Culture

A deadly long-distance hunter: DNA study reveals insights about the scimitar-toothed cat

image: Illustration of "Homotherium Latidens".

Image: 
University of Copenhagen

Along with the woolly mammoth and the giant ground sloth, the sabre-toothed cats were probably among the most famous animals that lived during the Pleistocene Epoch and went extinct before the end of last ice age. Over the years, sabre-toothed cats have also been the subject of many research projects.

Now, for the first time, researchers from the University of Copenhagen have succeeded in mapping the entire nuclear genome of a sabre-toothed cat, the scimitar-toothed cat "Homotherium latidens". Their DNA study reveals what genes were highly selected upon and important in evolution of the species.

'Their genetic makeup hints towards scimitar-toothed cats being highly skilled hunters. They likely had very good daytime vision and displayed complex social behaviours. They had genetic adaptations for strong bones and cardiovascular and respiratory systems, meaning they were well suited for endurance running. Based on this, we think they hunted in a pack until their prey reached exhaustion with an endurance-based hunting-style during the day light hours,' says co-first author Michael Westbury, Postdoc at the Section for Evolutionary Genomics, GLOBE Institute, University of Copenhagen.

Abundant species

The researchers extracted DNA from a Homotherium fossil recovered from Pleistocene permafrost sediments near Dawson City, Yukon Territory, Canada. This specimen was so old it could not be dated using conventional radio-carbon dating meaning that it was at least 47.5 thousand years old.

They then used a variety of modern genomic sequencing techniques to map the entire genome of the fossil. They used complex comparative analyses to modern living cat species such as lions and tigers and showed that this sabre-toothed cat were very genetically diverse, relative to modern cat species.

'We know that genetic diversity correlates to how many of a given species that exists. Based on this, our best guess is that there were a lot of these big cats around. This also makes perfect sense given that their fossils have been found on every single continent except Australia and Antarctica,' says Michael Westbury.

Synergies with medical research and bioinformatics

Their analysis also showed that the sabre-toothed cat is very distantly related to all modern cats. They diverged from them around least 22.5 million years ago. In comparison, humans and gibbons split between 15 and 20 million years ago.

'This was an extremely successful family of cats. They were present on five continents and roamed the earth for millions of years before going extinct. The current geological period is the first time in 40 million years that earth has lacked sabretooth predators. We just missed them' says co-first author Ross Barnett.

The researchers also emphasize that their study is an example of how different fields of research can benefit from each other. They hope to see similar bioinformatics methods used on many other extinct animals in the future.

'Modern advancements within medicine and genetic research means that the sequencing methods are a lot better for us now than they were just a few years ago. On top of that, we know what specific genes are associated with in animals and humans from medical research. This means that we can infer a lot of things about extinct animals as we have done here. You could say that the fast progression of medical research has made this study possible,' says professor Tom Gilbert.

Credit: 
University of Copenhagen - The Faculty of Health and Medical Sciences

Swallowing, communication management of tracheostomy, laryngectomy in context of COVID-19

What The Article Says: This review synthesizes the literature regarding tracheostomy and laryngectomy management in the context of the COVID-19 pandemic.

Authors: José Vergara, B.Sc., S.L.P., of the University of Campinas in São Paulo, Brazil, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamaoto.2020.3720)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

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Media advisory: The full study is linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/10.1001/jamaoto.2020.3720?guestAccessKey=40e269c2-0484-46ee-92fd-5c0899d17d9f&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=101520

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JAMA Network

Personality traits affect shelter at home compliance

WASHINGTON - A worldwide survey conducted during the first wave of the COVID-19 pandemic found that people with certain common personality traits were less likely to shelter at home when government policies were less restrictive, according to research published by the American Psychological Association.

"We found that people who scored low on two personality traits - openness to experience and neuroticism - were less likely to shelter at home in the absence of stringent government measures, but that tendency went away when more restrictive government policies were implemented," said Friedrich Götz, MPhil, a doctoral candidate at the University of Cambridge and lead author of the study. "Initially, this was a bit astounding, as open individuals have traditionally been shown to be prone to risk taking, willing to deviate from cultural norms and likely to seek out and approach novel and unfamiliar things - all of which would arguably put them at greater risk to ignore sheltering-in-place recommendations. However, at the same time, openness is also related to accurate risk perceptions, universalism and humankind identification. Thus, in the digitalized world in which the current pandemic occurred, these qualities may have led open individuals to follow the COVID-19 outbreak in other countries, realize its severity and act accordingly."

The researchers used data from the "Measuring Worldwide COVID-19 Attitudes and Beliefs" project, a global survey that sought to assess participants' behaviors and perceptions of others' behaviors during the COVID-19 crisis as the pandemic unfolded. Götz and his colleagues analyzed responses from more than 101,000 participants in 55 countries where at least 200 people responded to the survey between March 20 and April 5, 2020. In addition to providing information on behavior, participants also provided sociodemographic data and answered a series of questions designed to measure the so-called Big Five personality traits: conscientiousness, neuroticism, agreeableness, extraversion and openness.

To assess each country's national policy stringency, the researchers used the COVID-19 Government Response Stringency Index, which assigns stringency scores based on seven policy measures - school closing, workplace closing, cancellation of public events, suspension of public transport, implementation of public information campaigns, restrictions on internal movement and international travel controls.

"Our analyses reveal that both governmental stringency and personality independently predicted sheltering-in-place rates. Not surprisingly, in areas where government policies were more stringent, people were more likely to shelter in place," said Götz.

The researchers also found that, regardless of the stringency of government policy measures, personality traits were associated with shelter-in-place behavior. For instance, people who scored high on extraversion were significantly less likely to shelter in place, while higher scores on the other four personality traits were associated with greater likelihood to shelter in place, irrespective of how strictly the government enforced its policies.

But, while people who scored low on openness and neuroticism were less likely to shelter in place when government policies were lenient, that tendency was reduced when stricter government policies were in place.

Another explanation for the findings could be political, according to Götz. People who score high on openness tend to be more liberal in their political beliefs, and in the United States - the country with the second highest number of survey responses - compliance with social distancing behaviors during the COVID-19 pandemic appears to be strongly linked to partisanship, with liberals being much more likely to comply than conservatives.

"Taken together, the results reaffirm the power of personality as a central driver of behavior, a force that is not simply eclipsed by governmental policy," said co-author Jon Jachimowicz, PhD, of Harvard University. "Still, stringent governmental policies were able to decrease the influence of two personality traits, demonstrating how macro-level forces can diminish the influence of certain micro-level factors."

Because personality plays such a crucial role as governments continue to relax and reinstate tight government rules in reaction to changes in the spread of disease, it is important to understand why some people flout the rules more than others, according to Jachimowicz. Learning what characterizes such people can be informative in multiple ways, from helping to identify potential super-spreaders to tailoring public health messages to people's personalities in order to increase compliance.

Credit: 
American Psychological Association

New tool enables easy, effective disease tracking

image: IDseq, an open-source, cloud-based tool, allows laboratories and clinics anywhere in the world to carry out pathogen detection and identification of both novel and existing disease-causing pathogens, aiding in combating current pandemics and preventing them.

Image: 
IDseq.net

15th October 2020, Hong Kong: Published today in the journal GigaScience is a new open source, cloud-based tool called IDseq that makes it possible to rapidly detect, identify, and track emerging pathogens such as SARS-CoV-2. This tool can identify pathogens before there is an available complete genome sequence; thus, it can be used for current infectious disease outbreaks and also for emerging ones. This will substantially aid in preventing future pandemics.

The coronavirus pandemic demonstrates the importance of global infectious disease monitoring. Finding the cause of an infectious disease outbreak is challenging, especially if it stems from a previously unknown pathogen. IDseq, an open source, cloud-based metagenomic analysis platform, identifies both novel and existing disease-causing pathogens from a given sample -- be it a human, animal, or parasite -- to provide an actionable report of what is happening on the ground in labs and clinics anywhere in the world.

"IDseq can be thought of as an early warning radar for emerging or novel infectious agents," said Joe DeRisi, PhD, Co-President of the Chan Zuckerberg Biohub, who contributed to the identification of the SARS coronavirus in 2003 and whose research lab at the University of California, San Francisco initiated the IDseq tool. It is designed to enable the global health community to leverage the ever-decreasing cost of sequencing for tracking and identifying infectious disease in essentially any sample. "At the beginning of the coronavirus pandemic, researchers in Cambodia used IDseq to help confirm and sequence the whole genome of the country's first case of COVID-19 in a matter of days, and in California, we're providing critical SARS-CoV-2 genomic data to public health officials to inform contact tracing and intervention strategies."

In a study published in GigaScience, scientists use various approaches to demonstrate that the IDseq tool is indeed able to reliably identify emerging pathogens, among them, as proof of principle, a nasal swab from a COVID-19 patient in Cambodia. A partnership between the Chan Zuckerberg Biohub, the Chan Zuckerberg Initiative (CZI), and the Bill and Melinda Gates Foundation enabled these researchers to sequence and confirm the country's first case of COVID-19 in a matter of days -- not the weeks it could typically take. The results demonstrate that IDseq can detect the presence of an emerging pathogen prior to the existence of a full reference genome. IDseq also now contains a new workflow for building SARS-CoV-2 consensus genomes.

"Metagenomic sequencing (mNGS) is an incredibly useful tool for pathogen detection because of its highly sensitive and hypothesis-free nature," said Katrina Kalantar, Computational Biologist at CZI. "We've seen labs that are using IDseq for existing mNGS studies rapidly pivot their focus to more targeted sequencing of SARS-CoV-2, which has helped researchers better understand coronavirus transmission patterns."

In Cambodia, researchers uploaded the genome sequence to open source pathogen data repository GISAID (Global Initiative on Sharing All Influenza Data) and to Nextstrain, so scientists anywhere can see the full genome sequence of the SARS-CoV-2 coronavirus and study it within the broader context of SARS-CoV-2 coronavirus sequences uploaded globally. Researchers at the Cambodian National Center for Parasitology, Entomology and Malaria Control (CNM) and the National Institute of Allergy and Infectious Diseases (NIAID) partnered with the Institut Pasteur Cambodia to complete this research. These researchers are one of several teams around the world receiving molecular biology and bioinformatics training from the infectious disease team at the Biohub; free access, training, and compute on the IDseq platform from CZI; and the necessary equipment and supplies to begin work in their own countries through the Grand Challenges Explorations Grants.

Unlike tests that are specific for a known agent, such as the SARS-CoV-2 PCR test, mNGS is a universal method that can detect novel disease-causing pathogens, which can be especially useful in cases where researchers may not know what is causing an infection, or what pathogens are circulating in a particular area. A mNGS experiment starts with mass-amplifying DNA traces of pathogens from a patient's sample, resulting in millions of small bits of DNA sequences, or reads. This enormous dataset must then be analysed and interpreted using bioinformatic techniques. The aim is to assign individual DNA fragments from the clinical sample to specific pathogens by leveraging knowledge from sequence databases.

Analysing the massive amount of data from a typical mNGS experiment often requires a battery of specialized bioinformatic tools, including highly specialized expertise and expensive commercially licenced software -- making mNGS a hard-to-access method. The new user-friendly IDseq software is open source and freely available to the global health community, reducing the barrier of entry to metagenomics. Researchers can reuse and build upon the code, which works via a cloud-based service and a web application designed for collaboration and data sharing. The pipeline starts with raw sequencing data as the input, and then goes through steps of filtering, quality control, alignment, and reporting and visualization.

For more information, visit IDseq.net.

Further Reading
Kalantar KL et al., IDseq - An Open Source Cloud-based Pipeline and Analysis Service for Metagenomic Pathogen Detection and Monitoring. Gigascience. 2020;9(10):giaa085. doi:10.1093/gigascience/giaagiaa111

https://academic.oup.com/gigascience/article-lookup/doi/10.1093/gigascience/giaa111

Preprint available at https://www.biorxiv.org/content/10.1101/2020.04.07.030551v3

Contacts:
Scott Edmunds, Editor in Chief
GigaScience, BGI Hong Kong
Email: scott@gigasciencejournal.com

Leah Duran, Communications Manager, CZI
Email: lduran@chanzuckerberg.com

Sharing on social media?
Find GigaScience online on twitter @GigaScience; Facebook https://www.facebook.com/GigaScience/, and keep up-to-date with our blog http://gigasciencejournal.com/blog/.

About GigaScience
GigaScience is co-published by GigaScience Press and Oxford University Press. Winner of the 2018 PROSE award for Innovation in Journal Publishing (Multidisciplinary), the journal covers research that uses or produces 'big data' from the full spectrum of the biological and biomedical sciences. It also serves as a forum for discussing the difficulties of and unique needs for handling large-scale data from all areas of the life and medical sciences. The journal has a completely novel publication format -- one that integrates manuscript publication with complete data hosting, and analyses tool incorporation. To encourage transparent reporting of scientific research as well as enable future access and analyses, it is a requirement of manuscript submission to GigaScience that all supporting data and source code be made available in the GigaScience database, GigaDB, as well as in publicly available repositories. GigaScience will provide users access to associated online tools and workflows, and has integrated a data analysis platform, maximizing the potential utility and re-use of data.

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GigaScience

Examining CBD use for conditions with proven therapies

What The Study Did: Testimonials posted on a social media site were analyzed to examine whether individuals are using the cannabis-derived chemical compound cannabidiol (CBD) in an attempt to treat diagnosable conditions that have evidence-based therapies.

Authors: John W. Ayers, Ph.D., M.A., of the University of California, San Diego, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.20977)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Researchers deconstruct the "biological clock" that regulates birdsong

image: A team of researchers from Penn State and New York University has deconstructed an important "biological clock" in the zebra finch brain and found that the "wires" between neurons, called axons, play a critical role in the precise timing of the birds' courtship song.

Image: 
Christopher Auger-Dominguez

UNIVERSITY PARK, Pa. -- The precise timing of a bird's complex song is driven in part by the often-ignored "wires" connecting neurons in the bird's brain, according to a new study. A team of researchers from Penn State and New York University has deconstructed an important "biological clock" that regulates birdsong and other behaviors, leading to new ways of thinking about the function of neuronal networks.

"Many complex, learned behaviors, like hitting a golf ball or playing the violin, require incredibly precise timing at the level of neural firing," said Dezhe Jin, associate professor of physics at Penn State and an author of the paper. "But how the brain seamlessly regulates our muscles in such a precise way remains unclear. In this study, we created a model based on years of experimental observations which revealed that delays within the circuits of neurons play a critical role in the timing of their firing. We then pinpointed the source of the delays to the wires, or axons, that connect neurons."

In a paper appearing Oct. 15 in the journal Cell, Jin and colleagues address behavioral timekeeping using the zebra finch, a small Australian songbird capable of learning a courtship song with the skill of a master instrumentalist. To enable this vocal display, finches have a dedicated "clock" -- called HVC -- in their brains that regulates the timing of the song. In HVC, groups of neurons fire in a predictable sequence that correspond to the performance of the song.

"HVC is often thought of as a clock because it controls a very complicated movement -- the song -- where precise timing is so critical," said Robert Egger, a postdoctoral fellow at the NYU School of Medicine and lead author on this study. "We used cutting-edge methods to measure the simultaneous activity of up to 70 neurons within HVC during singing. In the past, we had to measure each neuron one by one and align their activity to the song."

To explore how a circuit can be so precise, Jin and his graduate student Eugene Tupikov developed a series of large-scale computational models describing the neuronal circuit. In one case, a cluster of neurons fires at the same time which triggers the next cluster of neurons that fire at the same time, triggering the next cluster, like falling dominos, in what researchers call a synfire chain. In an alternative model, delays in the wires allow neurons to fire at slightly different times. The result is a more precise clock.

"We used to think of each group of neurons firing together as a separate, discrete tick of the second hand," said Michael Long, associate professor of neuroscience and physiology at the NYU School of Medicine and corresponding author of the paper. "But what we actually see is more like a second hand that moves smoothly and continuously. The distribution of delays among the wires allows for higher resolution because you don't get these tick points."

The team found a wide distribution of delays in the circuit, meaning some signals reach other neurons very quickly and some take much longer.

"We knew that delays in neuronal circuits were important over a large distance, but within local circuits, they were thought to be negligible, and for that reason were often ignored," said Jin, who led the modeling effort. "These results suggest that axons play a critical role in the timing of neuronal circuits and should be incorporated into future models."

To determine if axonal delays may play a role in other brain networks, the researchers estimated the delays in an area of the rodent brain used to sense their environment while they move their whiskers.

"Our results were consistent with the delays we saw in the songbird, which suggests that axonal delays may play an important role in shaping neuronal activity across a range of complex behaviors," said Jin. "We need to incorporate axon delays into how we think about the brain and how it works."

Credit: 
Penn State

New study reveals how the nervous system mutes or boosts sensory information to make behavioral deci

image: Researchers captured 3D images of the regions of the Drosophila central nervous system that are activated in response to noxious stimulation. The posterior medial center (red), which is located between sensory- and motor-related regions of the nervous system, is important for making behavioral decisions.

Image: 
Yujia Hu, U-M Life Sciences Institute

Fruit flies may be able to teach researchers a thing or two about artificial intelligence.

University of Michigan biologists and their colleagues have uncovered a neural network that enables Drosophila melanogaster fruit flies to convert external stimuli of varying intensities into a "yes or no" decision about when to act.

The research, scheduled to publish Oct. 15 in the journal Current Biology, offers hints into how these decisions work in other species, and could perhaps even be applied to help AI machines learn to categorize information.

Imagine you are working near an open window. If the outside noise is low enough, you may not even notice it. As the noise level gradually increases, you start to notice it more--and eventually, your brain makes a decision about whether to get up and close the window.

But how does the nervous system translate that gradual, linear increase in intensity to a binary, "yes/no" behavioral decision?

"That's a really big question," said neuroscientist Bing Ye, a faculty member at the University of Michigan Life Sciences Institute and senior author of the study. "Between the sensory input and the behavior output is a bit of 'black box.' With this study, we wanted to open that box."

Brain imaging in humans or other mammals can identify certain regions of the brain that respond to particular stimuli. But to determine how and when the neurons transform linear information into a nonlinear decision, the researchers needed a much deeper, more quantitative analysis of the nervous system, Ye said.

They chose to work with the model organism Drosophila, due to the availability of genetic tools that make it possible to identify individual neurons responding to stimuli.

Using an imaging technique that detects neuronal activity through calcium signaling between neurons, the scientists were able to produce 3-D neuroactivity imaging of the flies' entire central nervous system.

"What we saw was that, when we stimulate the sensory neurons that detect harmful stimuli, quite a few brain regions light up within seconds," said Yujia Hu, a research investigator at the LSI and one of the lead authors on the study. "But these brain regions perform different functions. Some are immediately processing sensory information, some spark the behavioral output--but some are more for this transformation process that occurs in between."

When sensory neurons detect the harmful external stimuli, they send information to second-order neurons in the central nervous system. The researchers found that one region of the nervous system in particular, called the posterior medial core, responds to sensory information by either muting less intense signals or amplifying more intense signals, effectively sorting a gradient of sensory inputs into "respond" or "don't respond" categories.

The signals get amplified through increased recruitment of second-order neurons to the neural network--what the researchers refer to as escalated amplification. A mild stimulus could activate two second-order neurons, for example, while a more intense stimulus may activate 10 second-order neurons in the network. The larger network can then prompt a behavioral response.

But to make a "yes/no" decision, the nervous system needs a way not just to amplify information (for a "yes" response), but to also suppress unnecessary or less harmful information (for a "no" response).

"Our sensory system detects and tells us a lot more than we realize," said Ye, who is also a professor of cell and developmental biology in the U-M Medical School. "We need a way to quiet that information, or we would just constantly have exponential amplification."

Using the 3-D imaging, the researchers found that the sensory neurons actually do detect the less harmful stimuli, but that information is filtered out by the posterior medial core, through the release of a chemical that represses neuron-to-neuron communication.

Together, the findings decode the biological mechanism that the fruit fly nervous system uses to convert a gradient of sensory information into a binary behavioral response. And Ye believes this mechanism could have far wider applications.

"There is a dominant idea in our field that these decisions are made by the accumulation of evidence, which takes time," Ye said. "In the biological mechanism we found, the network is wired in a way that it does not need an evidence accumulation phase. We don't know yet, but we wonder if this could serve as a model to help AI learn to sort information more quickly."

Credit: 
University of Michigan

Researchers seek to end unexpected bills for screening colonoscopies

image: James M. Scheiman, MD, chief of UVA Health's Division of Gastroenterology and Hepatology, is concerned that surprise billing may deter patients from getting recommended colonoscopies.

Image: 
UVA Health

Nearly 1 in 8 commercially insured patients nationwide who underwent an elective colonoscopy between 2012 and 2017 performed by an in-network provider received "surprise" bills for out-of-network expenses, often totaling hundreds of dollars or more, new analysis from a team led by a UVA Health doctor shows.

James M. Scheiman, MD, chief of UVA's Division of Gastroenterology and Hepatology, has been deeply concerned that surprise billing may deter patients from getting recommended colonoscopies, increasing the chances that cancer and other digestive disorders remain undetected. So he and his collaborators set out to document the scope of the problem and develop potential solutions.

"Colonoscopy is the most effective colorectal cancer prevention strategy in our medical toolbox," Scheiman said. "We cannot let out-of-pocket costs deter patients from undergoing this potentially lifesaving screening test."

Colonoscopy Insurance Coverage

Scheiman and colleagues at the University of Michigan reviewed 1.1 million claims from a large national insurer for elective colonoscopies that were performed across the country between 2012 and 2017 where both the endoscopists and the hospital facilities were in-network. Of those, 12.1% involved out-of-network claims, with an average surprise bill of $418.

These bills often came because of the use of out-of-network anesthesiologists (64% of cases; median surprise bill of $488) and out-of-network pathologists (40% of cases; median surprise bill of $248). At UVA, colonoscopy anesthesia and pathology services are provided in-house, and there are no out-of-network costs for in-network patients.

"Particularly concerning was that 1 in 12 procedures that did not have an associated intervention had an out-of-network claim," the researchers write in a new Annals of Internal Medicine paper (link here). "This outcome is disconcerting since federal regulations eliminate consumer cost sharing for screening colonoscopy when performed in-network; and 2) a recent Federal Reserve Study reported that 40% of Americans do not have $400 to cover unexpected expenses."

Stopping Surprise Bills

The researchers go on to make important recommendations to spare patients surprise bills: Endoscopists and hospitals should partner with anesthesia and pathology providers who are in-network, and they should consider cost-saving strategies such as endoscopist-provided sedation rather than use of deeper anesthesia. Also, they say considerable healthcare dollars could be saved by adopting a strategy where not all low-risk polyps are sent for pathological evaluation. "In the longer term, we must enhance ongoing reform efforts to remove consumer cost sharing for all clinically indicated care associated with colonoscopy," the researchers write.

"In addition to insurance reform, which is essential to resolve this risk of cost sharing," Scheiman said,"we need tools to accurate predict out-of-pocket responsibilities for patients before the procedure is performed to allow opportunities to limit costs without impact on quality."

Credit: 
University of Virginia Health System

Small RNA as a central player in infections

image: Artistic representation of human stomach cells infected with Helicobacter pylori, showing the special Hummingbird cell shape induced by the bacterium.

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(Image: Chair of Molecular Infection Biology II / University of Wuerzburg / SCIGRAPHIX)

More than half of the world's population carries the bacterium Helicobacter pylori in their stomach mucosa. It often causes no problems throughout life, but sometimes it can cause inflammation, and in some cases, it can even lead to the development of stomach cancer.

Helicobacter pylori uses several "virulence" factors that allow it to survive in the stomach and can lead to the development of disease. In this issue of the journal Molecular Cell, Professor Cynthia Sharma's research team report that multiple of these factors are centrally regulated by a small RNA molecule called NikS. Prof. Sharma heads the Chair for Molecular Infection Biology II at Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany.

Among the target genes regulated by NikS are the two most important virulence factors of Helicobacter pylori as well as two encoding outer membrane proteins. In particular, the JMU researchers were able to show that NikS regulates the CagA protein, a bacterial oncoprotein that plays a central role in the development of cancer instigated by Helicobacter pylori. In addition, a protein with a so far unknown function that is released into the environment by H. pylori is also under the control of NikS.

The new findings are relevant for medicine and infectious disease research: "With the knowledge of the different functions and underlying molecular mechanisms of this small RNA during infection and the associated bacterial signaling pathways, we can gain new targets for the development of novel antimicrobial strategies," explains Cynthia Sharma.

Phase variation even in small RNA molecules

The fact that Helicobacter pylori can colonize such a hostile environment as the stomach so successfully is also due to a special genetic strategy: Like other pathogens, H. pylori uses a strategy known as phase variation to adapt as flexibly as possible to changes in its environment. Phase variation means that the bacteria constantly switch expression of a gene at random through genetic mutations, meaning that some bacteria in a population will always be ready to express the important gene when it becomes important - a sort of "bet-hedging" strategy.

Sharma's team has now been able to show for the first time that the expression of a small RNA molecule such as NikS, and not just of proteins, can also be subject to phase variation. Depending on the conditions prevailing in the stomach, different amounts of NikS might be beneficial. Levels of the small RNA can change to suit this through phase variation, thereby leading to different regulation of the disease-causing factors.

NikS helps to colonize host cells

"This mechanism could play a major role in enabling Helicobacter pylori to adapt successfully to the variable stomach environment and thus chronically colonize its host," says Sharma. In experiments, her team was able to show that NikS influences the internalization of the bacteria into host cells. In addition, the small RNA makes it easier for H. pylori to overcome epithelial barriers and, thus, might lead to better access of nutrients in deeper tissues in the stomach.

In further studies, the JMU researchers now aim to find out how the small RNA contributes to the colonization of different niches in the stomach and whether it regulates other genes that might also be involved in the bacterium's pathogenic properties.

Credit: 
University of Würzburg

Public health experts fear devastating impact of flu and COVID-19 on vulnerable adults

Washington, DC (October 15, 2020) -- The National Foundation for Infectious Diseases (NFID) issued a new Call to Action report detailing the risks of co-infection with influenza (flu) and COVID-19 in adults with chronic health conditions, and the importance of flu vaccination during the 2020-2021 season. The goals of the report, The Dangers of Influenza and COVID-19 in Adults with Chronic Health Conditions, have been supported by more than 35 leading medical organizations, including the American College of Cardiology, American College of Emergency Physicians, American Diabetes Association, and American Lung Association, who are now urging their stakeholders to prioritize flu vaccination for these high-risk populations.

In the US, six in ten adults have one or more chronic health conditions, including heart disease, lung disease, and diabetes, that put them at increased risk for flu and COVID-19. For this population, related complications include the potential exacerbation of underlying health condition(s), as a result of flu-related inflammation that may persist long after the acute infection, as well as increased risk of long-term complications, such as heart attack and stroke, after experiencing acute flu or COVID-19 infection.

According to the Centers for Disease Control and Prevention (CDC), annual flu vaccination has been proven to mitigate serious flu-related complications, preventing an estimated 7.5 million flu illnesses, 3.7 million flu-associated medical visits, 105,000 flu hospitalizations, and 6,300 flu deaths in 2019-2020 alone. Yet, a recent NFID survey found that nearly one in four US adults at high risk for flu-related complications said they did not intend to get vaccinated during the 2019-2020 flu season.

"Amidst the COVID-19 pandemic, patients with chronic health conditions are facing not one, but two viruses that pose a serious threat to their health and independence," said NFID Medical Director William Schaffner, MD. "While we currently don't have an approved COVID-19 vaccine in the US, we know that annual flu vaccination can help protect these patients from hospitalization, progressive disability, and even death. It is imperative that healthcare professionals educate patients with chronic health conditions about their risks and implement strategies to increase flu vaccination rates during the COVID-19 pandemic."

In advance of an unprecedented 2020-2021 flu season, NFID convened a multidisciplinary virtual roundtable with leading experts to explore the risks of co-circulation and co-infection with flu and SARS-CoV-2 (the virus that causes COVID-19) in adults with chronic health conditions. The resulting NFID Call to Action, which summarizes the roundtable discussions, includes best practices for administering flu vaccines in conjunction with COVID-19 mitigation efforts. Despite the limited data currently available on outcomes from co-infection with the two viruses, insights from the roundtable highlighted that the impact on patients and the US public health system could be catastrophic.

"It won't take a 'bad' flu season--just 'a' flu season to make things more difficult in the ER and elsewhere in the US healthcare system," said Nicholas F. Vasquez, MD, vice chair of the Diversity, Inclusion, and Health Equity Section of the American College of Emergency Physicians. "Further strain due to the co-circulation of flu and COVID-19 could disrupt routine care and have detrimental consequences for adults with chronic health conditions."

The relationship between flu and heart disease is of particular concern during the current pandemic, as severe COVID-19 outcomes have also been associated with pre-existing cardiovascular conditions and post-infection injury to heart tissue. Over the past eight US flu seasons, nearly 47 percent of patients hospitalized for flu had heart disease, making it the most common underlying health condition associated with flu-related complications. Fortunately, flu vaccination can serve as an effective prevention strategy in these patients. One study estimated the flu vaccine is between 15 to 45 percent effective in preventing heart attacks and strokes, making it equal to or more effective than smoking cessation, statins, and antihypertensive therapy.

"I am greatly concerned for heart disease patients this flu season. It is already well-documented that heart disease is a risk factor for severe flu-related illness, but with COVID-19, we are entering a dangerous and uncharted territory," said William B. Borden, MD, professor of medicine and health policy at George Washington University, representing the American College of Cardiology. "The most important thing we can do to protect these patients is to ensure they are getting their annual flu vaccine. I am making it a point this season to strongly recommend a flu vaccine to every heart patient I see and urge my colleagues to do the same."

To help increase flu vaccination rates, the NFID Call to Action offers strategies and tactics for healthcare professionals, particularly specialists treating adults with chronic conditions during the 2020-2021 flu season, including communication methods for discussions with both patients and office staff, vaccine implementation strategies specific to the COVID-19 pandemic, and techniques for addressing vaccine misinformation.

"All healthcare professionals, including specialty care providers, have a duty to understand the risks our patients face and advocate for any preventive measure that can preserve health and save lives," said NFID President Patricia N. Whitley-Williams, MD, also representing the National Medical Association. "If you treat a patient with heart disease, lung disease, diabetes, or another chronic health condition, then you have a responsibility to insist upon annual flu vaccination."

Credit: 
PadillaCRT

Anemic star cluster breaks metal-poor record

image: The RBC EXT8 globular cluster orbits the outskirts of the Andromeda Galaxy, a close companion to our Milky Way Galaxy, located 2.5 million light-years from Earth.

Image: 
ESASky/CFHT

Maunakea, Hawaii - In a surprising discovery, astronomers using two Maunakea Observatories - W. M. Keck Observatory and Canada-France-Hawaii Telescope (CFHT) - have found a globular star cluster in the Andromeda Galaxy that contains a record-breaking low amount of metals.

The stars in the cluster, called RBC EXT8, have on average 800 times less iron than our Sun and are three times more iron-poor than the previous globular cluster record-holder. RBC EXT8 is also extremely deficient in magnesium.

The study, led by Søren Larsen of Radboud University in the Netherlands, is published in today's issue of the journal Science.

"I'm amazed that this remarkable star cluster was just sitting under our noses. It is one of the brightest clusters in the Andromeda galaxy and known for decades, yet no one had checked it out in detail," said Aaron Romanowsky, a University of California Observatories (UCO) astronomer and professor at San José State University's Physics and Astronomy Department who co-authored the study. "It shows how the universe still has many surprises for us to discover. It also reminds us to check our assumptions - in this case, it was assumed enough clusters had been investigated to know how anemic they can be."

A globular cluster is a large, dense collection of thousands to millions of ancient stars that move together as a tight-knit group through a galaxy. Until now, astronomers thought large globular clusters had to contain a considerable amount of heavy elements.

Hydrogen and helium are the two main elements created after the Big Bang. Heavier elements such as iron and magnesium formed later. Finding a massive globular cluster like RBC EXT8 that is extremely impoverished in metals defies current formation models, calling into question some of our ideas about the birth of stars and galaxies in the young universe.

"Our finding shows that massive globular clusters could form in the early universe out of gas with only a small 'sprinkling' of elements other than hydrogen and helium. This is surprising because such pristine gas was thought to be in building blocks too small to form such massive star clusters," said Larsen.

"This discovery is exciting because the idea of a 'metallicity floor' for globular clusters, that must contain some minimum amount of heavy metals, underpinned so much of our thinking about how these very old star clusters formed in the early universe," said co-author Jean Brodie, Director, Centre for Astrophysics and Supercomputing at Swinburne University and Professor Emerita of Astronomy and Astrophysics at UCO. "Our finding contradicts the standard picture and that is always fun!"

The researchers observed RBC EXT8 using Keck Observatory's High-Resolution Echelle Spectrometer (HIRES) in October of 2019. The globular cluster was not originally on the program, but Larsen's team had a couple of hours of observing time left and decided to aim the Keck I telescope at the cluster, whose stellar content had not yet been studied in detail. The team made spectroscopic observations to determine RBC EXT8's metal content and used three archive images from CFHT to determine its size and estimate its mass. Their remarkable result came as quite a surprise.

"It is observationally challenging to obtain a detailed analysis of the chemical composition of globular clusters in the Andromeda Galaxy, which is in the Northern Hemisphere of the sky," said Brodie. "The HIRES capability at Keck is uniquely well-suited to meet this challenge."

In the future, the researchers hope to find more "metal-lite" globular clusters and solve the mystery about their origin.

Credit: 
W. M. Keck Observatory

Upgraded GMRT measures the mass of hydrogen in distant galaxies

image: A GMRT Antenna at night.

Image: 
Rakesh Rao

A team of astronomers from the National Centre for Radio Astrophysics (NCRA-TIFR) in Pune, and the Raman Research Institute (RRI), in Bengaluru, has used the upgraded Giant Metrewave Radio Telescope (GMRT) to measure the atomic hydrogen content of galaxies seen as they were 8 billion years ago, when the universe was young. This is the earliest epoch in the universe for which there is a measurement of the atomic gas content of galaxies. This research has been published in the 14 October 2020 issue of the journal Nature.

Galaxies in the universe are made up mostly of gas and stars, with gas being converted into stars during the life of a galaxy. Understanding galaxies thus requires us to determine how the amounts of both gas and stars change with time. Astronomers have long known that galaxies formed stars at a higher rate when the universe was young than they do today. The star formation activity in galaxies peaked about 8-10 billion years ago and has been declining steadily till today. The cause of this decline is unknown, mostly because we have had no information about the amount of atomic hydrogen gas, the primary fuel for star formation, in galaxies in these early times.

"We have, for the first time, measured the atomic hydrogen gas content of star forming galaxies about 8 billion years ago, using the upgraded GMRT. Given the intense star formation in these early galaxies, their atomic gas would be consumed by star formation in just one or two billion years. And, if the galaxies could not acquire more gas, their star formation activity would decline, and finally cease", said Aditya Chowdhury, a Ph.D. student at NCRA-TIFR and the lead author of the study. "The observed decline in star formation activity can thus be explained by the exhaustion of the atomic hydrogen."

The measurement of the atomic hydrogen mass of distant galaxies was done by using the upgraded GMRT to search for a spectral line in atomic hydrogen. Unlike stars which emit light strongly at optical wavelengths, the atomic hydrogen signal lies in the radio wavelengths, at a wavelength of 21 cm, and can only be detected with radio telescopes. Unfortunately, this 21 cm signal is very weak, and difficult to detect from distant individual galaxies even with powerful telescopes like the upgraded GMRT. To overcome this limitation, the team used a technique called "stacking" to combine the 21 cm signals of nearly 8,000 galaxies that had earlier been identified with optical telescopes. This method measures the average gas content of these galaxies.

K. S. Dwarakanath of RRI, a co-author of the study, mentioned "We had used the GMRT in 2016, before its upgrade, to carry out a similar study. However, the narrow bandwidth before the GMRT upgrade meant that we could cover only around 850 galaxies in our analysis, and hence were not sensitive enough to detect the signal." "The big jump in our sensitivity is due to the upgrade of the GMRT in 2017", said Jayaram Chengalur, of NCRA-TIFR, a co-author of the paper. "The new wide band receivers and electronics allowed us to use 10 times more galaxies in the stacking analysis, giving sufficient sensitivity to detect the weak average 21 cm signal."

Credit: 
Tata Institute of Fundamental Research

Researchers develop a plant-based thermotherapy patch

A team of researchers at Tampere University, Finland, has developed a biodegradable, transparent, flexible and fast-acting thermotherapy patch from plant leaves. The patch is compatible with flexible electronic applications. Plant material was used to reduce the amount of electronic waste.

The researchers used leaves from a Bodhi tree (Ficus religiosa). The veins of the leaves have a fractal pattern that makes the surface highly ?exible and shearable. Silver nanowires were attached to the leaf skeleton, and the surface was encapsulated in a biodegradable transparent tape.

The fractal-based design can also be used in flexible electronic applications, as it overcomes the limitations of conventional planar designs by maximizing the surface area at the microscale, or more speci?cally, maximizing the surface area to volume ratio via simple scaling. The large surface area enables effective heat transfer, allowing a rapid response time and preventing overheating. Due to the flexibile structure and uniform heating of the patch, it can also be attached to moving joints.

In orthopedics, medical thermotherapy pads are commonly used to reduce pain, improve blood circulation and decrease in?ammation. They are also used in the treatment of arthritis, stiff joints, cervical spondylosis and physical injuries.

Traditional thermotherapy pads are known to have caused burns, one reason being that some people have skin not very sensitive to heat. Part of the problem is that commercial heating pads are opaque, and users cannot see how their skin is reacting to the therapy.

As the thermotherapy patch is made entirely of plant-based materials, it can help reduce carbon footprints and electronic waste. All the materials used in the fabrication process are eco-friendly, economical, easily accessible and easy to fabricate.

"Electronc waste is a growing environmental problem worldwide. The use of biotic architectures and materials can help in the design of next-generation flexible electronic devices while also addressing e-waste problems," says Vipul Sharma, postdoctoral researcher appointed by the Academy of Finland.

Sharma works in the Bioinspired Materials and Robotics group, which is part of the BioMediTech institute of the Faculty of Medicine and Health Technology at Tampere University. The group is headed by Academy Research Fellow Veikko Sariola.

Electronics, especially flexible electronics, are increasingly integrated into medical devices, textiles, wellness trackers and other portable devices, among other things.

The concept can also be applied in various applications such as defogging/defrosting, wearable devices, industrial heat systems, sensors, thermochromic displays and micro?uidic chips.

Credit: 
Tampere University

Was Hong Kong once a coral reef paradise?

image: Cybulski collecting a "fossil time machine" or coral reef sediment core.

Image: 
Dr Kiho Kim

Researchers from The University of Hong Kong's School of Biological Sciences and The Swire Institute of Marine Science, have for the first time investigated the historical presence of coral communities in the Greater Bay Area, revealing a catastrophic range collapse and loss of diversity that occurred in the last several decades.

The research, published in the prestigious journal Science Advances, looks at fossil corals collected from over 11 sites around Hong Kong, and creates the first palaeoecological baseline for coral communities in the Greater Bay Area. Led by PhD candidate and National Geographic Explorer Jonathan CYBULSKI, the team revealed what coral genera were present in the past well before major human impacts, and these include: Acropora, Montipora, Turbinaria, Psammacora, Pavona, Hydnophora, Porites, Platygyra, Goniopora and Faviids.

Every fossil tells a story

"The data we collect helps us to create a sort of fossil time machine," said Cybulski. "As corals grow naturally, parts of them will break off and fall to seafloor becoming a part of the sediment. Over time, many different layers of these coral skeletons will stack on top of one another. With a bit of effort we can core through the sediments and collect the different layers and reveal what coral communities were like through time," Cybulski explained. By using this method, the team was able to collect skeletons from over 5,000 years ago, which they determined thanks to radiocarbon dating by collaborator Dr Yusuke YOKOYAMA of the Atmosphere and Ocean Research Institute at The University of Tokyo.

When the team compared their fossil data to a modern-day dataset collected by collaborators at Baptist University - Dr Jian Wen QIU and Dr James XIE, several striking conclusions were revealed. First, there has been about a 40% decrease in the number of different corals living in Southern Hong Kong waters. Second, the greatest loss was of the ecologically important yet highly-sensitive staghorn corals (Acropora), which now only lives in an area about 50% smaller than its historic range. Finally, the greatest impact and losses of corals occurred in waters that are closest to the Pearl River Estuary in the southwest and Tolo Harbor in the Northeast. Based on the data, the teams best guess for the timing of this coral community change is conservatively within the last century, but likely within the past few decades. The overall conclusion: poor water quality driven by increased development and lack of proper treatment is presently the regions greatest threat to the survival of corals.

More hope for corals

"This trend we saw of a diversity decline and the loss of Acropora is consistent with other research in different areas of the world," Cybulski continues: "It's particularly bad news for this region, as Acropora represents the only type of coral that is complex, and creates physical space that promotes greater biodiversity. The loss of this coral is similar to losing all the big trees in a forest." However, similar to trees in a forest, Cybulski continued by saying there is hope for Hong Kong's corals through conservation efforts.

Indeed, this historical research has already played a critical role in protecting and restoring corals locally. In July earlier this year, PhD Candidate Ms Vriko YU, also of the Baker Lab at HKU, pioneered a coral restoration project in Hoi Ha Wan Marine Park (Note 1). This project aims to restore and better understand what it will take to save Hong Kong corals, and was made possible due to the water quality improvements in the bay by the local government.

Using Cybulski's historical data to infer the appropriate steps needed, the team is now returning corals such as Acropora that previously thrived in Hoi Ha, back to their proper home. To date, 100% of the reintroduced coral have survived. Furthermore, the team has documented several coral associated invertabrates at the site, showing that this restored habitat is indeed increasing biodiversity. The team feels this multi-faceted model - historical research that identifies major stress targets for local improvements - can be used by other researchers who hope to give corals their greatest chance for future survival.

Credit: 
The University of Hong Kong

Repurposing drugs for a pan-coronavirus treatment

image: EMBL-EBI scientists and colleagues are studying the interactions of human
proteins, such as Tom70 (shown in green), and coronavirus proteins, such
as Orf9b (shown in pink), in colon epithelial cells. Cell nuclei are shown in
cyan.

Image: 
Image: Svenja Ulferts, University of Freiburg Editing: Spencer Phillips, EMBL-EBI

15 October, Cambridge - A large international consortium of almost 200 researchers from 14 leading institutions in six countries has studied three different coronaviruses - SARS-CoV-1, SARS-CoV-2, and MERS-CoV - with the aim of finding vulnerabilities shared by these three pathogens. The research, published in the journal Science, identifies important molecular mechanisms crucial for all three coronaviruses, as well as potential drugs that could be repurposed as pan-coronavirus treatments.

The consortium included researchers at EMBL's European Bioinformatics Institute (EMBL-EBI), the Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG) at University of California San Francisco (UCSF), Gladstone Institutes, Institut Pasteur, Cluster of Excellence CIBSS at the University of Freiburg, the Howard Hughes Medical Institute, and other collaborators including the biotechnology companies Aetion and Synthego.

There are three known human respiratory syndromes associated with coronaviruses: severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19). These are caused by SARS-CoV-1, MERS-CoV, and SARS-CoV-2, respectively.

The scientists identified drug targets and repurposed therapeutics that may have broad-spectrum activity across all three coronavirus strains. Repurposed therapeutics with known safety profiles may offer a rapid treatment response against emerging coronavirus strains in the future.

Identifying coronavirus drug targets

Building on their previous work published in Nature and Cell, the scientists determined how viral and human proteins interact, and where viral proteins are located within host cells infected by different coronaviruses. They subsequently used this data and functional genetic screening to identify host factors that prevent coronavirus propagation. The data analysed in this study will be made freely accessible through the COVID-19 Data Portal.

"These analyses demonstrate how biological and molecular information are translated into real-world implications for the treatment of COVID-19 and other viral diseases," says Pedro Beltrao, Group Leader at EMBL-EBI. "After more than a century of relatively harmless coronaviruses, in the last 20 years we've had three coronaviruses that have been deadly. By looking across the species, we have the capability to predict pan-coronavirus therapeutics that may be effective in treating the current pandemic, which we believe will also offer promising therapeutics for a future coronavirus as well."

Another step to treat COVID-19

The researchers also performed real-world analysis on clinical data regarding COVID-19 patient outcomes. To do this, they identified molecules in human cells that could be targeted with FDA-approved therapeutics and looked to see what effect these drugs had on COVID-19 patients in the clinic. This analysis involved over 740 000 patients in the United States with known SARS-CoV-2 infection.

The data and analysis carried out in this study demonstrate how molecular information can be translated into real-world implications for the treatment of COVID-19. This study also showcases a collaborative approach that can be applied to study other infectious agents in the future.

"This far-reaching international study elucidates for the first time commonalities and, importantly, vulnerabilities, across coronaviruses, including our current challenge with the COVID-19 pandemic," says Nevan Krogan, Director of QBI and Senior Investigator at Gladstone Institutes. "In unique and rapid fashion, we were able to bridge biological and functional insights with clinical outcomes, providing an exemplary model of a differentiated way to conduct research into any disease, rapidly identify promising treatments and advance knowledge in the fields of both science and medicine. This body of work was only made possible through the collaborative efforts of senior scientific thought leaders and the teams of next-generation researchers at premier institutions across the globe."

Credit: 
European Molecular Biology Laboratory - European Bioinformatics Institute