Researchers from Osaka University uncover a mechanism by which chromosomal rearrangements occur, with implications for novel cancer therapies
Gross chromosomal rearrangements–where portions of the genome become moved, deleted, or inverted–can lead to cell death and diseases such as cancer in complex multicellular organisms. However, the details of how exactly these occur remain unknown. Now, studies in a single-celled organism called fission yeast have found evidence for the involvement of a protein called Rad8.
When DNA replicates or repairs itself, three copies of a protein called PCNA bind together and form a ring-like structure surrounding the DNA strand. This ring structure acts like a clamp and slides along the DNA strand. The team showed that Rad8 attaches a small molecule called ubiquitin to this PCNA protein at the amino acid in the 107th position. This amino acid is a lysine molecule, termed “lysine 107,” located at the interface between the different PCNA molecules.
Ubiquitin attachment is a common biological process serving a variety of functions. “In this case, the attachment of ubiquitin at lysine 107 weakens the interactions between PCNA molecules and changes the structure of the ring of proteins,” says lead author of the paper Jie Su. This then alters how PCNA functions and leads to the formation of gross chromosomal rearrangements instead of accurate DNA repair.
Rad8 is a ubiquitin ligase, the molecule that is responsible for attaching a ubiquitin to a particular place on another protein. “We found that Rad8 works together with another protein called Mms2-Ubc4, a ubiquitin conjugating enzyme,” says Takuro Nakagawa, senior author. “Mms2-Ubc4 brings in the ubiquitin molecule, and Rad8 then transfers the ubiquitin to lysine 107 of PCNA.” The combined action of Rad8 and Mms2-Ubc4 is therefore responsible for causing gross chromosomal rearrangements.
But how does this information on a single-celled organism like yeast relate to cancer in complex organisms such as humans? Not much is known about HLTF, the human equivalent to Rad8, but it is seen to be activated and upregulated in cancer. Inhibition of HLTF, or inhibiting the attachment of ubiquitin to PCNA at the human equivalent of the lysine 107 position, could therefore be a very promising new strategy for cancer therapies.
Geneticists from Trinity College Dublin have discovered how a specific genetic mutation called H3K27M causes a devastating, incurable childhood cancer, known as diffuse midline glioma (DMG), and – in lab studies working with model cell types – successfully reverse its effects to slow cancer cell growth with a targeted drug.
Their landmark work – just published in leading international journal, Nature Genetics and supported by Worldwide Cancer Research and The Brain Tumour Charity – translates crucial new understanding of the genetics of DMG progression into a highly promising, targeted therapeutic approach and offers significant hope of improved treatments in the future.
The scientists now call for clinical trials to begin imminently, in which an already approved class of drugs called “EZH2 inhibitors” can be assessed. These drugs target the same key biological pathway involved in DMG as they do successfully in lymphomas and sarcomas — two cancers common in adults.
Key findings and implications
The scientists behind this important work discovered:
How a specific genetic mutation called H3K27M causes DMG
How to target this cancer-causing gene with a drug that slows cancer cell growth
They have also established a specific model cell line for evaluating further targeted DMG approaches
Adrian Bracken, Professor in Trinity’s School of Genetics and Microbiology, led the exciting research. He said: “We’ve taken a huge step forward in our study of DMG tumours and hope that the insights will help us design and implement precision oncology-based treatment approaches in DMG patients in the future. Crucially, ‘EZH2 inhibitor’ drugs have already received approval from the United States Food and Drug Administration for the treatment of two types of adult cancer. We propose these drugs could be impactful for children with DMG and, as a result, call for clinical trials to begin next.
“Ultimately, we hope that our work – together with that of others focused in this area – will lead to curative clinical approaches for what is a truly terrible disease that can devastate families and for which there are currently no therapeutic options.”
Paediatric gliomas like DMG are among the most devastating of childhood cancers. Tumours typically arise in the brain and are very challenging to treat, with prognosis extremely poor. As such, effective therapeutic options are urgently needed.
Dr Jane Pears, paediatric consultant oncologist at Our Lady’s Children’s Hospital, Crumlin, who treats children with this disease said: “Despite combined best efforts, these tumours remain a devastating diagnosis for children and their families. The best treatment we can currently offer may extend survival for a few months but is not curative. We are now entering an exciting era of expansion of our knowledge of this disease at a molecular level, which in turn will lead us towards more targeted treatments. Thanks to collaborative translational efforts between scientists, such as Prof. Bracken and his team working in the laboratory, and doctors in the clinical setting, this will hopefully lead to the improved outcomes that we all so dearly wish to see.”
Speaking to the importance of the work, Maeve Lowery, Professor of Translational Cancer Medicine at Trinity, and Academic Director of the Trinity St James’s Cancer Institute (TSJCI) said: “These findings have the potential to transform the treatment landscape of DMG tumours and improve outcomes for children with this challenging disease. Importantly, this pivotal work illustrates the success of a precision oncology approach – where understanding how cancers develop on a genomic level can accelerate the development of more effective treatments with less side effects. The Precision Oncology Research Program at TSJCI, led by Prof Bracken, will build on this success to continue to develop new and innovative treatment strategies for adult and childhood cancers.”
Dr Becky Birch, Head of Research at The Brain Tumour Charity, which helped fund the study, said: “This is a really promising discovery that we hope will now pave the way for new and targeted treatments to be developed for children with diffuse midline gliomas (DMGs). With average survival still heartbreakingly short at less than 12 months, we urgently need to find new options to help slow the growth of this rare and often-inoperable cancer and give children diagnosed more time to live. It’s really exciting that we now better understand how a specific genetic mutation may be driving the disease, and even more so that drugs that may inhibit this process have already been tested in other cancers. If further research can now design EZH2 inhibitors to more effectively target DMG cells, we hope these drugs can be quickly advanced into clinical trials for children diagnosed with this devastating disease.”
Developing cancer treatments – why this research is different
Ordinarily, developing effective cancer treatments can take decades; indeed, it can take years before scientists are able to develop model systems in relevant cell types that afford them the chance to “look under the genetic bonnet”.
Such investigations can first help us understand how cancers function. That information then provides the all-important clues as to how we can fight them. Further lab-based studies can hone these approaches, ultimately opening the doors to clinical trials and, if we’re lucky, improved treatments.
The scientists behind this study have therefore taken great strides in the battle against DMG, having discovered key aspects of this disease at a genetic level; proposed an available strategy to target it; and created a model of the disease that can be used in continued work to advance further improved treatment strategies.
Reference: Brien, G.L., Bressan, R.B., Monger, C. et al. Simultaneous disruption of PRC2 and enhancer function underlies histone H3.3-K27M oncogenic activity in human hindbrain neural stem cells. Nat Genet (2021). https://doi.org/10.1038/s41588-021-00897-w
An NIH-funded research project found that calcium modulator CaMKII protects the optic nerve in mice, opening the door to new sight-saving therapy
A form of gene therapy protects optic nerve cells and preserves vision in mouse models of glaucoma, according to research supported by NIH’s National Eye Institute. The findings suggest a way forward for developing neuroprotective therapies for glaucoma, a leading cause of visual impairment and blindness. The report was published in Cell.
Glaucoma results from irreversible neurodegeneration of the optic nerve, the bundle of axons from retinal ganglion cells that transmits signals from the eye to the brain to produce vision. Available therapies slow vision loss by lowering elevated eye pressure, however some glaucoma progresses to blindness despite normal eye pressure. Neuroprotective therapies would be a leap forward, meeting the needs of patients who lack treatment options.
“Our study is the first to show that activating the CaMKII pathway helps protect retinal ganglion cells from a variety of injuries and in multiple glaucoma models,” said the study’s lead investigator, Bo Chen, Ph.D., associate professor of ophthalmology and neuroscience at the Icahn School of Medicine at Mount Sinai in New York City.
The CaMKII (calcium/calmodulin-dependent protein kinase II) pathway regulates key cellular processes and functions throughout the body, including retinal ganglion cells in the eye. Yet the precise role of CaMKII in retinal ganglion cell health is not well understood. Inhibition of CaMKII activity, for example, has been shown to be either protective or detrimental to retinal ganglion cells, depending on the conditions.
Using an antibody marker of CaMKII activity, Chen’s team discovered that CaMKII pathway signaling was compromised whenever retinal ganglion cells were exposed to toxins or trauma from a crush injury to the optic nerve, suggesting a correlation between CaMKII activity and retinal ganglion cell survival.
Searching for ways to intervene, they found that activating the CaMKII pathway with gene therapy proved protective to the retinal ganglion cells. Administering the gene therapy to mice just prior to the toxic insult (which initiates rapid damage to the cells), and just after optic nerve crush (which causes slower damage), increased CaMKII activity and robustly protected retinal ganglion cells.
Among gene therapy-treated mice, 77% of retinal ganglion cells survived 12 months after the toxic insult compared with 8% in control mice. Six months following optic nerve crush, 77% of retinal ganglion cells had survived versus 7% in controls.
Similarly, boosting CaMKII activity via gene therapy proved protective of retinal ganglion cells in glaucoma models based on elevated eye pressure or genetic deficiencies.
Increasing retinal ganglion cell survival rates translated into greater likelihood of preserved visual function, according to cell activity measured by electroretinogram and patterns of activity in the visual cortex.
Three vision-based behavioral tests also confirmed sustained visual function among the treated mice. In a visual water task, the mice were trained to swim toward a submerged platform on the basis of visual stimuli on a computer monitor. Depth perception was confirmed by a visual cliff test based on the mouse’s innate tendency to step to the shallow side of a cliff. Lastly, a looming test determined that treated mice were more apt to respond defensively (by hiding, freezing or tail rattling) when shown an overhead stimulus designed to simulate a threat, compared with untreated mice.
“If we make retinal ganglion cells more resistant and tolerant to the insults that cause cell death in glaucoma, they might be able to survive longer and maintain their function,” Chen concluded.
This study was supported by NEI grants R01EY028921, R01EY024986. NEI is part of the National Institutes of Health.
Featured image: Graphical abstract by authors
Guo X, Zhou J, Starr C, Mohns EJ, Li Y, Chen E, Yoon Y, Kellner CP, Tanaka K, Wang H, Liu W, LR, Demb JB, Crair MC, and Chen B. “Preservation of vision after CaMKII-mediated protection of retinal ganglion cells.” Published online July 22, 2021 in Cell. DOI: https://doi.org/10.1016/j.cell.2021.06.031
HEIDELBERG CHEMISTS SUCCEED IN PRODUCING SYNTHESIS AND COMPLETE CHARACTERISATION FOR THE FIRST TIME
Silicon, a semi-metal, bonds in its natural form with four other elements and its three-dimensional structure takes the form of a tetrahedron. For a long time, it seemed impossible to achieve the synthesis and characterisation of a two-dimensional equivalent – geometrically speaking, a square. Now scientists from the field of Inorganic Chemistry at Heidelberg University have succeeded in producing a crystalline complex with such a configuration. PD Dr Lutz Greb from the Institute of Inorganic Chemistry underlines that it has surprising physical and chemical properties and, in the field of molecular chemistry, will open up new approaches to using the second most abundant element in the Earth’s crust for catalysis and materials research.
As a classical semi-metal, silicon possesses properties of both metals and non-metals, and belongs to the carbon group on the periodic table. Like carbon, silicon bonds with four elements. Its three-dimensional structure then corresponds to a tetrahedron, a body with four sides. Due to the high stability of a tetrahedron, other structures are not known in natural silicon with four bonds – silicon(IV) for short. Considered purely geometrically, the two-dimensional equivalent to a tetrahedron is a square. These configurations are already known for carbon but, according to Dr Greb, a square-planar structure has not yet been produced in the field of silicon(IV) chemistry, even after over 40 years of intensive effort.
Dr Greb’s working group has succeeded for the first time in synthesising and completely characterising a square-planar silicon(IV) species. It was possible to show this with the aid of X-ray crystallography. The scientists grew a monocrystal which they irradiated with a finely focused beam of X-rays. The diffraction of the X-rays when encountering the atoms of the monocrystal led to an unmistakable pattern from which it is possible to calculate the position of the atom nuclei. This measurement enabled the researchers to show that they were dealing with molecules with square-planar silicon(IV). Further studies with spectroscopic methods supported this configuration. It displays physical and chemical properties that the researchers did not expect, e.g. colour in a naturally colourless class of substances.
“Synthesising this configuration from the components we chose is comparatively simple once you have understood the key conditions,” explains Dr Fabian Ebner, who is meanwhile a postdoctoral researcher at the Institute of Inorganic Chemistry. It surprised the scientists, however, that the square-planar silicon(IV) molecule constitutes a stable, isolable compound at all. “Due to the high reactivity, there are many conceivable ways of decomposition. Still, we have always believed that it is possible to isolate this compound,” Dr Greb emphasises.
Lutz Greb received a Starting Grant from the European Research Council (ERC) for his research in the area of structurally constrained main-group elements. The Foundation of German Business supported Fabian Ebner’s work. The research results were published in the journal “Chem”.
Göttingen University researchers create new kind of environmentally friendly bioplastic with hydroplastic polymers
Plastics offer many benefits to society and are widely used in our daily life: they are lightweight, cheap and adaptable. However, the production, processing and disposal of plastics are simply not sustainable, and pose a major global threat to the environment and human health. Eco-friendly processing of reusable and recyclable plastics derived from plant-based raw materials would be an ideal solution. So far, the technological challenges have proved too great. However, researchers at the University of Göttingen have now found a sustainable method – “hydrosetting”, which uses water at normal conditions – to process and reshape a new type of hydroplastic polymer called cellulose cinnamate (CCi). The research was published in Nature Sustainability.
Plastics are polymers, meaning that their molecular structure is built up from a large number of similar units bonded together. Currently, most plastics are manufactured using petrochemicals as raw materials, which is damaging to our environment to both extract and dispose of. In contrast, cellulose, which is the main constituent of plant cell walls, is the most abundant natural polymer on earth, constituting an almost inexhaustible source of raw material. By slightly modifying a very small portion of the chemistry of cellulose by introducing a “cinnamoyl” group, the researchers succeeded in making a specific CCi that is suitable for the formation of a new type of bioplastic with hydroplastic (ie soft and mouldable on contact with water) polymers.
This means that it can be moulded using little more than water at everyday temperature and pressure. This unique method – known as hydrosetting – enabled the researchers to produce a variety of shapes simply by immersing the bioplastic in water and leaving it to dry in the air. The moulded shapes kept their stability in the long-term and could be reshaped over and over again into a variety of 2D and 3D shapes. Although the plastic should not be used for direct contact with water – because it will lose its shape – it can hold water and be used in humid conditions. The CCi bioplastics showed high quality mechanical properties when compared with plastics that are currently widely used.
“Our research provides a feasible method to design other eco-friendly hydroplastics from renewable resources,” explains Professor Kai Zhang from the University of Göttingen. “This should open up new avenues of research, stimulating further exploration of other sustainable bioplastics with superior mechanical properties and new features.”
The hydrosetting process avoids expensive and complex machinery and harsh processing conditions. This eco-friendly method highly simplifies plastics manufacture, making their processing and recycling more economical and sustainable. “This research offers tremendous potential for bioplastics like this to be applied in many different situations, such as biology, electronics and medicine,” says Zhang before adding: “In particular, the detrimental effects of plastics on the environment, which is damaging to all forms of life on earth, would be minimized by reusing hydroplastics with their unique features.”
Featured image: The newly produced bioplastic consists of “hydroplastic polymers”, which become soft and malleable on contact with water. Photo: K Zhang
Original publication: Jiaxiu Wang, Lukas Emmerich, Jianfeng Wu, Philipp Vana and Kai Zhang, “Hydroplastic polymers as eco-friendly hydrosetting plastics” 2021, Nature Sustainability, DOI: 10.1038/s41893-021-00743-1.
Game-changing discovery impacts tissue engineering, wound healing, and cancer research
A new study, led by University of Minnesota Twin Cities engineering researchers, shows that the stiffness of protein fibers in tissues, like collagen, are a key component in controlling the movement of cells. The groundbreaking discovery provides the first proof of a theory from the early 1980s and could have a major impact on fields that study cell movement from regenerative medicine to cancer research.
Directed cell movement, or what scientists call “cell contact guidance,” refers to a phenomenon when the orientation of cells is influenced by the alignment of fibers within soft tissues. Cells have protrusions, almost like multiple little arms, that move them within the tissue. Cells obviously don’t have eyes to sense where they are going, so understanding the mechanisms for how they align their movement with the fibers is considered by researchers to be a final frontier in controlling cell migration.
“It’s kind of like if someone dropped you in a swimming pool filled with water and thousands of skinny ropes aligned along the length of the pool and told you to swim laps—and then turned off the lights,” said Robert Tranquillo, the senior researcher on the study and a University of Minnesota professor in the Department of Biomedical Engineering and the Department of Chemical Engineering and Materials Science. “You’d reach out your arms and legs to try to move through the water and figure out the right direction using the ropes.”
Cells need to move for many reasons. They must move to the right places in a developing embryo to become the right cell types. In wound healing, skin cells need to enter into blood clots efficiently to convert the wound into a scar. And research shows that when cancer cells migrate away from solid tumors to spread throughout the body, they’re following tracks of a line of fibers. In more recent years, researchers have found that contact guidance is the underlying cellular mechanism by which they can make engineered tissues for regenerative medicine to regrow, repair, or replace damaged or diseased cells, organs, or tissues.
Video credit: Provenzano Lab, University of Minnesota
“Even though we use cell contact guidance for many processes in my lab to engineer tissues to mimic heart valves and blood vessels, the signal that induces the cell movement in an aligned fiber network has been unclear to us all of these years,” said Tranquillo, a Distinguished McKnight University Professor.
In this new study aimed at understanding contact guidance and improving tissue engineering, Tranquillo’s team partnered with researchers at the University of California, Irvine and University of California, Los Angeles to test the mechanical resistance (the stiffness of the fibers) in two different directions in gels of aligned fibers to see if that was a major factor in cell movement instead of the porosity of the fibers or the adhesion (stickiness) of the fibers.
“Using a special set of tools previously unavailable to us, we were able to test skin cells that we consider a ‘work horse’ for developing engineered tissues,” Tranquillo said. “What we found is that when we cross-linked the fibers (connecting them at intersections) and increased the difference in the stiffness in the two directions, but kept all the other factors the same, the cells aligned better. This is evidence that a directional difference in mechanical resistance of the fiber network influences cell orientation and movement.”
This is the first time anyone has been able to prove one major aspect of the contact guidance theory first proposed by Graham Dunn at King’s College in London back in 1982, Tranquillo said.
The next steps are to study the porosity and adhesion of the fibers to see if they have an impact on cell movement, as well as to study other cell types.
“This is just the first step to truly understand how cells move,” Tranquillo added. “If we can learn more about how cells move, it could be a game-changer in many scientific fields.”
In addition to Tranquillo, the team included University of Minnesota Twin Cities Department of Biomedical Engineering researchers Greeshma Thrivikraman (first author), Sandra L. Johnson, Alexander Nelson, and Billianne Schultz; University of Minnesota Twin Cities Department of Chemical Engineering and Materials Science researcher Connie Wang; University of Minnesota Duluth Department of Chemical Engineering researcher Victor K. Lai, University of California-Irvine researchers Alicja Jagiełło, Mark Keating, and Elliot L. Botvinick; and University of California Los Angeles researcher Alex J. Levine.
The study was funded primarily by the National Science Foundation and the National Institutes of Health.
The research paper entitled “Cell contact guidance via sensing anisotropy of network mechanical resistance,” published in PNAS July 20, 2021 118 (29) e2024942118; https://doi.org/10.1073/pnas.2024942118
Featured image: Top: Human skin cells entrapped in an aligned fibrin gel exhibit contact guidance by orienting themselves along the aligned protein fibers in tissues. Above: A University of Minnesota study provides the first proof of a 1982 theory that the mechanical resistance (the stiffness of the fibers) plays a key role in controlling the movement of cells. The discovery could have a major impact on regenerative medicine and cancer research. Image credits: Tranquillo group, University of Minnesota
Based on the analysis of marsquakes recorded by NASA’s InSight mission, the structure of Mars’s crust has now been determined in absolute numbers for the first time. Beneath the InSight landing site, the crust is either approximately 20 or 39 kilometers thick. That is the result of an international research team led by geophysicist Dr. Brigitte Knapmeyer-Endrun at the University of Cologne’s Institute of Geology and Mineralogy and Dr. Mark Panning at Jet Propulsion Laboratory, California Institute of Technology (Caltech). InSight stands for “Interior Exploration using Seismic Investigations, Geodesy and Heat Transport.” NASA’s lander, which landed on Mars on 26 November 2018, explores the crust, mantle and core of the red planet. The paper “Thickness and structure of the Martian crust from InSight seismic data’ will appear in Science on July 23.
In the past, only relative differences in the thickness of the Mars crust could be estimated, and additional assumptions were required to obtain absolute thicknesses. The resulting absolute values thus showed large scatter, depending on which assumptions were made. Seismology now replaces these assumptions with a direct measurement at the landing site, and thus calibrates the crustal thickness for the entire planet. This independent data point also allows estimating the density of the crust.
“What seismology can measure are mainly velocity contrasts. These are differences in the propagation velocity of seismic waves in different materials,” said Knapmeyer-Endrun, lead author of the paper. “Very similar to optics, we can observe phenomena like reflection and refraction. Regarding the crust, we also benefit from the fact that crust and mantle are made of different rocks, with a strong velocity jump between them.” Based on these jumps, the crust’s structure can be determined very precisely.
The data show that at the InSight landing site, the top layer is about 8 (+/-2) kilometers thick. Below that, another layer follows to about 20 (+/-5) kilometers. “It is possible that the mantle starts under this layer, which would indicate a surprisingly thin crust, even compared to the continental crust on Earth. Beneath Cologne, for example, the Earth’s crust is about 30 kilometers thick,” Knapmeyer-Endrun explained. Possibly, however, there is a third crustal layer on Mars, which would make the Martian crust under the landing site about 39 (+/-8) kilometers thick. That would be more consistent with previous findings, but the signal from this layer is not essential to match existing data. “In both cases, however, we can rule out the possibility that the entire crust is made of the same material known from surface measurements and from Martian meteorites,” the geophysicist said. “Rather, the data suggest that the uppermost layer is composed of an unexpectedly porous rock. Also, there could be other rock types at greater depths than the basalts seen at the surface.”
The single, independent measurement of crustal thickness at the InSight landing site is sufficient to map the crust across the entire planet. Measurements from satellites orbiting Mars provide a very clear picture of the planet’s gravity field, allowing the scientists to compare relative differences in crustal thickness to the measurement taken at the landing site. The combination of these data provides an accurate map.
The crustal thickness of Mars is particularly interesting because the crust formed at an early formation stage from the remnants of a molten mantle. Thus, data on its present-day structure can also provide information on how Mars evolved. In addition, a more precise understanding of the evolution of Mars helps to decipher how early differentiation processes unfolded in the solar system and why Mars, Earth, and other planets are so different today.
Featured image: The two largest quakes detected by NASA’s InSight appear to have originated in a region of Mars called Cerberus Fossae. Scientists previously spotted signs of tectonic activity here, including landslides. This image was taken by the HiRISE camera on NASA’s Mars Reconnaisance Orbiter. Credit: NASA/JPL-Caltech/University of Arizona
Reference: Brigitte Knapmeyer-Endrun et al., “Thickness and structure of the martian crust from InSight seismic data,” Science (2021). vol. 373 no. 6553 438-443. DOI: https://doi.org/10.1126/science.abf8966
Two powerful telescopes provide the most detailed radio maps of the Northern Galactic Plane
By combining two of the most powerful radio telescopes on Earth, an international team of researchers led by the Max Planck Institute for Radio Astronomy (MPIfR) in Bonn, created the most sensitive maps of the radio emission of large parts of the Northern Galactic plane so far. The data were taken with the Karl G. Jansky Very Large Array (VLA) in New Mexico in two different configurations and the 100-m Effelsberg telescope near Bonn. This provides for the first time a radio survey covering all angular scales down to 1.5 arc-seconds, the apparent size of a tennis ball lying on the ground and seen from a flying plane. Contrary to previous surveys, GLOSTAR observed not only the radio continuum in the frequency range from 4-8 GHz in full polarization, but simultaneously also spectral lines that trace the molecular gas (from methanol and formaldehyde) and atomic gas via radio recombination lines.
An overview and first results are published in a series of four related papers in Astronomy & Astrophysics.
The Global View on Star formation in the Milky Way (GLOSTAR) project provides the most sensitive maps of the radio emission of large parts of the Northern Galactic plane so far, taken with the Karl G. Jansky Very Large Array (VLA) in New Mexico in two different configurations and MPIfR’s 100-m Effelsberg radio telescope. The exciting set of new data is now being used to study the interstellar medium in the Milky Way as well as massive stars in their infancy and their death. Shortly after the 50th birthday of the Effelsberg radio telescope, a series of papers based on the GLOSTAR data have now been published by Astronomy & Astrophysics.
While an interferometer like the VLA can produce very sharp images of the sky, the large-scale emission is often lost. However, the diffuse radio emission can be recovered by adding data from the 100-m Effelsberg telescope, as shown in Fig. 1. “This clearly demonstrates that the Effelberg telescope is still very crucial, even after 50 years of operation”, says Andreas Brunthaler, lead author of the first paper which gives an overview of the survey and describes the challenging data reduction techniques involved. To map the full 145 square degrees of the survey, the team had to combine smaller images from almost 50,000 different positions. “We needed about 700 hours of observing time on the VLA, which generated almost 40 Terabyte in raw data”, explains Sergio Dzib, who led the data calibration efforts of the VLA data. While the Effelsberg part of the survey is ongoing, the survey data is already used for new and exciting science.
Previous surveys have detected only about 30% of the expected numbers of supernova remnants in the Milky Way. Thanks to the unprecedented sensitivity of the GLOSTAR survey, it was possible to find 80 new candidates in the VLA data alone, doubling the number in the observed area. With the addition of the Effelsberg data, this number is expected to rise. “This is an important step to solve this long-standing mystery of the missing supernova remnants”, explains Rohit Dokara, a doctoral student at the MPIfR and lead author on the second paper.
With the exciting results of the submm and far infrared wavelength surveys from the ground and space the massive and cold dust clumps from which massive clusters form are now detected galaxy wide. Complementary to these surveys, the GLOSTAR survey provides a very powerful and comprehensive images of, both, the ionized and molecular tracers of star formation in the Galactic plane.
The survey also covers the nearby Cygnus X star forming complex. Here, new sources with 6.7 GHz methanol maser emission were detected. “The 6.7 GHz line from methanol is exclusively found in regions where very massive stars of at least 8 Solar masses are formed”, says Karl Menten, director at the MPIfR, the initiator of GLOSTAR. He discovered this methanol maser, the second strongest radio wavelength spectral line, for the first time in the insterstellar medium exactly 30 years ago. While all methanol masers in the Cygnus X complex are associated with dust emission, less than half of the sources are also detected in the radio continuum.
“These masers are signposts for stars in a very early evolutionary stage, even before detectable radio emission can be seen”, explains Gisela Ortiz-León from the MPIfR, who leads the study of the Cygnus X region. Identifying genuine massive “proto”-stars has long been a goal of star formation research.
While optical light is heavily absorbed by interstellar dust, radio waves allow a peek into the most central regions of the Milky Way. Searching the new continuum map observed with the VLA towards the Galactic Center for radio emission associated with potential young stellar objects from a recently published catalogue, permits a better understanding of their evolutionary stage. “While we find radio emission for a good number of them, many of the objects lack radio counterparts and dust emission, suggesting that they are more evolved and have already dispersed their natal clouds”, reports Hans Nguyen, another doctoral student at the MPIfR, who is leading the study on these young stellar objects. The associated radio sources enable further constraints on the star formation rate in the Galactic Center.
To catalog the large number of sources is also challenging. The expected number of sources in the full GLOSTAR images is a few tens of thousands of sources of different nature. “There are nearly 100 sources per each square degree and we are using all available information to classify them”, explains Sac Medina, co-author of the four papers and a former PhD student at the MPIfR, who led the first source catalog paper and it is currently preparing the catalog of the full GLOSTAR D-configuration images.
Since its very early days, the MPIfR has conducted many extensive surveys of the radio sky, most of them at longer wavelengths. The GLOSTAR survey is the first survey in the 4-8 GHz regime that can rival with space IR surveys in terms of spatial scales and dynamical ranges and will therefore provide a unique data set with true legacy value for a global perspective on star formation in our Galaxy.
GLOSTAR, the Global view on Star formation in the Milky Way survey uses the wideband (4-8 GHz) C-band receivers of the VLA and the Effelsberg 100-m radio telescope to conduct an unbiased survey to characterize star-forming regions in the Milky Way. This survey of the Galactic mid-plane detects tell-tale tracers of early phases of high-mass star formation: compact, ultra- and hyper-compact HII regions, and 6.7 GHz methanol (CH3OH) masers, which trace some of the earliest evolutionary stages in the formation of high-mass stars and can be used to pinpoint the positions of very young stellar objects, many of them still deeply embedded in their natal material. The observations center at 5.8 GHz and also cover emission from the 4.8 GHz formaldehyde (H2CO) and multiple Radio Recombination Lines (RRLs), all of which will be presented in future publications. The GLOSTAR observations were made with the VLA B- and D-configurations and the Effelsberg 100-m telescope for the large-scale structure.
References: (1) A. Brunthaler et al, A global view on star formation: The GLOSTAR Galactic Plane Survey. I. Overview and first results for the Galactic longitude range 28° < l < 36°, Astronomy & Astrophysics (2021). DOI: 10.1051/0004-6361/202039856 (2) R. Dokara et al, A global view on star formation: The GLOSTAR Galactic plane survey. II. Supernova remnants in the first quadrant of the Milky Way, Astronomy & Astrophysics (2021). DOI: 10.1051/0004-6361/202039873 (3) G. Ortiz-Leon et al, A Global View on Star Formation: The GLOSTAR Galactic Plane Survey. III. 6.7 GHz Methanol maser survey in Cygnus X, Astronomy & Astrophysics (2021). DOI: 10.1051/0004-6361/202140817 (4) H. Nguyen et al, A global view on star formation: The GLOSTAR Galactic plane survey. IV. Radio continuum detections of young stellar objects in the Galactic Centre region, Astronomy & Astrophysics (2021). DOI: 10.1051/0004-6361/202140802
Research led by Queen Mary University of London provides new insight into the mechanisms that lead to uncontrolled inflammation in COVID-19 patients
In a new study, published recently in the journal Circulation Research, scientists discover how the production of protective molecules known as specialised pro-resolving mediators (SPM) is altered in patients with COVID-19.
The results suggest that treatments which increase SPM production, such as dexamethasone or SPM based drugs, could play a key role in limiting inflammation in these patients.
Currently there is little understanding around the mechanisms that lead to uncontrolled inflammation in patients with COVID-19.
The study found a link between decreased SPM blood levels and disrupted white blood cell responses in patients with a higher disease burden. The findings also revealed that dexamethasone, the first drug approved for treatment of patients with COVID-19, increased the levels of these protective molecules in these patients. Furthermore, treatment of white blood cells with SPM improved their function and reduced the expression of molecules linked to the spread of inflammation. Understanding these mechanisms will help provide new leads into the development of treatments to limit disease severity in patients with COVID-19.
This study offers a new insight into the disrupted biological processes that contribute to increased disease severity in COVID-19 patients. Results suggest that treatments which increase SPM production, such as dexamethasone or SPM based drugs, could play a key role in limiting inflammation in this patient group.
Jesmond Dalli, Professor in Molecular Pharmacology and Lipid Mediator Unit Director at Queen Mary University of London said: “The observation that dexamethasone increased the production of SPM was a surprising finding. This finding suggests that SPM may serve as biomarkers to determine the efficacy of this drug in limiting inflammation in patients with COVID-19. Another surprising finding was that blood levels of these molecules remained altered several weeks after resolution of clinical symptoms.”
“Our results are the first to relate the impact that COVID-19 infections on immune responses and to explore the utility of using SPM to rectify white blood cell behaviour. Given the extensive body of literature demonstrating the protective role of these molecules in limiting inflammation in both viral and bacterial infections these results suggest that SPM and SPM-based therapeutics may be useful in the treatment of infections to limit inflammation without compromising the ability of the immune system to deal with the invading pathogen”.
Mauro Perretti (Dean for Research, School of Medicine and Dentistry) said: “This study is a perfect example of a productive partnership between Barts and the London School of Medicine at Queen Mary and Barts NHS Trust, a partnership established in difficult circumstances yet successful thanks to the will and commitment of our scientists and clinicians. The paper presents world class data on how resolution pathways impact on COVID infection, opening opportunities for new therapies and new markers to predict patient outcome”.