Mice Treated with This Cytokine Lose Weight by ‘Sweating’ Fat (Medicine)

A seemingly unremarkable observation — greasy hair — showed Penn researchers how the immune system could be targeted to reverse obesity

Treating obese mice with the cytokine known as TSLP led to significant abdominal fat and weight loss compared to controls, according to new research published Thursday in Science from researchers in the Perelman School of Medicine at the University of Pennsylvania. Unexpectedly, the fat loss was notassociated with decreased food intake or faster metabolism. Instead, the researchers discovered that TSLP stimulated the immune system to release lipids through the skin’s oil-producing sebaceous glands.

“This was a completely unforeseen finding, but we’ve demonstrated that fat loss can be achieved by secreting calories from the skin in the form of energy-rich sebum,” said principal investigator Taku Kambayashi, MD, PhD,an associate professor of Pathology and Laboratory Medicine at Penn, who led the study with fourth-year medical student Ruth Choa, PhD. “We believe that we are the first group to show a non-hormonal way to induce this process, highlighting an unexpected role for the body’s immune system.”

The animal model findings, Kambayashi said, support the possibility that increasing sebum production via the immune system could be a strategy for treating obesity in people.

The Hypothesis

Thymic stromal lymphopoietin (TSLP) is a cytokine — a type of immune system protein —  involved in asthma and other allergic diseases. The Kambayashi research group has been investigating the expanded role of this cytokine to activate Type 2 immune cells and expand T regulatory cells. Since past studies have indicated that these cells can regulate energy metabolism, the researchers predicted that treating overweight mice with TSLP could stimulate an immune response, which could subsequently counteract some of the harmful effects of obesity.

“Initially, we did not think TSLP would have any effect on obesity itself. What we wanted to find out was whether it could impact insulin resistance,” Kambayashi said. “We thought that the cytokine could correct Type 2 diabetes, without actually causing the mice to lose any weight.”

The Experiment

To test the effect of TSLP on Type 2 diabetes, the researchers injected obese mice with a viral vector that would increase their bodies’ TSLP levels. After four weeks, the research team found that TSLP had not only affected their diabetes risk, but it had actually reversed the obesity in the mice, which were fed a high-fat diet. While the control group continued to gain weight, the weight of the TSLP-treated mice went from 45 grams down to a healthy 25 grams, on average, in just 28 days.

Most strikingly, the TSLP-treated mice also decreased their visceral fat mass. Visceral fat is the white fat that is stored in the abdomen around major organs, which can increase diabetes, heart disease, and stroke risk. These mice also experienced improved blood glucose and fasting insulin levels, as well as decreased risk of fatty liver disease.

Given the dramatic results, Kambayashi assumed that the TSLP was sickening the mice and reducing their appetites. However, after further testing, his group found that the TSLP-treated mice were actually eating 20 to 30 percent more, had similar energy expenditures, base metabolic rates, and activity levels, when compared to their non-treated counterparts.

The Findings

To explain the weight loss, Kambayashi recalled a small observation he had previously ignored: “When I looked at the coats of the TSLP-treated mice, I noticed that they glistened in the light. I always knew exactly which mice had been treated, because they were so much shinier than the others,” he said.

Kambayashi considered a far-fetched idea — was their greasy hair a sign that the mice were “sweating” out fat from their skin?

To test the theory, the researchers shaved the TSLP-treated mice and the controls and then extracted oils from their fur. They found that Kambayashi’s hypothesis was correct: The shiny fur contained sebum-specific lipids. Sebum is a calorically-dense substance produced by sebocytes (highly specialized epithelial cells) in the sebaceous glands and helps to form the skin barrier. This confirmed that the release of oil through the skin was responsible for the TSLP-induced fat loss.

The Conclusions

To examine whether TSLP could potentially play a role in the control of oil secretion in humans, the researchers then examined TSLPand a panel of 18 sebaceous gland-associated genes in a publicly-available dataset. This revealed that TSLPexpression is significantly and positively correlated with sebaceous gland gene expression in healthy human skin.

The study authors write that, in humans, shifting sebum release into “high gear” could feasibly lead to the “sweating of fat” and weight loss. Kambayashi’s group plans further study to test this hypothesis.

“I don’t think we naturally control our weight by regulating sebum production, but we may be able to highjack the process and increase sebum production to cause fat loss. This could lead to novel therapeutic interventions that reverse obesity and lipid disorders,” Kambayashi said.

This research was supported by grants from the National Institutes of Health (R01-HL111501, R01-10 AI121250, R01-AR070116, T32-HL07439), the Doris Duke Charitable Foundation, and the University of Pennsylvania Medical Scientist Training Program.

Penn researchers who contributed to this work include: Junichiro Tohyama, Shogo Wada, Hu Meng, Jian Hu, Mariko Okumura, Tanner F. Robertson, Ruth-Anne Langan Pai, Arben Nace, Christian Hopkins, Elizabeth A. Jacobsen, Malay Haldar, Garret A. FitzGerald, Edward M. Behrens, Andy J. Minn, Patrick Seale, George Cotsarelis, Brian Kim, John T. Seykora, Mingyao Li, and Zoltan Arany.

Reference: Thymic stromal lymphopoietin induces adipose loss through sebum hypersecretion, Science (2021). DOI: 10.1126/science.abd2893

Provided by Perelman School of Medicine at the University of Pennsylvania

Scientists Discover A Surprising New Way That Tuberculosis Suppresses Immunity (Medicine)

When Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, infects a person, the body’s immune response is critical to how the disease will progress—either helping the body fight the bacterium or exacerbating the infection.

University of Maryland researchers discovered a way that Mtb can cause a person’s immune cells to lower their defenses. Specifically, they identified a gene in the bacterium that suppresses immune defenses in infected human cells, which could exacerbate the infection.

This new finding may point to an effective target for a gene-based treatment or preventative therapy for tuberculosis, which sickens about 10 million people and kills 1-2 million people annually according to the World Health Organization. Available treatments are only 85% effective and multidrug-resistant forms of tuberculosis pose a public health threat in many parts of the world. The study was published on July 29, 2021, in the journal PLOS Pathogens.

“In order to develop novel therapeutic targets, an understanding of the molecular mechanisms of how bacterial proteins interact with human cells is essential,” said Volker Briken, a professor of cell biology and molecular genetics at UMD and the senior author of the study. “This is exciting that we have discovered an interaction that has never been observed before between the bacteria that causes tuberculosis and a signaling system in human cells that is important in the cell’s defense against pathogens.”

Briken and his team, which was led by postdoctoral fellow and lead author of the study Shivangi Rastogi, made their discovery by infecting a type of white blood cell called a macrophage with either Mtb—the bacterium that causes tuberculosis—or a non-virulent bacterium and observing the cell’s response. The researchers found that a complex of proteins called the inflammasome was dramatically limited in cells infected with Mtb, but not in those infected with the non-virulent bacteria. The inflammasome surveys a cell’s interior for pathogens and then signals the cell to launch an immune response.

“It was very unexpected for us to find this primary observation that Mtb can actually inhibit the inflammasome,” Briken said. “The infection also causes some minor activation of the inflammasome, and so no one bothered to look for a potential of Mtb to inhibit the process. It is a classic example of the tug of war between the pathogen wanting to suppress host immunity and the host cell sensing the pathogen to activate immune responses.”

Next, the team wanted to know if a specific Mtb gene was responsible for suppressing the inflammasome. The researchers inserted genes of Mtb into a non-virulent mycobacterium species and used these mutants to infect new macrophages. They discovered that infections with non-virulent bacteria carrying the Mtb gene named PknF limited the inflammasome response in host cells.

“We don’t know how this gene inhibits the inflammasome,” Briken said, “but the function of this gene is to regulate the production and/or secretions of lipids, so we think maybe the bacterium modifies lipid secretion in a way that influences the inflammasome. That is what we will be investigating in future studies.”

How PknF suppresses the inflammasome of host cells is just one of the questions Briken would like to answer. He and his team are also working to determine PknF’s role in the virulence of the disease. If it turns out that suppressing the inflammasome allows Mtb to be more virulent, then the PknF gene could become a good target for future drug therapies to treat the disease.

The research paper, “Mycobacterium tuberculosis inhibits the NLRP3 inflammasome activation via its phosphokinase PknF,” Shivangi Rastogi, Sarah Ellinwood, Jacques Augenstreich, Katrin D. Mayer-Barber and Volker Briken, was published on July 29, 2021, in of PLOS Pathogens.

Illustration Credit: Tatiana Shepeleva / Shutterstock

Provided by University of Maryland

Mechanism That Triggers Brain Neurone Response Revealed (Neuroscience)

It is the first time it has been possible to see how neurotransmitters and proteins interact at the atomic level to trigger neuronal responses.

Researchers from the G-protein-coupled receptor-based drug development research group at the Hospital del Mar Medical Research Institute (IMIM) have been able to verify, with a degree of precision never before achieved, how the process that triggers the response of neurones in the brain occurs. This is an essential mechanism for understanding how moods or even processes such as addictions are produced, and in which neurotransmitters, molecules that help transmit information between neurones through specialised receptors, the G protein-coupled receptors (GPCRs), play a vital role.

Neurotransmission is one of the most crucial physiological processes, as its dysregulation can result in various neuropsychiatric disorders”, explains Dr. Jana Selent, principal author of the study, published in the journal Chemical Science, and coordinator of the research group that led the work. Very small changes in how information is transmitted by these molecules can trigger different reactions in the brain, some of which are linked to behaviour, addictions and moods.

Jana Selent and Tomasz Stepniewski © IMIM

Possible new treatments for psychiatric illnesses

Researchers have analysed how neurotransmitters connect to proteins in the cell membrane of neurones at the atomic level. They were able to determine which connections between the neurotransmitter and its receptor protein control how the cell will respond. They observed that evolution has naturally caused small changes in the regions where these connections occur, giving rise to different proteins capable of generating different cellular responses. This allows our body to regulate, in a very precise way, the response that the same neurotransmitter causes in the neurone and in the brain. With this information, the authors of the study were able to predict what would happen on each occasion by studying different types of proteins and modified neurotransmitters, checking their conclusions with cell experiments conducted in laboratories in Sweden and Canada.

In this way, the researchers were able to relate the small differences that receptors in these important regions may have to the neuronal response they generate when interacting with the same neurotransmitter. It also shows how modified neurotransmitters can control which regions of the protein they can bind to, to be able to cause a different neuronal response. This makes it possible to “design molecules that only bind to certain regions of the receptor and to specific types of receptors, which may allow the neuronal response to be changed”, explains Dr Tomasz Stepniewski, first author of the study. This possibility is “particularly interesting in neuropsychiatric diseases like schizophrenia, certain addictions, and behavioural patterns, such as those that regulate appetite or mood”, he adds. The signalling pathways involved in each process must now be studied in order to develop the treatments, the molecules, for addressing these pathologies.

Reference article

Stepniewski TMMancini A, Agren R, Torrens-Fontanals M, M Semache, Bouvier M, Sahlholm K, Breton BSelent J. Mechanistic insights into dopaminergic and serotonergic neurotransmission-concerted interactions with helices 5 and 6 drive the functional outcome. Chem Sci, 2021 DOI: 10.1039/D1SC00749A.

Provided by IMIM

Researchers Synthesized Biological Compound Which Kill Cancer Cells Without Harming The Heart (Medicine)

With modern-day cancer therapeutics presenting adverse side effects to heart health, scientists are studying methods to attack cancer cells without the risk of damaging the heart. Researchers Steven Townsend, associate professor of chemistry, and Neil Osheroff, John Coniglio Professor of Biochemistry and professor of medicine, synthesized the biological compound arimetamycin A, shown to kill cancer cells in mice without harming the heart.

Natural isolated products from soil bacteria known as anthracyclines are currently being used as cancer therapeutics.  Chosen because of their inexpensive cost and high level of toxicity to tumors, specific anthracyclines, including doxorubicin and daunorubicin, also attack the heart in the process of killing cancer. To synthesize arimetamycin A, Townsend and his team modified the carbohydrate, or sugar, portions of anthracyclines and then fine-tuned their activity, increasing toxicity levels toward cancer cells while decreasing the adverse effects on the heart. The synthesis and promising results could lead to less harmful cancer drug discovery.

“One molecule [of doxorubicin] kills 10 cancer cells. Our improvement to the drug can kill 1,000,” Townsend said.

According to Townsend, in a clinical setting medical doctors play a delicate game when prescribing medication to kill cancer. They aim to prescribe enough to kill the cancer but not in an amount that could potentially harm the heart. With the synthesis of less cardiotoxic drugs, the future of healthier cancer therapeutics advances forward.

For decades, researchers have struggled with the improvement of drugs due to a lack of technology and resources. The difference between then and Townsend and Osheroff’s current discovery lies in access to molecular modeling, cellular-level imaging techniques and a deeper understanding of how these drugs work.

Chemists continue to build upon not only new discoveries but also standstills from previous research endeavors that advance our understanding of cancer therapeutics. “In 2021, we have a much better idea of exactly how these [drugs] slide and bind to DNA compared to previous decades. With that enhanced understanding, we know how to modify the drugs to fine-tune their activity,” Townsend said. “If you look at most famous chemists now, they are excellent at going back to the literature to see what ideas people had then that they couldn’t figure out. Modern skillsets, tools and better technology help us do this in a more designed way.”

Even though the research team validated that arimetamycin A is more cytotoxic than current cancer therapeutics, Townsend aims to further increase the drug’s toxicity levels while decreasing cardiotoxicity. Another avenue for new research will involve attaching the new anthracyclines (known as a payload) to an antibody, to study targeted delivery of the drug to tumors. These antibody-drug conjugates allow increased drug levels at the tumor site while avoiding cardiotoxicity completely.

Reference: Eric D. Huseman et al, Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids, ACS Central Science (2021). DOI: 10.1021/acscentsci.1c00040

Provided by Vanderbilt University

New Zealand is Best Placed To Survive Collapse (Amazing Places)

Study: UK also has favourable starting conditions to weather major global shock

New research has examined the factors that could lead to the collapse of global civilisation, with New Zealand identified as the country most resilient to future threats.

The study, carried out by Nick King and Professor Aled Jones of the Global Sustainability Institute at Anglia Ruskin University (ARU), focuses on “de-complexification” – a widespread reversal of the trends of recent civilisation, potentially seeing the collapse of supply chains, international agreements and global financial structures.

Published in the journal Sustainability, the study explains how a combination of ecological destruction, limited resources, and population growth could trigger a reduction in the overall complexity of civilisation, with climate change serving as a “risk multiplier”, exacerbating existing trends. 

This could happen during a “long descent”, over years or decades, or very rapidly, in the space of less than a year, with no warning of the coming disruption.  The academics suggest that a hybrid of these might also occur, with a gradual initiation which then gains momentum through “feedback loops”, leading to an abrupt collapse. The effects could spread quickly due to the increasing hyper-connectivity and interdependency of the globalised economy.

The study identified five countries with the most favourable starting conditions to survive a global collapse by examining self-sufficiency (energy and manufacturing infrastructure), carrying capacity (land available for arable farming and overall population) and isolation (distance from other large population centres which may be subject to displacement events).

It found that New Zealand – along with Iceland, the United Kingdom, Australia (specifically Tasmania) and Ireland – were the nations currently most suited to maintaining higher levels of societal, technological, and organisational complexity within their own borders if a global collapse were to happen.

All five are islands or island continents, with strong oceanic climatic influence. They currently have low temperature and precipitation variability and therefore have the greatest likelihood of relatively stable conditions continuing despite the effects of climate change.

New Zealand, Iceland, the UK, Australia (Tasmania) and Ireland were then qualitatively assessed for their individual, local-scale energy and agricultural characteristics. This identified New Zealand as having the greatest potential to survive relatively unscathed thanks to its ability to produce geothermal and hydroelectric energy, its abundant agricultural land, and its low population.

Iceland, Australia (Tasmania) and Ireland also have favourable characteristics, while the UK presents a more complex picture due to its complicated energy mix and high population density. Although the UK has generally fertile soils and varied agricultural output, it has low per capita availability of agricultural land, raising questions about future self-sufficiency.

Professor Aled Jones, Director of the Global Sustainability Institute at Anglia Ruskin University (ARU), said:“Significant changes are possible in the coming years and decades.  The impact of climate change, including increased frequency and intensity of drought and flooding, extreme temperatures, and greater population movement, could dictate the severity of these changes.

“As well as demonstrating which countries we believe are best suited to managing such a collapse – which undoubtedly would be a profound, life-altering experience – our study aims to highlight actions to address the interlinked factors of climate change, agricultural capacity, domestic energy, manufacturing capacity, and the over-reliance on complexity, are necessary to improve the resilience of nations that do not have the most favourable starting conditions.”

Reference: Nick King et al, An Analysis of the Potential for the Formation of ‘Nodes of Persisting Complexity’, Sustainability (2021). DOI: 10.3390/su13158161

Provided by Anglia Ruskin University

How ERF1 Regulates Flowering? (Botany)

Floral initiation must be strictly regulated to achieve reproductive success. ETHYLENE RESPONSE FACTOR1 (ERF1) functions as an important integrator of several phytohormone signals to regulate both development and stress responses. However, the underlying mechanism for its role in flowering-time regulation remained unclear. 

In a study published in Journal of Integrative Plant Biology, researchers from the Xishuangbanna Tropical Botanical Garden of the Chinese Academy of Sciences demonstrated that ERF1 played an important role in floral initiation by directly modulating the expression of FLOWERING LOCUS T (FT), a major integrator of inductive flowering pathways. 

The researchers first sought to investigate whether ERF1 also participated in flowering-time regulation. By analyzing flowering time in ERF1 knockdown and overexpression lines, they found that regulation of flowering time in Arabidopsis was closely correlated with ERF1 expression. Consistent with expression of ERF1 being induced by 1-aminocyclopropane-1-carboxylic acid, ERF1 contributed to ethylene-induced late flowering. ERF1 participated in flowering-time regulation under both normal and stressed conditions. 

To understand how ERF1 mediated flowering-time control, the researchers next compared the expression patterns of diverse flowering-related genes among ERF1 RNAi, wild type and expression of ERF1 (ERF1ox) plants. 

They revealed that an ethylene-induced delay in flowering may also be achieved through negative regulation of FT expression by ERF1. The ERF1 acted upstream of FT and negatively regulated floral initiation in a largely FT-dependent manner. ERF1 was also involved in modulation of ethylene-induced late flowering.  

“The molecular mechanisms revealed in this study may help us understand the sophisticated flowering-time regulatory networks controlled by ethylene response factors,” said CHEN Ligang, correspondence author of the study. 

Featured image: Loss of ERF1 function accelerates floral initiation. (Image by CHEN Yanli)

Reference: Chen, Y., Zhang, L., Zhang, H., Chen, L. and Yu, D. (2021), ERF1 delays flowering through direct inhibition of FLOWERING LOCUS T expression in Arabidopsis. J Integr Plant Biol. Accepted Author Manuscript. https://doi.org/10.1111/jipb.13144

Provided by Chinese Academy of Sciences

Collisions of Light Produce Matter/Antimatter from Pure Energy (Physics)

Study demonstrates a long-predicted process for generating matter directly from light — plus evidence that magnetism can bend polarized photons along different paths in a vacuum

Scientists studying particle collisions at the Relativistic Heavy Ion Collider (RHIC)—a U.S. Department of Energy Office of Science user facility for nuclear physics research at DOE’s Brookhaven National Laboratory—have produced definitive evidence for two physics phenomena predicted more than 80 years ago. The results were derived from a detailed analysis of more than 6,000 pairs of electrons and positrons produced in glancing particle collisions at RHIC and are published in Physical Review Letters

The primary finding is that pairs of electrons and positrons—particles of matter and antimatter—can be created directly by colliding very energetic photons, which are quantum “packets” of light. This conversion of energetic light into matter is a direct consequence of Einstein’s famous E=mc2 equation, which states that energy and matter (or mass) are interchangeable. Nuclear reactions in the sun and at nuclear power plants regularly convert matter into energy. Now scientists have converted light energy directly into matter in a single step.

The second result shows that the path of light traveling through a magnetic field in a vacuum bends differently depending on how that light is polarized. Such polarization-dependent deflection (known as birefringence) occurs when light travels through certain materials. (This effect is similar to the way wavelength-dependent deflection splits white light into rainbows.) But this is the first demonstration of polarization-dependent light-bending in a vacuum.

Both results depend on the ability of RHIC’s STAR detector—the Solenoid Tracker at RHIC—to measure the angular distribution of particles produced in glancing collisions of gold ions moving at nearly the speed of light.

Colliding clouds of photons 

Photo of STAR detector at the Relativistic Heavy Ion Collider
The STAR detector at the Relativistic Heavy Ion Collider measured the angular distribution of particles produced in glancing collisions of gold ions moving at nearly the speed of light to provide evidence for two physics phenomena predicted more than 80 years ago. © BNL

Such capabilities didn’t exist when physicists Gregory Breit and John A. Wheeler first described the hypothetical possibility of colliding light particles to create pairs of electrons and their antimatter counterparts, known as positrons, in 1934.  

“In their paper, Breit and Wheeler already realized this is almost impossible to do,” said Brookhaven Lab physicist Zhangbu Xu, a member of RHIC’s STAR Collaboration. “Lasers didn’t even exist yet! But Breit and Wheeler proposed an alternative: accelerating heavy ions. And their alternative is exactly what we are doing at RHIC.” 

An ion is essentially a naked atom, stripped of its electrons. A gold ion, with 79 protons, carries a powerful positive charge. Accelerating such a charged heavy ion to very high speeds generates a powerful magnetic field that spirals around the speeding particle as it travels—like current flowing through a wire.  

“If the speed is high enough, the strength of the circular magnetic field can be equal to the strength of the perpendicular electric field,” Xu said. And that arrangement of perpendicular electric and magnetic fields of equal strength is exactly what a photon is—a quantized “particle” of light. “So, when the ions are moving close to the speed of light, there are a bunch of photons surrounding the gold nucleus, traveling with it like a cloud.”  

At RHIC, scientists accelerate gold ions to 99.995% of the speed of light in two accelerator rings. 

“We have two clouds of photons moving in opposite directions with enough energy and intensity that when the two ions graze past each other without colliding, those photon fields can interact,” Xu said.  

Photo of Daniel Brandenburg presentingat the Quark Matter 2019 conference
Daniel Brandenburg, a Goldhaber Fellow at Brookhaven Lab, presented the STAR results related to this discovery at the Quark Matter 2019 conference. © BNL

STAR physicists tracked the interactions and looked for the predicted electron-positron pairs.  

But such particle pairs can be created by a range of processes at RHIC, including through “virtual” photons, a state of photon that exists briefly and carries an effective mass. To be sure the matter-antimatter pairs were coming from real photons, scientists have to demonstrate that the contribution of “virtual” photons does not change the outcome of the experiment.  

To do that, the STAR scientists analyzed the angular distribution patterns of each electron relative to its partner positron. These patterns differ for pairs produced by real photon interactions versus virtual photons. 

“We also measured all the energy, mass distributions, and quantum numbers of the systems. They are consistent with theory calculations for what would happen with real photons,” said Daniel Brandenburg, a Goldhaber Fellow at Brookhaven Lab, who analyzed the STAR data on this discovery.   

Other scientists have tried to create electron-positron pairs from collisions of light using powerful lasers—focused beams of intense light. But the individual photons within those intense beams don’t have enough energy yet, Brandenburg said.  

One experiment at the SLAC National Accelerator Laboratory in 1997 succeeded by using a nonlinear process. Scientists there first had to boost the energy of the photons in one laser beam by colliding it with a powerful electron beam. Collisions of the boosted photons with multiple photons simultaneously in an enormous electromagnetic field created by another laser produced matter and antimatter. 

“Our results provide clear evidence of direct, one-step creation of matter-antimatter pairs from collisions of light as originally predicted by Breit and Wheeler,” Brandenburg said. “Thanks to RHIC’s high-energy heavy ion beam and the STAR detector’s large acceptance and precision measurements, we are able to analyze all the kinematic distributions with high statistics to determine that the experimental results are indeed consistent with real photon collisions.” 

Bending light in a vacuum 

STAR’s ability to measure the tiny deflections of electrons and positrons produced almost back-to-back in these events also gave the physicists a way to study how light particles interact with the powerful magnetic fields generated by the accelerated ions.  

“The cloud of photons surrounding the gold ions in one of RHIC’s beams is shooting into the strong circular magnetic field produced by the accelerated ions in the other gold beam,” said Chi Yang, a long-time STAR collaborator from Shandong University who spent his entire career studying electron-positron pairs produced from various processes at RHIC. “Looking at the distribution of particles that come out tells us how polarized light interacts with the magnetic field.” 

Bending polarized light: This illustration shows how light with different polarization directions (indicated by black arrows) passes through a material along two different paths (yellow beams). This is called the birefringence effect. Results from RHIC provide evidence that birefringence also happens in a magnetic field in a vacuum. © BNL

Werner Heisenberg and Hans Heinrich Euler in 1936, and John Toll in the 1950s, predicted that a vacuum of empty space could be polarized by a powerful magnetic field and that such a polarized vacuum should deflect the paths of photons depending on photon polarization. Toll, in his thesis, also detailed how light absorption by a magnetic field depends on polarization and its connection to the refractive index of light in a vacuum. This polarization-dependent deflection, or birefringence, has been observed in many types of crystals. There was also a recent report of the light coming from a neutron star bending this way, presumably because of its interactions with the star’s magnetic field. But no Earth-based experiment has detected birefringence in a vacuum

At RHIC, the scientists measured how the polarization of the light affected whether the light was “absorbed” by the magnetic field.  

This is similar to the way polarized sunglasses block certain rays from passing through if they don’t match the polarization of the lenses, Yang explained. In the case of the sunglasses, in addition to seeing less light get through, you could, in principle, measure an increase in the temperature of the lens material as it absorbs the energy of the blocked light. At RHIC, the absorbed light energy is what creates the electron-positron pairs. 

“When we look at the products produced by photon-photon interactions at RHIC, we see that the angular distribution of the products depends on the angle of the polarization of the light. This indicates that the absorption (or passing) of light depends on its polarization,” Yang said.  

This is the first Earth-based experimental observation that polarization affects the interactions of light with the magnetic field in the vacuum—the vacuum birefringence predicted in 1936. 

“Both of these findings build on predictions made by some of the great physicists in the early 20th century,” said Frank Geurts, a professor at Rice University, whose team built and operated the state-of-the-art “Time-of-Flight” detector components of STAR that were necessary for this measurement. “They are based on fundamental measurements made possible only recently with the technologies and analysis techniques we have developed at RHIC.” 

Additional contributors to the analyses that led to these results include STAR co-spokesperson Lijuan Ruan of Brookhaven, Shuai Yang of Rice University, Janet Seger of Creighton University, and Wangmei Zha of the University of Science and Technology of China. The scientists made use of computational resources at Brookhaven’s Scientific Data and Computing Center, the National Energy Research Scientific Computing Center (NERSC) at DOE’s Lawrence Berkeley National Laboratory, and the Open Science Grid consortium. 

Brookhaven Lab’s role in the work and operations at RHIC are supported by the DOE Office of Science (NP). Additional funders include the U.S. National Science Foundation and a range of international agencies listed in the published paper. 

Featured image: Making matter from light: Two gold (Au) ions (red) move in opposite direction at 99.995% of the speed of light (v, for velocity, = approximately c, the speed of light). As the ions pass one another without colliding, two photons (γ) from the electromagnetic cloud surrounding the ions can interact with each other to create a matter-antimatter pair: an electron (e) and positron (e+). © BNL

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Scientists Discover New Regulators Of The Aging Process (Biology)

The attachment of the small protein ubiquitin to other proteins (ubiquitination) regulates numerous biological processes, including signal transduction and metabolism / Scientists at the University of Cologne discover the link to aging and longevity / Publication in ‘Nature’.

Scientists have discovered that the protein ubiquitin plays an important role in the regulation of the aging process. Ubiquitin was previously known to control numerous processes, such as signal transduction and metabolism. Prof. Dr. David Vilchez and his colleagues at the CECAD Cluster of Excellence for Aging Research at the University of Cologne performed a comprehensive quantitative analysis of ubiquitin signatures during aging in the model organism Caenorhabditis elegans, a nematode worm which is broadly used for aging research. This method – called ubiquitin proteomics – measures all changes in ubiquitination of proteins in the cell. The resulting data provide site-specific information and define quantitative changes in ubiquitin changes across all proteins in a cell during aging. A comparison with the total protein content of a cell (proteome) showed which changes have functional consequences in protein turnover and actual protein content during aging. The scientists thus discovered new regulators of lifespan and provide a comprehensive data set that helps to understand aging and longevity. The article, ‘Rewiring of the ubiquitinated proteome determines aging in C. elegans,‘ has now been published in Nature.

‘Our study of ubiquitin changes led us to a number of exciting conclusions with important insights for understanding the aging process,” said Dr Seda Koyuncu, lead author of the study. “We discovered that aging leads to changes in the ubiquitination of thousands of proteins in the cell, whereas longevity measures such as reduced food intake and reduced insulin signaling prevent these changes.’ Specifically, the researchers found that aging causes a general loss of ubiquitination. This is caused by the enzymes that remove ubiquitin from proteins become more active during aging. Normally, ubiquitinated proteins are recognized and destroyed by the proteasome, the cell’s garbage truck. The scientists showed that the longevity of organisms is determined by age-related changes in the degradation of structural and regulatory proteins by the proteasome. “We studied animals with a defective proteasome to identify proteins that become less ubiquitinated with age and thus are not cleaned up by the proteasome and accumulate in the cell. The resulting protein accumulation leads to cell death,” Koyuncu says. “Remarkably, we saw that reducing the protein levels of these untagged proteins was sufficient to prolong longevity, while preventing their degradation by the proteasome shortened lifespan.”

In addition to providing a comprehensive data set, the investigators showed that defining changes in the ubiquitin-modified proteome can lead to the discovery of new regulators of lifespan and aging traits. They focused their follow-up analyses on two specific proteins that lacked ubiquitin labeling during aging. IFB-2, a protein important for cell structure, and EPS-8, a modulator of a signaling pathway that regulates a variety of cellular processes. These proteins, which are no longer adequately labeled in aged organisms, affect longevity in a variety of tissues. Increased protein levels of IFB-2, for example, cause the intestine to fail to digest properly or absorb nutrients and also make it more susceptible to bacterial infections, which is a characteristic of aging animals. “Remarkably, knockdown of IFB-2 in adult C. elegans was enough to restore normal gut function,” Koyuncu says. Too much amounts of EPS-8 in cells over activate a specific signaling pathway (RAC) in muscle and brain cells. The team discovered here that the RAC signaling pathway determines longevity, muscle integrity and motility.

“Our findings may point to new ways to delay the aging process and improve quality of life in old age. In particular, we have established a novel link between aging and general changes in the ubiquitin-modified proteome, a process that actively influences longevity,” said study coordinator David Vilchez, research group leader at CECAD and the Center for Molecular Medicine Cologne (CMMC). “Our results and rich datasets may have important implications for several research priorities, including aging, ubiquitination and other cellular processes.”

Featured image: Left: Muscle actin cytoskeleton in young animals. Middle: Muscle actin cytoskeleton in old animals with destabilization of muscle cytoskeleton due to aging Right: Prevention of destabilization of muscle cytoskeleton in old animals by lowering the age-dysregulated high levels of EPS-8, a regulator of actin cytoskeleton. © David Vilchez

Koyuncu S, Loureiro R, Lee HJ, Wagle P, Krueger M, Vilchez D. Rewiring of the ubiquitinated proteome determines ageing in C. elegans. Nature 2021

Provided by University of Cologne

ATLAS Reports First Observation of WWW Production (Physics)

The ATLAS collaboration announces the first observation of WWW production: the simultaneous creation of three massive W bosons in high-energy LHC collisions.

Today, at the EPS-HEP Conference 2021, the ATLAS collaboration announced the first observation of a rare process: the simultaneous production of three W bosons.

As a carrier of the electroweak force, the W boson plays a crucial role in testing the Standard Model of particle physics. Though discovered nearly four decades ago, the W boson continues to provide physicists with new avenues for exploration.

ATLAS researchers analysed the full LHC Run-2 dataset, recorded by the detector between 2015 and 2018, to observe the WWW process with a statistical significance of 8.2 standard deviations – well above the 5 standard-deviation threshold needed to declare observation. This result follows an earlier observation by the CMS collaboration of inclusive three weak boson production.

Achieving this level of precision was no mean feat. Physicists analysed around 20 billion collision events recorded and pre-filtered by the ATLAS experiment in their search for just a few hundred events expected from the WWW process.

As one of the heaviest known elementary particles, the W boson is able to decay in several different ways. The ATLAS physicists focused their search on the four WWW decay modes that have the best discovery potential due to their reduced number of background events. In three of these modes, two W bosons decay into charged leptons(electrons or muons), carrying the same positive or negative charge, and neutrinos, while the third W boson decays into a pair of light quarks. In the fourth decay mode, all three W bosons decay into a charged lepton and a neutrino.

To pick out the WWW signal from the large number of background events, researchers used a machine-learning technique called Boosted Decision Trees (BDTs). BDTs can be trained to identify specific signals in the ATLAS detector, spotting small – but key – differences between the predicted event properties. The improved separation between signal and background provided by the BDTs – along with the massive dataset provided by Run 2 of the LHC – enhanced the precision of the overall measurement and enabled the first observation of WWW production.

This exciting measurement also allows physicists to look for hints of new interactions that might exist beyond the current energy reach of the LHC. In particular, physicists can use the WWW production process to study the quartic gauge boson coupling – where two W bosons scatter off each other – a key property of the Standard Model.New particles could alter the quartic gauge boson coupling through quantum effects, modifying the WWW production cross section. The continued study of WWW and other electroweak processes offers an enticing road ahead.

Featured image: Display of a candidate WWW→ 3 leptons + neutrinos event. The event is identified by its decay to a muon (red line), two electrons (blue lines) and missing transverse energy (white dashed line). (Image: CERN)


Provided by CERN