Culture

What The Study Did: Data for nearly 30,000 adults from six study groups in the U.S. were used to investigate associations between eating processed meat, unprocessed red meat, poultry or fish and the risk of cardiovascular disease and death from any cause.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Victor W. Zhong, Ph.D., of Cornell University in Ithaca, New York, is the corresponding author.

(doi:10.1001/jamainternmed.2019.6969)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

COLUMBUS, Ohio - By figuring out how a common virus hides from the immune system, scientists have identified a potential vaccine to prevent sometimes deadly respiratory infections in humans.

The research was conducted using the human metapneumovirus (HMPV). The virus was discovered in 2001, but follow-up research has shown that it has circulated in humans for at least 50 years and is considered around the world to be the No. 2 cause of respiratory infections that can be especially dangerous for infants and the elderly.

HMPV is in the same family as respiratory syncytial virus (RSV), the No. 1 cause of human respiratory infections that can also cause serious illness in infants and the elderly - which means these findings may hold promise for development of a vaccine against RSV.

"This is exciting because RSV was discovered in 1953, but we still don't have a vaccine. The virus inhibits the innate immune response, and can infect the same person again and again," said Jianrong Li, senior author of the study and a professor of virology in The Ohio State University Department of Veterinary Biosciences and member of Ohio State's Infectious Diseases Institute.

"Now we have a mutant strain of HMPV that can trigger a higher immune response. Right now we're working to translate this same concept to see if it can work for RSV, too."

For this study, published today (Feb. 3, 2020) in Nature Microbiology, researchers determined that HMPV capitalizes on a common modification of its RNA to hide from the innate immune response, which is the body's first line of defense against any foreign invader. Avoiding that response enables the virus to use host cells to copy itself and cause infection.

By blocking the RNA modification, researchers found in cell studies that the mutated form of the virus they created unexpectedly activated a stronger-than-normal innate immune response. A strong innate response is key to developing an adaptive immune response, the body's production of antibodies against a specific pathogen.

A test on cotton rats showed the mutant virus effectively functioned as a vaccine against HMPV, preventing infection and triggering both a strong innate immune response and an effective adaptive response.

The RNA modification central to this research is known as N6-methyladenosine modification (a form of epigenetic methylation), presumed to be a survival mechanism that evolved over time. This frequently seen change in RNA was discovered in the 1970s, but its biological function has largely been a mystery since then.

Li's lab is one of a handful in the United States studying HMPV, and he and colleagues set out to find out whether HMPV RNA even has this modification, known as m6A methylation - which they discovered it does - and then uncover how the modification affects the virus's behavior.

The team used sophisticated technology, called high-throughput sequencing, to identify the viral gene that contains the most m6A methylation. Researchers then developed a mutated form of the virus by knocking out these modifications so they could assess how the virus functioned without them.

When introduced to human cells, the mutant virus triggered production of a protein called type I interferon, an antiviral molecule, which indicated the innate immune response had been activated - and this protein's level was higher than it would be under normal immune response conditions.

"This opened up a big question," Li said. "Why would a virus lacking this methylation produce a much higher innate immune response?"

By tracing the cell signals required to generate the innate immune response, the scientists determined that the RNA modification allowed the virus to hide from the immune system by reducing a host immune protein's ability to recognize the difference between virus RNA (nonself-RNA) and host RNA (self-RNA).

"We know that when a virus infects cells, it produces RNA, and human cells in the innate response try to separate self-RNA and nonself-RNA," Li said. "The virus is smart: It gained this methylation, and now our host innate response is confused. That's how the virus escapes recognition by the innate immune response."

"We are very excited about this finding. This novel function of m6A may also be conserved in many viruses," said Mijia Lu, the first author and a postdoctoral researcher in Li's laboratory.

The production of a higher level of type I interferon was an important finding in cells. But to be truly effective, a vaccine must prompt the body to also generate an adaptive immune response, producing antibodies and T-cell immune responses against a specific virus or bacterium. The researchers conducted an experiment with the mutant virus in cotton rats to see if this would happen.

Compared to cotton rats given a placebo, the rats immunized with the mutant virus and then infected with HMPV produced both innate and adaptive immune responses and were completely protected from virus replication in their lungs and nasal cavities.

"In the case of cotton rats, the mutant virus produced a higher amount of type I interferon, and triggered a higher antibody response and a higher T-cell immune response. That means you've triggered higher protective ability against the virus infection. So mutating the virus enhances vaccine efficacy," Li said. "That is exactly what we want.

"We proved a concept that these mutant viruses are improved vaccine candidates for HMPV."

Li and his collaborators have filed an application to patent the concept of using the mutant virus as a vaccine candidate for RSV and HMPV.

New research has found that rates of disease caused by the bacterium Streptococcus pneumoniae could be substantially reduced by changing our approach to vaccination. Researchers from the Wellcome Sanger Institute, Simon Fraser University in Canada and Imperial College London combined genomic data, models of bacterial evolution and predictive modelling to identify how vaccines could be optimised for specific age groups, geographic regions and communities of bacteria.

The study, published today (3 February) in Nature Microbiology, simulated the performance of vaccines over time to assess the risk of vaccine-targeted strains being replaced by other potentially dangerous strains. Through this predictive modelling approach, the researchers identified new vaccine designs that could help reduce overall rates of disease.

S. pneumoniae is often found at the back of the nasal cavity, where it is normally harmless. But when it migrates to other parts of the body, it can cause serious bacterial infections such as pneumonia, sepsis and meningitis - known collectively as invasive pneumococcal disease (IPD). IPD was estimated to cause around 1.6 million deaths per year worldwide prior to the introduction of widespread vaccination, with higher rates of disease in many low- or middle- income countries*. Infants and the elderly are most at risk.

Vaccines against pneumococcus have prevented millions of infections. But like many bacteria, S. pneumoniae is difficult to target with vaccines because infection can be caused by different serotypes**. Each part of a vaccine usually protects against a single serotype, with the most complex pneumococcal conjugate vaccine (PCV13) targeting 13 serotypes.

Because there are approximately 100 S. pneumoniae serotypes around the world, vaccine effectiveness varies between countries depending on which serotypes are present. When serotypes are removed from circulation by a particular vaccine, other serotypes of S. pneumoniae rise to take their place.

In this study, researchers at the Wellcome Sanger Institute, Simon Fraser University and Imperial College London optimised a computer model to approximate the effect of vaccines targeting different serotype combinations. Analysis of vaccine effectiveness was then carried out on S. pneumoniae genomic data from Massachusetts, USA and the Maela refugee camp in Thailand.

The complexity of S. pneumoniae vaccines means many designs are possible, each with different effects on disease. In Maela, for example, the presence of 64 S. pneumoniae serotypes means around 100 trillion vaccine designs are possible. But it would take 19,000 years to simulate them all, with most being sub-optimal. The researchers developed a more efficient method that made it feasible to identify the best-performing designs from the trillions of possibilities.

The team discovered that rates of infant IPD in Maela could actually be reduced by omitting components from the PCV13 vaccine to keep certain serotypes in place, removing the possibility of their replacement by highly-invasive serotypes. In Massachusetts, a vaccine targeting 20 serotypes was found to be more effective than the current PCV13.

The results highlight the need for vaccine programmes to be tailored to specific communities of bacteria and to consider vaccination at different ages.

Dr Nicholas Croucher, of the MRC Centre for Global Infectious Disease Analysis, Imperial College London, said: "Our research shows that the best vaccine designs strongly depend on the bacterial strains present in the population, which vary considerably between countries. The best vaccine designs also depend on the age group being vaccinated. These ideas will be critical for applying lessons learned from introducing vaccines in high-income countries to combatting the disease where the burden is highest."

Vaccination of infants also affects IPD in adults. However, trends in IPD can differ between infants and the elderly in the same country, as seen recently in the UK. In many places, older adults already receive an S. pneumoniae vaccine, which was designed before the infant vaccine. The study also found that adult disease rates could be reduced by almost 50 per cent by redesigning adult vaccines to complement those administered to infants.

Professor Caroline Colijn, of Simon Fraser University and the Wellcome Sanger Institute, said: "This approach to optimising vaccines will help to address several problems, such as invasive disease among infants or adults and minimising antibiotic resistance in the post vaccine population. Such an approach also enables public health policy-makers to assess the likely effectiveness of an existing vaccine for a local population based on genomic surveillance data."

The findings coincide with growing alarm at the threat of antimicrobial resistance (AMR) to common medicines. S. pneumoniae infections are sometime resistant to multiple antibiotics and have been highlighted as a priority threat by the WHO***. This study highlighted how vaccines can be designed to reduce the chances that a person's S. pneumoniae would be resistant to common treatments.

Professor Jukka Corander, of the University of Oslo, University of Helsinki and the Wellcome Sanger Institute, said: "With the power of the latest DNA sequencing technology we are heading towards a future where large-scale genomic surveillance of major bacterial pathogens is feasible. The approach we describe in this study will play an important role in accelerating future vaccine discovery and design to help reduce rates of disease."

Bacteria in our environment can be difficult to study: They are tiny and often live under conditions hard to recreate in the lab, for example in the deep sea or as symbionts in an animal host (or both, as the symbiotic bacteria in the present study). Investigations of the bacterial genome tell us what the microbes are theoretically capable of. What they actually do, however, is not revealed. Thus, scientists study the so-called metabolome of the bacteria: It comprises every metabolite the cells produce or consume, for example proteins, sugars or fats.

A team of researchers around Benedikt Geier and Manuel Liebeke from the Max Planck Institute for Marine Microbiology in Bremen has now developed a method to identify individual bacteria and at the same time determine which metabolites are present in the cells. With the new method they investigate how bacteria live and survive as symbiotic tenants in deep-sea mussels. Liebeke and his group analysed hundreds of metabolic products on an area smaller than one square millimeter. This enables them to understand how the symbiotic microbes live and communicate in their host. "We virtually take a snapshot of bacteria at work - just as it functions in its natural environment, here within a single animal cell," says Liebeke. "And we can do this with an impressive resolution of a few micrometers, about ten times thinner than a human hair."

Snap-frozen for the best snapshot: Not just what is happening, but also who is involved!

„For our analyses, we use mussel tissue that has been snap-frozen and can thus be cut into wafer-thin slices," Benedikt Geier explains. „From these slices, we take a snapshot of the chemical compounds of the cells using a special mass spectrometry technique called MALDI-MS imaging. When analysing this snapshot in detail, we are able to distinguish many different metabolites on a very small area." They provide information about which metabolites the bacteria use for what purpose and how they cohabit with their mussel host. In addition to the MALDI-MSI at the Max Planck Institute in Bremen, Liebeke and his team used a new MS imaging prototype at the Justus Liebig University in Gießen in close cooperation with Professor Spengler, which enabled particularly high-resolution insights.

Correct conclusions from the images of the metabolites are only possible if we also know who produces or uses them. "To date, we have only been able to measure the metabolites," explains Geier, "but we did not know whether any bacteria were involved and if so, which ones." To solve this prob lem, the researchers added a second technique, the so-called fluorescence in situ hybridization, or FISH, to identify individual bacterial cells in the same sample. "The combination with FISH was the key for us to interpret the high-resolution MALDI-MS images in a meaningful way and correlate them with the bacteria in the mussel tissue."

From the deep sea, now on camera

For the present study, Geier and his colleagues used samples from black smokers in the deep sea - towering chimneys where hot, mineral-rich water gushes out of the seafloor. Animals and bacteria can only survive there in symbiotic community. Geier investigates the coexistence of bacteria and mussels, in particular the close linkage of their metabolism, as part of his PhD-thesis. With the new method, he was able to show that the composition of lipids in the mussel differs significantly in body regions with and without bacterial tenants. "Up to now, we were not able to gain such insights as the samples were homogenised, that is virtually blended, before analysis," Geier explains. "Moreover the fact that our method works on samples coming directly from the environment and not from the lab underlines its great potential," he continues.

All plants and animals as well as us humans live in association with microorganisms, sharing metabolites through close interactions. "Applying this method in other host-microbe interactions will allow for many exciting new insights into the secret life of microbes. I am curious to see whether we can use this imaging approach for looking into the shared chemistry between microbes and organs in whole animals. There is still a lot to discover!"

Beep beep beep or Beach Boys? The sounds you wake up to could be affecting how groggy and clumsy you are in the morning, according to new research.

A study by RMIT University suggests melodic alarms could improve alertness levels, with harsh alarm tones linked to increased levels of morning grogginess.

The surprising finding, published in PLoS One, could have important implications for anyone who needs to perform at their peak soon after waking, such as shift workers and emergency first responders.

Lead author, RMIT doctoral researcher Stuart McFarlane, said morning grogginess - or sleep inertia - was a serious problem in our 24-hour world.

"If you don't wake properly, your work performance can be degraded for periods up to four hours, and that has been linked to major accidents," McFarlane said.

"You would assume that a startling 'beep beep beep' alarm would improve alertness, but our data revealed that melodic alarms may be the key element. This was unexpected.

"Although more research is needed to better understand the precise combination of melody and rhythm that might work best, considering that most people use alarms to wake up, the sound you choose may have important ramifications.

"This is particularly important for people who might work in dangerous situations shortly after waking, like firefighters or pilots, but also for anyone who has to be rapidly alert, such as someone driving to hospital in an emergency."

The research involved 50 participants, using a specially designed online survey that enable them to remotely contribute to the study from the comfort of their own home.

Each person logged what type of sound they used to wake up, and then rated their grogginess and alertness levels against standardised sleep inertia criteria.

Co-author Associate Professor Adrian Dyer, from RMIT's School of Media and Communication and Digital Ethnography Research Centre, said the research could help contribute to the design of more efficient interventions for people to use on their own devices to wake up properly.

"This study is important, as even NASA astronauts report that sleep inertia affects their performance on the International Space Station," Dyer said.

"We think that a harsh 'beep beep beep' might work to disrupt or confuse our brain activity when waking, while a more melodic sound like the Beach Boys 'Good Vibrations' or The Cure's 'Close to Me' may help us transition to a waking state in a more effective way.

"If we can continue to improve our understanding of the connection between sounds and waking state, there could be potential for applications in many fields, particularly with recent advancements in sleep technology and artificial intelligence."

A UTSA researcher has discovered that, whether in a pair or in groups, success in primate social systems may also provide insight into organization of human social life.

Assistant professor Luca Pozzi in UTSA's Department of Anthropology in collaboration with Peter Kappeler, a colleague at the German Primate Center-Leibniz Institute for Primate Research, investigated how different primate societies evolved and which factors may be responsible for transitions among them.

Their reconstructions showed that the evolution from a solitary way of life to group living usually occurred via pair living. Pair living thus served as a stepping stone for group living and therefore plays a key role in the evolution of social systems.

In the course of evolution, species had to adapt to changing environmental conditions, according to Pozzi. A crucial adaptation in this process is the modification of social behavior. About half of all primate species live in groups and around one third in pairs; the rest live solitarily.

Why these different forms of social complexity evolved, how many transitions among them occurred and which factors led to the transitions was analyzed on the basis of genetic data and behavioral observations of 362 primate species.

"Living as a pair represents an evolutionary puzzle in the evolution of mammalian social systems because males could achieve higher rates of reproduction if they did not bond to a single female," says Pozzi.

Yet evolutionary biologists still struggle to find the advantages of pair living for males, according to Peter Kappeler, who is one of the lead researchers of the study.

At first glance the two current hypotheses on the development of pair living--the female distribution hypothesis and the paternal care hypothesis--seem to be mutually exclusive.

Yet results in this work indicate that the two factors may be complementary. Initially it was believed that an ecological change in the habitat led to female spatial separation and that solitary males, which previously had several females living in their territory, were subsequently only able to gain access to one female. Paternal care resulting from the pair formation in turn increased the survival probability of the offspring and thus reinforced pair living.

The further transition to group living was possible through an improvement of the ecological situation, which allowed related females to live in close proximity. These could then be joined by one or more males.

"However, the pair bond typical for humans within larger social units cannot be explained with our results, since none of our recent ancestors lived solitarily. Nevertheless, the advantages of paternal care also may have led to a consolidation of pair living in humans," said Kappeler.

The research, "Evolutionary transitions towards pair living in non-human primates as stepping stones towards more complex societies," was published in the December issue of Science Advances.

"The evolution of complex social systems in mammals, and more specifically in primates, is a challenging and exciting area of research. Our study shows that pair living--although rare--might have played a critical role in it," says Pozzi.

Patient-specific or personalised 3D printed models created from cardiac imaging data can be applied to research areas beyond the current domains of 3D printing in cardiovascular disease, which mainly focuses on pre-surgical planning and simulation, medical education and training, as well as doctor-patient communication. These areas represent the most commonly used applications of 3D printed models, in particular, use of 3D printing models on congenital heart disease is a very promising field with sufficient evidence provided by randomised controlled trials. Further, 3D printed heart models are shown to play an important role in guiding patient's surgical planning and treatment as reported by single and multi-center studies. 3D printed models are also useful to educate medical students, healthcare professionals or junior residents in improving their understanding of complex cardiac anatomy and pathology. In addition to these reported applications, the realistic physical models serve as a valuable tool in studying appropriate cardiac CT protocols for the purpose of optimizing CT scanning techniques.

Zhonghua Sun, a professor and medical imaging researcher from Curtin University, Australia has been in search of new ways to acquire accurate and efficient medical images. Prof Sun's research interests include 3D visualization and diagnosis of cardiovascular disease, 3D printing in medical applications. In his recent work, published in Current Medical Imaging, Prof. Sun presents a new research direction for using 3D printed personalised cardiovascular models in studying CT protocols for the purpose of minimizing radiation dose without compromising image quality. He has developed the research team to focus on 3D printing in congenital heart disease, aortic and coronary disease and pulmonary embolism.

In his latest review, Prof Sun provides readers with information on how 3D printed aorta, pulmonary and coronary models can be used as an alternative to conventional anthropomorphic phantoms in studying optimal CT imaging protocols. In particular, there are two challenging areas of cardiac CT imaging highlighted in the review: calcified coronary plaques and coronary stenting. Although improved spatial and temporal resolution with advanced CT scanners, coronary CT angiography has moderate diagnostic value in imaging calcified plaques due to blooming artifacts, and in coronary stents because of metal-related artifacts which significantly affect its visualization and assessment of coronary lumen, resulting in high false positive rates. Thus, these 3D printed coronary models represent a novel phantom since the models are printed using patient's CT data, which replicate normal coronary anatomy including coronary artery branches, curvature and angle. Preliminary results indicate the feasibility of simulating calcified plaques and coronary stents in these printed models with promising results reported in the literature, although further research is needed to validate these findings by testing different scanning parameters.

CTA is not only the reference method in preoperative imaging of aortic aneurysm and dissection but also a preferred modality in the follow-up of patients with aortic aneurysmal disease after treated with endovascular stent graft repair. Regular follow-ups of these patients with CTA at 3 months, 6 months and 12 months thereafter increase cumulative radiation dose. Therefore, dose optimization is clinically important. "3D printed aortic models play a role in this area, in addition to its reported value in guiding complex aortic surgery or endovascular aortic repair," says Prof. Sun, adding that "Printing aortic dissection models is very challenging compared to other cardiovascular models due to very thin membranous structure of the intimal flap."

Prof. Sun's team is continuing to carry out more research on the development of aortic dissection models. CT pulmonary artery (CTPA) is a widely recognised modality in the detection of pulmonary embolism with high accuracy, thus, serving as the first line technique in the clinical diagnosis. Due to its widespread use, reduction of radiation dose and contrast dose has become a necessity with many low-dose protocols available. "3D printed pulmonary models can replicate normal pulmonary arteries with simulation of pulmonary emboli in both large and peripheral artery branches with low-dose protocols identified," says Dr. Sun. However, he insists that further experiments with reduction of contrast medium dose need to be conducted.

"Our work encourages more research to be conducted along this pathway and we expect further interesting results available soon in medical imaging literature," notes Prof. Sun.

Houston Methodist neurosurgeons and neuroscientists are looking at a new way to classify pituitary tumors that could lead to more precise and accurate diagnosing for patients in the future.

Found in up to 10% of the population, pituitary tumors, also called adenomas, are noncancerous growths on the pituitary gland and very common. Although these pituitary tumors are benign in nature, they pose a major health challenge in patients.

The new tests being investigated at Houston Methodist not only have the potential to lead to better diagnoses for patients with pituitary adenomas, but also for many other types of brain tumors in the future. The findings, which were published Jan. 28 in Scientific Reports, an online journal from Nature Publishing Group, describe a new way being looked at to study the blood of patients with pituitary tumors to determine exactly what tumor type they have and whether they might respond to medical treatment rather than surgery.

"Often called the 'master gland,' the pituitary gland controls the entire endocrine system and regulates various body functions by secreting hormones into the bloodstream to control such things as metabolism, growth and development, reproduction and sleep," said corresponding author Kumar Pichumani, Ph.D., a research physicist at the Houston Methodist Research Institute. "When pituitary adenomas occur, they may secrete too much of one or more hormones that could lead to a variety of issues, ranging from infertility and sexual dysfunction to vision problems and osteoporosis, among many other health problems."

Neurosurgeon David S. Baskin, M.D., director of the Kenneth R. Peak Center for Brain and Pituitary Tumor Treatment and Research in the Department of Neurosurgery at Houston Methodist Hospital, collaborated with Pichumani on this study. He said some pituitary tumors can be treated with medication rather than surgery, but a precise diagnosis of the type of tumor someone has and what hormone it's secreting is essential for proper treatment. This is sometimes very difficult to do based on standard endocrine hormone testing.

"To guide our decisions on diagnosis and treatment, we currently rely on a blood-based hormone panel test that measures the levels of hormones in the blood to determine which hormones are overproducing in the tumor," Baskin said. "However, some tumors secrete too much of more than one hormone, making this test ambiguous for diagnosis."

Led by Pichumani and Baskin, a team of researchers from the Peak Brain and Pituitary Tumor Treatment and Research Center and Houston Methodist Neurological Institute studied 47 pituitary adenoma patients of different subtypes by collecting blood during surgery to remove their tumors. They confirmed that elevated blood levels of a non-hormonal compound called betahydroxybutyrate, also known as BHB, was found only in patients with the prolactinoma subtype of noncancerous pituitary gland brain tumor that overproduces the hormone prolactin. This compound is known to supply energy to the brain during starvation, which led the researchers to speculate that BHB might be providing non-hormonal energy to these prolactinoma tumors causing them to grow and spread. The discovery could be further developed into a diagnostic lab test.

This study is part of a developing field called metabolomics in which researchers study small molecules in tumors to see what's unique about their metabolism and how they're used as nutrients to supply energy. This contributes to better diagnoses and discovering new ways to kill tumors by poisoning the specific energy they use without causing damage to normal cells.

The researchers are now enrolling more patients in a larger study currently underway to validate the results of their pilot study. If successful, they say BHB could be used as a non-hormonal metabolic biomarker for prolactinoma pituitary tumor diagnosis and prognosis to supplement the current hormone panel tests. They're also looking for biological reasons why only prolactin-secreting tumors have elevated BHB blood levels to inform therapeutic intervention.

It was long believed that physical characteristics acquired by organisms during their lifetime could not be passed on to their offspring. However, in recent years, the theory of inheritance of acquired traits has gained support, with studies showing how offspring of rats and tiny worms inherit behaviours that were acquired by their parents in response to particular environmental stimuli, even when the stimulus is no longer present in the offspring's generation.

This theory is further supported by recent studies conducted by researchers from the National University of Singapore (NUS), in which they found that the inheritance of acquired traits also happens in butterflies, especially in the bush brown butterfly Bicyclus anynana.

Two research teams supervised by Associate Professor Antónia Monteiro, who is from the Department of Biological Sciences at the NUS Faculty of Science, as well as from Yale-NUS College, showed that both Bicyclus anynana caterpillars and adult butterflies can learn to prefer new odours if they are exposed to them during their development or early in life. The researchers also found that the offspring of the exposed caterpillars and butterflies show the same new preferences as their parents, even though they were not exposed themselves, indicating that their parents have passed their new acquired preferences to their children.

The findings of the two studies were published online in the scientific journals Evolution in October 2019 and Nature Communications in January 2020.

Learning to like new odours for feeding and mating

In the study that was published in Evolution, NUS doctoral student Ms V. Gowri, research fellow Dr Emilie Dion, and their collaborators exposed caterpillars and butterflies to new odours they typically do not experience in their natural environment. In the experiments, caterpillars were fed with corn leaves - their usual food - coated with banana or with mango essence throughout their development. Most of these caterpillars preferred to eat leaves with the fruit essence after only a few days of exposure.

In the second study, which was published in Nature Communications, Dr Dion and her collaborators exposed young female butterflies to new sex pheromone blends, a perfume produced by males to entice females to mate with them. The results showed that the exposed females later preferred to mate with males having the new pheromone blend.

"These results are significant because they show that insects are not only driven by their instincts, but can also learn from their previous experience and adjust their future behaviour accordingly. The consequences of their learning abilities on their survival and reproduction can be very important," shared Dr Dion.

Offspring acquired the learned preferences of their parents

Both studies examined the behaviour of the offspring of the exposed Bicyclus anynana caterpillars and butterflies. The results revealed that the new generation also exhibited the same preference for the new food odours, or the new sex pheromone blends, although they were never exposed to these odours themselves. The teams concluded that the offspring inherited the preferences acquired by their parents.

While these learning and inheritance processes are hypothesised to facilitate the evolution of diet diversity across insects, and mate selection over the course of insect diversification, the impact of this inheritance mechanism on evolution is still unknown.

"We are now investigating whether this behavioural transmission is maintained for more than one generation, and also probing the underlying molecular mechanisms in our model species, as these remain some of the most exciting unanswered questions in the field of evolutionary biology," said Assoc Prof Monteiro.

Recently discovered ripples of spacetime called gravitational waves could contain evidence to prove the theory that life survived the Big Bang because of a phase transition that allowed neutrino particles to reshuffle matter and anti-matter, explains a new study by an international team of researchers.

How we were saved from a complete annihilation is not a question in science fiction or a Hollywood movie. According to the Big Bang theory of modern cosmology, matter was created with an equal amount of anti-matter. If it had stayed that way, matter and anti-matter should have eventually met and annihilated one to one, leading up to a complete annihilation.

But our existence contradicts this theory. To overcome a complete annihilation, the Universe must have turned a small amount of anti-matter into matter creating an imbalance between them. The imbalance needed is only a part in a billion. But it has remained a complete mystery when and how the imbalance was created.

"The Universe becomes opaque to light once we look back to around a million years after its birth. This makes the fundamental question of 'why are we here?' difficult to answer," says paper co-author Jeff Dror, postdoctoral fellow at the University of California, Berkeley, and physics researcher at Lawrence Berkeley National Laboratory.

Since matter and anti-matter have the opposite electrical charges, they cannot turn into each other, unless they are electrical neutral. Neutrinos are the only electrical neutral matter particles we know, and they are the strongest contender to do this job. A theory many researchers support is that the Universe went through a phase transition so that neutrinos could reshuffle matter and anti-matter.

"A phase transition is like boiling water to vapor, or cooling water to ice. The behavior of matter changes at specific temperatures called critical temperature. When a certain metal is cooled to a low temperature, it loses electrical resistance completely by a phase transition, becoming a superconductor. It is the basis of Magnetic Resonance Imaging (MRI) for cancer diagnosis or maglev technology that floats a train so that it can run at 300 miles an hour without causing dizziness. Just like a superconductor, the phase transition in the early Universe may have created a very thin tube of magnetic fields called cosmic strings," explains paper co-author Hitoshi Murayama, MacAdams Professor of Physics at the University of California, Berkeley, Principal Investigator at the Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo, and senior faculty scientist at Lawrence Berkeley National Laboratory.

Dror and Murayama are part of a team of researchers from Japan, US and Canada who believe the cosmic strings then try to simplify themselves, leading up to tiny wobbling of spacetime called gravitational waves. These could be detected by future space-borne observatories such as LISA, BBO (European Space Agency) or DECIGO (Japanese Astronautical Exploration Agency) for nearly all possible critical temperatures.

"The recent discovery of gravitational waves opens up a new opportunity to look back further to a time, as the Universe is transparent to gravity all the way back to the beginning. When the Universe might have been a trillion to a quadrillion times hotter than the hottest place in the Universe today, neutrinos are likely to have behaved in just the way we require to ensure our survival. We demonstrated that they probably also left behind a background of detectable gravitational ripples to let us know," says paper co-author Graham White, a postdoctoral fellow at TRIUMF.

"Cosmic strings used to be popular as a way of creating small variations in mass densities that eventually became stars and galaxies, but it died because recent data excluded this idea. Now with our work, the idea comes back for a different reason. This is exciting!" says Takashi Hiramatsu, a postdoctoral fellow at the Institute for Cosmic Ray Research, University of Tokyo, which runs Japan's gravitational wave detector KAGRA and Hyper-Kamiokande experiments.

"Gravitational wave from cosmic strings has a spectrum very different from astrophysical sources such as merger of black holes. It is quite plausible that we will be completely convinced the source is indeed cosmic strings," says Kazunori Kohri, Associate Professor at the High Energy Accelerator Research Organization Theory Center in Japan.

"It would be really exciting to learn why we exist at all," says Murayama. "This is the ultimate question in science."

In her Social and Cultural Neuroscience Lab at the University of Miami, assistant professor of Psychology Elizabeth Losin investigates the mechanisms underlying racial and ethnic disparities related to pain and pain treatment. She looks at the role the brain plays using functional MRI (fMRI) and the impact of social and cultural factors, including the doctor-patient relationship and stressful life experiences such as discrimination.

In the study "Neural and sociocultural mediators of ethnic differences in pain," published today in the journal Nature Human Behaviour, Losin; Tor Wager, Diana L. Taylor Distinguished Professor in Neuroscience at Dartmouth College; and colleagues identify possible brain and social factors underlying racial and ethnic disparities in pain. The researchers found that African American participants reported greater pain in response to a controlled pain stimulation than Hispanic or non-Hispanic white participants did. African Americans also exhibited differences in their brain responses to pain, which correlated with their personal histories of experiencing discrimination.

"There's evidence that both the general public and clinicians believe that African Americans are less sensitive to pain than non-Hispanic whites; yet research, including our own, shows exactly the opposite." said Losin. "Minorities, particularly African Americans, actually report more pain."

These inaccurate racial and ethnic biases about pain could have medical consequences.

"If medical professionals, whether consciously or unconsciously, believe that African Americans feel less pain than others, clinicians may be less inclined to alleviate the pain of their African American patients," explained Losin. Understanding why these pain biases exist, therefore, is a key step toward closing the pain gap - in other words, eliminating racial and ethnic disparities in pain and its treatment.

In the study, Losin and her team measured brain responses using an MRI (magnetic resonance imaging) machine while simultaneously inducing pain in participants via a laboratory heating apparatus on the arm. Outside the MRI scanner, they asked participants questions about different aspects of their lives, including stressful life experiences and previous experiences with pain. The subject group consisted of 88 participants (28 African Americans, 30 Hispanic Americans, and 30 non-Hispanic white Americans) from the Denver metro area, who were recruited and tested by Losin in Wager's Cognitive and Affective Neuroscience Lab at the University of Colorado Boulder.

All of the study participants were administered the same controlled pain stimulation. African Americans, however, reported greater pain than Hispanic or non-Hispanic white participants, which is consistent with previous studies. During this study, the researchers also looked for differences in brain responses to pain. Using the MRI scanner, the researchers identified two specific areas of the brain, the ventral striatum and ventromedial prefrontal cortex, which responded to pain more strongly in African American participants than the other two groups. Prior research has found that these two brain regions also respond more strongly to pain in chronic pain patients.

The researchers think that the similarity between the increased pain sensitivity observed in African Americans in their study and that which is typically seen in chronic pain patients may be due to stress.

"We know that stressful experiences early in life predispose people to developing chronic pain," said Losin. The results of this study suggest that a history of other kinds of stressful experiences, including discrimination or having a mistrust of doctors, may change the brain in ways that may cause people to respond more strongly to physical pain.

"These findings exemplify how neuroimaging is teaching us that there are multiple contributions to pain," noted Wager, "and that we need to consider the broader psychological and cultural setting when we think about what is underlying pain and how to address it." This study suggests that racial and ethnic disparities in pain may be a symptom of a much broader problem, underscoring the impacts of racial and social discrimination in society.

The findings point to a promising avenue for reducing pain-related health disparities in the near term, however: building greater trust between African American patients and their doctors. Ongoing experiments in Losin's laboratory are aimed at understanding the relationship between patients' trust in their doctors and their experience of pain.

Despite the differences observed, Losin pointed out that the groups in this study were more alike than different. "An important part of studying group differences is also to look for similarities," Losin explained. "In our study, brain systems related to the sensory aspects of physical pain were responding very similarly across all ethnic groups."

"It's a common misconception that any difference you see between groups of people must be an intrinsic difference, rooted in our biology. But the differences we found in this study were related to people's life experiences."

This, according to Losin, is good news: "It reaffirms our similarities and provides hope that racial and ethnic disparities in pain can be reduced."

Climate change is affecting the health of agricultural soils. Increased heat and drought make life easy for the pathogenic fungus Pythium ultimum. As an international team of researchers led by the Universities of Kassel and Bonn has shown, the fungus causes almost total crop failure in peas after a hot and dry stress event. Short-term soil recovery seems to be possible only in exceptional cases. The study has now been published in the journal Applied Soil Ecology.

Pythium ultimum is an aggressive fungus that is transmitted through the soil and infects the roots in the seedling of important agricultural crops such as beets and peas but also corn, soybeans and potatoes. The plants develop root rot and die. "In some cases, there may be a total failure of the germinating seedlings," states Dr. Christian Bruns of the Section of Organic Farming and Cropping Systems at the University of Kassel. However, soils also have protective mechanisms against these pathogens. Certain fungi act like "bodyguards" and protect the roots of plants, while some microorganisms parasitize the harmful fungus or simply consume it.

The scientists took soil samples from very different locations in cool and damp Scotland, temperate northeast Germany and dry and warm eastern Hungary. The soil samples, including the microorganisms living there, were put under stress in climate chambers with heat (40 degrees Celsius) and drought (only half soil moisture) and then infected with the aggressive fungus Pythium ultimum. The researchers investigated the effects of this stress event on the pathogen and ultimately the plants by subsequently sowing peas in these pre-treated soils.

Dramatic effect: Hardly a pea plant survived

The effect was dramatic: "Only a few of the young pea plants survived, and these withered under the fungal attack," summarizes Prof. Dr. Thomas Döring from the Agroecology and Organic Farming Group at the University of Bonn. In all soils, the stress event of heat and drought led to a strong reduction in resistance to Pythium ultimum. Soils from Scotland suffered the most, and those from Hungary the least. "Apparently the protective microorganisms in the soils of cool, damp Scotland are less adapted to heat and drought than in Hungarian soils, which are often exposed to high temperatures and droughts in summer," assumes Döring.

The scientists investigated how well the various soils can recover by taking a break of several weeks after treatment with heat and drought before infecting the soil with the harmful fungus and sowing the peas. Whilst a soil sample from Scotland showed some recovery, with slightly more peas growing in it in comparison, the harmful effect of the fungus seemed to be made worse by the recovery phase in the samples from Hungary.

"The decisive factor seems to be how quickly the protective microorganisms are able to reproduce after the stress event," says Bruns, referring to the results of other studies. "This ability is apparently not so pronounced in the soil samples from Hungary." Soils that are highly resistant to drought and heat therefore do not seem to have such a high recovery capacity.

Heat and drought increase the susceptibility to soil pathogens

All this indicates that if the climate in temperate and northern latitudes heats up more, the microorganisms in the soil will not be able to adapt as quickly. "Heat and drought have a negative impact on the soil organisms protecting plants from diseases," says Döring. "This increases the plants' susceptibility to soil-borne pathogens," adds Bruns. In view of the advancing climate change, this may significantly increase the risk of plant diseases and crop failures. However, further research is still needed.

Sixty-six million years ago, in the emerged lands of Laurasia -now the northern hemisphere- a primitive land tortoise, measuring about 60 cm, managed to survive the event that killed the dinosaurs. It was the only one to do so in this area of the world, according to a Spanish palaeontologist who has analysed its peculiar fossils, found in France.

All turtle species we know of today are descendants of two lineages that separated during the Jurassic, more than 160 million years ago. But their members were not the only ones that existed. There had been many groups of primitive tortoises before them, in an earlier evolutionary position.

Some of these ancient reptiles managed to survive at a time when dinosaurs dominated the Earth. However, virtually all of the early groups of turtles disappeared after an asteroid impact that took place 66 million years and wiped out 70% of life on the planet.

Only the so-called "horned turtles" or meiolaniids managed to hold out, more specifically in Gondwana, the current southern hemisphere, according to fossils found in Oceania and South America. Their last representatives managed to co-exist relatively recently with humans, who hunted them to extinction. No other primitive turtle had appeared in the records of the last 66 million years.

After 10 years of study, the palaeontologist Adán Pérez García, from the Evolutionary Biology Group of the National University of Distance Education (UNED, Spain), now confirms that, in the northern hemisphere, on the ancient continent called Laurasia, a primitive land turtle also survived the mass extinction of the late Cretaceous period.

This was Laurasichersis relicta, an extinct turtle genus and species that corresponds to a new form, with very peculiar anatomical characteristics, and whose lineage evolved independently from that of the Gondwana tortoises, from which it separated 100 million years earlier.

"The reason why Laurasichersis survived the great extinction, while none of the other primitive North American, European or Asian land turtles managed to do so, remains a mystery," Pérez García, the sole author of the paper published in Scientific Reports magazine, has confided to Sinc.

A drastic change after extinction

The impact of the asteroid plunged the Earth into a spiral of gas emissions, molten material and acid rain that caused a sudden warming of the climate and transformed the landscapes in which the turtles lived.

"The fauna of European turtles underwent a radical change: most of the forms that inhabited this continent before the extinction disappeared, and their role in many ecosystems was left vacant until the relatively rapid arrival of new groups from various places in North America, Africa and Asia," the palaeontologist points out.

All of them, identified in these new ecosystems, seemed to belong to the two lineages that have persisted to this day, but the new study allows us to recognize that they were not alone. The appearance in a site in northeastern France of fossils of the shell, limbs and skull of Laurasichersis relicta shows that this primitive species also survived the mass extinction event in Laurasia.

However, its origin stems from another continent: "It is the last representative of a group previously identified in China and Mongolia, where it was known since the Jurassic, more than 100 million years before the new European Laurasichersis turtle existed. This group arrived on this continent very shortly after the end of the Mesozoic, 66 million years ago," says the researcher.

A special turtle

The shell of the newly discovered turtle was just over 60 cm long during adulthood and, like other primitive reptiles, it could not retract its neck into its shell to conceal its head from predators. This physical limitation allowed it to develop other protective mechanisms such as an armor with large, mutually linked spikes, which were hard structures located on the neck, legs and tail.

Its peculiar shell is one of the most remarkable features of this reptile and one of the characteristics that make it unique. This complex structure was made up of numerous plates. "Although the number of plates is usually the same in most turtles, the ventral shell region of the new species was provided with a greater number of these elements than those known in any other turtle," Pérez García stresses.

After the 10-km-diameter meteorite hit the Earth, the large dinosaurs ceased to be part of the landscape, but the turtle, which lived in humid environments with forest areas, coexisted with new predators. The latter quickly dominated the positions of the food chain that had remained available when most animals disappeared.

Researchers from Tokyo Medical and Dental University develop a novel gas imaging system to simultaneously visualize and measure gases that are released through the skin in real-time

Tokyo, Japan - Gases emitted from the human body have been used since ancient Greek times to diagnose the sick; the same principle with a modern, technological makeover could now become a simple tool to identify metabolic disorders, genetic diseases and cancer.

A new method, developed by researchers from Tokyo Medical and Dental University and recently published in the journal ACS Sensors, now makes it possible to image and measure gases, called volatile organic compounds or VOCs, that are released through the skin in real-time.

VOCs that are released through the skin reflect the VOCs present in circulating blood. It is known that certain VOCs, such as ethanol, which is a component of alcoholic beverages, are significantly related to alcohol metabolism. Besides, it has been reported that VOCs would be associated with certain skin diseases, such as psoriasis. Although VOCs can already be commonly analyzed in laboratories using big, expensive machines, convenient, practical devices that provide accurate measurements for routine use in the clinical setting have been lacking. In addition, being able to see how gases are released through the skin over time has remained a challenge.

"We wanted to develop a tool that makes it easy to monitor human health in a non-invasive way," says the corresponding author of the study Prof. Kohji Mitsubayashi. "Even dating back to ancient Greece, physicians knew that a patient's breath could offer clues to their ailments. And nowadays, everybody has heard of the breathalyzer. The problem with breath is that it is not suitable for long-term monitoring of VOCs. The skin, on the other hand, offers an easy way for the continuous monitoring of VOCs without putting extra burden on the individual."

To achieve their goal, the researchers mounted a ring light consisted of an array of UV light-emitting diodes on a camera lens, which together enabled the real-time imaging of VOCs emanated from the skin surface. In a proof-of-principle experiment, the researchers aimed to detect ethanol in a subject who had consumed alcohol. Because the skin surface can be uneven, they used a so-called "2D Mako" to equalize the complex skin surface and to enable the accurate measurement of ethanol over time. To facilitate the detection of ethanol, the researchers drew on the same principle as the human body uses to get rid of ethanol by placing a mesh with an enzyme called alcohol dehydrogenase (ADH) on the subject's skin via 2D Mako. Once gaseous ethanol hit this mesh, a byproduct of the enzymatic reaction, NADH was generated and emitted fluorescence, which was utilized to gas-imaging.

"We were able to show a dynamic change in the concentration of ethanol over time after alcohol consumption," says postdoctoral research fellow and lead author of the study Kenta Iitani. "Our results indicate that metabolic monitoring and early disease screening can be achieved by measuring blood VOCs via transcutaneous gas release".

Being able to reliably measure VOCs could help clinicians to evaluate how alcohol influences the skin and contributes to the development of skin disorders. Adaptation of this gas imaging system to other gases could further enable the study of other diseases by monitoring the release of VOCs.

Researchers at Helmholtz Zentrum München, Technical University of Munich (TUM) and the German Center for Infection Research (DZIF) have developed a novel therapeutic approach to cure chronic hepatitis B. The scientists found that the large amount of hepatitis B virus proteins expressed in the liver prevents the body's immune system to defeat the virus, consequently preventing an effective therapy. The researchers were able to show that knocking down the expression of the virus' proteins enables successful vaccination with TherVacB, a novel therapeutic vaccine.

Around 260 million humans, more than three percent of the world's population, are chronically infected by the hepatitis B virus. As a result, every year, 880,000 people worldwide die of liver failure or hepatocellular carcinoma. Currently no curative therapy is available. The therapies available to date inhibit virus replication, but need to be given long-term. As long as infected people cannot form an adequate immune response, the virus will survive. This is precisely where Prof. Ulrike Protzer, head of the Institute of Virology at Helmholtz Zentrum München and TUM, and her team start.

Novel therapeutic approach

Using a preclinical mouse model, the researchers found that proteins of the hepatitis B virus prevent that certain immune cells of the body, so-called CD8+ T-cells become effective. Based on these finding, the scientists developed a novel therapeutic approach: first, the expression levels of the virus proteins are knocked down, and then the immune cells are activated by therapeutic vaccination. In contrast to conventional vaccinations, which aim to prevent diseases before outbreak, such a therapeutic vaccination aims to cure already existing chronic diseases.

Successful suppression of virus proteins in mice

Consequently, the researchers first developed a method to suppress the hepatitis B virus proteins. They used siRNAs, small ribonucleic acid molecules that bind to the messenger RNA of the virus' proteins. By labelling the messenger RNA with siRNA, the infected cell receives the signal that the viral RNA is undesired and removes it. In this way protein expression is knocked down. However, the suppression of protein expression alone was not sufficient to reverse the inhibition of the CD8+ T-cells in chronically infected mice.

Infection cured in mice

The scientists therefore had to go one step further: "We then combined the siRNA method with a therapeutic vaccination developed by us. This enabled us to trigger a strong immune response against the virus. This led to cure of hepatitis B virus infection in two different mouse models," explains Dr. Thomas Michler, physician and one of the two first authors of the study.

Novel therapeutic vaccination soon in a clinical trial

The newly developed vaccine, called TherVacB, will be tested as an immunotherapy in a two-year clinical trial starting in 2021. "The therapeutic vaccine we have developed is indeed very promising as it induces neutralizing antibodies and T-cell responses," said Dr. Anna Kosinska, the other first author of the study. The vaccine will be administered in three doses every four weeks. It has been designed to target the majority of all hepatitis B viruses and therefore will be beneficial to most people infected worldwide.

"We are very pleased that for the clinical trials of TherVacB we are able to cooperate with a consortium of Europe's leading virologists, immunologists and hepatologist, guided by Helmholtz Zentrum München," adds Protzer. The consortium will receive funding of more than € 10 million from the European Union within the program Horizon 2020 (H2020-SC1-2019).