Culture

Sugar delivered to Earth from space

image: This is a Murchison meteorite. Sugars are found from this meteorite in this study.

Image: 
Yoshihiro Furukawa

Researchers from Tohoku University, Hokkaido University, JAMSTEC, and NASA Goddard Space Flight Center investigated meteorites and found ribose and other sugars. These sugars possessed distinct carbon-isotope compositions, differing from terrestrial biological sugars, indicating their extraterrestrial origin. The results suggest that the sugars formed in the early solar system and made their way to earth via meteorites.

The team analyzed three meteorites with their original protocol and found sugars in two meteorites. "Analysis of sugars in meteorites is so difficult. Over the past several years, we have investigated the techniques of sugar analysis in such samples and constructed our original method" says lead author, Yoshihiro Furukawa of Tohoku University.

Amino acids and nucleobases, other vitally important compounds in the building block of life, have been found in meteorites previously. Scientists have known of the existence of sugars in meteorites. However, research to date has largely revealed sugar-related compounds (sugar acids and sugar alcohols) and the simplest sugar (dihydroxy acetone), compounds not considered essential for life.

Formation of bio-essential sugars, including ribose, on the prebiotic Earth, is considered to have been possible. However, there is no geological evidence of their formation. Furthermore, it is not clear which and how much sugar(s) formed on the prebiotic Earth.

With the current research evidencing the delivery of bio-essential sugars, it is plausible that extraterrestrial sugar contributed to the formation of primordial RNA on the prebiotic Earth. This, in turn, has the possibility of being a factor in the origin of life.

"The next step is to investigate the chirality of the sugars in more meteorites and to investigate how much sugars were provided from space and how the extraterrestrial sugar influenced life's homochirality" says the team. NASA Jonson Space Center has provided the team other meteorites and the team will analyze them to see which meteorites contain the sugars and how theses sugars formed.

Credit: 
Tohoku University

Trials promise good news for countries with dengue and Zika virus

video: Scientists from the University of Melbourne and Glasgow work with local community to replace dengue-transmitting mosquito populations with populations unable to transmit dengue and Zika.

Image: 
Professor Ary Hoffman, University of Melbourne

An international team of scientists have reported an effective and environmentally sustainable way to block the transmission of mosquito-borne dengue virus, in trials carried out in Malaysia.

The breakthrough has major implications for countries with hot climates such as island nations in the South Pacific to Saudi Arabia, Africa and South America, all of which experience dengue, Zika, yellow fever and chikungunya.

Using a strain of the bacteria Wolbachia, which inhibit mosquitoes from transmitting viruses to humans, researchers at the Universities of Melbourne and Glasgow and the Institute for Medical Research in Malaysia were able to successfully reduce cases of dengue at sites in Kuala Lumpur. Their data, published today in Current Biology, shows that mosquitoes carrying the wAlbB strain of Wolbachia, when released into the wild, had the effect of reducing the incidence of dengue cases by 40 per cent.

Previously, scientists including Professor Ary Hoffmann from the University of Melbourne, have carried out successful mosquito releases using a different strain of the Wolbachia bacteria, but while this strain was able to invade wild populations in some conditions, it did not appear to be suitable for use in the very hot conditions experienced in equatorial countries such as Malaysia.

Now, this international team of researchers from Melbourne, Glasgow and Malaysia has shown that the wAlbB strain of Wolbachia is stable and effective, even in daily peak temperatures of 36°Celsius and higher, as commonly experienced in areas of Malaysia where dengue is prevalent.

Professor Hoffmann, from Melbourne University's Bio21 Institute, said the findings could make a difference to a number of countries who have dengue.

"This study provides us with a new Wolbachia strain for field release and highlights disease impact within a complex urban setting where dengue incidence rates are high," he said. "The intervention succeeded despite ongoing pesticide applications and other challenges that can make it hard for the Wolbachia to become established. The approach holds promise not only in Malaysia but also in other countries."

Each year there are around 90 million symptomatic cases of dengue, with severe disease in around 1 per cent of cases, including life-threatening haemorrhage or shock syndrome. In Malaysia alone, over 100,000 dengue cases were reported in 2016, with an annual cost estimated at $US175 million.

Researchers released batches of Aedes aegypti mosquitoes carrying the wAlbB strain of Wolbachia into the wild, in six different sites in greater Kuala Lumpur with high levels of dengue transmission. The Wolbachia carrying mosquitoes - both male and female - then went on to mate with the wild mosquito population, resulting in the spread and establishment of the virus-inhibiting bacteria. In some sites, Wolbachia-carrying mosquitoes were measured at over 90 per cent frequency more than a year after the mosquito releases ended.

The success of lowering dengue cases at these sites has led to a cessation of insecticide fogging in these areas, highlighting both the environmental and economic benefits of this method.

Professor Steven Sinkins, from the MRC-University of Glasgow Centre for Virus Research, said the breakthrough is promising news for countries that endure mosquito-borne diseases.

"These findings show that we have a strain of Wolbachia that can be used to effectively reduce the number of dengue cases in very hot climates. The next step is to deploy this strain in more and larger sites, but we are now confident that this will become an effective way to control dengue on a large scale."

Credit: 
University of Melbourne

Magnesium deprivation stops pathogen growth

image: This is an electron microscope image of a macrophage (blue) infected with Salmonella (red).

Image: 
University of Basel, Biozentrum

When pathogens invade the cells, our body combats them using various methods. Researchers at the University of Basel's Biozentrum have now been able to show how a cellular pump keeps such invading pathogens in check. As the researchers report in Science, this pump causes a magnesium shortage, which in turn restricts bacterial growth.

When pathogens infect an organism, the defense system immediately starts to fight the bacteria. To escape the patrolling immune cells, some bacteria invade and replicate inside host cells. However, the host has developed various strategies to keep the intracellular bacteria under control.

Olivier Cunrath and Prof. Dirk Bumann at the Biozentrum, University of Basel, have now discovered that magnesium is crucial for bacterial growth inside host cells. Magnesium starvation is a stress factor for the bacteria, which stops their growth and replication. The host cells limit magnesium supply to these intracellular pathogens using a transport protein called NRAMP1.

Host protein suppresses pathogens

In their study, the researchers investigated Salmonella, a bacterial pathogen that causes gastroenteritis and typhoid fever. The bacteria settle in small inclusions in the macrophages of the immune system. Whether and how quickly Salmonella replicate inside these vesicles and spread depends on the proper functioning of the NRAMP1 transporter.

"It has been known for decades that NRAMP1 makes the host more resistant, but how and why has remained unclear," says Bumann. "We were greatly surprised to find that this transport protein pumps magnesium ions out of the vesicles and thus restricts Salmonella growth. This is a new and completely unexpected mechanism."

Magnesium as an Achilles heel for bacteria

As magnesium is a central component of many metabolic enzymes, a shortage reduces bacterial metabolism and growth. "Magnesium seems to be the Achilles heel for intracellular pathogens. The less magnesium is available, the harder they try to get it. The bacteria go on alert and activate all magnesium uptake systems. Nevertheless, they do not manage to get enough," says first author Cunrath. "However, if the pump in the host cells is defective, magnesium is available in sufficient quantities to enable rapid Salmonella growth."

Transporter affects host resistance

The function of NRAMP1 determines host susceptibility to infections. Animals and humans with reduced NRAMP1 are more susceptible to various intracellular pathogens. If this transporter is completely absent, even a very small number of pathogens can cause a fatal infection.

Infections are always a race between the host and the pathogen. New drugs that would make it even harder for the bacteria to obtain magnesium, could slow down the pathogens even more and thus provide the host a decisive advantage in defeating the infection.

Credit: 
University of Basel

Women raised in poor neighborhoods face an increased risk of intimate partner violence

Women who spend longer periods of their early lives in less affluent neighbourhoods are at greater risk of experiencing violence during their early adulthoods at the hands of their intimate partners, finds a new study published in Epidemiology.

Intimate partner violence - physical, psychological, or sexual violence committed by a current or former partner - is the most common form of violence experienced by women worldwide. In the UK, an estimated 7% of women (approximately 1.1 million women) reported experiencing this violence in the last year alone according to the latest Crime Survey for England and Wales.

The research, led by the University of Oxford with the University of Bristol, looked at participants of Bristol's Children of the 90s study who were followed from birth and reported on their experiences of intimate partner violence between ages 18 to 21. The researchers examined the level of deprivation in women's neighbourhoods over the first 18 years of women's lives, according to England's official measure of area-level deprivation, the Indices of Multiple Deprivation. They found that women who had lived in the most deprived neighbourhoods for longer durations over their childhoods were 36% more likely to experience any intimate partner violence between ages 18 to 21. They also experienced this violence more frequently than women who had spent less or no time living in more deprived neighbourhoods, says the paper.

This is the first UK study to examine whether long-term exposure to neighbourhood deprivation affects the risk of intimate partner violence against women. Neighbourhood deprivation is often thought to increase this risk, in part because neighbourhoods with fewer social and economic resources tend to have higher rates of public forms of violence, like burglary and vandalism. However, whether these relationships translate to violence within the home, and between intimate partners, has been less certain. Prior to this study, nearly every study assessing the relationship between neighbourhood deprivation and intimate partner violence over time had been from the United States.

Lead author Dr Alexa Yakubovich, from the University of Oxford and Unity Health Toronto, said: 'Intimate partner violence is a major public health problem, in the UK and beyond. To develop more effective prevention strategies, we need a better understanding of what causes this violence in the first instance. Our study supports the idea that factors beyond individuals are important for determining women's risk of experiencing intimate partner violence. The effectiveness of strategies that address these structural inequities in preventing intimate partner violence should be evaluated.'

Senior author, Dr David Humphreys at the University of Oxford added: 'This is the first UK study, to our knowledge, to demonstrate that long-term exposure to deprived neighbourhoods appears to be an important factor contributing to increased risks of violent victimisation in young women by their partners. Further research is required to understand how communities can be assisted in supporting young women at risk of violence in the home.'

Professor Gene Feder at the University of Bristol's Centre for Academic Primary Care, also a study co-author, commented: 'The Children of the 90s study was one of the first to measure exposure to intimate partner violence alongside a wide range of individual, family, social and economic factors, over time. This research adds to the evidence that economic inequality and deprivation, even at a neighbourhood level increases a woman's risk of experiencing abuse. Reducing intimate partner violence requires reduction of economic as well as gender inequality, in addition to supporting survivors and their families.'

Credit: 
University of Oxford

Protection for pacemakers

image: This is a cellulose membrane for protecting pacemakers.

Image: 
Hylomorph

ETH scientists have developed a special protective membrane made of cellulose that significantly reduces the build-up of fibrotic tissue around cardiac pacemaker implants, as reported in the current issue of the journal Biomaterials. Their development could greatly simplify surgical procedures for patients with cardiac pacemakers.

"Every pacemaker has to be replaced at some point. When this time comes, typically after about five years when the device's battery expires, the patient has to undergo surgery," explains Aldo Ferrari, Senior Scientist in ETH Professor Dimos Poulikakos's group and at Empa. "If too much fibrotic tissue has formed around the pacemaker, it complicates the procedure," he explains. In such cases, the surgeon has to cut into and remove this excess tissue. Not only does that prolong the operation, it also increases the risk of complications such as infection.

Microstructure reduces fibrotic tissue formation

To overcome this issue, Ferrari and his colleagues at ETH Zurich spent the last few years developing a membrane with a special surface structure that is less conducive to the growth of fibrotic tissue than the smooth metal surface of pacemakers. This membrane has now been patented and Ferrari is working with fellow researchers at the Wyss Zurich research center, the University of Zurich and the German Center of Cardiovascular Research in Berlin to make it market-ready for use in patients.

As part of this process, the research consortium has now tested the membrane on pigs. In each pig, the scientists implanted two pacemakers, one of which was enveloped in the cellulose membrane.

Following the one-year test period, the researchers can report positive results: the pigs' bodies tolerate the membrane and do not reject it. "This is an important finding because tolerance is a core requirement for implant materials," Ferrari says. Just as importantly, the membrane did what it was supposed to: the fibrotic tissue that formed around it was, on average, only a third as thick as the tissue that formed around the unencapsulated pacemakers.

Next step: Clinical trials

The scientists attribute this reduction in fibrotic tissue formation in the first stage to the material itself - cellulose is fibrous by nature. "When fibrotic tissue forms, the first stage is the deposition of proteins on the surface. A fibrous membrane surface impedes this process," explains Francesco Robotti, lead author of the study and a scientist in ETH Professor Poulikakos's group. Another factor is that the researchers created the membrane with honeycomb-like indentations in the surface, each measuring 10 micrometres in diameter. "These indentations make it difficult for the cells that form fibrotic tissue to adhere to the surface - the second stage in the formation processes," Robotti says.

Now that the material has proved successful in animal trials, the scientists plan to apply for approval for clinical trials in humans in partnership with the ETH spin-off Hylomorph, which will be responsible for commercialisation of the membrane. The trials are slated to start next year at three large cardiac centres in Germany.

Credit: 
ETH Zurich

The simultaneous merging of giant galaxies

image: The irregular galaxy NGC 6240. New observations show that it harbours not two but three supermassive black holes at its core. The northern black hole (N) is active and was known before. The zoomed-in new high-spatial resolution image shows that the southern component consists of two supermassive black holes (S1 and S2). The green colour indicates the distribution of gas ionized by radiation surrounding the black holes. The red lines show the contours of the starlight from the galaxy and the length of the white bar corresponds to 1000 light years.

Image: 
P Weilbacher (AIP), NASA, ESA, the Hubble Heritage (STScI/AURA)-ESA/Hubble Collaboration, and A Evans (University of Virginia, Charlottesville/NRAO/Stony Brook University)

An international research team led by scientists from Göttingen and Potsdam proved for the first time that the galaxy NGC 6240 contains three supermassive black holes. The unique observations, published in the journal Astronomy & Astrophysics, show the black holes close to each other in the core of the galaxy. The study points to simultaneous merging processes during the formation of the largest galaxies in the universe.

Massive Galaxies like the Milky Way typically consist of hundreds of billions of stars and host a black hole with a mass of several million up to several 100 million solar masses at their centres. The galaxy known as NGC 6240 is known as an irregular galaxy due to its particular shape. Until now, astronomers have assumed that it was formed by the collision of two smaller galaxies and therefore contains two black holes in its core. These galactic ancestors moved towards each other at velocities of several 100 km/s and are still in the process of merging. The galaxy system which is around 300 million light years away from us - close by cosmic standards - has been studied in detail at all wavelengths, and has so far been regarded as a prototype for the interaction of galaxies.

"Through our observations with extremely high spatial resolution we were able to show that the interacting galaxy system NGC 6240 hosts not two - as previously assumed - but three supermassive black holes in its centre," reports Professor Wolfram Kollatschny from the University of Göttingen, the lead author of the study. Each of the three heavyweights has a mass of more than 90 million Suns. They are located in a region of space less than 3000 light-years across, i.e. in less than one hundredth of the total size of the galaxy. "Up until now, such a concentration of three supermassive black holes had never been discovered in the universe," adds Dr Peter Weilbacher of the Leibniz Institute for Astrophysics Potsdam (AIP). "The present case provides evidence of a simultaneous merging process of three galaxies along with their central black holes."

The discovery of this triple system is of fundamental importance for understanding the evolution of galaxies over time. Until now it has not been possible to explain how the largest and most massive galaxies, which we know from our cosmic environment in the "present time", were formed just by normal galaxy interaction and merging processes over the course of the previous 14 billion years approximately, ie the age of our universe. "If, however, simultaneous merging processes of several galaxies took place, then the largest galaxies with their central supermassive black holes were able to evolve much faster," Peter Weilbacher summarizes. "Our observations provide the first indication of this scenario."

For the unique high-precision observations of the galaxy NGC 6240 using the 8 metre VLT, a telescope operated by the European Southern Observatory in Chile, the 3D MUSE spectrograph was used in spatial high-resolution mode together with four artificially generated laser stars and an adaptive optics system. Thanks to the sophisticated technology, images are obtained with a sharpness similar to that of the Hubble Space Telescope but additionally contain a spectrum for each image pixel. These spectra were decisive in determining the motion and masses of the supermassive black holes in NGC 6240.

The scientists assume that the observed, imminent merging of the supermassive black holes in a few million years will also generate very strong gravitational waves. In the foreseeable future, signals of similar objects can be measured with the planned satellite-based gravitational wave detector LISA and further merging systems can be discovered.

Credit: 
University of Göttingen

Belgian-American research team uncovers a new mechanism of neurodegeneration

Charcot-Marie-Tooth disease (CMT) is an inherited neurodegenerative condition that affects 1 in 2500 individuals. Currently, however, it is still lacking effective treatment options. New research has demonstrated that a class of cytoplasmic enzymes called tRNA synthetases can cause CMT by interfering with the gene transcription in the nucleus. This breakthrough is the result of an international academic collaboration, where scientists from the VIB-UAntwerp Center for Molecular Neurology and the Scripps Research Institute were the driving force. The study was published in the leading journal Nature Communications.

A disease with many faces

Charcot-Marie-Tooth disease (CMT) is a condition that affects the peripheral nervous system. It leads to progressive muscle weakness and loss of sensation in the lower and - later on - upper limbs. It is the most commonly inheritable neuromuscular disorder and, at the moment, remains incurable. The first symptoms can appear both in early childhood or during adult life. Over 90 genes are implicated in the pathology so far and these are involved in a variety of processes. This complexity makes it a difficult condition to study and find a treatment for.

Now, researchers from the VIB-UAntwerp Center for Molecular Neurology and the Scripps Research Institute and their collaborators gained a better understanding of the CMT disease mechanisms that can be applicable for other neurogenerative disorders too.

A problem at the core

The scientists found that in the cell core - the nucleus - of human cell cultures and Drosophila models something went wrong. A major process that happens in the nucleus is the transcription of genetic information encrypted in DNA into RNA molecules, which are then exported in the cytoplasm of the cell and translated into proteins there. The researchers uncovered that an important group of molecules known as aminoacyl-tRNA synthetases - which help in translating RNA into proteins - can also interfere with the transcription of DNA into RNA. This interference was found to be at the core of CMT disease in both fly and cellular models.

Prof. Albena Jordanova explains: "The fundamental message from our work is that components of the translational machinery can function as transcriptional regulators in the nucleus. We demonstrate for the first time that their nuclear role has pathological implications and can cause a neurodegenerative disease. This breaks the current dogmas on the known function of aminoacyl-tRNA synthetases and changes our view on how to study their associated diseases."

From fly to human?

Dr. Sven Bervoets, first author of the study, explains: "Pharmaceutical inhibition of the tRNA synthetase entry into the nucleus prevented the onset of disease symptoms in our CMT Drosophila model, which could have great implications for CMT patients."

While this work provides hope for CMT patients, many questions remain.

Dr. Bervoets continues. "We will have to investigate the nuclear involvement of all the remaining aminoacyl-tRNA synthetases and identify all their interacting partners in the nucleus. It is also still unclear which other transcription factors are important. Only when these research questions have been addressed, we can start thinking about a therapeutic approach that cures the origin and not only the symptoms of the disease."

Credit: 
VIB (the Flanders Institute for Biotechnology)

Unable to reject increased suicide risk associated with use of anti-epileptic drugs

Three of the most common forms of anti-epileptic drugs in Denmark is associated with increase in patients' risk of suicide. However, the risk is low and should be seen in conjunction with the many beneficial effects of the medicines. This is the conclusion of a new study carried out by researchers from Aarhus University and Aarhus University Hospital.

In 2017, 180,000 Danes collected a prescription for anti-epileptic drugs which, in addition to being used for treatment of epilepsy, is also used to treat other conditions such as bipolar disorder and migraine. Researchers from Aarhus University and Aarhus University Hospital have now examined the risk of suicide associated with various forms of anti-epileptic drugs.

The results from the Danish researchers, which have been published in the scientific journal Annals of Neurology, support the American drug administration's warning from 2008 that suicidal thoughts and behaviour may occur as side effects arising from the use of anti-epileptic medicine.

"The study shows that people who are being treated with anti-epileptic drugs have a slightly increased risk of suicide. This applies to people who take the medicine for epilepsy, but also to those who take it for e.g. migraines or psychological disorders," explains Postdoc Julie Werenberg Dreier from the National Centre for Register-based Research, Aarhus University, who is behind the study.

The risk should be seen in conjunction with the effect

Utilising the Danish registers, the researchers identified persons with psychiatric disorders in the family or suicidal behaviour prior to the treatment with anti-epileptic durgs. It was previously suspected, that the risk of suicide associated with anti-epileptic drugs only appeared among people with a high risk of suicide, i.e. people with psychological disorders in the family or people who had previously attempted suicide.

"This study shows that the risk of suicide with the use of anti-epileptic drugs is found both among people that we already know have a particularly high risk, but actually also among people with no previous suicide attempts and psychological disorders in the family, who are basically low risk," says Julie Werenberg Dreier.

The researchers looked at 450,000 Danes who were being treated with anti-epileptic medicine during the period from 1997 to 2016.

"Our study identifies 40-60 suicides per year (in recent years) among people who were being treated with anti-epileptic drugs at the time when they committed suicide. During the same period, there were approximately 600 people in total who committed suicide in Denmark each year," explains Julie Werenberg Dreier.

The drugs phenobarbital, clonazepam and pregabalin are particularly associated with an increased risk of suicide.

Contact your general practitioner if you experience suicidal thoughts

However, in general the extra risk of suicide is very low, and according to the researchers it is therefore important to emphasise that the risk must always be viewed against the many beneficial effects that the medicine also has, such as reducing and preventing seizures and thus also accidents and death.

"Therefore, our recommendation is that people undergoing treatment with anti-epileptic drugs are particularly aware and contact their doctor if they experience suicidal thoughts," says Jakob Christensen, who has also contributed to the project. He is clinical associate professor at Aarhus University and consultant at the Department of Neurology at Aarhus University Hospital, and has carried out intensive research into epilepsy over a number of years.

He emphasises that the study ought to be followed up with additional research to examine whether there are differences between the individual types of anti-epileptic medicine.

"Suicide is a rare consequence of treatment with anti-epileptic drugs - but is of course also very serious. So this is why we should react so as to avoid as many cases as possible," says Jakob Christensen, who emphasises that there is a strong need to find anti-epileptic drugs with the lowest possible risk of suicidal behaviour.

Credit: 
Aarhus University

Detecting mental and physical stress via smartphone

image: The smartphone used as an instrument readily available, for simple self-monitoring of one's health.

Image: 
Politecnico di Milano

Can we use our smartphones without any other peripherals or wearables to accurately extract vital parameters, such as heart beat rate and stress level?

The team led by Professor Enrico Caiani of the Department of Electronics, Information and Bioengineering at Politecnico di Milano has shown that it is possible to do so, using the accelerometers inside a smartphone.

In fact, they can be used to acquire a signal associated with mechanical - cardiac activity, generated by heart's vibrations at every beat, which can be felt by simply placing the telephone on particular parts of the body.

In this study we focussed on positioning of the smartphone on the abdomen, at the belly-button, as part of an application scenario that looks at brief daily acquisition lasting 30 seconds, in a prone position, before getting out of bed in the morning. By suitably processing this signal, measurements can be acquired of the heart beat rate and status of activation of the sympathetic-vagal balance, associated with the stress level. By means of an experimental protocol, which calls for acquisition for each subject in base conditions and during a stressed state induced by mental calculation, it is possible to check the capacity of the indicators measured by the smartphone to capture the increase in stress, on the one hand, and, on the other hand, to determine the best correspondence of the results with the same observations made using an electrocardiogram taken at the same time.

This study, carried out in collaboration with the team led by Professor Gianfranco Parati of the I.R.C.C.S. Istituto Auxologico Italiano, in the Department of Cardiovascular, Metabolic, and Neurological Sciences at Ospedale San Luca in Milan, was recently published in Sensors, the leading open access, peer-reviewed international magazine, on science and technology for sensors and biosensors.

This result opens new horizons and possibilities for using the smartphone as an instrument readily available, for simple self-monitoring of one's health.

Credit: 
Politecnico di Milano

Scientists discover the origin of a microbial infection with lethal effects

image: This is the researcher Ana Fernández.

Image: 
URV

Some infections caused by bacteria can have devastating results on health. This is the case of the infections caused by Aeromonas hydrophila, which can be found in water and, if ingested orally, can sometimes cause gastrointestinal upsets that require treatment with antibiotics. However, when this aquatic bacterium penetrates the organism through a tissue (an open wound, for example) it gives rise to necrotizing fasciitis, a serious infection that attacks the tissues and in a few hours can even lead to the death of the patient. The researchers Ana Fernández and María José Figueras, of the Department of Basic Medical Sciences, in conjunction with the University of Texas (United States), have discovered why in some cases this bacterium can have lethal consequences, which makes it possible to find effective treatments to attack the infection.

Previous studies had already shown that infections that make such quick progress and do not respond to treatment are often caused by interaction between various microorganisms. A research group from the University of Texas studied a previous case of necrotizing fasciitis and found that two genetically different strains of the bacterium Aeromonas hydrophila were responsible for the virulence of the disease. This difference, however, could not be detected by current diagnostic techniques, which mistakenly attributed the infection to a monomicrobial origin. The research also suggested which virulence factors were involved in these infections.

The current study, which has just been published in the journal Proceedings of the National Academy of Sciences (PNAS), was a continuation of the research carried out by this group. Mutations of the virulence factors were made for the two strains of the bacterium (known as NF1 and NF2) and the infection was inoculated separately and together in an attempt to observe the response of each strain in mixed infections - in which they both intervene - and also when they act individually. The role of these virulence factors in the development of the disease was also studied.
To determine the role of the virulence factors of the strains when they cause infection, the studies were carried out in cell cultures and animal models (mice). The results show that, when microbes from the same species interact, they modulate the progress of the infection. And they also show that the virulence factors studied affect the way in which the strains interact with one another.

"Identifying and understanding the action of the two genes that cause the extremely aggressive reaction of the infection caused by Aeromonas hydrophila will make it possible to find therapies to attack it in the future," says the researcher Ana Fernández.

Credit: 
Universitat Rovira i Virgili

Nature's secret recipe for making leaves

video: Leaf shape movie

Music Jazz suite 2 Shostakovich

Image: 
Phil Robinson, Karen Lee, Jie Cheng, Enrico Coen

The secret recipe nature uses to make the diverse leaf shapes we see everywhere around us has been revealed in research.

The discovery comes in a study of the carnivorous plant Utricularia gibba (bladderwort) which has evolved unusual cup-shaped leaves with trap-doors to catch prey.

The team from the John Innes Centre has been investigating the aquatic plants as a model to understand the general principles by which plants produce their leaves.

In this study they discovered that simple shifts in gene activity in the leaf bud provide a flexible mechanism for how leaves of all shapes and sizes are made.

"We've discovered a general principle by which leaves from flat sheets to needle-like and curved shapes are formed," says Professor Enrico Coen of the John Innes Centre.

"We found that the complex leaf shapes of carnivorous plants evolved from species with flat leaves through simple shifts in gene activity in the leaf bud. What surprised us is that how such a simple mechanism could underlie such a wide diversity of leaf shapes."

Previous research by Professor Coen's lab had identified a polarity field - a kind of inbuilt cellular compass - which orients growth and shaping of the leaf from a sheet of cells.

Here, in a study which appears in the journal Science, they used molecular genetic analysis and computer modelling to show how the cellular sheet is formed in the first place, identifying a second polarity field and the domains of gene activity involved in setting it up.

Each Utricularia gibba leaf consists of several needle-like leaflets together with a trap. Their analysis showed that trap initiation and development was dependent on gene activity being restricted to a small region. Without the restrictions traps failed to develop and only needle-like leaflets form.

The study presents a model in which such shifts in gene activity establish a polarity field which orients tissue growth. Together it offers a simple mechanistic explanation of diverse leaf forms and accounts for how cup shaped leaves evolved from flat leaves.

Most leaves are flat to harvest light for photosynthesis. So why study these strange cup-shaped exceptions to the rule when you are looking to find the general principles of leaf making?

"If you want to understand why water boils at 100°C, look for situations in which it doesn't, like the top of Mount Everest where it boils at 70°C. From that we learn the general principle that boiling point depends on air pressure. Similarly, if you want to understand why most leaves are flat, you might study exceptions, like the leaves of some carnivorous plants which form pitchers to trap prey," explains Professor Coen.

Leaf flatness is important for how plants harvest light, providing energy and food that sustains life on the planet. By understanding the principles of leaf formation scientists and plant breeders may be able to develop more sustainable crops.

Credit: 
John Innes Centre

Turning to old remedies for new health challenges

The last thing anyone wants during a stay in the hospital is a hospital-acquired infection. Nosocomial infections, as they are called, are on the rise as more pathogens become resistant to drugs currently available. One pathogen tops the list as one of the most common, one of the most frequently fatal, and one of the most difficult to treat - Acinetobacter baumannii.

Kumar Venkitanarayanan, Associate Dean for Research and Graduate Studies, and professor in the College of Agriculture, Health, and Natural Resources, and his team recently published research in the journal Wound Medicine detailing how they are working to change that.

A. baumannii is included on the World Health Organization's ESKAPE list, a collection of bacteria that are becoming increasingly antibiotic-resistant. With resistance on the rise, research into alternative therapies is paramount, and in some cases returning to old therapies is proving effective.

Infections of A. baumannii are especially difficult to treat since the bacteria possess an arsenal of measures for acquiring antibiotic resistance, says Venkitanarayanan. The bacteria are also capable of forming biofilms that fortify the infection against antibiotics and affords them the increased chance of spreading, especially in hospital environments.

"A. baumannii is primarily a nosocomial pathogen impacting those especially with compromised immune systems, the very young, the very old, burn victims, and is also reported in the wounds of combat soldiers," says Venkitanarayanan. A. baumannii can infect wounds and lead to especially persistent skin and soft tissue infections and eventually spread, causing difficult and sometimes impossible to treat systemic infections such as pneumonia or urinary tract infections.

Rather than take the approach of developing new antibiotics, Venkitanarayanan's research group looks to older treatment methods to search for new strategies.

"In the olden days, metals were used as antimicrobial treatments, so we decided to revisit those to see if they could be applied to modern-day treatments," says Venkitanarayanan.

Metals and metalloids have long been recognized for their disinfecting qualities, and as such have been used in food preservation, water disinfection, cleaning products, and for wound treatment. The researchers screened metals for their antimicrobial efficacy and found selenium, a metalloid, to be promising. In addition to potential antimicrobial uses, selenium also happens to be a micronutrient important in immune system functioning, nucleic acid synthesis, as well as other physiological processes.

The researchers first determined the minimum amount of selenium needed to inhibit the bacteria's virulence, or ability to cause disease. With this approach, Venkitanarayanan says the bacteria are still able to grow, but are not able to infect the host as effectively.

Since bacteria develop resistance to drugs when their survival is impacted, at sub-lethal antivirulence concentrations, the bacteria are less likely to develop antibiotic resistance. Also, at these levels, the drugs are less likely to have negative impacts on the patient for instance, such as what is seen with antibiotics where the host microbiome is impacted by the treatment.

Next, the team simulated a wound by culturing cells and wound fluids in a model matrix. The wound matrix model was then inoculated with the bacteria, with or without the amount of selenium needed to inhibit A. baumannii virulence.

The biofilms treated with or without were observed under scanning electron microscopes, and DNA analysis was performed to assess if any genetic changes took place after exposure to selenium.

The researchers also performed assays to determine how effectively the bacteria could adhere to and invade skin cells both with and without selenium present.

Bacteria can employ different strategies to colonize a host, from thick coatings to avoid desiccation or penetration from drugs, to means of attaching to and making their way into the host. It appears selenium has ways to dismantle multiple strategies in A. baumannii.

What the researchers found was that for the cultures exposed to selenium, the biofilm architecture of those cultures was significantly decreased, leaving the biofilm appearing diffuse and broken down. Correspondingly, the post-treatment genetic analysis revealed significant down-regulation of genes associated with biofilm production. Selenium also reduced the bacterial ability to adhere to and invade skin cells.

"There are no clear data for how selenium works. There appears to be toxicity against the outer membrane of the bacteria and it might also cause toxicity against the DNA, potentially in genes that are involved in biofilm creation," says Venkitanarayanan.

Studying these exact mechanisms are the next steps the researchers will be taking, thus getting one step closer to clinical applications.

Even though the exact mechanisms of action for selenium are not known at this time, Venkitanarayanan says it is important to explore these types of options. His group has explored selenium's efficacy for treating other infections such as enterohemorrhagic Escherichia coli (EHEC) and Clostridium difficile (C. diff). As more antibiotic resistance is encountered in treating various bacterial infections, Venkitanarayanan says that looking back to treatments that worked once upon a time is important.

"Even if we make use of the old methods in concert with modern antibiotics, it is better than not being able to use anything at all."

Credit: 
University of Connecticut

Researchers discover how lungs cells respond to bacteria

(Boston)--Previous research has shown that recovery from bacterial pneumonia hugely improves our defense against further infections by seeding the lungs with immune cells called lung resident memory T (TRM) cells, but how these cells actually protect the lungs against future bacterial infections has been unknown until now.

Researchers have discovered that TRM cells tell surrounding lung cells to send out a signal to recruit bacteria killers called neutrophils. These finding show that immunity within the lung tissue is what provides the most protection for preventing pneumonia..

Worldwide, pneumonia remains a serious public health burden. Each year more than one million children under the age of 5 die from pneumonia and associated complications. In the U.S., pneumonia is the most common reason for the hospitalization of children and accounts for nearly half of the infectious disease-related hospitalizations and deaths of older adults.

Using experimental models researchers from Boston University School of Medicine (BUSM), developed ways to deplete TRM cells to determine how specifically it affected the lung's response to infection. "Because we found that the lung-lining cells changed their behavior when TRM cells were missing, we studied those lung-lining cells in culture, including how they responded to TRM-derived signals to generate neutrophil-recruiting signals," explained corresponding author Joseph Mizgerd, ScD, professor of medicine, microbiology and biochemistry at BUSM.

It was Mizgerd and his team who first identified that recovery from bacterial pneumonia changes lung tissue that was previously infected.

According to the researchers, this study was designed to generate knowledge about the immune components that are useful for fighting pneumonia. "Over the long-term, our study has implications for preventing and treating pneumonia which is important for keeping people out of the hospital and for preventing hospitalized patients from progressing to the intensive care unit and even worse outcomes."

Mizgerd envisions a future in which clinicians can measure and report a person's lung immunity and pneumonia susceptibility status. "Interventions could be developed to improve an individual's lung immunity in order to prevent pneumonia, and lung immunity is manipulated, triggered, or mimicked in pneumonia patients to accomplish a cure against drug-resistant organisms or microbes for which no drugs have yet been developed."

Credit: 
Boston University School of Medicine

Does frailty affect outcomes after traumatic spinal cord injury?

image: Journal of Neurotrauma focuses on the latest advances in the clinical and laboratory investigation of traumatic brain and spinal cord injury.

Image: 
Mary Ann Liebert, Inc., publishers

New Rochelle, NY, November 21, 2019--A new study has shown that frailty is an important predictor of worse outcome after traumatic spinal cord injury in patients less than 75 years of age. In patients younger than 75 years, frailty was a predictor of adverse events, acute length of stay, and in-hospital mortality, as reported in an article published in Journal of Neurotrauma, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article on the Journal of Neurotrauma website through December 21, 2019.

"The Effect of Frailty on Outcome after Traumatic Spinal Cord Injury" was coauthored by John Street, MD, PhD, University of British Columbia and Vancouver Spine Surgery Institute (Vancouver, Canada) and colleagues from University of British Columbia, Vancouver Spine Surgery Institute, Rick Hansen Institute (Vancouver), and Northern Ontario School of Medicine (Thunder Bay). The researchers examined the effect of patient age, Total Motor Score on admission, and score on a frailty index on adverse events, acute length of hospital stay, in-hospital death, and discharge destination (home or other). They identified the need for more accurate tools to measure frailty in the elderly.

"The observation that frailty is an important risk factor for poor post-operative outcomes in younger spinal cord injured individuals should help treating physicians reduce the risks of adverse events and other complications," says W. Dalton Dietrich, PhD, Deputy Editor of Journal of Neurotrauma, The Miami Project to Cure Paralysis, University of Miami (FL).

Credit: 
Mary Ann Liebert, Inc./Genetic Engineering News

Rise of the bots: Stevens team completes first census of Wikipedia bots

Since launching in 2001, Wikipedia has evolved into a sprawling repository of human knowledge, with 40 million collaboratively-written articles and almost 500 million monthly users. Maintaining that project requires more than 137,000 volunteer editors - and, increasingly, an army of automated, AI-powered software tools, known as bots, that continually scour the website to eliminate junk, add and tag pages, fix broken links, and coax human contributors to do better.

Researchers at Stevens Institute of Technology, in Hoboken, N.J., have now completed the first analysis of all 1,601 of Wikipedia's bots, using computer algorithms to classify them by function and shed light on the ways that machine intelligences and human users work together to improve and expand the world's largest digital encyclopedia. The work, published in Proceedings of the ACM on Human-Computer Interaction, could inform the development and use of bots in commercial applications ranging from online customer service to automated microchip design.

"AI is changing the way that we produce knowledge, and Wikipedia is the perfect place to study that," said Jeffrey Nickerson, a professor in the School of Business at Stevens and one of the study's authors. "In the future, we'll all be working alongside AI technologies, and this kind of research will help us shape and mold bots into more effective tools."

By leveraging Wikipedia's transparency and detailed record-keeping, Nickerson used automated classification algorithms to map every bot function as part of an interconnected network. By studying the places where functions clustered, the team identified bots' roles like "fixers", which repair broken content or erase vandalism; "connectors", which link pages and resources together; "protectors," which police bad behavior; and "advisors," which suggest new activities and provide helpful tips.

In total, bots play nine core roles on Wikipedia, accounting for about 10 percent of all activity on the site, and up to 88 percent of activity on some sub-sections such as the site's Wikidata platform. Most of that activity comes from more than 1,200 fixer-bots, which have collectively made more than 80 million edits to the site. Advisor-bots and protector-bots, by contrast, are less prolific, but play a vital role in shaping human editors' interactions with Wikipedia.

New members of online communities are more likely to stick around if they're welcomed by fellow members - but Nickerson and his team found that new Wikipedia users who interacted with advisor- and protector-bots were significantly more likely to become long-term contributors than those greeted by humans. That remained true even when the bots were contacting users to point out errors or delete their contributions, as long as the bots were cordial and clear about their reasons.

"People don't mind being criticized by bots, as long as they're polite about it," said Nickerson, whose team includes Feng Mai, graduate student Lei (Nico) Zheng and undergraduate students Christopher Albano and Neev Vora. "Wikipedia's transparency and feedback mechanisms help people to accept bots as legitimate members of the community."

Over time, some bots fell into obsolescence while others expanded and took on new roles. Studying the evolution of bots, and the ways that human-defined policies shape the bot ecosystem, remains a promising field for future research. "Are we heading for a world with a handful of multipurpose super-bots, or one with lots and lots of more specialized bots? We don't know yet," said Nickerson.

One thing is clear, though: Wikipedia's bots, and the governance and feedback systems that have sprung up around them, offer lessons for commercial bot-builders. "The things we're seeing on Wikipedia could be a harbinger of things to come in many different industries and professions," said Nickerson. "By studying Wikipedia, we can prepare for the future, and learn to build AI tools that improve both our productivity and the quality of our work."

Credit: 
Stevens Institute of Technology