The Northern Cross Enters the Frb Era (Astronomy)

For some years now, a small team has been involved in the technological reconversion of the Northern Cross, the historic low-frequency radio astronomy antenna of Medicina, near Bologna, to adapt this instrument to recently emerged research lines. Modernizations culminated in the observation of the first fast radio burst last March, an important step that opens up new scientific scenarios for the dean of Italian radio telescopes

A piece of this story begins on March 3, 2021 at the Radio Astronomy Station of Medicine of the National Institute of Astrophysics. We are in the lower Bologna area, 30 kilometers east of the Emilian capital, towards Ravenna and the Adriatic. In winter snow is not uncommon , in summer there is no shortage of mosquitoes , and legend has it that half a century ago, in this corner of the Po Valley, there was a restaurant that served fabulous tortelloni . It is here that, at 16:17:29 local time, a signal from the depths of the cosmos reaches six of the 64 metal cylinders that make up one of the two branches of Italy’s first radio telescope, the Northern Cross .

Despite the restrictions imposed by the third wave of the Covid-19 pandemic, a small group of radio astronomers is in Medicina. They work on different projects and continue to work even when the instrument, diligent and silent, picks up the very fast signal. Eight thousandths of a second. Ten, fifteen times faster than the proverbial blink of an eye. A timing that intuitively almost clashes with the not so lively dynamics of the Northern Cross which, on the other hand, is precisely what allowed the historic radio telescope to intercept this brief flash in low frequency radio waves.

«We can aim it only in declination», explains Germano Bianchi, Inaf researcher and head of the Northern Cross, “and can observe all objects that, during their apparent motion from east to west, pass on the local meridian”. Astronomers speak of a “transit” instrument. He stands there and watches the sky pass over him, like when you lie down on your stomach on a summer night, letting the earth’s rotation take its course, unrolling a continuous stream of astronomical springs on the celestial vault. Except that the Northern Cross, being a radio telescope, can scan the sky even during the day. Bianchi calls into question the blinders of a horse who, on the edge of a road, looks ahead and occasionally sees a car pass by: “the machines are the radio sources and the blinders are the field of view of the Cross”.

Technologies of yesterday (and today)

Transit radio telescopes like this, a technological avant-garde at the time of its construction, were very much in vogue until the 70s-80s of the last century because they were relatively simple to build, without expensive mechanical parts that often need maintenance. Inaugurated in 1964 , the Northern Cross is still one of the largest instruments of its kind in the world, with a collection area of ​​about 30,000 square meters – the equivalent of six football fields – which guarantees high sensitivity in observations.

Detail on the antennas of the Northern Cross in a photo taken in mid-March 2021; in the distance you can recognize the 32-meter dish. Credits: G. Bianchi

Then came the large orientable antennas, such as the 32-meter-diameter one that has flanked the Northern Cross in Medicine since 1983, or the Sardinia Radio Telescope (Srt), which with its powerful 64-meter dish has been the new for several years. flagship of Italian radio astronomy. The great transit instruments have faded into the background for many years, only to return surprisingly to the international astronomy scene only recently. The Canadian Hydrogen Intensity Mapping Experiment ( Chime ), operational since 2017 in British Columbia, the Canadian province overlooking the Pacific Ocean, is nothing more than a hyper-modern version of the Northern Cross.

One of the reasons for the great revival of these radio telescopes has a lot to do with the signal received on March 3 in Medicine, and can be summed up in three words: fast radio burst (Frb), or fast radio flashes. As the name implies, these are very short signals received in the radio band , almost exclusively from sources beyond our galaxy, discovered for the first time in 2007. To date, about a hundred sources of Frb are known, but their nature remains mysterious, with dozens and dozens of models proposed to try to explain the mechanism underlying these emissions that peep out unexpectedly in the radio firmament. A year ago, the discovery of the first Frb in the Milky Way , moreover in association with a magnetar, seems to indicate that these highly magnetized neutron stars may be hiding (at least) behind some of the flashes observed so far, but a general understanding of the phenomenon is still lacking. In the meantime, a lively research activity has developed around this enigma on all fronts, from radio band observations to the search for their high-energy counterparts, to theoretical modeling.

According to Gianni Bernardi, Inaf researcher in Bologna and coordinator of the research program of the Frb with the Northern Cross, there are many scientific cases today, “relevant above all for cosmology but in our case also for transients, where you do not necessarily have a favorite source to look at , but the event can happen anywhere ». If the direction in which you observe is not important, there is no need to move the telescope from one point of the sky to another, as is done with large orientable antennas to study specific radio sources in detail, and transit radio telescopes. In the case of Frb, which last a few milliseconds and can manifest without warning in any part of the sky, “you don’t have a great need to know where to point, you just need to stand there in the sky and wait for one to arrive.

Sometimes they come back: repeated flashes

Artistic impression of a Fast Radio Burst on its way to Earth. Credits: Jingchuan Yu, Beijing Planetarium

It takes time to frame a relatively new and decidedly inconstant phenomenon like the Frb. “In general, they are not periodicals,” underlines Maura Pilia , a researcher at INAF in Cagliari who is in charge of processing the data received from radio telescopes, in search of the elusive lightning. Yet, in the almost 14 years since the first survey, some lines among the many dots are beginning to be glimpsed. In particular, in 2016 the discovery that some Frb are repeated . “Out of a hundred who know each other now, only 20 repeat themselves, that is, they have been seen more than once.” Even when they recur, there doesn’t seem to be any regularity for these unpredictable lightning strikes in the sky of radio astronomy.

Or at least, this was the situation before January 2020, when the Chime collaboration first announces that it has found a fast radio burst that recurs regularly. It is called Frb 180916.J10158 + 56 , but experts are satisfied with the initials 180916, which identifies its first observation, in September 2018. Since then, as the authors explain in an article published in Nature last June, the Canadian radio telescope has observed the flash recur 38 timesover the course of a year and a half, on time every two weeks – 16.35 days to be exact – with an activity phase of about five days for each cycle. “It is not the periodicity that was expected, like that of pulsars for example,” comments Pilia. “The fact that it’s been days, tens of days, suggests that it’s a binary system.”

Regularity is not just a valuable indicator for trying to grasp the nature of these impenetrable springs. From a practical point of view, it means being able to optimize observations and data analysis. For the research program of the Frb with the Northern Cross, then recently started and still in an experimental form, the periodical reappearing of 180916 is a real well of information. As soon as the team learns of it, Pilia says, they immediately decide to start observing it.

In the foreground, some antennas of the north-south branch of the Northern Cross; in the distance, the antennas of the east-west branch. Credits: G. Bianchi

So for over a year, twice a month, for six days in a row, an hour every day, the Medicine observatory has turned its radio eyes towards the constellation of Cassiopeia, where the source of this Frb with a reassuring regularity, synchronizing the observations in the time interval in which it is very likely that this is active, waiting to capture a signal. “We are able to track the source during the transit within the field of view of the antenna”, explains Giovanni Naldi , an Inaf researcher who works in Medicine and who, together with his colleague Giuseppe Pupillo , takes care of the back-end of the radio telescope, including the planning of observations, data acquisition and preliminary processing using software ofpre-processing . “We have this automatic system that synthesizes an electronic beam that moves over time, effectively following the source that moves in the field of view. We are chasing this Frb for about an hour a day ».

Those who seek find …

The observing campaign started last year not only includes the Northern Cross but also Srt, which manages to capture three flashes from this source already between 22 and 24 February 2020. In addition to radio telescopes, optical band observers also participate, including including the Galileo National Telescope in La Palma and the Copernicus Telescope in Asiago, both of INAF, and satellites that scan the sky in high energy, including the Italian Agile , which is contributing to the wider monitoringnever made in X-rays for a source of Frb. “It was an important cover,” adds Pilia. “Among other things, in some situations, the Cross was the only Italian radio telescope capable of observing. We managed to make the observations, the analysis is still in progress ».

Yes, because the project of the group led by Bianchi and Bernardi was born without dedicated funds – a small allocation has arrived only recently – and is carried out, with passion and tenacity, by a small group engaged in various other activities. “The dedicated staff is very little, with FTE [ full-time equivalent , a measure that quantifies the time of the staff actually dedicated to a particular project – ed ] borrowed from other projects”, notes Bianchi. An observation program conducted so far between one project and another, but with a clear vision: redevelop an instrument to catch signals discovered for the first time more than forty years after its construction .

The first fast radio burst picked up by the Northern Cross. The top panel shows the profile of the received signal. In the second panel, the signal was corrected taking into account the dispersion in the interstellar medium; the third indicates the significance of the measure of dispersion, and the fourth shows the measure of dispersion, identified by the diagonal lines. Credits: G. Bernardi et al (2021)

Everything changes on March 12th. “For the first time I jumped on my chair”, recalls Pilia who, from Cagliari, processes the data with burst detection software and is therefore in charge of the group to say whether the Medicina antenna has actually seen a Frb or not . «Until now we had had some hopes of detection both with this source and with others, but they were at a level of significance that could be doubtful. Instead this time it was without a doubt our source, we got a nice burst ».

The unequivocal signature of the first Frb captured by the Northern Cross is the profile of the signal that stands out against the noise, much clearer than that of possible bursts recorded previously. Confirming the detection is also what astronomers call ‘dispersion measurement’, a delay caused by the interaction of the signal with the interstellar medium that pervades the Milky Way. When a signal arrives from far away, such as in the case of a Frb, it experiences a higher delay in the lower frequencies than in the higher ones. “We say that he is missing,” explains Pilia. And in this case, “we see that the peak is just around the measure of dispersion in which we expect it”.

A new life for the Northern Cross

The plan is to transform the Medicina radio telescope into an instrument dedicated to the search for these enigmatic and lightning-fast radio echoes, an ambitious goal for which numerous modernization interventions were necessary. Working at low frequencies, this radio telescope does not have a reflective surface formed by panels, as in satellite dishes, but is made up of a multitude of steel wires. “If a particularly windy day arrives in Medicina, the steel wires begin to vibrate,” recalls Bianchi. “As with a stringed instrument, the antenna starts to sound like a big harp: it makes a hiss that I find very pleasant to listen to.” A sound that could bring to the minds of cinema fans that “noise of the stars” that intrigued the protagonist of the film “The Red Desert” by Michelangelo Antonioni, played by Monica Vitti, in a scene shot right under the east-west branch of the iconic radio telescope, whose construction was then almost finished.

The antennas of the east-west branch of the Northern Cross and, below, some of the “cylinders” of the north-south branch. Credits: G. Bianchi

The branch of the Northern Cross immortalized in the Leone d’Oro film at the 1964 Venice Film Festival includes 25 structures that together form a single large cylindrical-parabolic antenna, 564 meters long. The technological upgrade in progress involves the other branch, the one oriented in a north-south direction, consisting of 64 individual antennas, also cylindrical-parabolic in shape, which follow each other for 625 meters at regular intervals, one every 10 meters . These “cylinders” collect the radio waves coming from the cosmos and reflect them, conveying the signals on the focal line, where they are then transformed into electrical impulses to be analyzed.

“Currently a cylinder has a single focal line,” explains Bianchi. “We divided it into 4 and so we expanded the field of view by 4 times.” This allows us to observe a slightly larger portion of the sky, in the hope of capturing some more bursts , but also satellites and space debris . «The first part of the upgradeof the first 8 cylinders began thanks to Stelio Montebugnoli ”, adds Naldi, recalling the previous manager of the Medicine radio astronomy station as“ the person who saw this great potential and had the foresight to give this new life back to the Northern Cross ”. Another piece of this story begins in those years, from 2006 onwards, when the radio telescope was proposed to the Ska consortium, which was then emerging , as the tool on which to test the algorithms that would then be applied for the Ska Observatory. , the largest facility in the world for radio astronomy, currently under construction between Australia and South Africa.

Above, aerial view of the Medicine Station, with the two perpendicular branches of the Northern Cross. Below, diagram of the “cylinders” that form the north-south branch. Source: N. Locatelli et al. Mnras, 2020

Since then, the transformation of the Northern Cross has proceeded by successive steps. After the first 8 cylinders it has gone to 16, this year it has reached 32, and by 2023 the update of the entire branch should be completed. The modernization of the structure also includes the installation of optical fiber for the transport of the signal, which replaced the old coaxial cables, and of new more powerful and efficient machines inside the control room. Technological innovations begin to bear fruit last year , when six cylinders of the north-south branch manage to capture radio pulses from pulsar B0329 + 54, a neutron star that rotates in less than a second. A quick signal, therefore, not too dissimilar to that of a Frb. This observation gives confidence to the small team, which in a year continues to accumulate data by chasing different sources of Frb, thanks also to the technical support of several colleagues working at the Medicine station and collaborators at the universities of Oxford and Malta.

Until that fateful March 12, when Pilia’s analysis software confirms the first detection . “I was actually in Srt, I was making other observations, in the meantime I was looking at the data from the Cross,” says the researcher. Meanwhile, in Bologna, Bernardi is attending a meeting remotely. Out of the corner of her eye she glimpses an email sent by her colleague from Cagliari, who she imagines contains a figure attached to it to be included in a document in preparation, precisely on the observation program of the Northern Cross. But he doesn’t have time to open it. Then a message on Whatsapp: “Didn’t you see the email?”

«When I opened the email I immediately called Maura and in the Skype call we added Germano, Giovanni and Giuseppe», recalls Bernardi. Magically, the sparkling wine was also ready. “I took this bottle that I had been keeping in the fridge for some time and we made a big toast.”

Left: Germano Bianchi learns from Maura Pilia about the first detection of a fast radio burst by the Northern Cross. Right: Bianchi, Pilia and Gianni Bernardi celebrate the result on Skype.

Data analysis continues. The telescope probably picked up some other bursts even before last March, but the traces are still hidden in the mass of data to be processed. A job that cannot overlap with the observational one, since the machine that acquires the data is the same one used by the team to analyze it. Frb are not uncommon: Chime, who looks at the whole sky every day – ten minutes per portion of the sky – has recorded a thousand in about two years of observations , many of which are burstsrepeated from the same sources. Of course, it is a somewhat different telescope from the Medicine one, which involves more staff and more substantial funding. Now, with the first observational feedback behind them, the researchers hope to be able to create a group dedicated to the study of Frb with the Northern Cross.

The biggest story

Sometimes, even here on Earth, certain stories set in motion well before they catapult into the lives of some of their protagonists. This is even more true in the cosmos, where light signals travel for millions, billions of years at 300,000 kilometers per second before reaching the telescopes and astronomers who, by interpreting those signals, try to decipher their origin. This is precisely the case of this story, which does not begin in March 2021 with the arrival of the signal in Medicine, nor in January 2020 with the announcement of the frequency of this Frb, nor in 2006 with the relaunch of the Northern Cross or even in 1964 with its inauguration. This story begins about 485 million years ago , when on Earth it was the dawn of the Ordovician geological period, was Paleozoic. No mammals had appeared yet, no birds or reptiles, and not even many of the plants we know today. Life on our planet was mainly aquatic, and the first vertebrate organisms were appearing in the underwater depths. At the same time, in the periphery of the spiral galaxy Sdss J015800.28 + 654253.0, an unidentified celestial body, possibly part of a binary system, emitted a rapid flash, one of many, in one of its regular cycles, punctuated every 16. , 35 rotations of a distant, insignificant rocky planet, the third orbiting a star much later to be called the Sun.

Image of the host galaxy of Frb 180916 (center) acquired with the Gemini-North telescope of 8 meters in Hawaii. The location of the fast radio flash in the spiral arm of the galaxy is marked with a green circle. Credits: Gemini Observatory / Nsf OiarLab / Aura

“This spring is very interesting, it is very close,” notes Pilia. Astronomically close, of course. Compared to other distant billions of light-years, the galaxy hosting the source of Frb 180916 is not terribly distant: “only” 485 million light-years. “It was quickly located and then it’s very active, so we can study it in great detail, at least hopefully.” The team continues to keep an eye on it with the Northern Cross, along with other sources of Frb, also in view of the possibility of observing these objects on the opposite side of the electromagnetic spectrum, in X and gamma rays. Among these sources there is also the only known in our galaxy, the one that has made so much talk of a possible correlation between fast radio bursts and magnetars over the last year.. And while the physical mechanisms behind this phenomenon remain unknown, the entry of a new telescope into such a compelling line of research can only be welcome.

“We understood that we had made a piece of history, that we had reached an important milestone “, comments Bernardi. Shortly after the group Skype call, the researcher sends the figure showing the detection to one of the collaborators of the project, Giancarlo Setti , professor emeritus of the University of Bologna, involved in the realization of the Northern Cross since the first developments . «He told me:“ Beautiful, to be framed ”. Afterwards he also told me: “In fact we knew from the beginning that it was possible”. I replied: “Let’s say that now that now that we have seen it, I am more convinced” ».

To know more:

Featured image: The Medicina station, with the two perpendicular branches of the Northern Cross in the center. On the left, the 32-meter satellite dish. Credits: G. Bianchi


Provided by INAF

Not Just For Finding Planets: Exoplanet-hunter TESS Telescope Spots Bright Gamma-ray Burst (Astronomy)

NASA has a long tradition of unexpected discoveries, and the space program’s TESS mission is no different. SMU astrophysicist and her team have discovered a particularly bright gamma-ray burst using a NASA telescope designed to find exoplanets – those occurring outside our solar system – particularly those that might be able to support life.

It’s the first time a gamma-ray burst has been found this way. 

Gamma-ray bursts are the brightest explosions in the universe, typically associated with the collapse of a massive star and the birth of a black hole. They can produce as much radioactive energy as the sun will release during its entire 10-billion-year existence.

Krista Lynne Smith, an assistant professor of physics at Southern Methodist University, and her team confirmed the blast – called GRB 191016A – happened on Oct. 16 and also determined its location and duration. A study on the discovery has been published in The Astrophysical Journal.  

“Our findings prove this TESS telescope is useful not just for finding new planets, but also for high-energy astrophysics,” said Smith, who specializes in using satellites like TESS (Transiting Exoplanet Survey Satellite) to study supermassive black holes and gas that surrounds them. Such studies shed light on the behavior of matter in the deeply warped spacetime around black holes and the processes by which black holes emit powerful jets into their host galaxies.

Smith calculated that GRB 191016A had a peak magnitude of 15.1, which means it was 10,000 times fainter than the faintest stars we can see with the naked eyes. 

That may sound quite dim, but the faintness has to do with how far away the burst occurred. It is estimated that light from GRB 191016A’s galaxy had been travelling 11.7 billion years before becoming visible in the TESS telescope.

Most gamma ray bursts are dimmer – closer to 160,000 times fainter than the faintest stars. 

The burst reached its peak brightness sometime between 1,000 and 2,600 seconds, then faded gradually until it fell below the ability of TESS to detect it some 7000 seconds after it first went off.

How SMU and a team of exoplanet specialists confirmed the burst

This gamma-ray burst was first detected by a NASA’s satellite called Swift-BAT, which was built to find these bursts. But because GRB 191016A occurred too close to the moon, the Swift-BAT couldn’t do the necessary follow-up it normally would have to learn more about it until hours later.

NASA’s TESS happened to be looking at that same part of the sky.That was sheer luck, as TESS turns its attention to a new strip of the sky every month. 

While exoplanet researchers at a ground-base for TESS could tell right away that a gamma-ray burst had happened, it would be months before they got any data from the TESS satellite on it. But since their focus was on new planets, these researchers asked if any other scientists at a TESS conference in Sydney, Australia was interested in doing more digging on the blast.

Smith was one of the few high-energy astrophysics specialists there at that time and quickly volunteered.

“The TESS satellite has a lot of potential for high-energy applications, and this was too good an example to pass up,” she said. High-energy astrophysics studies the behavior of matter and energy in extreme environments, including the regions around black holes, powerful relativistic jets, and explosions like gamma ray bursts.

TESS is an optical telescope that collects light curves on everything in its field of view, every half hour. Light curves are a graph of light intensity of a celestial object or region as a function of time. Smith analyzed three of these light curves to be able to determine how bright the burst was.

She also used data from ground-based observatories and the Swift gamma ray satellite to determine the burst’s distance and other qualities about it. 

“Because the burst reached its peak brightness later and had a peak brightness that was higher than most bursts, it allowed the TESS telescope to make multiple observations before the burst faded below the telescope’s detection limit,” Smith said. “We’ve provided the only space-based optical follow-up on this exceptional burst.”


Reference: Krista Lynne Smith, Ryan Ridden-Harper et al., “GRB 191016A: A Long Gamma-Ray Burst Detected by TESS”, The Astrophysical Journal, 911(1), 2021. Link to paper


Provided by SMU

Discovered: The Mechanism That Generates Huge White Dwarf Magnetic Fields (Planetary Science)

  • University of Warwick astronomer co-authors new study in Nature Astronomy that proposes solution to long-running question of how white dwarf stars generate magnetic fields
  • A dynamo mechanism, similar to how Earth generates its magnetic field, could be the answer
  • This research shows that sometimes very similar mechanisms can work in very different astronomical objects.

A dynamo mechanism could explain the incredibly strong magnetic fields in white dwarf stars according to an international team of scientists, including a University of Warwick astronomer.

One of the most striking phenomena in astrophysics is the presence of magnetic fields. Like the Earth, stars and stellar remnants such as white dwarfs have one. It is known that the magnetic fields of white dwarfs can be a million times stronger than that of the Earth. However, their origin has been a mystery since the discovery of the first magnetic white dwarf in the 1970s. Several theories have been proposed, but none of them has been able to explain the different occurrence rates of magnetic white dwarfs, both as individual stars and in different binary star environments.

This uncertainty may be resolved thanks to research by an international team of astrophysicists, including Professor Boris Gänsicke from the University of Warwick and led by Professor Dr. Matthias Schreiber from Núcleo Milenio de Formación Planetaria at Universidad Santa María in Chile. The team showed that a dynamo mechanism similar to the one that generates magnetic fields on Earth and other planets can work in white dwarfs, and produce much stronger fields. This research, part-funded by the Science and Technology Facilities Council (STFC) and the Leverhulme Trust, has been published in the prestigious scientific journal Nature Astronomy.

Professor Boris Gänsicke of the Department of Physics at the University of Warwick said: “We have known for a long time that there was something missing in our understanding of magnetic fields in white dwarfs, as the statistics derived from the observations simply did not make sense. The idea that, at least in some of these stars, the field is generated by a dynamo can solve this paradox. Some of you may remember dynamos on bicycles: turning a magnet produces electric current. Here, it works the other way around, the motion of material leads to electric currents, which in turn generate the magnetic field.”

According to the proposed dynamo mechanism, the magnetic field is generated by electric currents caused by convective motion in the core of the white dwarf. These convective currents are caused by heat escaping from the solidifying core.

“The main ingredient of the dynamo is a solid core surrounded by a convective mantle – in the case of the Earth, it is a solid iron core surrounded by convective liquid iron. A similar situation occurs in white dwarfs when they have cooled sufficiently,” explains Matthias Schreiber.

The astrophysicist explains that at the beginning, after the star has ejected its envelope, the white dwarf is very hot and composed of liquid carbon and oxygen. However, when it has sufficiently cooled, it begins to crystallize in the center and the configuration becomes similar to that of the Earth: a solid core surrounded by a convective liquid. “As the velocities in the liquid can become much higher in white dwarfs than on Earth, the generated fields are potentially much stronger. This dynamo mechanism can explain the occurrence rates of strongly magnetic white dwarfs in many different contexts, and especially those of white dwarfs in binary stars” he says.

Thus, this research could solve a decades-old problem. “The beauty of our idea is that the mechanism of magnetic field generation is the same as in planets. This research explains how magnetic fields are generated in white dwarfs and why these magnetic fields are much stronger than those on Earth. I think it is a good example of how an interdisciplinary team can solve problems that specialists in only one area would have had difficulty with,” Schreiber adds.

The next steps in this research, says the astrophysicist, are to perform a more detailed model of the dynamo mechanism and to test observationally the additional predictions of this model.

Featured image: Illustration of the origin of magnetic fields in white dwarfs in close binaries (to be read counter clockwise). Credit: Paula Zorzi

Engineering T Cells to Attack Cancer Broadly (Medicine)

Through T cell engineering, researchers at Virginia Commonwealth University Massey Cancer Center show that it’s possible to arrest tumor growth for a variety of cancers and squash the spread of cancer to other tissues. This research will be published in tomorrow’s print edition of Cancer Research.

The paper builds on decades of research by study co-senior author Paul B. Fisher, M.Ph., Ph.D., a member of Massey’s Cancer Biology research program, who discovered a protein called IL-24 that attacks a variety of cancers in several different ways.

In this latest study, Fisher teamed up with his colleague Xiang-Yang (Shawn) Wang, Ph.D., who co-leads the Developmental Therapeutics research program at Massey, to deliver the gene coding for IL-24, which is called MDA-7, to solid tumors using T cells.

Paul B. Fisher, M.Ph., Ph.D.
Paul B. Fisher, M.Ph., Ph.D. © Massey Cancer Center

“I think the beauty of what we’ve been involved in is that it expands the scope of immunotherapy,” said Fisher, professor and chair of the Department of Human and Molecular Genetics at the VCU School of Medicine, director of the VCU Institute of Molecular Medicine (VIMM) and Thelma Newmeyer Corman Endowed Chair in Oncology Research. “Our approach is less dependent on cancer cells expressing something specific to target.”

After all, this isn’t the first time T cells have been engineered for cancer immunotherapy. FDA-approved chimeric antigen receptor T (CAR-T) cell therapy – which is designed to destroy cancer cells expressing specific surface molecules – has shown tremendous success for treating advanced cancers of the blood and lymphatic systems.

But CAR-T has made limited progress on solid tumors, such as prostate cancer or melanoma, because the cells that make up those tumors aren’t all the same, which blocks the engineered T cells from recognizing and attacking.

Wang and Fisher armed T cells with MDA-7/IL-24 to target cancer more broadly.

Xiang-Yang (Shawn) Wang, Ph.D.
Xiang-Yang (Shawn) Wang, Ph.D. © Massey Cancer Center

“Engineering T cells to produce MDA-7/IL-24 allows killing of cancer cells regardless of their expression of target molecules. This will help prevent cancer cells from escaping immune attack,” said Wang, who is also a professor of human and molecular genetics at VCU, associate director of immunology in the VIMM and holds the Harry and Judy Wason Distinguished Professorship at Massey.

At the sub-cellular level, MDA-7/IL-24 binds to receptors on the surface of cells and instructs them to make and release more copies of the MDA-7/IL-24 protein. If the cell is normal, the protein is simply secreted and no damage occurs. But if the cell is cancerous, MDA-7/IL-24 causes oxidative stress damage and ultimately cell death, not only within the primary tumor but also among its distant metastases – the cause of death in 90% of patients.

As a result of this process, the immune system generates memory T cells that can theoretically kill the tumor if it ever comes back. At the whole tumor level, IL-24 also blocks blood vessel formation, starving tumors of the nutrients so badly needed to sustain their unchecked growth.

In mice with prostate cancer, melanoma or other cancer metastases, MDA-7/IL-24-expressing T cells slowed or stopped cancer progression better than unmodified T cells.

The researchers also discovered that arming T cells with MDA-7/IL-24 allowed them to survive better and multiply in the tumor microenvironment – the space right around the cancerous mass.

“tcell
Control mice (left panel) with prostate cancer show large areas of metastasis in their lungs (blue). When a subset of animals were treated with unmodified T cells (middle panel), these secondary tumors were smaller than in untreated mice. And when a separate group of mice received T cells engineered to produce MDA-7/IL-24 (right panel), the lung metastases shrunk even more, in some cases down to nothing. © Massey Cancer Center

“The tumor site is often very hostile to immune cells,” Wang said. “We discovered that MDA-7/IL-24 can help T cells to proliferate and outnumber cancer cells.”

In the clinic, this approach would involve extracting the patient’s own T cells from tumor samples, genetically engineering them to express MDA-7/IL-24, growing millions of copies of the cells in the lab and finally transplanting them back into the patient. With federally-mandated manufacturing standards, the procedure is generally safe and minimally invasive. CAR-T cells could also be engineered to express MDA-7/IL-24.

To be most effective, MDA-7/IL-24 T cells would likely be used in conjunction with other therapies.

Although it’s never easy bringing a technology from the bench to the bedside, Fisher is optimistic that much of the groundwork has already been laid.

Clinical trials using different methods of delivering IL-24 are already underway for several cancers. A phase 1 trial using an adenovirus – similar to the common cold – to deliver MDA-7/IL24 to the tumor demonstrated about 44% efficacy against multiple forms of cancer and generally proved non-toxic.

“I think we have a head start and a running ramp that could be really accelerated,” Fisher said.

Together, Wang and Fisher recently secured a grant from the National Cancer Institute to optimize their technology for the treatment of solid tumors and cancer metastases, in anticipation of future human trials.

Funding for this project was provided by the Department of Defense Prostate Cancer Research Program (grants W81XWH-11–1-0481 and W81XWH-13–1-0162), the National Foundation for Cancer Research, the National Cancer Institute (grants R01CA229812, R01CA099326 and R01CA259599), VCU Massey Cancer Center Research Development Funds and an NCI Cancer Center Support Grant to VCU Massey Cancer Center (grant P30CA16059).

Additional authors on the study include Zheng Liu, Ph.D., Xiaofei Yu, Ph.D., Anjan Pradhan, Ph.D., Xia Li, Ph.D., Yanxia Ning, M.D., Shixian Chen, M.D., and Wenjie Liu, Ph.D., of the VCU School of Medicine; and Chunqing Guo, Ph.D., Swadesh Das, Ph.D., Jolene Windle, Ph.D., Harry Bear, M.D., Ph.D., and Masoud Manjili, Ph.D., D.V.M., of the VCU School of Medicine and VCU Massey Cancer Center.


Reference: Zheng Liu, Chunqing Guo, Swadesh K. Das, Xiaofei Yu, Anjan K. Pradhan, Xia Li, Yanxia Ning, Shixian Chen, Wenjie Liu, Jolene J. Windle, Harry D. Bear, Masoud H. Manjili, Paul B. Fisher and Xiang-Yang Wang, “Engineering T cells to express tumoricidal MDA-7/IL-24 enhances cancer immunotherapy”, Cancer Research, 2021. DOI: 10.1158/0008-5472.CAN-20-2604


Provided by Massey Cancer Center

‘Pokemonas’: Bacteria Related to Lung Parasites Discovered, Named After Pokémon (Biology)

A research team at the University of Cologne has discovered previously undescribed bacteria in amoebae that are related to Legionella and may even cause disease. The researchers from Professor Dr Michael Bonkowski’s working group at the Institute of Zoology have named one of the newly discovered bacteria ‘Pokemonas’ because they live in spherical amoebae, comparable to Pokémon in the video game, which are caught in balls. The results of their research have been published in the journal Frontiers in Cellular and Infection Microbiology.

Bacteria of the order Legionellales have long been of scientific interest because some of these bacteria are known to cause lung disease in humans and animals – such as ‘Legionnaires’ disease’, which is caused by the species Legionella pneumophila and can sometimes be fatal. Legionellales bacteria live and multiply as intracellular parasites in the cells of organisms as hosts. In particular, the hosts of Legionellales are amoebae. The term ‘amoeba’ is used to describe a variety of microorganisms that are not closely related, but share a variable shape and crawling locomotion by means of pseudopods. ‘We wanted to screen amoebae for Legionellales and chose a group of amoebae for our research that had no close relationship to the hosts that were previously studied. The choice fell on the amoeba group Thecofilosea, which is often overlooked by researchers,’ explains Marcel Dominik Solbach.

Light microscope image and illustration of a Thecofilosea amoeba with intracellular Legionellales bacteria (‘Ca. Pokemonas kadabra’). The bacteria were stained red by so-called ‘fluorescence in situ hybridization’. © Marcel Dominik Solbach

And indeed, the spherical Thecofilosea serve as host organisms for Legionellales. In Thecofilosea amoebae from environmental samples, the scientists were able to detect various Legionellales species, including two previously undescribed genera and one undescribed species from the genus Legionella. ‘The results show that the range of known host organisms of these bacteria is considerably wider than previously thought. In addition, these findings suggest that many more amoebae may serve as hosts for Legionellales – and thus potentially as vectors of disease. To investigate this further, we are now sequencing the complete genome of these bacteria,’ said Dr Kenneth Dumack, who led the project.

In the future, these new findings should help to better understand how Legionellales bacteria are related amongst each other, and clarify their interactions with their hosts as well as the routes of infection in order to prevent outbreaks of the diseases in humans.

The researchers named one of the genera of bacteria they discovered ‘Pokemonas.’ The genus name ‘Pokemonas’ is a play on words based on the video game franchise ‘Pokémon,’ which celebrates its 25th anniversary this year and which most schoolchildren, students, and their parents should be familiar with. The name alludes to the intracellular lifestyle of the bacteria in the ball-shaped Thecofilosea amoebae, because in the ‘Pokémon’ series games, little monsters are caught in balls, much like ‘Pokemonas’ in the Thecofilosea.

Featured image: Light microscope image and illustration of a Thecofilosea amoeba with intracellular Legionellales bacteria (‘Ca. Pokemonas kadabra’). The bacteria were stained red by so-called ‘fluorescence in situ hybridization’. © Marcel Dominik Solbach


Reference: Marcel Dominik Solbach, Michael Bonkowski and Kenneth Dumack, “Novel Endosymbionts in Rhizarian Amoebae Imply Universal Infection of Unrelated Free-Living Amoebae by Legionellales”, Front. Cell. Infect. Microbiol., 08 March 2021 | https://doi.org/10.3389/fcimb.2021.642216


Provided by University of Cologne

Latest Observations by MUSER Help Clarify Solar Eruptions (Planetary Science)

Prof. YAN Yihua and his research team from the National Astronomical Observatories of the Chinese Academy of Sciences (NAOC) recently released detailed results of observations by the new generation solar radio telescope—Mingantu Spectral Radio Heliograph (MUSER)—from 2014 to 2019. 

The study was published in Frontiers in Astronomy and Space Sciences on March 29. It may help us better understand the basic nature of solar eruptions. 

Solar radio bursts are associated with different types of powerful eruptions like solar flares, coronal mass ejections, and various thermal and nonthermal processes. They are prompt indicators of disastrous space weather events. 

Solar radio observations, especially at centimeter and decimeter wavelengths, play an important role in revealing the key physics behind primary energy release, particle acceleration and transportation. They also help identify crucial precursors of solar storms.

Superfine spectral structure of a very small flare observed by MUSER. (Image by NAOC) 

As the most powerful solar radio telescope in the world today, MUSER consists of 100 antennas spread over three spiral-shaped arms with a maximum baseline length of 3 km on the grassland in Inner Mongolia. 

Its configuration is optimized to meet the needs of observing the full solar disk over an ultrawide frequency range of 0.4–15 gigahertz. Its images offer a temporal resolution of 25–200 milliseconds, spatial resolution of 1.3–51.6 arcseconds, spectral resolution of 25 megahertz and a high dynamic range of 25 decibels. 

MUSER provides a unique, powerful tool for measuring solar magnetic fields and tracing the dynamic evolution of energetic electrons in a wide frequency range, which will help scientists better understand the origin of various solar activities and the basic drivers of space weather. 

From MUSER, scientists can capture the most sensitive radio signals of even very small solar eruptive events. The observations also yield images of solar magnetic fields from the solar chromosphere up to the higher corona. 

“MUSER, with its extension to metric and decametric wavelengths, will further play the role of new generation radio heliograph. It will become the leading solar-dedicated radio facility in the world for solar physics and space weather studies,” said Prof. YAN, chief scientist of Solar Physics at NAOC and the first author of the study. 

Featured image: MUSER on the grassland in Inner Mongolia, China. (Image by NAOC)


Reference: Yihua Yan, Zhijun Chen et al., “Mingantu Spectral Radioheliograph for Solar and Space Weather Studies”, Front. Astron. Space Sci., 29 March 2021 | https://doi.org/10.3389/fspas.2021.584043


Provided by Chinese Academy of Sciences

IAC is Participating In The DALI Experiment, Searching For The Axion, Proposed Component of Dark Matter (Planetary Science)

The detection of the axion would mark a key episode in the history of science. This hypothetical particle could resolve two fundamental problems of Modern Physics at the same time: the problema of Charge and Parity in the strong interaction, and the mystery of dark matter. However, in spite of the high scientific interest in finding it, the search at high radio frequency -above 6 GHz- has been almost left aside for the lack of the high sensitivity technology which could be built at reasonable cost. Until now.

The Instituto de Astrofísica de Canarias (IAC) will participate in an international collaboration to develop the DALI (Dark-photons & Axion-Like particles Interferometer) experiment, an astro-particle telescope for dark matter whose scientific objective is the search for axions and paraphotons in the 6 to 60 GHz band. The prototype, proof of concept, is currently in the design and fabrication phase at the IAC. The white-paper describing the experiment has been accepted for publication in the Journal of Cosmology and Astroparticle Physics (JCAP).

Predicted by theory in the 1970’s, the axion is a hypothetical low mass particle which interacts weakly with standard particles such as nucleons and electrons, as well as with photons. These proposed interactions are studied to try to detect the axion with different types of instruments. One promising technique is to study the interaction of axions with standard photons.

“Axions ‘mix’ with photons under the action of a strong external magnetic field, such as those produced by the superconducting magnets in particle detectors or those used for medical diagnostics by magnetic resonance, and produce a weak radio or microwave signal. This signal has been looked for in a variety of experiments since the end of the 80’s, and it is just the signal that we want to detect now with DALI, although in a new almost unexplored range of parameters, which will be accessible for the first time thanks to this experiment”, explains Javier De Miguel, an IAC researcher and the first author of the study.

The first axion detectors, made in the 80’s and 90’s, used a resonant cavity which, inside a super-magnet, amplified the weak microwave signal predicted from the axion, trying to bring it into a power range detectable by scientific instruments. Unfortunately, the size of the cavity is inversely proportional to the scanning frequency and, for the axion, the cavies were too small to be made for frequencies greater than some 6 GHz.

For this reason, the new experiment brings together the most promising techniques for scanning at high frequencies, and includes it in a practical design to which is also added the capacity of astro-particle detectors for axionic dark matter. In this way, DALI comprises a powerful superconducting magnet, an axion detector with a novel resonator to make the weak signal caused by the axions detectable, and an altazimuth mount to allow it to scan objects and regions in the sky looking for dark matter.

This way, DALI could help in the detection of the axion, a pseudo-scalar particle whose nature is similar to that of the Higgs boson, discovered in 2012 at CERN, and a promising candidate for dark matter. Dark matter is a fundamental constituent of the Universe which interacts very weakly with ordinary matter, and so is very difficult to detect directly, but whose discovery would allow us to explain the rotation curves of the spiral galaxies, and why the formation of structure in the Universe has developed in the way it has until now, among other mysteries.

Featured image: Evolution of large-scale structure as calculated by supercomputers. Boxes show how filaments and superclusters of galaxies grow over time, from billions of years after the Big Bang to current structures. Credit: Modification of work by CXC/MPE/V.Springel


Article: Javier De Miguel. “A dark matter telescope probing the 6 to 60 GHz band”. Journal of Cosmology and Astroparticle Physics, May 10th, 2020. DOI: https://doi.org/10.1088/1475-7516/2021/04/075 – Arxiv: https://arxiv.org/pdf/2003.06874.pdf


Provided by IAC

A Milestone in Muscular Dystrophy Therapy (Medicine)

A new gene-editing technique can be used to correct mutations in muscle stem cells, paving the way for the first potential cell therapy for genetic muscle disorders. The ECRC team led by Professor Simone Spuler have published their findings in the journal “JCI Insight”.

Muscle stem cells enable our muscle to build up and regenerate over a lifetime through exercise. But if certain muscle genes are mutated, the opposite occurs. In patients suffering from muscular dystrophy, the skeletal muscle already starts to weaken in childhood. Suddenly, these children are no longer able to run, play the piano or climb the stairs, and often they are dependent on a wheelchair by the age of 15. Currently, no therapy for this condition exists.

“Now, we are able to access these patients’ gene mutations using CRISPR-Cas9 technology,” explains Professor Simone Spuler, head of the Myology Lab at the Experimental and Clinical Research Center (ECRC ), a joint institution of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité – Universitätsmedizin Berlin. “We care for more than 2,000 patients at the Charité outpatient clinic for muscle disorders, and quickly recognized the potential of the new technology.” The researchers immediately started working with some of the affected families, and have now presented their results in the journal JCI Insight. In the families studied, the parents were healthy and had no idea they possessed a mutated gene. The children all inherited a copy of the disease mutation from both parents.

Edited human muscle stem cells developed into muscle fibers in mice

The term “muscular dystrophy” is used to refer to some 50 different diseases. “They all take the same course, but differ due to the mutation of different genes,” explains Spuler. “And even within the genes, different sites can be mutated.” Following a genomic analysis of all patients, the researchers chose one family because of their particular form of the disease: Limb-girdle muscular dystrophy 2D/R3 is relatively common, progresses rapidly, and has a suitable docking site for the “genetic scissors” close to the mutation on the DNA.

“With this, we were able to show for the first time that it is possible to replace diseased muscle cells with healthy ones.”

— Simone Spuler, Head of the “Myology” research lab

For the study, the researchers took a sample of muscle tissue from a ten-year-old patient, isolated the stem cells, multiplied these in vitro, and used base editing to replace a base pair at the mutated site. They then injected the edited muscle stem cells into mouse muscles, which can tolerate foreign human cells. These multiplied in the rodent and most developed into muscle fibers. “With this, we were able to show for the first time that it is possible to replace diseased muscle cells with healthy ones,” says Spuler. Following further tests, the repaired stem cells will be reintroduced to the patient.

Base editing – a sophisticated technique

Base editing is a newer and highly sophisticated variant of the CRISPR-Cas9 gene-editing tool. Whereas in the “classic” method, both strands of DNA are cut by these molecular scissors, the Cas enzymes used for base editing merely snip off the residual glucose from a particular base and attach a different one, thus creating a different base at the targeted site. “This tool works more like tweezers than scissors, and is perfect for carrying out targeted point mutations in a gene,” says Dr. Helena Escobar, a molecular biologist in Spuler’s team. “It is also a much safer method, because unwanted changes are extremely rare. In the genetically repaired muscle stem cells, we have not witnessed any misediting at unintended regions of the genome.” Escobar is the study’s lead author and the one who developed the technique for the muscle cells.

“In the genetically repaired muscle stem cells, we have not witnessed any misediting at unintended regions of the genome.”

— Helena Escobar, Lead author of the study

Autologous cell therapy – which involves removing a patient’s own stem cells, editing them outside the body and then injecting them back into the muscle – will not enable sufferers who are already wheelchair-bound to walk again. “We cannot repair muscle that has already atrophied and been replaced by connective tissue,” Spuler stresses. And the number of cells that can be edited in vitro is also limited. However, the study provides the first proof that a form of therapy may even be possible for a group of previously incurable diseases, and it could be used to repair small muscle defects, such as those in the finger flexo.

One step closer to a cure

But this is just the first step. “The next milestone will be to find a way to inject the base editor directly into the patient. Once inside the body, it would ‘swim’ around for a short while, edit all the muscle stem cells, and then quickly break down again.” The team wants to start the first trials in a mouse model soon. If this also works, newborns could be tested for corresponding gene mutations in the future and the curative therapy could be initiated at a time when comparatively few cells would need to be edited.

The confocal microscope image shows the patient’s primary muscle stem cells, which have continued to proliferate after repair of the mutation using “base editing”. © AG Spuler, ECRC

So, what might an in vivo therapy for muscular dystrophy look like in concrete terms? This is something that scientists have been testing on animal models for some time using viral vectors. However, Helena Escobar explains that because these vectors remain in the body for too long, the risk of misediting and toxic effects is too high. “An alternative would be for mRNA molecules that contain the information for the editor to synthesize the tools in vivo,” says the molecular biologist. “mRNA breaks down very quickly in the body, so the therapeutic enzymes can only remain in an active state for a short time.” The therapy could probably also be repeated, if necessary. “We do not yet know whether this would need to be a therapy cycle involving several applications.”

This therapeutic avenue would mean that, unlike with autologous cell therapy, not every patient would need to be treated individually. For each form of muscle therapy, one “tool” would be sufficient to cure muscle atrophy before major damage even occurred. But, for now, that is still a long way off.

Featured image: The confocal microscope image shows the patient’s primary muscle stem cells, which have continued to proliferate after repair of the mutation using “base editing” © Spuler Lab, MDC


Literature

Helena Escobar et al. (2021): „Base editing repairs SGCA mutation in human primary muscle stem cells”. JCI Insight, DOI: 10.1172/jci.insight.145994


Provided by MDC Berlin

Researchers Describe Rare Case of Heart Rhythm Problem in Newborn With Turner Syndrome (Medicine)

Doctors treating babies born with Turner syndrome need to look for heart rhythm abnormalities, in addition to the usual heart problems of high blood pressure or left-sided structural heart defects, according to Meena Bolourchi, MD, assistant professor of pediatrics at Boston University School of Medicine.

Turner syndrome occurs in one out of 2,500 live female births and is caused by the complete or partial absence of one X chromosome. Compared to the general population, females with Turner syndrome have a three times higher risk of early death from cardiovascular disease.

In the general newborn population, cardiac arrhythmias occur in approximately 24.4 per 100,000 live births and may occur with or without congenital heart disease. The most common arrhythmia is supraventricular tachycardia (SVT) (abnormally fast heart rate coming from the top chambers of the heart) with an incidence of one per 250 to one per 1,000 pediatric patients depending on the source. Atrial flutter occurs less often, with an incidence of 2.1 per 100,000 live births and typically does not reoccur after treatment. While one study of newborns with atrial flutter showed that 25 percent had a second atrial arrhythmia, none of them had an underlying genetic syndrome.

Now for the first time, researchers report on a newborn with Turner syndrome having atrial flutter followed by SVT. “This is the first case of a baby with Turner’s syndrome who was found to have more than one type of arrhythmia. This case illustrates that arrhythmias from the top chambers of the heart (atrial arrhythmias) can be found in babies with Turner’s syndrome,” explains corresponding author Bolourchi.

To date, there had been no known associations between Turner syndrome and the development of atrial flutter with or without SVT. Bolourchi stresses that if a baby or child has been diagnosed with Turner syndrome, it would be important to look for heart rhythm abnormalities, in addition to the usual heart problems of high blood pressure or left-sided structural heart defects.

“This case illustrates that infants and children with Turner syndrome may be at risk for cardiovascular rhythm disorders, such as atrial flutter or supraventricular tachycardia. “Early and precise investigation of such cardiac abnormalities is important to reduce morbidity and mortality of these patients,” adds Bolourchi, a pediatric cardiologist at Boston Medical Center.

These findings appear online in the European Heart Journal.


Reference: Yeyoon Choi, Jodi Hoffman, Lizzeth Alarcon, Jennifer Pfau, Meena Bolourchi, Neonatal arrhythmias in Turner syndrome: a case report and review of the literature, European Heart Journal – Case Reports, Volume 5, Issue 4, April 2021, ytab160, https://doi.org/10.1093/ehjcr/ytab160


Provided by Boston University school of medicine