Culture

While the world waits eagerly for a safe and effective vaccine to prevent infections from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus behind the COVID-19 pandemic, researchers also are focusing on better understanding how SARS-CoV-2 attacks the body in the search for other means of stopping its devastating impact. The key to one possibility -- blocking a protein that enables the virus to turn the immune system against healthy cells -- has been identified in a recent study by a team of Johns Hopkins Medicine researchers.

Based on their findings, the researchers believe that inhibiting the protein, known as factor D, also will curtail the potentially deadly inflammatory reactions that many patients have to the virus.

Making the discovery even more exciting is that there may already be drugs in development and testing for other diseases that can do the required blocking.

The study is published in the Sept. 2, 2020, issue of the journal Blood.

Scientists already know that spike proteins on the surface of the SARS-CoV-2 virus -- making the pathogen look like the spiny ball from a medieval mace -- are the means by which it attaches to cells targeted for infection. To do this, the spikes first grab hold of heparan sulfate, a large, complex sugar molecule found on the surface of cells in the lungs, blood vessels and smooth muscle making up most organs. Facilitated by its initial binding with heparan sulfate, SARS-CoV-2 then uses another cell-surface component, the protein known as angiotensin-converting enzyme 2 (ACE2), as its doorway into the attacked cell.

The Johns Hopkins Medicine team discovered that when SARS-CoV-2 ties up heparan sulfate, it prevents factor H from using the sugar molecule to bind with cells. Factor H's normal function is to regulate the chemical signals that trigger inflammation and keep the immune system from harming healthy cells. Without this protection, cells in the lungs, heart, kidneys and other organs can be destroyed by the defense mechanism nature intended to safeguard them.

"Previous research has suggested that along with tying up heparan sulfate, SARS-CoV-2 activates a cascading series of biological reactions -- what we call the alternative pathway of complement, or APC -- that can lead to inflammation and cell destruction if misdirected by the immune system at healthy organs," says study senior author Robert Brodsky, M.D., director of the hematology division at the Johns Hopkins University School of Medicine. "The goal of our study was to discover how the virus activates this pathway and to find a way to inhibit it before the damage happens."

The APC is one of three chain reaction processes involving the splitting and combining of more than 20 different proteins -- known as complement proteins -- that usually gets activated when bacteria or viruses invade the body. The end product of this complement cascade, a structure called membrane attack complex (MAC), forms on the surface of the invader and causes its destruction, either by creating holes in bacterial membranes or disrupting a virus' outer envelope. However, MACs also can arise on the membranes of healthy cells. Fortunately, humans have a number of complement proteins, including factor H, that regulate the APC, keep it in check and therefore, protect normal cells from damage by MACs.

In a series of experiments, Brodsky and his colleagues used normal human blood serum and three subunits of the SARS-CoV-2 spike protein to discover exactly how the virus activates the APC, hijacks the immune system and endangers normal cells. They discovered that two of the subunits, called S1 and S2, are the components that bind the virus to heparan sulfate -- setting off the APC cascade and blocking factor H from connecting with the sugar -- and in turn, disabling the complement regulation by which factor H deters a misdirected immune response.

In turn, the researchers say, the resulting immune system response to chemicals released by the lysing of killed cells could be responsible for the organ damage and failures seen in severe cases of COVID-19.

Most notably, Brodsky says, the research team found by blocking another complement protein, known as factor D, which works immediately upstream in the pathway from factor H, they were able to stop the destructive chain of events triggered by SARS-CoV-2.

"When we added a small molecule that inhibits the function of factor D, the APC wasn't activated by the virus spike proteins," Brodsky says. "We believe that when the SARS-CoV-2 spike proteins bind to heparan sulfate, it triggers an increase in the complement-mediated killing of normal cells because factor H, a key regulator of the APC, can't do its job."

To better understand what happens, Brodsky says think of the APC like a car in motion.

"If the brakes are disabled, the gas pedal can be floored without restraint, very likely leading to a crash and destruction," he explains. "The viral spike proteins disable the biological brakes, factor H, enabling the gas pedal, factor D, to accelerate the immune system and cause cell, tissue and organ devastation. Inhibit factor D, and the brakes can be reapplied and the immune system reset."

Brodsky adds that cell death and organ damage from a misdirected APC associated with factor H suppression is already known to occur in several complement-related human diseases, including age-related macular degeneration, a leading cause of vision loss for people age 50 and older; and atypical hemolytic uremic syndrome (aHUS), a rare disease that causes clots to block blood flow to the kidneys.

Brodsky and his colleagues hope that their work will encourage more study into the potential use against COVID-19 of complement-inhibiting drugs already in the pipeline for other diseases.

"There are a number of these drugs that will be FDA-approved and in clinical practice within the next two years," Brodsky says. "Perhaps one or more of these could be teamed with vaccines to help control the spread of COVID-19 and avoid future viral pandemics."

The intertidal mudflats of Barr Al Hikman, a nature reserve at the south-east coast of the Sultanate Oman, are crucial nursery grounds for numerous crab species. In return, these crabs are a vital element of the ecology, as well as the regional economy, a new publication in the scientific journal Hydrobiologia shows. 'These important functions of the crabs should be considered when looking at the increasing human pressure on this nature reserve', first author and NIOZ-researcher Roeland Bom says.

Blue swimming crab

The mudflats of Barr Al Hikman are home to almost thirty crab species. For his research, Bom, together with colleagues in The Netherlands and at the Sultan Qaboos University in Oman, looked at the ecology of the two most abundant species. Bom: 'Barr Al Hikman is also home to the blue swimming crab Portunus segnis. That is the species caught by local fishermen. This crab uses the mudflats of Barr Al Hikman as nursery grounds.'

The counts of Bom and his colleagues show, that there are millions and millions of these crabs in Barr Al Hikman. They are food to hundreds of thousands of birds, both migrating species, as well as birds breeding in the area, such as crab plovers. The crabs live in holes in the ground. They forage on the seagrass beds that are still abundant in Barr Al Hikman. 'Apart from the high primary production (algae) in Barr al Hikman, this reserve is also well suited for crabs because of the vastness of the area', Bom assumes. 'The slopes of the mudflats are very gentle, so at low tide, the crabs have an immense area at their disposition.'

Eco value

The value of the crabs is not just ecological, Bom stresses. "Local fishermen that catch the blue swimming crabs, distribute them not only through Oman, but also through the rest of the Arabian Peninsula and even to Japan. At approximately € 2,- per kilo, these crabs represent an important economic pillar, both under the region around Barr Al Hikman, as well as for the whole of Oman.'

Reserve

The protection of the reserve of Barr Al Hikman is limited to national legislation. Efforts to acknowledge this reserve under the international Ramsar-convention were never effectuated. There is, however, increasing human pressure on the mudflats of Barr Al Hikman, the authors describe, that would justify further protection. For example, there are well-developed plans to start shrimp farming around this intertidal area. 'When looking at the cost and benefits of these activities, it is important to look at the role of this reserve in the local ecology, as well as in the broader ecology of the many migratory birds that use the area', Bom says. 'Moreover, our research shows that the unique ecosystem of Barr Al Hikman plays a key role in the economy as well.'

It is only 120 millionths of a millimetre in size but can bring entire countries to a standstill: the Corona virus. Even if it were to disappear one day, viral infections will still be among the most frequent and difficult-to-treat diseases in humans. Even decades of research have only produced a few standardized vaccines and strategies for treatment to combat just a small number of viruses. Nor has there been much research into viral mechanisms of action - which was a reason for Prof. Guiscard Seebohm and his team at the Institute for the Genetics of Heart Diseases of Münster University to focus their attention on precisely this topic. And the team has now succeeded in making a groundbreaking development: it has created a viral expression model which can be used to simulate and analyse a large number of viral infections - including the one with SARS-CoV-2. The results can be read in the current issue of Scientific Reports published by the "Nature" journal.

One virus that is much less well-known than SARS-CoV-2, but which can be transmitted in the same way, is the Coxsackie virus B3 (CVB3). "Its symptoms," explains Guiscard Seebohm, "are mostly similar to those for flu, as is the recovery time: after two or three weeks, any patients with a CVB3 infection are, as a rule, well again, and don't have any obvious long-term impairment." But - not always, says Guiscard Seebohm, who heads the Cellular Electrophysiology and Molecular Biology department. Apart from any acute infections, he explains, a viral infection also contains the risk of a chronic infection, with the consequence of continuous damage to certain internal organs - which can lead to death. This means that months or even years later, an inflammation of the heart muscle, or type 1 diabetes, can occur in some patients who had CVB3 in the past. Histological examinations of patients showed, in some cases, serious damage to the tissue structure. Also: even years after the acute infection occurred, tissue analyses prove the existence of a virus in the genes.

So far there has been an insufficient amount of study devoted to the question of how a CVB3 infection becomes chronic and how exactly an acute infection progresses. In this respect, the Guiscard Seebohm team has succeeded in taking a great step forward. It developed an expression model for CVB3, based on stem cells, in order to get to the bottom of the mechanisms of action in this virus - as a prototype for the effects of viruses in general. In a study, the model was tested for its controllability in heart muscle cells cultured from stem cells. In the process, the team of researchers was able to achieve a stable integration of the genetic information from a non-infectious variant of CVB3 into the genetic material in human stem cells. The latter can be converted into any kind of human tissue in the laboratory, making it possible to precisely investigate viral mechanisms. The CVB3 expression can be specifically activated by means of a chemical signal.

Guiscard Seebohm is delighted at this success, because, as he says, "As a result of this unique human viral expression system based on stem cells, it will now be possible to simulate a large number of diseases in their progression and, for the first time, analyse them with the utmost precision." In Guiscard Seebohm's view there is something else that is just as important: the system is completely controllable. The team of researchers managed to steer the CVB3 expression in the expression model time-wise, both in stem cells and in differentiated heart muscle cells. At the same time, the researchers were able to vary the quantity of viral proteins produced as well as their localization. In other words, the extent of the viral infection, the infection pattern and the time progression can all be adapted to whatever topics researchers are working on.

The production of the first fully controllable viral expression model in human cells, its proven functionality, and the transferability to patients all open up numerous new approaches for research. It is not only that any infection with CVB3 and other viruses such as Corona and influenza can be examined with a very high resolution; this new method also means that the borders of what can be researched can be extended. Follow-up studies on the controlled expression of CVB3 in hiPSC are already underway and showing promising results. Last but not least, Dr. Stefan Peischard, the lead author of the study now published, and his colleagues in the Seebohm team hope that their work will lead to significant benefits for patients.

Unforeseen circumstances force low-income families to quickly move from one home to the next, a process that helps to perpetuate racial and economic segregation in the United States, research shows.

Author Johns Hopkins University sociologist Stefanie DeLuca analyzed 17 years of her team's field work with 1,200 low-income households in five different cities. They found that low-income families are forced by urgent crises to choose the safest, most convenient locations necessary for immediate survival rather than take the time to find neighborhoods with great schools and job opportunities. These unpredictable shocks often include housing quality failure, housing policy changes, landlord behaviors, income changes and neighborhood violence.

"By listening to how low-income families make their housing decisions we can develop better policies to target what is really getting in their way of moving to higher opportunity neighborhoods with less racial and economic segregation," DeLuca said. "They're not making that move because there is seldom enough time before the next emergency arises and forces them out and demands an immediate solution."

The current pandemic will only exacerbate that pattern if evictions escalate amid record unemployment, say authors of the new paper, published this week in City & Community.

The findings of DeLuca and co-author Christine Jang-Trettien, a former Johns Hopkins graduate student who's now at Princeton University, demonstrate that lawmakers need to reconsider the extent to which federal, state and local policies make assumptions about how low-income families decide where to live and where to send their children to school. Decision-makers often assume that personal preferences and structural impediments such as racial discrimination in housing markets are the primary impediments to reducing segregation by income and race.

The researchers found that people who experience a lifetime of exposure to economically disadvantaged and racially segregated schools and neighborhoods make repeated reactive moves without first considering options for school.

DeLuca and her team conducted interviews over 17 years in Baltimore, Seattle, Cleveland, Dallas and Mobile, Alabama. They revealed how shocks that lead to reactive decision-making affect whether to move, where to move, what schools to choose and whether to rent or own. Residents shared that they did not have the luxury of waiting for the "package deal" of a home in a high-opportunity community. Instead, time and again, they took a "trial and error approach" that they hoped would improve their housing and school situation.

The federal government is already incorporating insights from the research into developing policies that could help support families' ability to choose higher opportunity areas that have been proven to improve physical and mental health and end the cycle of poverty by exposing children to better schools and more jobs.

The U.S. Department of Housing and Urban Development is currently considering applications from public housing authorities through December for a test program that seeks to expand on findings from public housing authorities in Seattle and King County, Washington. Pilot programs there show families with federal housing subsidies are often forced to live in higher poverty areas because of barriers, including "inadequate time to find a unit," not preferences.

The program is building upon research highlighted by DeLuca in this paper and other work conducted collaboratively with colleagues at Harvard, MIT and Columbia.

"The COVID-19 pandemic has deepened the already existing housing crisis in the United States; with unemployment rates more than tripling in the first three months of the pandemic, an enormous eviction wave looms on the horizon," the paper states. "As more families are forced to make 'reactive' moves under duress and financial constraints, our research has potential to highlight the consequences for households and neighborhoods, as well as provide guidance on how to respond to such a fast-moving crisis."

DALLAS - Oct. 8, 2020 - The COVID-19 pandemic has led to new rules and expectations for clinical trials. Following guidance from federal agencies, institutions such as UT Southwestern adjusted clinical trial operations. To protect patient safety, changes such as utilizing remote consents, conducting telehealth study visits, and shipping oral study treatment to patients' homes have streamlined the clinical trial participation process.

A survey of UTSW clinical research professionals found that most clinical trial coordinators, managers, and nurses report positive experiences with these COVID-related adjustments. In fact, a majority are in favor of keeping the new protocols even after the pandemic ends.

"With COVID-19, we've seen more changes to clinical trial practices than at any other time in my career," says David Gerber, M.D., a professor of internal medicine at UTSW, associate director of clinical research in the Harold C. Simmons Comprehensive Cancer Center, and first author of an article on the survey results published online this week in the Journal of the National Comprehensive Cancer Network. "My hope is that this whole ordeal leads to long-term simplification of the clinical research process."

On March 16, UT Southwestern announced restrictions on clinical trials in response to COVID-19, halting new enrollments and cutting back on in-person, nonessential research visits for ongoing trials. Two days later, the Food and Drug Administration issued its own guidance, allowing clinical researchers to make temporary changes to trial conduct, including implementing telehealth appointments and allowing electronic signatures. This guidance remains in effect until the official COVID-19 national emergency is ended by the federal government. The National Institutes of Health also issued revised trial guidance.

"Shutting everything down for new enrollment was a hard decision for us, but ultimately we had to consider what was best for patients," says Erin Williams, associate director of clinical research operations at the Simmons Cancer Center. "Our goal was to get everything reactivated as quickly as possible, but we needed time to figure out how to make clinical trials work in the wake of COVID-19."

Before ramping clinical trials back up, Williams' team had to cross many technical barriers. Those included putting systems into place for researchers and patients to remotely access documents and information, as well as new ways for researchers to communicate virtually with patients.

From April 27 to June 1, the Simmons Cancer Center gradually resumed clinical trial enrollments, but with new measures in place. For instance, patients no longer had to visit in person to consent to participate in a trial - a lengthy process that involves learning about the risks and benefits of participation. That process was shifted to video calls and electronic signatures. Moreover, some patients who previously had to visit the Simmons Cancer Center to receive drugs could now have them shipped to their homes. And some visits to check on patients' progress or symptoms were converted to telehealth calls.

"Things behind the scenes changed, too," says Williams. "Our workflow and that of any sponsoring pharmaceutical company are very different now."

Gerber, Williams, and their colleagues saw the changes as an opportunity for research. On May 22 - roughly a month after the new procedures were launched - they invited 108 UTSW clinical research professionals to participate in a webinar and respond to an emailed survey about the changes.

Ninety-four responded to the survey, including administrative professionals who coordinate trial logistics and finances, research nurses, research managers and coordinators, and data specialists. Of those, 58 percent had more than five years of professional experience with clinical research and 56 percent had personal experience with a COVID-19-related change.

Overall, survey respondents said that the changes had a positive impact on patient safety, treatment efficacy, patient and staff experience, and communication with patients, investigators, and sponsors. More than 90 percent thought that it was pretty important, important, or very important to continue any positive COVID-19-related clinical research adjustments after the pandemic ends.

For some specific changes, those who had firsthand experience with the new protocols were more likely to recommend continuation. For instance, 61 percent of respondents who had used telehealth were in favor of keeping it going, compared with 36 percent of those who had not used this technology. Similarly, 63 percent of those who had been involved in shipping therapies were in favor of the practice continuing, while only 29 percent of those without experience shipping therapies suggested the practice continue.

"It goes to show that things that might look or sound complicated from the outside are actually less scary when you're the one who gets it worked out and does it," Williams says.

Research professionals with more than five years of experience in the field also were more open to keeping the changes in place. "I think the longer someone works in clinical research, the more they tend to question the status quo," Gerber says.

Researchers from the Center for Algorithmic Biotechnology at St Petersburg University, as part of a group of Russian and American scientists, have developed the metaFlye assembler. It is designed to assemble DNA samples from microbial communities. With its help, it is possible to solve a wide range of fundamental and applied problems, among which is the control of the process of treating patients and even the creation of new drugs.

At present, to study the DNA of any living organism, scientists around the world use complex biotechnological instruments - DNA sequencers. These special machines cannot 'read' the genome from start to finish (like people read books). They do it in separate short fragments - reads. Combining reads into longer fragments, and ideally into a single sequence of the original genome, is an extremely complex computational problem. It is like assembling a million-piece puzzle. The problem is complicated by the fact that genomes often contain a large number of identical repetitive sequences, which often exceed the length of reads. It is possible to cope with this challenging problem using specialised software - genome assemblers.

Several dozen different assemblers are being developed in leading bioinformatics laboratories around the world, and they are available to scientists. This diversity is because the algorithms that assemblers are based on need to be adapted to: different types of input data obtained on different types of DNA sequencers; and different organisms. For example, approaches for assembling bacterial genomes may not be suitable at all for assembling the human genome and vice versa. Additionally, the developers of genomic assemblers are constantly striving to improve their solutions so that: their programmes run faster and use less memory; and the resulting assemblies are longer and more accurate than those produced by the competing software.

The new metaFlye assembler is designed for assembling metagenomes. These are DNA samples from microbial communities obtained from various environments, such as the deep sea, soil in a park, or human gut. Having received an assembly of such a sample, it is possible to determine what kind of and how many organisms are presented in it. Using additional assembly analysis, it is often possible to find out: what these organisms can feed on; how they interact; and what substances they synthesise. All this information can be used in the future, for example: to search for new drugs of natural origin; to determine the reasons underlying the extreme soil fertility; when checking the course of treating patients; and in solving many other fundamental and applied problems.

The metaFlye assembler is designed for data obtained using the current state-of-the-art sequencing technology - long-read sequencing. There are already several metagenomic assemblers working with short-read sequencing, or next-generation sequencing (NGS) data generated on Illumina instruments. Among these assemblers there is the metaSPAdes assembler. It was developed at the Center for Algorithmic Biotechnology at St Petersburg University in 2016. There are also software for assembling isolate genomes from long reads. metaFlye makes it possible to take advantage of the new technology for complex metagenomic data. It is the first metagenome assembler specially designed to work with Oxford Nanopore and PacBio technologies.

'The impetus to develop metaFlye was the absence of a specific metagenomic assembler for long-read technology,' says Mikhail Rayko, one of the project's authors, a senior research fellow at the Center for Algorithmic Biotechnology at St Petersburg University. 'This technology has already changed dramatically the whole modern genomic science. We have learned to obtain much more complete assemblies. For example, with its help, many missing fragments of the human genome have recently been sequenced and localised. The original Flye tool was used for that, and the members of our laboratory also took part in this project. However, such data have just begun to appear for metagenomes, and, of course, special tools are needed for processing it.'

Work on metaFlye started about two years ago. It is four years if we count from the creation of its predecessor, the genomic assembler Flye, on the basis of which the new project was implemented.

'In our study, published in the journal Nature Methods, we used metaFlye and other assemblers to analyse several simulated (i.e., computer generated, without real DNA sequencing) and real metagenomic samples from the gastrointestinal tract of a human, a cow and a sheep,' says Alexey Gurevich, a co-author of the assembler and a senior research fellow at the Center for Algorithmic Biotechnology at St Petersburg University. 'A sample of the sheep microbiome is perhaps of principal interest. It was first obtained and studied in this work, while the initial sequencing data for the other two samples were taken from the works of third-party authors. metaFlye made it possible to assemble an order of magnitude more viral genomes and one and a half times more plasmids in this sample than when using the best existing analogue programmes.'

Another intriguing result was that it was possible to assemble in the sample the genomes of not only bacteria and archaea, but also eukaryotes. At the same time, bioinformatics analysis revealed that almost half of eukaryotic genomic fragments belong to representatives of nematodes, or roundworms. This result fully complies with the autopsy report of the animal, which showed signs of parasitic infection.

'The metaFlye assembler is a tool for solving a wide range of tasks. It will be available to all researchers working with such data. Of the specific projects carried out in our laboratory, we use the assembler to study the soil composition in Chernevaya taiga - a unique biocoenosis of Western Siberia with abnormally high fertility,' says Alexey Gurevich.

The publication about metaFlye is the result of a collaboration of 11 Russian and American scientists from: St Petersburg University; the University of California San Diego (UCSD); Bioinformatics Institute (St Petersburg); and US Research Centers for Dairy Forage and Meat Animal. The metaFlye assembler itself is being mainly developed in UCSD. Its developer and main author of the publication is Mikhail Kolmogorov, a postdoc at UCSD. The research supervisor of the project is Pavel Pevzner, Professor at UCSD and Chief Advisor of the Center for Algorithmic Biotechnology at St Petersburg University.

New research from the University of California San Diego reveals that Democratic control of state houses leads to substantial improvement in women's incomes, wages and unemployment relative to men.

The study, to be published in Legislative Studies Quarterly, finds that especially in the recent period of pronounced partisan polarization, Democratic house control helps close the gender inequality gap. Across all states, women's wages averaged only 70 percent of men's wages in 2018, but just a few years after Democrats are elected in a state, that gap typically declines by 3.6 percentage points. Additionally, the researchers estimate that a slim Democratic majority in the house--as opposed to a slim Republican majority--leads to a 2.6 percent point reduction in the overall income gap between men and women.

"No voting bloc is more important in American elections than women," said first author Zoltan Hajnal, a professor of political scientist at UC San Diego's School of Global Policy and Strategy. "With women accounting for more than half of all votes, small shifts in the female vote can and likely will determine who wins in November."

Hajnal and co-author John Seungmin Kuk of the University of Oklahoma also assessed whether Democratic or Republican control of the White House could be linked to gains or declines in gender inequality, and the same pattern emerged. Over the last half century, women's incomes grew almost twice as fast under Democratic administrations than they did when Republicans held the Oval Office. The average gain in income for women was $443 per year under Democrats but only $284 per year under Republicans. And, poverty as well as unemployment rates also fell among females under Democratic administrations.

To test whether Democratic or Republican control of state houses impacts gender inequality, the authors tracked male and female wages, income, poverty, and employment in each state annually for the last five decades. Specifically, they looked to see if women were catching up to men faster when Democrats controlled the levers of state power then when Republicans did.

Their assessment was made by comparing changes in gender equality in states where Democrats barely won a majority in the House to states where Republicans barely won a majority. Further comparisons revealed that that Democratic control of the state House leads to significant improvement in female income (relative to male income), significant declines in female unemployment (relative to male unemployment), and near significant declines in the wage and poverty gaps.

"Just one year of Democratic control leads to a one percentage point increase in the female-male income ratio, a 0.7 percentage point decline in the wage gap, a 0.4 percent decline in the female-male employment gap, and a .28 percent decline in the male-female poverty gap," the authors wrote.

A gender gap that is no longer narrowing

These trends could be critical in closing the gender wage gap. The study points to ample evidence that women who work in the same job with the same level of experience still get paid considerably less than men. For example, National Women's Law Center recently estimated that women typically have to work 50 years to make what a man earns in 40 years. Moreover, there is evidence that after declining for many decades, the gap is no longer narrowing.

Several factors contribute to pronounced inequity, such as the fact that women are much more likely than men to be family caregivers means that the gender gap widens after women become mothers. However, 38 percent of the gender wage gap cannot be explained by factors that are easily measured such as occupation, educational attainment, or years of experience.

So, what do Democrats do differently to help close the gender the gap? While the researchers could not definitively answer this question, they find two factors are associated with the gains for women under Democrats.

"The first is gender policy," they write. "Democratic control of the state houses leads to significantly more liberal policies on gender discrimination and access to family planning. The other factor is female representation. We find that having more women in office also leads to more liberal gender policy and likely contributes to improvement on basic economic indicators for women."

However, just having more women hold office isn't necessarily the answer, according to the data.

"Any impact of female legislators is entirely contingent on having Democrats control the house majority," they write. "Having women in office greatly matters for gender policy, but only when Democrats control the agenda."

While Democratic vs. Republican control has meaningful effects for gender equality in some cases, it does not in others. Partisan control of the governor's office appears to have no clear impact on gender equality, and the same could be inferred regarding state senates. Data limitations prevented the authors from directly assessing the effect of Democratic control of the state senate, but their exploratory analysis revealed no clear effects.

Yet, they conclude that parties appear to have more meaning now as polarization has increased, relative to how a less-divided political system operated for much of the 20th Century.

BOSTON - People who survive serious COVID-19 infections have long-lasting immune responses against the virus, according to a new study led by researchers at Massachusetts General Hospital (MGH). The study, published in Science Immunology, offers hope that people infected with the virus will develop lasting protection against reinfection. The study also demonstrates that measuring antibodies can be an accurate tool for tracking the spread of the virus in the community.

The immune system produces proteins called antibodies in response to SARS-CoV-2, the virus that causes COVID-19. "But there is a big knowledge gap in terms of how long these antibody responses last," says Richelle Charles, MD, an investigator in the Division of Infectious Diseases at MGH and a senior author of the paper. To find out, she and her colleagues obtained blood samples from 343 patients with COVID-19, most of whom had severe cases. The blood samples were taken up to four months after a patient's symptoms emerged. The blood's plasma was isolated and applied to laboratory plates coated with the receptor-binding domain (RBD) of the virus's "spike" protein, which attaches to cells, leading to infection. The team studied how different types of antibodies in the plasma bound to RBD. The results were compared to blood samples obtained from more than 1,500 individuals prior to the pandemic.

The researchers found that measuring an antibody called immunoglobulin G (IgG) was highly accurate in identifying infected patients who had symptoms for at least 14 days. Since the standard PCR (nasal swab) test for SARS-CoV-2 loses sensitivity over time, augmenting it with a test for antibodies in patients who have had symptoms for at least eight days (at which time 50 percent are producing antibodies) will help identify some positive cases that might otherwise be missed, says Charles.

The researchers found that IgG levels remained elevated in these patients for four months, and were associated with the presence of protective neutralizing antibodies, which also demonstrated little decrease in activity over time. "That means that people are very likely protected for that period of time," says Charles. "We showed that key antibody responses to COVID-19 do persist."

In another finding, Charles and her colleagues showed that people infected with SARS-CoV-2 had immunoglobulin A (IgA) and immunoglobulin M (IgM) responses that were relatively short-lived, declining to low levels within about two and a half months or less, on average. "We can say now that if a patient has IgA and IgM responses, they were likely infected with the virus within the last two months," says Charles.

Knowing the duration of the immune response by IgA and IgM will help scientists obtain more accurate data about the spread of SARS-CoV-2, explains Jason Harris, MD, a pediatric infectious disease specialist at MGH and co-senior author of the study. "There are a lot of infections in the community that we do not pick up through PCR testing during acute infection, and this is especially true in areas where access to testing is limited," he says. "Knowing how long antibody responses last is essential before we can use antibody testing to track the spread of COVID-19 and identify 'hot spots' of the disease."

The public may have grown tired of candidates who say one thing on the election trail then do another when in office, but a new study suggests truthful candidates might be less likely to make it through to elected office.

Drawing on findings from a lab-based election experiment involving 308 people, research from economists at the University of Bath (UK) and University of Konstanz (Germany) highlights how even though voters indicate trust and legitimacy are important factors in deciding on how to cast their votes, candidates who progress in politics are those most prepared to renege on electoral promises.

In their study, the economists designed a game-theory experiment to test the importance of trustworthiness and to see how individuals react when faced with various different election scenarios. Their two-stage election process first involved individuals vying against each other to win their party's candidacy (similar to US primaries).

They then asked 'candidates' in the experiment how much they would invest (on a scale of 100) as a measure of how eager they were to gain selection in terms of money, time or effort they would put in to get through the selection phase. Those who invested the most had the highest probability of getting through to round two.

If selected to stand for office, candidates next had to choose how much money they would promise to voters in an election, attempting to win over an undecided public. This could reflect campaign promises on tax and spending, for example. Finally, if elected, politicians had to decide how to actually make decisions outside the election race, choosing how much they would transfer to voters or whether to renege on promises.

Their findings highlight that those most likely to make it through the selection process because of their high investments in the first stage were those who reneged on their promises most when elected into office. In other words, those who had been most eager to be selected were also those most likely to deviate from what they had promised.

Lead researcher from the University of Bath's Department of Economics Dr Maik Schneider explains: "Our study highlights why it may not be too surprising to find candidates on the campaign trail who lie. This should concern us all given the low levels of trust in politics.

"There is a clear paradox here in terms of an electorate which says what's missing in politics is greater trust, yet results which indicate that candidates who lie more, somehow still have a higher chance of gaining office.

"From a game theory perspective the reason why this is the case is clear, but these results should serve as a reminder about the importance of challenging untruths among candidates and, more broadly, increasing and improving transparency in the system."

The researchers stress that it is also the case that honest individuals invest time and resources to making it into office, however from these results they were unable to cut through in the same number as their more dishonest rivals.

The team behind the study suggest to improve trust, much more robust fact-checking, transparency around campaign finances and public scrutiny of campaign promises would help. They also argue that schemes to reduce the incentive for dishonesty could include new mechanisms to make campaign promises binding. In the study, when the first stage of the election process was transparent, they found the correlation between 'lie size' when in office and how eager a candidate had been to be selected disappeared.

The new research from Dr Schneider and colleagues, 'Honesty and Self-Selection into Cheap Talk' is published in the Economic Journal.

It builds on earlier work from the same team titled 'Honesty and Self-Selection into Politics'.

Using radio telescopes observing distant stars, scientists have connected optical atomic clocks on different continents. The results were published in the scientific journal Nature Physics (DOI: 10.1038/s41567-020-01038-6) by an international collaboration between 33 astronomers and clock experts at the National Institute of Information and Communications Technology (NICT, Japan), the Istituto Nazionale di Ricerca Metrologica (INRIM, Italy), the Istituto Nazionale di Astrofisica (INAF, Italy), and the Bureau International des Poids et Mesures (BIPM, France).

The BIPM in Sèvres near Paris routinely calculates the international time recommended for civil use (UTC, Coordinated Universal Time) from the comparison of atomic clocks via satellite communications. However, the satellite connections that are essential to maintaining a synchronized global time have not kept up with the development of new atomic clocks: optical clocks that use lasers interacting with ultracold atoms to give a very refined ticking. "To take the full benefit of optical clocks in UTC, it is important to improve worldwide clock comparison methods." said Gérard Petit, physicist at the Time Department at BIPM.

In this new research, highly-energetic extragalactic radio sources replace satellites as the source of reference signals. The group of SEKIDO Mamoru at NICT designed two special radio telescopes, one deployed in Japan and the other in Italy, to realize the connection using the technique of Very Long Baseline Interferometry (VLBI). These telescopes are capable of observations over a large bandwidth, while antenna dishes of just 2.4 meter diameter keep them transportable. "We want to show that broadband VLBI has potential to be a powerful tool not only for geodesy and astronomy, but also for metrology." commented SEKIDO. To reach the required sensitivity, the small antennas worked in tandem with a larger 34 m radio telescope in Kashima, Japan during the measurements taken from October 14 2018 to February 14 2019. For the Kashima radio telescope, these were among the last observations before the telescope was irreparably damaged by typhoon Faxai in September 2019.

The goal of the collaboration was to connect two optical clocks in Italy and Japan, separated by a baseline distance of 8700 km. These clocks load hundreds of ultra-cold atoms in an optical lattice, an atomic trap engineered with laser light. The clocks use different atomic species: ytterbium for the clock at INRIM and strontium at NICT. Both are candidates for a future redefinition of the second in the International System of Units (SI). "Today, the new generation of optical clocks is pushing to review the definition of the second. The road to a redefinition must face the challenge of comparing clocks globally, at the intercontinental scale, with better performances than today," said Davide Calonico, head of the "Quantum Metrology and Nanotechnology" division and coordinator of the research at INRIM.

The connection is possible by observing quasars billions of light-years away: radio sources powered by black holes weighing millions of solar masses, but so distant that they can be considered fixed points in the sky. The telescopes aim at a different star every few minutes to compensate for the effects of the atmosphere. "We observed the signal not from satellites, but from cosmic radio sources," commented IDO Tetsuya, director of the "Space-Time Standards Laboratory" and coordinator of the research at NICT. "VLBI may allow us in Asia to access the UTC relying on what we can prepare by ourselves." IDO added.

Antennas like the transportable ones used in these measurements can be installed directly at the laboratories developing optical clocks around the world. According to SEKIDO, "a global optical clock network connected by VLBI may be realized by collaboration between the international communities of metrology and geodesy, just like the broadband VLBI network of the VLBI Global Observing System (VGOS) has already been established," while Petit commented: "waiting for long-distance optical links, this research shows that there is still to gain from radio links, where VLBI with transportable antennas can complement the Global Navigation Satellite Systems and telecommunication satellites."

Besides improving international timekeeping, such an infrastructure also opens new ways to study fundamental physics and general relativity, to explore variations of Earth's gravitational field, or even the variation of fundamental constants underlying physics. Federico Perini, coordinator of the research at INAF, commented "We are proud to have been part of this collaboration helping to achieve such a big step forward in developing a technique which, using the most distant radio sources in the Universe, makes possible the measurement of the frequencies generated by two of the most accurate clocks here on the Earth." Calonico concludes "Our comparison using VLBI gives a new perspective to improve and investigate new methods for clock comparisons, also looking at the contamination between different disciplines."

Baltimore, MD-- Recent work led by Carnegie's Kamena Kostova revealed a new quality control system in the protein production assembly line with possible implications for understanding neurogenerative disease.

The DNA that comprises the chromosomes housed in each cell's nucleus encodes the recipes for how to make proteins, which are responsible for the majority of the physiological actions that sustain life. Individual recipes are transcribed using messenger RNA, which carries this piece of code to a piece of cellular machinery called the ribosome. The ribosome translates the message into amino acids--the building blocks of proteins.

But sometimes messages get garbled. The resulting incomplete protein products can be toxic to cells. So how do cells clean up in the aftermath of a botched translation?

Some quality assurance mechanisms were already known--including systems that degrade the half-finished protein product and the messenger RNA that led to its creation. But Kostova led a team that identified a new tool in the cell's kit for preventing damage when protein assembly goes awry. Their work was published by Molecular Cell.

Using CRISPR-Cas9-based genetic screening, the researchers discovered a separate, and much needed, device by which the cell prevents that particular faulty message from being translated again. They found two factors, called GIGYF2 and 4EHP, which prevent translation from being initiated on problematic messenger RNA fragments.

"Imagine that the protein assembly process is a highway and the ribosomes are cars traveling on it," Kostova explained. "If there's a bad message producing incomplete protein products, it's like having a stalled car or two on the road, clogging traffic. Think of GIGYF2 and 4EHP as closing the on-ramp, so that there is time to clear everything away and additional cars don't get stalled, exacerbating the problem."

Loss of GIGYF2 has previously been associated with neurodegenerative and neurodevelopmental problems. It is possible that these issues are caused by the buildup of defective proteins that occurs without the ability to prevent translation on faulty messenger RNAs.

NASA's OSIRIS-REx spacecraft mission, launched on Sept. 8, 2016, is the first U.S. mission designed to retrieve a pristine sample of an asteroid and return it to Earth for further study. The mission's target is Bennu, a carbon-rich near-Earth asteroid that is potentially hazardous, representing an approximately 1 in 2,700 chance of impacting the Earth late in the 22nd century.

Scientists believe Bennu may contain the molecular precursors to the origin of life and the Earth's oceans, so one of the mission's main objectives is to determine Bennu's physical and chemical properties.

"The spacecraft has been observing the asteroid for nearly two years now," said Joshua Emery, associate professor in NAU's Department of Astronomy and Planetary Science and a member of the OSIRIS-REx science team. "Bennu has turned out to be a fascinating small asteroid and has given us many surprises."

The mission's first attempt to pick up the sample is scheduled for Oct. 20, 2020, and the spacecraft is scheduled to return the sample back to Earth on Sept. 24, 2023. In advance of the sample collection, the science team published a set of six papers in Science and Science Advances, four of which Emery co-authored, to share its scientific findings to date while building interest in the upcoming event.

"We've been working for over a decade toward the upcoming sampling attempt," he said. "It's such an exciting time. The spacecraft will send back data pretty quickly to let us know if the maneuver itself was successful, and it'll be exciting to see images from the sampling event, which should be sent back within a day."

The papers describe the detailed characterization of the surface using images, spectroscopy (composition) and thermal measurements. Emery summarizes each of the four papers he co-authored:

Widespread carbon-bearing materials on near-Earth asteroid (101955) Bennu, published in Science: "OSIRIS-REx spectrometer data show absorptions ("fingerprints") of complex organic molecules and carbonate minerals on Bennu's surface. These materials do not appear to be spatially correlated to any specific geologic features or other compositions, but they are widespread across the surface. These data provide the first concrete detection of carbon-bearing materials on a near-Earth asteroid. The presence of organics on Bennu suggests that asteroids like Bennu may have brought organic molecules to Earth."

Bright carbonate veins on asteroid (101955) Bennu: Implications for aqueous alteration history, published in Science: "Detailed analysis of absorption features in OSIRIS-REx spectrometer data indicate that there are carbonates on Bennu and that these carbonates are similar to those found in certain meteorites. Images of Bennu show that some of the rocks contain bright veins that may be carbonate. Carbonates, and their occurrence in large abundance, mean that fluid flow and hydrothermal deposition on Bennu's parent body would have occurred over distances of kilometers for thousands to millions of years - conditions that suggest large-scale, open-system hydrothermal alteration of carbonaceous asteroids in the early solar system."

Asteroid (101955) Bennu's weak boulders and thermally anomalous equator, published in Science Advances: "By measuring and mapping the temperature of the surface of Bennu at different times of day, we can see how different rocks heat up and cool down, which enables us to determine physical properties of the surface rocks. This analysis distinguishes two boulder populations on Bennu that differ in thermal inertia (resistance to changes in temperature) and strength. Both have lower thermal inertia and inferred strength than expected for boulders and meteorites. The weaker boulder type probably would not survive atmospheric entry and thus may not be represented in the meteorite collection. Our findings imply that other NEAs likely have boulders similar to those on Bennu, rather than finer-particulate regoliths."

Heterogenous mass distribution of the rubble-pile asteroid (101955) Bennu, published in Science Advances: "We measured the gravity field of Bennu in great detail using the OSIRIS-REx spacecraft trajectory and by mapping the orbits of small particles ejected from Bennu's surface. The gravity field provides insight into the interior structure of Bennu. These data show that Bennu does not have a uniform interior. Bennu's center appears to have a lower density than its average. The equatorial bulge also has a relatively low density. The lower-density equator is consistent with recent movement of material to the equator. The lower-density center suggests that Bennu used to spin much faster than its current 4.29 period 'day'."

"It's been such thrill and honor to be part of the OSIRIS-REx team," Emery said. "As lead of the thermal analysis working group, it has been very exciting for me to be very involved in planning the observations the spacecraft has made in preparation for sampling and then figuring out from the data what the surfaces is like. The rocks on Bennu look strange, and we found from the thermal data that they are so weak that we could easily crush them in our hands. Still, they have existed on this asteroid for over a billion years! These rocks also contain complex organic molecules that form naturally in space, and asteroids like Bennu could have brought these organic molecules to Earth billions of years ago to seed the beginnings of life. When the sample is returned to Earth, scientists will be able to study these molecules in exquisite detail."

Emery, who joined NAU in 2019, applies the techniques of astronomical reflection and emission spectroscopy and spectrophotometry of primitive and icy bodies in the near- (0.8 to 5.0 microns) and mid-infrared (5 to 50 microns) to investigate the formation and evolution of the Solar System and the distribution of organic material.

The Jupiter Trojan asteroids have been a strong focus of his research, and he also regularly observes Kuiper Belt objects, icy satellites and other asteroid groups to understand the state of their surfaces as related to these topics. In addition to contributing to Solar System exploration as a science team member on the OSIRIS-REx asteroid sample return mission, he also collaborated on the upcoming Lucy Trojan asteroid flyby mission and the NEO Surveyor Mission infrared telescope mission.

New Rochelle, NY, October 8, 2020--The potential for treating cystic fibrosis (CF) using mRNA therapies or CRISPR gene editing is possible regardless of the causative mutation. CF clinical trials showing that a genotype-agnostic gene therapy for CF is possible are reviewed in the peer-reviewed journal Human Gene Therapy. Click here to read the full-text article free on the Human Gene Therapy website through November 4, 2020.

"Treating CF by delivering mRNA that encodes CFTR has the potential to work in any CF patient, independent of the underlying mutation," state James Dahlman, Georgia Institute of Technology, and coauthors. "Another potential treatment is utilizing mRNA encoding nucleases such as CRISPRCas9 accompanied by gRNA and using them to edit DNA in target cells."

Challenges remain to be able to utilize these approaches successfully. First among them is the need to identify drug delivery systems that can reach pulmonary epithelial cells at low doses.

"CF was the first disease target in humans for several vector platforms, including rAAV and rAd. It is gratifying to see these newer technologies applied to CF, particularly to the 5% of patients whose mutations are resistant to CFTR modulator drugs," according to Editor-in-Chief of Human Gene Therapy Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School.

PULLMAN, Wash. - Advertising and location of cannabis retailers influence adolescents' intentions to use marijuana, according to a new study in the Journal of Health Communication by Washington State University researchers.

Stacey J.T. Hust, associate dean in the Murrow College of Communication, and Jessica Fitts Willoughby, associate professor of communication, conducted a survey of 13- to 17-year-olds in Washington State to find out how marijuana advertising and the location of marijuana retailers influence adolescents' intentions to use the drug. The researchers also asked participants about their outcome beliefs--whether or not they thought using marijuana would be good for them personally and or socially.

Their research shows regular exposure to marijuana advertising on storefronts, billboards, retailer websites and other locations increased the likelihood of adolescents using marijuana.

"While there are restrictions against using advertising designed specifically to target youth, it does still appear to be having some influence," Willoughby said. "Our research suggests a need to equip adolescents with the knowledge and skills to critically evaluate marijuana advertisements."

Location of retail stores also played a role but the results of the survey were mixed.

While the actual density of marijuana retailers in an area was not associated with adolescents' intentions to use, study participants who said they lived within five miles of a marijuana shop were more likely to report intentions to use the drug than those who perceived they lived farther away.

"This was especially the case when they also reported having positive beliefs about marijuana use," Hust said. "The study participants who felt positively about marijuana and perceived living close to retailers were the most likely to report intentions to use marijuana."

The results of the research team's study could have significant policy implications as states that have legalized recreational marijuana use grapple with ways to adhere to the drug's legal status while trying to prevent adolescent marijuana use.

For instance, most states with legalized marijuana restrict placing retailers and advertisements next to schools, but other locations, where adolescents live and spend a lot of their time, remain largely unregulated.

"Our findings are particularly relevant given that most states that have legalized recreational marijuana have not restricted their proximity to neighborhoods or living areas, which may be particularly challenging in large metropolitan areas," Hust said. "States may want to consider using census data to identify the proportion of teens living in particular areas as they identify the location for marijuana retailers."

The researchers are currently in the process of conducting a new experiment where they are testing different types of advertisements to see how young people interpret and respond to them.

"One of the things this research and other studies suggest is that these advertisements are pretty prolific in certain areas and we want to see what type of appeals are used in the advertisements and how those appeals affect viewers," Hust said. "Our long-term goal is really to develop a better understanding of how adolescents can make heathy and informed decisions in an environment in which marijuana is legal."

University of Delaware Professor Kristi Kiick is leading collaborative research to create new drug delivery systems with the potential to improve treatment for diseases that affect connective tissues, such as osteoarthritis or rheumatoid arthritis, which is an autoimmune disease.

The UD researchers have devised tiny cargo-carrying systems many times smaller than a human hair. These systems, or carriers, are made from molecules called peptides that help provide structure for cells and tissues.

The research team is working to program these nanoparticle carriers to selectively bind to degrading collagen in the body. Collagen is a protein that helps plump up or provide structure to connective tissue--everything from our skin to our bones, tendons and ligaments.

When collagen degrades, as a result of disease or injury, the nanoparticles designed by the Kiick lab can attach and remain at the injury site longer than many current treatment options. This allows for the possibility of delivering site-specific medicines over longer periods of time--from days to weeks.

In one collaborative project that involves this work, Kiick is trying to develop drug carriers that could be useful in treating osteoarthritis. Osteoarthritis is a degenerative joint disorder characterized by inflammation, pain and stiffness. According to the Centers for Disease Control and Prevention, it affects 32.5 million Americans.

Early studies with Christopher Price, an associate professor in biomedical engineering, suggests that these nanoparticles can be retained in tissue and knee joints. In other related studies, Kiick and her students have shown that drugs can be encapsulated and retained in the nanoparticles, until released by changes in temperature.

"We are interested in learning how to release drugs that can help not just with pain management, but also with slowing down disease progression," said Kiick, Blue and Gold Distinguished Professor of Materials Science and Engineering. "It has been key that we have been able to collaborate with the Price laboratory in this type of work."

For a long time, small molecule corticosteroids have been a standard of care for managing pain in osteoarthritic joints. Because the joint is full of thick, sticky fluid and is under constant mechanical stress and motion, these small-molecule drugs get expelled from the fluid around the knee pretty quickly, in minutes.

"We are hopeful that by controlling the nanoparticle composition and structure," said Kiick, "we will be able to finely control, or tune, the drug delivery behavior to provide longer-lasting relief for people with inflammatory conditions, such as osteoarthritis."

Kiick and colleagues reported advances on the nanoparticle design on Wednesday, Oct. 7, in a paper published in Science Advances, a peer-reviewed journal of the American Association for the Advancement of Science. Co-authors on the work include Jingya Qin, a graduate student in the Kiick lab, and Jennifer Sloppy, a senior microscopy specialist in UD's Harker Interdisciplinary Science and Engineering Laboratory.

The paper's key findings demonstrate the research team's ability to control the shape of the nanoparticles, which will impact how well they can bind to tissue in the body and stay in a particular location. The research team also can precisely control the size of the nanoparticles, which has implications for how they might be retained at the injection site and also how they may be used by particular cells before being removed from the body. Finally, the paper describes some of the very fine details of how the specific building blocks inside these peptide molecules can affect the temperature at which those different shaped and sized nanoparticles can be disassembled to release a medicine.

The research builds on Kiick's previous patented and patent-pending work in this area, but she said it is collaboration with others that is driving forward promising results. While the Kiick lab brings expertise in creating novel materials that can be used as delivery systems; Arthi Jayaraman, Centennial Term Professor for Excellence in Research and Education in the Department of Chemical and Biomolecular Engineering, is helping the team understand factors related to temperature sensitivity of the delivery vehicles and to develop computational tools that can help the research team characterize the vehicle's shape.

Meanwhile, Price's expertise in understanding post-traumatic osteoarthritis has been key to developing methods to use these nanoparticles to potentially treat disease. Price is exploring how particular drugs and cells interact, which may inform what specific classes of medicines are useful in treating osteoarthritis that develops following traumatic injury. The collaboration will help the Kiick lab tailor what types of nanoparticle devices can be used to deliver these different classes of medicines.

According to Kiick, thinking big, the team could imagine loading a custom cocktail of medicines into the drug-delivering nanoparticles capable of delivering relief over varying timescales and temperatures. The researchers already have the right material nanostructure that can allow this to happen; now they are exploring how to trigger the nanoparticles to release specific medications under particular conditions.

"You could imagine injecting these encapsulated medications at the knee," she explained. "Then, when you want one medication to be released, the patient could ice their knee. If another drug is needed to provide relief over a longer time-period, heat could be applied."

It could be a really simple way to help people manage chronic conditions that cause a lot of pain and reduce mobility. And because the treatment is local, it could reduce side effects that can occur when drugs have to be taken at high doses or over prolonged periods of time.

"If these delivery vehicles could reduce painful effects of osteoarthritis, or delay when osteoarthritis symptoms emerge, there could be important implications for improving quality of life for many people," Kiick said.