Culture

Hershey, Pa. -- Financial instability, lack of infrastructure, a deteriorating sense of community and family fragmentation are key contributors to diseases of despair in Pennsylvania communities, according to Penn State College of Medicine and Highmark Health researchers. The researchers conducted four focus groups in Pennsylvania communities identified as having high rates of despair-related illnesses.

Diseases of despair are medical diagnoses involving alcohol-related disorders, substance-related disorders and suicidal thoughts and behavior. Princeton economists Anne Case and Angus Deaton proposed the concept of deaths of despair in 2015 after observing a decline in life expectancy of middle-aged white men and women between 1999 and 2015 -- the first such decline since the flu pandemic of 1918. They theorized that this decline is associated with the social and economic downturn in rural communities and small towns over the last several decades, leading to feelings of despair and loss of hope for the future.

"The crisis in recent years has broadened past this initial demographic that Case and Deaton established, and we are now seeing rising excess mortality in other groups of working-class Americans, including people of color," Daniel George, associate professor of humanities and public health sciences, Penn State College of Medicine, said. George is a researcher with a Penn State Clinical and Translational Science Institute project looking at diseases of despair in Pennsylvania.

The first phase of this project analyzed Highmark Health insurance claims and found that the rate of diagnoses related to diseases of despair -- alcohol-related disorders, substance-related disorders and suicidal thoughts and behaviors -- increased significantly in the past decade.

"Nearly one in 20 people in the study sample of 12 million people were diagnosed with a disease of despair in our earlier research," Emily Brignone, Highmark Health, said. "Following Case and Deaton's findings, we saw the most substantial percentage increase in disease of despair diagnoses among men ages 35 to 74, followed by women ages 55 to 74 and 18 to 34. The issue is one of great importance that we are proud to be addressing with Penn State."

Using the data from the first study, the researchers then identified hotspots in Pennsylvania with a high rate of diagnoses related to diseases of despair for the second phase of the project. A disease of despair rate was determined by dividing the number of unique members with a qualifying diagnosis during that year by the total number of members. Researchers selected communities in Dauphin and Lebanon counties and conducted focus groups through existing community partnerships. Researchers report their results in the journal JAMA Network Open.

"Most of the research on deaths and diseases of despair have been at the epidemiological level; in other words, looking at large data sets and trying to identify patterns over time," George said. "There has been less done qualitatively - basically exploring the perceptions and beliefs of people who are affected by diseases of despair, trying to understand what is happening on the ground."

Four focus groups included a total of 60 participants. Focus group members were both residents and community health workers who interact with those affected by diseases of despair. The research team analyzed transcripts of the focus groups to identify themes.

The first theme researchers identified was the role of financial instability and how United States domestic policy contributes to self-harming behavior.

"One of the main findings was that financial distress is at the heart of it," George said. "It is something that has been driving instability in people's lives and increases the risk for drug abuse and escape through drugs and drink. People identified jobs with full benefits and a living wage not being as available as they used to be and people having to choose groceries over medical care and their anti-anxiety medications."

The second theme that researchers identified was a lack of infrastructure, especially in rural communities.

"Focus group participants noted a lack of public transportation that could help people get to their jobs or to their health care appointments, and the role that played in compounding distress in people's lives," George said. "They also identified failures in our school systems that were resulting in schools not preparing kids to have trades or skills to make them competitive in a 21st-century economy."

The third theme that researchers identified was a deteriorating sense of community. Participants discussed fragmentation over the last several decades that has led to rising isolation and distrust, and a lack of neighborly support. These trends have been worsened, in part, by social media.

"There was a really interesting perception that there has just been a general decline in the community," George said. "There is more loneliness, more alienation, a loss of trust among people, less neighborly interactions. People talked about just feeling an absence of actual human connection online with technology and electronic devices, and that it has taken the place of tangible, real human connection-- and that that compounds loneliness."

The final theme researchers identified was the fragmentation of the family.

"There is more pressure on two-earner families, and that was leading to kids being less bio-psychosocially developed and leaving home at greater risk for despair-related behaviors," George said.

Researchers will next consider potential solutions, including the role of health care facilities in identifying despair-related risk factors, partnerships with community organizations that work with those most at risk and the use of big data analysis and machine learning to identify at-risk communities and guide state-level policy changes. Focus group attendees shared their beliefs that more needed to be done at the local and state levels to address the causes of despair, including non-profit initiatives, peer support, infrastructure building, economic development and rebuilding a sense of community as well as social safety nets.

"A key message is really that we do not want to blame the victims here," George said. "Despair is something that is an indictment of the way that we have organized our society rather than a personal failing or an individuated sense of despair that somebody may feel. People are responding to objectively worsening material circumstances in their lives. What we are trying to do with the diseases of despair construct is essentially create a parameter whereby we can measure it, study it, try to understand what is going on and then address root causes."

University of Virginia School of Medicine researchers have discovered a previously unknown repair process in the brain that they hope could be harnessed and enhanced to treat seizure-related brain injuries.

Common seizure-preventing drugs do not work for approximately a third of epilepsy patients, so new and better treatments for such brain injuries are much needed. UVA's discovery identifies a potential avenue, one inspired by the brain's natural immune response.

Using high-powered imaging, the researchers were able to see, for the first time, that immune cells called microglia were not just removing damaged material after experimental seizures but actually appeared to be healing damaged neurons.

"There has been mounting generic support for the idea that microglia could be used to ameliorate seizures, but direct, visualized evidence for how they could do this has been lacking," said researcher Ukpong B. Eyo, PhD, of UVA's Department of Neuroscience, the UVA Brain Institute and UVA's Center for Brain Immunology and Glia (BIG). "Our results indicate that microglia may not be simply clearing debris but providing structural support for neuronal integrity that may have implications even beyond the scope of seizures and epilepsy."

A Surprising Response to Seizures

The new findings come from a collaboration of scientists at UVA, Mayo Clinic and Rutgers University. They used an advanced imaging technique called two-photon microscopy to examine what happened in the brains of lab mice after severe seizures. What they saw was strange and unexpected.

Rather than simply cleaning up debris, the microglia began forming pouches. These pouches didn't swallow up damaged material, as many immune cells do. Instead, they began tending to swollen dendrites - the branches of nerve cells that transmit nerve impulses. They weren't removing, the scientists realized; they appeared to be healing.

These odd little pouches - the scientists named them "microglial process pouches" - stuck around for hours. They often shrank, but they were clearly doing something beneficial because the dendrites they targeted ended up looking better and healthier than those they didn't.

"We did not find microglia to be 'eating' the neuronal elements in this context," Eyo said. "Rather, we saw a strong correlation between these interactions and a structural resolution of injured neurons suggestive of a 'healing' process."

The new insights into the brain's immune response points scientists in promising new directions. "Although these findings are exciting, there is yet a lot to follow-up on them. For example, the precise mechanisms that regulate the interactions remain to be identified. Moreover, at present, the 'healing' feature is suggested from correlational results and more definitive studies are required to certify the nature of the 'healing,'" Eyo said. "If these questions can be answered, they will provide a rationale for developing approaches to enhance this process ... in seizure contexts."

Eyo has already received two grants totaling almost $5 million from the National Institutes of Health to continue his study of microglia. The funding will allow him to study how the immune cells help regulate vascular function, which could be important in diseases such as Alzheimer's, and their role in brain-hyperactivity disorders such as febrile seizures that can trigger epilepsy.

"With this new funding, we are eager to clarify roles for microglia in seizure disorders and vascular function," he said. "UVA's continued investment is neuroscience research provides a suitable home for our lab's research."

Many disease-causing bacteria such as Pseudomonas aeruginosa crawl on surfaces through a walk-like motility known as "twitching". Nanometers-wide filaments called type IV pili are known to power twitching, but scientists ignore which sensory signals coordinate the microbes' movements.

Now, EPFL researchers have found that Pseudomonas bacteria use a mechanism similar to our sense of touch to navigate on surfaces. "This study changes the way we think about motility in bacteria," says senior author Alexandre Persat, a tenure track assistant professor at EPFL's School of Life Sciences.

Scientists have known that cells from humans and other animals can direct themselves in the direction of stiffer or looser surfaces, but it was unclear whether bacteria could also guide their movement based on mechanical force, Persat says. That's because most studies have focused on identifying mechanisms that guide bacteria to swim towards chemicals such as food, a phenomenon known as chemotaxis.

Research in the Persat lab has instead focused on how bacteria sense and respond to mechanical forces. Previous studies showed that Pseudomonas' pilus works like a harpoon: after it extends and touches a surface, the pilus activates a molecular motor that retracts the filament, thus propelling the cell forward.

To understand what coordinates the pili motors, researchers in the Persat group and their collaborators at the University of California, San Francisco, looked at how individual Pseudomonas bacteria move on surfaces such as the bottom of a laboratory dish. The team suspected that a network of proteins called Chp system regulates twitching, so they analyzed bacteria that lacked different components of the Chp system. Some of these mutant bacteria could barely move as they kept twitching back and forth; others always moved forward, even when they bumped into an obstacle.

By combining fluorescent tags with a microscopy technique that helps to look at single pili in living cells, the researchers found that one messenger protein activates the pili to extend, propelling the cell forward, whereas another protein inhibits the formation of pili at the front of the moving cell. The two opposing messengers aren't found in the same place within the cell. "The activator localizes to the front, where the cell feels the surface with its pili, while the inhibitor localizes everywhere else," says study co-first author Marco Ku?hn.

When bacteria bump into an obstacle such as another cell, the inhibitor allows them to stop and change direction, the researchers found. "This helps the cells navigate based on what they feel in front of them -- like a blind person using a white cane," Persat says. The ability to sense the surrounding environment is useful when bacteria move as a group, he adds, as it helps the microbes to all crawl forward in the same direction.

The findings, published in PNAS, shed light on how bacteria move and could have important implications for human health. Pseudomonas aeruginosa, an opportunistic pathogen that is commonly found in soil, is a leading cause of hospital-acquired infections. Aggregates of Pseudomonas bacteria typically form on surfaces such as catheters and respirators and can be extremely resistant to disinfectants and antimicrobial drugs.

What's more, past research from the Persat group showed that Pseudomonas uses its pili to regulate the secretion of toxins. For this reason, understanding more about the microbes' "sense of touch" could help to develop new therapeutic strategies, Persat says.

Next, the researchers aim to uncover how the bacteria convert a mechanical stimulus into a cellular response, says study co-first author Lorenzo Talà. "We would like to understand the molecular mechanism behind the [bacteria's] sense of touch," he says.

How does a view of nature gain its gloss of beauty? We know that the sight of beautiful landscapes engages the brain's reward systems. But how does the brain transform visual signals into aesthetic ones? Why do we perceive a mountain vista or passing clouds as beautiful? A research team from the Max Planck Institute for Empirical Aesthetics has taken up this question and investigated how our brains proceed from merely seeing a landscape to feeling its aesthetic impact.

In their study, the research team presented artistic landscape videos to 24 participants. Using functional magnetic resonance imaging (fMRI), they measured the participants' brain activity as they viewed and rated the videos. Their findings have just been published in the open-access journal Frontiers in Human Neuroscience. First author A. Ilkay Isik encapsulates:

"We would have expected the aesthetic signals to be limited to the brain's reward systems, but surprisingly, we found them already present in visual areas of the brain while the participants were watching the videos. The activations occurred right next to brain regions deployed in recognizing physical features in movies, such as the layout of a scene or the presence of motion."

Senior author Edward Vessel suggests that these signals may reflect an early, elemental form of beauty perception:

"When we see something beyond our expectations, local patches of brain tissue generate small 'atoms' of positive affect. The combination of many such surprise signals across the visual system adds up to make for an aesthetically appealing experience."

With this new knowledge, the study not only contributes to our understanding of beauty, but may also help clarify how interactions with the natural environment can affect our sense of well-being. The results might have potential applications in a variety of fields where the link between perception and emotion is important, such as clinical health care and artificial intelligence.

Alexandria, Va., USA - Ruth Lipman, American Dental Association (ADA) Science and Research Institute, Chicago, Ill., U.S., presented the poster "Strategies for Disseminating Guidance to Dentists during the COVID-19 Pandemic" at the virtual 99th General Session & Exhibition of the International Association for Dental Research (IADR), held in conjunction with the 50th Annual Meeting of the American Association for Dental Research (AADR) and the 45th Annual Meeting of the Canadian Association for Dental Research (CADR), on July 21-24, 2021.

Rapidly formulated, actionable infection risk mitigation strategies for dental care professionals were needed during the initial acceleration phase of the COVID-19 pandemic. Between March 2020 and February 2021, the content developed by the ADA to address dentists' needs for COVID-19 related practice guidance has been cataloged. Insight about the strategies and approaches to their formulation, intended use, publication/posting date and utility as assessed by number of downloads and visits from ADA.org was evaluated with respect to the chronology of the pandemic.

The ADA established a centralized hub online to disseminate the latest COVID-19 evidence, policy and guidance. In April 2020, the ADA received more than 2,360 COVID-19 related member queries. Initial ADA guidance to mitigate virus transmission relied on information about safety considerations extrapolated from medical rather than dental settings to produce several decision algorithms (16,529 downloads) and a reference document (22,176 downloads) citing supporting information sources.

The initial guidance algorithms were for provision of urgent and emergency care and addressed patient screening, use of professional protective equipment, operatory disinfection and patients' treatment. A companion document that defined urgent and emergency care (58,551 downloads) was reviewed by the ADA Board of Trustees. As restrictions on provision of dental care were lifted, increased member volunteer engagement was considered prudent to better ensure the relevance and feasibility of the guidance informing about a more comprehensive range of dental care. The resultant return-to-work toolkit (32,441 downloads) has been accessed more than 640,370 times.

This presentation summarizes and evaluates the clinical guidance and other evidence-based resources developed for dentists and patients by the American Dental Association (ADA) during the COVID-19 pandemic.

A new optogenetic tool, a protein that can be controlled by light, has been characterized by researchers at Ruhr-Universität Bochum (RUB). They used an opsin - a protein that occurs in the brain and eyes - from zebrafish and introduced it into the brain of mice. Unlike other optogenetic tools, this opsin is not switched on but rather switched off by light. Experiments also showed that the tool could be suitable for investigating changes in the brain that are responsible for the development of epilepsy.

The teams led by Professor Melanie Mark from the Behavioural Neurobiology Research Group and Professor Stefan Herlitze from the Department of General Zoology and Neurobiology describe the experiments and results in the journal Nature Communications, published online on 23 July 2021.

Role assumed in various conditions

The opsin Opn7b is a G protein-coupled receptor which is found in zebrafish. Unlike many other light-activated G protein-coupled receptors, it can be activated without a light stimulus and is thus permanently active; researchers call this constitutively active. Normally, activation of G protein-coupled receptors leads to an opening of certain ion channels and thus to the influx of ions into the cell as well as to further signalling processes in the cell. In the case of Opn7b, light deactivates this permanently active signalling chain.

Little research has so far been conducted on G protein-coupled receptors that are activated without stimulation, although it is presumed that they play a role in various neuropsychiatric conditions and night blindness. They also appear to be involved in the development of virally induced cancers.

Receptor characterized more precisely

Dr. Raziye Karapinar, Dr. Ida Siveke and Dr. Dennis Eickelbeck characterized the function of Opn7b in detail and, to their surprise, identified that the receptor is deactivated by light. In contrast, conventional optogenetic tools are switched on by light.

The researchers consider Opn7b well-suited to gain further insights into the function of G protein-coupled receptors that are constitutively active - and obtain new knowledge of their role in the development of diseases in which the receptors can be examined in a time-controlled manner in specific cell types.

Epileptic seizures

The Bochum researchers Dr. Jan Claudius Schwitalla and Johanna Pakusch changed certain cells in the cerebral cortex of mice in such a way that they produced Opn7b. If they deactivated the receptor with light, it triggered epileptiform activity in the animals, which could be specifically controlled with light and interrupted with the help of other light-controlled proteins. The researchers hope that it will be possible to use this optogenetic tool to understand more precisely both the underlying mechanisms and the timescales in the development of epileptic seizures.

As the SARS-CoV-2 virus that causes COVID-19 continues to evolve, immunologists and infectious diseases experts are eager to know whether new variants are resistant to the human antibodies that recognized initial versions of the virus. Vaccines against COVID-19, which were developed based on the chemistry and genetic code of this initial virus, may confer less protection if the antibodies they help people produce do not fend off new viral strains. Now, researchers from Brigham and Women's Hospital and collaborators have created an "atlas" that charts how 152 different antibodies attack a major piece of the SARS-CoV-2 machinery, the spike protein, as it has evolved since 2020. Their study, published in Cell, highlights antibodies that are able to neutralize the newer strains, while identifying regions of the spike protein that have become more resistant to attack.

"Emerging data show that vaccines still confer some protection from new SARS-CoV-2 variants, and our study shows how that works from an antibody standpoint," said corresponding author Duane Wesemann, MD, PhD, of the Division of Allergy and Clinical Immunology and Division of Genetics at the Brigham and an associate professor at Harvard Medical School. "These data can help us think about what the best kind of booster vaccine might be by studying how the repertoire of human antibodies recognizes the spike protein."

The researchers examined the antibody-producing Memory B cells of 19 patients who were infected with SARS-CoV-2 in March of 2020, before the emergence of new variants. They studied how these antibodies, as well as other antibodies that have been characterized by researchers, bind to spike protein models of the B.1.1.7 (Alpha), B.1351 (Beta) and P.1 (Gamma) variants of SARS-CoV-2, which were first identified in the United Kingdom, South Africa, and Brazil, respectively. An analysis of the Delta variant is currently underway.

Overall, the authors confirmed that the hundreds of antibodies they studied largely bind to seven major "footprints" on the spike protein. While many of these antibodies "compete" to bind to the same regions of the early version of the SARS-CoV-2 spike protein, when it comes to newer strains, some of these antibodies lose their potency while others emerge as broadly responsive neutralizers.

In particular, antibodies binding to two of these spike protein regions, dubbed RBD-2 and NTD-1, were the most potent neutralizers of initial forms of the spike protein. The B.1.351 spike variant proved to exhibit the greatest ability to evade existing antibody arsenals, escaping many RBD-2- and NTD-1-binding antibodies. Some antibodies binding another region, called S2-1, could recognize spike proteins from more distantly related viruses such as MERS, SARS, and common cold coronaviruses.

"Making different antibodies that compete for one region of the virus allows the immune system to be more flexible," Wesemann said. "Otherwise-redundant recognition by antibodies targeting the same footprint of one version of the virus confers recognition depth of the same footprint on variants, and some antibodies maintain high neutralization potency against all the variants. Now that we can identify the antibodies that are more broadly reactive to all of the variants, we can think about how to elicit them more strongly in a vaccine."

The body's first encounter with SARS-CoV-2, the virus behind COVID-19, happens in the nose and throat, or nasopharynx. A new study in the journal Cell suggests that the first responses in this battleground help determine who will develop severe disease and who will get through with mild or no illness.

Building on work published last year identifying SARS-CoV-2-susceptible cells, a team of collaborators at Boston Children's Hospital, MIT, and the University of Mississippi Medical Center comprehensively mapped SARS-CoV-2 infection in the nasopharynx. They obtained samples from the nasal swabs of 35 adults with COVID-19 from April to September 2020, ranging from mildly symptomatic to critically ill. They also got swabs from 17 control subjects and six patients who were intubated but did not have COVID-19.

"Why some people get more sick than others has been one of the most puzzling aspects of this virus from the beginning," says José Ordovás-Montañés, PhD, of Boston Children's, co-senior investigator on the study with Bruce Horwitz, MD, PhD of Boston Children's, Alex K. Shalek, PhD, of MIT and Sarah Glover, DO, of the University of Mississippi. "Many studies looking for risk predictors have looked for signatures in the blood, but blood may not really be the right place to look."

COVID-19's first battlefield: the nasopharynx

To get a detailed picture of what happens in the nasopharynx, the researchers sequenced the RNA in each cell, one cell at a time. (For a sense of all the work this entailed, each patient swab yielded an average of 562 cells.) The RNA data enabled the team to pinpoint which cells were present, which contained RNA originating from the virus -- an indication of infection -- and which genes the cells were turning on and off in response.

It soon became clear that the epithelial cells lining the nose and throat undergo major changes in the presence of SARS-CoV-2. The cells diversified in type overall. There was an increase in mucus-producing secretory and goblet cells. At the same time, there was a striking loss of mature ciliated cells, which sweep the airways, together with an increase in immature ciliated cells (which were perhaps trying to compensate).

The team found SARS-CoV-2 RNA in a a diverse range of cell types, including immature ciliated cells and specific subtypes of secretory cells, goblet cells, and squamous cells. The infected cells, as compared to the uninfected "bystander" cells, had more genes turned on that are involved in a productive response to infection.

A failed early immune response

The key finding came when the team compared nasopharyngeal swabs from people with different severity of COVID-19 illness:

In people with mild or moderate COVID-19, epithelial cells showed increased activation of genes involved with antiviral responses -- especially genes stimulated by type I interferon, a very early alarm that rallies the broader immune system.

In people who developed severe COVID-19, requiring mechanical ventilation, antiviral responses were markedly blunted. In particular, their epithelial cells had a muted response to interferon, despite harboring high amounts of virus. At the same time, their swabs had increased numbers of macrophages and other immune cells that boost inflammatory responses.

"Everyone with severe COVID-19 had a blunted interferon response early on in their epithelial cells, and were never able to ramp up a defense," says Ordovás-Montañés. "Having the right amount of interferon at the right time could be at the crux of dealing with SARS-CoV-2 and other viruses."

Boosting interferon responses in the nose?

As a next step, the researchers plan to investigate what is causing the muted interferon response in the nasopharynx, which evidence suggests may also occur with the new SARS-CoV-2 variants. They will also explore the possibility of augmenting the interferon response in people with early COVID-19 infections, perhaps with a nasal spray or drops.

"It's likely that, regardless of the reason, people with a muted interferon response will be susceptible to future infections beyond COVID-19," Ordovás-Montañés says. "The question is, 'How do you make these cells more responsive?'"

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.