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Monday, 4 November 2019

Live skin can now be printed in 3D, including blood vessels

In order to treat the severely burned and for the treatment of various diseases affecting the skin, the development of artificial skin grafts has become a field of future research, but so far, the absence of functional vascular system in the grafts is a significant barrier to their integration. To remedy this problem, researchers at the Rensselaer Polytechnic Institute have developed a way to 3D-print "living skin" by incorporating blood vessels.

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" Right now, all that is available as a clinical (transplant) product is more like a sophisticated dressing ," said Pankaj Karande, associate professor of chemical and biological engineering and a member of the Center for Biotechnology and Biotechnology. Interdisciplinary Studies (CBIS), which led this research project at the Rensselaer Polytechnic Institute (USA). " They allow accelerated healing of wounds, but they eventually fall; they never really integrate with host cells  . "

The absence of a functional vascular system in skin grafts constitutes a major obstacle to this integration. Karande has been trying to meet this challenge for several years. He has published previously one of the first articles showing that it was possible, from two types of living human cells, to turn them into "bio-inks" to print skin with more natural biological properties. Since then, he and his team have been working with researchers at the Yale School of Medicine to incorporate blood vessels into artificial grafts.

Their new design, detailed in a document published last week in the journal Tissue Engineering Part A , represents an important step in the creation of artificial grafts with properties close to those of human skin.

Allow cellular communication to interconnect vascular structures

In their article, the researchers show that if they add some key elements, the cells begin to communicate and form a biologically relevant vascular structure within a few weeks. These key elements include: human endothelial cells (keratinocytes) (lining the inside of blood vessels), human pericytes (which surround endothelial cells) as well as animal collagen and other structural cells commonly found in grafts skin.

" As engineers working on the reenactment of biology, we have always appreciated and understood that biology is much more complex than the simple systems we make in the lab,  " said Karande. " We were pleasantly surprised to see that as soon as we tackle this complexity, biology takes over and begins to get closer to what exists in nature  ."

Once the Yale team grafted the new skin onto a special type of mouse, the blood vessels printed by the Rensselaer team began to communicate and connect with the natural vessels of the mouse.

" This is extremely important because we know there is actually a transfer of blood and nutrients to the graft, which keeps it alive,  " said Karande.

Make the graft compatible using the CRISPR genetic editing technique

In order to make artificial skin usable at the clinical level, researchers must be able to edit donor cells using CRISPR technology, so that vessels can integrate and be accepted by the patient's body. " We're not at this point yet, but we're getting closer ," Karande said.

" This significant development (presented in the study) highlights the vast potential of 3D bioimprinting in precision medicine, where solutions can be tailored to specific situations and ultimately to individuals,  " said Deepak Vashishth, director of CBIS. " This is a perfect example of how Rensselaer's engineers solve human health problems  ."

Karande said more studies will be needed to address the challenges associated with burns, including the loss of nerve and vascular endings. But the plugins created by his team will encourage other researchers to help people with more discreet problems, such as diabetes or pressure ulcers.

" For these patients, it would be perfect because ulcers usually appear in separate parts of the body and can be treated with smaller pieces of skin,  " said Karande. " Wound healing usually takes longer in diabetic patients, which could also help speed up this process  ."

In the video below, Karande presents her design:


Recycle heat to electricity with ultracentrifed liquids

 By circulating liquids in charged nanoscale channels, it is possible to convert heat into electricity as efficiently as the best thermoelectric materials.

When subjected to a temperature difference, a nanofluidic channel can generate electricity , with a performance comparable to that of the best thermoelectric solids.
© ILM (CNRS / University of Lyon 1)

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The materials solid thermoelectric can convert a temperature difference into electric energy . They thus constitute an important energy resource for the years to come. However, the best performing materials are rare, expensive and often toxic. Physicists of theInstitut light material in Lyon (. CNRS / University Lyon 1) explored an alternative possibility: using nanofluidic channels confining the water salty. Such systems have received much attention recently because they are able to produce electricity from the osmotic energy of seawater . This "blue energy" comes from the phenomenon of osmosis , that is to say the spontaneous flow of the liquid from the most concentrated to the least concentrated medium. But the application of these devices for recycling in heat electricity lost by many industrial processes in electricity is only beginning to be studied. This lower interest is explained by the standard image of the thermoelectricity of charged liquids, developed in the 1980s, and which predicted performance far below that of thermoelectric materials.

Scientists have tested these models using simulations of the behavior of matter at the atomic level. In this type of simulation, the motion of each atom is explicitly described, which allows to measure independently the influence of the various parameters (interactions with the walls, electrostatic contribution) on the movement of the atoms and therefore of the electric current.. Against all odds, they showed that the performance of nanofluidic systems was a hundred times better than the predictions of standard models, and could be comparable to those of the best thermoelectric solid materials. This work demonstrates the potential of nanofluidic systems, and by understanding their mechanisms, they can serve as a guide for the development of high performance devices, a cost-effective and non-toxic alternative to thermoelectric materials.


Listen to the energy of lightning

Everyone knows that counting the seconds between the appearance of a lightning and the arrival of thunder gives the distance at which the lightning falls. Researchers at the Jean Le Rond Institute in Alembert and CEA have shown that this sound can also be used to estimate the energy of a lightning bolt. In this work published in Geophysical Research Letters , scientists deduce the geometry of lightning through a network of microphones, then calculate the energy.

© Institut Jean le Rond d'Alembert The acoustic energy of thunder as a function of the observation distance in km at the point of impact on the ground of the lightning. Squares represent simulated flashes and triangles measure HyMeX. Both follow a similar behavior.

Lightning rebalances the electrostatic charge between two clouds, or between a cloud and the ground. This electrostatic discharge locally increases the temperature of several tens of thousands of degrees, causing a shock wave that spreads in the atmosphere : thunder. If we know how to use this sound to estimate the distance at which a lightning struck, researchers at the Jean-Rond d'Alembert Institute (CNRS / Sorbonne University) and the CEA managed to use it to measure the distance power of lightning. A parameter that suffers from an uncertainty of up to three orders of magnitude.

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The team used the data measured in 2012 as part of the European project HyMeX, which studies the Mediterranean climate . Four microphones recorded for two months , and continuously, the sound emanating from the sky of the Cevennes, a region particularly struck by the storms. These recordings were first used to reconstruct the geometry of lightning, proving the correlation between the location of acoustic and electromagnetic sources. Then, the researchers used them again to isolate, within the thunder, the signalacoustics from some of its branches, including the main channel that connects the storm cloud and the ground. Now we can calculate the thunder of a flash from its geometry and its energy. The researchers compared field-collected thunders to a simulated thunderstorm database of 72 virtual flashes, statistically consistent with true lightning. This has shown that acoustic measurements give very good results in estimating the energy of negative-lightning flashes, which represent 90% of the cloud-to-cloud discharges, and at a distance of between three and twelve kilometers from the pickups.


How are psychiatric disorders in children related to infections during pregnancy?

Infections contracted by a pregnant woman during pregnancy can affect the child's development in different ways. Beyond the purely somatic anatomical and physiological alterations, the alteration of certain precursor neuronal cells can lead to the appearance of psychiatric disorders later in the child, particularly in the schizophrenic and autistic spectrum. This is the conclusion of a new study that highlights the severity of infections and the importance of when they occur.

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Serious infections during pregnancy have been linked to various psychiatric disorders by different studies conducted in humans and animals. Researchers at the University of Copenhagen have shown in mice how infections affect neuronal development and the timing of infection.

Infections, brain development and psychiatric disorders

The health of the mother is very important for the development of the fetal brain during pregnancy. Many factors play a key role in healthy brain development, including nutrition, stress, hormonal balance, and the mother's immune system.

It has been observed in humans and animals that serious infections in pregnant women are a risk factor for developing psychiatric disorders such as schizophrenia and autism spectrum disorders later in the life of the child.

The authors of the study, published in the journal Molecular Psychiatry, showed how infections in the mother can alter the development of stem cells and neuronal precursors of the brain.

Maternal inflammation affects the development of multi-stage interneurons, such as proliferation, migration, differentiation and maturation, resulting in increased vulnerability to mental disorders. Credits: Navneet A. Vasistha et al. 2019

" The connection has already been made in animal studies and clinical observation studies. However, this is the first time we show how infections during pregnancy affect brain development and can lead to cognitive impairment. Although many factors have been assumed or indicated, it is important to show the stages of neuronal development actually affected, "says Konstantin Khodosevich

Infections: the mother's immune response impairs the brain cells of the child

The researchers studied the development of neurons in mice. The mother's immune response to infection has had an effect that extends from stem cells and precursor cells to neuronal cells, causing a profound disruption of their development in the brain. More specifically, the development of cortical GABAergic interneurons - the class of neurons that allows inhibition in the brain - was impaired.

Infections during pregnancy impair neuronal development, resulting in a decrease in the number of motor and somatosensory (bley) neurons. Credits: Navneet A. Vasistha et al. 2019

The effect was immediate and had profound consequences through lasting alterations, resulting in multiple "impacts" during the neuronal development process - from the birth of neurons to their maturity.

In addition, the researchers also concluded that newborn mice exhibited symptoms similar to those of human psychiatric disorders, including reduced prepulsion inhibition, impaired social interaction, and cognitive decline.

The importance of the moment of infection during pregnancy

" The study in humans poses big technological and ethical problems, because of the vulnerability of pregnant women. This is why we study the functioning of mechanisms in mice. Psychiatric disorders are very complex and for some, we still do not know how they present themselves. We really want to contribute to the scientific understanding of these diseases, "explains Khodosevich.

Depending on the time of infection during pregnancy, different precursor cells and, consequently, different neurons, were affected. This means that the moment of infection is very important and can lead to variable results depending on the stage of development of the affected brain. This can potentially underlie the complexity of psychiatric disorders.

The researchers are now hoping to deepen their knowledge of the molecular mechanisms and signaling pathways that cause the degradation of interneuron development.


Sunday, 3 November 2019

Polymers that degrade in the body and the environment

Researchers have succeeded in developing polymers that are more easily degradable in the body as well as in the environment by simply adding an additional monomer to the basic formulation. These polymers may be as useful for administering drugs or carrying medical imaging agents as for replacing certain industrial plastics.

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The polymerization by ring opening metathesis (ROMP) is the name the experts give a chemical reaction that enables the production of polymers for various uses. Most often from norbornene (C 7 H 10 ), a bridged hydrocarbon to which it is easy, before the polymerization reaction , to add drugs or medical imaging agents. The problem is that the polymers thus produced do not degrade easily.

But researchers at the Massachusetts Institute of Technology (MIT, USA) have developed a method that makes them more degradable by simply adding a monomer . A silyl ether which forms chemical bonds that weak acids or bases as well as fluoride ions are able to decompose.

A new type of polymer designed by chemists from the  Massachusetts Institute of Technology (MIT, USA) incorporates a special monomer - here in yellow - that helps polymers break down more easily under certain conditions. © Demin Liu, MIT 

A single monomer in addition

Employed in a 1: 1 ratio with norbornene, silyl ether - evenly distributed over the entire molecular structure of the polymer - aids in degrading polymeric structures similar to those prepared by the ROMP method.

Tests on mice have shown that these new polymers remain as present in the body as the old ones during the two weeks following the injection. But after six weeks, the concentrations were between three and ten times lower. So what to rid the body much faster of these polymers used as drug carriers , for example.

MIT researchers also believe that the process could also be economically profitable for the plastics and adhesives industry, among others. What make these products also more degradable.


Brain recognizes familiar music at lightning speed

One snippet of music suffices: our brain recognizes familiar songs with surprising speed. It takes only 100 to 300 milliseconds to classify a piece of music as known, as experiments reveal. But the recognition does not only show in the brain: Our pupils react too. They widen with excitement when we hear a familiar and popular song.

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Music is deeply rooted in our human nature: There is hardly a culture worldwide that knows no music, and unborn children in the womb react to melodious sounds. Above all, the sound of music develops a strong emotional effect . It can make us cry, awaken memories - or cause uproar.

How certain music affects a person, however, is completely different. This is evidenced, for example, by the fact that everyone has a different favorite song. Where one of them turns off the radio annoyed, the other one turns up loud and sings along at the top of his voice.

Song recognized?

Interestingly enough, our most popular pieces of music seem to be anchored in the brain in a special way: often just a few notes are enough to recognize the song. But how fast can the thinking organ identify familiar melodies? Robert Jagiello from University College London and his colleagues have now taken the test.

For their study, the researchers recruited five men and five women, each of whom named five pop songs known to them, connecting them with positive feelings and memories. For each of these songs, Jagiello's team chose a counterpart - a song that sounded similar in tempo, melody, harmony, and song, but was unknown to the participants.

A matter of milliseconds

In the crucial experiment, the scientists then alternately played less than a second of the known and unknown songs to the study participants. They used electroencephalography (EEG) to observe how the brain responded to these musical snippets. They also measured the dilation of the pupils, which is considered a sign of excitement.

The results revealed that the mind recognized familiar songs surprisingly quickly. It took only 100 to 300 milliseconds to classify a music excerpt as known. This was shown on the one hand by a clear pupil reaction. On the other hand, Jagiello and his colleagues found an activation of cortical brain regions involved in recalling memories.

Benefit for the therapy

"Our results show that familiar music is recognized remarkably quickly. This points to a fast temporal circuit and underlines how deeply such pieces of music are anchored in our memory, "says Jagiello's colleague Maria Chait. The scientists suspect that this particular reaction to the music has to do with the positive emotions associated with it.

According to the team, the results may also be relevant to therapeutic approaches: "Understanding how the brain recognizes familiar melodies can be very useful for music therapy. For example, there is a growing interest in learning about people with dementia through music. Because the memory of music is often kept for a surprisingly long time, "explains Chait.

Identifying the neural processes that enable the recognition of music could thus help to better understand this and other phenomena.


Saturday, 2 November 2019

Researchers develop light-activated insulin-producing cells for diabetes

The researchers caused the beta cells in the artificial pancreas to secrete insulin when exposed to blue light. Insulin is shown here as an atomic model filling the space. Credit: Tufts University

Researchers at Tufts University transplanted beta cells from the modified pancreas into diabetic mice and allowed the cells to produce more than two to three times the typical level of insulin by exposing them to light. Light-switchable cells are designed to compensate for lower insulin production or reduced insulin response in diabetic individuals. The study published in ACS Synthetic Biology shows that glucose levels can be controlled in a mouse model of diabetes without pharmacological intervention.

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Insulin is a hormone that plays a central role in the precise control of circulating glucose levels, the essential fuel used by cells. Diabetes affects more than 30 million Americans according to the Centers for Disease Control and Prevention (CDC). In type II diabetes - the most common form of the disease - the body's cells react ineffectively with insulin and, as a result, the circulating glucose can become dangerously high (hyperglycemia) while the pancreas can not not produce enough insulin to compensate. In type I diabetes, beta cells, which are the only insulin-producing cells in the body, are destroyed by the immune system, resulting in a complete absence of the hormone.

Current treatments include the administration of drugs that enhance insulin production by pancreatic beta cells, or direct injection of insulin to supplement the natural supply. In both cases, the regulation of blood glucose becomes a manual process, the intervention of a drug or insulin being performed after periodic readings of blood glucose, often leading to spikes and troughs that can have adverse effects long-term.

The researchers sought to develop a new way to boost insulin production while maintaining the important real-time link between insulin release and glucose concentration in the blood. They did this by taking advantage of optogenetics, a protein-based approach that modifies their on-demand activity with light. The pancreatic beta cells have been modified with a gene that encodes a photoactivatable adenylate cyclase enzyme (PAC). PAC produces cyclic adenosine monophosphate (cAMP) when exposed to blue light, which increases the production of glucose-stimulated insulin in the beta cell. Insulin production can increase two to three times, but only when the amount of blood glucose is high. When blood glucose is low, insulin production remains low. This avoids the common disadvantages of diabetes treatments, which can overcompensate insulin exposure and leave the patient with a harmful or dangerously low blood sugar level (hypoglycaemia).

The researchers found that transplanting artificial pancreatic beta cells into the skin of diabetic mice improved tolerance and glucose regulation, reduced hyperglycemia, and increased plasma insulin levels during blue light illumination.

"It's a retrograde analogy, but we actually use light to activate and deactivate a biological switch," said Emmanuel Tzanakakis, professor of chemical and biological engineering at the School of Engineering at Tufts University and corresponding author of the 'study. "In this way, we can help, in the diabetic context, to better control and maintain the appropriate glucose levels without pharmacological intervention.The cells naturally perform the work of insulin production and the regulatory circuits within them work from the In the same way, we simply increase the amount of transient cAMP in beta cells to produce more insulin than is needed. "

Blue light simply switches the switch from normal mode to fast mode. Such optogenetic approaches using light-activatable proteins to modulate cell function are being explored in many biological systems and have fueled efforts to develop a new kind of treatment.

"The use of light to control treatment has several advantages," said Fan Zhang, a graduate student at Tzanakakis Lab in Tufts and the first author of the study. "Obviously, the response is immediate, and despite the increased secretion of insulin, the amount of oxygen consumed by the cells does not change significantly, as our study shows." Oxygen deficiency is a common problem in studies involving transplanted pancreatic cells. "


The 2 million years ancient ice reveals crucial information about the Earth's carbon cycle

A team of scientists worked more than two years to achieve these results: the oldest complete ice core provided a reliable snapshot of the atmosphere of our planet as it was nearly 2 million years ago. years. And the data presented is not what we would have expected.

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We know that about a million years ago, the cycle of the Earth's ice ages suddenly changed: since that change, deeper and longer gels only occur every 100,000 years or so, once every 40,000 years.

Nothing on our planet could explain this "brutal" change, better known as the middle Pleistocene transition known  as  MPT  (English Mid-Pleistocene transition), and with few other explanations, some hypothesized long-term decline in CO2 concentrations in the atmosphere, cooling the planet to a new threshold.

But the old air bubbles trapped in the Antarctic ice floe revealed somewhat different information. Indeed, dating back to about 1.5 million years ago, these tiny amounts of our ancient atmosphere reveal " incredibly low " CO2 levels , according to palaeoclimatologist Yige Zhang, of Texas A & M University, who did not participate in the study and stated that he found the results "quite interesting".

These are the first direct observations of greenhouse gases in the atmosphere before the intervals between the Ice ages on Earth begin to lengthen. These observations also suggest that something else that a long-term decline in CO2 has been involved in the change in the complete cycle of the ice age of our planet.

Blue ice near the Allan Hills area in Antarctica. Environmental conditions in this area attract old ice to the surface. Scientists analyzed the air trapped in a core of ice drilled in this region, to obtain the first direct measurements of carbon dioxide levels in the atmosphere, dating back two million years ago. Credits: Sean Mackay

The oldest ice sample that we could test for CO2 levels prior to this new core, dates back only 800,000 years ago: other estimates based on sediment chemistry Earth are only useful as indirect indicators of greenhouse gas levels, they are not useless, but additional verifications are needed.

But the new ice analysis, which exploited more precise measurements than before, revealed that: " although the CO2 levels during the glaciations have remained much higher than the troughs recorded in the ice depths during the 800 ' In the last few years, maximum CO2 concentrations during the interglacial periods have not decreased,  "said Eric Wolff, Earth Science Scientist at the University of Cambridge, who wrote a report on the research.

"  One of the important results of this study is that the carbon dioxide level is temperature-related at the beginning of this period, " said Atmosphere Specialist Ed Brook of Oregon State University. " This is an important baseline for understanding climate science and calibrating predictive models of future change ," he added.

In other words, the relationship between CO2 levels and temperature in Antarctica has not changed much during this period. And, according to scientists, the low levels of CO2 during ice ages are probably only a consequence of the shorter glacial periods that occurred before TWA.

The authors also found that the lowest levels of CO2 did not occur during the first 40'000 years after MPT. " Our results seem to contradict the assumptions that attribute the transition to a world from 100,000 years before a change, to a long-term decline in atmospheric CO2, both interglacial and glacial," the researchers write.

In his report of the research, Wolff congratulated the researchers for their precise estimates, but also argues that "  s complete and undisturbed chronological eries" is needed to bring CO2 levels in context.

Fortunately, the old ice core, discovered in the Allan Hills, Antarctica, may soon have company. Indeed, researchers predict that the ice cover dates back to 2.7 million years or more. " We do not know the age limit in this area,  " Brook said.

And, given the extent of ice movement in this region, new cores that researchers will be analyzing soon will most likely come in discontinuous sections. "  There could be much older elements in some places. That's why we're going back. To grow beyond two million years would be truly incredible, "added Brook. As a result, their future information can help us learn more about some of the mysteries of the planet.

VIDEO: Ice reveals crucial information about the ancient Earth's atmosphere


For the first time, astrophysicists could have detected a "mini black hole"

The black holes are certainly part of the most mysterious objects in the cosmic catalog. Planned from the beginning of the 20th century as part of general relativity, current models describe several types: stellar black holes, intermediate black holes and supermassive black holes. Each of these types has been detected in recent years. But the models also provide other hypothetical black holes, such as primordial black holes, black micro holes or even mini black holes. The latter would be black holes whose mass would be between that of a neutron star and that of a stellar black hole . And for the first time, cosmologists could have detected one.

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Astronomers generally look for black holes in our galaxy by observing the X-rays that are emitted when black holes absorb material from nearby stars. The thermal friction within the accretion disk generates, in fact, the emission of a powerful electromagnetic radiation. In more distant galaxies , this search may involve the detection of gravitational waves produced by the fusion of two black holes.

But a group of researchers wondered if there might be relatively low mass black holes that do not emit the tell-tale X-ray signals. Such hypothetical black holes would probably exist in a binary system with another star, although they orbit sufficiently far from this star not to absorb too large quantities.

Mini black holes: they would betray themselves by the variations of brightness of their companion star

The researchers speculated that these small black holes would not emit detectable X-rays and would therefore remain invisible to astronomers, according to Todd Thompson, a professor of astronomy at Ohio State University. " We are pretty sure there must be many, many of these black holes in the binary systems with stars in the galaxies, but we have not detected them because they are hard to find ."

Thompson and his colleagues looked for evidence of these black holes in the stellar companions of the proposed objects. They screened the data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE), containing information on the light spectrum of more than 100,000 stars in our galaxy.

The information in this study revealed changing spectra for each of these stars. Such a change could mean that a particular star is gravitating around an invisible companion. After conducting this analysis, the researchers examined changes in brightness of a subset of stars that could gravitate around black holes, using data from another mission called ASA-SN (All-Sky Automated Survey). for Supernovae).

An object too massive to be a neutron star ... but not massive enough to be a stellar black hole

This is how the researchers discovered a massive black object, caught in a gravitational embrace with a giant star in rapid rotation, located about 10'000 light-years from Earth, on the edge of our galaxy (near the constellation of the Coachman).

They estimated that the mass of this object was about 3.3 times that of our Sun, too massive to be a neutron star and not massive enough compared to that of known black holes. The results were published in the journal Science.

Graphic presenting the observational constraint posed on the mass of the object. The most accurate result indicates about 3.3 solar masses. Credits: Todd A. Thompson et al. 2019

The most massive neutron stars that astrophysicists know are 2.1 solar masses, while the least massive black hole known is about five to six times the mass of our Sun, according to Thompson. However, the lower mass limit of the new object found corresponds to 2.6 times the mass of the Sun, which, according to astronomers, constitutes the theoretical upper limit of star mass. More massive than that, the neutron star would collapse into a black hole.

The realistic hypothesis of the detection of a black mini-hole

So, this dark and mysterious object " could be the most massive neutron star ever seen. Just at the border after which she can no longer exist. In fact, I would be even more excited if that were true. But it is more than likely a relatively low mass black hole, theorized but never discovered before, "says Thompson.

Mini black holes, black holes whose mass is located between that of neutron stars and stellar black holes, have been theorized for many years. Credits: LIGO-Virgo, Frank Elavsky, Northwestern (Modified by Todd Thompson)

Dejan Stojkovic, a cosmologist and professor of physics at the University of Arts and Sciences, Buffalo, confirms these results. " It's probably a black hole, because it's too massive to be a neutron star, unless it's a kind of unusual star. The discovery seems very reasonable, but not unexpected, because astronomers know that there are black holes of lower mass .

Thompson said he was eagerly awaiting future discoveries, such as information on the inclination of the star's orbit around the dark object that the European Space Agency's Gaia spacecraft could muster during the day. a next mission. This could help researchers to more accurately measure the mass of the dark object.


New powerful ranavirus discovered that can spread among amphibians

Of the invasive pathogens that are decimating the reptile populations in various areas the United States we have already mentioned and now a new study, appeared in the journal Ecological Modeling and produced by researchers of the University of Tennessee, shows the existence of a new ranavirus similar to a Frog virus 3 (FV3).

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The new ranavirus, called RCV-Z2, can, according to researchers who have developed a specific model to predict its spread, spread just as quickly in a tadpole population of North American wood frogs ( Lithobates sylvaticus ) and transmission can occur in a very efficient through direct contact, through necrophagy (if the subjects feed on the bodies of other infected subjects) or even by water.

The ranaviruses are pathogens that are emerging globally and affect mainly reptiles, amphibians and fish threatening the ecological diversity of these species and therefore all the eco-environments in which they are found.
To combat the ranavirus emergency, which has become global, researcher Matt Gray founded and directs the Global Ranavirus Consortium.

The same Gray states in the press release published on the University of Tennessee website:
"In our previous work, we discovered that RCV-Z2 is a recombinant ranavirus that has the DNA of a strain in North America and one from Europe and Asia. We think these viruses mixed DNA on a frog farm in South Georgia: the result was a highly virulent hybrid virus. The point of this modeling effort was to demonstrate how this virus evolved with the DNA of the eastern hemisphere can infect and spread into a kind of amphibian. The news is not good ".

And this without counting the trade in amphibians and other wild animals that may be subject to these infections: with a trade of this type their pathogens can be moved around the world, something that could make the infection truly global.

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Measles clears some of the immune memory, preventing the body from fighting other infections

Measles is a highly contagious viral infection that usually affects young children. Although the main symptoms may at first seem relatively benign, the virus can spread to the brain or lungs, leading to dangerous life-threatening complications such as encephalitis or pneumonia. In two recent studies, virologists have shown that measles clears some of the body's immune memory, preventing it from fighting infections during or after the disease, even though the patient had already faced to these infections before.

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Once infected, the amnesic immune system no longer recognizes the pathogens it has fought in the past. This means that measles survivors can remain exposed to dangerous diseases - such as influenza and pneumonia - for years, even though they have overcome their initial illness.

" Measles essentially removes their ability to protect themselves effectively, " says Michael Mina, an epidemiologist at Harvard University and co-author of the new study published in the journal Science . The article is associated with another published in the journal Science Immunology .

Using data from a group of unvaccinated children in the Netherlands, both studies revealed what virologists suspected for a long time: the measles virus paralyzes the immune system in a deep and lasting way.

" This work specifies exactly how immunosuppression occurs, and gives us an idea of ​​the magnitude of the immunosuppression in question," says William Schaffner, Professor of Preventive Medicine and Infectious Diseases at Vanderbilt University. The results also point out that this year's record measles outbreaks in the United States will have lingering effects.

Measles is an infectious disease transmitted by a morbillivirus of the family Paramyxoviridae . It manifests itself in many symptoms and can lead to serious complications. Credits: CDC / WHO

These children are currently going through a post-measles period more exposed to other infections ." According to the World Health Organization, the number of measles cases has increased by more than 280% since 2018, which means that hundreds of thousands of people who have caught the virus this year could now also be infected. secondary.

Suppression of some of the body's immune memory

Virologists have long believed that the measles virus can cause "immune amnesia," but the underlying mechanism remains unclear. They know that once the virus has infected a person, it reduces the reserves of white blood cells that kill pathogens. The number of immune cells returns to normal levels once the infection is eliminated, but even then the affected person may remain immunocompromised for years.

" But paradoxically, it leaves a solid immunity to measles, " said Duane Wesemann, a professor of medicine at Brigham and Women's Hospital. In other words, while measles survivors struggle to defend themselves against other pathogens, their bodies can prevent a new attack from the measles virus itself.

In fact, before the introduction of the measles vaccine in the 1960s, about 50% of child deaths could have been associated with infections they contracted after surviving a measles crisis, according to a 2015 study released in the journal Science . How, then, does measles cause such damage to the immune system even after the disappearance of the infection?

To find out, the authors of the new articles took blood samples from 82 unvaccinated Dutch children. In a measles outbreak that hit the country in 2013, five of the children managed to avoid infection but most caught the virus. The authors compared blood samples taken from children before and after infection to determine the evolution of their immune system.

Massive loss of B-cells after measles infection

The authors of the Science Immunolog study examined the white blood cells of children, including a type of white blood cell called B cells. When the body detects a new pathogen, B cells produce proteins that target the germ and transmit it. to another protein for destruction. B cells continue to develop these antibodies even after the pathogen disappears, so the body remembers the disease if it should return.

Graphs showing the loss of B and T lymphocytes during infection. B-lymphocytes constitute an acquired immune memory; their loss thus means a disappearance of this immune memory. Credits: Velislava N. Petrova et al. 2019

The researchers found that children infected with the measles virus lose many B-cells trained to recognize common infections.

Forty to fifty days after infection, once the virus is eliminated, the affected children have assembled a new army of B cells to replace those lost during the disease. However, the effectiveness of these in the fight against specific infections is not yet determined - this could be a question for future studies, according to Wesemann.

Antibodies: they partially disappear during infection

Rather than take stock of B cells, the authors of the study published in Science have looked directly at the first line of the immune defense: the antibodies themselves. Trillions of antibodies can be found in every microliter of blood. Many of these antibodies are produced by bone marrow cells called "long-lived plasma cells", which also perish because of the measles virus.

Using a tool called VirScan, researchers determined which antibodies appeared in the blood of children before and after measles. The screening tool allowed researchers to go through the children's medical history and see what pathogens they had encountered in their lifetime. But the measles virus has erased much of this story.

Graph showing the loss of antibodies (in red) during measles infection, compared to control groups (gray and green). Credits: Michael J. Mina et al. 2019

After catching the virus, children lost between 11% and 72% of their total antibody diversity, indicating that measles had partially erased their immune memory. In general, the number of antibodies lost seems to depend on the severity of the measles infection. Vaccinated children, as well as unimmunized individuals who did not contract measles, retained approximately 90% of their antibody repertoire during the same period.

Re-enter pathogens to rebuild immune memory

Measles survivors can recover from immune amnesia, but only by re-familiarizing themselves with all their previous pathogens. In the Science study , some children quickly recovered new antibodies to fight against staphylococcal infections, influenza and adenoviruses, the family of viruses that cause sore throats and pneumonia.

The researchers found that all these children lived together or in the same neighborhoods, which accelerated the spread of pathogens. " What we were actually attending was the re-education of their immune system, " says Mina. Although healthy Dutch children have resisted these secondary infections, malnourished or immunosuppressed children may not be able to cope as well after measles.

Vaccine against measles: the best defense against disease

Wesemann wondered whether antibody replacement therapy, in which people received antibodies from donors, could help maintain children's immune systems after measles infection, while strengthening their defenses. Questions also remain about why some children lose more measles antibodies than others and how the evolution of white blood cell diversity affects survivors.

One thing is clear: the measles vaccine is fantastic. It endows the body with an arsenal of anti-measles antibodies, just like the virus itself. But unlike infection, inoculation does not diminish the body's ability to build antibodies against other pathogens. You get all the benefits and no inconvenience with the vaccine, "Wesemann concludes.

Source Source1

Friday, 1 November 2019

Two new anti-tumor molecules neutralize protein considered impossible to target so far

During the cancer process, tumor growth is ensured by uncontrolled cell proliferation. A specific protein plays a key role in this mechanism: the KRAS protein. However, the structure of the latter contains no cite allowing the attachment of therapeutic molecules, so much so that for a long time, it was considered impossible to target. But recently, two laboratories have succeeded in developing two new molecules that effectively target this protein. This achievement is an extremely important step in the fight against cancer.

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Oncology researchers are moving towards a goal that has been elusive for more than 30 years: reducing the number of tumors by inhibiting a protein called KRAS, one of which mutates to promote the growth of many types of cancer. A new type of drug targeting KRAS has resulted in the disappearance of tumors in mice and the reduction of tumors in patients with lung cancer.

It is unclear whether the drugs will prolong the life of patients, but the results spark a wave of excitement. And a company, Amgen, reports an unexpected bonus: its drug also appears to stimulate the immune system to attack tumors, suggesting that it could be even more potent if combined with immunotherapy treatments widely available. " It's a great demonstration that a combination of drugs could really work, " says Channing Der, a researcher at the University of North Carolina.

New molecules targeting the KRAS protein

KRAS is one of three genes in the RAS family (for rat sarcoma) that produce proteins that control an on-off switch for cell growth; mutated forms of these genes are found in about 25% of all cancers. But RAS proteins have been considered "non-targetable", in part because their smooth surfaces offer no site to target with a drug.

In 2013, however, the laboratory of molecular biologist Kevan Shokat of the University of California identified a small molecule that could target a KRAS mutant called G12C (for glycine mutated to cysteine ​​at position 12).

The mutant is present in about 13% of the most common lung tumors, 3% of colorectal cancers and 2% of other solid tumors. A company called Wellspring Biosciences later showed that when mice with human tumors carrying KRAS (G12C) were given an improved version of the Shokat molecule reduced their growth.

Computer graphics explaining the role played by KRAS protein in cell growth. When it malfunctions, cell proliferation becomes anarchic. Credits: Amgen

Amgen's drug, AMG510, targets a second groove in the same KRAS protein. This seems to make it more powerful and specific than Wellspring's compound, the company reports in the journal Nature . After administering sufficient doses of the drug to mice with several types of tumors with KRAS (G12C), most tumors have decreased or even disappeared

Inhibition of KRAS: a significant reduction in the number of tumors in humans

Amgen also describes the preliminary results of the first human trial of a KRAS inhibitor, revealing that his drug partially reduced the tumor in two of four patients with advanced lung cancer after six weeks of treatment. At meetings this year, the company also showed that tumors were declining in about half of a larger group of 13 lung cancer patients.

Early results for colon cancer are not as encouraging; only one in 12 patients responded. But " it was planned, " says Jude Canon, Director of Research at Amgen, because colon cancer is more biologically complex and may require combinations of drugs.

Another company, Mirati, also announced promising human results this week at a meeting and in an article published in the journal Cancer Discovery . Its KRAS inhibitor (G12C) reduced tumors in three of six patients with lung cancer, as well as in one of four colon cancer patients.

Eliminate tumors while stimulating the immune system

In addition to blocking the protein KRAS (G12C), Amgen's drug stimulates immune cells called T cells to attack the tumor. When AMG510 was combined with a drug called PD-1 inhibitor, which removes T-cell blockade, tumors disappeared permanently in 9 of 10 mice. PD-1 inhibitors alone can eliminate some cancers, but most patients do not respond.

KRAS-G12C protein is represented in gray; the yellow zone indicates the binding site of the AMG 510 molecule developed by the Amgen laboratory. Credits: Amgen

The results suggest that treatments may be possible if PD-1 drugs are combined with Amgen's KRAS. Amgen has already started testing this drug combination in cancer patients. Although it is not the first targeted cancer drug that stimulates the tumor microenvironment to attract T cells, " it's nice to see it in action as well, " says David Tuveson, a biologist at the Cold Spring Harbor Laboratory.

The new findings are an "encouraging" step toward "a clinically effective KRAS inhibitor," says Harold Varmus of Weill Cornell Medicine, who launched the RAS initiative, an effort to target these proteins, in 2013. Der, who is consulting for Mirati warns that since the tumors are likely to develop resistance to these KRAS inhibitors, patients will probably need drug combinations.


Excessive regulation of genetically modified rice crops would cost the lives of many children around the world

According to scientific writer Ed Regis, golden rice would cause millions of unnecessary deaths as well as many cases of blindness among poor children. Indeed, he describes in detail the tragic situation of the golden rice in his last book.

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What is golden rice? It is a genetically modified variety of rice (Oryza sativa). It was created at the ETH Zurich (Swiss Federal Institute of Technology Zurich). Golden rice has been genetically modified to include beta-carotene, a chemical that our body can use to produce vitamin A. Namely, vitamin deficiency is a major cause of preventable childhood blindness in the world. In fact, nearly 500,000 children become blind each year.

Lack of vitamin A can also increase the risk of death from childhood diseases and infections. According to the World Health Organization (WHO), this problem is widespread in more than half of the world's countries, especially in Africa and South-East Asia. Although supplements can help fill this gap, WHO notes that fortification is a more direct way to tackle the problem, but in the long run. And it is exactly for this purpose that the golden rice was developed at first.

Although yellow rice has existed since the beginning of the century, it has not yet found its way to the populations that need it most in Asia ... In the new book by Ed Regis, titled Golden Rice: The Imperiled Birth of a Superfood GMO (Golden Rice: The Dangerous Birth of a GMO Superfood ), the author claims that the authorities are mainly to blame.

It should be noted that Greenpeace has strongly expressed its opposition to the introduction of golden rice and genetically modified crops in general. The organization claimed that the promotion of golden rice was motivated by commercial interests, that it had not been proven that it actually increased vitamin A levels (although clinical trials seem to indicate otherwise) and that it was diverting attention from other attempts to end child poverty.

Although many controversies over gold rice research continue to fuel debate among scientists, the main problem, according to Regis, is the Cartagena Protocol on Biosafety. This international treaty, concluded in 2003, makes it very difficult to introduce GM crops around the world, assuming that these foods are dangerous until their safety is proven, not the other way around.

Such regulations exist because of the irrational fears of GMOs, ignorance of the science involved and over-observance of the precautionary principle ," said Regis.

Although we can all agree that health should always be a priority, Regis says that the potentially life-saving effects of golden rice (we are talking about 670,000 lives a year!), Would "  mitigate a little the approach "Prevention is better than cure ".

" In Bangladesh, China, India and elsewhere in Asia, many children survive only through a few bowls of rice a day, and almost nothing else,  " says Regis in his book. "  For them, a daily supply of golden rice could help preserve the gift of life that is sight,  " he continues.

This is a debate that has raged for many years: in 2016, more than 100 Nobel laureates signed a petition condemning the blockage of genetically modified products such as golden rice, noting that no negative results for health had been registered for humans or animals.

In 2018, a review of more than 6,000 studies concluded that GMOs lead to increased yields and important health benefits: this is convincing evidence that foods like golden rice are worthy of mention. to be grown to potentially improve diets in the poorest regions of the world.

Hope for golden rice?

It should be noted that it is currently approved only in four countries: Australia, New Zealand, the United States and Canada. But some scientists hope that it will also get the green light in Bangladesh and the Philippines by the end of the year, where it is sorely lacking.


MIT develops modular robots that can move, jump, recognize and coordinate

The rise of robotics in recent years has found many practical applications in everyday life. If individual robots perform certain tasks correctly, swarms of robots are usually more efficient. However, achieving optimal communication and coordination between all robots is a big challenge. In an attempt to remedy this situation, a team at MIT's Computer Science and Artificial Intelligence Laboratory (CSAIL) has developed a surprisingly simple concept: self-assembled robotic cubes that can overlap, jump into the air, and roll. On the ground.

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Six years after the first iteration of the project, robots can now communicate with each other using a barcode-type system on each side of the block, allowing the modules to identify themselves. The Autonomous Fleet of 16 Blocks can now perform simple tasks or behaviors, such as forming a line or wall, following arrows or a light source.

Inside each modular "M-Block" is a flywheel that rotates at 20,000 rpm using kinetic momentum when the steering wheel is braked. On each edge and each face are permanent magnets allowing two cubes to attach to each other.

Interconnected modular robot swarms: many potential applications

The team envisions powerful applications for inspection and possibly disaster response. Imagine a building in flames where a staircase has disappeared. In the future, you can simply throw M-Blocks on the ground and watch them build a temporary staircase to climb the roof or go down to the basement to rescue the victims.

"'M' means movement, magnetism, and magic, " says Daniela Rus, MIT professor and director of CSAIL. " Movement, because the cubes can move by jumping. Magnetism, because they can connect to others using magnets and, once connected, they can move and connect to form structures. Magic, because we do not see any moving parts and the cube seems to be magically driven . "

Swarms of modular robots could be used in many areas: inspection and rescue, manufacturing, public health, construction, etc. Credits: Jason Dorfman / MIT CSAIL

While the mechanism is quite complex inside, the outside is on the contrary much simpler, allowing more robust connections. Beyond inspection and rescue, researchers also imagine using blocks for tasks such as games, manufacturing and care.

" What's unique in our approach is that it's inexpensive, robust, and potentially easier to fit into millions of modules, " says Romanishin. " M-Blocks can move in a general way. Other robotic systems have much more complicated motion mechanisms, which require many steps, but our system is more scalable . "

A displacement by inertial movement
Previous modular robotic systems typically approach movements using modules with small robotic arms called external actuators. These systems require a lot of coordination, even for the simplest movements, with several commands for a jump.

In 2013, the team developed its mechanism for M-Blocks. They created cubes that move using so-called "inertia forces". This means that, instead of using moving arms, the blocks have a mass inside that they "throw" against the side of the module, causing rotation and movement of the block.

Each module can move in four cardinal directions when it is placed on one of the six faces, giving 24 different directions of movement. Without small arms and appendages protruding from blocks, it's much easier for them to stay safe from damage and avoid collisions.

Optimized coordination via barcode communication

On the communication side, other attempts have involved the use of infrared light or radio waves, which can quickly become clumsy: if many robots in a small area are all trying to send signals to each other, quickly leads to confusion. When a system uses radio signals to communicate, they can interfere with each other when there are multiple radio signals in a small volume.

Romanishin has developed algorithms designed to help robots perform simple tasks, or "behaviors," which has led to the idea of ​​a barcode-like system, where robots can detect identity other blocks to which they are connected.

In one experiment, the team ordered the modules to form a line from a random structure, and checked if they could determine the specific way they were connected to each other. Otherwise, they should choose a direction and "roll" until they finish at the end of the line.

Essentially, the blocks used the connection pattern (the way they were connected to each other) to guide the chosen move - and 90% of the M-Blocks managed to form a line.

This video from MIT introduces the recently developed modular robots:


New Lithium Ion Battery Could Charge Electric Car in Just 10 Minutes

In recent years, electric cars have become popular, to the point of today investing a certain share of the automotive market. If they are more and more common, their charging time still repels many potential users. To remedy this, a team of engineers from Penn State University has developed a new battery that can charge in just 10 minutes, thanks to a rapid heating process, increasing the rate of ion transport.

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The key to making electric cars more commercially attractive is the development of batteries that can reach 80% charge (or a range of about 300km) in 10 minutes, explains Chao-Yang Wang of Penn State University . But this requires that batteries quickly absorb 400 kilowatts, which is not possible with those currently available on the market.

When the batteries are charged quickly - the phase in which the lithium ions move from the positive electrode to the negative electrode - the lithium tends to form on the surface of the electrode deposits in the form of plates, likely to reduce the life of the battery.

Heat the battery to minimize the formation of lithium plates

Wang and his colleagues thought they could minimize this problem by first heating the battery to a temperature too high to allow the formation of lithium plates. To test this, they took a commercially available industrial battery and inserted micron nickel sheets into a stack of electrode layers.

Charged at a temperature of 20 ° C, lithium plates gradually appear on the electrodes. But the higher the charging temperature, the less the plates develop. At 60 ° C, no plaque is formed. Credits: Wang et al. 2019

This structure allows the electrode to heat in less than 30 seconds, thereby creating the conditions for ions to move rapidly in the negative electrode without causing plaque formation on its surface. They then tested cell function when charged at 40 ° C, 49 ° C or 60 ° C and compared their performance to that of a control battery charging at 20 ° C.

High temperature charge: optimized performance

They found that at 20 ° C, the battery could maintain a fast charge for only 60 cycles before lithium plating caused problems that significantly reduced performance. In contrast, heating the electrode to 60 ° C allowed the battery to recharge for 2500 cycles without forming lithium plating. This equates to 14 years of use or approximately 750,000 kilometers. The results were published in Joule magazine .

This calls into question the old idea that lithium batteries should not be charged at high temperatures because they would degrade. Instead, the results suggest that the benefits of a brief, high-temperature surge greatly outweigh the disadvantages, Wang explains.


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