Culture

Coffee shops and casual restaurants are an important part of American life. Even beyond the food and drinks they sell, they offer us a place to use the restroom or rest our feet while we're out and about, and they provide internet access to those on the go, those in need of a temporary office, or those who don't have an internet connection at home. Many of us take for granted that a nearby Starbucks or McDonald's can offer us a little respite, even if we don't always make a purchase.

But access to these sorts of quasi-public spaces isn't always equal in America, particularly for Black people and other people of color. One such example of this is the infamous 2018 incident in Philadelphia when two Black men waiting at Starbucks for an acquaintance were arrested for loitering. The national outcry over their biased and unjust treatment led to a change in Starbucks' corporate policy. It also begs the question: how often does this kind of incident happen around the country and what implications does it have?

A new study published in the Journal of Communication from researchers at the Annenberg School for Communication at the University of Pennsylvania investigated the ways that institutions control who has access to Wi-Fi. The findings indicate that powerful institutions and privileged people use quality-of-life policing -- the report and/or arrest of individuals engaged in nonviolent offenses such as loitering, noise violations, and public intoxication -- to keep those with less privilege, including people of color, from accessing resources like the internet.

The inspiration for the study came from a story Professor Julia Ticona heard while interviewing gig workers for her forthcoming book, Left to Our Own Devices: Coping with Insecure Work in a Digital Age (Oxford University Press). One of her interviewees, a 20-year-old Black man named Alex, had a Starbucks manager threaten to call the police on him because he was using an outlet and the internet.

"I was so frustrated for him personally," says Ticona. "And I was also frustrated that we so often talk about the digital divide as a matter of people not being able to afford access, entirely omitting from the discussion that people are actively being threatened for using the internet."

Ticona shared her frustration with Professor Yphtach Lelkes and doctoral candidate Tian Yang, and the three scholars joined forces to develop a method for investigating whether and how institutions are policing access to the internet.

"This paper is a great example of disciplinary cross-fertilization" says Lelkes. "Julia and I have offices across the hall from one another, and Tian was working with me as a research fellow and taking Julia's class at the time. This project came about because Annenberg is such a big tent when it comes to methods and ways of thinking, and the school encourages collaborations between its various scholars."

The researchers analyzed publicly available data to determine whether quality-of-life policing increased, decreased, or remained the same once free Wi-Fi was introduced to restaurants -- namely Burger King, McDonald's, Panera, Starbucks, and Wendy's -- in various neighborhoods in Chicago between 2008 and 2016. They compiled their own dataset for the study, combining crime data from the police department, neighborhood information from the U.S. Census Bureau, and the locations of stores listed on business licenses.

"We were excited to be able to establish a causal relationship between institutional dynamics and their outcomes in perpetuating social inequalities," says Yang. "To do this, we applied methods used in economics and other fields to develop a way to analyze the data for answers to our questions."

The researchers found that wealthier, whiter neighborhoods had a 5% increase in quality-of-life complaints to the police after restaurants began offering internet access, while other neighborhoods did not. They also found that those same wealthy, white neighborhoods did not have an increase in the report of other kinds of crime, like assault or burglary. The researchers believe their findings suggest that economic hurdles aren't the only factor shaping people's internet access, but that active exclusion from public spaces -- where some people are allowed to enjoy Wi-Fi and others aren't -- also contributes to the digital divide.

"This paper connects ongoing conversations about the role of institutions in perpetuating white supremacy and privilege in the digital age to long-standing questions about digital access," says Ticona. "We hope this study can contribute to the efforts to have a different kind of conversation in the field of Communication about the role of policing, race, and class in reinforcing digital inequalities."

Rainforests are a powerful, natural solution to combat climate change -- providing water filtration, capturing carbon and regulating global temperatures. But major threats like large-scale land use changes, including agricultural expansion and clearcutting, have turned these biodiversity havens into one of the most endangered habitats on our planet.

In 2019, select scientists, including the University of Delaware's Rodrigo Vargas, met at the National Geographic headquarters in Washington, D.C., to discuss the threats to rainforests. The researchers pinpointed a need to develop a worldwide tracking system, which would find trends to help fight land degradation and promote conservation.

In the paper published on Friday, July 22 in the scientific journal One Earth, these researchers introduce the unique tropical rainforest index (TFVI), a baseline for rainforests across the entire globe. The scientist's goal is to detect and evaluate the vulnerability of rainforests to increasing threats. National Geographic and the Rolex Perpetual Planet Initiative funded the endeavor.

TFVI provides a snapshot of long-term observations, which began in 1982.

"Through this new index, we now have not only global coverage, but uniformity. We can summarize critical information about the health of rainforests," said Vargas, professor of ecosystem ecology and environmental change. "It gives us a benchmark and provides information about looming, future changes."

Using advanced satellite measurements, the research team systematically analyzed the climate and vegetation of each tropical region on Earth. The study's findings suggest that rainforests are losing their capacity to cycle carbon and water.

"We are losing major hotspots for biodiversity and carbon pools," Vargas said. "These are not small patches of land across the world; these are large sections of the Earth's surface."

The study's findings also indicate different regions of tropics have different responses to climate threats. Some regions, like Africa's Congo basin, are more resilient than other parts of the world. The Amazon Basin shows large-scale vulnerability to drying conditions of atmosphere, frequent droughts and large-scale land-use changes. In Southeast Asia, rainforests are stressed more from land use and species fragmentation than they are from climate, except for areas of peatlands that are, during El Nino years, now more vulnerable to fire.

"There is no single solution, no silver bullet that will work in every tropical rainforest. This highlights the needs for localized solutions," Vargas said. "But a general, global index also illuminates the need to design unified strategies to maximize the natural solutions that rainforests provide."

The unique tropical rainforest index methodically illustrates that the susceptibility of rainforests is actually much greater than previous predictions. Disturbed and fragmented areas have lost resilience to climate warming and droughts. Perhaps even more distressing were study findings suggesting that rainforests are losing their capacity to cycle carbon and water.

Tropical forests provide critical environmental services and benefits to society. These rainforests are changing from their historically, highly-diverse status to heavily transformed areas and managed land -- one that lacks the ability to, for example, sequester carbon from the atmosphere and support biodiversity.

"In addition to our moral responsibility to preserve our planet's biodiversity, because human's actions are influencing the global climate, we must be prepared to manage the consequences of these changes," Vargas said.

Attitudes toward diversity vary, and its meaning can often be difficult to find consensus about in an increasingly diverse but politically polarized nation such as the United States.

In a report published by Personality and Social Psychology Bulletin, University of Illinois Chicago researchers detail findings from three studies that explore the connection between political ideology, attitudes, and beliefs toward diversity.

"Our studies explored the possibility that atti­tudes toward 'diversity' are multidimensional rather than unidimensional and that ideological differences in diversity attitudes vary as a function of diversity subtype," said the report's lead author Kathryn Howard, UIC doctoral candidate in psychology.

The first study investigated ideological differences in attitudes towards a wide variety of diversity features. Participants rated how much diversity or homogeneity they would desire in 23 different community features that could be considered relevant to diversity.

The study found more conservative participants preferred viewpoint diversity and more liberal participants preferred demographic diversity.

The second study assessed participants' attitudes towards the general concept of diversity without providing a definition of the term. By investigating whether general attitudes towards diversity actually predict how people feel about specific types of diversity, the findings suggest that demographic features may be central to peoples' prototypes of diversity and that positive attitudes towards the general concept of diversity predicted demographic diversity preferences for both conservatives and liberals.

According to the researchers, "liberals were more likely than conservatives to endorse the general concept of diversity. Further, general diversity did not predict viewpoint diversity, but did significantly predict demographic diversity preferences. Thus, it may be that when people think of diversity in the abstract, people primarily imagine differences in ethnic and cultural groups, and do not necessarily consider diversity in attitudes."

Because the first two studies found that diversity is multidimensional and contains at least two distinct factors -- viewpoint and demographic diversity -- the third study aimed to investigate possible variations in the perceived meaning of "diversity" by asking participants to judge the relevance of a set of features to diversity.

Respondents were asked to imagine "a very diverse community," and to think about "the types of people and places that exist in a very diverse community." They also had to determine how relevant 29 different community features were to their image of a diverse community.

"People do not perceive diversity as a unidimensional or even bi-dimensional construct, but rather likely perceive at least three categories of diversity. Further, people rated demographic features as most relevant to diversity, followed by viewpoint and consumer features. Lastly, conservatives rated viewpoint features as more relevant to diversity than liberals, and liberals rated demographic features as more relevant to diversity than conservatives," the report states.

"Conservatives and liberals do not differ only in their attitudes toward diversity, but they also differ in their understanding of what 'diversity' means. When asked to think about 'diversity,' liberals and conservatives think about different things; different aspects of social life come to mind," Howard said.

The divergent political and social media realms where liberals and conservatives are centered, combined with increased political and affective polarization, likely accounts for the difference of perspective on both sides, according to the researchers, who add that the results provide hope for bridging the liberal-conservative political divide.

"Once you recognize that existence of multiple components of 'diversity,' it opens the door to identifying some aspects of diversity on which liberals and conservatives agree," said Daniel Cervone, UIC professor of psychology and study co-author. "Breaking the concept of 'diversity' into parts and identifying those parts on which people agree could be one small step toward reducing political polarization."

Small and seemingly specialized, the brain's locus coeruleus (LC) region has been stereotyped for its outsized export of the arousal-stimulating neuromodulator norepinephrine. In a new paper and with a new grant from the National Institutes of Health, an MIT neuroscience lab is making the case that the LC is not just an alarm button but has a more nuanced and multifaceted impact on learning, behavior and mental health than it has been given credit for.

With inputs from more than 100 other brain regions and sophisticated control of where and when it sends out norepinephrine (NE), the LC's tiny population of surprisingly diverse cells may represent an important regulator of learning from reward and punishment, and then applying that experience to optimize behavior, said Mriganka Sur, Newton Professor of Neuroscience in The Picower Institute for Learning and Memory and the Department of Brain and Cognitive Sciences at MIT.

"What was formerly considered a homogenous nucleus exerting global, uniform influence over its many diverse target regions, is now suggested to be a heterogeneous population of NE-releasing cells, potentially exhibiting both spatial and temporal modularity that govern its functions," wrote Sur, postdoc Vincent Breton-Provencher and graduate student Gabrielle Drummond in a review article published last month in Frontiers in Neural Circuits.

The article presents copious emerging evidence from Sur's group and many others, suggesting that that the LC may integrate sensory inputs and internal cognitive states from across the brain to precisely exert its NE-mediated influence to affect actions - by throttling NE to the motor cortex - and the processing of resulting feedback of reward or punishment - by throttling NE to the prefrontal cortex.

To investigate that hypothesis, the team has begun working with a $2.1 million, 5-year NIH grant awarded in April. In this study they are engaging mice in learning tasks where they are cued by tones of varying pitches and volumes. Over the course of training the mice will learn that when a tone is high pitched, pressing a lever will yield a reward and when the tone is low pitched, the correct response would be to not push lest it experience an unpleasant air puff. By varying the tone volume, the experimenters will vary the certainty the mice can feel that they heard the cue correctly.

The hypothesis (borne out by preliminary data) predicts that the NE will matter in multiple crucial ways, Sur said. When the mouse hears the cue tone, if the pitch is low the LC would send less NE via a cadre of neurons to the motor cortex, reflecting the animal's belief that the lever should not be pushed because no reward will be forthcoming. Meanwhile the lower the volume, the less certainty the animal has in its decision. Conversely, a high tone of high volume would send more NE, reflecting the animal's certainty that pushing the lever would produce a reward.

After the mouse has acted, the more surprising the feedback, the more NE it will produce and send via a distinct group to the prefrontal cortex, stimulating greater learning. So for instance, if the mouse hears a faint, high tone and gingerly presses the lever, the surprise of a resulting reward will stimulate a strong output of NE to instruct the prefrontal cortex because its expectations weren't very high. Whenever a mouse guesses wrong and feels an air puff, that will stimulate the strongest NE release to the prefrontal cortex. After such dynamics, Sur's team has observed consistent performance changes on the subsequent trial.

"This is a way by which norepinephrine can be thought of as an arousal signal, but it's also, importantly, in the context of ongoing function a learning signal," Sur said. "It is both an execution signal and a learning signal, for both of which we can describe the actual quantitative relationships."

Not only will the team be measuring the activity of LC-NE neurons, they'll also take them over using optogenetics (in which neurons can be controlled with light), so that they can silence or amplify LC-NE output to show how doing each affects action and learning.

Understanding the true nature of how the LC works could be useful for improving treatments for certain disorders, Sur said. A potential treatment for PTSD, for instance, involves damping receptiveness to NE, but that also promotes drowsiness. A more principled and precise treatment could improve efficacy and reduce those side effects, he said.

"The hope is to affect the anxiety but not make you sleepy, if we understand the targets and theory behind it," Sur said. "That is the hope of basic science for treating disorders--to make things more and more specific, to define the circuits and the specificity of functions that a system is involved in."

Moreover the LC is an early region affected in Alzheimer's disease, he said. Addressing that loss in the right way could help sustain forms of learning and cognition.

At a glance:

Researchers studied cells collected by nasal swabs at the moment of diagnosis for both mild and severe COVID-19 patients

Cells taken from patients who went on to develop severe disease had a muted antiviral response compared to those who went on to develop mild disease

This suggests that it may be possible to develop early interventions that prevent severe COVID-19 from developing

The team also identified infected host cells and pathways associated with protection against infection that may enable new therapeutic strategies for COVID-19 and other respiratory viral infections

CAMBRIDGE, MA (July 23, 2021) -- Over the past 18 months, researchers have learned much about COVID-19 and its viral cause, SARS-CoV-2. They know how the virus enters the body, coming in through the nose and mouth and beginning its infection in the mucus layers of the nasal passageway. They know that infections that remain in the upper airway are likely to be mild or asymptomatic, while infections that progress down the airway to the lungs are much more severe and can lead to fatal disease. And they have identified common risk factors for severe disease, like age, gender, and obesity. But there are still many unanswered questions -- such as when, and where, the course of severe COVID-19 is determined. Does the pathway to severe disease begin only after the body has failed to control mild disease, or could it start much earlier than that?

Researchers at the Ragon Institute of MGH, MIT, and Harvard; the Broad Institute of MIT and Harvard; Boston Children's Hospital (BCH); MIT; and the University of Mississippi Medical Center (UMMC) wondered whether this path towards severe disease could start much earlier than expected -- perhaps even within the initial response created when the virus enters the nose.

To test this, they studied cells taken from nasal swabs of patients at the time of their initial COVID-19 diagnosis, comparing patients who went on to develop mild COVID-19 to those who progressed into more severe disease and eventually required respiratory support. Their results showed that patients who went on to develop severe COVID-19 exhibited a much more muted antiviral response in the cells collected from those early swabs, compared to patients who had a mild course of disease. The paper appears in Cell.

"We wanted to understand if there were pronounced differences in samples taken early in the course of disease that were associated with different severities of COVID-19 as the disease progressed," said co-senior author José Ordovás-Montañés, an associate member in the Klarman Cell Observatory at Broad and assistant professor at BCH and Harvard Medical School. "Our findings suggest that the course of severe COVID-19 may be determined by the body's intrinsic antiviral response to initial infection, opening up new avenues for early interventions that could prevent severe disease."

To understand the early response to infection, Sarah Glover of the Division of Digestive Diseases at UMMC and her laboratory collected nasal swabs from 58 people. Thirty-five swabs came from COVID-19 patients, taken at the time of diagnosis, representing a variety of disease states from mild to severe. Seventeen swabs came from healthy volunteers and six came from patients with respiratory failure due to other causes. The team isolated individual cells from each sample and sequenced them, looking for RNA that would indicate what kind of proteins the cells were making -- a proxy for understanding what a given cell is doing at the moment of collection.

Cells use RNA as instructions to make proteins -- tools, machinery, and building blocks used within and by the cell to perform different functions and respond to its environment. By studying the collection of RNA in a cell -- its transcriptome -- researchers understand how a cell is responding, at that particular moment in time, to environmental changes such as a viral infection. Researchers can even use the transcriptome to see if individual cells are infected by an RNA virus like SARS-CoV-2.

Alex Shalek, co-senior author on the study, a member of the Ragon Institute of MGH, MIT, and Harvard, and institute member at Broad, specializes in studying the transcriptomes of individual cells. His lab has helped develop innovative approaches to sequence thousands of single cells from low-input clinical samples, like the nasal swab of COVID-19 patients, and uses the resulting data to create high-resolution pictures of the body's orchestrated response to infection at the sample site.

"Our single-cell sequencing approaches allow us to comprehensively study the body's response to disease at a specific moment in time," said Shalek, who is also an associate professor at MIT in the Institute for Medical Engineering & Science, the Department of Chemistry, and the Koch Institute for Integrative Cancer Research. "This gives us the ability to systematically explore features that differentiate one course of disease from another as well as cells that are infected from those that are not. We can then leverage this information to guide the development of more effective preventions and cures for COVID-19 and other viral infections."

Ordovás-Montañés's lab studies inflammatory responses and their memory, specializing in those found in epithelial cells -- the top layer of cells, like those that line your nasal passageways and are collected by nasal swabs. Working with the Shalek lab and that of Bruce Horwitz, a senior associate physician in the BCH Division of Emergency Medicine, the researchers interrogated how both epithelial and immune cells were responding to early COVID-19 infection from the single-cell transcriptome data.

First, the team found that the antiviral response, driven by a family of proteins called interferons, was much more muted in patients who went on to develop severe COVID-19. Second, patients with severe COVID-19 had higher amounts of highly inflammatory macrophages, immune cells that contribute to high amounts of inflammation, often found in severe or fatal COVID-19.

Since these samples were taken well before COVID-19 had reached its peak state of disease in the patients, both these findings indicate that the course of COVID-19 may be determined by the initial or very early response of the nasal epithelial and immune cells to the virus. The lack of strong initial antiviral response may allow the virus to spread more rapidly, increasing the chances that it can move from the upper to lower airways, while the recruitment of inflammatory immune cells could help drive the dangerous inflammation in severe disease.

Finally, the team also identified infected host cells and pathways associated with protection against infection -- cells and responses unique to patients that went on to develop a mild disease. These findings may allow researchers to discover new therapeutic strategies for COVID-19 and other respiratory viral infections.

If, as the team's evidence suggests, the early stages of infection can determine disease, it opens a path for scientists to develop early interventions that can help prevent severe COVID-19 from developing. The team's work even identified potential markers of severe disease, genes that were expressed in mild COVID-19 but not in severe COVID-19. 

"Nearly all our severe COVID-19 samples lacked expression of several genes we would typically expect to see in an antiviral response," said Carly Ziegler, a graduate student in the Health Science and Technology program at MIT and Harvard and one of the study's co-first authors. "If further studies support our findings, we could use the same nasal swabs we use to diagnose COVID-19 to identity potentially severe cases before severe disease develops, creating an opportunity for effective early intervention."

Oncotarget published "Role for Fgr and Numb in retinoic acid-induced differentiation and G0 arrest of non-APL AML cells" which reported that retinoic acid is a fundamental regulator of cell cycle and cell differentiation.

Using a leukemic patient-derived in vitro model of a non-APL AML, these authors previously found that RA evokes activation of a macromolecular signaling complex, a signalosome, built of numerous MAPK-pathway-related signaling molecules; and this signaling enabled Retinoic-Acid-Response-Elements to regulate gene expression that results in cell differentiation/cell cycle arrest. Toward mechanistic insight into the nature of this novel signaling, they now find that the NUMB cell fate determinant protein is an apparent scaffold for the signalosome.

Numb exists in the cell bound to an ensemble of signalosome molecules, including Raf, Lyn, Slp-76, and Vav.

Fgr binds NUMB, which is associated with phosphorylation of NUMB and enhanced NUMB-binding and phosphorylation of select signalosome components, thereby betraying signalosome activation.

Signalosome activation is associated with cell differentiation along the myeloid lineage and G1/0 cell cycle arrest. If RA-induced Fgr expression is ablated by a CRISPR-KO; then the RA-induced phosphorylation of NUMB and enhanced NUMB-binding and phosphorylation of select signalosome components are lost. The cells now fail to undergo RA-induced differentiation or G1/0 arrest. In sum, this research team found that NUMB acts as a scaffold for a signaling machine that functions to propel RA-induced differentiation and G1/0 arrest, and that Fgr binding to NUMB turns the function on.

Dr. Andrew Yen from The Cornell University said, "Retinoic acid (RA) is a biologically fundamental regulator of cell proliferation and differentiation [1-3]. It is evolutionarily conserved and has widespread effects in numerous tissues."

It has been found that transcriptional activation by RAR/RXR to control cell differentiation and cell cycle arrest requires MAPK pathway related signaling to enable transcriptional activation necessary for driving cell differentiation/cell cycle G1/0 arrest.

The main finding is that the Numb fate determinant protein appears to act as a scaffold for the signalsome, binding a "spine" of molecules to which all other signalsome molecules are attached; and that RA induced expression of the Fgr SFK and its binding to Numb with phosphorylation> of Numb, as well as other prominent signalsome phosphorylation events, indicating activation of the signalsome.

SLP-76 gets phosphorylated with RA-induced Fgr in parental wt, but not in Fgr KO, cells; so phosphorylation of Slp-76, one of the most prominent RA-induced p-tyr phosphorylations, where Slp-76 is known to IP with Fgr and Lyn, is also associated with Fgr binding Numb.

Numb also binds Lyn, which is known to become Y416 phosphorylated with RA treatment; indicating that Fgr binding Numb is associated with phosphorylation of Lyn, where Slp-76 and Lyn are the closest associates of Fgr in the signalsome force node representation of known IP partners.

In sum the Oncotarget data support a paradigm where signaling molecules bound to a Numb scaffold in a signalsome are activated by RA-induced Fgr expression and its binding to Numb to propel RA-induced differentiation and G1/0 arrest. In essence, RA is ergo increasing the amount of signalsome and increasing the amount of Fgr to activate them, thereby driving the cell to differentiate.

The Yen Research Team concluded in their Oncotarget Research Output that a major challenge to RA differentiation therapy is the emergence of resistance to RA after the initial RA-treatment.

In an attempt to gain insight into how it develops, HL-60 cells resistant to RA were derived by sustained culture in progressively increasing RA concentrations.

A survey of expression of potentially responsible candidate molecules revealed that the biggest divergence between the parental cells and the RA-resistant derivatives was the failure of resistant cells to upregulate Fgr in response to RA.

Using drugs in lieu of Fgr to activate the signalsome in combination with RA may thus be a means of overcoming resistance.

Thus, the paradigm presented here may provide insights on candidates, the dysfunction of which are seminal to resistance.

Researchers from George Mason University, University of Manitoba, Colorado State University, and Georgetown University published a new paper in the Journal of Marketing that examines an unintended customer consequence of lobbying, decreased customer satisfaction, and also explains marketing-focused efforts that can help prevent it.

The study, forthcoming in the the Journal of Marketing, is titled "Shedding Light on the Dark Side of Firm Lobbying: A Customer Perspective" and is authored by Gautham Vadakkepatt, Sandeep Arora, Kelly Martin, and Neeru Paharia.

Lobbying, or attempts to sway government officials to make decisions beneficial to the lobbying firm, is an important means for businesses to manage their regulatory environment. Lobbying spending has increased by more than 130% since 1998 (Center for Responsive Politics) and many large firms maintain their own government affairs divisions, which retain dozens of lobbyists.

This new study reveals a dark side to lobbying. The research findings emphasize to managers that it is important to consider customer effects (e.g., potential loss of customer focus and reduction in customer satisfaction) of firm lobbying. These effects are surprising given that previous research has shown lobbying to have positive accounting and financial market returns, with some evidence that lobbying returns can be even higher than returns to investment in activities such as R&D. Investors view lobbying as favorable toward market value projections and it can signal critical firm influence when policies that affect them are being debated. Vadakkepatt explains, though, that "These assessments of lobbying's benefits have been conducted absent consideration of the firm's customers. Our findings show this is a significant oversight."

In an investigation of the lobbying effects on customer outcomes, the research team finds that increased lobbying spending leads to decreased customer satisfaction, which in turn reduces the effect of lobbying on firm value. Yet, it is unclear if customers are aware of a firm's specific lobbying efforts. Because of this, as Arora says, "Our team took a close look at what is happening inside the firm that causes increased lobbying spending to reduce customer satisfaction. Our research shows that lobbying leads to a loss of customer focus. That loss of customer focus can reduce customer satisfaction. This is an important finding for firms because it reveals an unintended customer consequence of lobbying."

The study's longitudinal analysis of firms shows that when accounting for customer satisfaction loss, the benefits firms otherwise receive from lobbying can be reduced. So, what, if anything, can firms do to prevent or minimize such losses? Several marketing-focused moderators can shift firm attention back to customers and reduce customer satisfaction losses from lobbying. First, firms with a marketing CEO suffer less customer satisfaction loss from lobbying. A CEO with a marketing background (as opposed to a CEO with some other functional area expertise) understands the need to monitor customer expectations and create customer value and thereby can align firm lobbying efforts with customer priorities. Firm spending on marketing-focused activities such as R&D and advertising also helps reduce customer focus loss. And finally, when firms lobby specifically for product market issues, they experienced reduced customer satisfaction loss. "These mitigating forces reveal that if firms choose to engage in lobbying, those efforts should be either aligned with customer-focused activities or counterbalanced by customer-focused resource allocations," says Martin.

There are public policy implications from these results as well. Paharia says that "Public sentiment suggests a growing distaste for lobbying and close ties between business and government. Our findings suggest that greater limits may be warranted in some areas to promote positive customer outcomes. Although counterintuitive, greater lobbying limits may work to benefit firms by redirecting focus to customers and by improving the quality of the firm's long-term customer outcomes."

Regardless of whether greater limits on lobbying are imposed, the study supports the need for continued disclosure mandates. Due to the Lobbying Disclosure Act, customers, special interest groups, advocates, and researchers can better understand the role of lobbying in modern business practice. Although this reporting necessarily creates a burden for firm compliance, it may have the unexpected benefit of showcasing when firms lobby for product market issues s, which can reduce otherwise negative effects on customer satisfaction.

In summary, lobbying is a source of firm spending that can have a negative connotation, even though finance and economics fields have long demonstrated the positive effects of lobbying for firm performance. This investigation sheds light on a critical dark side and reveals that the firm's focus on customers may be diminished when it also lobbies. Firm focus can be reoriented to customers, but doing so requires intentional, marketing-focused efforts.

A network of over 100 herbaria spread out across the southeastern United States recently completed the herculean task of fully digitizing more than three million specimens collected by botanists and naturalists over a span of 200 years. The project, which was funded by the National Science Foundation, is part of a larger, ongoing effort by natural history institutions worldwide to make their biological collections easily accessible to researchers studying broad patterns of evolution, extinction, range shifts, and climate change.

In a new study published in the journal Applications in Plant Sciences, researchers involved in the project analyzed the rate at which specimens could be reliably photographed, digitized, and databased to assess how much similar efforts might cost in the future.

"Everybody who was interested in this recognized very early on just how much labor and money we were talking about," said senior author Joey Shaw, associate professor of biology and herbarium curator at the University of Tennessee at Chattanooga.

Although digitization efforts had been underway at large institutions since the turn of the century, to date, no one had developed a robust framework for determining how much it cost to bring a set of collections online, noted Shaw.

"No one had really been doing it at any sort of scale to understand how many specimens you could catalog per minute."

Such information can be vitally important for smaller institutions that rely on a dwindling fraction of administrative funding to maintain their collections. At universities and liberal arts colleges, these efforts are also heavily reliant on students, who perform the work for college research credit or as student employees, which comes with its own associated set of benefits and pitfalls.

Digitizing specimens is often the first direct experience students have with natural history, and, for many, it blossoms into a lifelong appreciation for biology. For some, as was the case for four authors on the study, this appreciation later culminates in graduate studies and careers in the natural sciences.

Student employment, however, is by nature transient, and resources invested in training students is often duplicated when they graduate or move on to other projects. So, at the outset of the project's conception, Shaw and his colleagues wanted to integrate into their analyses the lag associated with student training along with the subsequent increase in productivity as students gained experience.

The resulting estimates were incredibly precise, to the extent that Shaw and his colleagues could pinpoint exactly when classes let out by analyzing the rates at which specimen photographs were uploaded.

"The students ended up being so efficient that the computer and internet speed actually starting slowing down the process when classes let out, when there's a surge of people picking up their phones," Shaw said.

With hundreds of thousands of specimens now freely accessible online, Shaw hopes that their data will help inform workers at other herbaria hoping to replicate their results. All of the partnering institutions in this study are members of the SouthEast Regional Network of Expertise and Collections (SERNEC), which supports more than 200 herbaria in the region that house a combined 15 million specimens, the majority of which have yet to be digitized.

With increasing amounts of habitat loss due to urbanization and deforestation, herbaria offer researchers a valuable window into ecosystems long-since developed or demolished. Many collections include specimens that are now extinct in the wild, while others have yielded the discovery of entirely new species. And as average global temperatures continue to rise, scientists are increasingly turning to herbaria collection data to analyze the effects climate change has already had on plant communities.

"Biologists have accumulated species data from all over the world, in the form of biological specimens, since at least the Renaissance, and we continue this practice today," Shaw said. "Our recent work has been to convert the data of these biological specimens into a freely accessible online database. It will be the largest dataset assembled on Earth's biodiversity, and we are only at the beginning of dreaming up research, conservation, and land management questions that will be answered with this database."

Levels of omega-3 fatty acids in the blood are as good a predictor of mortality from any cause as smoking, according to a study involving the Hospital del Mar Medical Research Institute (IMIM), in collaboration with The Fatty Acid Research Institute in the United States and several universities in the United States and Canada. The study, published in The American Journal of Clinical Nutrition, used data from a long-term study group, the Framingham Offspring Cohort, which has been monitoring residents of this Massachusetts town, in the United States, since 1971.

Researchers have found that omega-3 levels in blood erythrocytes (the so-called red blood cells) are very good mortality risk predictors. The study concludes that "Having higher levels of these acids in the blood, as a result of regularly including oily fish in the diet, increases life expectancy by almost five years", as Dr. Aleix Sala-Vila, a postdoctoral researcher in the IMIM's Cardiovascular Risk and Nutrition Research Group and author of the study, points out. In contrast, "Being a regular smoker takes 4.7 years off your life expectancy, the same as you gain if you have high levels of omega-3 acids in your blood", he adds.

2,200 people monitored over eleven years

The study analysed data on blood fatty acid levels in 2,240 people over the age of 65, who were monitored for an average of eleven years. The aim was to validate which fatty acids function as good predictors of mortality, beyond the already known factors. The results indicate that four types of fatty acids, including omega-3, fulfil this role. It is interesting that two of them are saturated fatty acids, traditionally associated with cardiovascular risk, but which, in this case, indicate longer life expectancy. "This reaffirms what we have been seeing lately", says Dr Sala-Vila, "not all saturated fatty acids are necessarily bad." Indeed, their levels in the blood cannot be modified by diet, as happens with omega-3 fatty acids.

These results may contribute to the personalisation of dietary recommendations for food intake, based on the blood concentrations of the different types of fatty acids. "What we have found is not insignificant. It reinforces the idea that small changes in diet in the right direction can have a much more powerful effect than we think, and it is never too late or too early to make these changes", remarks Dr Sala-Vila.

The researchers will now try to analyse the same indicators in similar population groups, but of European origin, to find out if the results obtained can also be applied outside the United States. The American Heart Association recommends eating oily fish such as salmon, anchovies or sardines twice a week because of the health benefits of omega-3 acids.

An international collaborative study led by University of Helsinki has conducted a holistic study to investigate the effects of COVID-19 restrictions on several air quality pollutants for the Po Valley region in northern Italy. The area is well known to have one of the worst air quality standards in Europe and is highly influenced by anthropogenic (human-led) activities. The study was done between research groups in Finland, Italy and Switzerland and the results were published in the journal Environmental Science: Atmospheres.

Scientists have combined air quality measurements and computer simulation data over several locations in the region. The resulting studies show that reduced emissions from traffic lead to a strong reduction of nitrogen oxides, while have had limited impact on aerosol concentrations, contributing to a better understanding of how the air pollution is formed in the Po Valley.

The studies show that despite the large reduction in mobility of people and emissions from cars (which raise for instance nitrogen oxides concentrations), aerosols concentrations remained almost unchanged compared to previous years. Secondary formed pollutants like ozone, on the other hand, showed an increase in concentrations. These findings were confirmed by a computer model simulation that simulates the COVID-19 restriction on traffic, indicating that the increased overall oxidation capacity of the atmosphere might have enhanced the formation of new aerosols.

Furthermore, model simulations indicated that as nitrogen oxides emissions were largely reduced, chemical reactions of organic gases against atmospheric oxidants increased, slightly favoring the formation of new organic particles.

"You can think of the Po Valley region as a massive batch reactor with all sort of chemicals. Altering one of the "ingredients" can trigger non-linear responses in air pollutants concentrations", says Dr Federico Bianchi from the Institute for Atmospheric and Earth System Research (INAR) of University of Helsinki.

These studies shade new lights on the formation of air pollutants in the Po Valley region and on their sources. The conclusion is that the reduction in traffic emissions had little impact on particulate matter concentrations, possibly highlighting the importance of other emissions sources in the Po Valley area.

Carefully characterizing the evolution of such emission categories are of a vital importance to improve the understanding of the air pollution and to reduce the uncertainties in future air quality scenarios.

SAN FRANCISCO, CA--July 22, 2021--To speed up a chemical reaction, a chemist might place the reactants over a Bunsen burner. Adding heat increases the degree of random movements and collisions of particles, accelerating the reaction.

In cell biology, one important "reaction" is the transformation of stem cells into all the other cells in the body, a process known as differentiation. Gladstone Institutes researchers have now discovered a molecular mechanism that acts like a Bunsen burner to "turn up the heat" and accelerate differentiation.

However, instead of boosting temperature, this process amplifies random fluctuations in levels of gene expression--or which genes are turned on or off within a cell. Boosting these fluctuations, also known as "noise," appears to aid the switch from one cell type to another.

"Researchers have studied and characterized these fluctuations, or 'noise' in gene expression, for decades," says Leor Weinberger, PhD, William and Ute Bowes Distinguished Professor, and director of the Center for Cell Circuitry at Gladstone. "But it was unclear if this noise was simply an unavoidable by-product of gene expression, which was widely assumed, or if it played some functional role."

Now, as reported in the journal Science, he and his team have discovered a pathway they named discordant transcription through repair (DiThR, pronounced "dither"). The DiThR pathway appears to boost the noisiness of gene expression in stem cells and enhance their ability to differentiate.

A New Fundamental Mechanism

The discovery of the DiThR pathway arose from the team's earlier work on HIV.

"We'd been tackling a long-standing problem in HIV, namely how to alter HIV's ability to persist in a long-lived latent state in patients," says Weinberger, who is also a professor of biochemistry and biophysics, and pharmaceutical chemistry at UC San Francisco (UCSF). "We discovered that molecules that alter viral expression noise also reduced HIV persistence."

"It was pretty startling when these same molecules worked in stem cells," he adds. "And, trying to understand how these molecules work turned into a search for a fundamental biological mechanism."

When a gene is turned on, or expressed, the information stored in the gene is used to build substances that a cell needs to function. But the vast majority of genes do not stay on all the time.

Most genes toggle--or switch between active and inactive states, turning on and off--every few minutes to every few hours. This creates noise in gene-expression levels. HIV, once it infects a cell, acts very much like a human gene and exhibits similar noise properties.

While studying HIV, Weinberger's team uncovered the existence of molecules that could enhance noise, or switch the expression machinery between active and inactive states, but, curiously, without affecting the average level of expression. They called them noise-enhancer molecules. These molecules acted like Bunsen burners for gene expression and increased the efficiency of drugs designed to wake HIV from a silent state, which is part of a strategy to cure patients.

But how these noise-enhancer molecules could boost noise without altering expression levels was completely unknown.

On a whim, the scientists examined what happened when noise-enhancer molecules were applied to embryonic stem cells without HIV. Amazingly, these molecules had the same effect on stem cells as they did on HIV, amplifying noise without changing the expression level. They also accelerated the stem cells' ability to transform into other cell types.

The team's main findings were that the mechanism by which noise-enhancer molecules boost noise involves a process for repairing certain errors in DNA that may arise when genes are turned on. A key component of this DNA repair process is a protein known as AP endonuclease 1 (Apex1).

"We found that Apex1 directly alters the shape of the DNA double helix in a way that first impedes and then accelerates gene expression," says the study's first author, Ravi Desai, an MD/PhD student in the UCSF Medical Scientist Training program in Weinberger's lab.

The team showed that Apex1 is the critical factor in this new DiThR pathway, which increases noise across the entire array of genes in the genome.

Making Differentiation More Efficient

Next, because some noise-enhancer molecules are found naturally in stem cells, the team asked how the newly discovered mechanism might affect the transformation of stem cells into other cell types. They treated mouse embryonic stem cells with both noise-enhancer molecules and substances that prompt differentiation into other types of cells.

They found that the increased noise imparted by DiThR allowed the stem cells to differentiate more efficiently, like the Bunsen burner does for chemical reactions.

What's more, the mechanism also worked in the opposite direction. It improved the efficiency of a process that turns differentiated cells back into pluripotent stem cells, which have the potential to become several different cell types--a finding that earned Gladstone scientist Shinya Yamanaka, MD, PhD, a Nobel Prize in 2012.

"Our findings suggest that the DiThR pathway makes cells more responsive to the signals that guide their fate," says Desai. "That means this mechanism may play a fundamental biological role in the development of embryos."

Looking ahead, the research team plans to further map out the various components of the DiThR pathway.

"Our goal now is to understand how DiThR is regulated and if associated noise-control pathways exist," Weinberger says. "Ultimately, approaches to harness these pathways could dramatically improve cellular engineering and stem cell-based therapies."

CHAPEL HILL, North Carolina--Researchers at the UNC Lineberger Comprehensive Cancer Center demonstrated in a clinical trial in Malawi that a five-drug combination chemotherapy provided curative benefit compared to current standard-of care-therapy in people diagnosed with lymphoma, and now they have determined this option is also cost-effective. The economic finding appeared July 22, 2021, in Lancet Global Health.

The clinical trial results, reported May 19, 2021, in Lancet Global Health involved 37 people with diffuse large B-cell lymphoma (DLBCL). The majority of patients were also HIV-positive, which greatly increased their risk of DLBCL; all HIV-positive patients were treated with anti-viral drugs. The trial participants received a standard four-drug chemotherapy combination known as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) along with rituximab, an antibody therapy. After two years of follow-up, 55 percent of the patients were still alive, an outcome that is higher than CHOP alone based on earlier studies.

With the trial results in hand, the researchers wanted to know if either CHOP or CHOP plus rituximab were cost-effective treatments in a resource-limited setting. Demographically, Malawi is a sub-Saharan country in Africa with roughly 19 million residents. The healthcare resources available in the 2017-2018 government budget for Malawi were $170 million dollars (about $9 per person); external donors contribute approximately another $350 million annually to health expenditures.

UNC Lineberger's Matthew Painschab, MD, lead author of the economic analysis and co-lead author of the treatment efficacy study, said cost-effectiveness analyses allow comparisons across diverse diseases so that limited resources can be optimally allocated.

"Without such analyses, relatively expensive upfront costs for cancer medicines will often seem prohibitively costly for a relatively small number of patients compared to other available public health interventions," said Painschab, assistant professor in the Division of Hematology at UNC School of Medicine and a member of UNC-Project Malawi. "We demonstrated that an upfront, time-limited expense followed by decades of healthy life may be a prudent investment, relative to other accepted interventions such as daily, lifelong antiretroviral treatment for HIV."

On a per-patient basis, comparing supportive care (no chemotherapy) to chemotherapy with CHOP, chemotherapy prevented more than seven disability-adjusted life years (DALYs) at a cost of $193 per DALY prevented. One DALY is a year of life lived in perfect health and therefore losses represent both years lost from dying early as well as quality life-years lost to disability. Adding rituximab to CHOP prevented about three DALYs at a cost of $1,145 per DALY.

"Our analysis has important implications for saving lives," said Painschab. "Though precise estimates of cancer incidence are lacking, we estimate it would cost about one million dollars annually to treat all cases of DLBCL in Malawi with CHOP, saving an estimated 252 lives. For two million dollars more annually, we could add rituximab, which costs about $500 a dose in Malawi, and the five-drug regimen could save an additional 100 lives."

In addition to the recently published studies, the researchers are conducting some of the first molecular profiling studies for HIV-associated lymphoma in the world. They hope that greater biologic understanding of DLBCL in Malawi may lead to more targeted, safe and effective treatment strategies. They note there is still much work to be done in this area, both in the U.S. and Malawi.

"Proving that treating DLBCL in Malawi can be cost-effective was not necessarily intuitive, as upfront costs of treating cancer patients often seem daunting for countries facing many competing health priorities," noted Stephen Kimani, MD, a fellow in Hematology/Oncology at UNC-Chapel Hill and research fellow at UNC Project Malawi and first author of the study that found the combination therapy was effective. "Investments in high-quality, potentially curative cancer care may be very prudent when short-term costs result in a normal life expectancy thereafter. These sorts of demonstrations will hopefully spur a treatment access movement for cancer that is analogous to what has occurred for HIV."

ROCHESTER, Minn. -- A new study by Fergus Couch, Ph.D., of Mayo Clinic Cancer Center, along with collaborators from the CARRIERS consortium, suggests that most women with breast cancer diagnosed over 65 should be offered hereditary cancer genetic testing. The study was published Thursday, July 22, in the Journal of Clinical Oncology.

Dr. Couch says that women over 65 rarely qualify for hereditary cancer genetic testing based on current testing guidelines because they are thought to exhibit low rates of genetic mutations in breast cancer genes.

"Most studies of breast cancer genes have not looked at older women, those who were diagnosed over the age of 65," says Dr. Couch. He says these studies have mainly tested women with a strong family history of breast or ovarian cancer rather than those in the general breast cancer population. By studying older women from the general breast cancer population, the investigators aimed to determine if these women should be routinely offered genetic testing.

"We were not sure what this study of the older breast cancer population would yield, but our results support broader testing, regardless of age or family history," says Dr. Couch.

The researchers evaluated women with breast cancer diagnosed after 65 and matched unaffected women from the large population in the CARRIERS study for age, race, and ethnicity.

"We found that mutations in actionable breast cancer risk genes were present in 3.2% of the women with breast cancer," says Dr. Couch.

When the researchers considered only high-risk breast cancer genes, including BRCA1, BRCA2 and PALB2, they found that 1.35% of women with breast cancer exhibited mutations and that more than 2.5% of women with estrogen receptor-negative breast cancer had high-risk mutations, regardless of their age.

"As 2.5% mutation frequency is often used to trigger genetic testing, these results suggest that all women with estrogen receptor-negative breast cancer ? and perhaps all women with breast cancer, including those diagnosed over age 65 ? should be offered hereditary breast cancer testing," says Dr. Couch.

Dr. Couch also notes that women over 65 with high-risk mutations may benefit from targeted therapies and improved risk assessment for secondary breast cancers. He adds that family members of these women also may benefit from risk assessment.

Osaka, Japan - Gross chromosomal rearrangements—where portions of the genome become moved, deleted, or inverted—can lead to cell death and diseases such as cancer in complex multicellular organisms. However, the details of how exactly these occur remain unknown. Now, studies in a single-celled organism called fission yeast have found evidence for the involvement of a protein called Rad8.

When DNA replicates or repairs itself, three copies of a protein called PCNA bind together and form a ring-like structure surrounding the DNA strand. This ring structure acts like a clamp and slides along the DNA strand. The team showed that Rad8 attaches a small molecule called ubiquitin to this PCNA protein at the amino acid in the 107th position. This amino acid is a lysine molecule, termed "lysine 107," located at the interface between the different PCNA molecules.

Ubiquitin attachment is a common biological process serving a variety of functions. "In this case, the attachment of ubiquitin at lysine 107 weakens the interactions between PCNA molecules and changes the structure of the ring of proteins," says lead author of the paper Jie Su. This then alters how PCNA functions and leads to the formation of gross chromosomal rearrangements instead of accurate DNA repair.

Rad8 is a ubiquitin ligase, the molecule that is responsible for attaching a ubiquitin to a particular place on another protein. "We found that Rad8 works together with another protein called Mms2-Ubc4, a ubiquitin conjugating enzyme," says Takuro Nakagawa, senior author. "Mms2-Ubc4 brings in the ubiquitin molecule, and Rad8 then transfers the ubiquitin to lysine 107 of PCNA." The combined action of Rad8 and Mms2-Ubc4 is therefore responsible for causing gross chromosomal rearrangements.

But how does this information on a single-celled organism like yeast relate to cancer in complex organisms such as humans? Not much is known about HLTF, the human equivalent to Rad8, but it is seen to be activated and upregulated in cancer. Inhibition of HLTF, or inhibiting the attachment of ubiquitin to PCNA at the human equivalent of the lysine 107 position, could therefore be a very promising new strategy for cancer therapies.

UNIVERSITY PARK, Pa. -- Infection with dengue virus makes mosquitoes more sensitive to warmer temperatures, according to new research led by Penn State researchers. The team also found that infection with the bacterium Wolbachia, which has recently been used to control viral infections in mosquitoes, also increases the thermal sensitivity of the insects. The findings suggest that global warming could limit the spread of dengue fever but could also limit the effectiveness of Wolbachia as a biological control agent.

"Dengue fever, a potentially lethal disease for which no treatment exists, is caused by a virus, spread by the bite of the mosquito Aedes aegypti. This mosquito is also responsible for transmitting a number of disease-causing viruses, including Zika, chikungunya and yellow fever," said Elizabeth McGraw, professor and head of the Department of Biology, Penn State. "Aided by increasing urbanization and climate change, this mosquito's range is expected to overlap with 50% of the world's population by 2050, dramatically increasing the number of people who could potentially be exposed to these viruses."

In recent years, research groups around the world have attempted to control these viruses by infecting Ae. aegypti with the bacterium Wolbachia pipientis and then releasing the mosquitoes into the environment, McGraw explained.

"Wolbachia have been shown to prevent viruses, including dengue, from replicating inside mosquitoes," she said. "Importantly, Wolbachia are passed down to the mosquitoes' offspring, making them a self-propagating and lower-maintenance approach to disease control in the field."

McGraw noted that both dengue virus and Wolbachia infect a variety of tissues throughout a mosquito's body, and although they are not toxic, they do evoke an immune stress response.

"Since mosquitoes that are infected with dengue virus and/or Wolbachia are already suffering a stress response, we thought that they would be less well equipped to deal with an additional stressor, such as heat," she said.

To investigate the effects of heat on dengue and Wolbachia-infected mosquitoes, the team placed infected mosquitoes in sealed vials and then submerged the vials into a water bath heated to 42°C -- a realistic temperature extreme that a mosquito might encounter in the wild. The researchers then measured how long it took for the mosquitoes to become immobilized and compared the time to uninfected control mosquitoes. Their findings appear today (July 22) in the journal PLOS Neglected Tropical Diseases.

"After a lot of trial and error, we were successfully able to adapt a heat-based physiological assay commonly used in Drosophila [a model fruit fly species] to our mosquito species to examine the impact of both dengue virus and Wolbachia infections on thermal sensitivity," said Fhallon Ware-Gilmore, graduate student in the Department of Entomology and Center for infectious Disease Dynamics at Penn State who led the project.

The team found that mosquitoes infected with dengue virus showed greater sensitivity to heat; they became immobilized almost three times faster than uninfected mosquitoes when placed in the hot water bath. Similarly, mosquitoes infected with Wolbachia became immobilized four times faster than uninfected mosquitoes.

Interestingly, Ware-Gilmore said, the two agents -- dengue virus and Wolbachia bacteria -- did not have an additive effect on mosquito thermal tolerance.

"You might expect that mosquitoes infected with both dengue virus and Wolbachia might become immobilized even faster than mosquitoes infected with only one or the other microbe, but we did not find an additive effect," she said. "We are, however, the first to show that viral infection can affect mosquito thermal tolerance, specifically by reducing mosquito survival during exposure to high heat. And, while there are some known interactions between heat and Wolbachia, particularly in immature stages, this is also the first study to show that adult infected-mosquitoes have reduced survival during heat stress."

Ware-Gilmore noted that future climate models point to increasing frequencies of extreme temperature events, making short exposures to high temperatures a threat to the survival of dengue and Wolbachia infected mosquitoes.

"At lower temperatures, we know that dengue virus may fail to replicate fast enough to make it through the mosquito body and be transmitted, thereby reducing transmission risk," she said. "At higher temperatures, while the virus may replicate faster, our work suggests that a corresponding reduction in mosquito thermal tolerance may act as a counterforce on mosquito survival that could help to reduce transmission and potentially human disease incidence in hotter, more climate-variable regions. Similarly, our work suggests that Wolbachia may fail to work as a biocontrol agent in hotter regions given its effect on mosquito survival."