team surveyed hundreds of nearby galaxies using imagery from the W.M. Keck Observatory in Hawaii and NASA's Hubble Space Telescope. The Hubble observations represent more than 20 years' worth of images from the telescope's lengthy archive. The team described their findings in a research paper published on November 8, 2018, in the journal Nature.

"Seeing the pairs of merging galaxy nuclei associated with these huge black holes so close together was pretty amazing," Koss said. "In our study, we see two galaxy nuclei right when the images were taken. You can't argue with it; it's a very 'clean' result, which doesn't rely on interpretation."

The high-resolution images also provide a close-up preview of a phenomenon that astronomers suspect was more common in the early universe, when galaxy mergers were more frequent. When the black holes finally do collide, they will unleash powerful energy in the form of gravitational waves--ripples in space-time recently detected for the first time by the twin Laser Interferometer Gravitational-wave Observatory (LIGO) detectors.

The images also presage what will likely happen in a few billion years, when our Milky Way galaxy merges with the neighboring Andromeda galaxy. Both galaxies host supermassive black holes at their center, which will eventually smash together and merge into one larger black hole.

The team was inspired by a Hubble image of two interacting galaxies collectively called NGC 6240, which later served as a prototype for the study. The team first searched for visually obscured, active black holes by sifting through 10 years' worth of X-ray data from the Burst Alert Telescope (BAT) aboard NASA's Neil Gehrels Swift Observatory.

"The advantage to using Swift's BAT is that it observes high-energy, 'hard' X-rays," said study co-author Richard Mushotzky, a professor of astronomy at UMD and a fellow of the Joint Space-Science Institute (JSI). "These X-rays penetrate through the thick clouds of dust and gas that surround active galaxies, allowing the BAT to see things that are literally invisible in other wavelengths."

The researchers then combed through the Hubble archive, zeroing in on the merging galaxies they spotted in the X-ray data. They then used the Keck telescope's super-sharp, near-infrared vision to observe a larger sample of the X-ray-producing black holes not found in the Hubble archive.

The team targeted galaxies located an average of 330 million light-years from Earth--relatively close by in cosmic terms. Many of the galaxies are similar in size to the Milky Way and Andromeda galaxies. In total, the team analyzed 96 galaxies observed with the Keck telescope and 385 galaxies from the Hubble archive.

Their results suggest that more than 17 percent of these galaxies host a pair of black holes at their center, which are locked in the late stages of spiraling ever closer together before merging into a single, ultra-massive black hole. The researchers were surprised to find such a high fraction of late-stage mergers, because most simulations suggest that black hole pairs spend very little time in this phase.

To check their results, the researchers compared the survey galaxies with a control group of 176 other galaxies from the Hubble archive that lack actively growing black holes. In this group, only about one percent of the surveyed galaxies were suspected to host pairs of black holes in the later stages of merging together.

This last step helped the researchers confirm that the luminous galactic cores found in their census of dusty interacting galaxies are indeed a signature of rapidly-growing black hole pairs headed for a collision. According to the researchers, this finding is consistent with theoretical predictions, but until now, had not been verified by direct observations.

"People had conducted studies to look for these close interacting black holes before, but what really enabled this particular study were the X-rays that can break through the cocoon of dust," explained Koss. "We also looked a bit farther in the universe so that we could survey a larger volume of space, giving us a greater chance of finding more luminous, rapidly-growing black holes."

It is not easy to find galactic nuclei so close together. Most prior observations of merging galaxies have caught the coalescing black holes at earlier stages, when they were about 10 times farther away. The late stage of the merger process is so elusive because the interacting galaxies are encased in dense dust and gas, requiring very high-resolution observations that can see through the clouds and pinpoint the two merging nuclei.

"Computer simulations of galaxy smashups show us that black holes grow fastest during the final stages of mergers, near the time when the black holes interact, and that's what we have found in our survey," said Laura Blecha, an assistant professor of physics at the University of Florida and a co-author of the study. Blecha was a JSI Prize Postdoctoral Fellow in the UMD Department of Astronomy prior to joining UF's faculty in 2017. "The fact that black holes grow faster and faster as mergers progress tells us galaxy encounters are really important for our understanding of how these objects got to be so monstrously big."

Future infrared telescopes such as NASA's highly anticipated James Webb Space Telescope (JWST), slated for launch in 2021, will provide an even better view of mergers in dusty, heavily obscured galaxies. For nearby black hole pairs, JWST should also be capable of measuring the masses, growth rates and other physical parameters for each black hole.

"There might be other objects that we missed. Even with Hubble, many nearby galaxies at low redshift cannot be resolved--the two nuclei just merge into one," said study co-author Sylvain Veilleux, a professor of astronomy at UMD and a JSI Fellow. "With JWST's higher angular resolution and sensitivity to the infrared, which can pass through the dusty cores of these galaxies, searches for these nearby objects should be easy to do. Also with JWST, we will be able to push toward larger distances, to see objects at higher redshift. With these observations, we can begin to explore the fraction of objects that are merging in the youngest, most distant regions of the universe--which should be fairly frequent."

The human genome has its own proofreaders and editors, and their handiwork is not as haphazard as once thought.

When DNA's double helix is broken after damage from, say, exposure to X-rays, molecular machines perform a kind of genetic "auto-correction" to put the genome back together -- but those repairs are often imperfect. Just as your smartphone might amend a misspelled text message into an incoherent phrase, the cell's natural DNA repair process can add or remove bits of DNA at the break site in a seemingly random and unpredictable manner. Editing genes with CRISPR-Cas9 allows scientists to break DNA at specific locations, but this can create "spelling errors" that alter the function of genes.

This response to CRISPR-induced damage, called "end joining," is useful for disabling a gene, but researchers have deemed it too error-prone to exploit for therapeutic purposes.

A new study upends this view. By creating a machine-learning algorithm that predicts how human and mouse cells respond to CRISPR-induced breaks in DNA, a team of researchers discovered that cells often repair broken genes in ways that are precise and predictable, sometimes even returning mutated genes back to their healthy version. In addition, the researchers put this predictive power to the test and successfully corrected mutations in cells taken from patients with one of two rare genetic disorders.

The work suggests that the cell's genetic auto-correction could one day be combined with CRISPR-based therapies that correct gene mutations by simply cutting DNA precisely and allowing the cell to naturally heal the damage.

The study, published this week in Nature, was led by David Liu, the Richard Merkin Professor and director of the Merkin Institute of Transformative Technologies in Healthcare, and vice chair of the faculty at the Broad Institute; David Gifford, professor of computer science and biological engineering at MIT; and Richard Sherwood, an assistant professor of medicine in the Division of Genetics at Brigham and Women's Hospital.

"Machine learning offers new horizons for the development of human therapeutics", said Gifford, "This study is an example of how combining computational experiment design and analysis with therapeutic goals can produce an unexpected therapeutic modality."

"We don't currently have an efficient way to precisely correct many human disease mutations," said Liu. "Using machine learning, we've shown we can often correct those mutations predictably, by simply letting the cell repair itself."

Many disease-associated mutations involve extra or missing DNA, known as insertions and deletions. Researchers have tried to correct those mutations with CRISPR-based gene editing. To do this, they cut the double helix with an enzyme and insert missing DNA, or remove extra DNA, using a template of genetic material that serves as a blueprint. The approach, however, only works in rapidly dividing cells like blood stem cells and even then it is only partly effective, making it a poor choice for therapeutics aimed at the majority of cell types in the body. To restore gene function without templated repair requires knowing how the cell will fix CRISPR-induced DNA breaks--knowledge that did not exist until now.

Evidence of a pattern to CRISPR repair outcomes had been noted previously, and Gifford's lab began to think that such outcomes might be predictable enough to model accurately; however, they needed much more data to turn those patterns into an accurate predictive understanding.

Led by MIT graduate student Max Shen and Broad Institute postdoctoral researcher Mandana Arbab, the researchers developed a strategy to observe how cells repaired a library of 2,000 sites targeted by CRISPR in the mouse and human genomes. After observing how the cell repaired those cuts, they poured the resulting data into a machine-learning model, inDelphi, prompting the algorithm to learn how the cell responded to cuts at each site -- that is, which bits of DNA the cell added to or removed from each damaged gene.

They found that inDelphi could discern patterns at cut sites that predicted what insertions and deletions were made in the corrected gene. At many sites, the set of corrected genes did not contain a huge mixture of variations, but rather a single outcome, such as correction of a pathogenic gene.

Indeed, after querying inDelphi for disease-relevant genes that could be corrected by cutting in just the right place, the researchers found nearly two hundred pathogenic genetic variants that were mostly corrected to their normal, healthy versions after being cut with CRISPR-associated enzymes. They were also able to correct mutations in cells from patients with two rare genetic disorders, Hermansky-Pudlak syndrome and Menkes disease.

"We show that the same CRISPR enzyme that has been used primarily as a sledgehammer can also act as a chisel," said Sherwood. "The ability to know the most likely outcome of your experiment before you do it will be a real advance for the many researchers using CRISPR."

"We had hoped that we would be able to repair disease-associated genes to their native forms, and it was quite rewarding to see that our hypothesis was correct," said Gifford.

A University of Kent study into post partum depression found the odds of developing this condition increased by 79% when mothers had baby boys compared to baby girls.

Overall the researchers identified that women who give birth to males are 71-79% more likely to develop post partum depression. Furthermore, women whose births had complications were 174% more likely to experience post partum compared to those women who had no complications.

As a result of their findings, Dr Sarah Johns and Dr Sarah Myers in the University's School of Anthropology and Conservation (SAC), conclude that recognising that both male infants and birth complications are post partum risk factors should help health professionals in identifying and supporting women who may by more likely to develop this condition.

Their research also showed that while women with a tendency towards symptoms of depression, anxiety, and stress were always at increased risk of post partum, they had reduced odds of developing post partum after experiencing birth complications. This is likely because these women may receive greater post-birth support because their mental health concerns were previously recognised. This finding suggests interventions to support women can be effective in preventing post partum developing.

Dr Johns said: 'Post partum is a condition that is avoidable, and it has been shown that giving women at risk extra help and support can make it less likely to develop. The finding that having a baby boy or a difficult birth increases a woman's risk gives health practitioners two new and easy ways to identify women who would particularly benefit from additional support in the first few weeks and months'

Dr Johns and Dr Myers decided to assess whether there was a relationship between the sex of infants and post partum because of the known link between inflammatory immune response and the development of depressive symptoms.

Both the gestation of male foetuses and the experience of birth complications have documented associations with increased inflammation, yet, until this study, their relationships with post partum were unclear.

Many known risk factors for depressive symptoms are associated with activation of inflammatory pathways, opening up the potential for identifying new risk factors based on their inflammation causing effects - an idea supported by this study.

The study used complete reproductive histories of 296 women from contemporary, low fertility populations.