Magnetic Fields On The Moon Are The Remnant Of An Ancient Core Dynamo (Planetary Science)

Simulations show that alternative explanatory models such as asteroid impacts do not generate sufficiently large magnetic fields.

Presently, the moon does not have an internal magnetic field as it can be observed on Earth. However, there are localized regions on its surface up to several hundred kilometers in size where a very strong magnetic field prevails. This has been shown by measurements on rocks from the Apollo missions. Since then, research has puzzled about the origin of these magnetic spots. One theory is that they are in some way remnants of an ancient core magnetic field. Possibly similar to what can still be observed on Earth today. Here, the core consists of molten and solid iron and its rotation generates the earth’s magnetic field. Why the inner field of the Moon has extinguished at some point remains a subject of research.

Another long discussed theory about the local magnetic spots of the moon suggests that they are the result of magnetization processes caused by impacts of massive bodies on the moon surface. A study recently published in the journal Science Advances now shows, that the Moon must have had an internal core dynamo in the past. The researchers came to their conclusion by disproving this second theory with the help of complex computer simulations. It is the result of a large international cooperation between MIT, GFZ-Potsdam, UCLA, the University of Potsdam, the University of Michigan and the Australian Curtin University.

The second thesis was supported among other things by the fact that large and strong magnetic spots were found on the other side of the moon, exactly opposite large lunar craters. Their origin was assumed to be as follows: Because the Moon – unlike the Earth – has no atmosphere to protect it from meteorites and asteroids, such massive bodies can hit it with full force and pulverize and ionize material on its surface. A cloud of charged particles, also called plasma, created in this way flows around the Moon, compresses the magnetic solar wind present in space and thus strengthens its magnetic field. At the same time, the solar wind induces a magnetic field in the moon itself. At the surface opposite the impact, all these fields are amplified and create the observed magnetism in the crustal rock.

Using the examples of some well-known Moon craters as the one we regard as its “right eye”, the researchers have now simulated the impact including the plasma formation, the propagation of the plasma around the moon and the course of the field induced in the moon’s interior. Using software that was originally developed for space physics and space weather applications, they simulated very different impact scenarios. In this way, the scientists were able to show that the amplification of the magnetic fields due to collisions and ejected material alone was not sufficient to generate the large field strengths as originally estimated and measured on the moon: The resulting magnetic field is a thousand times weaker than necessary to explain the observations. This does not mean, however, that these effects do not exist; they are only comparatively weak. In particular, the simulations showed that the field amplification by the plasma cloud on the rear side of the impact is more likely to occur above the crust, and that the magnetic field inside the moon loses much of its energy via dissipation due to turbulence in the mantle and crust.

“How exactly the magnetic spots were formed still requires more research. But now it is clear that at some point in time an internal magnetic field of the Moon had to be present for this to happen,” says Yuri Shprits, Professor at the University of Potsdam and head of the Magnetospheric Physics Section at GFZ-Potsdam. “In addition, this study can help us to better understand the nature of the dynamo-generated magnetic field and the dynamo process on Earth, the outer planets and exoplanets”.

References: “Was the moon magnetized by impact plasma?”, Rona Oran, Benjamin P. Weiss, Yuri Shprits, Katarina Milijkovi, Gábor Tóth, Science Advances 02 Oct 2020: Vol. 6, no. 40, eabb1475, DOI: 10.1126/sciadv.abb1475

Provided by GFZ GEOFORSCHUNGSZENTRUM POTSDAM, HELMHOLTZ CENTRE

Upgraded GMRT Measures The Mass Of Hydrogen In Distant Galaxies (Planetary Science)

A team of astronomers from the National Centre for Radio Astrophysics (NCRA-TIFR) in Pune, and the Raman Research Institute (RRI), in Bengaluru, has used the upgraded Giant Metrewave Radio Telescope (GMRT) to measure the atomic hydrogen content of galaxies seen as they were 8 billion years ago, when the universe was young. This is the earliest epoch in the universe for which there is a measurement of the atomic gas content of galaxies. This research has been published in the 14 October 2020 issue of the journal Nature.

An image of the stacked 21 cm signal detected with the upgraded GMRT, arising from atomic hydrogen gas in galaxies 22 billion light years away. ©Chowdhury et al.

Galaxies in the universe are made up mostly of gas and stars, with gas being converted into stars during the life of a galaxy. Understanding galaxies thus requires us to determine how the amounts of both gas and stars change with time. Astronomers have long known that galaxies formed stars at a higher rate when the universe was young than they do today. The star formation activity in galaxies peaked about 8-10 billion years ago and has been declining steadily till today. The cause of this decline is unknown, mostly because we have had no information about the amount of atomic hydrogen gas, the primary fuel for star formation, in galaxies in these early times.

“We have, for the first time, measured the atomic hydrogen gas content of star forming galaxies about 8 billion years ago, using the upgraded GMRT. Given the intense star formation in these early galaxies, their atomic gas would be consumed by star formation in just one or two billion years. And, if the galaxies could not acquire more gas, their star formation activity would decline, and finally cease”, said Aditya Chowdhury, a Ph.D. student at NCRA-TIFR and the lead author of the study. “The observed decline in star formation activity can thus be explained by the exhaustion of the atomic hydrogen.”

A GMRT Antenna at night. ©Rakesh Rao

The measurement of the atomic hydrogen mass of distant galaxies was done by using the upgraded GMRT to search for a spectral line in atomic hydrogen. Unlike stars which emit light strongly at optical wavelengths, the atomic hydrogen signal lies in the radio wavelengths, at a wavelength of 21 cm, and can only be detected with radio telescopes. Unfortunately, this 21 cm signal is very weak, and difficult to detect from distant individual galaxies even with powerful telescopes like the upgraded GMRT. To overcome this limitation, the team used a technique called “stacking” to combine the 21 cm signals of nearly 8,000 galaxies that had earlier been identified with optical telescopes. This method measures the average gas content of these galaxies.

K. S. Dwarakanath of RRI, a co-author of the study, mentioned “We had used the GMRT in 2016, before its upgrade, to carry out a similar study. However, the narrow bandwidth before the GMRT upgrade meant that we could cover only around 850 galaxies in our analysis, and hence were not sensitive enough to detect the signal.” “The big jump in our sensitivity is due to the upgrade of the GMRT in 2017”, said Jayaram Chengalur, of NCRA-TIFR, a co-author of the paper. “The new wide band receivers and electronics allowed us to use 10 times more galaxies in the stacking analysis, giving sufficient sensitivity to detect the weak average 21 cm signal.”

References: Chowdhury, A., Kanekar, N., Chengalur, J.N. et al. H I 21-centimetre emission from an ensemble of galaxies at an average redshift of one. Nature 586, 369–372 (2020). https://doi.org/10.1038/s41586-020-2794-7

Provided by Tata Institute Of Fundamental Research

Scientists Discover A New Mechanism For Cellular Defense Against Viral And Bacterial Infections (Medicine)

This study discovers an evolutionarily conserved cellular strategy that could be used in the design of more efficient and essential therapeutic approaches in the era of antibiotic resistance.

A study published in the journal Science and coordinated by researchers of IDIBAPS, the UB and teh Spanish National Center of Cardiovascular Research (CNIC) describes a new immune defence mechanism unknown until now. It is a mechanism orchestrated by lipid droplets (LDs), the cellular organelles capable of attracting and eliminating invading pathogens.

Researchers from Spain, the United States, Australia and Brazil have participated in the international project, financed by the Human Frontier Science Program, with the collaboration of scientists from the CNIC and IIBB-CSIC. Albert Pol, ICREA professor at IDIBAPS, where he leads the Lipid Trafficking and Diseases team and associate professor at the UB School of Medicine and Health Sciences, and Robert G. Parton, from the Institute of Molecular Biosciences at the University of Queensland, are the study coordinators. The first authors of the work are Marta Bosch, a researcher from the IDIBAPS group, and Miguel Sánchez-Álvarez, from the CNIC Mechanoadaptation and Caveolas Biology group.

LDs are the organelles where our cells accumulate nutrients that, in the form of fat, provide the necessary energy for them to develop their function. For example, LDs provide the energy for the heart to beat, the liver to do its metabolic function, or the muscle to move. “The lipid droplet is like the pantry of our cells, where we accumulate the food that we will use later. This happens in all eukaryotic cells, from yeasts or insects to plants or mammals,” says Albert Pol.

When viruses or bacteria infect the host cell, they need great amounts of nutrients to multiply and to get them to reach the LD. In the study published in Science the researchers have shown that, in response to infection, DLs organize complexes of antibiotic and antiviral proteins that act cooperatively to fight the pathogen and eliminate it. It is a mechanism that would work in all cells of the body, not just professional cells of the immune system such as macrophages. This defence strategy has also been observed in insects, suggesting its importance during the evolution of our innate immunity.

The key to the innate immunity of cells

Researchers have shown that to protect themselves from infection, cells place large amounts of antibiotics and antiviral proteins on LDs. In total, comparing the surface area of DL in normal cells and infected cells, the study has identified 400 candidates that would perform the protective function of LDs when they are in contact with the pathogen. “In this study, we have focused on six of these proteins and we have shown that they protect the cell during the infection of different types of bacteria” explains Marta Bosch.

“The concentration of these antibiotic and antiviral proteins in a single compartment inside the cell allows creating synergies while reducing their toxicity and allowing the rest of the cellular machinery to function normally,” says Miguel Sánchez-Álvarez.

Furthermore, the study shows that this strategy allows a broad-spectrum response, that is, there are many antibiotics and antivirals with different mechanisms of action. It also allows the generation of cooperative mechanisms to attack the infection. “There are synergies between proteins, and, for example, one breaks the membrane of the pathogen and the other destroys its genomic material,” authors explain.

“This study represents a paradigm shift since until now it was thought that LDs were at the service of viruses or bacteria during infection,” says Albert Pol. “Given the widespread resistance to current antibiotics, this study has deciphered an important defence mechanism that could be used for the development of new therapeutic strategies to stop infections,” he concludes.

Provided by CNIC

Star Clusters Are Only The Tip Of The Iceberg (Planetary Science)

“Clusters form big families of stars that can stay together for large parts of their lifetime. Today, we know of roughly a few thousand star clusters in the Milky Way, but we only recognize them because of their prominent appearance as rich and tight groups of stars. Given enough time, stars tend to leave their cradle and find themselves surrounded by countless strangers, thereby becoming indistinguishable from their neighbours and hard to identify” says Stefan Meingast, lead author of the paper published in Astronomy & Astrophysics. “Our Sun is thought to have formed in a star cluster but has left its siblings behind a long time ago” he adds.

A panoramic view of the nearby Alpha Persei star cluster and its corona. The member stars in the corona are invisible. These are only revealed thanks to the combination of precise measurements with the ESA Gaia satellite and innovative machine learning tools. © Stefan Meingast, made with Gaia Sky

Thanks to the ESA Gaia spacecraft’s precise measurements, astronomers at the University of Vienna have now discovered that what we call a star cluster is only the tip of the iceberg of a much larger and often distinctly elongated distribution of stars.

“Our measurements reveal the vast numbers of sibling stars surrounding the well-known cores of the star clusters for the first time. It appears that star clusters are enclosed in rich halos, or coronae, more than 10 times as large as the original cluster, reaching far beyond our previous guesses. The tight groups of stars we see in the night sky are just a part of a much larger entity” says Alena Rottensteiner, co-author and master student at the University of Vienna. “There is plenty of work ahead revising what we thought were basic properties of star clusters, and trying to understand the origin of the newfound coronae.”

To find the lost star siblings, the research team developed a new method that uses machine learning to trace groups of stars which were born together and move jointly across the sky. The team analyzed 10 star clusters and identified thousands of siblings far away from the center of the compact clusters, yet clearly belonging to the same family. An explanation for the origin of these coronae remains uncertain, yet the team is confident that their findings will redefine star clusters and aid our understanding of their history and evolution across cosmic time.

“The star clusters we investigated were thought to be well-known prototypes, studied for more than a century, yet it seems we have to start thinking bigger. Our discovery will have important implications for our understanding of how the Milky Way was built, cluster by cluster, but also implications for the survival rate of proto-planets far from the sterilizing radiation of massive stars in the centers of clusters”, says João Alves, Professor of Stellar Astrophysics at the University of Vienna and a co-author of the paper. “Dense star clusters with their massive but less dense coronae might not be a bad place to raise infant planets after all.”

References: S. Meingast, J. Alves, A. Rottensteiner, “Extended stellar systems in the solar neighborhood. V. Discovery of coronae in nearby star clusters”, A&A, 2020. https://doi.org/10.1051/0004-6361/202038610

Provided by University Of Vienna

Small RNA As A Central Player In Infections (Biology)

More than half of the world’s population carries the bacterium Helicobacter pylori in their stomach mucosa. It often causes no problems throughout life, but sometimes it can cause inflammation, and in some cases, it can even lead to the development of stomach cancer.

Artistic representation of human stomach cells infected with Helicobacter pylori, showing the special Hummingbird cell shape induced by the bacterium.© (Image: Chair of Molecular Infection Biology II / University of Wuerzburg / SCIGRAPHIX)

Helicobacter pylori uses several “virulence” factors that allow it to survive in the stomach and can lead to the development of disease. In this issue of the journal Molecular Cell, Professor Cynthia Sharma’s research team report that multiple of these factors are centrally regulated by a small RNA molecule called NikS. Prof. Sharma heads the Chair for Molecular Infection Biology II at Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany.

Among the target genes regulated by NikS are the two most important virulence factors of Helicobacter pylori as well as two encoding outer membrane proteins. In particular, the JMU researchers were able to show that NikS regulates the CagA protein, a bacterial oncoprotein that plays a central role in the development of cancer instigated by Helicobacter pylori. In addition, a protein with a so far unknown function that is released into the environment by H. pylori is also under the control of NikS.

The new findings are relevant for medicine and infectious disease research: “With the knowledge of the different functions and underlying molecular mechanisms of this small RNA during infection and the associated bacterial signaling pathways, we can gain new targets for the development of novel antimicrobial strategies,” explains Cynthia Sharma.

Phase variation even in small RNA molecules

The fact that Helicobacter pylori can colonize such a hostile environment as the stomach so successfully is also due to a special genetic strategy: Like other pathogens, H. pylori uses a strategy known as phase variation to adapt as flexibly as possible to changes in its environment. Phase variation means that the bacteria constantly switch expression of a gene at random through genetic mutations, meaning that some bacteria in a population will always be ready to express the important gene when it becomes important – a sort of “bet-hedging” strategy.

Sharma’s team has now been able to show for the first time that the expression of a small RNA molecule such as NikS, and not just of proteins, can also be subject to phase variation. Depending on the conditions prevailing in the stomach, different amounts of NikS might be beneficial. Levels of the small RNA can change to suit this through phase variation, thereby leading to different regulation of the disease-causing factors.

NikS helps to colonize host cells

“This mechanism could play a major role in enabling Helicobacter pylori to adapt successfully to the variable stomach environment and thus chronically colonize its host,” says Sharma. In experiments, her team was able to show that NikS influences the internalization of the bacteria into host cells. In addition, the small RNA makes it easier for H. pylori to overcome epithelial barriers and, thus, might lead to better access of nutrients in deeper tissues in the stomach.

In further studies, the JMU researchers now aim to find out how the small RNA contributes to the colonization of different niches in the stomach and whether it regulates other genes that might also be involved in the bacterium’s pathogenic properties.

References: Sara K. Eisenbart, Mona Alzheimer, Sandy R. Pernitzsch, Sascha Dietrich, Stephanie Stahl, Cynthia M. Sharma, “A Repeat-Associated Small RNA Controls the Major Virulence Factors of Helicobacter pylori”, Molecular Cell, 80(2), pp. 210-226, 2020. DOI: https://doi.org/10.1016/j.molcel.2020.09.009

Provided by University Of Wuerzberg

Monash Discoveries Suggest New Breast Cancer Treatment (Oncology / Cancer)

Findings by Monash Biomedicine Discovery Institute (BDI) researchers have pointed to a new combination of treatments that may help breast cancer patients with certain gene mutations.

3D image of mammary organoids used to test response to new combination drugs. In pink, cytokeratin 8 staining marking luminal epithelial cells; in white, cytokeratin 14 staining basal epithelial cells; cell nuclei are in blu, dapi. © Kelvin Yip – Monash Mico Imaging (MMI)

The study, published in Molecular Cell and led by Dr Antonella Papa, identified potential new treatments for patients who lacked PTEN, a gene that suppresses tumours, and/or have mutations in the cancer gene PI3K.

The researchers demonstrated using animal models, organoids and proteomic screening, that the loss of PTEN synergises with mutant PI3K gene in forming tumours in mammary glands. They then found that inhibiting the protein AKT suppressed the growth of PTEN and PI3K mutant mammary organoids.

In a surprising finding, the team also discovered that loss of PTEN function increased levels of the glucocorticoid receptor (GR) and made the tumour cells more prone to death.

The researchers found that combining a treatment called dexamethasone (an anti-inflammatory medication currently available), which activates GR, with an AKT inhibitor, better suppressed growth of PTEN/PI3K mutant cancer cells than treatment with a single compound.

The scientists are now testing the efficacy of their combination therapy in pre-clinical animal models with a view to future testing in clinical trials for breast cancer treatment.

PTEN gives instructions for making an enzyme found in most tissues in the body and functions by stopping cells from growing and dividing too rapidly or too uncontrollably. In contrast, PI3K is an enzyme that promotes cell growth and sustains proliferation in cancer when mutated.

Mutations in either PTEN or PI3K alone occur in almost 50 per cent of breast cancer patients. In addition, 10 per cent of breast cancer patients have combined genetic alterations in these two genes.

“These patients could benefit from our findings,” Dr Papa said.

“The finding that GR sensitises PTEN mutant cells to death is absolutely new; it was the opposite of what you would expect,” Dr Papa said.

Dr Papa said while the research had concentrated on breast cancer, the two genes could cause tumours to form in many of the body’s cells.

References: Hon Yan K. Yip, Annabel Chee, Ching-Seng Ang, Catriona A. McLean, Christina A. Mitchell, Antonella Papa, “Control of Glucocorticoid Receptor Levels by PTEN Establishes a Failsafe Mechanism for Tumor Suppression”, Molecular cell, 80(2), pp. 279-295. 2020. DOI: https://doi.org/10.1016/j.molcel.2020.09.027

Provided by Monash University

Neuroscientists Uncovered a New Part Of The Brain In Our Understanding (Neuroscience)

Imagine going to a café you have never been to. You will remember this new environment, but when you visit it again and again fewer new memories about the environment will be formed, only the things that changed will be really memorable. How this long-term memory are regulated is still not fully understood. Ryuichi Shigemoto from the Institute of Science and Technology Austria (IST Austria) in cooperation with researchers from Aarhus University and the National Institute for Physiological Sciences in Japan now have uncovered a new keystone in the formation of memories. In their study published in Current Biology, they investigated a signaling path in the hippocampus area of the brain and showed how it controls making new memories about experiencing new environments.

Layers of the hippocampus. The mossy cell bodies are red, interneuron cells connecting neurons are green, and other neurons are blue. © Ryuichi Shigemoto

The hippocampus is a central area in the brain that plays an important role in transferring information from the short-term memory to the long-term memory. Of the many interlocking parts of the hippocampus, the researchers focused on the connection between the so-called mossy cells that receive novelty signals of sensory input about the environment and the so-called granule cells to which this information is relayed. In diseases like Alzheimer’s this part of the brain is one of the first ones affected.

Watching Neurons

The scientists used four different approaches for this study in order to rigorously investigate these new findings. First, they put the hippocampus under the microscope and studied the structure of how the mossy cells are connected to the granule cells showing their many complex connections.

Second, they used the technique of calcium imaging that allows live monitoring of neuron activity as these genetically modified cells light up when activated. When exposing the animals a new environment for several days, the activity of the mossy cells sending signals to the granule cells first was high and then became less and less. When they then put the mice into another new environment, the activity sprung up again, therefore showing that these neurons are specifically relevant to process new environmental input.

Third, the researchers followed traces in the neuron left by the signals. Neural activity in these cells triggers the expression of a certain gene, meaning the production of the corresponding protein that is encoded in it. The more activity there was, the more of this protein they can find afterwards. In the granule cells they found production of this protein, which correlated with activity of the mossy cells.

Dreading New Places

And lastly, the scientists used behavioral studies to see the effects of this pathway in the hippocampus on memory formation. This is especially important, because the connection between memory formation and behavior can tell them a lot about the brain’s functions. They combined a negative sensory stimulus, a small electric shock, with putting the animals in a new environment. The mice then quickly learned to associate the new environment with unpleasant feelings and their negative reaction of freezing on the spot was measured.

When the researches used drugs to inhibit the activity of the mossy cells–the ones receiving the signals about the new environment–and then did the negative conditioning, the mice did not remember the connection between the new environment and the unpleasant feeling. Additionally, when the animals were first accustomed to the new environment and then conditioned, there was also no activation of the mossy cells, and therefore no association between the environment and the shocks.

On the other hand, if the mossy cells were artificially activated, this association could be formed even after the animals were already used to the new environment. This clearly shows how the mossy cells in the hippocampus react to novel input and trigger the formation of new long-term memories in mice.

Next Steps in Understanding

Whether the exact same processes happen in the human brain is still an open question, but these new findings are an important first step in understanding this part of our most complex organ. Ryuichi Shigemoto and his collaborators are conducting fundamental research that may one day help to address degenerative brain diseases that affect memory formation, but this is still a while away.

He cautiously states: “This research field is very competitive and new findings arise quickly. There are many disputed mechanisms on memory formation, but our findings corroborate an existing hypothesis and are very robust, thus opening up a new field of neuroscience research and furthering our understanding of the brain.”

Animal welfare

Understanding how the brain stores and processes information is only possible by studying the brains of animals while they carry out specific behaviors. No other methods, such as in vitro or in silico models, can serve as alternatives. The animals were raised, kept and treated according to the strict regulations of Austrian law.

References: Felipe Fredes, Maria Alejandra Silva, Peter Koppensteiner, Kenta Kobayashi, Maximilian Joesch, Ryuichi Shigemoto, “Ventro-dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation”, 2020. DOI: https://doi.org/10.1016/j.cub.2020.09.074

Provided by Institute Of Science And Technology, Austria

Pancreatic cancer: Subtypes With Different Aggressiveness Discovered (Medicine)

Tumors of the pancreas are particularly feared. They are usually discovered late and mortality is high. Until now, no targeted and personalized therapies exist. Scientists at the German Cancer Research Center (DKFZ) and the Heidelberg Institute for Stem Cell Technology and Experimental Medicine* (HI-STEM) have now succeeded for the first time in defining two differently aggressive molecular subtypes of pancreatic carcinoma. This provides new insights into the origin of the tumors. In the more aggressive group of tumors, a phenomenon known as “viral mimicry” leads to a cancer-promoting inflammatory reaction. This could possibly be the starting point for the development of a targeted, subtype-oriented therapy. The results have now been published in the journal Cancer Discovery.

©gettyimages

Pancreatic carcinoma is particularly insidious. The disease usually progresses without symptoms over a long period of time and is only diagnosed in advanced stages – when it is difficult to treat. The mortality rate for this tumor disease is therefore particularly high. In contrast to many other cancers, scientists have not yet succeeded in identifying efficient targets for a targeted personalized therapy. Most patients with an advanced tumor disease receive a similar treatment – usually consisting of a combination chemotherapy.

About 95 percent of all cases of pancreatic cancer are so-called adenocarcinomas. “In the past, there have been attempts to work out genetic differences, but it turned out that all adenocarcinomas of the pancreas carry a similar collection of mutations,” explains Andreas Trumpp, stem cell researcher at DKFZ and HI-STEM. Trumpp’s team has now chosen a different approach in collaboration with the Department of Surgery at Heidelberg University Hospital. From tissue samples from patients, they first isolated pure cancer cells from the tumors’ complex cell mixture, which contains large amounts of connective tissue, vessels and immune cells. The researchers then searched the genome of the purified tumor cells for differences in the methylation pattern. These are chemical labels attached tot he DANN molecule that determine whether a gene segment is active or not.

“Based on the methylation patterns of the tumor genomes, we were able to define two completely different subtypes of adenocarcinomas, which differ in the course of carcinogenesis and in their aggressiveness,” says Elisa Espinet, first author of the current publication. One of the two subtypes is much more aggressive and actually develops directly from the ductal cells lining the ductal system of the pancreas, while the less aggressive tumors develop from glandular cells. “We have thus discovered a molecular signature that allows us to distinguish between two subtypes of pancreatic carcinoma that are also clinically different,” explains Espinet.

What’s more, upon closer analysis of the methylation patterns, the Heidelberg researchers discovered that very specific regions in the genome carry fewer methyl groups in the more aggressive subtype. These genome regions contained sequences of so-called endogenous retroviruses, remnants of viruses that have remained in the human genome during evolution. Due to the methylation of their DNA, they are normally silenced and do not play a significant role in healthy individuals. In this subtype, however, they become active again when the methyl groups are removed and form double-stranded RNA strands.

This type of RNA molecule does not normally occur in the body and is therefore a warning signal for the immune system that viruses have entered the cell. As a result, the interferon system is activated and tries to fight the invading viruses. As a result, inflammatory messengers are also released in the vicinity of the tumor. “Feigning a viral infection in genetically modified tumor cells is called “viral mimicry”, says Espinet. In the tumor, the viral mimicry promotes certain inflammatory reactions that further drive cancer growth and, in addition, probably stimulates metastasis, i.e. the formation of the dreaded daughter tumors.

The DKFZ researchers found viral mimicry only in the ductal subtype and in traces also in healthy ductal cells, but not in the healthy glandular cells of the pancreas or the pancreatic cancer cells of the less aggressive subtype. This explained why pancreatic tumors that develop directly from the cells of the pancreatic ducts, which accounted for about one third of the tumors studied, are particularly aggressive.

At the same time, the result opens up new perspectives for a more targeted and personalized therapy of pancreatic cancer. “By blocking the interferon signaling pathways at various sites, we were able to significantly slow down cancer growth in mice to which human pancreatic cancer cells had been transferred. However, the regulation of these signals is highly complex. We are now looking for ways to not only slow down the tumor cells, but actually eliminate them,” says Trumpp, explaining the further progress of preclinical research.

Provided by DKFZ

We Now Know, How The Nervous System Mutes Or Boosts Sensory Information To Make Behavioral Deci (Biology)

Fruit flies may be able to teach researchers a thing or two about artificial intelligence.

University of Michigan biologists and their colleagues have uncovered a neural network that enables Drosophila melanogaster fruit flies to convert external stimuli of varying intensities into a “yes or no” decision about when to act.

Researchers captured 3D images of the regions of the Drosophila central nervous system that are activated in response to noxious stimulation. The posterior medial center (red), which is located between sensory- and motor-related regions of the nervous system, is important for making behavioral decisions. © Yujia Hu, U-M Life Sciences Institute.

The research, scheduled to publish Oct. 15 in the journal Current Biology, offers hints into how these decisions work in other species, and could perhaps even be applied to help AI machines learn to categorize information.

Imagine you are working near an open window. If the outside noise is low enough, you may not even notice it. As the noise level gradually increases, you start to notice it more–and eventually, your brain makes a decision about whether to get up and close the window.

But how does the nervous system translate that gradual, linear increase in intensity to a binary, “yes/no” behavioral decision?

“That’s a really big question,” said neuroscientist Bing Ye, a faculty member at the University of Michigan Life Sciences Institute and senior author of the study. “Between the sensory input and the behavior output is a bit of ‘black box.’ With this study, we wanted to open that box.”

Brain imaging in humans or other mammals can identify certain regions of the brain that respond to particular stimuli. But to determine how and when the neurons transform linear information into a nonlinear decision, the researchers needed a much deeper, more quantitative analysis of the nervous system, Ye said.

They chose to work with the model organism Drosophila, due to the availability of genetic tools that make it possible to identify individual neurons responding to stimuli.

Using an imaging technique that detects neuronal activity through calcium signaling between neurons, the scientists were able to produce 3-D neuroactivity imaging of the flies’ entire central nervous system.

“What we saw was that, when we stimulate the sensory neurons that detect harmful stimuli, quite a few brain regions light up within seconds,” said Yujia Hu, a research investigator at the LSI and one of the lead authors on the study. “But these brain regions perform different functions. Some are immediately processing sensory information, some spark the behavioral output–but some are more for this transformation process that occurs in between.”

When sensory neurons detect the harmful external stimuli, they send information to second-order neurons in the central nervous system. The researchers found that one region of the nervous system in particular, called the posterior medial core, responds to sensory information by either muting less intense signals or amplifying more intense signals, effectively sorting a gradient of sensory inputs into “respond” or “don’t respond” categories.

The signals get amplified through increased recruitment of second-order neurons to the neural network–what the researchers refer to as escalated amplification. A mild stimulus could activate two second-order neurons, for example, while a more intense stimulus may activate 10 second-order neurons in the network. The larger network can then prompt a behavioral response.

But to make a “yes/no” decision, the nervous system needs a way not just to amplify information (for a “yes” response), but to also suppress unnecessary or less harmful information (for a “no” response).

“Our sensory system detects and tells us a lot more than we realize,” said Ye, who is also a professor of cell and developmental biology in the U-M Medical School. “We need a way to quiet that information, or we would just constantly have exponential amplification.”

Using the 3-D imaging, the researchers found that the sensory neurons actually do detect the less harmful stimuli, but that information is filtered out by the posterior medial core, through the release of a chemical that represses neuron-to-neuron communication.

Together, the findings decode the biological mechanism that the fruit fly nervous system uses to convert a gradient of sensory information into a binary behavioral response. And Ye believes this mechanism could have far wider applications.

“There is a dominant idea in our field that these decisions are made by the accumulation of evidence, which takes time,” Ye said. “In the biological mechanism we found, the network is wired in a way that it does not need an evidence accumulation phase. We don’t know yet, but we wonder if this could serve as a model to help AI learn to sort information more quickly.”

Provided by University Of Michigan