Culture

Philadelphia, April 14, 2021 - In late 2020, several concerning SARS-CoV-2 variants emerged globally. They are believed to be more easily transmissible, and there is concern that some may reduce the effectiveness of antibody treatments and vaccines. An extensive genome sequencing program run by the Houston Methodist health system has identified all six of the currently identified SARS-CoV-2 variants in their patients. A new study appearing in The American Journal of Pathology, published by Elsevier, finds that the variants are widely spread across the Houston metropolitan area.

"Before the SARS-CoV-2 virus arrived in Houston, we planned an integrated strategy to confront and mitigate this microbial threat to our patients," explains lead investigator James M. Musser, MD, PhD, chair of the Department of Pathology and Genomic Medicine at Houston Methodist and Fondren Presidential Distinguished Chair with Houston Methodist Research Institute, Houston, TX, USA. "We instituted a plan to sequence the genome of every positive specimen from patients within the Houston Methodist system with the goal of understanding pathogen spread in our community and identifying biologically-important mutant viruses."

Dr. Musser notes that Greater Houston is the first metropolitan multiplex in the United States that has documented all of these important and concerning variants circulating among its residents. The Houston Methodist health system has one of the largest SARS-CoV-2 genome sequencing operations in the US and has so far sequenced 20,453 genomes from clinical specimens collected from patients from March 2020 to February 2021. Patient home address zip codes were used to see how the variants spread across Greater Houston's large, multiethnic, and geographically and socioeconomically diverse population.

The UK variant known as B.1.1.7 was first identified in a patient in Houston in January 2021 and has been found in 23 patients through February 2021. The California variants, B.1.429 and B.1.427 were first found in Houston in late December 2020. Variant B.1.429 has been identified in 143 patients in Houston and variant B.1.427 in 19 patients. The South African variant B.1.351 was first detected in Houston in two patients in December 2020 and January 2021. The Brazil variant P.1 has been identified in four patients since mid-January 2021 and P.2 in 39 patients since late December 2020.

With the exception of B.1.351, the investigators found geographically widespread dissemination of the variants, indicating successful patient-to-patient transmission among the communities. None of the patients were from a common household or reported recent international travel, suggesting that every infection was independently acquired locally or during domestic travel.

Initially Dr. Musser and co-investigators had observed that although the P.2 infection was numerically a minor cause of all Houston-area infections, it was the most common variant of concern in their population because its mutation has the potential to neutralize treatments and vaccines. Continued monitoring of the Houston area shows that the UK B.1.1.7 variant is now the most prevalent variant. According to Dr. Musser, "Emergence of new variants underscores the need for ongoing extensive genomic sequencing efforts for early identification and public health warning."

By linking the SARS-CoV-2 whole genome sequencing data to patient metadata in the electronic medical record, Houston Methodist is able to use analytic tools such as high-performance compute clusters and machine learning to investigate the genomic diversity and characteristics such as strain virulence or patient outcomes. "Our goal is to sequence the SARS-CoV-2 genome of every infected patient in our healthcare system in near-real time and expand outward to other patients in our community," Dr. Musser states. "Our results underscore the need to greatly increase genome surveillance to rapidly identify and track the introduction of new SARS-CoV-2 variants in the U.S. and in local areas."

Dr. Musser and his co-investigators have noted that in the last three weeks, Houston Methodist cases of the UK variant have increased to almost 1,600 from 648. They advise that because vaccination is the best way to decrease the number of circulating COVID-19 variants, a much larger percentage of the population needs to get vaccinated. In the meantime, the team is keeping a very close eye on the variants and the type of disease they cause.

A new study co-authored by University of Colorado Cancer Center researcher Srinivas Ramachandran, PhD, shows how DNA segments known as enhancers function in cells.

The paper published last month in Molecular Cell highlighted the work from Ramachandran, along with Satyanarayan Rao, both part of the Department of Biochemistry and Molecular Genetics at the CU School of Medicine, and Kami Ahmad from the Fred Hutchinson Cancer Research Center.

Enhancers are DNA sequences that drive cell-type-specific gene expression, developmental transitions, and cellular responses to external stimuli. They typically have multiple binding sites for transcription factors, which are proteins that help turn specific genes "on" or "off" by binding to nearby DNA. Ramachandran wanted to find out what the role of those multiple binding sites was in driving enhancer function, and if the transcription factors were binding to the multiple enhancer sites randomly or in a coordinated fashion (which in biology is called "cooperativity").

"Think of the two binding sites in the enhancer as two chairs at a table in a coffee shop. The chairs could be occupied by strangers. They arrive and leave the table at random times, and any time they overlap would be purely by chance. If two friends show up to the coffee shop, they will spend much more time together at the table compared to random strangers," he says.

"Biologically, the implication for transcription factors occupying enhancers at the same time is very big. Our starting assumption was that the transcription factors were more like strangers than friends at a coffee shop. We wanted to develop methods to first measure if there is any cooperativity, and if we found any, then ask how the cell might make the factors work together."

The researchers observed the binding process in the cells of fruit flies, developing two methods to see if multiple transcription cells were binding together or separately at two adjacent binding sites in enhancers.

"Then we could actually say, what is the expectation of them spending time together?" Ramachandran says. "If we know one is bound 50% of the time and the other is bound 50% of the time, then my expectation for no cooperativity is, by multiplying these probabilities, that two of them are together 25% of the time just by chance. But if two of them are together 40% of the time, that means there's some cooperativity. That somehow the enhancer is having conditions that make the transcription factors bind at the same time."

The researchers found that up to 60% of the enhancers they observed had at least one coordinated binding event, meaning the transcription factors were turning on and off together and working together to turn genes off and on. If scientists can better understand why that process happens, he says, they may be able to better understand how enhancers are coopted by diseases like cancer.

"It gets back to how enhancers evolved and how enhancers function," Ramachandran says. "If you think about cancer, it's cells changing their identity from normal cells. They are taking advantage of systems that exist but are usually silenced in that cell type. Understanding how enhancers work actually lets us understand how they are taken advantage of as cells change their identity during disease."

By Luciana Constantino | Agência FAPESP – Adults with periodontitis transmit bacteria that can cause the disease in future to their children, and the bacteria remain in the oral cavity even when the children undergo treatment of various kinds, reinforcing the need for preventive care in the first year of a baby’s life. This is the main conclusion of a study conducted at the University of Campinas (UNICAMP) in the state of São Paulo, Brazil. An article on the study is published in Scientific Reports.

Periodontitis is an inflammation of the periodontium, the tissue that supports the teeth and maintains them in the maxillary and mandibular bones. The disease is triggered by bacterial infection. Symptoms include bleeding of the gums and halitosis. In severe cases, it leads to bone and tooth loss. If the bacteria or other microorganisms that cause the disease enter the bloodstream, they may trigger other kinds of inflammation in the body. Treatment includes cleaning of the pockets around teeth by a dentist or hygienist and administration of anti-inflammatory drugs or antibiotics.

“The parents’ oral microbiome is a determinant of the subgingival microbial colonization of their children,” the article’s authors state in their conclusions, adding that “dysbiotic microbiota acquired by children of periodontitis patients at an early age are resilient to shift and the community structure is maintained even after controlling the hygiene status”.

According to dental surgeon Mabelle de Freitas Monteiro, first author of the article, she and her group have been researching periodontitis for ten years, observing parents with the disease and its impact on their children’s health.

“If the findings are applied to day-to-day dental practice, the study can be said to help design more direct approaches. Knowing that periodontal disease may affect the patient’s family is an incentive to use preventive treatment, seek early diagnosis and mitigate complications,” said Monteiro, who was supported by FAPESP via two projects (16/03704-7 and 16/19970-8).

The principal investigator for both projects was Renato Corrêa Viana Casarin, a professor at UNICAMP’s Piracicaba Dental School (FOP) and last author of the article.

For Casarin, parents should start caring for the health of their children’s gums when they are infants. “This pioneering study compares parents with and without periodontitis. In children of the former, we found subgingival bacterial colonization at a very early age. However, ‘inheriting’ the problem doesn’t mean a child is fated to develop the disease in adulthood. Hence the importance of keeping an eye open for the smallest signs and seeking specialized help,” Casarin said.

Data on the Brazilian population’s oral health is scarce. According to the last national dental epidemiological survey, conducted by the Ministry of Health in 2010, 18% of children aged 12 had never been to the dentist and 11.7% had experienced bleeding of the gums. In the 15-19 age group, 13.6% had never visited a dental clinic. Another survey was scheduled for 2020 but had to be postponed because of the COVID-19 pandemic.

The São Paulo State Department of Health published the findings of its latest oral health survey in 2019, showing among other things that 50.5% of adults aged 35-44 complained of toothache, bleeding gums and periodontitis (read more at: agencia.fapesp.br/30260/).

Bacteria

In the FOP-UNICAMP study led by Casarin and Monteiro, samples of subgingival biofilm and plaque were collected from 18 adults with a history of generalized aggressive (grade C) periodontitis, their children aged 6-12, and 18 orally healthy adults.

In addition to a clinical analysis, the samples were also subjected to a microbiological analysis and genetic sequencing by researchers at Ohio State University in the United States under the supervision of Professor Purnima Kumar.

“Children of periodontitis parents were preferentially colonized by Filifactor alocis, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Streptococcus parasanguinis, Fusobacterium nucleatum and several species belonging to the genus Selenomonas even in the absence of periodontitis,” the article states. “These pathogens also emerged as robust discriminators of the microbial signatures of children of parents with periodontitis.”

Casarin told Agência FAPESP that despite bacterial plaque control and vigorous brushing the children of people with the disease still had the bacteria in their mouths, whereas the effects of dental hygiene and prophylaxis were more significant in the children of healthy subjects.

“Because the parents had periodontitis, their children assumed this community with disease characteristics. They carried the bacterial information into their adult lives,” he said, adding that the analysis of bacterial colonization pointed to a greater likelihood of transmission by the mother. The research group will now work with pregnant women in an effort to “break the cycle” by preventing bacterial colonization of their children’s mouths.

“We’ll treat the mothers during pregnancy, before the babies are born, and try to find out if it’s possible to prevent bacterial colonization from occurring,” Casarin said, noting that studies with patients will proceed only when control of the pandemic permits.

Recognition

The periodontitis research group led by Casarin has won prizes at home and abroad. In 2019, Monteiro topped the clinical research category of the IADR’s Hatton Competition. The IADR (International Association for Dental Research) hosts the world’s leading conference on dentistry, and the competition is designed to provide an opportunity for the best junior investigators to present their research (read more in Portuguese at: www.fop.unicamp.br/index.php/pt-br/doi-odontopediatria/2352.html).

Years earlier the group won an award from the American Academy of Periodontology for the study with the most significant clinical impact.

The article “Parents with periodontitis impact the subgingival colonization of their offspring” is at: www.nature.com/articles/s41598-020-80372-4.

Journal

Scientific Reports

DOI

10.1038/s41598-020-80372-4

HERSHEY, Pa. -- People who trust television and Facebook to provide them with accurate news about the coronavirus pandemic are less knowledgeable about COVID-19, according to a new study, which assessed people's knowledge of the virus in the earliest stages of the pandemic.

The study, published in the peer-reviewed journal Current Medical Research & Opinion, surveyed 5,948 adults in Pennsylvania between March 25-31, 2020, and found that those who relied on social media and TV for news were less likely to get the facts right about the coronavirus.

In fact, adults that used Facebook as an additional source of news in any way were less likely to answer COVID-19 questions correctly than those who did not.

"The rise of social media has changed the way people around the world keep up with current events, with studies showing that up to 66% of Americans rely on social media for news," said Dr. Robert Lennon, associate professor of family and community medicine at Penn State College of Medicine, one of the authors of the paper.

"This is worrying, as misinformation and misunderstanding about COVID-19 and how it spreads is likely to have fueled the pandemic, the death toll of which now surpasses 2.5 million worldwide." said Lennon.

In early March 2020, the COVID-19 outbreak had become alarming enough that Lennon and other Penn State researchers rapidly developed a survey to explore public knowledge, perceptions and preferred information sources regarding COVID-19. Within hours of being told that they had been awarded funding, the World Health Organization declared COVID-19 a pandemic, and two days later the president declared a national emergency.

The survey was disseminated to 5,948 adults in Pennsylvania, offering insight into the public use of information in the midst of a national emergency. The respondents answered questions about where they got their news about coronavirus from, and which news sources they trusted most. They were then given 15 statements about COVID-19 and asked if they thought the statements were true or false, and how confident they were in their answer.

The questions covered knowledge across several domains -- transmission, severity, treatment - and asked questions felt to be of easy, moderate and hard difficulty in each. As media coverage of COVID-19 escalated, developing knowledge questions became increasingly difficult -- a nearly impossible question on Monday was by Thursday so easy it couldn't be used.

The results showed that the most trusted news sources were government websites (42.8%), followed by television (27.2%) and health system communications (9.3%).

There was a clear relationship between where people got their news from and their knowledge of coronavirus. For example, participants who said that their most trusted source of information was government health websites were more likely to correctly answer COVID-19 questions than other groups. On the other hand, individuals whose most trusted source was television news were less likely to correctly answer COVID-19 questions than other groups. Respondents who selected "Facebook" as either their single most trusted source or as an additional information source were less likely to answer knowledge questions correctly.

The findings highlight the importance of considering where people get their news from when designing public health interventions. Guidance such as "stay at home," "wash your hands," "wear a mask" and "socially distance" are only effective if understood and followed.

"Effective communication is a critical element of successfully managing a pandemic response," said Lennon. "Until vaccination is widespread and proven to be effective, public compliance with public health recommendations is our best chance of containing the disease."

"The first step in compliance is an understanding of those recommendations, so it is vital that health communicators -- such as those working for government agencies, academic institutions and health care organizations -- consider how the public get their information and monitor these venues to correct misinformation when it appears."

ITHACA, N.Y. - Just as humans are challenged from the social isolation caused by the coronavirus pandemic, a new study finds that a solitary lifestyle has profound effects on the brains of a social insect: paper wasps.

Paper wasps recognize the brightly colored faces of other paper wasps, an ability they lose when reared in isolation. The wasps' ability to remember faces is similar to primates and humans, but unlike other social insects.

The study revealed that when adult wasps are housed in solitude, visual areas of their brains - especially those involved with identifying nuanced color patterns and shapes - are smaller and less developed than their peers who lived with other wasps.

"To my knowledge, this is the first empirical study to propose a candidate brain region in an insect that is involved with individual identity processing," said first author Christopher Jernigan, a postdoctoral researcher in the lab of Michael Sheehan, assistant professor of neurobiology and behavior at Cornell University.

Paper wasps, native to the eastern United States, live in smaller colonies (up to a few hundred individuals) than honeybees (tens of thousands). Unlike honeybees, whose hives have a single queen, paper wasps can have multiple queens. When starting nests each spring, these future queens can form small groups that collaborate on labor. Still, colonies have social hierarchies and competition. The dominant queen monopolizes egg-laying and subordinate queens do most of the work. Subordinates may leave the nest to join another or start their own colony if they feel the arrangement isn't fair.

"There's tension of balancing conflicts among the cooperating queens, and that seems to be the thing that has favored individuals to recognize each other, to know who's who, how work is being divided up, whether they are getting their fair share," Sheehan said. "It seems to help manage conflicts."

This study tests the effects of maturation and social experience on the wasps' brain development, with a focus on regions involved in visual and olfactory processing, as paper wasps also sense individuals through smells and chemical communication.

Researchers from the HSE Center for Language and Brain https://www.hse.ru/en/neuroling/ have, for the first time, described the language abilities of Russian children with Autism Spectrum Disorder (ASD) at all linguistic levels (e.g., phonology, lexicon, morphosyntax, and discourse), using a language test that takes into account the psycholinguistic variables most relevant for Russians. The study was published in Journal of Autism and Developmental Disorders.

In 2020, the US Centers for Disease Control and Prevention reported that one in every 54 children in the country is diagnosed with ASD. Usually, 75% of children with ASD have comorbid language impairments. Although numerous studies in the USA, UK and Europe have concentrated on these problems, in terms of the specific language profiles of children with ASD at the levels of phonology, lexicon, grammar, and discourse, hardly anything was known about the language abilities of Russian children with ASD.

Researchers from the HSE Center for Language and Brain conducted a comprehensive language assessment of Russian children with ASD. They relied on the Russian Child Language Assessment Battery (RuCLAB), which allows researchers to assess language production and comprehension in terms of the levels of phonology, lexicon, grammar, and discourse, with due consideration of such relevant psycholinguistic variables as word length, the age of acquisition of certain words, word frequency, the number of verb arguments, different sentence types, etc.

A total of 82 Russian primary-school-aged children with ASD participated in the study. Each child was screened with 11 subtests from the RuCLAB, along with two additional subtests on lexicon and phonology. Furthermore, the non-verbal IQ of children, as well as the severity of autistic traits, were measured.

The results showed that there was a significant difference between groups in all subtests, except for the simplest word repetition. Children with ASD had a lower accuracy than typically developing children. The researchers note that the lexicon of children with ASD was the least affected linguistic level, which is consistent with the studies on English-speaking children with ASD.

'In this work, it was important for us to identify the specific language profiles of Russian-speaking children with ASD at different linguistic levels, as well as understand how children's age, non-verbal IQ, and the severity of autistic traits may account for the extent of language impairments,' comments Vardan Arutiunian, author of the paper and Junior Research Fellow at the HSE Center for Language and Brain.

The results also demonstrate that non-verbal IQ dramatically influences language abilities, whereby the higher children's non-verbal intelligence, the higher their language performance. Interestingly, age and the severity of autistic traits were not related to language abilities in children with ASD.
The final goal of the study was to subgroup children with ASD according to their language abilities in each subtest. With this in mind, the researchers divided autistic children into three subgroups, i.e., with normal, borderline, and impaired language abilities.

The total number of children with normal language abilities was related to their linguistic levels. For instance, in terms of word comprehension (lexicon), 22% of children were within the normal range; sentence repetition (morphosyntax) - 8% of children had scores within the normal range; discourse production (discourse) - the normal language group consisted of only 4% of children with ASD.

'We found that the more complex the linguistic level, the lower the percentage of children with normal language abilities. Note that the same child may be in the normal group, according to their lexical abilities, but in the impaired group according to their grammatical development,' comments Vardan Arutiunian, adding: 'That is why the formal language of children with ASD needs to include all linguistic levels, from low-level phonology to high-order discourse. This will help experts to correctly determine the level of children's language development, as well as provide the appropriate speech-language therapy.'

Ultralight bosons are hypothetical particles whose mass is predicted to be less than a billionth the mass of an electron. They interact relatively little with their surroundings and have thus far eluded searches to confirm their existence. If they exist, ultralight bosons such as axions would likely be a form of dark matter, the mysterious, invisible stuff that makes up 85 percent of the matter in the universe.

Now, physicists at MIT's LIGO Laboratory have searched for ultralight bosons using black holes -- objects that are mind-bending orders of magnitude more massive than the particles themselves. According to the predictions of quantum theory, a black hole of a certain mass should pull in clouds of ultralight bosons, which in turn should collectively slow down a black hole's spin. If the particles exist, then all black holes of a particular mass should have relatively low spins.

But the physicists have found that two previously detected black holes are spinning too fast to have been affected by any ultralight bosons. Because of their large spins, the black holes' existence rules out the existence of ultralight bosons with masses between 1.3x10-13 electronvolts and 2.7x10-13 electronvolts -- around a quintillionth the mass of an electron.

The team's results, published today in Physical Review Letters, further narrow the search for axions and other ultralight bosons. The study is also the first to use the spins of black holes detected by LIGO and Virgo, and gravitational-wave data, to look for dark matter.

"There are different types of bosons, and we have probed one," says co-author Salvatore Vitale, assistant professor of physics at MIT. "There may be others, and we can apply this analysis to the growing dataset that LIGO and Virgo will provide over the next few years."

Vitale's co-authors are lead author Kwan Yeung (Ken) Ng, a graduate student in MIT's Kavli Institute for Astrophysics and Space Research, along with researchers at Utrecht University in the Netherlands and the Chinese University of Hong Kong.

A carousel's energy

Ultralight bosons are being searched for across a huge range of super-light masses, from 1x10-33 electronvolts to 1x10-6 electronvolts. Scientists have so far used tabletop experiments and astrophysical observations to rule out slivers of this wide space of possible masses. Since the early 2000s, physicists proposed that black holes could be another means of detecting ultralight bosons, due to an effect known as superradiance.

If ultralight bosons exist, they could interact with a black hole under the right circumstances. Quantum theory posits that at a very small scale, particles cannot be described by classical physics, or even as individual objects. This scale, known as the Compton wavelength, is inversely proportional to the particle mass.

As ultralight bosons are exceptionally light, their wavelength is predicted to be exceptionally large. For a certain mass range of bosons, their wavelength can be comparable to the size of a black hole. When this happens, superradiance is expected to quickly develop. Ultralight bosons are then created from the vacuum around a black hole, in quantities large enough that the tiny particles collectively drag on the black hole and slow down its spin.

"If you jump onto and then down from a carousel, you can steal energy from the carousel," Vitale says. "These bosons do the same thing to a black hole."

Scientists believe this boson slow-down can occur over several thousand years -- relatively quickly on astrophysical timescales.

"If bosons exist, we would expect that old black holes of the appropriate mass don't have large spins, since the boson clouds would have extracted most of it," Ng says. "This implies that the discovery of a black hole with large spins can rule out the existence of bosons with certain masses.

Spin up, spin down

Ng and Vitale applied this reasoning to black hole measurements made by LIGO, the Laser Interferometer Gravitational-wave Observatory, and its companion detector Virgo. The detectors "listen" for gravitational waves, or reverberations from far-off cataclysms, such as merging black holes, known as binaries.

In their study, the team looked through all 45 black hole binaries reported by LIGO and Virgo to date. The masses of these black holes -- between 10 and 70 times the mass of the sun -- indicate that if they had interacted with ultralight bosons, the particles would have been between 1x10-13 electronvolts and 2x10-11 electronvolts in mass.

For every black hole, the team calculated the spin that it should have if the black hole was spun down by ultralight bosons within the corresponding mass range. From their analysis, two black holes stood out: GW190412 and GW190517. Just as there is a maximum velocity for physical objects -- the speed of light -- there is a top spin at which black holes can rotate. GW190517 is spinning at close to that maximum. The researchers calculated that if ultralight bosons existed, they would have dragged its spin down by a factor of two.

"If they exist, these things would have sucked up a lot of angular momentum," Vitale says. "They're really vampires."

The researchers also accounted for other possible scenarios for generating the black holes' large spins, while still allowing for the existence of ultralight bosons. For instance, a black hole could have been spun down by bosons but then subsequently sped up again through interactions with the surrounding accretion disk -- a disk of matter from which the black hole could suck up energy and momentum.

"If you do the math, you find it takes too long to spin up a black hole to the level that we see here," Ng says. "So, we can safely ignore this spin-up effect."

In other words, it's unlikely that the black holes' high spins are due to an alternate scenario in which ultralight bosons also exist. Given the masses and high spins of both black holes, the researchers were able to rule out the existence of ultralight bosons with masses between 1.3x10-13 electronvolts and 2.7x10-13 electronvolts.

"We've basically excluded some type of bosons in this mass range," Vitale says. "This work also shows how gravitational-wave detections can contribute to searches for elementary particles."

New research has found that the most reliable indicators of willingness to be vaccinated against SARS-CoV-2, the virus that causes COVID-19, are rejection of conspiracy suspicions about COVID-19 and a positive attitude towards vaccines in general. The study by King's College London and the University of Bristol is published in the leading peer-reviewed journal Psychological Medicine.

The researchers' analysis was based on a large representative sample survey carried out in November-December 2020. They looked at a range of factors that previous studies had found to be related to hesitancy about getting vaccinated against the coronavirus and found that:

Women, young people, less-educated people, and members of other than white ethnic groups are more hesitant about getting vaccinated

People who get their information about COVID-19 from social media are more hesitant about getting vaccinated

However, the researchers also found that many of these differences can be explained by people's attitudes towards vaccines in general and also by whether or not they suspect that there has been a conspiracy or cover-up connected with COVID -19. In particular, they found that:

Vaccine hesitancy among people who get their information about COVID-19 from social media is completely accounted for by more negative vaccine attitudes and stronger conspiracy suspicions

Vaccine hesitancy among members of other than white ethnic groups and members of low-income households is almost completely accounted for by more negative vaccine attitudes and stronger conspiracy suspicions

Among those who have negative views of vaccines or who suspect that COVID-19 conspiracy theories may be true, more highly educated people appear to be more vaccine hesitant than less highly educated people

On the other hand, the researchers found that greater vaccine hesitancy among women and young people is not explained by conspiracy suspicions or by attitudes to vaccines in general.

Dr Daniel Allington, lead author of the article and Senior Lecturer in Social and Cultural Artificial Intelligence at King's College London, said:

"These findings provide a powerful insight into why heavy users of social media appear to be less confident about being vaccinated against coronavirus: they tend to have more negative attitudes to vaccines in general and they are more likely to suspect that conspiracy theories about the pandemic may be true."

Dr Siobhan McAndrew, principal investigator of the research project and Senior Lecturer in Quantitative Social Science at the University of Bristol, added: "This study gives insight into the connections between fundamental characteristics such as ethnicity and education, and attitudes to vaccination against coronavirus. We have found that conspiracist suspicions and attitudes to vaccines in general form part of the connection - attitudes which likely preceded the current pandemic. The question for policy-makers is how to restore fundamental trust over the long-term, in the interests of public health."

Dr Vivienne Moxham-Hall, Research Associate at the Policy Institute at King's College London with a background in immunology and health policy, explained: "These findings can inform government and public health organisation's communication about the coronavirus vaccine. In order to increase vaccine compliance, communication strategies need to account for the polarising nature of conspiracy theories by providing clear advice to those who may be unsure about vaccine safety and integrity."

Irvine, CA - April 14, 2021 - A new study, led by the University of California, Irvine (UCI), reveals how chronic inflammation promotes muscle fibrosis, which could inform the development of new therapies for patients suffering from Duchenne muscular dystrophy (DMD), a fatal muscle disease.

Titled, "A Stromal Progenitor and ILC2 Niche Promotes Muscle Eosinophilia and Fibrosis-Associated Gene Expression," the study was published today in Cell Reports.
Chronic inflammation is a major pathological process contributing to the progression and severity of several degenerative disorders, including Duchenne muscular dystrophy (DMD). Studies directed at establishing a causal link between muscular dystrophy and muscle inflammation have revealed a complex dysregulation of the immune response to muscle damage.

During muscular dystrophy, chronic activation of innate immunity causes scarring of skeletal muscle, or fibrosis, compromising motor function. How immunity is linked to the molecular and cellular regulation of muscle fibrosis was not well defined, until now.

"In our study we found the interaction between two types of cells--a novel stromal progenitor, which is similar to a stem cell, and group 2 innate lymphoid cells (ILC2), which are a type of immune cell that reside in skeletal muscle--promotes the invasion of white blood cells in muscle. This condition is associated with the elevation of genes that promote muscle tissue scarring found in DMD," said lead author Jenna Kastenschmidt, PhD, an assistant specialist in the UCI School of Medicine Department of Physiology & Biophysics.

The new study not only reveals the interaction of cells contributing to DMD, but it illuminates how muscle eosinophilia is regulated. Eosinophils are white blood cells that infiltrate dystrophic muscle causing fibrosis. In this study, researchers found that eosinophils were elevated in DMD muscle compared to control patients. In addition, researchers found the deletion of ILC2s in dystrophic mice mitigated muscle eosinophilia, reducing the expression of genes associated with muscle fibrosis. These findings contribute to the understanding of the complex regulation of muscle inflammation and fibrosis during muscular dystrophy.

"By further defining the interaction between skeletal muscle-resident immune and stromal cells, we can better understand how chronic inflammation promotes muscle fibrosis and, more importantly, we can facilitate development of novel therapies for DMD," said senior author Armando Villalta, PhD, assistant professor in UCI's Department of Physiology & Biophysics.

Ongoing work from Villalta's lab continues to focus on how distinct facets of the immune system regulate DMD pathogenesis and how these processes influence the efficacy and long-term stability of gene replacement therapy.

New research published in Science Advances provides a template for how to develop directly-acting antivirals with novel modes of action, that would combat COVID-19 by suppressing the SARS-CoV-2 viral infection. The study focused on the macrodomain part of the Nsp3 gene product that SARS-CoV-2 uses to suppress the host cell's natural antiviral response. This part of the virus's machinery, also known as Mac1, is essential for its reproduction: previous studies have shown that viruses that lack it cannot replicate in human cells, suggesting that blocking it with a drug would have the same effect.

The study involved a crystallographic fragment screen of the Nsp3 Mac1 protein by an open science collaboration between researchers from the University of Oxford, the XChem platform at Diamond Light Source, the UK's national synchrotron, and researchers from the QCRG Structural Biology Consortium at the University of California San Francisco. The international effort discovered 234 fragment compounds that directly bind to sites of interest on the surface of the protein, and map out chemical motifs and protein-compound interactions that researchers and pharmaceutical companies can draw on to design compounds that could be developed into antiviral drugs. This work is thus foundational for preparing for future pandemics.

"Robustly identifying this kind of chemical matter for promising and tractable targets like Nsp3 is a first step in rational drug discovery. This is always a long journey fraught with difficulty and failure, but the battery of new structural biology methods that we combined in this study, including fragment screening at Diamond and computational docking at UCSF, are helping to change drug discovery and make it easier to find effective drug candidates," comments Principal Beamline Scientist, Frank von Delft.

These fragments cover a wide range of chemical motifs, and the study lays out the next steps of designing more elaborate molecules that combine the observed themes, synthesizing them and confirming experimentally whether they strongly bind the protein and have a biological effect. The most promising compounds can then be progressed in fully-fledged drug discovery programmes, which includes not only improving the biological potency but also ensuring the final molecule has important drug properties such as easy absorption and minimal side effects.

Most drugs contain a few key components that cause the desired, effect while the rest of the molecule may be important for other reasons, such as solubility, uptake from the gut or how the drug is processed by our metabolism. Traditional high-throughput screening entails testing very large collections of bigger, generally sub-optimal molecules, which are experiment of great complexity.

Instead, fragment screening is an approach for identifying building blocks of the future drug molecule, observing how they interact with the protein under study, contextualizing those interactions, and providing starting points for molecules that directly influence the biology of the protein. This method significantly reduces the number of compounds that need to be screened to find one that really binds, while still informing a broad range of potential molecules. Doing the experiment by structural biology, as implemented at the XChem platform, yields this information directly in 3D, greatly accelerating up the design process and ensuring a far more cost-effective overall experiment.

The UCSF collaborators also used another innovative drug discovery technique, Computational Docking. This deploys computer models and simulations to assess the likely interactions of virtual molecules for favourable interactions with Mac1 and their promise as starting points for drug discovery. The team identified 60 candidates from a virtual library of 20 million molecules, which were then experimentally tested using X-ray crystallography, yielding 20 good hits.

"This is a significantly higher-than-random hit rate, validating the new specific docking methodologies developed by our UCSF colleagues. The high quality structural data of Mac1 that we obtained by X-ray crystallography was essential, but the validation of the approach means that in future, we have additional power for exploring compounds that are not physically available. Overall, this work not only accelerates our ability to validate whether targeting NSP3 Mac1 is an effective way to develop antivirals; it also is hugely valuable in improving the template of methodologies for future inhibitor discovery and development throughout the community of drug discovery," concludes Frank von Delft.

"Family clustering is a confirmed phenomenon associated with Covid-19, and harrowing stories of this disease ravaging families continue to be reported," a new article explains in the March-April issue of the Hastings Center Report. In one extreme example, 28 extended family members in California reportedly tested positive for Covid-19. Two of the family members who quarantined together required hospitalization, and one of them died from the infection. In family clustering cases, multiple loved ones may suffer from the symptoms of Covid-19 and be hospitalized, in quarantine, or recovering; and family members may also have died from the infection.

Family clustering can so devastate a family that there are no healthy, qualified surrogates available to support decision-making, or it can render the emotional burden of decision-making almost unbearable, as it must now be borne in near isolation. In "Navigating Ethical Challenges Posed by Family Clustering during the Covid-19 Pandemic," authors Nicole R. Van Buren, Elijah Weber, Mark J. Bliton, and Thomas V. Cunningham cite cases resulting in death, for instance, when a floor nurse unwittingly transmitted Covid-19 to her elderly father, when an urgent care physician unknowingly transmitted it to his elderly mother whom he lived with and cared for, and when an airport worker transmitted it to his wife, who in turn inadvertently transmitted it to her elderly father. In cases like these, the others observed family members experience guilt and shame, stemming from their belief that they caused their loved one's infection and death.

The authors provide several strategies for patients, doctors, nurses, and families to apply when confronting this phenomenon.

The March-April issue also examines the ethical challenges of consent in a pandemic in several essays, including a piece that looks at calls for prisoners to participate in research on vaccines for Covid-19, in part because the disease has hit prison populations particularly hard. Another essay examines informed consent at the intersection of clinical care and research.

The table of contents of the March-April Hastings Center Report is available here: https://onlinelibrary.wiley.com/toc/1552146x/2021/51/2

The slurred speech, poor coordination, and sedative effects of drinking too much alcohol may actually be caused by the breakdown of alcohol products produced in the brain, not in the liver as scientists currently think. That is the finding of a new study led by researchers from the University of Maryland School of Medicine (UMSOM) and the National Institute on Alcohol Abuse and Alcoholism. It was published recently in the journal Nature Metabolism and provides new insights into how alcohol may affect the brain and the potential for new treatments to treat alcohol misuse.

It is well known that the liver is the major organ that metabolizes alcohol, using the enzyme alcohol dehydrogenase to convert alcohol into a compound called acetaldehyde. Acetaldehyde, which has toxic effects, is quickly broken down into a more benign substance called acetate. This occurs through a different enzyme called acetaldehyde dehydrogenase 2 (ALDH2). Until now, alcohol and acetaldehyde, produced by the liver, have been considered important players in triggering the cognitive impairment associated with imbibing. Acetate, on the other hand, was considered relatively unimportant in producing effects like motor impairment, confusion, and slurred speech. Researchers also did not know which brain region or particular brain cells were most important for alcohol metabolism.

To learn more about the role played by the brain in alcohol metabolism, the researchers measured the distribution of ALDH2 enzyme in the cerebellum, using magnetic resonance (MR) scanners in both mice and in human tissue. They observed that ALDH2 was expressed in the cerebellum, in a type of nerve cell called an astrocyte, in both human brain tissue and in living mice.

The researchers found that this enzyme controlled the conversion of acetaldehyde into acetate in the brain. They also found alcohol-induced cellular and behavioral effects in specific regions of the brain where this enzyme was expressed. Acetate was found to interact with the brain messenger chemical called GABA, which is known to decrease activity in the nervous system. This decreased activity can lead to drowsiness, impair coordination, and lower normal feelings of inhibition.

"We found ALDH2 was expressed in cells known as astrocytes in the cerebellum, a brain region that controls balance and motor coordination," said Qi Cao, PhD, Assistant Professor of Diagnostic Radiology and Nuclear Medicine at the University of Maryland School of Medicine. "We also found that when ALDH2 was removed from these cells, the mice were resistant to motor impairment inducted by alcohol consumption."

Su Xu, PhDHe and his team also found the enzyme ALDH2 in other brain regions responsible for emotional regulation and decision-making (both impaired by excess alcohol consumption), including in the hippocampus, amydala, and prefrontal cortex.

These findings suggest that certain brain regions are important for alcohol metabolism and that abnormalities in the enzyme production in these brain regions can lead to detrimental effects associated with alcohol misuse. They also suggest that acetate produced in the brain and in the liver differ in their ability to affect motor and cognitive function.

"Our next step is to determine whether these mechanisms observed in mice also exist in people," said Dr. Cao. "We would like to know whether alcohol metabolism is directly regulated in the human brain. If further research confirms this to be the case, it could lead to potential new targets for treating alcohol use disorder.

Most people by now have memorized the public health guidelines meant to help minimize transmission of COVID-19: wash your hands, wear a mask, keep six feet apart from others. That part is easy.

What some may not realize is that upholding these guidelines in certain urban areas can present new challenges.

For example, how are you supposed to stay six feet apart from other people when the standard width of a sidewalk is only four feet? What do you do when you want to cross an intersection that requires pressing a button to activate the pedestrian signal, but you are avoiding touching any surfaces?

The COVID-19 pandemic has drastically altered the way individuals interact with other people and their environment, but some public health guidelines meant to protect people conflict with the way public spaces and transport in urban areas are built.

Drive, bike, or walk? The illusion of choice

Dr. David Rojas, an epidemiologist in the Department of Environmental and Radiological Health Sciences at Colorado State University, works with policy makers to improve urban design to make cities more inclusive and sustainable, resulting in better health outcomes for people.

In the case of COVID-19, he noticed that when urban areas were not optimized to accommodate mitigation strategies, it put some people in the awkward position of compromising certain public health guidelines to make a necessary trip to their place of work, school, or worship. Or fear of coming in contact with COVID-19 and the inability to safely travel outside the home kept other people inside.

"The decisions we make are dictated by the options we have. How we decide to move, for example, like whether we take a car or walk to work," Rojas said.

Choosing to travel by car may result in a shorter commute, but it can also mean less daily physical activity compared to bicycling or walking. Likewise, taking a bicycle on the road may get the muscles moving, but riding alongside vehicles every day increases exposure to air pollution from car exhaust.

"Some people don't have the time or opportunity to consider other options," Rojas said. "They have to take their kids to school and get to work within a short period of time, but public transportation is too slow or there aren't any bus stations nearby."

Try taking a bicycle to work when there aren't clearly marked bike lanes and traffic moves too quickly to ride safely. Or walking where the intersections and sidewalks are too narrow and the pedestrian crossings are dangerous.

The options available differ for everyone depending on a range of contributing factors, and any number of sustained detriments impact health, causing long-term issues like obesity, cardiovascular disease, or diabetes, among others. Even an increase of vehicles on the road raises the risk of traffic accidents, in turn putting pressure on the health care system that is responsible for treating resulting injuries.

Designing urban areas with everyone in mind leads to better health outcomes all the time, not only during a pandemic. But, when COVID-19 hit in 2020, people all over the world slowed down and cities adapted their mobility patterns and use of space. This shift created the perfect environment for Rojas to highlight opportunities for improvement in urban design geared toward improving health.

"We need to think about how people experience public spaces differently," Rojas said. "If we have better sidewalks, better connectivity, larger parks that are better designed for everyone, it will be good for chronic diseases, cancer, and many other relevant health outcomes."

10 interventions for long-term health

In an effort to help communities around the world adapt urban areas in light of COVID-19, Rojas worked with an urban planner to create an infographic that details 10 low-cost, temporary interventions to promote urban improvements and public health. The infographic not only identifies interventions that support COVID-19 mitigation strategies, but also explains that many of the changes can be made permanent to contribute to a long-term health vision.

Some of the interventions include adjusting traffic light timing to favor pedestrians and cyclists, expanding public open spaces, and concentrating freight traffic on main roads and at nighttime to improve traffic safety.

The tactical urbanism interventions as an expansion of short-term COVID-19 mitigation strategies are detailed in an article published in Current Environmental Health Reports.

With a projected two-thirds of the human population living in cities by 2050, Rojas asserts that urban designers should plan ahead in the interest of public health. Reponses to the COVID-19 pandemic could provide a push in the right direction.

"We can do two things: make the same mistake of 'copy and paste' regulations or make a change," Rojas said. "We can work with policy makers to not only impact how our cities are designed now, but also to implement better designs for cities created in the future."

To better understand how RNA in bacteria gives rise to protein--and along the way, target these processes in the design of new antibiotics--researchers are turning their attention to the unique way this process happens in bacteria.

In eukaryotic cells, transcription (the process by which information in a DNA strand is copied into messenger RNA) and translation (the process by which a protein is synthesized by the ribosome from the mRNA) are two successive steps. In bacteria, they occur simultaneously: As the RNA is being synthesized by RNA polymerase, the ribosome comes in to make the proteins.

This synchronicity allows for so-called "transcription-translation coupling," wherein the first ribosome can immediately follow and couple with the transcribing RNA polymerase. It is a new area of research that promises to bring insights into processes unique to bacteria that could be targeted with great specificity in the design of antibiotics.

Now, University of Michigan researchers have directly observed previously hidden RNA regulatory mechanisms within such couplings. The results, spearheaded jointly by postdoctoral fellows Surajit Chatterjee and Adrien Chauvier of the U-M Department of Chemistry and the U-M Center for RNA Biomedicine, are published in the Proceedings of the National Academy of Sciences.

The new results promise to have important implications for the future design of antibiotics that could target the coupling mechanism instead of targeting the transcription or translation processes separately.

"With RNA emerging as a major factor in our daily lives--note the SARS-CoV-2 viral genome and the mRNA vaccines to combat its replication--we are at a crossroads where the interplay between RNAs and proteins in their ubiquitous complexes becomes an attractive prospective target for the medicines of the future, including to fight drug-resistant bacterial strains," said senior author Nils Walter, professor of chemistry.

In particular, the researchers found that modulating the translation of a nascent mRNA affects the downstream synthesis of the mRNA itself. When translation is stopped or delayed, the transcription rate is slowed down to avoid overproduction of RNA that would only be degraded in the cell.

To conveniently modulate translation efficiency, the researchers exploited the features of a structured RNA, called a translational riboswitch, embedded near the start of an mRNA of the anthrax bacterium Bacillus anthracis. This RNA changes structure when binding a specific small ligand to reduce translation in response to environmental cues.

The current study shows that the riboswitch--generally thought to only affect translation--can in fact regulate both translation and transcription by exploiting their coupling. By using the riboswitch ligand to slow translation initiation, or inhibitors to delay or stop translation, the scientists observed effects also on the speed of RNA polymerase.

The authors expanded a combination of single-molecule fluorescence microscopy techniques to monitor the dynamic interactions of the transcription and translation machineries during different stages of coupling. They also developed a unique strategy to directly watch transcription-translation coupling in real-time, detecting that the small riboswitch controls the much larger transcription and translation machineries. The work thus surpasses and brings to life previous structure-based studies that provided only snapshots of the already coupled machineries.

The researchers say their results establish important foundations for future RNA research. They explain that the question of how other cellular factors contribute to establishing and maintaining transcription-translation coupling is still enigmatic, raising questions that remain to be investigated. This work could also bring insights into similar biological processes in other pathogenic organisms.

"It is fascinating to see how the huge transcription and translation machineries are held by a tiny mRNA for a controlled gene expression process in bacteria," said Chatterjee.

Chatterjee and Chauvier are senior postdoctoral fellows in the Walter lab within the U-M Department of Chemistry. They are interested in translational and transcriptional riboswitches, respectively. In this study, they combined their knowledge and interest for each aspect of the coupling.

"To me, it's not so much about bacteria, but rather about the biological processes of translation and transcription," Chauvier said. "Genetic regulation is a timely coordinated process and synchronization is the key for the bacteria to adapt to external threats."

Chatterjee, Chauvier and Walter were joined in the effort by graduate student Shiba Dandpat and collaborator Professor Irina Artsimovitch of Ohio State University.

"New evidence of the importance of the Roman/Byzantine Mons Smaragdus settlement within the emerald mining network"

A new paper published in the Journal of Near Eastern Studies presents the results of and images from the resuming of the archaeological seasons in the Mons Smaragdus region in the Egyptian Eastern Desert. The region is known for Roman-era emerald mines, chronicled by authors like Pliny the Elder and Claudius Ptolemy, were rediscovered in the 19th century by the French mineralogist Fréderic Cailliaud. During the 1990s a team from the "Berenike Project" started to survey the area and conducted the first excavations, focusing on the main site identified, Sikait, where the archaeological seasons resumed in January of 2018 and January 2020.

In "New evidence regarding emerald production in Roman Egypt coming from Wadi Sikait (Eastern Desert)" authors J. Oller Guzmán, D. Fernández Abella, V. Trevín Pita, O. Achon Casas, and S. García-Dils de la Vega detail what was found in three buildings. The first structure, referred to as the "Administrative building," was likely a temple long occupied between the 1st and the 4th-5th centuries. Nineteen coins were recovered at the site, along with other items indicating ritual use like incense burners and bronze and steatite figurines. The "Large Temple," one of the most well-preserved structures standing in Sikait, also contained religious artifacts like bones, terracotta body parts, and amulets, and was likely occupied between the 4th and the 5th centuries AD, although inner shrines were possibly used earlier, based on surviving traces of Egyptian hieroglyph and other materials. Finally, the "Six Windows Building" complex, possibly a residential space, included an older inner cavity, which may have been related to mining activity. However, concerning this type of structures, common in Sikait, the authors write, "After analyzing most of these spaces, we can conclude that almost none of them can be identified as beryl mines, and mainly we are dealing with storage or living spaces." Nevertheless, the study of the underground structures presents in Sikait and the surrounding areas allowed the documentation of several beryl mining spaces. The detailed analysis of some mines showed relevant evidence concerning their structure, typology, and evolution, including the discovery of the first register inscription ever found in an ancient emerald mine.

These excavation seasons, the authors write, add to knowledge about emerald production in Roman Egypt. "First, it confirmed the significance of the religious aspect in mining settlements like ancient Senskis." This shows the importance of the settlement within the emerald mining network, as there is no other site in which a similar concentration of cult spaces has been recorded. "This links Sikait to other productive regions in the Eastern Desert, which also offer plentiful evidence of the importance of cult and religion, like the imperial quarries."

The authors propose this work will provide key evidence in the future for determining how exactly were the mines exploited. Future seasons will focus on documenting the mining complexes to get a complete overview of the process of extraction and commercialization of emeralds, which will provide greater historical context. "According to literary sources such as Olympiodorus, in the 5th century AD a permit from the king of the Blemmyes was required to enter the emerald mines." Considering that most of the surviving structures in Sikait date to this period, archaeological information from such sites are fundamental for understanding the progressive abandonment of the Roman/Byzantine control in this area and the gradual substitution by the Blemmyan power.