Culture

Correction 6/18/21: The original version of this article stated that polymerase theta was the first mammalian polymerase with the ability to transcribe RNA into DNA. In fact, other polymerases have been shown to perform this function, albeit with much lower efficiency than HIV reverse transcriptase. The article has been corrected and we regret the error.

PHILADELPHIA – Cells contain machinery that duplicates DNA into a new set that goes into a newly formed cell. That same class of machines, called polymerases, also build RNA messages, which are like notes copied from the central DNA repository of recipes, so they can be read more efficiently into proteins. But polymerases were thought to only work in one direction DNA into DNA or RNA. This prevents RNA messages from being rewritten back into the master recipe book of genomic DNA. Now, Thomas Jefferson University researchers provide evidence that RNA segments can be written back into DNA via a polymerase called theta, which could have wide implications affecting many fields of biology.

“This work opens the door to many other studies that will help us understand the significance of polymerases that can write RNA messages into DNA,” says Richard Pomerantz, PhD, associate professor of biochemistry and molecular biology at Thomas Jefferson University. “That polymerase theta can do this with high efficiency, raises many questions.” For example, this finding suggests that RNA messages can be used as templates for repairing or re-writing genomic DNA.

The work was published June 11th in the journal Science Advances.

Together with first author Gurushankar Chandramouly and other collaborators, Dr. Pomerantz’s team started by investigating one very unusual polymerase, called polymerase theta. Of the 14 DNA polymerases in mammalian cells, only three do the bulk of the work of duplicating the entire genome to prepare for cell division. The remaining 11 are mostly involved in detecting and making repairs when there’s a break or error in the DNA strands. Polymerase theta repairs DNA, but is very error-prone and makes many errors or mutations.

The researchers therefore noticed that some of polymerase theta’s “bad” qualities were ones it shared with another cellular machine, albeit one more common in viruses -- the reverse transcriptase. Like Pol theta, HIV reverse transcriptase acts as a DNA polymerase, but can also bind RNA and write RNA back into a DNA strand.

In a series of elegant experiments, the researchers tested polymerase theta against the reverse transcriptase from HIV, which is one of the best studied of its kind. They showed that polymerase theta was capable of converting RNA messages into DNA, which it did as well as HIV reverse transcriptase, and that it actually did a better job than when duplicating DNA to DNA. Polymerase theta was more efficient and introduced fewer errors when using an RNA template to write new DNA messages, than when duplicating DNA into DNA, suggesting that this function could be its primary purpose in the cell.

The group collaborated with Dr. Xiaojiang S. Chen’s lab at USC and used x-ray crystallography to define the structure and found that this molecule was able to change shape in order to accommodate the more bulky RNA molecule – a feat unique among polymerases.

“Our research suggests that polymerase theta’s main function is to act as a reverse transcriptase,” says Dr. Pomerantz. “In healthy cells, the purpose of this molecule may be toward RNA-mediated DNA repair. In unhealthy cells, such as cancer cells, polymerase theta is highly expressed and promotes cancer cell growth and drug resistance. It will be exciting to further understand how polymerase theta’s activity on RNA contributes to DNA repair and cancer-cell proliferation.”

BOSTON - Vitamin D deficiency strongly exaggerates the craving for and effects of opioids, potentially increasing the risk for dependence and addiction, according to a new study led by researchers at Massachusetts General Hospital (MGH). These findings, published in Science Advances, suggest that addressing the common problem of vitamin D deficiency with inexpensive supplements could play a part in combating the ongoing scourge of opioid addiction.

Earlier work by David E. Fisher, MD, PhD, director of the Mass General Cancer Center's Melanoma Program and director of MGH's Cutaneous Biology Research Center (CBRC), laid the foundation for the current study. In 2007, Fisher and his team found something unexpected: Exposure to ultraviolet (UV) rays (specifically the form called UVB), causes the skin to produce the hormone endorphin, which is chemically related to morphine, heroin and other opioids--in fact, all activate the same receptors in the brain. A subsequent study by Fisher found that UV exposure raises endorphin levels in mice, which then display behavior consistent with opioid addiction.

Endorphin is sometimes called a "feel good" hormone because it induces a sense of mild euphoria. Studies have suggested that some people develop urges to sunbathe and visit tanning salons that mirror the behaviors of opioid addicts. Fisher and his colleagues speculated that people may seek out UVB because they unknowingly crave the endorphin rush. But that suggests a major contradiction. "Why would we evolve to be behaviorally drawn towards the most common carcinogen that exists?" asked Fisher. After all, sun exposure is the primary cause of skin cancer, to say nothing of wrinkles and other skin damage.

Fisher believes that the only explanation for why humans and other animals seek out the sun is that exposure to UV radiation is necessary for production of vitamin D, which our bodies can't formulate on their own. Vitamin D promotes uptake of calcium, which is essential for building bone. As tribes of humans migrated north during prehistoric times, an evolutionary alteration might have been needed to compel them to step out of caves and into the sunshine on bitterly cold days. Otherwise, small children would have died of prolonged vitamin D deficiency (the cause of rickets) and weak bones might have shattered when people ran from predators, leaving them vulnerable.

This theory led Fisher and colleagues to hypothesize that sun seeking is driven by vitamin D deficiency, with the goal of increasing synthesis of the hormone for survival, and that vitamin D deficiency might also make the body more sensitive to the effects of opioids, potentially contributing to addiction. "Our goal in this study was to understand the relationship between vitamin D signaling in the body and UV-seeking and opioid-seeking behaviors," says lead author Lajos V. Kemény, MD, PhD, a postdoctoral research fellow in Dermatology at MGH.

In the Science Advances paper, Fisher, Kemény and a multidisciplinary team from several institutions addressed the question from dual perspectives. In one arm of the study, they compared normal laboratory mice with mice that were deficient in vitamin D (either through special breeding or by removing vitamin D from their diets). "We found that modulating vitamin D levels changes multiple addictive behaviors to both UV and opioids," says Kemény. Importantly, when the mice were conditioned with modest doses of morphine, those deficient in vitamin D continued seeking out the drug, behavior that was less common among the normal mice. When morphine was withdrawn, the mice with low vitamin D levels were far more likely to develop withdrawal symptoms.

The study also found that morphine worked more effectively as a pain reliever in mice with vitamin D deficiency--that is, the opioid had an exaggerated response in these mice, which may be concerning if it's true in humans, too, says Fisher. After all, consider a surgery patient who receives morphine for pain control after the operation. If that patient is deficient in vitamin D, the euphoric effects of morphine could be exaggerated, says Fisher, "and that person is more likely to become addicted."

The lab data suggesting that vitamin D deficiency increases addictive behavior was supported by several accompanying analyses of human health records. One showed that patients with modestly low vitamin D levels were 50 percent more likely than others with normal levels to use opioids, while patients who had severe vitamin D deficiency were 90 percent more likely. Another analysis found that patients diagnosed with opioid use disorder (OUD) were more likely than others to be deficient in vitamin D.

Back in the lab, one of the study's other critical findings could have significant implications, says Fisher. "When we corrected vitamin D levels in the deficient mice, their opioid responses reversed and returned to normal," he says. In humans, vitamin D deficiency is widespread, but is safely and easily treated with low-cost dietary supplements, notes Fisher. While more research is needed, he believes that treating vitamin D deficiency may offer a new way to help reduce the risk for OUD and bolster existing treatments for the disorder. "Our results suggests that we may have an opportunity in the public health arena to influence the opioid epidemic," says Fisher.

The term "doomscrolling" describes the act of endlessly scrolling through bad news on social media and reading every worrisome tidbit that pops up, a habit that unfortunately seems to have become common during the COVID-19 pandemic.

The biology of our brains may play a role in that. Researchers at Washington University School of Medicine in St. Louis have identified specific areas and cells in the brain that become active when an individual is faced with the choice to learn or hide from information about an unwanted aversive event the individual likely has no power to prevent.

The findings, published June 11 in Neuron, could shed light on the processes underlying psychiatric conditions such as obsessive-compulsive disorder and anxiety -- not to mention how all of us cope with the deluge of information that is a feature of modern life.

"People's brains aren't well equipped to deal with the information age," said senior author Ilya Monosov, PhD, an associate professor of neuroscience, of neurosurgery and of biomedical engineering. "People are constantly checking, checking, checking for news, and some of that checking is totally unhelpful. Our modern lifestyles could be resculpting the circuits in our brain that have evolved over millions of years to help us survive in an uncertain and ever-changing world."

In 2019, studying monkeys, Monosov laboratory members J. Kael White, PhD, then a graduate student, and senior scientist Ethan S. Bromberg-Martin, PhD, identified two brain areas involved in tracking uncertainty about positively anticipated events, such as rewards. Activity in those areas drove the monkeys' motivation to find information about good things that may happen.

But it wasn't clear whether the same circuits were involved in seeking information about negatively anticipated events. After all, most people want to know whether, for example, a bet on a horse race is likely to pay off big. Not so for bad news.

"In the clinic, when you give some patients the opportunity to get a genetic test to find out if they have, for example, Huntington's disease, some people will go ahead and get the test as soon as they can, while other people will refuse to be tested until symptoms occur," Monosov said. "Clinicians see information-seeking behavior in some people and dread behavior in others."

To find the neural circuits involved in deciding whether to seek information about unwelcome possibilities, first author Ahmad Jezzini, PhD, and Monosov taught two monkeys to recognize when something unpleasant might be headed their way. They trained the monkeys to recognize symbols that indicated they might be about to get a puff of air to the face. For example, the monkeys first were shown one symbol that told them a puff might be coming but with varying degrees of certainty. A few seconds after the first symbol was shown, a second symbol was shown that resolved the animals' uncertainty. It told the monkeys that the puff was definitely coming, or it wasn't.

The researchers measured whether the animals wanted to know what was going to happen by whether they watched for the second signal or averted their eyes or, in separate experiments, letting the monkeys choose among different symbols and their outcomes.

Much like people, the two monkeys had different attitudes toward bad news: One wanted to know; the other preferred not to. The difference in their attitudes toward bad news was striking because they were of like mind when it came to good news. When they were given the option of finding out whether they were about to receive something they liked -- such as juice -- they both consistently chose to find out.

"We found that attitudes toward seeking information about negative events can go both ways, even between animals that have the same attitude about positive rewarding events," said Jezzini, who is an instructor in neuroscience. "To us, that was a sign that the two attitudes may be guided by different neural processes."

By precisely measuring neural activity in the brain while the monkeys were faced with these choices, the researchers identified one brain area, the anterior cingulate cortex, that encodes information about attitudes toward good and bad possibilities separately. They found a second brain area, the ventrolateral prefrontal cortex, that contains individual cells whose activity reflects the monkeys' overall attitudes: yes for info on either good or bad possibilities vs. yes for intel on good possibilities only.

Understanding the neural circuits underlying uncertainty is a step toward better therapies for people with conditions such as anxiety and obsessive-compulsive disorder, which involve an inability to tolerate uncertainty.

"We started this study because we wanted to know how the brain encodes our desire to know what our future has in store for us," Monosov said. "We're living in a world our brains didn't evolve for. The constant availability of information is a new challenge for us to deal with. I think understanding the mechanisms of information seeking is quite important for society and for mental health at a population level."

Researchers at University of California San Diego School of Medicine used an artificial intelligence (AI) algorithm to sift through terabytes of gene expression data -- which genes are "on" or "off" during infection -- to look for shared patterns in patients with past pandemic viral infections, including SARS, MERS and swine flu.

Two telltale signatures emerged from the study, published June 11, 2021 in eBiomedicine. One, a set of 166 genes, reveals how the human immune system responds to viral infections. A second set of 20 signature genes predicts the severity of a patient's disease. For example, the need to hospitalize or use a mechanical ventilator. The algorithm's utility was validated using lung tissues collected at autopsies from deceased patients with COVID-19 and animal models of the infection.

"These viral pandemic-associated signatures tell us how a person's immune system responds to a viral infection and how severe it might get, and that gives us a map for this and future pandemics," said Pradipta Ghosh, MD, professor of cellular and molecular medicine at UC San Diego School of Medicine and Moores Cancer Center.

Ghosh co-led the study with Debashis Sahoo, PhD, assistant professor of pediatrics at UC San Diego School of Medicine and of computer science and engineering at Jacobs School of Engineering, and Soumita Das, PhD, associate professor of pathology at UC San Diego School of Medicine.

During a viral infection, the immune system releases small proteins called cytokines into the blood. These proteins guide immune cells to the site of infection to help get rid of the infection. Sometimes, though, the body releases too many cytokines, creating a runaway immune system that attacks its own healthy tissue. This mishap, known as a cytokine storm, is believed to be one of the reasons some virally infected patients, including some with the common flu, succumb to the infection while others do not.

But the nature, extent and source of fatal cytokine storms, who is at greatest risk and how it might best be treated have long been unclear.

"When the COVID-19 pandemic began, I wanted to use my computer science background to find something that all viral pandemics have in common -- some universal truth we could use as a guide as we try to make sense of a novel virus," Sahoo said. "This coronavirus may be new to us, but there are only so many ways our bodies can respond to an infection."

The data used to test and train the algorithm came from publicly available sources of patient gene expression data -- all the RNA transcribed from patients' genes and detected in tissue or blood samples. Each time a new set of data from patients with COVID-19 became available, the team tested it in their model. They saw the same signature gene expression patterns every time.

"In other words, this was what we call a prospective study, in which participants were enrolled into the study as they developed the disease and we used the gene signatures we found to navigate the uncharted territory of a completely new disease," Sahoo said.

By examining the source and function of those genes in the first signature gene set, the study also revealed the source of cytokine storms: the cells lining lung airways and white blood cells known as macrophages and T cells. In addition, the results illuminated the consequences of the storm: damage to those same lung airway cells and natural killer cells, a specialized immune cell that kills virus-infected cells.

"We could see and show the world that the alveolar cells in our lungs that are normally designed to allow gas exchange and oxygenation of our blood, are one of the major sources of the cytokine storm, and hence, serve as the eye of the cytokine storm," Das said. "Next, our HUMANOID Center team is modeling human lungs in the context of COVID-19 infection in order to examine both acute and post-COVID-19 effects."

The researchers think the information might also help guide treatment approaches for patients experiencing a cytokine storm by providing cellular targets and benchmarks to measure improvement.

To test their theory, the team pre-treated rodents with either a precursor version of Molnupiravir, a drug currently being tested in clinical trials for the treatment of COVID-19 patients, or SARS-CoV-2-neutralizing antibodies. After exposure to SARS-CoV-2, the lung cells of control-treated rodents showed the pandemic-associated 166- and 20-gene expression signatures. The treated rodents did not, suggesting that the treatments were effective in blunting cytokine storm.

"It is not a matter of if, but when the next pandemic will emerge," said Ghosh, who is also director of the Institute for Network Medicine and executive director of the HUMANOID Center of Research Excellence at UC San Diego School of Medicine. "We are building tools that are relevant not just for today's pandemic, but for the next one around the corner."

For centuries, scientists, aeronautic designers and adventure-seekers have sought to replicate the qualities that allow birds to fly, namely wing-structure and balance. However, without an external mechanism such as a hot air balloon or airplane, humans have remained earth-bound, unable to use their own bodies to propel themselves into the stratosphere.

While researchers have long-focused on structural factors, like wings, that define the category of bird, a recent study published Science Advances by Professor Avihu Klar at the Hebrew University of Jerusalem's Faculty of Medicine and Prof. Claudio Mello from Oregon Health and Science University found that there are specific molecular characteristics that distinguish birds from animals, and these differences allow birds to flap their wings and take to the sky.

In previous studies, researchers found that the ability of mammals and reptiles to walk is embedded within their spinal cord. In this new study, the scientists found that the ability to fly is embedded in birds' spinal cords. The team closely examined the neural networks of chicken and mice embryos and discovered that the genetic coding of the ephrin-B3 molecule in birds is fundamentally different than those of mammals and reptiles.

"The molecule ephrin-B3 is present in mammals but mutated or absent in birds. This simple but profound difference is what allows birds to flap their wings and take flight," shared Klar. Animals, such as rodents, present this molecule in its fullest form and therefor move in a stepping motion from left to right with their front and back limbs. On the other hand, mice with an ephrin-B3 mutation move with a synchronous jumping motion of both left and right sides at the same time, similar to birds.

These findings reinforced their theory that evolution--genetic changes over time--helped birds to develop a network of neurons that activates a very coordinated movement pattern, namely: the simultaneous flapping of wings.

"Our study provides a clue to the evolutionary enigma: How did the nervous system evolve to support stepping, flying and swimming," said Klar. "It paves the way for future experiments to reveal the evolution of neuronal networks that enable the different modes of movement of legs and hands, a characteristic of bipedal animals, such as birds and human."

What The Study Did: Researchers examined the associations between Medicare Advantage star ratings, which are created using data from all enrollees in a plan, and disparities in care for racial/ethnic minorities and enrollees with lower income and less education.

Authors: David J. Meyers, Ph.D., M.P.H., of the Brown University School of Public Health in Providence, Rhode Island, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamahealthforum.2021.0793)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Reston, VA (Embargoed until 6:15 p.m. EDT, Friday, June 11, 2021)--An advanced artificial intelligence technique known as deep learning can predict major adverse cardiac events more accurately than current standard imaging protocols, according to research presented at the Society of Nuclear Medicine and Molecular Imaging 2021 Annual Meeting. Utilizing data from a registry of more than 20,000 patients, researchers developed a novel deep learning network that has the potential to provide patients with an individualized prediction of their annualized risk for adverse events such as heart attack or death.

Deep learning is a subset of artificial intelligence that mimics the workings of the human brain to process data. Deep learning algorithms use multiple layers of "neurons," or non-linear processing units, to learn representations and identify latent features relevant to a specific task, making sense of multiple types of data. It can be used for tasks such as predicting cardiovascular disease and segmenting lungs, among others.

The study utilized information from the largest available multicenter SPECT dataset, the "REgistry of Fast myocardial perfusion Imaging with NExt generation SPECT" (REFINE SPECT), with 20,401 patients. All patients in the registry underwent SPECT MPI, and a deep learning network was used to score them on how likely they were to experience a major adverse cardiac event during the follow-up period. Subjects were followed for an average of 4.7 years.

The deep learning network highlighted regions of the heart that were associated with risk of major adverse cardiac events and provided a risk score in less than one second during testing. Patients with the highest deep learning scores had an annual major adverse cardiac event rate of 9.7 percent, a 10.2-fold increased risk compared to patients with the lowest scores.

"These findings show that artificial intelligence could be incorporated in standard clinical workstations to assist physicians in accurate and fast risk assessment of patients undergoing SPECT MPI scans," said Ananya Singh, MS, a research software engineer in the Slomka Lab at Cedars-Sinai Medical Center in Los Angeles, California. "This work signifies the potential advantage of incorporating artificial intelligence techniques in standard imaging protocols to assist readers with risk stratification."

Abstract 50. "Improved risk assessment of myocardial SPECT using deep learning: report from REFINE SPECT registry," Ananya Singh, Yuka Otaki, Paul Kavanagh, Serge Van Kriekinge, Wei Chih-Chun, Tejas Parekh, Joanna Liang, Damini Dey, Daniel Berman and Piotr Slomka, Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, California; Robert Miller, Department of Cardiac Sciences, University of Calgary, Calgary, Alberta, Canada, and Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, California; Tali Sharir, Department of Nuclear Cardiology, Assuta Medical Centers, Tel Aviv, and Ben Gurion University of the Negev, Beer Sheba, Israel; Andrew Einstein, Division of Cardiology, Department of Medicine and Department of Radiology, Columbia University, Irving Medical Center and New York-Presbyterian Hospital, New York, New York; Mathews Fish, Oregon Heart and Vascular Institute, Sacred Heart Medical Center, Springfield, Oregon; Terrence Ruddy, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Philipp Kaufmann, Department of Nuclear Medicine, Cardiac Imaging, University Hospital Zurich, Zurich, Switzerland; Albert Sinusas and Edward Miller, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine New Haven, Connecticut; Timothy Bateman, Department of Imaging, Cardiovascular Imaging Technologies LLC, Kansas City, Missouri; Sharmila Dorbala and Marcelo Di Carli, Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Brigham and Women's Hospital, Boston, Massachusetts.

What The Study Did: Editorial team composition by gender, race, ethnicity and sexual orientation was assessed at 25 leading medical and scientific journals in this survey study.

Authors: James W. Salazar, M.D., M.A.S., of the University of California San Francisco, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2021.2363)

Editor's Note: The article includes conflicts of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

The Fenton reaction is a chemical transition involving hydrogen peroxide (H2O2) and the ferrous (iron) ion, which acts as a catalyst. This process is used to destroy hazardous contaminants in wastewater through oxidation. In the atmosphere, a similar reaction, or "Fenton-like" reaction, occurs continuously with ferric oxalate([Fe(III)(C2O4)3]3-) and aerosols suspended in the air. This is the most frequent chemical reaction that occurs in the atmosphere. A particle's ability to oxidize is directly related to its phase, either gaseous or aqueous, which has an important impact on secondary organic aerosol (SOA) formation. Therefore, research is necessary not only to evaluate the contribution of this Fenton-like reaction to atmospheric oxidation, but also to improve the consistency of model-simulated and field-observed SOA budgets.

"It is generally believed that the contribution of the Fenton reaction to atmospheric oxidation comes from the generation of hydroxyl radicals." said Prof. Wenbo Dong from the Department of Environmental Science & Engineering, Fudan University. "Scientists have not frequently addressed the role of superoxide radicals, which is generally regarded as the source of hydrogen peroxide and hydroxyl radicals."

Methacrolein (CH2=C(CH3)CHO) is the primary oxidation product of isoprene(CH2=C(CH3)CH=CH2), which is the most abundant biological volatile organic compound (VOC) in the atmosphere. It can directly react with superoxide radicals to generate SOAs. While this is a common reaction, this process shows that other paths to VOC oxidation exist.

"Previous studies believed that superoxide radicals do not react with most organic compounds." remarked Prof. Dong.

Some VOCs in the atmosphere may react with superoxide radicals just like methacrolein. However, SOA production potential from any VOC with attendant superoxide radicals and hydroxyl radicals is distinct from the methacrolein reaction. Researchers focused on the oxidation process of organic pollutants caused by these free radicals. They found that the oxidation process is related to the reaction mechanism of the organic matter accompanying these free radicals.

Previous studies have shown that the change in aqueous aerosol absorbance is attributed to the formation of brown carbon. However, in the case of photo-oxidation of methacrolein with ferric oxalate, Prof. Dong's research group noticed a substantial increase in aerosol absorbance without formation of brown carbon. Further analysis is provided in their research article titled "Photooxidation of Methacrolein in Fe(III)-Oxalate Aqueous System and Its Atmospheric Implication" published in Advances in Atmospheric Sciences.

"When the Fenton-like reaction with a high concentration of iron occurs, the absorbance of the solution will change significantly, with the solution turning yellow." said Prof. Dong. "This may not be the only situation with methacrolein, as it can come up with the Fenton-like reaction of other organic compounds."

Prof. Dong continued, "The formation of insoluble or colloidal iron hydroxide increases the absorbance of atmospheric aerosols, affecting the radiative forcing, which has been overlooked for a long time."

Researchers from University of Adelaide published a new paper in the Journal of Marketing that examines how advertising can increase the informativeness of a firm's stock price by reducing its stock price synchronicity.

The study, forthcoming in the Journal of Marketing, is titled "Tarred with the Same Brush? Advertising Share of Voice and Stock Price Synchronicity" and is authored by Chee Cheong, Arvid Hoffmann, and Ralf Zurbruegg.

Firms are sometimes "tarred with the same brush" by investors instead of being traded based on firm-specific information. This is problematic when influential incidents happen, such as product recalls, because firms in the same industry as the offender also experience a drop in firm value despite not being involved in the incident themselves. This study demonstrates that advertising can help firms avoid such a situation by differentiating themselves from their financial market competitors through communicating firm-specific information to investors.

The researchers argue that advertising provides information to investors in financial markets, analogous to its role for customers in product markets. Hoffmann explains that "Although advertising is typically intended to increase awareness of and provide information about a firm's products rather than its shares, it also attracts investor attention, constitutes an important source of information, and is eventually internalized by investors to affect stock trading behavior. We expect that advertising can increase the informativeness of a firm's stock price by reducing its stock price synchronicity, or the extent to which its stock price is driven by general market and industry trends instead of firm-specific information."

The study uses a comprehensive data set based on all U.S. publicly listed firms from 1994 to 2018 and supplements this quantitative data with qualitative data from in-depth interviews with executives of such publicly listed firms to examine three interrelated research questions.

First, if a firm advertises more relative to its industry peers, does this increase its stock price informativeness and thus reduce its stock price synchronicity? The researchers expect that the larger a firm's so-called "advertising share of voice," the more visible it will be among (potential) investors, thus making it more likely that investors incorporate in their pricing the firm-specific information conveyed in the firm's advertising.

Second, is the effect of advertising more pronounced if there is more demand for information about the firm in the financial market (for example, because the firm has more complex products)? In such situations, advertising would potentially be more valuable and informative for investors.

Third, is the effect of advertising less pronounced if there is more supply of information about the firm in the financial market (for example, because institutional ownership is greater as these professional investors have access to better information)?

Cheong says that "We find support for our expectation that firms with a larger advertising share of voice are more successful in differentiating themselves in the financial market, as expressed by having a lower stock price synchronicity. Furthermore, this effect is stronger for firms with more complex products and weaker for firms with a larger proportion of institutional ownership." Sensitivity analyses show that the effect of advertising is also more pronounced when there is congruence between a firm's corporate name and its ticker symbol and when a firm has a corporate branding strategy, providing actionable insights for managers. An event study analyzing product recalls as influential marketing-relevant incidents illustrates the practical importance of the results. Firms with high synchronicity are "tarred with the same brush" in terms of experiencing negative abnormal returns when competitors have a recall, while firms with low synchronicity are not affected.

Managers can tap advertising not just to help consumers understand the benefits of the firm's products, but also to communicate firm-specific information to (potential) investors. Ultimately, when stock prices are more informative, investors experience less information asymmetry and are more willing to provide capital to a firm, allowing it to invest in profitable projects.

"To maximize the benefit of the positive spillover effects between product-market advertising and financial market outcomes, managers of publicly listed firms should ensure that investors can easily link the product names as used in advertising campaigns to their corporate name in the stock market; for example, by having a congruent ticker symbol and a corporate branding strategy instead of a house of brands or mixed branding strategy," says Zurbruegg. Finally, it is critical to realize that the results of advertising are above and beyond the effect of a firm's news coverage, meaning that advertising provides new information to investors that they did not yet obtain from other media. Accordingly, the marketing and finance functions of firms should work together when designing ad campaigns.

When is a weed not a weed?

Can native plants be weeds?

Sweet pittosporum (Pittosporum undulatum) was once a well-behaved tree growing in gullies from Gippsland in Victoria up to Brisbane in Queensland.

But it is now a major problem, leading to an almost complete suppression of native vegetation where it has invaded. Programs to clear it have successfully allowed indigenous plants to return, and within 15 years, with moderate follow up, treated sites are well on the way to successful restoration.

However, there has been some debate on whether this is good or bad for birds such as the threatened Powerful Owl.

New research by Monash University scientists from the School of Biological Sciences published today in Ecological Solutions and Evidence shows that the richness and abundance of birds is much reduced in areas with dense Pittosporum canopies.

"The almost complete absence of any understory vegetation and no ground cover means there is very little for birds to eat in invaded sites," said lead study author Dr Ben O'Leary, who conducted the surveys as part of his PhD.

"Most habitat components for birds exists within the Eucalyptus overstorey and mid canopy. The presence or removal of Pittosporum doesn't appear to greatly influence ground storey bird species, which have been in long-term decline."

The study found that there are also fewer carnivorous birds in Pittosporum-invaded sites, probably because there is less prey on the ground and the dense Pittosporum canopy makes it hard for these large birds to navigate through these areas.

"While invaded sites are not great habitat, restoration projects need to ensure that the full range of habitats continue to be available during the transition period," Dr O'Leary said.

One difficulty in overseeing the removal of an invasive tree species is that these trees, in certain circumstances, provide structural value to local flora and fauna. There is a lag time between the invaders' removal and its replacement by indigenous alternatives.

"The trick is balancing the progression of weed control with the retention of enough structure to support local plants and animals," Dr O'Leary said.

Project leader and co-author Professor Ros Gleadow also from the School of Biological Sciences, has been studying Pittosporum for over 40 years.

"It is important to get rid of the Pittosporum now," Professor Gleadow said.

"Not only does it suppress the understorey, but in all these years, I have never seen a eucalypt seedling growing under a Pittosporum canopy," she said.

"Once the old eucalypts at a site die, that's it and it of both native vegetation and birds is impossible without major intervention".

Previous work by the group showed that areas can be restored to their original state if there are healthy remnant sites nearby.

"For areas where Pittosporum is native, like around Sydney, management is philosophically complicated but there is no doubt that clearing will to help preserve biodiversity," Professor Gleadow said.

Progressively clearing the Pittosporum over time, leaving some canopy in place in adjacent areas has the double benefit of providing potential roosting sites for the Powerful Owls, as well as increasing the number of prey.

Once the new shrubs and trees have grown, then clearing could progress to the next area.

Astronomers from University of Warwick and University of Exeter modelling the future of unusual planetary system found a solar system of planets that will 'pinball' off one another

Today, the system consists of four massive planets locked in a perfect rhythm

Study shows that this perfect rhythm is likely to hold for 3 billion years - but the death of its sun will cause a chain reaction and set the interplanetary pinball game in motion

Four planets locked in a perfect rhythm around a nearby star are destined to be pinballed around their solar system when their sun eventually dies, according to a study led by the University of Warwick that peers into its future.

Astronomers have modelled how the change in gravitational forces in the system as a result of the star becoming a white dwarf will cause its planets to fly loose from their orbits and bounce off each other's gravity, like balls bouncing off a bumper in a game of pinball.

In the process, they will knock nearby debris into their dying sun, offering scientists new insight into how the white dwarfs with polluted atmospheres that we see today originally evolved. The conclusions by astronomers from the University of Warwick and the University of Exeter are published in the Monthly Notices of the Royal Astronomical Society.

The HR 8799 system is 135 light years away and comprises a 30-40 million year-old A type star and four unusually massive planets, all over five times the mass of Jupiter, orbiting very close to each other. The system also contains two debris discs, inside the orbit of the innermost planet and another outside the outermost. Recent research has shown that the four planets are locked in a perfect rhythm that sees each one completing double the orbit of its neighbour: so for every orbit the furthest completes, the next closest completes two, the next completes four, while the closest completes eight.

The team from Warwick and Exeter decided to learn the ultimate fate of the system by creating a model that allowed them to play 'planetary pinball' with the planets, investigating what may cause the perfect rhythm to destabilise.

They determined that the resonance that locks the four planets is likely to hold firm for the next 3 billion years, despite the effects of Galactic tides and close flybys of other stars. However, it always breaks once the star enters the phase in which it becomes a red giant, when it will expand to several hundred times its current size and eject nearly half its mass, ending up as a white dwarf.

The planets will then start to pinball and become a highly chaotic system where their movements become very uncertain. Even changing a planet's position by a centimetre at the start of the process can dramatically change the outcome.

Lead author Dr Dimitri Veras from the University of Warwick Department of Physics said: "The planets will gravitationally scatter off of one another. In one case, the innermost planet could be ejected from the system. Or, in another case, the third planet may be ejected. Or the second and fourth planets could switch positions. Any combination is possible just with little tweaks.

"They are so big and so close to each other the only thing that's keeping them in this perfect rhythm right now is the locations of their orbits. All four are connected in this chain. As soon as the star loses mass their locations will deviate, then two of them will scatter off one another, causing a chain reaction amongst all four."

Dr Veras was supported by an Ernest Rutherford Fellowship from the Science and Technology Facilities Council, part of UK Research and Innovation.

Regardless of the precise movements of the planets, one thing that the team is certain of is that the planets will move around enough to dislodge material from the system's debris discs into the atmosphere of the star. It is this type of debris that astronomers are analysing today to discover the histories of other white dwarf systems.

Dr Veras adds: "These planets move around the white dwarf at different locations and can easily kick whatever debris is still there into the white dwarf, polluting it.

"The HR 8799 planetary system represents a foretaste of the polluted white dwarf systems that we see today. It's a demonstration of the value of computing the fates of planetary systems, rather than just looking at their formation."

Co-author Professor Sasha Hinkley of the University of Exeter said: "The HR 8799 system has been so iconic for exoplanetary science since its discovery nearly 13 years ago, and so it is fascinating to see into the future, and watch it evolve from a harmonious collection of planets into a chaotic scene."

Astronomers have spotted a giant 'blinking' star towards the centre of the Milky Way, more than 25,000 light years away.

An international team of astronomers observed the star, VVV-WIT-08, decreasing in brightness by a factor of 30, so that it nearly disappeared from the sky. While many stars change in brightness because they pulsate or are eclipsed by another star in a binary system, it's exceptionally rare for a star to become fainter over a period of several months and then brighten again.

The researchers believe that VVV-WIT-08 may belong to a new class of 'blinking giant' binary star system, where a giant star ? 100 times larger than the Sun ? is eclipsed once every few decades by an as-yet unseen orbital companion. The companion, which may be another star or a planet, is surrounded by an opaque disc, which covers the giant star, causing it to disappear and reappear in the sky. The study is published in Monthly Notices of the Royal Astronomical Society.

The discovery was led by Dr Leigh Smith from Cambridge's Institute of Astronomy, working with scientists at the University of Edinburgh, the University of Hertfordshire, the University of Warsaw in Poland and Universidad Andres Bello in Chile.

"It's amazing that we just observed a dark, large and elongated object pass between us and the distant star and we can only speculate what its origin is," said co-author Dr Sergey Koposov from the University of Edinburgh.

Since the star is located in a dense region of the Milky Way, the researchers considered whether some unknown dark object could have simply drifted in front of the giant star by chance. However, simulations showed that there would have to be an implausibly large number of dark bodies floating around the Galaxy for this scenario to be likely.

One other star system of this sort has been known for a long time. The giant star Epsilon Aurigae is partly eclipsed by a huge disc of dust every 27 years, but only dims by about 50%. A second example, TYC 2505-672-1, was found a few years ago, and holds the current record for the eclipsing binary star system with the longest orbital period ? 69 years ? a record for which VVV-WIT-08 is currently a contender.

The UK-based team has also found two more of these peculiar giant stars in addition to VVV-WIT-08, suggesting that these may be a new class of 'blinking giant' stars for astronomers to investigate.

VVV-WIT-08 was found by the VISTA Variables in the Via Lactea survey (VVV), a project using the British-built VISTA telescope in Chile and operated by the European Southern Observatory, that has been observing the same one billion stars for nearly a decade to search for examples with varying brightness in the infrared part of the spectrum.

Project co-leader Professor Philip Lucas from the University of Hertfordshire said, "Occasionally we find variable stars that don't fit into any established category, which we call 'what-is-this?', or 'WIT' objects. We really don't know how these blinking giants came to be. It's exciting to see such discoveries from VVV after so many years planning and gathering the data."

While VVV-WIT-08 was discovered using VVV data, the dimming of the star was also observed by the Optical Gravitational Lensing Experiment (OGLE), a long-running observation campaign run by the University of Warsaw. OGLE makes more frequent observations, but closer to the visible part of the spectrum. These frequent observations were key for modelling VVV-WIT-08, and they showed that the giant star dimmed by the same amount in both the visible and infrared light.

There now appear to be around half a dozen potential known star systems of this type, containing giant stars and large opaque discs. "There are certainly more to be found, but the challenge now is in figuring out what the hidden companions are, and how they came to be surrounded by discs, despite orbiting so far from the giant star," said Smith. "In doing so, we might learn something new about how these kinds of systems evolve."

Oncotarget published "The presence of polymorphisms in genes controlling neurotransmitter metabolism and disease prognosis in patients with prostate cancer: a possible link with schizophrenia" reported that polymorphisms of neurotransmitter metabolism genes were studied in patients with prostate cancer (PC) characterized by either reduced or extended serum prostate-specific antigen doubling time corresponding to unfavorable and favorable disease prognosis respectively.

The following gene polymorphisms known to be associated with neuropsychiatric disorders were investigated:

A. The STin2 VNTR in the serotonin transporter SLC6A4 gene;

B. The 30-bp VNTR in the monoamine oxidase A MAOA gene;

C. The Val158Met polymorphism in the catechol-ortho-methyltransferase COMT gene;

D. The promoter region C-521T polymorphism and the 48 VNTR in the third exon of the dopamine receptor DRD4 gene.

The STin2 12R/10R variant of the SLC6A4 gene and the -521T/T homozygosity of the DRD4 gene tended to be overrepresented in PC patients with unfavorable disease prognosis.

These gene variants are regarded as protective against schizophrenia, and the observed trend may be directly related to a reduced PC risk described for schizophrenia patients.

These results warrant further investigation of the potential role of neurotransmitter metabolism gene polymorphisms in PC pathogenesis.

Dr. Vladimir N. Anisimov from The Petrov National Medical Research Center of Oncology said, "The importance of complex networks of heterotypic interactions between multiple distinct cell types (both malignant and normal) and regulatory circuits has now become widely recognized."

The importance of complex networks of heterotypic interactions between multiple distinct cell types (both malignant and normal) and regulatory circuits has now become widely recognized.

The traditional tumor-centric view focused exclusively on malignant cell populations has largely been replaced with a concept of tumor microenvironment, the latter being regarded as a "dynamic interaction arena in which tumor cells interact with the extracellular matrix, resident and recruited cells, and soluble factors".

Although there is a general consensus that chronic stress and depression tend to result in an impairment of the immune responses and might facilitate cancer initiation and progression, while the risk of developing some cancers appears to be decreased in patients with schizophrenia.

Pancreatic Cancer is not only the second most common cancer in men, but this is also a condition characterized by a wide variation of severity that ranges from indolent to highly aggressive disease.

The latter feature of PC makes tumor growth monitoring a very important prerequisite for successful disease management, and repeated measurement of the concentration of a blood biomarker of PC, prostate-specific antigen, is generally accepted as an important prognostic tool for routinely monitoring patients with this condition.

It was noted above that psychiatric disorders may be associated with a seriously altered PC risk, but little is known about possible influences of patients' genetic background both on this phenomenon and on disease prognosis when PC is already present.

The Anisimov Research Team concluded in their Oncotarget Research Output that oncological conditions are known to occur less frequently in schizophrenia patients, and this phenomenon primarily affects men, being especially pronounced for PC.

Interestingly, PC has recently emerged as a cancer, development of which strongly depends on neurogenic regulatory pathways provided by nerves growing as an important TME component.

Furthermore, neurotransmitters, such as serotonin and dopamine, are now regarded as major factors modulating neoplastic growth through influences on angiogenesis and neoplastic cell proliferation.

The results presented in this paper indicate that the presence of certain polymorphic variants of the SLC6A4 and DRD4 genes related to serotonin and dopamine signaling pathways respectively appears to correlate with PC prognosis.

Further larger studies are needed for clarifying the role of neurotransmitter metabolism gene polymorphisms in PC pathogenesis.

Scientists at Tokyo Institute of Technology (Tokyo Tech) and NEC Corporation jointly develop a 28-GHz phased-array transceiver that supports efficient and reliable 5G communications. The proposed transceiver outperforms previous designs in various regards by adapting fast beam switching and leakage cancellation mechanism.

With the recent emergence of innovative technologies, such as the Internet of Things, smart cities, autonomous vehicles, and smart mobility, our world is on the brink of a new age. This stimulates the use of millimeter-wave bands, which have far more signal bandwidth, to accommodate these new ideas. 5G can offer data rates over 10 Gbit/s through the use of these millimeter-waves and multiple-in-multiple-out (MIMO) technology--a technology that employs multiple transmitters and receivers to transfer more data at the same time.

Large-scale phased-array transceivers are crucial for the implementation of these MIMO systems. While MIMO systems boost spectral performance, large-scale phased-array systems face several challenges, such as increased power dissipation and implementation costs. One such critical challenge is latency caused by beam switching time. Beam switching is an important feature that enables the selection of the most optimal beam for each terminal. A design that optimizes beam switching time and device cost is, thus, the need of the hour.

Motivated by this, scientists from Tokyo Institute of Technology and NEC Corporation in Japan collaborated to develop a 28-GHz phased-array transceiver that supports fast beam switching and high-speed data communication. Their findings will be discussed at the 2021 Symposia on VLSI Technology and Circuits, an international conference that explores emerging trends and innovative concepts in semiconductor technology and circuits.

The proposed design facilitates dual-polarized operation, in which data is transmitted simultaneously through horizontal and vertical-polarized waves. However, one issue with these systems is cross-polarization leakage, which results in signal degradation, especially in the millimeter-wave band. The research team delved into the issue and developed a solution. Prof. Kenichi Okada, who led the research team, says, "Fortunately, we were able to devise a cross-polarization detection and cancellation methodology, using which we could suppress the leakages in both transmit and receive mode."

One critical feature of the proposed mechanism is the ability to achieve low-latency beam switching and high-accuracy beam control. Static elements control the building blocks of the mechanism, while on-chip SRAM is used to store the settings for different beams (Figure 1). This mechanism leads to fast beam switching with ultra-low latency being achieved. It also enables fast switching in transmit and receive modes due to the use of separate registers for each mode.

Another aspect of the proposed transceiver is its low cost and small size. The transceiver has a bi-directional architecture, which allows for a smaller chip size of 5 × 4.5 mm2 (Figure 2). For a total of 256-pattern beam settings stored within the on-chip SRAM, a beam switching time of only 4 nanoseconds was achieved! Error vector magnitude (EVM)--a measure to quantify the efficiency of digitally modulated signals such as quadrature amplitude modulation (QAM)--was calculated for the proposed transceiver. The transceiver was supported with EVMs of 5.5% in 64QAM and 3.5% in 256QAM.

When compared with state-of-the-art 5G phased-array transceivers, the system has a faster beam switching time and excellent MIMO efficiency. Okada is optimistic about the future of the 28-GHz 5G phased-array transceiver. He concludes, "The technology we developed for the 5G NR network supports high-volume data streaming with low latency. Thanks to its rapid beam switching capabilities, it can be used in scenarios where enhanced multi-user perception is required. This device sets the stage for a myriad of applications, including machine connectivity and the construction of smart cities and factories."