Culture

NIH scientists find that salmonella use intestinal epithelial cells to colonize the gut

image: Scanning electron micrograph of Salmonella Typhimurium invading a human epithelial cell

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NIAID

WHAT:

The immune system's attempt to eliminate Salmonella bacteria from the gastrointestinal (GI) tract instead facilitates colonization of the intestinal tract and fecal shedding, according to National Institutes of Health scientists. The study, published in Cell Host & Microbe, was conducted by National Institute of Allergy and Infectious Diseases (NIAID) scientists at Rocky Mountain Laboratories in Hamilton, Montana.

Salmonella Typhimurium bacteria (hereafter Salmonella) live in the gut and often cause gastroenteritis in people. The Centers for Disease Control and Prevention estimates Salmonella bacteria cause about 1.35 million infections, 26,500 hospitalizations and 420 deaths in the United States every year. Contaminated food is the source for most of these illnesses. Most people who get ill from Salmonella have diarrhea, fever and stomach cramps but recover without specific treatment. Antibiotics typically are used only to treat people who have severe illness or who are at risk for it.

Salmonella bacteria also can infect a wide variety of animals, including cattle, pigs and chickens. Although clinical disease usually resolves within a few days, the bacteria can persist in the GI tract for much longer. Fecal shedding of the bacteria facilitates transmission to new hosts, especially by so-called "super shedders" that release high numbers of bacteria in their feces.

NIAID scientists are studying how Salmonella bacteria establish and maintain a foothold in the GI tract of mammals. One of the first lines of defense in the GI tract is the physical barrier provided by a single layer of intestinal epithelial cells. These specialized cells absorb nutrients and are a critical barrier that prevent pathogens from spreading to deeper tissues. When bacteria invade these cells, the cells are ejected into the gut lumen--the hollow portion of the intestines. However, in previous studies, NIAID scientists had observed that some Salmonella replicate rapidly in the cytosol--the fluid portion--of intestinal epithelial cells. That prompted them to ask: does ejecting the infected cell amplify rather than eliminate the bacteria?

To address this question, the scientists genetically engineered Salmonella bacteria that self-destruct when exposed to the cytosol of epithelial cells but grow normally in other environments, including the lumen of the intestine. Then they infected laboratory mice with the self-destructing Salmonella bacteria and found that replication in the cytosol of mouse intestinal epithelial cells is important for colonization of the GI tract and fuels fecal shedding. The scientists hypothesize that, by hijacking the epithelial cell response, Salmonella amplify their ability to invade neighboring cells and seed the intestine for fecal shedding.

The researchers say this is an example of how the pressure exerted by the host immune response can drive the evolution of a pathogen, and vice versa. The new insights offer new avenues for developing novel interventions to reduce the burden of this important pathogen.

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NIH/National Institute of Allergy and Infectious Diseases

Study finds ongoing evolution in Tasmanian Devils' response to transmissible cancer

image: University of Idaho led a study on the evolution of Tasmanian devils in response to a transmissible cancer.

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Photo courtesy of Menna Jones.

MOSCOW, Idaho -- May 26, 2021 -- University of Idaho researchers partnered with other scientists from the United States and Australia to study the evolution of Tasmanian devils in response to a unique transmissible cancer.

The team found that historic and ongoing evolution are widespread across the devils' genome, but there is little overlap of genes between those two timescales. These findings, published in Proceedings of the Royal Society B, suggest that if transmissible cancers occurred historically in devils, they imposed natural selection on different sets of genes.

Tasmanian devils suffer from a transmissible cancer called devil facial tumor disease (DFTD). Unlike typical cancers, tumor cells from transmissible cancers are directly transferred from one individual to another like an infectious disease. DTFD is most commonly transmitted from host to host as devils bite each other during mating season. The tumors become malignant and can kill their hosts within six months.

DFTD was first discovered in 1996, and the recent discovery of a second transmissible cancer in Tasmanian devils in 2016 suggests that they may be prone to this unique type of disease. The threat of these two cancers has prompted conservation efforts.

"For the conservation of Tasmanian devils, our work adds to the growing list of genes that we have observed to be evolving in response to DFTD," said Paul Hohenlohe, U of I Department of Biological Sciences associate professor, Institute for Bioinformatics and Evolutionary Studies (IBEST) principal investigator and senior author on the paper. "We can monitor genetic diversity of these genes in wild populations to understand whether and how these populations can adapt and survive in the face of DFTD."

Using genomic sequencing and data analysis, the research team tested for natural selection in Tasmanian devils in response to DFTD to find out whether they are evolving as a result of the disease. They also looked for evidence of natural selection in the devils' evolutionary history to test whether the genes that are evolving under DFTD show evidence of historical natural selection.

Finding little overlap in what genes are involved at historical and modern timescales, the team determined that if transmissible cancers have occurred historically in devils, they caused natural selection on different sets of genes. Their results and analysis of historical selection suggest that DFTD is a newly emerging selective force that distinctly shapes today's wild devils.

This information can be used to inform conservation efforts by identifying targets for genetic monitoring and guiding maintenance of adaptive potential in Tasmanian devil populations.

"Our work suggests that maintaining genetic diversity across a wide set of functionally important genes is critical to make sure Tasmanian devils are able to adapt to transmissible cancers and other threats to their survival," Hohenlohe said.

Credit: 
University of Idaho

A comprehensive profile of California's 'homegrown' coronavirus

image: A new study by researchers at Gladstone Institutes and UC San Francisco provides a comprehensive portrait of the California variant of COVID-19. Shown here: Mir Khalid, graduate student working in Melanie Ott's lab at Gladstone.

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Photo: Michael Short/Gladstone Institutes

SAN FRANCISCO, CA--May 26, 2021--In January 2021, reports of a new coronavirus variant that had emerged in California raised many concerns. Preliminary data suggested that it is more transmissible than the unmutated strains of SARS-CoV-2 (the virus that causes COVID-19) from which it evolved.

Now, a multifaceted collaboration between researchers at UC San Francisco, Gladstone Institutes, and other organizations across California provides a comprehensive portrait of the variant--including its interaction with the immune system and its potential to spread.

"Our findings suggest that California's homegrown variant can infect people who already had COVID-19, but that it is vulnerable to vaccines," says Charles Chiu, MD, PhD, director of the UCSF-Abbott Viral Diagnostics and Discovery Center, and one of the co-senior authors of the study published in the journal Cell. He helped discover and report the new variant as a "variant of concern" earlier this year to the Centers for Disease Control and other health agencies.

"The take-home message is that everyone should get vaccinated, even if you've been infected before," says Chiu. The new findings appear in the journal Cell.

Tracking the Rise of the New Variant

Like all viruses, SARS-CoV-2 mutates over time, and new variants with distinct combinations of mutations arise continuously. Not all variants are cause for concern, but some variants appear to spread faster than others. This is thought to be due to mutations that enhance the function of the virus's spike protein, which it uses to latch onto and infect human cells.

California's variant actually comes in two different forms, dubbed B.1.427 and B.1.429, and each have a unique combination of mutations. But they are paired as a single variant because they share a few distinct mutations that affect the spike protein.

"When this variant emerged in California, it was important to determine how much of a risk it might pose," says Melanie Ott, MD, PhD, director of the Gladstone Institute of Virology and a co-senior author on the study. "But we needed to sequence--or analyze--its genome and conduct follow-up experiments to really understand it."

The researchers sequenced samples from 2,172 COVID-19 swab tests conducted in dozens of California counties. Analysis of the sequences suggested that the variant emerged in May 2020 and subsequently gave rise to the two current forms.

Between September 1, 2020, and January 29, 2021, the prevalence of the variant in the sequenced samples rose from 0 percent to more than 50 percent of cases. Its transmissibility appeared to be as much as 24 percent higher than unmutated viral strains, and people infected with the new variant had two times more virus present in their swab samples than people infected with unmutated strains.

"In a matter of months, this variant went from being practically undetectable to being the predominant variant circulating in California," says Raul Andino, PhD, a professor of microbiology and immunology at UCSF, and a co-senior author on the study.

Lab Tests Reveal Variant's Characteristics

Next, the researchers sought to better understand how the distinct mutations to the spike protein affected the California variant's ability to infect human cells.

To perform these studies safely, Ott and her team at Gladstone generated "pseudoviruses," harmless viruses that contain SARS-CoV-2 spike proteins with different mutations. This allowed the scientists to compare how the mutations affect the virus's ability to infect both individual cells and lung organoids--lab-grown, multicellular, miniature versions of a lung.

Specifically, the researchers compared three different spike protein mutations: two that are found in the California variant, and one that is commonly found in predominant variants worldwide. They found that pseudoviruses with one of the California variant's mutations, known as L452R, was better able to infect human cells than pseudoviruses carrying other mutations.

"This suggests that the L452R mutation enhances the ability of the virus to enter a cell, which could explain why the California variant has increased transmissibility," Ott says.

The researchers also conducted lab experiments to study how well the immune system's antibodies can neutralize--or block infection by--the new variant. They tested the variant against blood samples from people who had received both doses of either the Pfizer or Moderna vaccine, as well as from people who had previously been infected with what was most likely an unmutated form of SARS-CoV-2.

These experiments showed that the new variant was only moderately neutralized by antibodies from previously infected patients. But antibodies from vaccinated patients showed a higher degree of neutralization.

"Our results send a very strong message that, even if you've already had COVID-19, you may not necessarily be protected against reinfection by this variant," Andino says. "However, the vaccines do appear to protect against it."

Remaining Vigilant

These findings highlight the importance of getting vaccinated--and making sure to receive both doses to maximize the effects of vaccination. This is in line with research on other concerning variants emerging around the world.

"It appears that vaccination largely remains effective against all of the circulating variants that are known so far," Chiu says.

However, Chiu notes, the new study underscores the need for a robust surveillance system to closely monitor the emergence and spread of new variants. Such a system was lacking in California at the time the new variant emerged, Chiu says, but recent improvements mean that future variants may be detected more quickly.

"We are entering a new phase of the pandemic, where the virus continues to spread despite the availability of vaccines," Andino says. "We may eventually see the emergence of a variant that's partially or completely resistant to vaccination, so we must stay vigilant."

Ott notes that this is a quickly evolving situation, because it is unclear for how long the new variant will remain prevalent in California or other locations. In fact, a different variant known as B.1.1.7 is currently increasing in prevalence in California.

"What's more, our antibody experiments were performed with blood plasma from newly vaccinated people, so it will be important to see how the vaccine holds up in the long term," Ott says.

For now, the researchers are getting to know the new variant in even greater detail. They are conducting studies in animal models to tease out any subtle differences between the two lineages, which have so far appeared to be quite similar. They are also examining patient data to see if the new variant causes more severe cases of COVID-19 than other variants.

Key to the new findings and ongoing investigations is the researchers' dedication to fruitful collaboration.

"Our work is a great example of how the scientific community has rapidly risen to the occasion in a time of need and concern for the public," Ott says. "With this collaborative sprit, we are reaching across institutions and scientific disciplines; just doing whatever is necessary to help."

Credit: 
Gladstone Institutes

New research deepens mystery about evolution of bees' social behavior

image: A new study has mounted perhaps the most intricate, detailed look ever at the diversity in structure and form of bees, offering new insights in a long-standing debate over how complex social behaviors arose in certain branches of bees' evolutionary tree. Published today in Insect Systematics and Diversity, the report is built on an analysis of nearly 300 morphological traits in bees, how those traits vary across numerous species, and what the variations suggest about the evolutionary relations between bee species. The result offers strong evidence that complex social behavior developed just once in pollen-carrying bees, rather than twice or more, separately, in different evolutionary branches--but researchers say the case is far from closed. The bee varieties studied were all "corbiculate" bees--those that possess corbicula, or pollen baskets, on their hind legs--which encompass honey bees, stingless bees, bumble bees, and orchid bees. Examples of bee species analyzed include (clockwise from top left) Apis dorsata, a member of the honey bee tribe Apini; Bombus pauloensis, of the bumble bee tribe Bombini, Melipona quadrifasciata, of the stingless bee tribe Meliponini, and Exaerete smaragdina, of the orchid bee tribe Euglossini. Note: Images are not to scale. (Photos by Eduardo Alemeida, Ph.D., University of São Paulo)

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Eduardo Alemeida, Ph.D., University of São Paulo

Annapolis, MD; May 26, 2021--A new study has mounted perhaps the most intricate, detailed look ever at the diversity in structure and form of bees, offering new insights in a long-standing debate over how complex social behaviors arose in certain branches of bees' evolutionary tree.

Published today in Insect Systematics and Diversity, the report is built on an analysis of nearly 300 morphological traits in bees, how those traits vary across numerous species, and what the variations suggest about the evolutionary relations between bee species. The result offers strong evidence that complex social behavior developed just once in pollen-carrying bees, rather than twice or more, separately, in different evolutionary branches--but researchers say the case is far from closed.

Diego Sasso Porto, Ph.D., has been studying the structure and form, or morphology, of bees for more than a decade, and his latest effort ventures into a longstanding conundrum about bee evolution. Corbiculate bees--those that possess corbicula, or pollen baskets, on their hind legs--encompass honey bees, stingless bees, bumble bees, and orchid bees. Among them, honey bees and stingless bees are the only groups with highly complex social behaviors, such as forming large colonies with queens, workers, and drones. Bumble bees display less complex sociality, and orchid bees are mostly solitary. Traditional morphological analyses have long indicated that honey bees and stingless bees are most closely related and that complex social behavior developed in their common ancestor before the groups diverged. However, in the 1990s, emergent techniques in molecular genetic analysis began to show that stingless bees and bumble bees were the more closely related "sister" groups, which would mean that honey bees and stingless bees each developed their complex social behavior independently, after their ancestral paths diverged.

Ever since, these different lines of evidence have persisted as a notorious case of incongruence between molecular and morphological data sets in animals. Porto, now a postdoctoral researcher in the Department of Biological Sciences at Virginia Tech, made his foray into the debate amid his doctoral work at the University of São Paulo in Brazil, under the guidance of Eduardo Almeida, Ph.D., co-author on the new study.

"The main criticism from some molecular researchers against morphology, and even from morphologists themselves, was we don't have enough data," Porto says. "This work was a big effort to try to get the best morphological data set we could ever get for this group of bees, and we tried several analyses to see if the problem is with morphological data itself or the way we interpret morphological data."

Porto evaluated past morphological studies of bees and then conducted new analysis of specimens from 53 species, dissecting each, imaging anatomical structures under optical and scanning electron microscopes, and ultimately scoring all of the specimens across 289 different traits. Often minute or even microscopic in detail, these traits ranged from the number of teeth on a bee's mandibles to the arrangement of barbs on its stinger.

With this massive trove of morphological data in hand, Porto applied multiple types of computerized statistical analyses to evaluate the possible phylogenies, or "family trees," that delineate the relationships among bee species. The results strongly support previous morphological findings, that honey bees (tribe Apini) and stingless bees (Meliponini) are most closely related. "The evidence from our dataset, if we just take it at plain sight, is really strong. We have a lot of traits supporting this," says Porto.

But, he sought to further explore the discrepancy between what molecular genetic analysis shows and what his own morphological data supports. To do so, Porto ran his data through a separate analysis that evaluated how well the morphological data could fit with the evolutionary tree supported by molecular analysis--that Meliponini and Bombini (bumble bees) are most closely related. As expected, it was not a great fit--a bit like putting a square peg in a round hole--but they were not completely incompatible, he says.

In their report in Insect Systematics and Diversity, Porto and Almeida offer a few hypotheses for evolutionary processes that could explain the continuing discrepancy in lines of evidence about corbiculate bee evolution.

"Morphological data is telling us one story, and molecular data is telling us another story. We are not going anywhere if we just keep these conflicting discussions," says Porto. "So, our decision was ... let's try to interpret the alternative scenario with our data. If the hypothesis given by molecular data is true, how can we interpret our strong morphological evidence for the other hypothesis?"

One possible explanation, they say, is that, if bumble bees and stingless bees share a common ancestor that first branched away from honey bees, they then rapidly diverged in a short time frame and evolved separately for much longer, gradually obscuring the shared traits bumble bees and stingless bees once had. Moreover, the earliest ancestor of stingless bees is believed to have been relatively small, and "miniaturization" is known to drive structural simplifications in anatomical traits, which would have further contributed to erasing similarities between bumble bees and stingless bees.

However, these possibilities don't explain why stingless bees then evolved to become more morphologically similar to honey bees, but Porto and Almeida posit that similar functional roles or similar social behaviors among stingless bees and honey bees could have driven them to evolve in similar ways.

Testing these hypotheses is what Porto says he would like to explore next--and encourages other researchers to do, as well. "It would be really good to have maybe the same data set, but including more specimens from fossils, and run the analysis again," he says.

Credit: 
Entomological Society of America

Studies reveal that social isolation and quarantine throughout the COVID-19 pandemic may have a detrimental impact on physical and mental health of people living with pre-existing conditions

Abstract 803: Impact of social isolation and quarantine on the course of diabetes mellitus and its complications during Covid 19 pandemic in Adjara Region Country of Georgia

Abstract 1337: Psychological distress in patients with hypocortisolism during mass quarantine for Covid-19 epidemic in Italy

Studies reveal that social isolation and quarantine throughout the COVID-19 pandemic may have a detrimental impact on people living with pre-existing conditions.

Social isolation and quarantine can have a detrimental impact on physical and mental health of people living with pre-existing conditions, according to two studies being presented at the 23rd European Congress of Endocrinology (e-ECE 2021) on Wednesday 26 May at 14:14 CET (http://www.ece2021.org).

The studies bring together research on the impact of social isolation and quarantine for people living with diabetes in the Adjara Region of Georgia, and on patients with hypocortisolism in Italy. Both studies reported that social isolation during the pandemic caused significant psychological and/or physical distress on the observed individuals.

Data from the first study revealed that the impact of quarantine on people living with diabetes in the Adjara Region caused blood pressure (BP) levels to increase in 88.2% of patients with 50% of these cases resulting in high BP hospitalisation. In addition to these physical factors, increased feelings of anxiety and fear were observed on 82% of patients. In the second study, patients with hypocortisolism experienced increased anxiety and depression, associated with a dissatisfaction feeling of self and a reduced resiliency, when compared with Italian healthy controls. As these are all contributing factors to overall health deterioration, these findings suggest further research is required to allow patients with pre-existing conditions to remain fit and healthy during the current pandemic.

In the Adjara Region study, Dr Liana Jashi and the research team disseminated an online questionnaire and collected answers from 16 endocrinologists and 22 family and general practice doctors. The study confirmed the negative, indirect effects social isolation and quarantine had on people living with diabetes. It reported a list of negative effects such as the reduced access to medical care, weight gain and increased cigarette and alcohol consumption. Physical activity decreased by 29.8%, a vital preventative to further physical and psychological problems.

"This study highlights that people living with diabetes require greater support during pandemics to maintain exercise and protect their physical and mental health. National health services should use these data and future studies to implement better social care around supporting people with pre-existing conditions," commented Dr Jashi.

In the second study, Dr Chiara Simeoli reported data collected during the last three weeks of the mass quarantine lasted 2 months in Italy, in a web-survey-based, multicenter, case- control research involving 12 different Italian centres. The study confirmed that a large cohort of 478 patients with hypocortisolism, and particularly, 363 with adrenal insufficiency and 115 with congenital adrenal hyperplasia, adequately treated with glucocorticoids, showed higher anxiety and depression, associated with a dissatisfaction feeling of self and a reduced resiliency, when compared with Italian healthy controls, suggesting the detrimental impact of social isolation on mental health of these patients, particularly frail and vulnerable to infections and stress. Moreover, patients with adrenal insufficiency reported a worse quality of life than patients with congenital adrenal hyperplasia.

"These findings confirmed that beyond the huge impact on physical health, COVID-19 epidemic, social isolation and mass quarantine represent significant psychological stressors, causing severe effects on mental health, even more on people with pre-existing conditions. An empowerment of psychological counselling for these vulnerable patients during COVID-19 should be considered by national health-care services," adds Dr Simeoli.

Both studies indicate that additional larger studies over a longer period of time are needed for further investigation.

Credit: 
European Society of Endocrinology

Real-world flight data shows continued need for social distancing

image: Dr Anna Sigridur Islind and Dr Maria Oskarsdottir used real-world flight data to show that there is continued need for social distancing to curb the spread of COVID in the US.

Image: 
Dr. Islind

REYKJAVIK, Iceland 26 May 2021 - Current vaccination programmes alone will have a limited effect in stopping the second wave of COVID infections in the US, according to a study conducted by scientists from Reykjavik University, University of Lyon, University of Southern Denmark and University of Naples Federico II, and published in the Nature Group journal Scientific Reports today. The findings suggest that strict social distancing and other non-pharmaceutical methods are still necessary to end the ongoing second wave in the US and prevent a new one from rising.

The study fed real-world data on human mobility into a mathematical model previously used to predict the second wave of COVID in the US. As a proxy for general human mobility between regions in the US, the authors use data from the OpenSky Network, a non-profit association that provides open access to real-world air traffic control data for research purposes. The mathematical model, previously developed by the authors, was first tested and calibrated using data on the pandemic's progression in the first wave. Here, deploying the model on flight-control data, they show that given current rates of mobility in the US and the rate of vaccination, the vaccination campaign alone will not stop the ongoing wave of infections.

Dr Anna Sigridur Islind and Dr Maria Oskarsdottir, assistant professors in the Department of Computer Science at Reykjavik University, led the work with the OpenSky Data. "Our analysis clearly demonstrates that continued vigilance is needed regarding social distancing and other non-pharmaceutical methods in the US, since not everyone can be vaccinated at once and because there is a considerable time lag from vaccination to immunity," Dr Islind said.

"Our results underscore the importance of using real-world data on human mobility relating to the pandemic and to inform public health strategies. This is especially important in a pandemic as complex as COVID and that has had such an uneven public health response, with huge variability in vaccination rates, social distancing regulations, and other measures. The flight-control data is very useful, as it comprises real-world information about rates of interstate travel and so provides a valuable broader view of human mobility on a large scale," Dr Oskarsdottir added.

Credit: 
Reykjavik University

Scent trails could boost elephant conservation

image: An elephant investigating elephant dung with his trunk at the Boteti river.

Image: 
Connie Allen

Travelling elephants pay close attention to scent trails of dung and urine left by other elephants, new research shows.

Scientists monitored well-used pathways and found that wild African savannah elephants - especially those travelling alone - were "highly attentive", sniffing and tracking the trail with their trunks.

This suggests these scents act as a "public information resource", according to researchers from the University of Exeter and Elephants for Africa.

More research is now needed to find out whether humans can create artificial elephant trails to divert elephants away from farms and villages, where conflict with humans can cause devastation to communities.

Alternatively, scent trails could be placed to improve the efficiency of routes connecting elephant populations between protected areas.

"Our findings suggest an important role of an elephant's sense of smell in long-distance navigation," said lead author Connie Allen, of Exeter's Centre for Research in Animal Behaviour.

"As elephants follow these trails, they deposit their own urine and dung, which reinforces the pathway's presence for future elephants.

"We see great potential for these findings to be applied to elephant management and conservation - primarily as a method for manipulating elephant movements.

"We carried out this study in Botswana, where the main threat to elephants is conflict with humans.

"By removing the existing scent paths that lead elephants to close contact with humans in problem areas, and redirecting them, perhaps we could reduce such conflicts happening."

The proposed technique could also aid efforts in Botswana to reconnect elephants with populations across southern Africa.

The study, which examined a predominantly male population, also found that urine deposits from adult elephants were more likely to attract attention than that of younger (subadult) males.

"African elephants may therefore be able to discern the age and maturity of individuals they can expect to encounter from remote urine cues on pathways," Allen explained.

Credit: 
University of Exeter

Memory details fade over time, with only the main gist preserved

What information is retained in a memory over time, and which parts get lost? These questions have led to many scientific theories over the years, and now a team of researchers at the Universities of Glasgow and Birmingham have been able to provide some answers.

Their new study, which is published today in Nature Communications, demonstrates that our memories become less vibrant and detailed over time, with only the central gist eventually preserved. Moreover, this 'gistification' of our memories is boosted when we frequently recall our recent experiences.

The work could have implications in a number of areas, including the nature of memories in post-traumatic stress disorder, the repeated questioning of eye-witness testimonies and even in best practice for exam studying.

While memories are not exact carbon copies of the past - remembering is understood to be a highly reconstructive process - experts have suggested that the contents of a memory could change each time we bring it back to mind.

However, exactly how our memories differ from the original experiences, and how they are transformed over time, has until now proven difficult to measure in laboratory settings.

For this study the researchers developed a simple computerised task that measures how fast people can recover certain characteristics of visual memories when prompted to do so. Participants learned word-image pairs and were later required to recollect different elements of the image when cued with the word. For example, participants were asked to indicate, as fast as possible, if the image was coloured or greyscale (a perceptual detail), or whether it showed an animate or inanimate object (a semantic element).

These tests, probing the quality of the visual memories, happened immediately after learning and also after a two-day delay. Reaction time patterns showed that participants were faster to recollect meaningful, semantic elements than surface, perceptual ones.

Julia Lifanov, lead author of the study from the University of Birmingham, said: "Many memory theories assume that over time, and as people re-tell their stories, they tend to forget the surface details but retain the meaningful, semantic content of an event.

"Imagine reminiscing about a pre-COVID dinner with a friend - you realize that you cannot recall the table décor but know exactly what you ordered; or you remember the conversation with the bartender, but not the colour of his shirt. Memory experts call this phenomenon 'semanticization'."

Prof Maria Wimber, senior author on the study from the University of Glasgow, said: "The pattern towards recollection of meaningful semantic elements we demonstrate in this study indicates that memories are biased towards meaningful content in the first place - and we have shown in previous studies that this bias is clearly reflected in brain signals too.

"Our memories change with time and use and that is a good and adaptive thing. We want our memories to retain the information that is most likely to be useful in the future, when we encounter similar situations."

The researchers found that the bias towards semantic memory content becomes significantly stronger with the passage of time, and with repeated remembering. When participants came back to the lab two days later, they were much slower at answering the perceptual-detailed questions, but they show relatively preserved memory for the semantic content of the images. However, the shift from detail-rich to more concept-based memories was far less pronounced in a group of subjects who repeatedly viewed the images, rather than being asked to actively bringing them back to mind.

The study has implications for probing the nature of memories in health and disease. It provides a tool to study maladaptive changes, for example in post-traumatic stress disorder where patients often suffer from intrusive, traumatic memories, and tend to over-generalize these experiences to novel situations. The findings are also highly relevant for understanding how eyewitness memories may be biased by frequent interviews and repeatedly recalling the same event.

The findings also demonstrate that testing yourself prior to an exam (for example, by using flashcards) will make the meaningful information stick for longer, especially when followed by periods of rest and sleep.

Credit: 
University of Birmingham

Why a vacation seems like it will end as soon as it begins

COLUMBUS, Ohio - Time not only flies when you're having fun - sometimes anticipating a fun event makes it feel like it will be over as soon as it begins, a new study suggests.

Researchers found that people judge future positive events as being both farther away as well as shorter in duration than negative or neutral events.

Combining those two elements has a strange effect when people look forward to a positive event like a vacation, said Selin Malkoc, co-author of the study and associate professor of marketing at The Ohio State University's Fisher College of Business.

"The seemingly endless wait for the vacation to start combined with the feeling that the vacation will fly by leads people to feel like the beginning and the end of their time off as similarly far from the present," Malkoc said.

"In other words, in their mind's eye, the vacation is over as soon as it begins. It has no duration."

The study was published online recently in the Journal of Consumer Psychology.

This phenomenon has another interesting effect: It makes people feel like the endpoints of positive and negative events are similarly distant from the present.

That's because anticipating a negative event - like a dreaded work trip - reverses the effects of a positive event: People feel like the negative event is right around the corner and will last a long time.

"Thinking about future positive and negative events leads people to take two different paths to the same conclusion, with the ends of both events seeming similarly far away," said study co-author Gabriela Tonietto, assistant professor of marketing at Rutgers Business School - Newark and New Brunswick.

The Journal of Consumer Psychology paper included four related studies that came to similar conclusions. In one study, 451 online participants considered the upcoming weekend, which was either expected to be fun, terrible, or just OK.

They then indicated how far away the beginning and then the end of the weekend felt on a 0-100 slider scale (0=very near, 100=very far.)

Findings showed that a good weekend seemed farther away and shorter, while a terrible weekend seemed closer to the present day and longer in duration. An OK weekend fell in between.

On the slider scale, people rated a bad weekend as ending significantly farther away than its beginning. But for people who expected a good weekend, the slider scale ratings for how far away the beginning and the end seemed to them were nearly identical.

In fact, 46% of participants evaluated the positive weekend as feeling like it had no duration at all as they thought about both the event and the time leading up to it.

Thinking about how far the beginning and the end of the event is from the present is key to this phenomenon, Malkoc said. Another study showed that when people were asked to directly indicate how long they expected a positive event to last, they thought it would go quickly, but they did indicate it would take up some time.

It was only when people also considered the time leading up to the fun event - which they expected to crawl - that they thought a future positive experience would feel like it had no duration.

These findings have some interesting implications as people start planning vacations and other fun events as the COVID-19 pandemic ends, Malkoc said.

"If a vacation seems like it is going to end as soon as it begins, it may make people less likely to plan specific events during their time off," she said.

"It may also lead people to spend more on hotels and other luxuries, since it seems like the vacation is such a short time anyway."

Credit: 
Ohio State University

New paper establishes context for myopia control axial length targets

image: Paul Chamberlain, BSc (Hons), MCOptom, is the paper's lead author and Director of Research Programs for CooperVision.

Image: 
CooperVision

SAN RAMON, Calif., May 26, 2021--A new paper that has been accepted for publication in Ophthalmic & Physiological Optics, the peer-reviewed journal of The College of Optometrists (UK), furthers understanding of myopia control efficacy in the context of normal childhood eye growth. Axial Length Targets for Myopia Control (Chamberlain P, et al.) is now available online via Open Access.

Since young eyes grow, even when not myopic, the paper compares axial elongation among children who remain emmetropic, children with untreated myopia progression, and children with myopia managed with CooperVision MiSight® 1 day myopia control contact lenses. The comparison uses data from the three-year MiSight® 1 day clinical study, the Orinda Longitudinal Study of Myopia (OLSM)[1] and the Singapore Cohort Study of the Risk Factors for Myopia (SCORM).[2]

The analysis revealed that the predicted three-year axial elongation for emmetropic children (0.24 mm) is similar to the mean three-year elongation in MiSight® 1 day-treated children with myopia (0.30 mm).[3,4] In contrast, the axial elongation (0.63 mm) observed in the control group in the MiSight® 1 day clinical study was much higher, and similar to virtual cohorts based on the OLSM (0.70 mm) and SCORM (0.65 mm) models for myopia development.3,4

This observation suggests that while abnormal myopic eye growth may be managed with MiSight® 1 day in age-appropriate* children, normal, physiological eye growth may continue as the child ages. It supports the hypothesis that myopic axial elongation may be superimposed on underlying physiological axial elongation.

"Some eye growth as part of the aging process is normal--myopic axial elongation is not. Our work further validates that evidence-based interventions can be highly effective in slowing that myopic eye growth," said Paul Chamberlain, BSc (Hons), MCOptom, the paper's lead author and Director of Research Programs for CooperVision. "This offers hope to healthcare systems, currently bearing the growing burden of visual impairment linked to the increasing prevalence and severity of myopia."

MiSight® 1 day contact lenses designed for myopia control have been shown to reduce the rate of axial elongation in children (aged 8-12 at the initiation of treatment*) by 52% on average over a three-year period.†4 As measured by spherical refraction, the lens reduced the rate of myopia progression in age-appropriate children* by 59% on average over the same period. †[4]

"In assessing treatment effectiveness, we caution our industry away from applying arbitrary correction factors to account for normal, physiological eye growth until this has been better understood. Efficacy percentages may seem higher presented in that light, but it complicates understanding and valid comparisons," said co-author Mark Bullimore, MCOptom, PhD, FAAO. "Eye care professionals must be able to rely on the ever-growing body of myopia literature to make evidence-based clinical decisions."

Credit: 
McDougall Communications

UCSF improves fetal heart defect detection using machine learning

UC San Francisco researchers have found a way to double doctors' accuracy in detecting the vast majority of complex fetal heart defects in utero - when interventions could either correct them or greatly improve a child's chance of survival - by combining routine ultrasound imaging with machine-learning computer tools.

The team, led by UCSF cardiologist Rima Arnaout, MD, trained a group of machine-learning models to mimic the tasks that clinicians follow in diagnosing complex congenital heart disease (CHD). Worldwide, humans detect as few as 30 to 50 percent of these conditions before birth. However, the combination of human-performed ultrasound and machine analysis allowed the researchers to detect 95% of CHD in their test dataset.

The findings appear in the May issue of Nature Medicine.

Fetal ultrasound screening is universally recommended during the second trimester of pregnancy in the United States and by the World Health Organization. Diagnosis of fetal heart defects, in particular, can improve newborn outcomes and enable further research on in utero therapies, the researchers said.

"Second-trimester screening is a rite of passage in pregnancy to tell if the fetus is a boy or girl, but it is also used to screen for birth defects," said Arnaout, a UCSF assistant professor and lead author of the paper. Typically, the imaging includes five cardiac views that could allow clinicians to diagnosis up to 90 percent of congenital heart disease, but in practice, only about half of those are detected at non-expert centers.

"On the one hand, heart defects are the most common kind of birth defect, and it's very important to diagnose them before birth," Arnaout said. "On the other hand, they are still rare enough that detecting them is difficult even for trained clinicians, unless they are highly sub-specialized. And all too often, in clinics and hospitals worldwide, sensitivity and specificity can be quite low."

The UCSF team, which included fetal cardiologist and senior author Anita Moon-Grady, MD, trained the machine tools to mimic clinicians' work in three steps. First, they utilized neural networks to find five views of the heart that are important for diagnosis. Then, they again used neural networks to decide whether each of these views was normal or not. Then, a third algorithm combined the results of the first two steps to give a final result of whether the fetal heart was normal or abnormal.

"We hope this work will revolutionize screening for these birth defects," said Arnaout, a member of the UCSF Bakar Computational Health Sciences Institute, the UCSF Center for Intelligent Imaging, and a Chan Zuckerberg Biohub Intercampus Research Award Investigator. "Our goal is to help forge a path toward using machine learning to solve diagnostic challenges for the many diseases where ultrasound is used in screening and diagnosis."

Credit: 
University of California - San Francisco

UVA develops new tools to battle cancer, advance genomics research

image: UVA's Chongzhi Zang, PhD, and his colleagues and students have developed a new computational method to map the folding patterns of our chromosomes in three dimensions.

Image: 
Courtesy Zang lab at UVA

University of Virginia School of Medicine scientists have developed important new resources that will aid the battle against cancer and advance cutting-edge genomics research.

UVA's Chongzhi Zang, PhD, and his colleagues and students have developed a new computational method to map the folding patterns of our chromosomes in three dimensions from experimental data. This is important because the configuration of genetic material inside our chromosomes actually affects how our genes work. In cancer, that configuration can go wrong, so scientists want to understand the genome architecture of both healthy cells and cancerous ones. This will help them develop better ways to treat and prevent cancer, in addition to advancing many other areas of medical research.

Using their new approaches, Zang and his colleagues and students have already unearthed a treasure trove of useful data, and they are making their techniques and findings available to their fellow scientists. To advance cancer research, they've even built an interactive website that brings together their findings with vast amounts of data from other resources. They say their new website, bartcancer.org, can provide "unique insights" for cancer researchers.

"The folding pattern of the genome is highly dynamic; it changes frequently and differs from cell to cell. Our new method aims to link this dynamic pattern to the control of gene activities," said Zang, a computational biologist with UVA's Center for Public Health Genomics and UVA Cancer Center. "A better understanding of this link can help unravel the genetic cause of cancer and other diseases and can guide future drug development for precision medicine."

Bet on BART

Zang's new approach to mapping the folding of our genome is called BART3D. Essentially, it compares available three-dimensional configuration data about one region of a chromosome with many of its neighbors. It can then extrapolate from this comparison to fill in blanks in the blueprints of genetic material using "Binding Analysis for Regulation of Transcription", or BART, a novel algorithm they recently developed. The result is a map that offers unprecedented insights into how our genes interact with the "transcriptional regulators" that control their activity. Identifying these regulators helps scientists understand what turns particular genes on and off - information they can use in the battle against cancer and other diseases.

The researchers have built a web server, BARTweb, to offer the BART tool to their fellow scientists. It's available, for free, at http://bartweb.org. The source code is available at https://github.com/zanglab/bart2. Test runs demonstrated that the server outperformed several existing tools for identifying the transcriptional regulators that control particular sets of genes, the researchers report.

The UVA team also built the BART Cancer database to advance research into 15 different types of cancer, including breast, lung, colorectal and prostate cancer. Scientists can search the interactive database to see which regulators are more active and which are less active in each cancer.

"While a cancer researcher can browse our database to screen potential drug targets, any biomedical scientist can use our web server to analyze their own genetic data," Zang said. "We hope that the tools and resources we develop can benefit the whole biomedical research community by accelerating scientific discoveries and future therapeutic development."

Credit: 
University of Virginia Health System

Hundreds of antibiotic resistant genes found in the gastrointestinal tracts of Danish infants

Hundreds of antibiotic resistant genes found in the gastrointestinal tracts of Danish infants

Danish one-year-olds carry several hundred antibiotic resistant genes in their bacterial gut flora according to a new study from the University of Copenhagen. The presence of these genes is partly attributable to antibiotic use among mothers during pregnancy.

An estimated 700,000 people die every year from antibiotic resistant bacterial infections and diseases. The WHO expects this figure to multiply greatly in coming decades. To study how antibiotic resistance occurs in humans' natural bacterial flora, researchers from the University of Copenhagen's Department of Biology analysed stool samples from 662 Danish one-year-old children.

Within the samples, the researchers discovered 409 different genes, providing bacteria with resistance to 34 types of antibiotics. Furthermore, 167 of the 409 genes found are resistant to multiple types of antibiotics, including those classified as 'critically important' by the WHO for being able to treat serious diseases in the future.

"It's a wake-up call that one-year-old children are already carrying gut bacteria that are resistant to very important types of antibiotics. New resistant bacteria are becoming more widespread due to increased antibiotic consumption. The horror scenario is that we will one day lack the antibiotics needed to treat life-threatening bacterial infections such as pneumonia or foodborne illnesses," explains Department of Biology professor Søren Sørensen, who led the study.

Antibiotic use during pregnancy is an important factor

The important factor for whether an infant had more antibiotic-resistant genes in bacteria in the gut was if the child's mother had been administered antibiotics during late pregnancy or if the year-old infant had received antibiotics in the months prior to the collection of their stool samples.

"We found a very strong correlation between a mother's antibiotic treatment during late pregnancy and of infants and gut bacteria with many resistant genes, although it appears that other influences come into play as well," says Xuan Ji Li of the Department of Biology, the study's lead author.

At the same time, the researchers found a link between how well-developed the gut flora of children were and the concentration of resistant bacteria. Well-developed gut flora equated with a lesser incidence of resistant bacteria. Previous studies from the same group of children demonstrated that the development of gut flora is linked to asthma risk later in life.

E. coli collect resistant genes

Escherichia coli (E. coli) is common in the intestine and can lead to intestinal infections. But in this study, the researchers also learned that E. coli appears to act as a main collector and a potential spreader of antibiotic-resistant genes to other gut bacteria.

The researchers also found E. coli in infants with high concentrations of resistance genes in their intestinal tracts.

"The new findings have expanded our understanding of antibiotic resistance by showing us which bacteria act as collectors and potential spreaders of resistance genes. While we know that resistance is transferred among bacteria, we also now know that E. coli is one of the ones we need to keep a particularly close eye on," says Xuan Ji Li of the Department of Biology. Søren Sørensen adds:

"The new knowledge brought about by this study may prove useful in the effort to better manage antibiotic treatments among pregnant women and serve as a basis for more targeted methods of eliminating the types of bacteria which collect resistance genes."

Credit: 
University of Copenhagen - Faculty of Science

An 1% Hubble parameter estimation from LISA-Taiji gravitational wave observatory network

image: Averaged event number in 1-year, 3-year and 5-year observation time.

Image: 
©Science China Press

The Hubble parameter is one of the central parameters in the modern cosmology. Their values inferred from the late-time observations are systematically higher than those from the early-time measurements by about 10%. This is called the "Hubble tension". To come to a robust conclusion, independent probes with accuracy at percent levels are crucial. With the self-calibration by the theory of general relativity, gravitational waves from compact binary coalescence open a completely novel observational window for Hubble parameter determination. Hence, it can shed some light on the Hubble tension. Depends on whether being associated with electromagnetic counterparts or not, gravitational wave events can be categorized into bright sirens and dark sirens. The future space-borne gravitational wave observatory network, such as the LISA-Taiji network, will be able to measure the gravitational wave signals in the Millihertz bands with unprecedented accuracy. This advantage could help the measurement of Hubble constant.

A group of Chinese scientists from Beijing and Shenzhen forecast the ability of constraining the Hubble parameter by using GW sirens data from the future space-borne gravitational wave observatories, such as LISA (ESA/NASA space mission) and Taiji (Chinese space project). The signals are generated by the inspirals and mergers of massive black hole binary. Astronomers believe each galaxies host a central massive black hole, whose mass is about one part per thousand of their bulge mass. However, there are outliers. These galaxies just experienced a very violent collision with their neighbors. In the long history of universe, these galaxy merger events happened frequently and will trigger the star formation. Besides of that, the central massive black holes associated with the galaxies will also merge with each other and emit significant GW radiation in the very final phase of coalescence. There is a time delay between massive black hole merger and the galaxy merger. In the view of cosmic time scale, this delay is an instant. However, from the point of view of human lifetime, this delay is about million years. Hence, some galaxies will host two or three massive black holes. If the separation of these massive black holes are less than 0.001 persec, the gravitational wave emission will dominate the radiation transfer process and drive the hardening of the black hole binaries. Thanks to the excellent sensitivity of space gravitational wave observatories, we will be able to measure this tiny signal. And more importantly, this gravitational wave signal carries fruitful cosmological information.

By including several statistical and instrumental noises, the Chinese team show that "within 5 years operation time, the LISA-Taiji network is able to constrain the Hubble parameter within 1% accuracy, and possibly beats the scatters down to 0.5% or even better". Besides of that, they also calculate the averaged event numbers for different massive black hole formation models and several observation times. After 5-year network observation, for the optimistic heavy seed model, the averaged event number with the Hubble parameter accuracy better than 1% could reach 0.9 and its 95% confidence interval will up-cross unity. "We will very probably capture one gold or diamond event after 5-year network observation." the scientists forecast.

See the article:
Renjie Wang, Wen-Hong Ruan, Qing Yang, Zong-Kuan Guo, Rong-Gen Cai, Bin Hu
Hubble parameter estimation via dark sirens with the lisa-taiji network
Natl Sci Rev
https://doi.org/10.1093/nsr/nwab054

Credit: 
Science China Press

Coronavirus testing made quick and easy

image: KAUST scientists have combined state-of-the-art bioelectronic hardware, materials science engineering and synthetic biology protein design to simplify and accelerate coronavirus testing.

Image: 
© 2021 KAUST; Xavier Pita

A new rapid coronavirus test developed by KAUST scientists can deliver highly accurate results in less than 15 minutes.

The diagnostic, which brings together electrochemical biosensors with engineered protein constructs, allows clinicians to quickly detect bits of the virus with a precision previously only possible with slower genetic techniques. The entire set-up can work at the point of patient care on unprocessed blood or saliva samples; no laborious sample preparation or centralized diagnostic laboratory is required.

"The combination of state-of-the-art bioelectronic hardware, materials science engineering and synthetic biology protein design really makes it possible to simplify and accelerate coronavirus testing," says Raik Grünberg, a biochemist at KAUST who co-led the study.

Grünberg and his KAUST colleagues, including Sahika Inal and Stefan Arold, are now working with commercial partners to adapt their lab-scale prototype. They hope to create a bench-top, portable device that can be deployed to help contain the COVID-19 pandemic.

"This biosensor technology could be adapted to detect other pathogens and, as such, will have a major impact on controlling pandemics -- today and in the future," Inal says.

Coronavirus testing remains as important as ever. Despite increasing rates of vaccination in Saudi Arabia and around the world, global case numbers of COVID-19 remain at worryingly high levels, and public health officials need ways of rapidly identifying individuals who have contracted the disease so that they can limit virus transmission.

Current testing paradigms generally fall into two camps: either they detect viral RNA through genetic means, which can be slow and involves enzymatic amplification of trace molecular signals, or they capture viral proteins (known as antigens) in ways that are fast but not nearly as accurate.

The new KAUST technique now combines the speed of protein detection with the precision of genetic tests. "Even if there's only a single virus particle in a sample, our platform will detect it," says Keying Guo, a postdoc in Inal's lab and co-author of the study with his KAUST colleagues Shofarul Wustoni and Anil Koklu.

The system starts with a virus-specific nanobody, a type of binding protein that can be designed to stick to fragments of different coronaviruses, including those responsible for COVID-19 and Middle East respiratory syndrome (MERS). The nanobody is tethered through a series of biochemical linkers to a thin layer of gold that, when an electric current is added, controls the flow of electricity through the semiconducting film it is connected to. The presence of any nanobody-bound viral proteins changes that flow, creating a signal that is amplified to measurable levels by a device known as an organic electrochemical transistor.

The researchers initially honed their test on human saliva and blood samples spiked with bits of protein from the coronaviruses that cause MERS and COVID-19. They then collaborated with doctors from KAUST Health in Thuwal and with scientists from King Faisal Specialist Hospital and Research Center in Riyadh to validate the assay on clinical specimens, both saliva and nasal swabs, collected from patients.

The speed, versatility and performance compared to standard genetic testing highlight the potential for the new method to complement or possibly replace existing diagnostics for COVID-19 and any future pandemics.

Credit: 
King Abdullah University of Science & Technology (KAUST)