Culture

Taking advantage of powerful advances in CRISPR gene editing, scientists at the University of California San Diego have set their sights on one of society's most formidable threats to human health.

A research team led by Andrés Valderrama at UC San Diego School of Medicine and Surashree Kulkarni of the Division of Biological Sciences has developed a new CRISPR-based gene-drive system that dramatically increases the efficiency of inactivating a gene rendering bacteria antibiotic-resistant. The new system leverages technology developed by UC San Diego biologists in insects and mammals that biases genetic inheritance of preferred traits called "active genetics." The new "pro-active" genetic system, or Pro-AG, is detailed in a paper published December 16 in Nature Communications.

Widespread prescriptions of antibiotics and use in animal food production have led to a rising prevalence of antimicrobial resistance in the environment. Evidence indicates that these environmental sources of antibiotic resistance are transmitted to humans and contribute to the current health crisis associated with the dramatic rise in drug-resistant microbes. Health experts predict that threats from antibiotic resistance could drastically increase in the coming decades, leading to some 10 million drug-resistant disease deaths per year by 2050 if left unchecked.

The core of Pro-AG features a modification of the standard CRISPR-Cas9 gene editing technology in DNA. Working with Escherichia coli bacteria, the researchers developed the Pro-AG method to disrupt the function of a bacterial gene conferring antibiotic resistance. In particular, the Pro-AG system addresses a thorny issue in antibiotic resistance presented in the form of plasmids, circular forms of DNA that can replicate independently of the bacterial genome. Multiple copies of, or "amplified," plasmids carrying antibiotic-resistant genes can exist in each cell and feature the ability to transfer antibiotic resistance between bacteria, resulting in a daunting challenge to successful treatment. Pro-AG works by a cut-and-insert repair mechanism to disrupt the activity of the antibiotic resistant gene with at least two orders of magnitude greater efficiency than current cut-and-destroy methods.

Valderrama and Kulkarni, working in the UC San Diego labs of study coauthors Professors Victor Nizet and Ethan Bier, respectively, demonstrated the effectiveness of the new technique in experimental cultures containing a high number of plasmids carrying genes known to confer resistance to the antibiotic ampicillin. The system relies on a self-amplifying "editing" mechanism that increases its efficiency through a positive feedback loop. The result of Pro-AG editing is the insertion of tailored genetic payloads into target sites with high precision.

Eventual human applications include potential treatments for patients suffering from chronic bacterial infections.

While Pro-AG is not yet ready for treating patients, "a human delivery system carrying Pro-AG could be deployed to address conditions such as cystic fibrosis, chronic urinary infections, tuberculosis and infections associated with resistant biofilms that pose difficult challenges in hospital settings," said Nizet, distinguished professor of Pediatrics and Pharmacy and the faculty lead of the UC San Diego Collaborative to Halt Antibiotic-Resistant Microbes (CHARM).

When combined with a variety of existing delivery mechanisms for spreading the Pro-AG system through populations of bacteria, the scientists say the technology also could be widely effective in removing, or "scrubbing," antibiotic-resistant strains from the environment in areas such as sewers, fish ponds and feedlots. Because Pro-AG "edits" its targets rather than destroys them, this system also enables engineering or manipulating bacteria for a broad range of future biotechnological and biomedical applications rendering them harmless or even recruiting them to perform beneficial functions.

"The highly efficient and precise nature of Pro-AG should permit a variety of practical applications, including dissemination of this system throughout populations of bacteria using one of several existing delivery systems to greatly reduce the prevalence of antibiotic resistance in the environment," said Bier, a distinguished professor in the Section of Cell and Developmental Biology and science director of the UC San Diego unit of the Tata Institute for Genetics and Society (TIGS).

Mercury contamination of the marine environment is a global public health concern. Human exposure occurs primarily by eating seafood, especially large predatory fish such as swordfish and albacore tuna. Those most vulnerable - pregnant women: mercury exposure during pregnancy has been associated with cognitive impairment, including memory, attention, fine motor skills, and other markers of delayed neurodevelopment, although results are conflicting.

Researchers from Florida Atlantic University's Harbor Branch Oceanographic Institute and collaborators conducted a study to assess mercury concentrations in the hair of pregnant women living in coastal Florida and to determine the relationships between hair total mercury concentrations, fish consumption, sources of seafood, knowledge of the risks of mercury exposure, and seafood consumption during pregnancy.

This latest study follows their previous research showing that bottlenose dolphins in the Indian River Lagoon have some of the highest concentrations of mercury in this species worldwide. The lagoon is an estuary that extends more than 250 kilometers and traverses 40 percent of the eastern coastline in Florida and is a highly impacted environment. To "close the loop" between this wildlife sentinel and human health, they also conducted a prior study in recreational anglers and coastal residents. They found mercury concentrations in the hair of 135 participants that was higher than those previously reported for similar populations in the United States.

"In Florida the average adult consumes almost 10 times as many grams of seafood per day compared to the general U.S. population, potentially increasing the risk of mercury exposure above safe limits, especially for pregnant women," said Adam M. Schaefer, MPH, lead author, and an epidemiologist at FAU's Harbor Branch. "Because the sensitivity of the developing brain to the effects of mercury deposition has been shown in studies of pregnant women exposed through the consumption of seafood, even at relatively low levels of prenatal mercury, we wanted to test this vulnerable coastal Florida population."

Researchers also described the complex relationship between mercury and neurobehavioral outcomes. Specifically, the well-described benefits of seafood consumption and omega-3 fatty acids during pregnancy.

Results of the study, published in the International Journal of Environmental Research and Public Health, show that despite the fact that southern Florida is an area of selective deposition of atmospheric mercury, and that mercury is bioaccumulated in local fish species and apex predators, the mean total hair mercury concentration of the 229 participants was lower or similar to U.S. data for women of child-bearing age. Hair mercury concentration was associated with consumption of locally caught seafood and all seafood, a higher level of education, and first pregnancy.

Those who reported eating seafood three times a week had the highest concentration of mercury in their hair - almost four times as high as those who did not consume any seafood. The highest concentrations were in women over the age of 33 with the highest levels observed among Asian women. Mercury concentrations in hair among those pregnant women who consumed seafood from the Indian River Lagoon were significantly higher than among women who reported never consuming locally caught items. Level of education and the number of children also were related to hair mercury concentration.

Knowledge and education were important components of the study. The majority of participants (85.5 percent) reported being aware that high levels of mercury may be harmful to the unborn fetus. Similarly, 89 percent of women were aware that some fish can contain high levels of mercury. When asked how often one should consume tuna steaks and swordfish, 76.8 percent of women answered that the consumption of these items should be avoided during pregnancy. However, only 53.7 percent of women knew that store-bought swordfish can contain high concentrations of mercury.

"In view of the serious consequences of prenatal exposure to high concentrations of mercury, continued education on safe sources and species of seafood is warranted," said Schaefer. "Educational efforts must provide a balanced approach to include information regarding the benefits of fish consumption while minimizing risk by avoiding locally caught seafood or fish species known to contain high levels of mercury."

When we hear the phrase 'a pink banana', we can understand what it means and form the intended thought - even though bananas are typically yellow. This is because we compose the meanings of separate words into a new whole. "Meaning composition is the lynchpin of cognition, necessary for explaining the creativity of human thought and communication", says co-editor Andrea Martin, Group Leader at the Max Planck Institute and Principal Investigator at the Donders Centre for Cognitive Neuroimaging. "It is a capacity that sets us apart from other species and computational devices."

So how does the mind 'make meaning'? This question is not only a hot topic in linguistics, it has also long vexed philosophers. Do we mechanically combine language parts such as "Ann" (a part that linguists may call the "argument") and "laughed" (the "predicate") to arrive at an understanding of "Ann laughed"? Or does "Ann laughed" only make sense once we interpret this sequence of words in its context, integrated with our knowledge of the world?

One focus of the special issue is the neurobiology of meaning composition. Peter Hagoort, director of the Neurobiology of Language Department at the MPI and of the Donders Centre for Cognitive Neuroimaging, emphasises that people interpret language by using multi-modal cues from rich conversational settings, rather than just syntax to combine words. For instance, the combination 'The finger fell in the soup' triggers negative emotions, even though the words themselves are neutral. In Hagoort's model, based on neuroimaging methods such as MEG and fMRI, meaning is composed in a dynamic interaction between brain regions, such as the temporo-parietal and inferior frontal cortex.

A second focus is computational models. MPI's Andrea Martin collaborated with Leonidas Doumas from the University of Edinburgh to model the neurophysiological mechanisms of meaning composition. Martin and Doumas show that previous models are not able to accurately capture human judgments. For instance, when people hear 'fuzzy cactus' and 'fuzzy penguin', they treat 'cactus' and 'penguin' as similar - belonging to the set of fuzzy things - even when the separate words are judged dissimilar. This shows that humans and artificial intelligence systems still have vastly different ways of representing meaning.

The final seven contributions are experimental studies. For instance, Jonathan Brennan from the University of Michigan and Andrea Martin use existing EEG data, recorded as adults listened to an audiobook of 'Alice in Wonderland'. The authors show that brain waves differ depending on the number of phrases that are processed, revealing how the brain is actively computing meaning across linguistic units (words and phrases).

A large-scale ERP experiment by MPI's Mante Nieuwland and his colleagues addresses the well-known N400 response that occurs in the brain as we process unexpected meanings. When we encounter 'You never forget how to ride an elephant', the brain shows a 'surprise' N400 signal at 'elephant', which is absent when the sentence has a more predictable ending ('You never forget how to ride a bicycle'). The authors argue that 'bicycle' is not only more predictable than 'elephant' (speeding up activation of the word's meaning), it also makes the sentence more plausible (speeding up the integration of the word into the sentence) - given our knowledge of the world. The effects of predictability on the N400 occur before those of plausibility, again showing that the brain actively composes the meaning of both words and sentences in context.

The editors are hopeful that the definite model of how the brain makes meaning is within reach. "It would be a significant leap forward in the search for cognitive science's Holy Grail", concludes Martin. "A mechanistic model of meaning composition would offer solutions to a number of open problems in various fields of science, including philosophy, linguistics, neuroscience, psychology, computer science, and artificial intelligence".

Are you ready for the future? Back in 1869, Russia's Dmitri Mendeleev began to classify the elements according to their chemical properties, giving rise to the Periodical Table of Elements. "I saw in a dream a table where all elements fell into place as required. Awakening, I immediately wrote it down on a piece of paper," Mendeleev recalled.

Fast forward 150 years to Israel where a team of scientists, led by Professor Uri Banin at the Hebrew University of Jerusalem's Institute of Chemistry and Center for Nanoscience and Nanotechnology, is reinventing the concept of the periodic table but for artificial atoms, otherwise known as colloidal quantum dots. The nanoscience research team developed a method that enables quantum dots to join together and form new molecular structures. Their findings were published in the latest edition of Nature Communications.

Quantum dots are nano-sized chunks of crystal, each containing hundreds to thousands of semiconductor atoms. When viewed through an electron microscope they look like dots. As with real atoms, when you combine artificial atoms together, they create a new (artificial) molecule with unique properties and characteristics. These molecules are referred to as "artificial" because they're not one of the 150 million original molecules that have been formed by combining atoms from the 118 known elements in our Periodic Table.

Unlike their Periodic Table counterparts, quantum dot atoms are mercurial in nature, changing their physical, electronic and optical properties when their size changes. For example, a larger quantum dot will emit a red light, while a smaller one, of the same material, will emit a green light. Banin and his team devised a method wherein scientists may create new quantum dot molecules while still retaining control over their composition. "I began considering the infinite possibilities that could arise from creating artificial molecules from artificial atom building blocks," Banin shared.

In the past twenty years, both scientists' understanding of the physical properties of quantum dots and their levels of control over these tiny particles have increased tremendously. This has led to a widespread application of quantum dots in our daily lives--from bio-imaging and bio-tracking (relying on the fact that quantum dots emit different colors based on their size) to solar energy and next-generation TV monitors with exceptional color quality.

This new development lays the foundations for the formation of a wide variety of fused quantum dot molecules. "Considering the rich selection of size and composition among colloidal quantum dots, we can only imagine the exciting possibilities for creating a selection of artificial molecules with great promise for their utilization in numerous opto-electronic, sensing and quantum technologies applications," explained Banin.

200 years ago, a doctor from France used a stethoscope for the first time and countless efforts to observe human body have been made since then. Up to now, the best tool that provides anatomical, functional, and molecular information of human and animal is the photoacoustic microscopy. Super-resolution localization photoacoustic microscopy which is 500 times faster than the conventional photoacoustic microscopy system is developed by the research team from POSTECH in Korea.

Professor Chulhong Kim of Creative IT Engineering from POSTECH with Jinyoung Kim, a research professor and Jongbeom Kim, a PhD student presented a fast photoacoustic microscopy system with custom-made scanning mirror in the international journal published by Nature, Light: Science and Applications. This newly developed microscopy uses a stable and commercial galvanometer scanner with a custom-made scanning mirror and can find blocked or burst blood vessels by monitoring the flow of red blood cells without using a contrast absorber.

The photoacoustic microscopy images cells, blood vessels, and tissues by inducing vibrations when the optic energy is converted to heat after an object absorbs light from the laser beam fired. The conventional photoacoustic microscopy systems using a galvanometer scanner have a narrow field of view because they do not scan photoacoustic waves but only the optical beam. The conventional photoacoustic microscopy systems using a linear motorized stage also have temporal limitation in making images.

The research team developed a new photoacoustic microscopy system with improved performances. It can scan both photoacoustic waves and optical beams simultaneously as they implemented the custom-made scanning mirror in the existing photoacoustic microscopy system. Also, it can monitor very small vessels using intrinsic red blood cells without a contrast absorber which helps the system to image blood vessels well. Furthermore, the new system is 500 times faster than that of the conventional ones. With this improvement, it can demonstrate super-resolution image by localizing photoacoustic signals and the spatial resolution is enhanced by 2.5 times.

Their research accomplishment is meaningful in many ways. Especially, this system is expected to be very promising in diagnosis and treatment of stroke and cardiovascular disease. Because it can monitor and image the blood vessels with the flow of blood cells in real time, it can also be used in vascular disease which needs urgent diagnosis and treatment. Moreover, it allows direct monitoring of hemodynamics in the microvessels. It is anticipated to be applied in various fields including hemodynamic response, contrast agent dynamics in blood vessels and transient microcirculatory abnormalities.

Professor Chulhong Kim said, "We successfully imaged microvessels in the ears, eyes, and brains of mice and a human fingertip with this new photoacoustic microscopy system. What we have developed can be a complimentary tool to the conventional brain imaging system and it can also be a promising tool for future preclinical and clinical studies."

Tsukuba, Japan - When you're only one of trillions, it can be hard to get ahead. That's the problem faced by aquatic bacterium Leptothrix cholodnii, which is often found in the slime-like microbial mats common to mineral-rich bodies of water. Therefore, to establish itself in these communities, L. cholodnii forms long, rigid filaments that become an integral part of the structure of the microbial mat.

In a study published last week in ACS Nano, a team led by researchers from the University of Tsukuba used microfluidic chambers to enable visualization of L. cholodnii and study the contribution of nanofibrils to filament formation. A deeper understanding of this process could help researchers make significant inroads in the use of sheath-forming bacteria for processes such as the development of novel amorphous iron oxides for lithium-ion battery anodes and the industrial harvesting of pigments and heavy metals.

L. cholodnii filaments are composed of chains of cells initially surrounded by a soft sheath made of thousands of tiny intertwined hair-like structures called nanofibrils. During filament formation, the bacteria release proteins that oxidize iron and manganese in the water, producing metal oxides that accumulate in the nanofibrils, causing them to harden into a microtube. The nanofibrils can also incorporate precious metals such as gold, silver, titanium, and zirconium. However, the exact role of nanofibrils in filament formation is not known.

"Because microbial mats are often found on stream beds, we used microfluidic chambers to replicate the running water found in these locations," explains lead author of the study Tatsuki Kunoh. "We allowed individual cells to pass into the chambers and then used time-lapse and intermittent fluorescent straining of nanofibrils and atmospheric scanning electron microscopy to examine the behaviour of individual cells and the developing multicellular filaments."

The researchers showed that nanofibrils are essential for bacterial cell attachment to solid surfaces, which is required for filament formation. Confirming this observation, variant "sheathless" L. cholodnii cells, which did not produce nanofibrils, roamed around the chambers throughout the experiment, unable to attach or form a filament.

"By fluorescently staining the nanofibrils, we could monitor their distribution on the bacterial cell surface," says Dr Kunoh. "Interestingly, the positioning of the nanofibrils seemed to dictate the direction of filament elongation--during unilateral elongation, nanofibrils were clustered around the non-dividing end of the cell, while in bilateral elongation, nanofibrils were only present around the central portion of the cell."

The researchers also observed that nanofibrils were densely woven around the mature sections of the growing filaments but formed a more open web-like structure around the newly divided cells.

These new insights into the role of nanofibrils in the development of filaments could enable researchers to tailor L. cholodnii for use in industrial applications such as bioremediation, the extraction of heavy and precious metals, and microwire fabrication.

Non-native plants are providing new homes for Britain's insects - some of which are rare on native plants, a new study has found.

Researchers at the University of York discovered that foreign plants - often found in our gardens and parks - were supporting communities of British insects, including pollinators like butterflies, bees and hoverflies as well as beetles, bugs, and earwigs. For example, native Loosestrife weevils were commonly found consuming the non-native European wand loosestrife, and solitary bees were found visiting the flowers of non-native agave-leaved sea holly plants.

Lead author PhD student Roberto Padovani, from the Department of Biology, said: "We are rapidly altering the face of our planet, and creating more and more man-made habitats which are providing unexpected homes for nature, and in this case, it is foreign plants supporting the UK's insect communities."

"It was fascinating to observe the diversity of insects on non-native plants, from pollinators to bugs like crickets and lacewings and beetles like ladybirds and weevils."

Professor Chris Thomas, Director of the Leverhulme Centre for Anthropocene Biodiversity at York and one of the co-authors, added: "The movement of plants into new regions has been a defining feature of the past few centuries, and non-native plants are now present in very high numbers in most countries across the globe."

"This trend is almost certain to continue, and so it is vital that we understand the processes that determine how insects associate with these non-native plants."

The work represents a collaboration between the University of York, the Centre for Ecology and Hydrology, and the Royal Horticultural Society. They observed that insects were associated with both native and non-native garden plants in a highly controlled experiment that ran for six years. They additionally tested the data within a national-scale database that details a century of insects associating with plants in the UK.

The largest numbers of insect species were found on non-native plants that are closely related to native British plants, and on plants which today grow over a larger geographical area, and hence have become more fully integrated into the British flora.

Not surprisingly, the greatest numbers and diversity of insects were typically found on native plant species. However, non-native plants supported unique communities of British insects, including many species that were rare on native plants.

Roberto Padovani added: "A balance of both native and non-native plants may help provide a home for the widest variety of insects in our gardens. It is important to ensure that at least a third of plants are native, as the research suggests that these plants provide the best home for most insects. However, the presence of some non-native plants may help provide a home for unusual or rare British insects that may be struggling to find a home on our native plants."

Patients with atrial fibrillation, the most frequent cardiac arrhythmia, are closer to accessing personalized medicine. This is the claim of a new study led by Dr David Filgueiras, of the Centro Nacional de Investigaciones Cardiovasculares (CNIC), the Hospital Clínico San Carlos de Madrid, and the Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV). The study, results show that it is possible to monitor and predict individual progression of atrial fibrillation from cardiac electrical signals obtained from implantable devices (pacemakers or defibrillators). This project has been supported by the Fundación Interhospitalaria para la Investigación Cardiovascular (Fundación FIC).

The study, published in the latest edition of Europace, involved the participation of 51 Spanish hospitals and the Fundación Interhospitalaria para la Investigación Cardiovascular. The results show that cardiac electrical signals from patients fitted with pacemakers or implantable cardioverter-defibrillators can be used to monitor and predict the progression of the arrhythmia in a personalized and specific manner.

This is achieved with standard data transmission technology installed in implantable devices such as pacemakers. This technology can be used to monitor cardiac electrical activity during episodes of atrial fibrillation, thus establishing disease status and the rate of progression.

Atrial fibrillation is the most frequent chronic sustained arrhythmia, affecting more than 30 million people worldwide and an estimated 600,000 or more people in Spain. One in every three people will develop the condition in their lifetime. The risk is higher in people with certain diseases, such as diabetes or hypertension. Risk is also increased by lifestyle habits such as excessive consumption of alcohol or other substances.

Atrial fibrillation, explained Dr Filgueiras, tends to begin with episodes of short duration that resolve themselves. As the condition progresses, episodes become more prolonged until they become persistent. At this stage, episodes no longer terminate spontaneously, and the heart struggles to recover a healthy, stable rhythm, even after medication or surgery.

In recent years, several risk scales have been developed to estimate individual risk of developing atrial fibrillation over a 10-year period. However, according to Dr Filgueiras, "once atrial fibrillation develops, its progression varies significantly between patients; in some, a pattern of repeated short episodes is maintained for years, whereas in others it progresses rapidly to longer episodes associated with atrial dilatation and major difficulties in controlling heart rhythm."

There is thus a need for methods to individually monitor and predict the progression of atrial fibrillation. This would allow, after the initiation of atrial fibrillation episodes, "optimal timing of the most appropriate medical treatment, avoiding delays until the arrhythmia has progressed to a state that is harder to control," explained CNIC researcher Dr José Jalife, an author on the study.

According to Dr Filgueiras, "this technology opens up enormous possibilities in personalized medicine for atrial fibrillation patients because it allows us to determine the progression rate of the arrhythmia in each individual and to optimize the timing of medical intervention with current treatment options."

In addition, Dr Julián Villacastín, director of the Instituto Cardiovascular del Hospital Clínico San Carlos and an author on the study, this new approach to atrial fibrillation diagnosis "will allow us to monitor the influence of different interventions on disease progression."

The study findings were obtained by independent big-data screening of databases held at leading national hospitals in Spain together with interdisciplinary collaboration between physicians and engineers, including first author Dr José María Lillo of the CNIC and the Fundación Interhospitalaria para la Investigación Cardiovascular. Dr Lillo explained that "tools based on signals from pacemakers or defibrillators could in the near future be adapted to exploit signals from other devices such as smart watches or even holter devices for long-duration ECG recording." This has the potential to expand this type of personalized medicine to a much larger population of patients with conditions other than atrial fibrillation.

Discovering them merited their discoverers a Nobel Prize in the 1990s. MicroRNAs are small RNA molecules that do not code for proteins, however, they take care of an essential function: they act as regulators in gene expression, and so they have become a focus of attention for medical science. Despite there being thousands of different sequences of this genetic material, the individual role that each one plays in several illnesses continues to be unknown for the most part.

Recently, research done at the University of Cordoba, among other places, and published in Nature Microbiology, was able to determine the specific function of certain microRNAs in Salmonella Typhimurium and Shigella flexneri infections. These are two similar bacteria that are passed on to humans upon ingesting food or water infected by people or animals with the disease.

These are two intracellular pathogens that invade healthy cells and cause similar symptoms. Nevertheless, in spite of their many similarities, the results show that infections from these two bacteria are controlled by different microRNAs that have a radically opposite function.

In order to come to this conclusion, an array of over 1,400 different microRNAs were studied individually so as to verify what effect they produce in cells upon being infected by these two bacteria, explains University of Cordoba Genetics Department researcher Sara Zaldívar.

In the case of Shigella, the results show that upon infection, three specific kinds of microRNA silence the expression of the gene responsible for spreading the bacteria within the infected organism by means of filaments called filopodia. This is an immune response mechanism of the infected organism that, as a result, lessens the bacteria's movement.

In the case of Salmonella, almost the opposite occurs. Once the cell is infected, a kind of microRNA activates the expression of a gene responsible for the bacteria reproducing. This is the pathogen's attack mechanism in order to reproduce, something that was not only demonstrated in the laboratory but also was corroborated in vivo in pig intestinal mucosa.

Implications and consequences

The results show two mechanisms of how microRNAs act in completely different ways and that were not described ever before. While in some infections, such as Shigella, these small molecules of genetic material perform a function in the immune response of the infected organism, in others, like Salmonella, they are part of the strategies developed by the bacterium to benefit itself in order to reproduce.

One of the main takeaways from the research, as pointed out by another author, Professor Juan José Garrido, is the need to understand the specific response mechanisms of each pathogen so as to not err by extrapolating treatment. "If we do not know exactly how microRNA regulation works, then we are blindly assigning treatment and we will end up haphazardly using a wide range of antibiotics that build up resistance to the bacteria", says the researcher. "In our laboratory alone", adds Sara Zaldívar, "we have strains of Salmonella that have built up resistance to 14 different antibiotics". For this reason, knowing about the mechanisms of each pathogen in particular is key to developing more effective drugs by means of searching for target genes involved in the process.

In order to help people with fear of childbirth, there must be trust between the patient and the healthcare staff. But for many lesbian and bisexual women and transgender people, this trust never develops. These are the results of a study in the journal Midwifery from researchers at Linköping University.

Fear of childbirth (FOC) in heterosexual people is a well-researched field, but we know little about how lesbian and bisexual women and transsexual people experience pregnancy, childbirth and reproductive healthcare . Anna Malmquist and Katri Nieminen, researchers at Linköping University, have investigated the topic in depth. The study has been published in the journal Midwifery.

"This study shows that fear of childbirth is the same, regardless of sexuality. The difference is that in addition to this fear, lesbian and bisexual women and transsexual people are afraid of being questioned or offended because of their identity. That is, their fear has an added dimension", says Anna Malmquist.

The study includes interviews with 17 people who identify as either lesbian, bisexual or transgender. Many of the interviewees state that they have numerous positive experiences of maternal care and obstetrics, but also negative experiences. The additional layer of fear and stress felt by this group in its encounter with health care is called minority stress. This is the stress experienced by people who challenge norms when they must repeatedly explain their relationship or are forced to deal with comments, misunderstanding or incomprehension.

The study's conclusion is that lesbian and bisexual women and transsexual people with FOC are particularly vulnerable in healthcare. In order to help people with FOC, there must be trust between the healthcare staff and the patient. If instead the staff stress the patient more, for instance by assuming the patient is heterosexual, this trust will never develop to a level where the FOC can be addressed.

Anna Malmquist explains that improving the situation for lesbian and bisexual women and transsexual people with FOC requires training. Healthcare staff must be familiar with the various groups they can encounter at work, keep in mind that not everyone is heterosexual, and understand what minority stress is.

"It's not enough that healthcare staff feel they are 'open-minded' in their interaction with this group. They need knowledge. These patients are already having a lot of difficulty with their fear of childbirth. They shouldn't have to train their midwife as well", says Anna Malmquist.

Looking forward, Anna Malmquist and Katri Nieminen will study whether FOC is more common in lesbian and bisexual women and transsexual people than in heterosexual people.

One of the first studies to examine the effect of climate change on diseases such as influenza that are transmitted directly from person to person has found that higher temperatures and increased rainfall could make outbreaks less severe but more common, particularly in North America.

Princeton University-led researchers studied how climate conditions influence annual outbreaks of respiratory syncytial virus (RSV) in the United States and Mexico, where the common pathogen can cause serious respiratory infections. The researchers created a model of the virus' peaks during the year using county-level observations of RSV infection from the United States and state-level data from Mexico.

The researchers reported in the journal Nature Communications that RSV epidemics are subject to different climatic factors depending on location. Fluctuations in humidity are the driving force behind the virus' spread in temperate northern locations, while RSV epidemics track the rainy season in tropical locales. The virus is governed by both humidity and rainfall in "crossover" locations such as Mexico's Sinaloa state that typically experience two epidemic peaks each year.

When the researchers coupled their results with climate change models, they found that while outbreaks of RSV became generally less severe, the virus' peak-infection cycle shifted northward, explained first author Rachel Baker, a postdoctoral research associate in the Princeton Environmental Institute (PEI). In many areas, particularly in the northern United States, epidemics of RSV could become more common and strike earlier in the year.

"Right now, we see RSV cases throughout the year in tropical locations. In the majority of the United States, we see annual seasonal outbreaks with no cases in the summer months, and we see biennial dynamics in the northern parts of the United States where there are large numbers of cases every two years," said Baker, who is based in the research group of co-author and PEI associated faculty member C. Jessica Metcalf, Princeton assistant professor of ecology and evolutionary biology and public affairs.

"It is those patterns that could shift northward," Baker said. "Essentially we will see few of the biennial dynamics and more of the persistent tropical-type dynamics in the future. We also predict an earlier timing of the epidemic."

On average, RSV epidemics could see fewer individual cases as the climate changes and be more similar from year to year, the researchers found. In their climate models, projected increases in temperature-driven humidity resulted in less intense outbreaks of RSV, although epidemics became more severe in locations that experienced extreme rainfall, usually in the tropics.

While toned down RSV epidemics are in some ways a positive outcome, there will be more persistent occurrences of the virus throughout the year, Baker said. In short, infections will be spread out rather than be concentrated in certain seasons. That could leave people more vulnerable to the virus over the long term, particularly children. More than half of infants born in the United States contract the virus during their first RSV "season."

"We should expect to see more cases outside of the RSV season, so public health workers should be prepared for changes to the timing and frequency of cases," Baker said. "Changing dynamic patterns also could alter the age at which children get RSV, and we hope to consider in future work how climate change may affect this. The earlier a child gets RSV, the more likely they are to be hospitalized."

The paper is the first publication to stem from PEI's Climate Change and Infectious Disease initiative, which brings together climate scientists and epidemiologists to better understand the direct and indirect impacts of climate on human health. Co-authors on the paper include Gabriel Vecchi, professor of geosciences and the Princeton Environmental Institute, and PEI associated faculty Bryan Grenfell, the Kathryn Briger and Sarah Fenton Professor of Ecology and Evolutionary Biology and Public Affairs, as well as Princeton postdoctoral researchers Caroline Wagner in ecology and evolutionary biology and Wenchang Yang in geosciences.

The research team also included Ayesha Mahmud, assistant professor of demography at the University of California-Berkeley; Virginia Pitzer, associate professor of epidemiology at Yale University; and Cécile Viboud, a staff scientist at the National Institutes of Health.

Most research related to climate change and infectious disease has focused on maladies that are spread by vectors such as mosquitoes, Baker said. But the Nature Communications study expands into new territory by investigating a disease that passes through direct contact among infected hosts, she said. Their work could provide a model for projecting how climate change could affect pathogens similar to RSV and influenza, Baker said.

"Our modeling approach, which allowed us to disentangle the effect of climate from other drivers of disease transmission, can be applied to other pathogens," Baker said. "Our results suggest that climate can play a central role in driving the timing and dynamic patterns of infectious disease. Characterizing this role is crucial for understanding the future effect of climate change."

The researchers provided an important "unified explanation" that answers enduring questions about RSV, Baker said. Previous work had found different patterns of RSV epidemics in tropical and temperate locations, and there had been speculation that different drivers are at play. Baker and her co-authors, however, show that a common underlying humidity and precipitation effect can explain these different spatial patterns.

A challenge in studying RSV has been that the virus cannot be studied in a laboratory, Baker said. Existing work on climate and influenza, for example, was made possible by using guinea pigs, which contract and transmit influenza much like humans do. By presenting results from a model that were similar to data from the lab, the research offers hope for accurately studying other pathogens that are difficult to observe experimentally.

"There is no animal that can be used to study RSV, which makes large-scale observational studies such as ours particularly important for understanding the climate drivers of transmission," Baker said. "The fact that we get results similar to those found for influenza transmission in guinea pigs is incredibly interesting."

Air pollution is associated with detrimental effects on human health, including increased risk of heart disease and stroke. Research published today in The Journal of Physiology by researchers at The University of Manchester shows that the knowledge we have about how pollution harms the hearts of marine species can be applied to humans, as the underlying mechanisms are similar. In other words, knowledge gained from the marine ecosystem might help protect the climate and health of our planet, whilst also helping human health.

Around 11,000 coronary heart disease and stroke deaths in the UK each year are attributable to air pollution, specifically due to particulate matter (PM), or small particles in the air that cause health problems. PM2.5 is one of the finest and most dangerous type of PM, is a compound for which the UK has failed to meet EU limits.

Researchers of this study looked across all vertebrates and particularly focused on a set of compounds that binds to the surface of PM, called polycyclic aromatic hydrocarbons (PAH) as the amount of PAH on PM is associated with the detrimental affect air pollution has on the heart.

While air pollution is known to be dangerous to humans, it actually only became a widely-researched topic in the past five years or so. In marine species however, the mechanism of how PAH pollution causes heart problems is well understood.

Studies after the 1999 Exxon Valdez oil spill showed that the ecosystem still has not recovered 20 years on. In 2010, research on fish after the Deepwater Horizon oil spill, which released large quantities of PAHs into the marine environment, showed that the heart's ability to contract was impaired.

Dr Holly Shiels, senior author on the study, from The University of Manchester said:

"Pollution affects all of us living on Planet Earth. Due to the conserved nature of cardiac function amongst animals, fish exposed to PAH from oil spills can serve as indicators, providing significant insights into the human health impacts of PAHs and PM air pollution."

Dr Jeremy Pearson, Associate Medical Director at the British Heart Foundation, which partly funded the research presented in this review, commented:

"We know that air pollution can have a hugely damaging effect on heart and circulatory health, and this review summarises mechanisms potentially contributing to impaired?heart function. Reducing air pollution is crucial to protecting our heart health, which is why the BHF is calling on the next Government to commit to reducing air pollution to within WHO limits."

A new approach is needed to help reduce undernutrition and obesity at the same time, as the issues become increasingly connected due to rapid changes in countries' food systems. This is especially important in low- and middle-income countries, according to a new four-paper report published in The Lancet. More than a third of such countries had overlapping forms of malnutrition (45 of 123 countries in the 1990s, and 48 of 126 countries in the 2010s), particularly in sub-Saharan Africa, south Asia, and east Asia and the Pacific.

Undernutrition and obesity can lead to effects across generations as both maternal undernutrition and obesity are associated with poor health in offspring. However, because of the speed of change in food systems, more people are being exposed to both forms of malnutrition at different points in their lifetimes, which further increases harmful health effects.

"We are facing a new nutrition reality," says lead author of the report Dr Francesco Branca, Director of the Department of Nutrition for Health and Development, World Health Organization. "We can no longer characterize countries as low-income and undernourished, or high-income and only concerned with obesity. All forms of malnutrition have a common denominator - food systems that fail to provide all people with healthy, safe, affordable, and sustainable diets. Changing this will require action across food systems - from production and processing, through trade and distribution, pricing, marketing, and labelling, to consumption and waste. All relevant policies and investments must be radically re-examined." [1]

In a Lancet editorial accompanying the report, Dr Richard Horton, Editor-in-Chief of The Lancet, says: "Today's publication of the WHO Series on the Double Burden of Malnutrition comes after 12 months of Lancet articles exploring nutrition in all its forms... With these and other articles across
Lancet journals throughout 2019, it has become clear that nutrition and malnutrition need to be approached from multiple perspectives, and although findings have sometimes converged, there is still work to be done to understand malnutrition's multiple manifestations... With 6 years remaining in the UN Decade of Action on Nutrition, this Series and Comment define the future direction required to achieve the global goal of eradicating hunger and preventing malnutrition in all its forms."

Globally, estimates suggest that almost 2.3 billion children and adults are overweight, and more than 150 million children are stunted. However, in low- and middle-income countries these emerging issues overlap in individuals, families, communities and countries. The new report explores the trends behind this intersection - known as the double burden of malnutrition - as well as the societal and food system changes that may be causing it, its biological explanation and effects, and policy measures that may help address malnutrition in all its forms.

The authors used survey data from low- and middle-income countries in the 1990s and 2010s to estimate which countries faced a double burden of malnutrition (ie, in the population, more than 15% of people had wasting, more than 30% were stunted, more than 20% of women had thinness, and more than 20% of people were overweight).

In the 2010s, 14 countries with some of the lowest incomes in the world had newly developed a double burden of malnutrition, compared with the 1990s. However, fewer low- and middle-income countries with the highest incomes were affected than in the 1990s. The authors say that this reflects the increasing prevalence of being overweight in the poorest countries, where populations still face stunting, wasting and thinness.

High-quality diets reduce the risk of malnutrition in all its forms by promoting healthy growth, development, and immunity, and preventing obesity and non-communicable diseases (NCDs) throughout life. The components of healthy diets are: optimal breastfeeding practices in the first two years; a diversity and abundance of fruits and vegetables, wholegrains, fibre, nuts, and seeds; modest amounts of animal source foods; minimal amounts of processed meats, and minimal amounts of foods and beverages high in energy and added amounts of sugar, saturated fat, trans fat, and salt.

"Emerging malnutrition issues are a stark indicator of the people who are not protected from the factors that drive poor diets. The poorest low- and middle-income countries are seeing a rapid transformation in the way people eat, drink, and move at work, home, in transport and in leisure," says report author Professor Barry Popkin, University of North Carolina, USA. "The new nutrition reality is driven by changes to the food system, which have increased availability of ultra-processed foods that are linked to increased weight gain, while also adversely affecting infant and pre-schooler diets. These changes include disappearing fresh food markets, increasing supermarkets, and the control of the food chain by supermarkets, and global food, catering and agriculture companies in many countries." [1]

Exposure to undernutrition early in life followed by becoming overweight from childhood onwards increases the risk of a range of non-communicable diseases - making the double burden of malnutrition a key factor driving the emerging global epidemics of type 2 diabetes, high blood pressure, stroke, and cardiovascular disease. Negative effects can also pass across generations - for example, the effect of maternal obesity on the likelihood of the child having obesity may be exacerbated if the mother was undernourished in early life.

Despite physiological links, actions to address all forms of malnutrition have historically not taken account of these or other key factors, including early-life nutrition, diet quality, socioeconomic factors, and food environments. In addition, there is some evidence that programmes addressing undernutrition have unintentionally increased risks for obesity and diet-related NCDs in low-income and middle-income countries where food environments are changing rapidly.

While it is critical to maintain these programmes for undernutrition, they need to be redesigned to do no harm. Existing undernutrition programmes delivered through health services, social safety nets, educational settings, and agriculture and food systems present opportunities to address obesity and diet-related NCDs.

The report identifies a set of 'double-duty actions' that simultaneously prevent or reduce the risk of nutritional deficiencies leading to underweight, wasting, stunting or micronutrient deficiencies, and obesity or NCDs, with the same intervention, programme, or policy. These range from improved antenatal care and breastfeeding practices, to social welfare, and to new agricultural and food system policies with healthy diets as their primary goal. [2]

"Continuing with business-as-usual is not fit for purpose in the new nutrition reality. The good news is that there are some powerful opportunities to use the same platforms to address different forms of malnutrition. The time is now to seize these opportunities for 'double duty action' to get results," says Professor Corinna Hawkes, Centre for Food Policy, City, University of London, UK. [1]

To create the systemic changes needed to end malnutrition in all its forms, the authors call on governments, the UN, civil society, academics, the media, donors, the private sector and economic platforms to address the double burden of malnutrition and bring in new actors, such as grass-roots organizations, farmers and their unions, faith-based leaders, advocates for planetary health, innovators and investors who are financing fair and green companies, city mayors and consumer associations.

"Given the political economy of food, the commodification of food systems, and growing patterns of inequality worldwide, the new nutrition reality calls for a broadened community of actors who work in mutually reinforcing and interconnected ways on a global scale," says Dr Branca. "Without a profound food system transformation, the economic, social, and environmental costs of inaction will hinder the growth and development of individuals and societies for decades to come." [1]

Fast Facts:

Exoplanets are planets that orbit stars outside the Solar System

Some exoplanets are thought to have liquid water on their surface and therefore the potential to host life - these exoplanets lay in the 'habitable zones' of stars

A researcher at NYU Abu Dhabi has discovered that exoplanets lacking sufficient shielding can be impacted by high radiation bursts from the star, known as 'flares'

Abu Dhabi, UAE - December 15 2019 - The discovery of terrestrial exoplanets, planets that orbit stars outside the solar system, has been one of the most significant developments in modern astronomy. Several exoplanets lie in the "habitable zones" of stars, where planets are thought to be able to maintain liquid water on their surface, and have the potential to host life. However, an exoplanet that is too close to its host star is highly sensitive to radiation bursts from the star, also known as flares.

In this new study, NYUAD Center for Space Science Research Scientist Dimitra Atri found that not all exoplanets in habitable zones will be able to maintain hospitable conditions for life. Exoplanets in close proximity to stars are subject to radiation bursts which can disrupt habitable conditions unless the exoplanet has significant atmospheric or magnetic shielding.

In the study, published in the journal Monthly Notices of the Royal Astronomical Society: Letters, Atri explores how flares from stars affect a planet's surface radiation dose, and if that can disrupt the planet's ability to host life. The role of a planet's magnetic field strength and its atmosphere in providing shielding from these bursts was also examined. The factors measured include flare strength and spectrum, as well as the planetary atmospheric density and magnetic field strength. To calculate the surface radiation dose, particle spectra from 70 major flare emitting events (observed between 1956 and 2012) were used as proxy, and the GEANT4 Monte Carlo model was used to simulate flare interaction with exoplanetary atmospheres.

From this study it was concluded that flares can abruptly increase the radiation level on planetary surfaces and have the capability to disrupt potentially habitable conditions on planets. It was also found that the atmospheric depth (column density) and planetary magnetic field are major factors in protecting planets from flares and maintaining a substantial planetary atmosphere.

"As we continue to explore the planets of the solar system and beyond, discovering if these planets have the ability to support life continues to be of immense importance," said Atri. "More progress in this area will improve our understanding of the relationship between extreme solar events, radiation dose, and planetary habitability."

A team of South Australian researchers has cracked a rare gene variant for a disorder that causes severe neurodegeneration in infants.

The previously baffling condition sees a normal healthy child start to lose muscle tone and motor skills, ultimately losing the capacity to walk and use language. The children go on to experience epileptic encephalopathy and cycles of serious gastric disruption, including severe vomiting.

The condition has an onset at between 12 and 14 months.

Using a genomics approach, where a patient's entire DNA sequence is examined, University of South Australia PhD student Alicia Byrne made the significant find, identified in just three infants worldwide, two of those in one South Australian family.

"When we started working with this local family, the disorder the children presented with had never been described but since our research began there has been one more case identified," Byrne says.

"We discovered that the children carried genetic changes which meant they were unable to absorb vital B group vitamins, which are essential for normal development and function of the nervous system."

While the Adelaide family tragically lost one child to this disorder, with the cause now identified, the family's paediatric neurologist at the Women's and Children's Hospital in Adelaide, Dr Nicholas Smith, and colleagues were able to devise a targeted therapy to overcome the problem.

Dr Smith, a senior lecturer in paediatric medicine at the University of Adelaide, says the treatment has made a huge difference.

"For the family's second child, weekly injections of the B group vitamins in which he is deficient have been able to halt and even reverse some of the impacts of this devastating disease," Dr Smith says.

Byrne's PhD supervisor, UniSA Adjunct Professor at the Centre for Cancer Biology, Hamish Scott says, ironically, rare diseases are actually a broad and significant area of genomics research.

"While a rare genetic disease may only impact a handful of people, what we are quickly understanding in our work on the human genome is that there are myriad different rare diseases," he says.

"Genomic research opens an important path in identifying and, with strong partnerships such as we have here in South Australia between universities, government and our hospitals, in developing personalised precision medicine to treat rare diseases."

"In addition, the work we do in understanding genes and how they make the body work, constantly informs human biology and provides deeper understandings of human health that have population-wide relevance."

"Our goal is to develop genomic testing so that children can be diagnosed at or before birth and treatments can be delivered as early as possible."