Culture

The share of U.S. adults who support an active government role in society increased by more than 40 percent during the initial pandemic response--up from 24 percent in September 2019 to 34 percent in April 2020--according to a new national public opinion survey conducted by researchers at the Johns Hopkins Bloomberg School of Public Health and the Johns Hopkins University SNF Agora Institute.

The survey, fielded April 7 through April 13, 2020, also found that, among U.S. adults who endorsed a strong government role in society, a majority supported health, unemployment, and income-related policies aimed at bolstering the social safety net for vulnerable groups in society.

The findings, to be published online October 15 in the American Journal of Public Health, measured public support for social safety net policies during the initial outbreak of the novel coronavirus to assess how public support was associated with beliefs about the role of government.

Among the adults who supported a stronger government role, 88 percent supported two-weeks paid sick leave, 80 percent supported increased minimum federal wage, 77 percent supported employment education and training as unemployment benefits, and 73 percent supported universal health insurance.

"Critical safety net policies passed in the initial phase of the pandemic are expiring or have expired, and finding common ground on extending them has proved difficult," says the lead author, Colleen L. Barry, PhD, MPP, Fred and Julie Soper Professor and Chair of the Department of Health Policy and Management at the Bloomberg School. "An awareness on the part of policymakers of heightened support for the government aiding individuals and families who have experienced pandemic-related dislocations could make a difference."

In the initial phase of the coronavirus outbreak in the U.S., 22 million individuals filed for unemployment benefits and an estimated 9.2 million lost their employer-based health insurance. On March 18, 2020, the U.S. Congress quickly passed the Families First Coronavirus

Response Act, which is in effect through December 2020, and included paid sick days and other leave benefits related to COVID-19. The Coronavirus Aid, Relief, and Economics Security (CARES) Act offers tax credits to support worker retention and is in effect through January 1, 2021. In addition, the CARES Act had increased unemployment benefits by an extra $600 per week through July 31, 2020 to workers affected by the pandemic. Efforts by Congress to extend these expanded unemployment benefits have repeatedly stalled.

The survey, fielded using NORC's Amerispeak Panel, drew from a nationally representative sample of 1,468 U.S. adults. The respondents were asked about their support for 11 safety net policies such as paid sick leave and universal health insurance; income support and unemployment policies; tax credits for businesses; and employment education and training.

The survey found that a majority of U.S. adults strongly supported seven of the 11 social safety net policies. Among the findings:

77 percent of adults supported employer-guaranteed two-weeks paid sick leave

60 percent supported universal health insurance

58 percent supported increasing the federal minimum wage

52 percent supported extension of unemployment benefits

66 percent supported tax credits to businesses to retain and hire workers

68 percent supported employment education and training programs

71 percent supported public spending on construction projects like building roads or highways

The researchers found less support for single payer health insurance, 47 percent; government-funded paid sick leave, 39 percent; and government-funded family leave, 48 percent. There was also less support for universal basic income, at 39 percent.

"As Congress debates continued relief for Americans suffering health and economic consequences from the pandemic, our data shows there is growing support for passing the kind of policies that they have been unable to pass in the last few months," says co-author Hahrie Han, PhD, director of the SNF Agora Institute at Johns Hopkins University.

"Public Support for Social Safety-Net Policies for Covid-19 in the US, April 2020" was written by Colleen Barry, Hahrie Han, Rachel Presskreischer, Kelly Anderson, and Emma McGinty.

Tumors of the pancreas are particularly feared. They are usually discovered late and mortality is high. Until now, no targeted and personalized therapies exist. Scientists at the German Cancer Research Center (DKFZ) and the Heidelberg Institute for Stem Cell Technology and Experimental Medicine* (HI-STEM) have now succeeded for the first time in defining two differently aggressive molecular subtypes of pancreatic carcinoma. This provides new insights into the origin of the tumors. In the more aggressive group of tumors, a phenomenon known as "viral mimicry" leads to a cancer-promoting inflammatory reaction. This could possibly be the starting point for the development of a targeted, subtype-oriented therapy. The results have now been published in the journal Cancer Discovery.

Pancreatic carcinoma is particularly insidious. The disease usually progresses without symptoms over a long period of time and is only diagnosed in advanced stages - when it is difficult to treat. The mortality rate for this tumor disease is therefore particularly high. In contrast to many other cancers, scientists have not yet succeeded in identifying efficient targets for a targeted personalized therapy. Most patients with an advanced tumor disease receive a similar treatment - usually consisting of a combination chemotherapy.

About 95 percent of all cases of pancreatic cancer are so-called adenocarcinomas. "In the past, there have been attempts to work out genetic differences, but it turned out that all adenocarcinomas of the pancreas carry a similar collection of mutations," explains Andreas Trumpp, stem cell researcher at DKFZ and HI-STEM. Trumpp's team has now chosen a different approach in collaboration with the Department of Surgery at Heidelberg University Hospital. From tissue samples from patients, they first isolated pure cancer cells from the tumors' complex cell mixture, which contains large amounts of connective tissue, vessels and immune cells. The researchers then searched the genome of the purified tumor cells for differences in the methylation pattern. These are chemical labels attached tot he DANN molecule that determine whether a gene segment is active or not.

"Based on the methylation patterns of the tumor genomes, we were able to define two completely different subtypes of adenocarcinomas, which differ in the course of carcinogenesis and in their aggressiveness," says Elisa Espinet, first author of the current publication. One of the two subtypes is much more aggressive and actually develops directly from the ductal cells lining the ductal system of the pancreas, while the less aggressive tumors develop from glandular cells. "We have thus discovered a molecular signature that allows us to distinguish between two subtypes of pancreatic carcinoma that are also clinically different," explains Espinet.

What's more, upon closer analysis of the methylation patterns, the Heidelberg researchers discovered that very specific regions in the genome carry fewer methyl groups in the more aggressive subtype. These genome regions contained sequences of so-called endogenous retroviruses, remnants of viruses that have remained in the human genome during evolution. Due to the methylation of their DNA, they are normally silenced and do not play a significant role in healthy individuals. In this subtype, however, they become active again when the methyl groups are removed and form double-stranded RNA strands.

This type of RNA molecule does not normally occur in the body and is therefore a warning signal for the immune system that viruses have entered the cell. As a result, the interferon system is activated and tries to fight the invading viruses. As a result, inflammatory messengers are also released in the vicinity of the tumor. "Feigning a viral infection in genetically modified tumor cells is called "viral mimicry", says Espinet. In the tumor, the viral mimicry promotes certain inflammatory reactions that further drive cancer growth and, in addition, probably stimulates metastasis, i.e. the formation of the dreaded daughter tumors.

The DKFZ researchers found viral mimicry only in the ductal subtype and in traces also in healthy ductal cells, but not in the healthy glandular cells of the pancreas or the pancreatic cancer cells of the less aggressive subtype. This explained why pancreatic tumors that develop directly from the cells of the pancreatic ducts, which accounted for about one third of the tumors studied, are particularly aggressive.

At the same time, the result opens up new perspectives for a more targeted and personalized therapy of pancreatic cancer. "By blocking the interferon signaling pathways at various sites, we were able to significantly slow down cancer growth in mice to which human pancreatic cancer cells had been transferred. However, the regulation of these signals is highly complex. We are now looking for ways to not only slow down the tumor cells, but actually eliminate them," says Trumpp, explaining the further progress of preclinical research.

Your advance look at two new studies publishing online on October 15, 2020 in The American Journal of Tropical Medicine and Hygiene.

EMBARGOED UNTIL 5:00 pm US Eastern Time, October 15, 2020

Researchers find hypochlorous acid could combat latrine odor and infectious microbes--and promote greater latrine use--in developing countries

As part of an effort to establish new means to encourage toilet and pit latrine use in developing countries, researchers from the University of Washington and Briotech, a manufacturer of hypochlorous acid (HOCl), found that HOCl chemically modified the malodorous, off-putting compounds identified in the air of latrines in developing countries. This study also showed the potential of HOCl to rapidly inactivate infectious particles that can cause gastrointestinal diseases. The study was published today in the American Journal of Tropical Medicine and Hygiene.

According to the authors, promoting greater use of latrines in developing countries could limit transmission of fecal bacteria and viruses readily spread via environmental contamination of water and food sources. But they cite the odor of latrines, and the associated impression of uncleanliness, as one reason people avoid using them in favor of open defecation. "Odor control," the study authors said, "clearly needs to be included as part of improving sanitation."

Laboratory experiments tested the ability of stable, pure HOCl - in solution and spray form - to modify the malodorous compounds indole, p-cresol, dimethyl disulfide, dimethyl trisulfide and butyric acid. The studies found that after five minutes of contact with HOCl in concentrations of about 100 parts per million, greater than 94% of those compounds were modified. Spray delivery of HOCl gave comparable results after 25 sprays.

In addition, smell studies involving 80 volunteers indicated that there was a significant difference in odor between the untreated and HOCl-treated compounds, suggesting that hypochlorous acid will improve latrine odor in field studies when sprayed in the latrine headspace or swabbed on surfaces.

Importantly, the study also demonstrated that aerosolized HOCl brought about meaningful reductions in the infectivity of MS2 bacteriophage particles, which the researchers used as a surrogate for human norovirus and other diarrhea-associated viruses that can be found in latrines.

The researchers hope that HOCl could be an alternative to perfumes when it comes to making latrine use more pleasant to the nose while also inactivating infectious microbes and, to that end, are conducting further studies to optimize dosing to inactivate human noroviruses. This work was supported by an NIH grant (R03AI137626).

>> Abstract (will go live at 5 p.m. EDT, October 15; please contact us if you want to see the study PDF)

New study finds artificial light at night is increasing Aedes aegypti mosquito biting behavior

Artificial light at night abnormally increases Aedes aegypti mosquito biting behavior, according to new research published today in the American Journal of Tropical Medicine and Hygiene, highlighting the concern that increasing levels of light pollution could be enhancing transmission of diseases such as dengue fever, yellow fever, chikungunya and Zika.

Ae. aegypti normally flies and bites in the daytime. Activity terminates during or at the end of dusk, and little or no flight activity or biting occurs during the night.

Researchers at the University of Notre Dame examined the effect of artificial light at night on female Ae. aegypti biting of human arms in a laboratory setting and found that nocturnal biting activity doubled when the mosquitoes were exposed to artificial light. With no light, 29% of the mosquitoes blood-fed at night, while with artificial light 59% of the mosquitoes blood-fed.

These findings, the authors say, will help epidemiologists better understand the true risk of disease transmission by Ae. aegypti mosquitoes. The findings also suggest that sleeping under bednets meant to deter nocturnal biting insects like malaria-transmitting mosquitoes may provide some protection against yellow fever, dengue, Zika and other diseases transmitted by typically day-biting Ae. aegypti mosquitoes.

>> Abstract (will go live at 5 p.m. EDT, October 15; please contact us if you want to see the study PDF)

Australia was not spared as a 30-year global rise in chronic illness and related risk factors such as obesity, high blood sugar, and outdoor air pollution created a perfect storm to fuel coronavirus (COVID-19) deaths, new research shows.

The latest Global Burden of Disease Study findings also reveal that people globally are living more years in poor health, despite treatment advancements in many countries. While Australia has done relatively well with COVID-19 despite Victoria's second wave, experts are concerned about worrying levels of cardiovascular disease and stagnating life expectancy.

Published today in The Lancet, the latest results outline how well countries were prepared for COVID-19 in terms of underlying population health, and the scale of the challenge to protect the population against further pandemic threats.

The 30-year global study, which involves several University of Melbourne experts, analysed 286 causes of death, 369 diseases and injuries, and 87 risk factors in 204 countries and territories.

It found urgent action was needed to address the global syndemic--the aggregation of two or more concurrent or sequential epidemics, including chronic diseases, social inequalities, and COVID-19--to ensure more robust health systems and healthier people, making countries more resilient to future pandemic threats.

Several risk factors and non-communicable diseases highlighted, including obesity, smoking, diabetes, and cardiovascular disease, are associated with increased risk of serious illness and death from COVID-19.

Although global healthy life expectancy--the number of years a person can expect to have good health--increased steadily (by over 6.5 years) from 1990 to 2019, it has not risen as much as overall life expectancy in almost all of the 204 countries assessed, indicating that people are living more years in poor health.

The study also reveals that the rise in exposure to key risk factors, including high blood pressure, high blood sugar, high body-mass index (BMI), and elevated cholesterol, combined with rising deaths from cardiovascular disease in some countries or regions (e.g. the USA and the Caribbean), suggests that parts of the world might be approaching a turning point in life expectancy gains.

Healthy life expectancy in Australia has increased steadily over 30 years to 70.0 years in 2019 (a 4.1 year increase from 1990), but it has not risen as much as overall life expectancy (82.9 years in 2019; a 5.9-year increase from 1990), indicating that people are living longer in poor health.

Australian data also revealed:

* Ischaemic heart disease was the leading cause of health loss in Australia in 2019, followed by lower back pain, falls, major musculoskeletal disorders, and chronic obstructive pulmonary disease (COPD)

* The top-five risk factors for death in 2019 were high systolic blood pressure (contributing to an estimated 25,500 deaths), dietary risks (21,600 deaths), tobacco use (20,100), high BMI (18,700), and high blood sugar (17,700)

* Over the past 30 years, overall rates of death among 15-49-year-olds declined by 31 per cent. But rates of death due to drug use disorders rose substantially in this age group (by 55.2 per cent), as did rates of death due to endocrine, metabolic, blood, and immune disorders (by 75.2 per cent).

Senior author and University of Melbourne Laureate Professor Alan Lopez said while Australia had been comparatively "remarkably successful" in controlling COVID19 cases and especially deaths, despite Victoria's second wave, it had been much less so in controlling obesity and risks associated with poor diet. As a result, the long-term Australian decline in cardiovascular disease had ceased.

"Australian life expectancy has not increased in the past five years," Professor Lopez said.

"While the immediate global public health priority is understandably the rapid control of the COVID-19 pandemic, these findings about the state of the world's health are a wake-up call that large, avoidable causes of health loss such as smoking, alcohol, obesity and poor blood pressure and cholesterol control continue to claim millions of lives prematurely each year."

"Of even greater concern is that the impact of this risk factor 'cocktail' of smoking, poor diet and inadequate control of blood pressure and other metabolic factors is increasing in many countries, including Australia, as evidenced by the stagnation in life expectancy over the past five years."

Study authors from a range of countries and institutions stressed that government actions to prevent disease through incentivisation of healthier behaviours and facilitation of better access to healthcare are not being realised globally.

Professor Christopher Murray, Director of the Institute for Health Metrics and Evaluation at the University of Washington, USA, led the research.

"Most of these risk factors are preventable and treatable, and tackling them will bring huge social and economic benefits," Professor Murray said.

"We are failing to change unhealthy behaviours, particularly those related to diet quality, caloric intake, and physical activity, in part due to inadequate policy attention and funding for public health and behavioural research."

UNIVERSITY PARK, Pa. -- People may be skeptical about medical and health articles they encounter on crowdsourced websites, such as Wikipedia and Wikihealth, according to researchers. While that may be good news for health officials who are worried that these sites allow non-experts to easily add and edit health information, the researchers added that having medical professionals curate content on those sites may not reduce the skepticism.

"There are major concerns about health misinformation that's floating around, especially now with COVID-19," said S. Shyam Sundar, James P. Jimirro Professor of Media Effects, co-director of the Media Effects Research Laboratory and affiliate of Penn State's Institute for Computational and Data Science (ICDS). "Now that anybody and everybody can generate health-related posts, it is natural to be concerned that information on these crowdsourced websites might influence people. Our study suggests that health practitioners need not get too worked up about these sites. Laypersons, like the participants in our study, do not trust the crowd, nor do they think that the information they provide is comprehensive."

In prior research, scientists have found that people tend to trust online content that appears popular with the crowd, such as posts that earn likes and retweets, a phenomenon that is also referred to as the bandwagon effect, said Yan Huang, assistant professor of integrated strategic communication, University of Houston, lead-author of the study, who worked with Sundar. However, Huang said that the findings suggest that, as far as trust goes, people draw a line between content that has been endorsed by the crowd and content that has been edited by the crowd.

"The effect of crowdsourcing may be different from the bandwagon effect because in this case, the crowd is not just liking or recommending existing content; the crowd is actually generating it," said Huang. "And it seems that participants in our experiment were able to make that psychological distinction between the bandwagon effect -- when people are just endorsing the content -- versus people who are creating the content. Overall, participants didn't trust the content that's been collaboratively created by other people."

The researchers, who report their findings in Health Communication, added that their experiment also revealed another side of the story: When participants noticed interactive features on the site that allowed them to edit the content, they trusted crowdsourced health articles more.

"When they realize that they could serve as the editor or author of the content, they are imbued with a sense of control on the site. The more aware they are of this interactivity, the more they trust the content," said Huang.

According to Sundar, the findings suggest that while people trust themselves as a source of credible content, they may be reluctant to extend that trust to other people.

"When you are the source, you think that the information is credible because you can add content, but if other people can also supply content, that seems to take away the credibility," said Sundar.

Because crowdsourced content could be manipulated to include non-scientific advice or results, many health experts may think that credentialing their crowdsourced posts may add credibility to their articles. However, the researchers found that when content was curated, or even created by an expert, such as a doctor, participants did not find the information any more credible to the reader. To signal that the source was a professional, the researchers added a doctor symbol and the name and title of a doctor on the experimental website.

"Adding that professional source layer did increase the perception that there was a gatekeeper behind the content, in other words, people did think that the crowdsourced site had more gatekeeping when there were indications of a professional source, but it did not affect credibility judgments," said Sundar.

The researchers added that because the findings show a lack of trust in health content on crowdsourced sites, webmasters of these sites may want to make sure that interactive features are added and that they are prominent in the design. Interactive features tend to boost users' positive perceptions of the source and content, which could lead to better credibility on crowdsourced sites, they said.

The researchers created eight different versions of a website called "Healthpedia" to test the various conditions of the experiment. The site mimicked the interface of common crowdsourcing websites, such as Wikipedia and WikiHow, for testing the effects of crowdsourcing. While some versions identified a doctor as content editor, others offered editing functions and showed that the content was collaboratively created by over 45 individuals.

The study was conducted with a sample of 192 participants recruited from Amazon Mechanical Turk. They were exposed to articles that featured either the negative effects of sunscreen products or the potential risks of pasteurized milk. The researchers said that the content was intentionally made controversial to better test the credibility of the crowd as a source. According to the researchers, because the health articles were somewhat outlandish, future work may test whether the perception holds for fairly routine health content.

Sexually transmitted infections (STIs) are at record levels in the United States, with the Centers for Disease Control and Prevention reporting recent “steep and sustained” increases. STIs are particularly common among young adults (aged 18-24 years), yet most sexually active college students have never been tested. This presents an urgent challenge, as well as a unique opportunity, for universities to increase STI testing among their students.

New research led by George Mason University’s College of Health and Human Services found that the vast majority of sexually active students (88%) said they were "likely" or "extremely likely" to use STI self-testing services if they could take a test kit home and test themselves in the privacy of their own home/residence, while 59% said they would use STI self-testing services if they could test themselves in a private room at Student Health Services.

Dr. Lisa Lindley led the study published in the Journal of American College Health this week. This is the first study to explore college students’ comfort with and intention to use self-collection STI testing services on campus, and to identify students’ questions and concerns about the “self-testing” process before offering the service.

The researchers conducted an online survey of more than 400 students at a large mid-Atlantic university to assess their HIV/STI testing behaviors, comfort with self-collection procedures, and intention to use self-collection services for STI testing if offered on campus.

“We already know that in settings where self-collection options have been made available, there have been significant increases in testing and the detection of STIs,” explains Lindley. “This presents an opportunity to increase the detection of asymptomatic infections among sexually active students who traditionally don’t get tested, link these students to care, and prevent further transmission, as well as harmful health outcomes of untreated infections.”

Students who were older (25+ years), lived off campus, and identified as “lesbian, gay, bisexual, or an identity other than heterosexual” were significantly more likely to have ever been tested for HIV and other STIs than students who were younger (18–24 years), lived on campus, and identified as heterosexual.

“We hope to be able to offer STI self-testing options on campus in the near future and encourage other universities to consider the same, as we found that most students, regardless of age, sexual experience, and previous testing experience, were interested in self-testing,” explains Lindley. “These findings are especially timely during the COVID-19 pandemic, as access to HIV/STI testing in traditional settings has become more challenging and the CDC is recommending at-home HIV tests.”

Collection of specimens for some of the most common STIs (chlamydia and gonorrhea) as well as those for HIV can easily be collected by most people. Tests for others—such as syphilis, genital herpes, and human papilloma virus (HPV)—will continue to be conducted by clinicians due to the procedures required for sample collection.

The study offers important takeaways not just regarding the use of self-testing services among asymptomatic students, but also for increasing STI testing in clinical settings more broadly. It suggests that college students may be more likely to pursue STI testing if their contact with clinical staff could be reduced. Lindley recommends using online registration and sexual risk assessments, where appropriate, to collect necessary information and reduce interactions students find particularly embarrassing.

Supersized alcopops are single-serving flavored beverages with very high alcohol content. Consumption of these drinks is linked to dangerous consequences such as blacking out, vomiting, being injured or worse, and they are popular among underage drinkers, which is where prior research has typically focused.

However, supersized alcopops can be dangerous for everyone - regardless of age. New research led by George Mason University's College of Health and Human Services was the first to examine individual factors linked to recent consumption of supersized alcopops among adults on probation. The study was published today in Alcoholism: Clinical and Experimental Research.

Dr. Matthew Rossheim led the study that found that among adults on probation, those who were gang-affiliated or recently experienced homelessness were far more likely to have recently consumed supersized alcopops in the past 30 days.

Among those who experienced homelessness, 30% consumed supersized alcopops, compared to 11% of those who did not experience homelessness. Further, 57% of those who were gang-affiliated reported consuming a supersized alcopop within the past 30 days compared to 11% of those who were not gang-affiliated.

Adults on probation who had consumed supersized alcopops in the past 30 days had higher scores for hostility and risk-taking, and lower scores for self-esteem on the Criminal Justice Client Evaluation of Self and Treatment Intake (CJ-CEST) than non-consumers.

The researchers surveyed 253 adults (70% male) on probation in two large metropolitan areas: Baltimore City, MD and Dallas, TX who reported heavy drinking or any illicit drug use in the past 90 days.

"The marketing and retail availability of these products may be creating and perpetuating health disparities, by targeting historically disenfranchised communities," explains Rossheim. "Better regulation of supersized alcopop marketing is urgently needed to reduce dangerous alcohol consumption--particularly among high-risk groups, including people who are homeless, gang members, and display more hostility and risk-taking traits."

University of South Carolina scientists are exploring ways to make nerve regeneration happen faster and more successfully.

A new study published in Current Biology identifies the biological triggers that promote quicker nerve regeneration. From their previous studies, the researchers knew that damaged nerves regrow more quickly when "stress granules" in the site of the nerve injury are broken apart. Now they know what causes those stress granules to disassemble through a process called protein phosphorylation.

"The important thing is that we identified the protein that drives that process and showed how that's regulated," Jeff Twiss, a UofSC biology professor and co-author on the paper, said.

"It actually opens something new," Pabitra Sahoo, the paper's lead author, said. "In the future, it could help us design molecules that can promote phosphorylation."

Twiss said nerves typically regrow at 1 to 2 millimeters per day, meaning that an adult with nerve damage around their kneecap might require a year to recover as the nerve re-extends back to the foot. Given such a prolonged time to regenerate the nerve, atrophy makes a full recovery difficult.

"Finding ways to speed that up is critical to decreasing the amount of time that a person has loss of function, sensation and movement," said Twiss, the UofSC SmartState Chair in Childhood Neurotherapeutics. "But also, when you allow the nerve to find its way back to the target quicker, you can recover much more function."

Nerve cells contain the protein G3BP1 in clusters known as stress granules. When a nerve is severed, those granules begin to break apart through phosphorylation, a modification that makes G3BP1 become more negatively charged. This process releases mRNAs, important building blocks that the cell can use to build new proteins that extend the nerve. This phosphorylation makes the nerve grow faster, according to research that Sahoo and Twiss's team published in 2018.

The 2020 study took a step back to look for the processes that trigger the phosphorylation, in hopes that the entire process could be accelerated. The researchers determined that an enzyme known as Casein kinase 2-alpha (CK2α) is responsible for breaking up the G3BP1 granules through phosphorylation. When they increased CK2α levels, nerves grew faster, and the cell contained more phosphorylated G3BP1. When they decreased CK2α, the process slowed.

But where does the CK2α come from? The researchers placed a piece of nerve in a test tube, damaged it, and monitored the CK2α levels. Those levels increased, indicating that the damaged nerve synthesizes CK2α on its own at the injury site, rather than receiving it from its cell body. The process seems to be regulated by calcium ions.

These discoveries offer promising areas for further study. The UofSC researchers are already looking at methods for spurring the CK2α synthesis to speed up the nerve growth. Finding that key could lead to advances in medicine that result in faster healing after nerve injuries.

For a tiny embryo to develop into an adult organism, its cells must develop in precise patterns and interact with their neighbors in carefully orchestrated ways. To create complex tissues and organs -- from the pattern of rods and cones in the retina to the Byzantine filtration systems of the kidney -- all these developing cells must constantly answer a fundamental but surprisingly difficult question: Where am I?

"In the field of regenerative medicine, we can use stem cells to make organoids to study disease, but we can't yet put them into a person and have them repair a wound or heal sick tissue. A big part of that is that we don't have right signals to tell the cells where to go and what to do when they get there," said synthetic biologist Wendell Lim, PhD, Byers Distinguished Professor and chair of the UCSF Department of Molecular and Cellular Pharmacology.

One of the ways cells in developing organisms keep track of where they are and what they are supposed to be doing is through a type of chemical signal called a morphogen. These signals are produced by so-called organizer cells and diffuse outward through the local tissue. As the signal diffuses its concentration fades, telling local cells exactly how far they are from the source. With multiple organizer cells churning out different morphogens from key locations in a growing organism, cells can create a 3D spatial map that guides their development into complex tissues, much like a cellular GPS coordinate system.

Scientists are still working to understand how morphogens' signals are broadcast over just the right distances and how cells are calibrated to respond to the proper concentration at the appropriate time. But these questions are difficult to investigate because natural morphogens interact with their environment in many complex, hard to define ways.

Instead of deconstructing morphogens one interaction at a time, Lim's synthetic biology team at UCSF and a pair of research groups at the Francis Crick Institute in London -- led by Guillaume Salbreux, PhD, and Jean-Paul Vincent, PhD (himself once a post-doc with UCSF's Patrick O'Farrell, PhD) -- independently took the innovative approach of engineering a synthetic morphogen from the ground up. Their goals, as reported in two papers published October 16, 2020, in Science, were to study what makes morphogens work, and perhaps one day to create synthetic signals that could help control tissue regeneration or guide cellular therapies to heal wounds or fight cancers.

Lim's team, led by postdoctoral fellow Satoshi Toda, PhD, now an assistant professor at Kanazawa University's Nano Life Science Institute in Japan, started with an inert molecule called GFP, to which cells are normally completely deaf. To give cells the ability to respond to this new signal, the researchers used special types of antibodies to create GFP-responsive receptors. They genetically inserted these receptors into cells in laboratory dishes and linked them up to a cellular control system called SynNotch, which the lab had previously developed.

When the researchers instructed a subset of organizer cells at one end of the dish to produce GFP, the clouds of the fluorescent protein diffusing away from these anointed organizers activated the engineered receptors and imparted patterned gene activity in surrounding cells.

"I think it's pretty striking that a crude morphogen is not very hard to make," Lim said. "It gives us a sense of how simpler signaling molecules might have evolved to become morphogens in early days of multicellular evolution."

At UCSF, the researchers showed that these engineered morphogens could direct the formation of novel, user-defined striped patterns. At the Crick Institute, scientists used a similar approach in living flies -- showing that engineered morphogens could take the place of natural signals in successfully organizing the intricate patterns of the fly wing.

Because all the interactions in these systems are engineered, their characteristics are known and therefore amenable to mathematical modeling, the researchers say. These studies open the way to a testable theory of pattern formation by morphogens, and one day could help scientists program cells like robots to follow molecular trails to find and regenerate injured or diseased tissues.

Greenwood, SC (October 15, 2020) - A research team at the Greenwood Genetic Center (GGC) has successfully used small molecules to restore normal heart and valve development in an animal model for Mucolipidosis II (ML II), a rare genetic disorder. Progressive heart disease is commonly associated with ML II. The study is reported in this month's JCI Insight.

The small molecules included the cathepsin protease K inhibitor, odanacatib, and an inhibitor of TGFß growth factor signaling. Cathepsin proteases have been associated with later-onset heart disease including atherosclerosis, cardiac hypertrophy, and valvular stenosis, but their role in congenital heart defects has been unclear. The current study offers new insight into how mislocalizing proteases like cathepsin K alter embryonic heart development in a zebrafish model of ML II.

"Mutations in GNPTAB, the gene responsible for ML II, alter the localization and increase the activity of cathepsin proteases. This disturbs growth factor signaling and disrupts heart and valve development in our GNPTAB deficient zebrafish embryos," said Heather Flanagan-Steet, PhD, Director of the Hazel and Bill Allin Aquaculture Facility and Director of Functional Studies at GGC. "By inhibiting this process, normal cardiac development was restored. This finding highlights the potential of small molecules and validates the need for further studies into their efficacy."

Flanagan-Steet noted that she hopes the current work with ML II zebrafish will provide the basis to move one step closer to a treatment.

It's not a coincidence that dogs are cuter than wolves, or that goats at a petting zoo have shorter horns and friendlier demeanors than their wild ancestors. Scientists call this "domestication syndrome" -- the idea that breeding out aggression inadvertently leads to physical changes, including floppier ears, shorter muzzles and snouts, curlier tails, paler fur, smaller brains, and more.

The link appears to come from certain neural crest cells, present before birth and in newborns, that have a versatility akin to stem cells. These neural crest cells can turn into a handful of different things, specifically adrenal cells -- which boost the strength of the "fight or flight" response -- as well as physical traits like larger teeth and stiffer ears.

Ever since Darwin's time, some scientists have speculated that humans "self-domesticated" -- that we chose less aggressive and more helpful partners, with the result that we have shifted the trajectory of our own evolution.

"The evidence for this has been largely circumstantial," said Asif Ghazanfar, a professor of psychology and neuroscience. "It's really a popular and exciting idea but one that lacks direct evidence, a link between friendly behavior and other features of domestication."

To see if the story could be put on a robust foundation, Ghazanfar turned to marmoset monkeys. Like humans, marmosets are extremely social and cooperative, plus they have several of the physical markers consistent with domestication, including a patch of white fur on their foreheads that is common in domesticated mammals.

What does cooperation look like in a monkey? Friendly vocal exchanges, caring for each other's young, and sharing food, among other signs, said Ghazanfar.

The research team showed that the size of a marmoset's white fur patch was strongly related to how frequently it produced friendly vocal responses to another. This is the first set of data to show an association between a friendly behavior and a physical domestication trait in individual animals.

To show a causal link between the white patch and vocal behavior, the researchers tested infant twins in different ways. In very brief sessions, one twin got reliable vocal feedback from a simulated parent -- a computer programmed with adult calls that responded to 100% of their vocalizations -- while the other twin only heard parental responses to 10% of their sounds.

These experimental sessions lasted 40 minutes, every other day, for most of the first 60 days of the monkeys' lives. For the other 23+ hours of each day, the monkeys were with their families.

In previous work, Ghazanfar and his colleagues showed that the infants who received more feedback learned to speak -- or more precisely, developed their adult-sounding calls -- faster than their siblings. By also measuring the white fur patches on the developing monkeys' foreheads at the same time and for three more months, the researchers discovered that the rate of the white facial coloration development was also accelerated by increased parental vocal responses. This shows a developmental connection between facial fur coloration and vocal development -- they are both influenced by parents.

That connection may be via those neural crest cells that can turn into "fight or flight" cells and that also contribute to parts of the larynx, which is necessary for producing vocalizations.

Domestication in other species has also been linked to changes in vocal behavior. Foxes selected for tameness have altered their vocalizations in response to the presence of humans. Similarly, a tame Bengalese finch learns and produces a more complex song, and retains greater song plasticity in adulthood, than its wild cousins.

But this is the first study linking the degree of a social trait with the size of a physical sign of domestication, in any species, said the researchers. Their findings are detailed in an article published online in the journal Current Biology. Ghazanfar's co-authors include Daniel Takahashi, a former postdoctoral researcher who is now a professor of neuroscience at Federal University of Rio Grande do Norte, Brazil; Rebecca Terrett of the Class of 2016; Lauren Kelly, Ghazanfar's former lab manager, who now works at Rutgers-Robert Wood Johnson Medical School; and two collaborators from New York University, James Higham and Sandra Winters.

"If you change the rate of the marmosets' vocal development, then you change the rate of fur coloration," said Ghazanfar. "It's both a fascinating and strange set of results!"

HOUSTON - (Oct. 15, 2020) - Education has long been linked to health -- the more schooling people have, the healthier they are likely to be. But a new study from Rice University sociologists found that the health benefits of a good education are less evident among well-educated bisexual adults.

"Education and health: The joint role of gender and sexual identity" examines health among straight, bisexual, gay and lesbian adults with various educational backgrounds. Authors Zhe Zhang, a postdoctoral research fellow at Rice, Bridget Gorman, a professor of sociology at Rice, and Alexa Solazzo, a postdoctoral research fellow at the Harvard University T.H. Chan School of Public Health, were particularly interested in bisexual adults, since they may experience distinctive health vulnerabilities.

The researchers found that while having at least a bachelor's degree was linked to better health among bisexual adults, they received less benefit than heterosexual and gay or lesbian adults with similar education. This effect was especially true for bisexual women.

"The health benefits of education are well established -- so much so that anything we do to promote and improve public education should really be viewed as health policy," Gorman said. "It's that impactful on health and well-being. That our analysis showed less health benefit associated with education among bisexual adults compared to heterosexual, gay and lesbian adults is concerning."

While the researchers could not pinpoint the exact cause, they theorized the problem might be social stigma and additional anxiety among women due to gender discrimination, Zhang said.

"Discrimination of any kind can take a heavy toll on health," Zhang said. "While we cannot say with certainty that is what is happening in this study, it's a very real possibility."

The authors based their study on data from the Behavioral Risk Factor Surveillance System, which included a sample of more than 1.2 million adults living in 44 U.S. states and territories from 2011-2017. They hope the study will raise awareness of the issue and help health professionals provide better care.

E-cigarettes might not be a safer alternative to smoking during pregnancy, according to the first known study into the effects of prenatal nicotine exposure on babies.

Psychologists at Durham University, UK, found that babies of mothers who smoked e-cigarettes during pregnancy displayed similar abnormal reflexes to infants whose mothers smoked traditional cigarettes.

Abnormal reflexes can include a baby not grasping a finger with their hand or not being startled if the hand supporting their head is suddenly removed.

When there are a number of these abnormal reflexes, this could be a sign of impaired brain development, which should be further investigated. Normal reflexes support the development of early motor milestones, such as crawling and rolling over.

The researchers say their findings have important implications for policy guidelines regarding the use and safety of e-cigarettes during pregnancy as a method of reducing the harm caused by smoking.

They recommend that more investigation is needed into the potential effects of e-cigarettes on babies and say the only safe way of reducing harm is not to smoke during pregnancy, whether that be traditional cigarettes or e-cigarettes.

Their findings are published in the journal E Clinical Medicine.

E-cigarettes are often considered as a less harmful alternative to cigarettes for pregnant smokers because they don't produce toxins like carbon monoxide, but they do contain nicotine.

The Durham study looked at the neurobehavioural outcomes of 83 one-month-old babies including 44 born to mothers who did not smoke during pregnancy, 29 who smoked cigarettes and ten who smoked e-cigarettes. Babies were born at least 37 weeks into pregnancy.

Overall the researchers found that the birthweight, gestation period and head circumference of babies did not differ between those born to mothers who smoked e-cigarettes during pregnancy and those who did not smoke at all.

Babies of mothers who smoked traditional cigarettes during pregnancy had significantly lower birthweight and head circumference in comparison.

However, babies exposed to nicotine in the womb, either from cigarettes or e-cigarettes, did have a greater number of abnormal primitive reflexes, as well as marginally decreased self-regulation abilities compared to the babies of non-smokers.

Self-regulation in infants can include self-relaxation when held, how consolable they are after crying, self-quieting skills and hand-to-mouth movements. Babies who show fewer self-regulation abilities are often more irritable and have difficulty consoling themselves or being consoled by others.

The study also found that higher amounts of nicotine correlated with less motor maturity in babies, such as how floppy or rigid a baby is when held.

The researchers acknowledge that while the sample size in their study is small, their findings do give a strong indication that nicotine exposure from smoking e-cigarettes could be harmful to the development of fetuses and have called for more studies to be carried out.

Lead author Suzanne Froggatt, a PhD Researcher in the Department of Psychology, Durham University, said: "Nicotine can cause widespread negative effects on the central nervous system, subsequently affecting brain development, with animal studies indicating the devastating effects within the brain.

"Although e-cigarettes might expose the mother to fewer toxins than cigarettes, given the uncontrolled amount of nicotine in e-cigarette consumption and the effects on the fetus which can be seen post-natally, we don't believe that mothers should be encouraged to use e-cigarettes during pregnancy.

"More investigation is needed into the potential harm to fetuses from e-cigarettes so health professionals can provide women with a better informed choice about harm reduction during pregnancy."

The researchers added that their findings suggest the effects of other forms of nicotine replacement therapy, such as nicotine patches, on fetal development might also need further research.

Co-author Professor Nadja Reissland, in the Department of Psychology, Durham University, said: "Mothers should not be encouraged to use e-cigarettes during pregnancy, while other forms of nicotine replacement therapy need to be researched in relation to neurobehavioural outcomes.

"Public health policymakers need to be aware that e-cigarette use is not risk free and that nicotine alone is not relatively harmless, but in fact it can have effects on the infant, despite not affecting birth outcomes."

ORLANDO, Fla. (October 15, 2020) - A group of three gene variants, commonly inherited together, may provide clues to more successful treatment of pediatric eosinophilic esophagitis (EoE), a chronic inflammation of the food pipe often confused with gastroesophageal reflux disease (GERD). A new study, led by researchers from Nemours Children's Health System and published in Clinical Gastroenterology and Hepatology, identifies genetic variants that help predict which children with EoE may not respond to proton pump inhibitor (PPI) medication therapy as a long-term solution.

"Our goal is to personalize therapy for children with EoE based on their unique genetic profile - finding the right medication, at the right dose for the right child," said James P. Franciosi, MD, senior author and Chief of Gastroenterology, Hepatology and Nutrition at Nemours Children's Hospital. "This novel research study identifies genetic variants that can help us predict which children with EoE will respond to PPI therapy over the course of one year and potentially avoid relapse and additional invasive procedures."

EoE is a chronic immune condition, often caused by reactions to certain foods, that leads to inflammation of the esophagus. Symptoms may include difficulty swallowing, chest pain, heart burn, abdominal pain, nausea, and vomiting. EoE is becoming increasingly more common with both new diagnoses and total number of patients increasing yearly. More than 30 percent of children receiving long-term treatment for EoE experience relapse, but currently it is not possible to predict who is likely to suffer a relapse. Children with this condition are often treated with PPI medications, which are also prescribed for common acid reflux-related conditions.

The research team found that having any of three STAT6 variants that are commonly inherited together increases the odds that PPI therapy will fail children with EoE at some point, either in the initial high-dose therapy phase or the subsequent year of low-dose maintenance therapy.

This prospective, longitudinal cohort study involved 73 children ages 2-16 years old who met the diagnostic criteria for EoE, responded to an initial eight weeks of 2mg/kg daily PPI therapy and were subsequently stepped down to 1 mg/kg daily PPI maintenance therapy for one year. Genomic DNA was isolated, and genotyping conducted. The research team found that patients who initially respond to PPI therapy but carry any of three specific STAT6 variants are at increased risk of relapse after one year of PPI maintenance therapy.

Franciosi noted that a dosage that is too low or too high could lead to treatment failure or PPI-associated side effects including upper respiratory and GI tract infections.

"There is more work to be done before we can say with certainty which children will respond to PPI therapy for this painful condition," said Edward B. Mougey, PhD, lead author of the study, and a researcher with Nemours' Center for Pharmacogenomics and Translational Research. "Research is ongoing, and our goal continues to be to personalize, as much as possible, the treatment and care we provide to each child."

"My son is currently in remission and has been responsive to PPIs, but EoE is still a constant condition he is managing - from determining what he can eat, to maintaining his weight and energy levels," said Laura Moore, of Jacksonville, Fla. and mother of a child with EoE. "This research will help improve my son's treatment going forward, but also help other kids will have better experiences in the future."

Anyone who has experienced "butterflies in the stomach" before giving a big presentation will be unsurprised to learn there is a physical connection between their gut and their brain. Neuroscientists and medical professionals call this connection the "gut-brain axis" (GBA); a better understanding of the GBA could lead to the development of treatments and cures for neurological disorders such as depression and anxiety, as well as for a range of chronic auto-immune inflammatory diseases such as irritable bowel syndrome (IBS) and rheumatoid arthritis.

Right now, these conditions and diseases are primarily diagnosed by patients' reports of their symptoms. However, neuroscientists and doctors are investigating the GBA in order to find so-called "biomarkers" for these diseases. In the case of the GBA, that biomarker is likely serotonin.

By targeting this complex connection between the gut and the brain, researchers hope they can uncover the role of the gut microbiome in both gut and brain disorders. With an easily identifiable biomarker such as serotonin, there may be some way to measure how dysfunction in the gut microbiome affects the GBA signaling pathways. Having tools that could increase understanding, help with disease diagnosis, and offer insight into how diet and nutrition impacts mental health would be extremely valuable.

With $1 million in National Science Foundation funding, a team of University of Maryland experts from engineering, neuroscience, applied microbiology, and physics has been making headway on building a platform that can monitor and model the real-time processing of gut microbiome serotonin activity. Three new published papers detail the progress of the work, which includes innovations in detecting serotonin, assessing its neurological effects, and sensing minute changes to the gut epithelium.

In "Electrochemical Measurement of Serotonin by Au-CNT Electrodes Fabricated on Porous Cell Culture Membranes" (https://www.nature.com/articles/s41378-020-00184-4), the team developed a platform that provides access to the specific site of serotonin production. The platform included a porous membrane with an integrated serotonin sensor on which a model of the gut lining can be grown. This innovation allowed researchers to access both top and bottom sides of the cell culture--important because serotonin is secreted from the bottoms of cells. The work is the first to demonstrate a feasible method for detection of redox molecules, such as serotonin, directly on a porous and flexible cell culture substrate. It grants superior access to cell-released molecules and creates a controllable model gut environment to perform groundbreaking GBA research without the need to perform invasive procedures on humans or animals.

The team's second paper, "A Hybrid Biomonitoring System for Gut-Neuron Communication" (https://ieeexplore.ieee.org/document/9123494), builds on the findings of the first: the researchers developed the serotonin measuring platform further so it could assess serotonin's neurological effects. By adding and integrating a dissected crayfish nerve model with the gut lining model, the team created a gut-neuron interface that can electrophysiologically assess nerve response to the electrochemically detected serotonin. This advance enables the study of molecular signaling between gut and nerve cells, making possible real-time monitoring of both GBA tissues for the first time.

Finally, the concept, design, and use for the entire biomonitoring platform is described in a third paper, "3D Printed Electrochemical Sensor Integrated Transwell Systems" (https://www.nature.com/articles/s41378-020-00208-z). This paper delves into the development of the 3D-printed housing, the maintenance of a healthy lab-on-a-chip gut cell culture, and the evaluation of the two types of sensors integrated on the cell culture membrane. The dual sensors are particularly important because they provide feedback about multiple components of the system--namely, the portions that model the gut lining's permeability (a strong indicator of disease) and its serotonin release (a measure of communication with the nervous system). Alongside the electrochemical sensor--evaluated using a standard redox molecule ferrocene dimethanol--an impedance sensor was used to monitor cell growth and coverage over the membrane. Using both these sensors would allow monitoring of a gut cell culture under various environmental and dietary conditions. It also would enable researchers to evaluate changes to barrier permeability (a strong indicator of disease), and serotonin release (a measure of communication with the nervous system).