Culture

Nearly extreme black holes which attempt to regrow hair become bald again

image: An artist's conception of a spinning black hole with accretion flow and a jet.

Image: 
NASA/JPL-Caltech

The black holes of Einstein's theory of relativity can be completely described by just three parameters: their mass, spin angular momentum, and electric charge. Since two black holes that share these parameters cannot be distinguished, regardless of how they were made, black holes are said to "have no hair": they have no additional attributes that can be used to tell them apart.

In the early 1970s the late Jacob Bekenstein provided a proof for the nonexistence of hair made of scalar fields given a set of assumptions on the properties of the latter. Researcher Lior Burko of Theiss Research said, "Since Bekenstein's proof, several papers found examples for scalar hair, and all these examples violate one or another of the assumptions made by Bekenstein. But in all cases, the hair was made of the scalar field itself."

Recently, it was shown that black holes that are charged by the maximum possible electric charge ("extreme black holes") can have an additional property, permanent hair that is made of a massless scalar field, and that this newly found hair can be observed from a great distance. "A massless scalar hair does not violate any of the assumptions underlying Bekenstein's proof. It was a big surprise for me when this new hair was found by Angelopoulos, Aretakis, and Gajic, so I wanted to look at it in greater detail. It is hair in a different sense than the kinds of hair that were found before. It is not the scalar field itself, but a certain integral on a derivative of the scalar field that is to be calculated on the surface of the black hole, on its event horizon," said Burko. The new hair can be observed at a great distance, by calculating a different quantity there. "The measurement at a great distance that Angelopoulos, Aretakis, and Gajic found is strictly speaking precise only at infinitely late time," added Burko. "These would be observers who are very distant from the black hole, and who make the measurements in the infinite future. We wanted to see what happens at late but finite times, to see the time dependence of the measurement and how it approaches its asymptotic value. Another special thing about this new hair is that it is applies only for exactly extreme black holes, and we wanted to understand what happens when the black hole is nearly extreme, but not exactly extreme."

Burko and his colleagues Gaurav Khanna of the University of Massachusetts Dartmouth and his former student Subir Sabharwal, currently with the Eastamore Group, showed in a paper just published in Physical Review Research that measurements from a great distance are approaching the hair value, with the difference between them decaying with inverse time. But then they went beyond the original model used by Angelopoulos, Aretakis, and Gajic, and generalized the hair to black holes that rotate at the maximum possible spin rate or just close to it. "In addition to a maximal value of charge, there is also a limit for how fast a black hole can spin. Black holes that spin at the maximal allowed rate are therefore also called extreme black holes. We describe both maximally charged and maximally spinning black holes by the name extreme black holes, as there are many similarities between the two. The new hair was originally found for a very useful toy model for black holes, specifically black holes that are spherically symmetric and electrically charged. But black holes in reality are neither. Instead, we wanted to find out if this hair can be found also for spinning black holes," said Burko. "In the movie Interstellar the monster black hole is nearly extreme. We wanted to see if Gargantua has hair."

The team used very intensive numerical simulations to generate their results. The simulations involved using dozens of the highest-end Nvidia graphics-processing-units (GPUs) with over 5,000 cores each, in parallel. "Each of these GPUs can perform as many as 7 trillion calculations per second; however, even with such computational capacity the simulations took many weeks to complete" said Khanna.

The team showed that for the nearly extreme spinning black holes the hair is a transient behavior. At intermediate times nearly extreme black holes behave like extreme black holes would, but at late times they behave like regular, non-extreme black holes. "Nearly extreme black holes can pretend that they are extreme for only so long. But eventually their non-extremality becomes manifest," Burko summarized. "Nearly extreme black holes that attempt to regrow hair will lose it and become bald again." The team also discusses the observational features, e.g., with gravitational waves observatories such as LIGO/VIRGO or LISA, of the smoking-gun detection of nearly extreme black holes.

Credit: 
Theiss Research

eDNA reveals where endangered birds of a feather flock together

video: Snap freezing the filter paper from samples taken from gouldian finch waterholes.

Image: 
National Environmental Science Program - Northern Australia Environmental Resources Hub

For the first time, Australian scientists have shown that environmental DNA (eDNA) can be used to detect the presence of an endangered bird species simply by collecting a cupful of water from the pools where they drink.

eDNA has emerged as powerful tool to trace rare and threatened aquatic species but its application in the detection of threatened terrestrial species is still largely untested. Researchers from Charles Darwin University, The University of Western Australia, and the Northern Territory's Department of Environment and Natural Resources (DENR) have developed a genetic probe that targets and identifies the eDNA of the endangered Gouldian finch (Erythrura gouldiae), a rainbow-coloured grassfinch endemic to the savanna woodlands of northern Australia.

"When it worked in the real world at the waterholes, even where the water was poor quality in places - where it was hot and looked a bit oily - we were really excited" says Professor Karen Gibb of Charles Darwin University, who led the study funded by the Australian Government's National Environmental Science Program.

The eDNA test has the potential to increase our knowledge of the distribution and habitat use of Gouldian finches; essential information to guide land management decisions that will assist the recovery of wild populations.

Gouldian finches were once found in their thousands from the Kimberley region of Western Australia across to Cape York Peninsula in Queensland. The expansion of pastoralism in the first half of the 20th century and changes in the timing and intensity of fires has been linked to the historical decline in the numbers of Gouldian finches, most likely owing to the reduced availability of the grass seeds that form the major part of their diet. Because the finches are found in small groups across the vast, remote and sparsely populated north of Australia, researchers can't always predict where they need to be and when they need to be there to encounter the birds. This makes it difficult to track changes in the numbers of Gouldian finches from year to year.

Yet there is one aspect of their behaviour that researchers can predict: the granivorous Gouldian finches need to drink water each day. As the northern dry season progresses, suitable waterholes become smaller and rarer. The burst of concentrated activity as flocks of finches drink from shrinking waterholes meant they were likely to shed traceable amounts of their DNA into the water.

The researchers developed a two-in-one eDNA test that uses a PCR primer to amplify a fragment of mitochondrial DNA found in estrildid finches and a species-specific probe to detect Gouldian finch DNA. Gouldian finches often drink at waterholes in mixed flocks with masked finches (Poephila personata) and long-tailed finches (P. acuticauda), which are also members of the estrildid family of finches.

"It's a much more accurate test," Professor Gibb says. "By having primers that pick-up other finches it tells us that the eDNA is good enough quality to be amplified. If the Gouldian test is then negative we can be confident that the eDNA test worked, but there just weren't Gouldian finches at that site."

They trialled the eDNA test in aviaries at the Territory Wildlife Park before field trials at the Yinberrie Hills near Katherine. Scientists from the NT Department of Environment and Natural Resources and Indigenous Jawoyn Rangers have been monitoring Gouldian finches at the Yinberrie Hills since 1996, so there was concurrent count data to validate the eDNA results.

The study, published in Endangered Species Research, showed that Gouldian finch eDNA could be reliably detected from a 200 mL water sample collected from waterholes visited by the birds in the previous 48 hours. At waterholes with the highest number of birds, Gouldian finch DNA was still detectable 14 days after sample collection, regardless of whether the sample was stored at room temperature or refrigerated. A more comprehensive field trial, where protocols for sampling, storage and the eDNA test will be refined, is currently underway.

Having a reliable and accurate eDNA test for Gouldian finches means that Indigenous Rangers and other land managers, as well as scientists, could collect water samples as they move across the landscape undertaking other activities.

"People who are travelling around will be able to put a cup of water into an appropriate container and then into a car fridge, and be able to take a lot of samples," Professor Gibb says. "We can cover a much larger area."

Credit: 
NESP Northern Australia Environmental Resources Hub

Link between inflammation and mental sluggishness shown in new study

Scientists at the University of Birmingham in collaboration with the University of Amsterdam have uncovered a possible explanation for the mental sluggishness that often accompanies illness.

An estimated 12M UK citizens have a chronic medical condition, and many of them report severe mental fatigue that they characterize as 'sluggishness' or 'brain fog'. This condition is often as debilitating as the disease itself.

A team in the University's Centre for Human Brain Health investigated the link between this mental fog and inflammation - the body's response to illness. In a study published in Neuroimage, they show that inflammation appears to have a particular negative impact on the brain's readiness to reach and maintain an alert state.

Dr Ali Mazaheri and Professor Jane Raymond of the University's Centre for Human Brain Health, are the senior authors of the study. Dr Mazaheri says: "Scientists have long suspected a link between inflammation and cognition, but it is very difficult to be clear about the cause and effect. For example, people living with a medical condition or being very overweight might complain of cognitive impairment, but it's hard to tell if that's due to the inflammation associated with these conditions or if there are other reasons."

"Our research has identified a specific critical process within the brain that is clearly affected when inflammation is present."

The study focussed specifically on an area of the brain which is responsible for visual attention. A group of 20 young male volunteers took part and received a salmonella typhoid vaccine that causes temporary inflammation but has few other side effects. They were tested for cognitive responses to simple images on a computer screen a few hours after the injection so that their ability to control attention could be measured. Brain activity was measured while they performed the attention tests.

On a different day, either before or after, they received an injection with water (a placebo) and did the same attention tests. On each test day they were unaware of which injection they had received. Their inflammation state was measured by analysing blood taken on each day.

The tests used in the study assessed three separate attention processes, each involving distinct parts of the brain. These processes are: "alerting" which involves reaching and maintaining an alert state; "orienting" which involves selecting and prioritising useful sensory information; and "executive control" used to resolving what to pay attention to when available information is conflicting.

The results showed that inflammation specifically affected brain activity related to staying alert, while the other attention processes appeared unaffected by inflammation.

"These results show quite clearly that there's a very specific part of the brain network that's affected by inflammation," says Dr Mazaheri. "This could explain 'brain fog'."

Professor Raymond says, "This research finding is major step forward in understanding the links between physical, cognitive, and mental health and tells us that even the mildest of illnesses may reduce alertness."

Dr Leonie Balter the first author of the study which was completed as part of her PhD, concluded : "Getting a better understanding of the relationships between inflammation and brain function will help us investigate other ways to treat some of these conditions. For example, further research might show that patients with conditions associated with chronic inflammation, such as obesity, kidney disease or Alzheimer's, could benefit from taking anti-inflammatory drugs to help preserve or improve cognitive function."

"Furthermore, subtle changes in brain function may be used as an early marker cognitive deterioration in patients with inflammatory diseases."

The next step for the team will be to test the effects of inflammation on other areas of brain function such as memory.

Credit: 
University of Birmingham

The global distribution of freshwater plants is controlled by catchment characteristics

Globally, photosynthetic modes of terrestrial plants are influenced by climatic factors such as adaptations to variation in air temperature and water availability. In water, CO2 often limits photosynthesis because it moves 10,000-times slower than in air and, thus, rapid photosynthesis can deplete CO2 in dense plant stands. In order to meet the requirements of water plants, CO2 concentrations must be 10-20 times higher than in air. This never happens in lakes, where microscopic algae may reduce the CO2 content to 10% of that in air.

The solution among many water plants is to use bicarbonate, which is dissolved in high concentrations in lakes located in calcareous catchments.

' "Use of bicarbonate is energy demanding and much less efficient than CO2 use, when concentrations are the same", explains Professor Ole Pedersen. "However, in bicarbonate-rich lakes, the photosynthesis yield is much higher when water plants can use bicarbonate. Globally, this can account for the increasing abundance of bicarbonate users relative to non-users in lakes located in calcareous catchments."

- "In order to establish the ability, or lack of ability to use bicarbonate of many species, we first had to diagnose several tropical species and then establish their abundance in relation to water chemistry", explains Professor Kaj Sand-Jensen.

The increase in abundance of bicarbonate users with higher bicarbonate concentrations was consistent among temperate and tropical lakes. In streams, however, where CO2 concentrations are high because of continuous inflow of CO2-rich soil water, CO2 use is the most cost-effective and the abundance of bicarbonate users is low and remains independent of bicarbonate concentrations.

The implications of the study are, that species richness and composition of water plants are expected to change with ongoing and future changes of bicarbonate concentrations in lakes that are caused by anthropogenic changes of acidification, forest cover and use of nitrogen fertilizers. The changes can be dramatic, since CO2 users are generally small individuals compared to the much larger bicarbonate users. Therefore, a change in the balance between the two plant types alters the three-dimensional structure of the underwater meadows and the protection of small animals and juvenile fish against predation.

Credit: 
University of Copenhagen - Faculty of Science

Relevant social stimuli may reduce interest in drugs

image: She proposes social support as a key tool in the treatment of drug addiction.

Image: 
University of Malaga

Researchers of the Faculty of Psychology of the University of Malaga (UMA), specialized in addictive disorders, have demonstrated in an animal model that the presence of a relevant social stimulus reduces interest in cocaine.

These members of the "Neuropsychopharmacology Applied to Neurological and Neuropsychiatric Disorders" group of the Institute of Biomedical Research in Malaga (IBIMA), have evidenced that providing animals with a positive and relevant stimulus, like social interaction with another animal, may diminish the preference towards this drug.

For this study, they have used the so-called "place preference conditioning paradigm" that, according to researcher Patricia Sampedro, main author of the study, enables them to study the animal preference towards two different contexts, one of them paired with cocaine administration and the opposite where the animal receives saline. "After four days of observation, we detected that the animals preferred spending more time in the drug-paired compartment", says the expert.

Positive stimulus

In the next stage of the study, the scientists introduced a juvenile mouse, a highly positive stimulus for mice, into the compartment where the animals had received saline and analyzed whether they preferred spending more time in this place or in the compartment they had associated with the drug effect. "We realized that most of the animals preferred spending more time in this social stimulus to exploring the context where they had received cocaine", says Sampedro, who emphasizes, therefore, the key role that social interaction plays in reducing cocaine-seeking and the salience of the drug.

The conclusions of this scientific article, published in Journal of Psychopharmacology, show similar results both in animal models that live independently and those that live in group, also considering the novelty factor.

"We carried out the same experiment but using an inanimate object as stimulus -a Rubik's cube- and, this time, we observed that the animals preferred the drug-paired compartment, which means that the social stimulus is in itself a highly relevant component to catch their attention", she concludes.

This research group proposes social support as a key tool in the treatment of drug addiction. In future stages, the researchers seek to progress in new strategies that reduce the attractiveness of the drug and change preferences towards healthier activities, such as physical exercise.

Credit: 
University of Malaga

First research results from the Estonian-Finnish FinEstBeAMS beamline

image: One of the authors of the recently published research, Vambola Kisand, working on the FinEstBeAMS beamline in Lund.

Image: 
Photo Mati Kook, University of Tartu.

The public might not even know that scientists from the University of Tartu in cooperation with Finnish colleagues have established our "own" Estonian-Finnish beamline at the Swedish national MAX IV Laboratory in Lund. The FinEstBeAMS, which was completed two years ago and opened for research in late 2018, belongs to the Estonian research infrastructure roadmap and it is one of a few objects built by Estonians abroad. FinEstBeAMS, which cost about €7 million, was the first beamline at the MAX IV Laboratory completed as a result of international cooperation.

When all previous activities of the physicists from the University of Tartu were related to designing, building and commissioning the beamline, then by now, the first scientific experiments have been conducted, and as a significant milestone, the first research paper has been published based on results of these experiments.

The research takes a look into the complex electronic structure of three ionic liquids, [EMIM][TFSI], [DEME][TFSI] and [PYR1,4][TFSI], which were studied in a gaseous phase using photoelectron spectroscopy. Ionic liquids are basically molten salts, which are in the liquid phase already at room temperature. One of their most advanced applications is their use in supercapacitors instead of conventional electrolytes. Supercapacitors are able to store remarkable amounts of energy and deliver very large electrical power in a short time. So far, it is not completely clear why some ionic liquids are more suitable as electrolytes of supercapacitors than others. For better understanding application potential of ionic liquids, it is necessary, among other things, to determine their electronic structure using cutting-edge experimental methods, as well as advanced theory for modelling and calculation of their properties. Detailed understanding of the electronic structure on a fundamental level helps to reveal major factors influencing the properties of various ionic liquids.

"The beamline pleasantly surprised us with its intense photon flux, which allowed the studies to be conducted with extremely good spectral resolution and short data acquisition times. The obtained high-quality data provides excellent comparison and helps to verify theoretical results derived from modelling of the properties of ionic liquids carried out in our research group," noted the head of the Laboratory of X-Ray Spectroscopy at the UT Institute of Physics, Vambola Kisand.

The MAX IV accelerator is the world's brightest light source

MAX IV is a circular accelerator called a synchrotron. Many bunches of electrons circulating in the accelerator emit bright shortwave radiation, which allows to reveal the internal structure of matter (fragments with the size of a few nanometres) to be studied, e.g., biological molecules or nano-sized materials. It is also well suited for the investigation of the electronic structure and properties of various substances. In a stainless-steel tube with a diameter of one centimetre, in an ultra-high vacuum the bunches of electrons are accelerated on a 528-metre storage ring to a speed of up to 99.9999999985 per cent of the speed of light. The electrons "tamed" by a magnetic field circulate 24/7 and the radiated light is directed into beamlines with various endstations, where state-of-the-art experiments are conducted. The MAX IV is the first fourth generation synchrotron, being currently one of the world's most modern synchrotrons and the brightest light source.

As a public research infrastructure, the synchrotron is intended to be used by anyone who is interested, from university research groups to entrepreneurs. In 2018, the six beamlines of the MAX IV Laboratory in operation had about 500 users per year; as several new beamlines will be brought into operation, it is expected that by 2025, the number of users will rise above 2,500 per year. Naturally, it is also expected increased interest of Estonian users to exploit the benefits of this large-scale research centre, which is only a 1.5-hour flight away.

At the same time, the European Spallation Source (ESS) delivering neutrons for high-quality research is being built next to the MAX IV Lab synchrotron radiation centre. When complete, the MAX IV and the ESS will jointly form in Northern Europe the largest research infrastructure which experimental methods are complementary.

Beamline also open to Estonian entrepreneurs

The beamline provides photons covering energy range between 5 and 1,400 eV and it is equipped with three end stations for various experiments. FinEstBeAMS offers to scientists, as well as high-tech companies, high-quality shortwave VUV-XUV radiation for investigation of the electronic structure of single atoms, molecules, clusters and nanoparticles in a gaseous state as well as deposited on surfaces. It is an important tool to study particle and surface interaction, multi-layered structures and the surface characteristics of various materials, as well as the luminescence processes in solids.

So far, the capabilities of the MAX Laboratory have been exploited by Estonian companies like Clifton and Lumifor. The former analysed the properties of novel semiconductor materials for microelectronics and the latter studied new dosimetric materials for developing more efficient radiation detectors, which are used for measuring ionising radiation in the ambient environment, e.g., for monitoring the radiation levels of medical radiographs.

Credit: 
Estonian Research Council

Pesticides: Improved effect prediction of low toxicant concentrations

image: Pesticides can have negative effects on sensitive individuals even in the lowest concentrations. This is exemplary shown by experiments with crustacean Daphnia magna.

Image: 
©André Künzelmann / UFZ

Toxic substances such as pesticides can cause effects on sensitive individuals in concentrations up to ten thousand times lower than previously assumed. This was shown by Researchers at the UFZ in their latest study published in Scientific Reports. For understanding these results, one must consider that the level of stress plays an important role. Most surprisingly: not only too much, but also too little stress can lead to a higher sensitivity to toxicants!

Whether a toxicant harms or kills an organism, and if so to which extent, depends on its concentration and the sensitivity of the individuals exposed: the dose makes the poison. "But that's not all," says UFZ ecotoxicologist Prof. Dr. Matthias Liess. „Also, the magnitude of environmental stress is very important to determine the effect of a toxicant." Toxicant concentration, individual sensitivity and environmental stress thus interact in a triad of effects. In their current study, the researchers have investigated the role of these individual components. They wanted to find out how sensitive individuals can be better protected by risk assessment. "Previous model calculations could not sufficiently predict the effects of low toxicant concentrations on sensitive individuals and species," explains Liess. "But this is very important in both human and ecotoxicological risk assessment". This is because sensitive persons - such as children, sick or elderly people - or more sensitive species of an ecosystem obviously suffer damage even at much lower concentrations than previously assumed.

Our extensive investigation was triggered by an observation: "At very low pesticide concentrations - far below concentrations that led to effects in previous studies - effects on sensitive organisms were observed," says the ecotoxicologist. These effects have hardly been observed since such low concentrations are very rarely tested. Previously, it was assumed that pollutants only elicit effects in high concentrations after a threshold value has been exceeded. However, at such extremely low concentrations this is obviously not the case. Liess said: "We observed these unexpected effects at very low concentrations in almost all existing studies in which effects of such concentrations of toxicants were investigated. Also, in their own investigations in which they exposed the crustacean Daphnia magna to very low concentrations of the pesticide esfenvalerate (is used as an insecticide with contact and feeding action in plant protection products in fruit, vegetable and arable farming and is approved in the EU). The question that arises is: which process can induce effects in these low concentration ranges? The hypothesis of the UFZ scientists is that toxicant stress meets internal stress. But what does that mean?

Under the influence of environmental stress - such as predation pressure, parasites and heat organisms become more sensitive to toxicants and therefore can be affected, or die at much lower toxicant concentrations than in the absence of environmental stress. "We were already able to quantify this relationship in earlier studies," says Liess. "Additionally, we are now able to show that individuals develop internal stress when they are exposed to too little stress from the environment. In fact, it seems like organisms are adapted to a certain degree of "external" stress. If it is missing, they develop "internal" stress. "And since external and internal stress add up, the sensitivity to toxicants increases drastically," explains Liess. The result: Sensitive individuals already react to extremely low concentrations of toxicants. These can be up to 10,000 times lower than the concentrations previously considered harmful so far. "Thus, too much - but also too little - stress increases sensitivity to pollutants," says the UFZ researcher. "Optimal with regard to resilience against toxicant exposure would therefore be some fluctuating environmental stress, which reduces internal stress.

In order to make effects visible at low concentrations, the scientists developed a model that enables a calculation of the internal stress and the resulting survival. Liess: "We hope that our study will contribute to a more realistic environmental and human risk assessment - especially for sensitive individuals".

The model of the UFZ researchers can be used in generally accessible and free software: http://www.systemecology.eu/indicate/

Credit: 
Helmholtz Centre for Environmental Research - UFZ

Pulmonary arterial hypertension targeted for new treatment by Sheffield scientists

Scientists at the University of Sheffield have identified an antibody that has the ability to stop and reverse the progression of pulmonary arterial hypertension

Pulmonary arterial hypertension is a rare but fatal disease which is only currently cured by lung transplantation

These research findings will now be prioritised for the development of a new drug treatment for pulmonary arterial hypertension

Scientists at the University of Sheffield, working in collaboration with drug and vaccine developer Kymab Ltd, Cambridge, have identified a novel antibody that has the potential to become a new treatment for pulmonary arterial hypertension (PAH).

Research published today in Nature Communications (Friday 15 November 2019) from the University's Department of Infection, Immunity and Cardiovascular Disease shows that treatment with a specific antibody can reverse the process behind the development of PAH, and will now be considered for clinical development.

Pulmonary arterial hypertension or PAH is a rare but fatal disease with the only cure being lung transplantation. It results in high blood within the lungs due to the constriction and overgrowth of the cells within the arteries that supply blood to the lungs.

Over time this growth restricts blood flow through these vessels, putting strain on the heart and eventually causing heart failure.

The study found osteoprotegerin (OPG) - which has primarily been thought to just regulate bone density - drives the process behind the growth of the cells within the blood vessel walls affected in PAH.

A therapeutic human anti-OPG antibody was found to stop the progress of the disease in experimental lab rodent and cell models, and reverse the proliferation of cells which cause the arteries to thicken.

Allan Lawrie, Professor of Translational Cardiopulmonary Science at the University of Sheffield, said: "Current treatments for PAH ease the symptoms by relaxing and dilating the affected blood vessels which can help extend the life expectancy for those living with PAH, but they do not stop the underlying drivers of the disease.

"The great benefit of this research is the potential for this new drug to be used in conjunction with current treatments, to ease symptoms and further halt or reverse the progression of the disease."

PAH is a rare disease, affecting less than 1 in 2000 people and has 'orphan disease' designation, meaning that despite smaller numbers of patients affected there is a recognised need for effective treatments to be developed.

Sheffield Teaching Hospitals NHS Foundation Trust and the University of Sheffield are one of the largest specialist centres in the world for diagnosis, treatment and leading research into PAH, with this study being the first time that this particular mechanism of the disease has been targeted with a therapeutic human antibody.

"The support from the Medical Research Council in collaboration with Kymab Ltd - which generated the antibody - and the British Heart Foundation to fund this research through the recently formed Donald Heath Research Programme in Sheffield is a hugely significant recognition of the importance of research in this field of medicine which aims to improve the outcome for patients suffering from PAH," added Professor Lawrie.

Credit: 
University of Sheffield

Bacterial protein impairs important cellular processes

image: Pseudomonas aeruginosa lectin LecB can block the cell cycle.

Image: 
AG Römer

Areas of skin that have been damaged by an injury are ideal niches for the concentration of Pseudomonas aeruginosa, a bacterium which impairs the healing process in tissue and creates favorable conditions for infections. Because of its resistance to most available antibiotics, this bacterium is in the "Priority 1 / CRITICAL" category of the World Health Organization's (WHO) global list of priority pathogens. Prof. Dr. Winfried Römer and his research team at the University of Freiburg have recently discovered a new function of the Pseudomonas aeruginosa lectin LecB: LecB can block the cell cycle, meaning that host cells can no longer divide and ultimately die. Wound healing is therefore considerably slowed down or halted altogether. The team of scientists recently published their research in the online scientific journal "Life Science Alliance."

LecB of Pseudomonas aeruginosa is a bacterial virulence factor that impairs signaling of growth factor receptors- in other words, proteins found on the surface of host cells that transmit signals to promote the growth and reproduction of tissues. As a result, the cell cycle is blocked.

Lectins are proteins that bind to sugar residues on surface receptors and are not catalytically active, meaning they do not accelerate chemical processes. Many bacteria use lectins to bind effectively to the epithelium and endothelium layers of cells coating the body's surface area, thus facilitating the colonization of tissue. The researchers discovered that the bacterial lectin LecB is present in chronically infected human wounds, therefore making it possible for Pseudomonas aeruginosa to remain in those wounds. They also determined that LecB is capable of inducing the internalization - in other words, the uptake into the cell's interior - and the degradation of growth factor receptors in keratinocytes, a type of cell in the epidermis. Normally, the binding of growth factors to growth factor receptors activates so-called downstream signaling pathways, which accelerate tissue growth. "We were surprised that LecB does not contribute to the activation of growth factor signaling pathways, but that it triggers this silent internalization of receptors without activation," says Alessia Landi, one of the researchers from the University of Freiburg and the paper's first author.

The scientists also demonstrated that LecB blocks the cell cycle and causes cell death. This process is preceded by intense vacuolization, which is the development of several larger, enclosed sacs (vacuoles) within the host cell. These vacuoles, which display unique morphological characteristics, are formed by structures of plasma membranes in which LecB is enriched. "Although lectins are not catalytically active, LecB appears to interfere with important host cell processes, like the cell cycle, in a way we don't yet understand," says Römer, adding: "This likely occurs through a restructuring of the cell membrane triggered by LecB."

The discovery of this new function of the Pseudomonas aeruginosa lectin LecB has motivated the team to pursue more research. As Römer says, it is possible that LecB also has this function of promoting the further damage of tissue and facilitating the spread of bacteria in other cell types as well, including immune cells. Future studies will therefore focus on the effects of LecB on immune responses in chronic wound infections.

Credit: 
University of Freiburg

15,000 Spaniards may unknowingly have hypophosphatasia bone disease

image: 15,000 Spaniards may unknowingly have hypophosphatasia bone disease.

Image: 
UGR Divulga

Hypophosphatasia (HPP) is a rare and serious hereditary disease that is potentially life-threatening and is caused by one or more mutations in the gene coding for alkaline phosphatase (ALPL). It is frequently misdiagnosed.

To progress toward its correct clinical evaluation, researchers from the Centre for Biomedical Research in Fragility and Healthy Ageing (CIBERFES) of the research group led by UGR researcher Dr Manuel Muñoz Torres in Granada's Biohealth Research Institute of Granada (San Cecilio University Hospital) have implemented a protocol to assess the real proportion of patients affected by this disease. They have also validated the phenotype associated with the two new mutations identified, by means of bioinformatics studies and in vitro assays at the cellular level.

They concluded that almost half of the patients in the study had not been correctly diagnosed and that, extrapolating the data to the Spanish population, there could be as many as 15,000 cases potentially undetected.

Researchers Cristina and Beatriz García Fontana explain that this study, published in Scientific Reports, "provides evidence that it is essential to perform a correct clinical assessment to make a correct diagnosis of this disorder and provide suitable treatment to those patients affected". Due to its low prevalence, this metabolic disorder is usually misdiagnosed and is often confused with more common bone disorders such as osteoporosis, leading to erroneous treatments that could actually worsen the prognosis.

Scientists in the CIBERFES research group estimate that the prevalence in Spain could be twice that quantified in previous studies. To perform this extrapolation, an evaluation of serum levels of total alkaline phosphatase was carried out on a sample of 78,590 patients (76,083 adults and 2,507 children) over the course of 2016. Among the adult population, 1,907 people were identified as having ALP levels below the reference range. After studying the clinical histories of each patient, those subjects who did not meet the criteria established in the proposed protocol were eliminated from the study. Finally, out of the 56 individuals selected, 16 adults (81% of whom were women) agreed to participate. Most of these individuals presented no symptoms at all, or they presented mild symptoms but had never been diagnosed with this condition.

"Using the protocol described in our study, we discovered that 7 of these 16 patients were affected by hypophosphatasia, which indicates that almost half of the population we studied was not correctly diagnosed in normal clinical practice," observes Dr. García Fontana of CIBERFES. Extrapolating these data to the Spanish population, there could be 4,000 potential cases of hypophosphatasia currently undiagnosed--and there could be many more.

"Taking into account the proportion of patients who did not participate in the study for different reasons (71%), and according to our results, the current estimate of possible cases of HHP undetected in Spain could be as high as 15,000," continues Dr. García Fontana. This implies that the estimated prevalence of mild HPP in Spain would be twice that previously published for Europe (1/3,100 vs. 1/6,370).

History of bone fracture and dental abnormalities

Of the patients analysed at the hospital, none presented a family history of HPP or rickets in childhood, but 8 patients (7 of them women) did suffer from prevalent fractures, six of them suffered from symptomatic chondrocalcinosis, and 5 presented dental anomalies. Regarding the biochemical evidence, 10 adults presented lower alkaline phosphatase and higher levels of the PLP substrate compared to the reference values. Of these ten, 7 presented mutations of the ALPL gene, two of which had not previously been described.

Hypophosphatasia in adults involves a loss of mineralization, which gives rise to recurrent fractures, femoral fractures, a history of rickets, and musculoskeletal pain, plus certain dental conditions. Among children it is much more serious, and can cause brain damage, respiratory problems, and even premature death in babies.

Credit: 
University of Granada

Study shows digital media has damaging impact on reintegration of 'white collar' criminals

Offenders convicted of occupational crime and corruption are having their rehabilitation negatively affected by long term 'labels' attached to them on digital media, according to new research by the University of Portsmouth.

The study, published in the Journal of Criminological Research, Policy and Practice, shows these 'labels' can lead to economic strains and social fractures that hinder productive reintegration into society.

It had been thought that those convicted of white collar crimes, such as fraud and bribery were less likely to experience long lasting negativity after finishing their sentence. However, researchers discovered media coverage published online was having a much larger detrimental effect than had been previously assumed.

The archive, search and sharing features of digital media ensures that the online identity of offenders is dominated by their crime long after a sentence is completed. The study shows this ultimately ends up with individuals having a "personal digital criminal legacy" (PDCL). This sticks with them, disrupting their lives and the lives of their families, long after the reported crimes.

Lead author, Dr David Shepherd, from the Institute of Criminal Justice Studies at the University of Portsmouth, said: "Historically it has been assumed that white-collar crime was un-newsworthy and offenders were unlikely to be confronted by the negative impacts of adverse publicity. Consequently, there has been very little research in this field. We wanted to assess this perception and explore the accounts of some white-collar criminals who have experienced the attention of the press."

This is believed to be a rare study into white collar criminals after release from prison. It shows outcomes that directly conflict with the idea that criminal justice is most successful when it encourages the positive reintegration of offenders back into society. Seventeen participants, aged 30 - 65, were questioned and their answers analysed. Overall the group became less economically productive after release from prison. Two remained long-term
unemployed and five could only find work in the gig economy where fewer questions are asked. The association of stymied employment opportunities, a permanent criminalised digital identity and Google was keenly felt by all the participants.

Tony, an employee convicted of occupational fraud, said: "I was all over the Internet, all over the BBC news, so if I typed in my details on Google you will find everything about me."

Frank, a businessman convicted of corporate fraud, said: "You can't erase Google. And the problem is the media portrayal of what went on. It wasn't the truth and it's rarely the truth. But that's what people read, and if they read it, they believe it."

The research concludes that the Internet poses a major challenge to the confidentiality provisions included in the Rehabilitation of Offenders Act (1974). Dr Shepherd said: "The analysis of digital media shows that even local press stories now have a sustained destructive vitality through the creation of a PDCL. The resulting widespread and enduring stigmatisation impacts for offenders, as well as for families and those wrongly accused, have significant implications for productive reintegration, criminal and social justice."

Credit: 
University of Portsmouth

Something old, something new in the ocean's blue

image: Microbial research ranged from unraveling molecular principles in the laboratory to verifying their significance for the marine ecosystem.

Image: 
Max Planck Institute for Marine Microbiology/Gerdts

Microbiologists at the Max Planck Institutes in Marburg and Bremen have discovered a new metabolic process in the ocean. Ranging from molecular structures of individual genes and detection of their global distribution, their results give insight into the pathway process and its degradation products and thus provide valuable information for future calculations of the ocean's carbon dioxide balance.

Charles Darwin suspected something in the "clear blue water" of the ocean that was even smaller than the protozoa he could see under the microscope. "Today we know that every litre of ocean water is swarming with hundreds of millions of microorganisms," explains marine researcher Rudolf Amann, Director at the Max Planck Institute for Marine Microbiology in Bremen. His colleague Tobias Erb from the sister institute of terrestrial Microbiology in Marburg adds: "Although only micrometers in size, the microorganisms with their sheer number and high rate of metabolism have a strong impact on energy flow and biomass turnover in the oceans."

Whilst the unicellular algae, also known as phytoplankton, convert carbon dioxide into biomass, other microorganisms come onto action when the algae excrete the fixed carbon - either during their life, or when they die - sometimes in mass, as after the so-called algae bloom. Even in surface water, single-cell organisms process many thousands of tons of algae biomass: a central process in the marine life cycle. One of the most important compounds in the ocean is glycolic acid, a direct by-product of photosynthesis that is partly converted back into carbon dioxide by marine bacteria. But here, the picture becomes blurred - the exact fate of the carbon in glycolic acid was unknown so far.

In order to come to gain a useful assessment of the global carbon cycle, however, the equation must not have too many unknowns. As we know today, too much carbon dioxide influences life in the ocean. Increased concentrations of carbon dioxide in seawater acidify the oceans, disturb the balance between phytoplankton and microorganisms and ultimately influence global climate. In order to understand the consequences for climate change on a global scale, a precise knowledge of the bacterial degradation of algae biomass is indispensable. For this, however, we need precise basic knowledge of the location, rate and extent of nutrient networks in the ocean. So what exactly is the fate of the glycolic acid's carbon, which globally means substance quantities in the range of one billion tons per year?

The forgotten pathway

Researchers do not always have to start from scratch - sometimes there are already known puzzle pieces, they just have to be recognized and placed correctly. One such piece is the β-hydroxyaspartate cycle. It was discovered more than 50 years ago in the soil bacterium Paracoccus. At that time, the metabolic pathway received little attention and its exact biochemical processes remained unexplored. Lennart Schada von Borzyskowski, first author of the current publication, is a postdoctoral fellow in Tobias Erb's department at the Max Planck Institute for Terrestrial Microbiology in Marburg, discovered this metabolic pathway in the course of literature research. "Looking at this metabolic pathway, I noticed that it should be more efficient than the process previously assumed for the degradation of glycolic acid, and I wondered whether it might be more important than originally assumed," the scientist reports.

Equipped with only a single gene sequence, he came across a cluster of four genes in databases that provided the construction instructions for four enzymes. In combination, three of the enzymes were sufficient to process a compound derived from glycolic acid. But what was the fourth enzyme responsible for? Schada von Borzyskowski tested this enzyme in the laboratory and discovered that it catalyzed an imine reaction previously unknown in this context. This fourth reaction closes the metabolic pathway to an elegant cycle through which the carbon of glycolic acid can be recycled without the loss of carbon dioxide.

Globally distributed, ecologically significant

A cooperation with scientists from the University of Marburg made it possible to study the glycolic acid metabolism and its regulation in living microorganisms. "Now our task was to look for the presence and activity of these genes in marine habitats and their ecological significance," Tobias Erb explains. The cooperation between the Marburg biochemists and the marine researchers at the Max Planck Institute in Bremen proved to be highly fruitful, as the latter have been studying the marine communities near Helgoland for years, in particular the bacterial populations during and after algal blooms. In several excursions on the high seas, the scientists from Marburg and Bremen measured formation and consumption of glycolic acid during algal bloom in spring 2018. Indeed: the metabolic cycle was actively involved in the metabolism of glycolic acid.

The blueprints of the metabolic cycle also were found repeatedly in the bacterial genome sequences that the TARA Oceans Expedition had collected from the world's oceans over a distance of 10,000 kilometres, with a on average 20 times higher prevalence than all other postulated degradation routes for glycolic acid. Thus the rediscovered metabolic pathway is not a niche existence, but on the contrary widespread. These new findings still amaze Rudolf Amann: "The discovery of our colleagues in Marburg turns our previous understanding of the fate of glycolic acid upside down. Our data show that we have to reassess the cycle of billions of tons of carbon in the oceans." As Tobias Erb continues: "This work makes us aware of the global dimensions of the metabolism of microorganisms, and at the same time it shows us how much we still have to discover together."

Credit: 
Max-Planck-Gesellschaft

Amazon deforestation and number of fires show summer of 2019 not a 'normal' year

video: This is drone footage of recently deforested land in the Amazon.

Image: 
Marizilda Cruppe/Rede Amazônia Sustentável

The fires that raged across the Brazilian Amazon this summer were not 'normal' and large increases in deforestation could explain why, scientists show.

The perceived scale of the Amazon blazes received global attention this summer. However, international concerns raised at the time were countered by the Brazilian Government, which claimed the fire situation in August was 'normal' and 'below the historical average'.

An international team of scientists writing in the journal Global Change Biology say the number of active fires in August was actually three times higher than in 2018 and the highest number since 2010.

Although fires in the Amazon can occur in a number of ways, the scientists show that there is strong evidence to link this year's increases to deforestation.

They have used evidence collected from the Brazilian Government's DETER-b deforestation detection system - which calculates deforestation by interpreting images taken by NASA satellites.

This shows that deforestation in July this year was almost four times the average from the same period in the previous three years. This is important as deforestation is almost always followed by fire - the cut vegetation is left to dry before being burned.

Professor Jos Barlow, lead author of the paper said: "The marked upturn in both active fire counts and deforestation in 2019 therefore refutes suggestions by the Brazilian Government that August 2019 was a normal fire month in the Amazon."

August's blazes occurred at a time without a strong drought. Droughts can provide conditions favourable to the spreading of man-made fires. The scientists also show that the 'enormous' smoke plumes that reached high into the atmosphere, which were captured by media footage of the blazes, could only have been caused by the combustion of large amounts of biomass.

The researchers acknowledge that the number of active fires decreased in September by 35 per cent. Though they say it is not clear whether that fall is due to rains or President Bolsonaro's two-month moratoria on fires.

Images from DETER-b show that deforestation continued at a rate well above the average in September, despite the President's moratoria.

The extent of August's fires is unclear. Although the numbers of fires are counted, their extent is not, the researchers acknowledge in their paper 'Clarifying Amazonia's burning crisis'.

Dr Erika Berenguer, a Brazilian researcher jointly affiliated with Lancaster University and the University of Oxford, said: "Our paper clearly shows that without tackling deforestation, we will continue to see the largest rainforest in the world being turned to ashes. We must curb deforestation.

"Brazil has for the past decade been an environmental leader, showing to the world that it can successfully reduce deforestation. It is both economically and environmentally unwise to revert this trend."

Credit: 
Lancaster University

Direct-to-patient telemedicine cardiology follow-ups may safely save families time, cost

Philadelphia - (November 17, 2019) - Health provider follow-ups delivered via computer or smartphone is a feasible alternative to in-person patient follow-ups for some pediatric cardiac conditions, according to the findings of a pilot study presented at the AHA Scientific Sessions this week.

"We've used telemedicine in pediatric cardiology for physician-to-physician communications for years at Children's National, thanks to cardiologists like Dr. Craig Sable," says Ashraf Harahsheh, M.D., cardiologist at Children's National Hospital and senior author of the study. "But this is the first time we've really had the appropriate technology to speak directly to patients and their families in their homes instead of requiring an in-person visit."

"We developed it [telemedicine] into a primary every day component of reading echocardiograms around the region and the globe," says Craig Sable, M.D., associate chief of cardiology at Children's National. "Telemedicine has enabled doctors at Children's National to extend our reach to improve the care of children and avoid unnecessary transport, family travel and lost time from work."

Participants in the virtual visit pilot study were previously established patients with hyperlipidemia, hypercholesterolemia, syncope, or who needed to discuss cardiac testing results. The retrospective sample included 18 families who met the criteria and were open to the virtual visit/telehealth follow up option between 2016 and 2019. Six months after their virtual visit, none of the participants had presented urgently with a cardiology issue. While many (39%) had additional visits with cardiology scheduled as in person, none of those subsequent in- person visits were a result of a deficiency related to the virtual visit.

"There are many more questions to be answered about how best to appropriately use technology advances that allow us to see and hear our patients without requiring them to travel a great distance," adds Dr. Harahsheh. "But my team and I were encouraged by the results of our small study, and by the anecdotal positive reviews from families who participated. We're looking forward to determining how we can successfully and cost-effectively implement these approaches as additional options for our families to get the care they need."

Credit: 
Children's National Hospital

NTU scientists discover new way to promote insulin production in pre-diabetes phase

image: Leading an international team of scientists, NTU Asst Prof Yusuf Ali discovered that a type of immune cell known as 'pancreatic islet macrophages' is capable of promoting insulin production during the pre-diabetes phase, which could be harnessed through new targeted treatments to help prevent Type 2 pre-diabetic patients from turning fully diabetic.

Image: 
NTU Singapore

Nanyang Technological University, Singapore (NTU Singapore) scientists have discovered that a type of immune cell known as 'pancreatic islet macrophages' is capable of promoting insulin production during the pre-diabetes phase.

The scientists believe that the macrophages could be harnessed through new targeted treatments to help prevent Type 2 pre-diabetic patients from turning fully diabetic. Macrophages were not previously known to produce or regulate insulin, and had often been overlooked in diabetes research.

Working with an international team of scientists, the five-year study was led by Assistant Professor Yusuf Ali from NTU's Lee Kong Chian School of Medicine. He wanted to investigate pre-diabetes research due to the general lack of awareness, understanding, and diagnoses for the condition.

"There are currently more than 300,000 people in Singapore and many more around the world who are living and coping with Type 2 diabetes," Asst Prof Ali said. "However, even more people are living in the pre-diabetes phase and if we could detect it early, it would be much easier to reverse any negative progression of the condition."

The study was published in the peer-reviewed journal, American Journal of Physiology - Endocrinology and Metabolism, and is supported by the Singapore Eye Research Institute (SERI), which provided the advanced imaging equipment for the research.

Macrophages - the key to increase insulin production

Located in various organs such as the heart, lungs, and liver, macrophages are large, specialised cells that identify, envelope and even destroy certain cells. Pancreatic islet macrophages reside closely to "beta cells" in the pancreas - key cells responsible for the synthesis and secretion of the hormone insulin, which regulates blood sugar levels.

In pre-diabetic patients, cells in the muscles, body fat and liver start resisting the signals from insulin to remove glucose from the bloodstream, and the beta cells by increasing insulin secretion. This is further supported by an increase in the mass and number of beta cells in a process called 'islet remodelling'.

Asst Prof Ali and his team used pre-diabetes mice models as well as human insulin-producing cell preparations in the laboratory, to show that the findings are translatable for humans. This was conducted in accordance with Singapore's research ethical permits and reporting guidelines.

Over the course of 16 weeks, macrophages near beta cells multiplied through cell division. When the scientists removed this subset of macrophages, islet remodelling and insulin levels fell, causing a transition from the pre-diabetes phase into full Type 2 diabetes.

The scientists believe the results indicate that pancreatic islet macrophages could be successfully manipulated through new targeted treatments during the pre-diabetes phase, in order to increase the supply of insulin secretion and reduce the progression of the pre-diabetes phase.

"The pre-diabetes phase varies from individual to individual. Some get pre-diabetes in a matter of months and develop full blown diabetes, while others live with pre-diabetes for years. Building on our discovery, we now hope to fully uncover the role islet macrophages play and hopefully find ways to delay or reverse the progression of diabetes," said Asst Prof Ali.

Dr Daniel Chew, Head & Senior Consultant, Department of Endocrinology at Singapore's Tan Tock Seng Hospital, who is not involved in the study, said, "In the course of development of Type 2 diabetes, initially insulin secreting beta cells respond to the challenge of insulin resistance by producing more insulin, but later they 'fail' and produce less insulin. This research explores a novel mechanism for the compensatory phase of this phenomenon, sometimes called Starling's Law of the pancreas. The investigators have demonstrated the importance of vascular remodelling of the pancreatic islets in which the beta cells reside and provide strong evidence that it is aided by resident macrophages (immune regulatory cells). Further elucidation of the mechanism by which macrophages enhance beta cell function could lead to novel therapies for prevention and treatment of Type 2 diabetes."

The NTU team aims to conduct deeper research in macrophage subsets, to spur better targeted drugs and treatments for pre-diabetic patients to potentially reverse their ailment.

Acknowledging the support of the research agencies in Singapore and individuals who donated their bodies to science after they had passed away, Asst Prof Ali said, "We took years to validate this study using human islet preparations and we are appreciative of our clinical partners SERI and SingHealth, and especially to the people who donated their organs for research."

Credit: 
Nanyang Technological University