ETH Zurich researchers conducted an experiment to investigate the initial steps in the formation of aerosols. Their findings are now aiding efforts to better understand and model that process – for example, the formation of clouds in the atmosphere.
Clouds are water droplets dispersed in the air and thus an aerosol. (Photograph: Colourbox)
Aerosols are suspensions of fine solid particles or liquid droplets in a gas. Clouds, for example, are aerosols because they consist of water droplets dispersed in the air. Such droplets are produced in a two-step process: first, a condensation nucleus forms, and then volatile molecules condense onto this nucleus, producing a droplet. Nuclei frequently consist of molecules different to those that condense onto them. In the case of clouds, the nuclei often contain sulphuric acids and organic substances. Water vapour from the atmosphere subsequently condenses onto these nuclei.
Scientists led by Ruth Signorell, Professor at the Department of Chemistry and Applied Biosciences, have now gained new insights into the first step of aerosol formation, nucleation. “Observations have shown that the volatile components can also influence the nucleation process,” Signorell says, “but what was unclear was how this was happening at the molecular level.” Previously it was impossible to observe the volatile components during nucleation in an experimental setting. Even in a famous CERN experiment on cloud formation, the “Cloud” experiment, certain volatile components could not be directly detected.
The experimental setup in an ETH Zurich laboratory. (Photograph: ETH Zurich / Ruth Signorell)
Volatile components detected for the first time
The ETH researchers developed an experiment aimed at the first microseconds of the nucleation process. In the experiment, the particles formed remain intact during this time and can be detected using mass spectrometry. The scientists looked at nucleation in various gas mixtures containing CO2 and for the first time, they were able to detect the volatile components as well – in this case, the CO2. The researchers could show that the volatile components were essential for the formation of nuclei and also accelerated this process.
An analysis of the experimental data revealed that this acceleration is the result of the volatile components catalysing the nucleation of other, less volatile components. They do this by forming short-lived, heterogeneous molecular aggregates, known as chaperon complexes. “Because temperature determines the volatility of gas components, it also plays a decisive role in these processes,” Signorell explains.
One reason the new research results are interesting is that they improve the understanding of nucleation, its molecular mechanisms and speed, in order to properly account for it in models for, say, cloud formation in the atmosphere. In addition, the results should help to improve the efficiency of technical processes for producing aerosols – such as the use of rapid cooling to capture CO2 from natural gas.
A new study looked at triple galaxy mergers to learn what happens to their supermassive black holes.
The results find a single, four doubles, a triple giant black hole remain in six of the seven mergers.
A team used several telescopes including Chandra plus specially-developed software to identify these growing black holes.
This helps astronomers better understand what role mergers play in how galaxies and their giant black holes grow.
A new study helps reveal what happens to supermassive black holes when three galaxies merge, as reported in our latest press release. This result, which used data from NASA’s Chandra X-ray Observatory and several other telescopes, tells astronomers more about how galaxies and the giant black holes in their centers grow over cosmic time.
While there have been previous studies of mergers between two galaxies, this is one of the first to systematically look at the consequences for supermassive black holes when three galaxies come together. This panel of images contains data from two of seven galactic collisions in the new study containing two supermassive black holes left growing after the collision. The pair of mergers are seen in X-rays from Chandra (left in purple) and optical data (right) from NASA’s Hubble Space Telescope and the Sloan Digital Sky Survey (SDSS). Circles in a labeled version of the Chandra image show X-rays from hot gas falling towards each black hole.
These triple galaxy mergers were first identified by sifting through data from the SDSS and NASA’s WISE mission and then comparing the results to X-ray data in the Chandra archive. This method identified seven triple galaxy mergers located between 370 million and one billion light years from Earth.
Using specialized software, the team went through Chandra data targeting these systems to detect X-ray sources marking the location of growing supermassive black holes. As material falls toward a black hole, it gets heated to millions of degrees and produces X-rays. The combination of the new software and Chandra’s sharp X-ray vision enabled the researchers to identify the black holes despite their close proximity in the images.
Out of seven triple galaxy mergers, there results are: one with a single growing supermassive black hole, four with double growing supermassive black holes (two of which are shown in the main graphics), and one that is a triple. The final merger of three galaxies they studied seems to have no X-ray emission detected from the supermassive black holes. This means that none of the supermassive black holes were left rapidly pulling in matter. In the systems with multiple black holes, the separations between them range between about 10,000 and 30,000 light years.
Once they found evidence for bright X-ray sources as candidates for growing supermassive black holes in the Chandra data, the researchers incorporated archival data from other telescopes such as WISE mission, the Infrared Astronomical Satellite, and the Two Micron All Sky Telescope as another check in the process.
Studies of triple mergers can help scientists understand whether pairs of supermassive black holes can approach so close to each other that they make ripples in spacetime called gravitational waves. The energy lost by these waves will inevitably cause the black holes to merge.
Adi Foord presented the new study, which she worked on as part of her Ph.D. at the University of Michigan, at the 237th meeting of the American Astronomical Society, which is being held virtually from January 11-15, 2021. Two papers describing this work have recently been accepted for publication in The Astrophysical Journal and preprints are available here and here.
NASA’s Marshall Space Flight Center manages the Chandra program. The Smithsonian Astrophysical Observatory’s Chandra X-ray Center controls science from Cambridge Massachusetts and flight operations from Burlington, Massachusetts.
New CU research shows a wider variety of T cells means a better immune system response.
New research from CU Cancer Center member Jing Hong Wang, MD, PhD, and recent University of Colorado Immunology program graduate Rachel Woolaver, PhD, may help researchers develop more effective personalized immunotherapy for cancer patients.
Working within Wang’s specialty of cancer immunology and head and neck squamous cell carcinomas (HNSCCs), the researchers worked to establish a mouse model that would help them understand why some hosts’ immune systems reject tumors easily, while others have a harder time doing so. Their research was published last week in the Journal for ImmunoTherapy of Cancer.
“It’s particularly interesting now because the field of cancer treatment has really been going in the direction of immunotherapy, where you give drugs that can reactivate the immune system and get it to kill the tumors on its own,” Woolaver says.
That’s in contrast to chemotherapy and radiation, which can kill other cells along with tumor cells. “We’re just trying to figure out how can we contribute to the field of understanding what causes heterogeneity (differences) in anti-tumor immune responses,” she says.
The T cell solution
Wang, Woolaver and other cancer researchers on the Anschutz Medical Campus started the research by transplanting HNSCC tumors into genetically identical mice. Theoretically, their response to the cancer would be identical, but it turned out that 25% of the mice spontaneously rejected the tumor. The researchers started looking more closely at both the mice and the tumor cells to try to understand what was causing the mice to kill the cancer on their own.
What they discovered is that it all depended on the types of the immune cells known as CD8 T cells that were present in the mouse. Even identical twins have different T cells due to the random DNA recombination event generating these T cells, Wang explains, so the genetically identical mice had different arrays of the T cells as well. The mice’s response to cancer depended on how their specific T cells matched up with the set of mutated proteins known as neoantigens that were present in the tumor they were fighting.
“Each of your T cells has a different receptor, and each T cell will be specific to a neoantigen,” Woolaver says. “If you have T cells that are specific to all of them or majority of them, you’re going to be able to get rid of your tumor and have a good anti-tumor immune response.”
What the researchers showed in the publication, Wang explains, is that the mice that spontaneously rejected tumors had vastly different T cell receptors from those that succumbed to tumor development.
Applications in immunotherapy
For the next phase of their research, Wang and her team members plan to study how to enable a cancer patient to develop a more diverse T cell response so they have a better chance of successfully fighting off a tumor.
“Because patient tumors are very heterogenous from each other, it’s very difficult to study them,” Woolaver says. “In our paper, we characterize a new model of tumor heterogeneity that has a lot of interesting immunological aspects that we can study to try to help improve the immune response to cancer.”
Wang adds that the research can be important in developing new types of immunotherapy.
“I don’t think it’s well recognized in the field that intrinsic differences in the immune system can make an impact,” Wang says. “Most people just focus on ‘Why are all the T cells not activated,’ or ‘The T cells are exhausted,’ or something like that. But maybe a patient doesn’t have the right T cells from the beginning. If they don’t have the right T cells that can recognize neoantigens, how can they have the effective anti-tumor immune response?”
Reference: Rachel Woolaver, Jing Hong Wang et al., “Differences in TCR repertoire and T cell activation underlie the divergent outcomes of antitumor immune responses in tumor-eradicating versus tumor-progressing hosts”, Journal for Immunotherapy of Cancer, 9(1), 2021. https://jitc.bmj.com/content/9/1/e001615
Researchers at the Technion – Israel Institute of Technology and EMBL Hamburg have discovered remarkable molecular properties of an antimicrobial peptide from the skin of the Australian toadlet. The discovery could inspire the development of novel synthetic drugs to combat bacterial infections.
The peptide uperin 3.5 is secreted by the Australian toadlet’s skin. When exposed to bacterial membranes, it rapidly changes its structure and transforms into a deadly antimicrobial weapon. The pictures were taken using a transmission electron microscope (TEM) in the Electron Microscopy Centers in the Technion Department of Materials Science and Engineering and in the Department of Chemical Engineering. The cross-α atomic structure was determined by data collected at the ESRF synchrotron. Credit: Nir Salinas/Technion
An antibacterial peptide that turns on and off
The researchers solved the 3D molecular structure of an antibacterial peptide named uperin 3.5, which is secreted on the skin of the Australian toadlet (Uperoleia mjobergii) as part of its immune system. They found that the peptide self-assembles into a unique fibrous structure, which via a sophisticated structural adaptation mechanism can change its form in the presence of bacteria to protect the toadlet from infections. This provides unique atomic-level evidence explaining a regulation mechanism of an antimicrobial peptide.
The antibacterial fibrils on the toadlet’s skin have a structure that is reminiscent of amyloid fibrils, which are a hallmark of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. Although amyloid fibrils have been considered pathogenic for decades, it has recently been discovered that certain amyloid fibrils can benefit the organisms that produce them, from human to microbes. For example, certain bacteria produce such fibrils to fight human immune cells.
The findings suggest that the antibacterial peptide secreted on the toadlet’s skin self-assembles into a “dormant” configuration in the form of highly stable amyloid fibrils, which scientists describe as a cross-β conformation. These fibrils serve as a reservoir of potential attacker molecules that can be activated when bacteria are present. Once the peptide encounters the bacterial membrane, it changes its molecular configuration to a less compact cross-α form, and transforms into a deadly weapon. “This is a sophisticated protective mechanism of the toadlet, induced by the attacking bacteria themselves,” says structural biologist Meytal Landau, the lead author of this study. “This is a unique example of an evolutionary design of switchable supramolecular structures to control activity.”
Potential for future medical applications
Antimicrobial peptides are found in all kingdoms of life, and thus are hypothesised to be commonly used as weapons in nature, occasionally effective in killing not only bacteria, but also cancer cells. Moreover, the unique amyloid-like properties of the toadlet’s antibacterial peptide, discovered in this study, shed light on potential physiological properties of amyloid fibrils associated with neurodegenerative and systemic disorders.
The researchers hope that their discovery will lead to medical and technological applications, e.g. development of synthetic antimicrobial peptides that would be activated only in the presence of bacteria. Synthetic peptides of this kind could also serve as a stable coating for medical devices or implants, or even in industrial equipment that requires sterile conditions.
The study is a result of a collaboration between scientists at EMBL Hamburg and Technion, and groups in Israel and Spain. It is an example of EMBL’s approach to life science research in its next scientific Programme Molecules to Ecosystems. EMBL will integrate interdisciplinary approaches to understand the molecular basis of life in the context of environmental changes, and to provide translational potential to support advances in human and planetary health.
Based on preclinical studies of an investigational drug to treat peripheral nerve tumors, researchers at Children’s Hospital of Philadelphia (CHOP) as part of the Neurofibromatosis Clinical Trials Consortium have shown that the drug, cabozantinib, reduces tumor volume and pain in patients with the genetic disorder neurofibromatosis type 1 (NF1). The results of the Phase 2 clinical trial, co-chaired by Michael J. Fisher, MD at CHOP, were published recently in Nature Medicine.
“This is the second class of drugs to demonstrate a very promising response rate for NF1 patients with these tumors,” said first author Fisher, Chief of the Section of Neuro-Oncology and Director of the Neurofibromatosis Program at CHOP, and Group Chair for the NF Clinical Trials Consortium, which includes 25 sites developing innovative biologically-based clinical trials for complications of NF. “Collectively, the data presented in this study illustrate a true bench-to-bedside approach, coordinating translational and clinical efforts to advance targeted therapies for a rare disease like NF1.”
NF1 is a rare tumor predisposition syndrome, affecting approximately 1 in 3000 people worldwide. The condition involves the proliferation of tumors throughout the central and peripheral nervous system. One of the most prevalent type of tumors in NF1 are plexiform neurofibromas (PN), multicellular tumors composed of tumorigenic Schwann cells, fibroblasts, perineural cells, macrophages, mast cells, and secreted collagen. The tumors arise within nerves, affect up to half of patients with NF1, grow rapidly during childhood, and can lead to motor and sensory dysfunction, pain, and disfigurement. When the tumors impinge on vital structures like the airway or the spinal cord, they can be life-threatening, and although the tumors are not malignant, they can become so over time.
Because chemotherapy and radiation are ineffective at treating these tumors, surgery is the current standard of care. However, given that the tumors can be intertwined with nerves and other vital structures, surgery is often not possible. Recent studies have shown that a MEK inhibitor called selumetinib can be an effective treatment in some children with NF1-related PNs, but not all patients respond to this treatment, so there is a need for more treatment options.
Based on preclinical studies of cabozantinib, a tyrosine kinase inhibitor that targets both the tumorigenic Schwann cells in PNs as well as the complex tumor microenvironment, the researchers enrolled patients in a single arm, multicenter Phase 2 clinical trial. Twenty-three patients between the ages of 16 and 34 enrolled in the trial; twenty-one were evaluable for drug toxicity and 19 were evaluable for their response to the treatment. Of the 19 patients studied for response, eight (42%) had a partial response, defined as having greater than a 20% decrease in tumor volume, and 11 had stable disease after 12 rounds of treatment. No patient had disease progression while participating in the trial. The eight patients who had a partial response to treatment also reported a significant reduction in tumor pain intensity and pain interference in daily life.
Patients enrolled in the trial reported several adverse events, including diarrhea, nausea, asymptomatic hypothyroidism, fatigue, and palmar plantar erythrodysesthesia, a condition that causes redness, swelling, and pain on the palms of the hands and/or the soles of the feet. However, none of the side effects were reported as being severe.
Based on the benefit of cabozantinib demonstrated in this study, the NF Clinical Trials Consortium opened a pediatric cohort as well, enrolling patients ages 3 to 15. Enrollment is complete, and the study is ongoing.
“It’s incredibly exciting that we now have two classes of drugs that result in tumor responses, given that we had no promising agents only a few years ago,” Dr. Fisher said. “However, despite this excitement, neither cabozantinib nor MEK inhibitors shrink all tumors or make them go away completely. Therefore, we are building on these results as well as ongoing laboratory studies and are planning future exploration of combination therapies, so that we can further improve outcomes for these patients with these debilitating and life-threatening tumors.”
The research was supported by an NF Clinical Trials Consortium award from the Department of Defense NF Research Program (W81XWH-12-1-0155), a Developmental and Hyperactive Ras Tumor SPORE funded through the NIH/NCI (U54- CA196519-04), and Exelixis.
Reference: Fisher et al. “Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: a phase 2 trial,” Nature Medicine, January 13, 2021, DOI: 10.1038/s41591-020-01193-6 https://www.nature.com/articles/s41591-020-01193-6
Many animal and insect species use Batesian mimicry – mimicking a poisonous species – as a defense against predators. The common palmfly, Elymnias hypermnestra (a species of satyrine butterfly), which is found throughout wide areas of tropical and subtropical Asia, adds a twist to this evolutionary strategy: the females evolved two distinct forms, either orange or dark brown, imitating two separate poisonous model species, Danaus or Euploea. The males are uniformly brown. A population group is either entirely brown (both males and females) or mixed (brown males and orange females).
Photo of butterfly in the wild, Elymnias hypermnestra beatrice. Photo credit: Gan Cheong Weei.
City College of New York entomologist David Lohman and his collaborators studied the genome of 45 samples representing 18 subspecies across Asia to determine their evolutionary history and to establish what genes were responsible for the color variation in females. They found that neither the orange nor brown females had a common recent ancestor.
“The conventional wisdom is that once something evolves and you lose it, it’s hard to re-evolve it,” said Lohman. “That suggests something is acting like a switch, switching the gene on or off.”
The researchers found two DNA nucleotides on the Elymnias hypermnestra genome that regulate WntA, a gene associated with color patterning in butterfly species.
The WntA gene can be switched on to recreate the phenotypic shift, even where it hasn’t appeared for several generations. Reaching back into genetic history allows a species to create a variant without having to re-evolve the intermediate biochemical pathways.
“Evolution of a phenotype can be more plastic than we thought,” said Shen-Horn Yen, one of Lohman’s collaborators from the Department of Biological Sciences, National Sun Yat-Sen University, Taiwan.
To Lohman, studying Elymnias hypermnestra encapsulates the study of biodiversity in its entirety. There’s a universe of variety in color, form and size and genetic variability all found in a single genus of butterfly.
Since 1847, The City College of New York has provided a high-quality and affordable education to generations of New Yorkers in a wide variety of disciplines. CCNY embraces its position at the forefront of social change. It is ranked #1 by the Harvard-based Opportunity Insights out of 369 selective public colleges in the United States on the overall mobility index. This measure reflects both access and outcomes, representing the likelihood that a student at CCNY can move up two or more income quintiles. In addition, the Center for World University Rankings places CCNY in the top 1.8% of universities worldwide in terms of academic excellence. Labor analytics firm Emsi puts at $1.9 billion CCNY’s annual economic impact on the regional economy (5 boroughs and 5 adjacent counties) and quantifies the “for dollar” return on investment to students, taxpayers and society. At City College, more than 16,000 students pursue undergraduate and graduate degrees in eight schools and divisions, driven by significant funded research, creativity and scholarship. CCNY is as diverse, dynamic and visionary as New York City itself. View CCNY Media Kit.
An analysis of immune status to predict treatment success.
In patients with bladder cancer, chemotherapy effectiveness is partially determined by the body’s immune system response to the malignancy. This is the conclusion of research conducted by a team of scientists from Charité – Universitätsmedizin Berlin and the Berlin Institute of Health. The findings, which have been published in Science Translational Medicine*, can be used to predict treatment success and may increase survival in patients with bladder cancer.
The research team plans to study patients with bladder cancer and other cancers to establish whether cell therapy might be used to encourage and enhance the immune system’s fight against the cancer. Photo: Hirscher/Charité
Bladder cancer is one of the ten most common types of cancer in Germany, and one of the five most common cancers in men. Nationwide, the disease affects approximately 30,000 people a year. The risk of the cancer spreading (metastasizing) is particularly high once it invades the muscle layer inside the bladder wall. In patients with non-metastatic muscle-invasive bladder cancer, treatment usually consists of the surgical removal of the bladder. According to current professional guidelines, patients must undergo chemotherapy prior to surgery; they receive drugs which will target the cancer’s fast-growing cells. The aim of this ‘neoadjuvant’ chemotherapy is to shrink the tumor prior to surgery in order to reduce the risk of recurrence and/or metastases. However, in more than fifty percent of patients, chemotherapy will not shrink the tumor. Not only do these people not benefit from neoadjuvant chemotherapy, they are losing valuable time – time during which the cancer can continue to grow and metastasize.
An international team of researchers led by Dr. Michael Schmück-Henneresse, a scientist at the Berlin Institute of Health Center for Regenerative Therapies (BCRT) as well as Charité’s Institute of Medical Immunology and the Berlin Center for Advanced Therapies (BeCAT), has discovered a way to differentiate between patients who will benefit from chemotherapy and those who will not. The status of the patients’ immune systems before the start of treatment was found to hold the key. Subsequent chemotherapy only proved effective if the cancerous tissue contained large quantities of two specific immune system components known as CXCL11 and CXCR3alt. “The process of measuring these two components in the laboratory is relatively straightforward and only requires the biopsy sample which is collected in order to diagnose the cancer,” says Dr. Schmück-Henneresse. “This technologically simple method will make it possible to predict the likelihood of chemotherapy success in a specific patient at the point of diagnosis. If neoadjuvant chemotherapy is unlikely to be successful, one could dispense with this therapy altogether and directly move to the bladder cancer’s surgical removal. This type of personalized approach would not only spare patients the side effects of an ineffective treatment, it would probably increase their chances of survival. However, our results will need to be confirmed by further, independent studies before we can get to a stage where CXCL11 and CXCR3alt measurements become standard in patients with bladder cancer.”
As part of this research, the team studied tumor samples from 20 patients with muscle-invasive bladder cancer who had completed their chemotherapy treatment at Umeå University in Sweden. Dating back to before the start of treatment, the samples had been collected by Dr. Amir Sherif and his team during diagnostic cytoscopy procedures. The research group identified which immunological messengers were present in the biopsy tissue and which receptors (effectively the ‘recipients’ of these messengers) the immune cells inside the tumors were producing. For each of the components identified, they then tested whether there was a link between the quantities at which these were present and treatment success. Results confirmed this was the case for both the messenger substance CXCL11 and the receptor CXCR3alt. Chemotherapy only had an effect if the immune cell attractant CXCL11 was present at particularly high levels inside the tumor tissue and if specific immune system cells known as T cells produced the corresponding CXCR3alt receptor. The team subsequently examined their observations using existing data from ‘The Cancer Genome Atlas’. Their comparison confirmed that, out of a total of 68 patients with bladder cancer who had received chemotherapy, patients whose tumor tissue contained large quantities of CXCL11 were more likely to survive.
“The signaling molecule CXCL11 attracts specific T cells into the tumor tissue, where it prompts them to proliferate and fight the cancer,” explains the study’s first author, Tino Vollmer, a doctoral student at Charité’s Institute of Medical Immunology and scientist at the BCRT and BeCAT. “Chemotherapy appears to support the body’s own fight against the tumor, possibly because the resulting degradation of cancerous tissue makes it easier for T cells to invade it.” The immune system’s effect on treatment outcome directly contradicts established scientific consensus, which posits that the effect of chemotherapy drugs is solely due to the ability of cancer cells to divide and replicate. “Along with other studies, our research demonstrates the importance of the immune system’s active involvement in fighting the tumor,” says Vollmer.
As a next step, the researchers plan to study whether cell therapy could be used to activate the T cells of patients whose immune systems show a weak response to their bladder cancer. To do this, the team wants to harvest T cells from affected patients, fit them with synthetic CXCR3alt receptors in the laboratory, and then reintroduce them into these patients. The researchers will also study the same approach in relation to the treatment of other cancers. Furthermore, they plan to advance the use of personalized chemotherapy in patients with bladder cancer. To achieve this, the researchers intend to test the predictive power of both immune system components (CXCL11 and CXCR3alt) using a process known as ‘predictive validation’, which will involve the study of independent groups of patients with muscle-invasive bladder cancer at various European hospitals. “Should the method’s predictive reliability be confirmed, the analysis of a patient’s immune status could become a routine tool to support decision-making in the treatment of bladder cancer,” says Dr. Schmück-Henneresse.
Reference: Vollmer T et al., The intratumoral CXCR3 chemokine system is predictive of chemotherapy response in human bladder cancer. Sci Transl Med 2021 Jan 13. https://stm.sciencemag.org/content/13/576/eabb3735 doi: 10.1126/scitranslmed.abb3735
The hallmarks of cancer include rapid cell reproduction and metabolic activity. But these processes also lead to increased cellular stress and oxidation, and the risk of cell death. To circumvent these negative consequences of supercharged growth, cancer cells stimulate pathways to reduce oxidative stress and avoid cell death. In an article published in Cell Metabolism, Moffitt Cancer Center researchers report on a newly discovered biochemical pathway that protects cells from a type of cell death called ferroptosis.
Graphical abstract by Kang et al.
Ferroptosis is a specialized type of cell death that is caused by imbalances in oxidation within cells. Ferroptosis results in changes to molecules in the cell membrane called lipids and can be caused by cysteine starvation. Cysteine is a type of amino acid that is one of the building blocks of proteins and is also used by the body for numerous important physiological processes, including cell survival, regulation of oxidative-reduction reactions and energy transfer. Because of its critical role in normal processes, cysteine is highly regulated to prevent excess or insufficient amounts of the amino acid.
Several different types of cancer overexpress molecules that play an important role in cysteine regulation. This suggests that reducing cysteine levels may negatively affect cancer growth. In fact, studies have shown that cancer cells can be induced to undergo cell death by either inhibiting cysteine uptake or starving cells of cysteine. However, the downstream processes that are stimulated by cysteine starvation are unclear. Moffitt researchers performed a series of laboratory investigations to learn what molecules become activated after cysteine deprivation and how this impacts cells.
The researchers discovered that cancer cells can activate signaling pathways to protect themselves against cell death due to cysteine starvation. When the team starved non-small cell lung carcinoma cells of cysteine, the cells began to undergo ferroptosis. However, cysteine starvation also resulted in an unexpected accumulation of small molecules called γ-glutamyl-peptides, which protected the cells against ferroptosis. The researchers found that the peptides were synthesized through the activity of the protein GCLC. Under normal conditions, GCLC is involved in the first step of the synthesis of the antioxidant glutathione from the amino acids cysteine and glutamate. However, this newly discovered activity of GCLC occurred in the absence of cysteine and was important to limit both glutamate accumulation and oxidant production.
The researchers further analyzed signaling mechanisms controlling GCLC-mediated peptide synthesis and discovered that GCLC was regulated by the protein NRF2. They found that under normal conditions, NRF2 regulated GCLC to produce glutathione, but under cysteine-starved conditions, NRF2 regulated GGLC to produce γ-glutamyl-peptides.
“NRF2 is known to play an important role in the protection against cellular oxidation and is often deregulated in lung cancer,” said lead author Gina DeNicola, Ph.D., assistant member of the Cancer Physiology Department at Moffitt. “The ability of NRF2 to protect against ferroptosis has important implications for cancer, particularly lung cancers that commonly have NRF2 activation via mutations in KEAP1 and NRF2.”
This work was supported the National Institutes of Health (R37 CA230042, R01 DK123738, R01 CA189623, P30 CA076292), the AACR-Takeda Oncology Lung Cancer Research Fellowship (19-40-38-KANG ), the National Pancreas Foundation, a Florida Bankhead-Coley grant, and a Miles for Moffitt award and additional funding from the Moffitt Foundation.
About Moffitt Cancer Center Moffittis dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 51National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s scientific excellence, multidisciplinary research, and robust training and education. Moffitt is the No. 11 cancer hospital and has been nationally ranked by U.S. News & World Report since 1999. Moffitt’s expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. With more than 7,000 team members, Moffitt has an economic impact in the state of $2.4 billion. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the momentum onFacebook, Twitter,Instagram and YouTube.
Astronomers and citizen scientists produce the most complete 3D map of cool brown dwarfs in the Sun’s neighborhood.
Astronomers have curated the most complete list of nearby brown dwarfs to date thanks to discoveries made by thousands of volunteers participating in the Backyard Worlds citizen science project. The list and 3D map of 525 brown dwarfs — including 38 reported for the first time — incorporate observations from a host of astronomical instruments including several NOIRLab facilities. The results confirm that the Sun’s neighborhood appears surprisingly diverse relative to other parts of the Milky Way Galaxy.
This visualization represents a three-dimensional map of brown dwarfs (red dots) that have been discovered within 65 light-years of the Sun. The Sun, which is not shown, is located at the center of the view. The disk of the Milky Way appears in the background. Other stars close to the Sun appear as variously colored points in the field. Credit:NOIRLab/NSF/AURA/J. da Silva
Mapping out our own small pocket of the Universe is a time-honored quest within astronomy, and the results announced today have added to this long-running effort by cataloging the locations of more than 500 cool brown dwarfs in the vicinity of the Sun. An international team of astronomers — assisted by the legions of volunteer citizen scientists in the Backyard Worlds: Planet 9 collaboration — have announced an unprecedented census of 525 cool brown dwarfs within 65 light-years of the Sun, including 38 new discoveries. By determining the distances to all the objects in the census, astronomers have been able to build a 3D map of the distribution of cool brown dwarfs in the Sun’s local neighborhood.
This breakthrough relied on novel datasets published by the DESI Legacy Imaging Surveys, which blend huge quantities of astronomical data from a variety of sources: archival images from the Nicholas U. Mayall 4-meter Telescope at Kitt Peak National Observatory (KPNO) and the Víctor M. Blanco 4-meter Telescope at Cerro Tololo Inter-American Observatory (CTIO), which are Programs of NSF’s NOIRLab, plus critical sky maps from NASA’s Wide-field Infrared Survey Explorer (WISE). These powerful survey datasets were combined with new distance measurements from the NASA Spitzer Space Telescope to create the best three-dimensional map of the Sun’s local neighborhood to date.
Brown dwarfs are sometimes referred to as “failed stars.” They are thought to form the way stars do, but they do not become massive enough to trigger nuclear fusion in their cores. Their faintness and relatively small sizes make them difficult to identify without careful analysis of data from sensitive telescopes — meaning that many have gone undiscovered until now. However, by finding and studying brown dwarfs, astronomers can learn more about star formation and also about planets around other stars.
“Brown dwarfs are the low-mass byproducts of the process that forms stars, yet the least massive of them have many characteristics in common with exoplanets,” says J. Davy Kirkpatrick, California Institute of Technology scientist and lead author of the research paper. “They’re exoplanet laboratories, but since they are usually by themselves and lack the complications caused by a blinding host sun, they’re much easier to study.”
Video: CosmoView Episode 20 for press release noirlab2015: Mapping Our Sun’s Backyard Credit: KPNO/NOIRLab/NSF/AURA/P. Marenfeld, International Gemini Observatory/Jacqueline Faherty (American Museum of Natural History)/OpenSpace/Lynette Cook Music: zero-project – The Lower Dungeons (zero-project.gr)
To help identify elusive brown dwarfs in massive datasets, astronomers enlisted the help of the Backyard Worlds collaboration, a worldwide network of more than 100,000 citizen scientists.[1]Astro Data Lab at NOIRLab’s Community Science and Data Center (CSDC) was instrumental in providing these volunteers with data, allowing citizen scientists to easily hunt through the astronomical archives in search of brown dwarf candidates. The Backyards Worlds project announced the discovery of almost 100 nearby cool brown dwarfs in August last year, and today’s announcement is a continuation of their work.
“The Backyard Worlds project shows that the general public can play an important role in cutting-edge astronomy,” commented NOIRLab scientist Aaron Meisner, co-author of this study and co-founder of Backyard Worlds. “Volunteers ranging from high school students to retired engineers are helping uncover groundbreaking discoveries lurking in existing telescope data.”
One of the most intriguing results of this study is that it provides more evidence that the Sun’s immediate neighborhood (within roughly 7 light-years) is rather unusual. While most stars in the Milky Way are red dwarfs, earlier results revealed that the Sun’s closest neighbors are much more diverse, with different types of objects, from Sun-like stars to Jupiter-like brown dwarfs, appearing in roughly equal numbers.[2] The new results add to this disparity by turning up no more extremely cold brown dwarfs like our close-by neighbor WISE 0855, the coldest known brown dwarf, even though the team expected to find at least several more within 65 light-years of the Sun, given the new study’s sensitivity.
This result hints at the possibility that yet more cold brown dwarfs have so far eluded detection. “Thanks to the efforts of volunteers around the world, we have a better idea than ever of the objects in our cosmic backyard,” concluded Meisner. “But we suspect that more of the Sun’s cold and close neighbors still await discovery within our vast data archives.”
Notes
[1] Backyard Worlds: Planet 9 is hosted by Zooniverse. [2] Stars and brown dwarfs are classified by their temperature and other spectral characteristics using letters of the alphabet. For example, our Sun is a G star, a K star is considered an orange dwarf star, and M stars are often called “red dwarfs,” while brown dwarfs are classified as L, T, and Y dwarfs. Earlier studies have revealed that, collectively, the four nearest star systems to the Sun include one G-dwarf star, one K dwarf, two M dwarfs, one L dwarf, one T dwarf, and one Y dwarf.
Reference: J. Davy Kirkpatrick, Christopher R. Gelino, Jacqueline K. Faherty, Aaron M. Meisner, Dan Caselden, Adam C. Schneider, Federico Marocco, Alfred J. Cayago, R. L. Smart, Peter R. Eisenhardt, Marc J. Kuchner, Edward L. Wright, Michael C. Cushing, Katelyn N. Allers, Daniella C. Bardalez Gagliuffi, Adam J. Burgasser, Jonathan Gagne, Sarah E. Logsdon, Emily C. Martin, James G. Ingalls, Patrick J. Lowrance, Ellianna S. Abrahams, Christian Aganze, Roman Gerasimov, Eileen C. Gonzales, Chih-Chun Hsu, Nikita Kamraj, Rocio Kiman, Jon Rees, Christopher Theissen, Kareem Ammar, Nikolaj Stevnbak Andersen, Paul Beaulieu, Guillaume Colin, Charles A. Elachi, Samuel J. Goodman, Leopold Gramaize, Leslie K. Hamlet, Justin Hong, Alexander Jonkeren, Mohammed Khalil, David W. Martin, William Pendrill, Benjamin Pumphrey, Austin Rothermich, Arttu Sainio, Andres Stenner, Christopher Tanner, Melina Thevenot, Nikita V. Voloshin, Jim Walla, Zbigniew Wedracki, “The Field Substellar Mass Function Based on the Full-sky 20-pc Census of 525 L, T, and Y Dwarfs”, ArXiv, pp. 1-101, 2021. https://arxiv.org/abs/2011.11616
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