Culture

Stretches of repeating DNA predispose to systemic sclerosis

image: Extension of GA repeats in the FLI1 gene is associated with low expression of FLI1 mRNA and susceptibility to systemic sclerosis. The molecular mechanism behind the association between extended repeat and low expression of FLI1 remains to be shown.

Image: 
University of Tsukuba

Tsukuba, Japan - Systemic sclerosis is an autoimmune disorder that is characterized by excess deposition of connective tissue in the skin, lungs, kidneys and vessels, resulting in lung, heart and kidney dysfunction. In a new study, researchers from the University of Tsukuba revealed that patients with long stretches of repeat DNA sequences, also called microsatellite repeat polymorphism, in the gene for Friend leukemia integration 1 transcription factor (FLI1) are more likely to develop systemic sclerosis.

Systemic sclerosis is an intractable disease, and as of now immunosuppressive therapies are one of the few options to limit its progression. To date, a number of genes have been identified as potential contributors to the development of systemic sclerosis through genome-wide association studies (GWAS), whereby genetic variants in different individuals are compared to see if they are associated with the disease. However, genes identified through GWAS are shared between various autoimmune diseases and therefore do not seem to directly account for the molecular mechanisms leading to the deposits of connective tissue in the pattern seen in systemic sclerosis.

"We wanted to specifically go after FLI1 that has been shown to be produced to a lesser extent in the lesional skin of systemic sclerosis patients. We thought that downregulation of FLI1 may be a trigger for systemic sclerosis," says corresponding author of the study Professor Naoyuki Tsuchiya. "Interestingly, the gene encoding for FLI1 contains a microsatellite region, and it is known that extended repeats of microsatellites result in reduced FLI1 expression. We hypothesized that patients with systemic sclerosis may also have these extended DNA repeats in the FLI1 gene."

To achieve their goal, the researchers collected DNA of 639 systemic sclerosis patients and 851 healthy patients and specifically looked at the length of repeats of the DNA bases GA (guanine adenine) that make the microsatellite region in the FLI1 gene. The researchers investigated the DNA to determine the number of GA repeats beyond which the likelihood to develop systemic sclerosis significantly increases, and found that this value is 22. On the basis of this finding, the researchers defined a FLI1 gene with more than 22 repeats as an L (long) allele and with fewer than 21 as an S (short) allele.

"Our results show an association between GA repeats over 22 in the FLI1 gene and systemic sclerosis," says lead author of the study Keita Yamashita. "We next wanted to have a closer look at the clinical characteristics of systemic sclerosis patients with FLI1 L alleles".

The researchers found that FLI1 L alleles were significantly increased in patients with a modified Rodnan total skin thickness score (mRSS) over 10 compared with those with a score under 10. The mRSS is a measure of skin thickness and is frequently used to quantify the extent of connective tissue deposition in the skin of systemic sclerosis patients. The researchers next found that FLI1 mRNA levels were decreased in systemic sclerosis patients compared with healthy controls, and further reduced in healthy controls with FLI1 L alleles compared with healthy controls with FLI1 S alleles, showing that long GA repeats may be disruptive to the production of FLI1.

"These are striking results that show how extended repeat alleles of FLI1 GA microsatellites may affect the expression of FLI1 and the development of systemic sclerosis. Our results provide a novel insight into the pathogenesis of systemic sclerosis, as well as into the relevance of microsatellite polymorphisms in human diseases," says Professor Tsuchiya.

Credit: 
University of Tsukuba

Novel approach improves graphene-based supercapacitors

image: An efficient pathway to improve performance of supercapacitors

Image: 
Dawei Su

Demand for integrated energy storage devices is growing rapidly as people rely more and more on portable and wireless electronics, and the global need grows for clean energy sources such as solar and wind energies.

This is creating an exponential need for advanced energy storage technologies - reliable and maintenance-free batteries and supercapacitors (SC) with high power density capability as storage devices. Supercapacitors are prominent candidates to meet this need due to their environmentally friendly and long cyclability characteristics.

Researchers from the Integrated Nano Systems Lab (INSys Lab), in the Centre for Clean Energy Technology, have been working on a pathway to improve the performance of supercapacitors, and meet that demand for increased storage capacity.

Dr Mojtaba Amjadipour and Professor Francesca Iacopi (School of Data and Electrical Engineering) and Dr Dawei Su (School of Mathematical and Physical Sciences) describe their cutting-edge work in the July 2020 issue of the journal Batteries and Supercaps. The prominence given to Graphitic-Based Solid-State Supercapacitors: Enabling Redox Reaction by In Situ Electrochemical Treatment - designated a Very Important Paper with front coverage placement - signifies just how innovative their research is in developing alternate ways to extend storage capacity.

Dr Iacopi said the multi-disciplinary approach within the team was beneficial in discovering what she says is a simple process.

"This research has originated from our curiosity of exploring the operation limits of the cells, leading us to unforeseen beneficial results. The control of this process would not have been possible without understanding the fundamental reasons for the observed improvement, using our team's complementary expertise."

Traditionally, supercapacitors are fabricated with liquid electrolytes, which cannot be miniaturised and can be prone to leakage, prompting research into gel-based and solid-state electrolytes. Tailoring these electrolytes in combination with carbon-based electrode materials such as graphene, graphene oxide, and carbon nanotubes is of paramount importance for an enhanced energy storage performance.

Graphene or graphitic carbon directly fabricated on silicon surfaces offers significant potential for on-chip supercapacitors that can be embedded into integrated systems. The research insights indicate a simple path to significantly enhance the performance of supercapacitors using gel-based electrolytes, which are key to the fabrication of quasi-solid-(gel) supercapacitors.

"This approach offers a new path to develop further miniaturized on-chip energy storage systems, which are compatible with silicon electronics and can support the power demand to operate integrated smart systems," Dr Iacopi said.

Credit: 
University of Technology Sydney

Cold-sensitive staphylococci reveal a weakness

image: Staphylococcus aureus (in yellow) magnified using an electron microscope.

Image: 
@ UNIGE

"Staphylococcus aureus" - also known as "golden staph" - has the ability to develop in highly variable environmental conditions (on the skin, in the nose, on sterile surfaces, and so forth). Its great adaptability depends especially on a protein (an RNA helicase) involved in the degradation of RNA messengers that have become useless. In their attempts to have a better understanding of how this helicase works, scientists from the University of Geneva (UNIGE) discovered that it contributes to another physiological process, without any apparent link to the first: the synthesis of the fatty acids that are the essential constituents of the bacterial membrane. This advance, to be published in the journal PLoS Genetics, offers an interesting insight since fatty acid synthesis is precisely one of the targets favoured by numerous laboratories to fight this pathogen that is difficult to treat due to its resistance to antibiotics.

Golden staph (Staphylococcus aureus) is an opportunistic pathogenic bacterium that is capable of adapting to highly variable environments. It can be found in the nostrils of 25 to 30% of the population, although this is generally not a problem. However, the bacterium can take advantage of a drop in immunity or a surgical operation to trigger a real infection. And the problem with golden staph is its ability to develop resistance to antibiotic drugs, which often makes it difficult - sometimes impossible - to treat.

"My laboratory studies a protein, RNA helicase, which plays an important role in golden staph's ability to adapt to very different environments," begins Patrick Linder, a professor in the Department of Microbiology and Molecular Medicine in UNIGE's Faculty of Medicine. "When the environment changes, the bacterium has to be able to synthesise new proteins that are more suitable and stop the production of others that are no longer useful. The helicase we're interested in - called CshA - is involved in the degradation of the RNA, those molecules derived from the DNA and used in protein synthesis."

Cold-sensitive bacteria

Oddly enough, when the helicase is absent (due, for example, to a genetic mutation), the researchers found that the cultured bacteria could no longer form colonies if the temperature dropped below a certain threshold (around 25°C).

The Geneva-based biologists undertook a series of experiments designed to improve our understanding of the link between golden staph's sensitivity to cold, the degradation of the RNA and the adaptation capacity. They discovered that the same helicase is probably also required in another physiological process, namely the synthesis of fatty acids, which are the constituents of bacterial membranes.

"Using cultured golden staph stripped of helicases, we succeeded in isolating 82 gene mutations (appearing spontaneously in many different bacteria), which meant that their holders regained the ability to form colonies at 25°C," continues Vanessa Khemici, a researcher in Patrick Linder's laboratory and the article's first author. "We identified almost all the affected genes, and no less than two thirds of them are involved in the fatty acid synthesis."

The findings also helped the researchers understand that the lack of the helicase has the effect of deregulating the fatty acid synthesis and decreasing the flexibility of the membrane when the temperature drops. This prevents the membrane from fulfilling its functions properly and the bacterium from growing. In a second step, each of the 82 mutations succeeded in its own way in restoring the initial balance by acting on the different genetic levers involved in fatty acid synthesis.

Scientific controversy

"A section of the scientific community supports the idea that a future treatment against staphylococcus will involve a drug capable of inhibiting fatty acid synthesis," notes Professor Linder, "but there is a controversy about it because some studies contradict this point of view."

The results of the Geneva scientists do not provide a clear-cut answer or make it possible to directly develop a drug against these bacteria. Nevertheless, they fit into this context and provide a better understanding of golden staph's fundamental mechanisms. The discovery of this unprecedented link between the fluidity of the membrane and adaptation to environmental change represents an important step in the fight against the bacterium. It is undoubtedly for these reasons that the journal decided to publish an overview in parallel with the article.

Credit: 
Université de Genève

Scientists led by NTU Singapore identify new catalysts for more efficient water splitting

image: NTU Assoc Prof Jason Xu Zhichuan and his team have discovered the parameters that determine the efficiency of a class of low-cost catalysts called spinel oxides - a discovery that breaks a bottleneck in the extraction of hydrogen from water through electrolysis, the process of splitting water with electricity. (L-R) NTU Assoc Prof Jason Xu Zhichuan and NTU research fellow Dr Sun Yuanmiao

Image: 
NTU Singapore

A team of scientists led by Nanyang Technological University, Singapore (NTU Singapore) have discovered the parameters that determine the efficiency of a class of low-cost catalysts called spinel oxides - a discovery that breaks a bottleneck in the extraction of hydrogen from water through electrolysis, the process of splitting water with electricity.

A major challenge of this process lies in the energy loss as the chemical reactions involved in water electrolysis take place, driving up the cost to produce hydrogen through this method. Catalysts are therefore necessary to speed up these chemical reactions.

Spinel oxides, which are typically made of cheap transition metals, have garnered interest in recent years as a stable, low-cost catalyst that could overcome this challenge, but the design of high-performing spinel oxides has been hampered by the lack of understanding of how they work.

Now, NTU Singapore's Associate Professor Jason Xu Zhichuan and his team have made two important advances. They have unravelled, at the atomic scale, how spinel oxides work to speed up water electrolysis. Primed with that new understanding, the team then used machine learning to select new spinel oxides with increased catalytic activity, making water electrolysis more efficient.

These findings bring the team a step closer to making water splitting a suitable approach for large-scale manufacture of hydrogen gas, which has been highlighted by the Energy Market Authority as one possible low-carbon alternative for reducing Singapore's carbon footprint as it targets to halve its peak greenhouse gas emissions by 2050. This is in line with global trends - the European Union, for instance, recently unveiled its "hydrogen strategy" as an important part of the solution to meet the 2050 climate neutrality goal of the European Green Deal.

Associate Professor Xu of the NTU School of Materials Sciences and Engineering said: "To improve the performance of spinel oxides, we need a deeper understanding of how they work as catalysts to make water electrolysis more efficient. Now, by identifying the parameters that make spinel oxides good catalysts for this process, we can create new, better spinel oxides based on these parameters, bringing us one step closer to a hydrogen-powered economy."

The findings were published in scientific journal Nature Catalysis in July.

A step closer to a hydrogen-fuelled economy

Extracting hydrogen from water electrolysis, when powered by renewable energy sources such as wind or solar energy, is an attractive approach to produce hydrogen fuel, which has the potential to replace fossil fuels used in power plants, transport, and the process of bunkering.

Hydrogen is also attractive as a viable alternative to traditional energy storage options such as lithium ion batteries, which gradually lose their charge over time.

The water electrolysis process takes place in an electrolyser, where two main chemical reactions take place as water is split: one results in hydrogen production, while the other leads to oxygen production, and the two gases are kept separate by a membrane.

Assoc Prof Xu, who is also part of NTU's Energy Research Institute, said the main bottleneck lies in the chemical reaction that leads to oxygen generation from the other side known as the oxygen revolution reaction.

He said: "The oxygen evolution reaction is critical to the efficiency of devices that split water to produce hydrogen fuel, but it is also a sluggish chemical reaction that lowers the overall energy conversion efficiency. This is why we need catalysts such as metal oxides to speed things up."

While precious metal oxides have proven to be state-of-the-art catalysts that reduce energy consumption and enhance energy conversion efficiency, their scarcity, high cost and poor durability have limited their application at large scale.

Spinel oxides, with their low cost and availability in abundance, could become a viable alternative if they were designed with the right parameters, such as the type of transition metal in the spinel oxide, to increase catalytic activity, said Assoc Prof Xu.

Based on key parameters that the team had identified, the team trained a machine learning model with a dataset of over 300 spinel oxides in order to screen and predict the efficiency of any spinel oxide catalyst in a matter of seconds.

Using this method, the team found that a new oxide comprising manganese and aluminium was predicted to show superior catalytic activity. This was validated experimentally.

Assoc Prof Xu said: "While the ability to design highly efficient catalysts greatly pushes forward the technique of water electrolysis in hydrogen production, there are two other major bottlenecks we have to look at before widespread adoption of this technique is possible. Firstly, we have to improve the membrane in such alkaline electrolysers to support long-term hydrogen production.

"When that's done, then we can work with our engineering colleagues to see how we can put all of these upgrades into an electrolyser that can function on an industrial level."

Credit: 
Nanyang Technological University

How a gooey slime helps bacteria survive

Tsukuba, Japan - Bacteria have the ability to adapt to their environment to survive the host's immune defense. One such survival strategy includes the formation of a biofilm that prevents the immune system or antibiotics from reaching the bacteria. In a new study, researchers from the University of Tsukuba revealed that modulations to biofilm structure as a result of temperature changes are regulated by the production of a novel extracellular protein called BsaA in the bacterium C. perfringens produces.

C. perfringens lives in various environments, soil and the intestines of animals, and can cause food poisoning, gas gangrene and antibiotics-associated diarrhea. It is anaerobic bacterium that is not able to grow outside a host due to the presence of oxygen. While it is common knowledge that it can turn into spores to evade environmental attacks, it was not until recently that C. perfringens was shown to also have the ability to form biofilms. In these biofilms, a community of C. perfringens bacteria cover themselves in a dense matrix of so-called extracellular polymeric substances (EPS)--which contain proteins, nucleic acids, and sugar molecules--thus protecting themselves from external hazards. To date, it has remained unclear how C. perfringens is using biofilms to survive in oxygen-rich environments.

"We have previously shown that temperature is an environmental cue that influences C. perfringens biofilm morphology," says corresponding author of the study Professor Nobuhiko Nomura. "Although at higher temperatures, such as 37°C, the bacteria attach to surfaces and pack densely in an adherent biofilm, at lower temperatures they build a thicker, pellicle-like biofilm. We wanted to know how they are able to modulate the structure of their biofilm in response to temperature changes."

To achieve their goal, the researchers constructed a library of 1,360 mutant (gene knockout) cells in C. perfringens to see which proteins are required to form a pellicle-like biofilm at 25°C. Throughout their screening, they noticed the presence of a new protein called BsaA that is produced inside the bacteria and transported to the exterior. Without BsaA, the bacteria formed either a fragile pellicle biofilm or an adherent biofilm only. The researchers then showed that multiple BsaA proteins assemble at a polymer outside the cells to enable the formation of a stable biofilm. When exposed to the antibiotic penicillin G or oxygen, C. perfringens lacking BsaA had a significantly decreased survival rate compared with normal C. perfringens.

"Our results show that BsaA is necessary for pellicle-like biofilm formation at 25°C and conferral of tolerance to antibiotics," says lead author of the study Professor Nozomu Obana. "We know that biofilms contain heterogeneous cell populations, which leads to multicellular behaviors. We therefore wanted to know whether cellular heterogeneity affects the production of BsaA and thus the formation of a pellicle-like biofilm".

The researchers found that the protein SipW controls the polymerization of BsaA to a biofilm, and used this to study biofilm formation. By constructing C. perfringens that produced a fluorescent protein when SipW is produced, thus allowing these cells to be tracked by fluorescent microscopy, the researchers were able to show that not all bacteria produced SipW. Additionally, they found that the population of SipW-producing bacteria started to drop significantly when the temperature was increased from 25°C to 37°C. Intriguingly, at 25°C, cells that did not produce SipW were located next to the surface the bacteria were sitting on, and were covered by SipW-producing cells. Heterogeneous production of SipW, and thus BsaA, might therefore ensure that those cells that have a higher tolerance to external hazards protect the bacterial subpopulation at risk.

"At 25°C, C. perfringens are more likely to be exposed to external stresses. Our results provide an explanation for how a community of C. perfringens ensures that it stays protected when the temperature changes. Our study aids understanding of biofilm properties and provides insights into the development of new antibacterial strategies," says Professor Nomura.

Credit: 
University of Tsukuba

The six strains of SARS-CoV-2

image: The most extensive study ever carried out on SARS-CoV-2 sequencing revealed six strains of the virus.

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Frontiers in Microbiology

The virus causing the COVID-19 pandemic, SARS-CoV-2, presents at least six strains. Despite its mutations, the virus shows little variability, and this is good news for the researchers working on a viable vaccine.

These are the results of the most extensive study ever carried out on SARS-CoV-2 sequencing. Researchers at the University of Bologna drew from the analysis of 48,635 coronavirus genomes, which were isolated by researchers in labs all over the world. This study was published in the journal Frontiers in Microbiology. It was then possible for researchers to map the spread and the mutations of the virus during its journey to all continents.

The first results are encouraging. The coronavirus presents little variability, approximately seven mutations per sample. Common influenza has a variability rate that is more than double.

"The SARS-CoV-2 coronavirus is presumably already optimized to affect human beings, and this explains its low evolutionary change", explains Federico Giorgi, a researcher at Unibo and coordinator of the study. "This means that the treatments we are developing, including a vaccine, might be effective against all the virus strains".

Currently, there are six strains of coronavirus. The original one is the L strain, that appeared in Wuhan in December 2019. Its first mutation - the S strain - appeared at the beginning of 2020, while, since mid-January 2020, we have had strains V and G. To date strain G is the most widespread: it mutated into strains GR and GH at the end of February 2020.

"Strain G and its related strains GR and GH are by far the most widespread, representing 74% of all gene sequences we analysed", says Giorgi. "They present four mutations, two of which are able to change the sequence of the RNA polymerase and Spike proteins of the virus. This characteristic probably facilitates the spread of the virus".

If we look at the coronavirus map, we can see that strains G and GR are the most frequent across Europe and Italy. According to the available data, GH strain seems close to non-existence in Italy, while it occurs more frequently in France and Germany. This seems to confirm the effectiveness of last months' containment methods.

In North America, the most widespread strain is GH, while in South America we find the GR strain more frequently. In Asia, where the Wuhan L strain initially appeared, the spread of strains G, GH and GR is increasing. These strains landed in Asia only at the beginning of March, more than a month after their spread in Europe.

Globally, strains G, GH and GR are constantly increasing. Strain S can be found in some restricted areas in the US and Spain. The L and V strains are gradually disappearing.

Besides these six main coronavirus strains, researchers identified some infrequent mutations, that, at the moment, are not worrying but should nevertheless be monitored.

"Rare genomic mutations are less than 1% of all sequenced genomes", confirms Giorgi. "However, it is fundamental that we study and analyse them so that we can identify their function and monitor their spread. All countries should contribute to the cause by giving access to data about the virus genome sequences".

Credit: 
Università di Bologna

New species of fungus sticking out of beetles named after the COVID-19 quarantine

image: Thalli of the newly described species Laboulbenia quarantenae, named after the COVID-19 quarantine period. The scale bar represents 0.1 mm.

Image: 
André De Kesel

A major comprehensive study on Herpomycetales and Laboulbeniales, two orders of unique ectoparasitic fungi associated with insects and other arthropods (class Laboulbeniomycetes) in Belgium and the Netherlands was published in the open-access, peer-reviewed scholarly journal MycoKeys.

Having surveyed arthropod fauna using pitfall traps and an illuminated white screen at night, and with the help of a network of entomologists, Dr. Danny Haelewaters (Purdue University, University of South Bohemia and Ghent University) and Dr. André De Kesel (Botanic Garden Meise) provide identification details about a total of 140 fungal species. The list includes nine species that are reported for the first time for either of the two countries and two newly described species.

Interestingly, one of the novel fungi was described during the 2020 global quarantine period, imposed to curb the COVID-19 pandemic. This prompted the researchers to dedicate the newly discovered species to this extraordinary time. In the annals of science, the species will be going by the name of Laboulbenia quarantenae.

Laboulbenia quarantenae grows externally on the body of ground beetles belonging to the species Bembidion biguttatum and is thus far only found at the Botanic Garden Meise in Belgium. This new fungus is considered to be very rare compared to Laboulbenia vulgaris, another, well-documented species that is more commonly found on the same host. So far, there has been no evidence that L. quarantenae parasitizes other host species.

Herpomycetales and Laboulbeniales--unlike common mushrooms--do not form branching thread-like hyphae, nor a mycelium. Rather, they grow a single three-dimensional thallus of a few thousand cells sticking out of the body of the host organism. While some species of Laboulbeniales, like Laboulbenia quarantenae, are superficially attached to their host, others are more invasive, such as Hesperomyces halyziae, the second fungus newly described in this study. These fungi produce a haustorium, which is a hyphal outgrowth used to penetrate the tissues of their arthropod hosts, so that they can reach to the primary body cavity and the circulatory fluid in there. By doing so, it is thought that the parasites can both increase surface area for nutrient uptake and tighten their grip on their host.

In their study, the scientists hypothesize that, because of their invasive nature, these haustorial parasites maintain close interactions with their hosts in a process referred to as an "evolutionary arms race". This means that whenever the host evolves a defence mechanism against the fungus, the parasite promptly evolves in its own turn, and adapts accordingly. Eventually, specialization leads to the evolution of new species.

The present study compiles all available data from Belgium and the Netherlands and serves as an appropriate starting point for an updated checklist of thallus-forming fungi in the class Laboulbeniomycetes found across Europe. Such a checklist is an ongoing project meant to summarize decades of research and will undoubtedly continue to uncover significant fungal diversity. The last update of this piece of knowledge dates back to 1991.

Credit: 
Pensoft Publishers

Autism spectrum disorder can be predicted from health checkups at 18 months

Research results

An early diagnosis of autism spectrum disorder, a type of developmental disorder was found to be effective from routine health checkups of infants at 18 months of age.

Overview

Health checkups are provided at no cost to all children at 18 months and 3 years of age in Japan. Doctors at Shinshu University School of Medicine designed a study to utilize the 18-month health checkup as an opportunity to screen for autism spectrum disorder (ASD), because early detection of ASD can lead to better prognosis for children with ASD.

Infants born between the year 2009 to 2012 in Okaya city, located in Nagano prefecture, participated in the study to investigate the incidence and risk factors of ASD organized by Shinshu University School of Medicine, Department of Child and Adolescent Developmental Psychiatry and Department of Psychiatry; Associate Professor Daimei Sasayama, Professor Hideo Honda, Professor Shinsuke Washizuka, and Professor Tetsuo Nomiyama of the Department of Preventative Medicine and Public Health.

1067 children, or 85% of the children born in Okaya city during the 3-year period received the 18-month health checkup. With the help of Shinano Medical and Welfare Center, 3.1% of the children examined were later diagnosed to have ASD by the time they became of school age (6 years old by April 1st). Many of these children were noted to have impaired motor skills and social communication skills at 18-months. The results of this study suggest that the medical examination that most children in Japan receive at 18 months can be an effective method to screen for ASD.

This study was published online July 21, 2020 in the Journal of Autism and Developmental Disorders, one of the most prestigious international autism journals.

Background

The proportion of people diagnosed with ASD has increased worldwide over the last two decades. A 2014 US survey reported a prevalence of 1.68% in 8 year-olds. One of the main reasons for the increase in prevalence in recent years is the improvement of screening accuracy.

Early detection and early intervention of ASD is important for improving the prognosis of children with ASD. However, it is considered difficult to detect ASD in children under the age of 2 using common screening tools used today. Okaya City strives to improve the accuracy of early detection of autism spectrum disorders during the 18-month health checkup and experienced public health nurses carefully screen each child. In addition, they have established a system in which children who are suspected of having ASD are referred to the Shinano Medical and Welfare Center for early diagnosis and support. This study investigated the cumulative incidence of autism spectrum disorders in Okaya city, where an early diagnosis system is in place. In addition, the team examined the features that were found at age 18-months in children who were later diagnosed with ASD.

Research methods and results

The research subjects were 1,067 children who were born between April 2, 2009 to April 1, 2012, who received the 18-month old health checkup in Okaya City. A survey of the medical information provided by the Shinano Medical and Welfare Center found that 33 of the 1,067 subjects (22 boys, 11 girls) has been diagnosed with autism spectrum disorder before entering elementary school (cumulative incidence 3.1% [4.3% of boys, 2.0% of girls]). A comparison of 33 children with ASD and 1,034 children without autism revealed that children diagnosed with ASD tended to have lower fine and gross motor skills and social communication skills at the time of the 18-month health checkup.

Implications/ Future Plans

The cumulative incidence reported in this study was the highest incidence of medically diagnosed ASD in the general population reported compared to previous studies. These results suggest that a diagnosis with high sensitivity would be possible by establishing a careful screening system at the 18-month health checkups. In addition, children with ASD have been shown to have underdeveloped fine and gross motor skills and social communication abilities at the age of 18-months, which are factors that predict ASD at an early stage. It is anticipated that the continuation of research will lead to the development of an early diagnosis system for autism spectrum disorders that utilizes infant health checkups.

Paper title and author

Title: Brief Report: Cumulative Incidence of Autism Spectrum Disorder

Before School Entry in a Thoroughly Screened Population

Author: Daimei Sasayama· Tetsuya Kudo · Wakako Kaneko · Rie Kuge · Noriaki Koizumi · Tetsuo Nomiyama · Shinsuke Washizuka · Hideo Honda

Journal: Journal of Autism and Developmental Disorders (online publication)

Credit: 
Shinshu University

LSU Health study suggests snap diagnoses may be more accurate

New Orleans, LA - A pilot study conducted by a team of LSU Health New Orleans School of Medicine faculty has found that Snapchat is an effective tool to teach residents emergency radiology. The results are published online in Emergency Radiology available here.
The team compared image analysis and interpretation by radiology residents using Snapchat on smartphones with conventional analysis on a single screen in the resident conference room.

"All cases used were diagnoses considered to require emergent, non-routine communication on the order of minutes to the ordering health care provider," notes Bradley Spieler, MD, Vice Chairman of Research in the Department of Radiology at LSU Health New Orleans School of Medicine. "As such, these types of diagnoses demand prompt imaging recognition as they are considered critical findings which could result in death or significant illness if not acted upon expeditiously."

The team chose Snapchat, a social media app allowing communication via video and digital images with text messaging functionality, not only because of its popularity with young adults, but most importantly because unlike other image based social media platforms, Snapchat allows for the timing of image visibility by users. The ability to specify the length of time an image is visible to a user (or trainee in this scenario) in rendering an image-based diagnosis creates an intriguing potential for innovation in radiologic curricula, particularly as it relates to assigning a metric to diagnostic performance.

Over a four-week period, LSU Health New Orleans radiology residents, who are all millennials, were shown five emergent radiologic cases using Snapchat and five cases of similar content and duration on a classroom projector. All images depicted diagnoses requiring immediate communication to ordering physicians. Performance was scored 0-2 (0?=?complete miss, 1?=?major finding, but missed the diagnosis, 2?=?correct diagnosis) by two attending radiologists in consensus.

"All residents performed better on Snapchat each week," says Dr. Spieler, who is also an Associate Professor of Radiology, Internal Medicine, Urology, & Cell Biology and Anatomy at LSU Health New Orleans. "Their accuracy rate was higher using Snapchat than a traditional classroom screen."

The authors maintain that new challenges presented by the COVID-19 pandemic underscore the need to alter curricular landscapes through innovative teaching methods and connectivity with students and residents. Smartphones and mobile devices are used daily in hospitals in patient care. The comfort level with this technology is high, which simplifies its integration into graduate medical education. Radiology is a specialty particularly suited to visual social media platforms, and it is only natural that the technologically bound craft of radiology continues to push this medium in innovative ways.

Spieler says, "We believe that the results from this pilot study could facilitate a promising and novel training method in enhancing recognition of imaging diagnoses, particularly those of life-threatening nature, which could be applied to the evolving landscape of distance learning."

Other LSU Health New Orleans authors include Drs. Dane Mackey, Caitlin Henry, Raman Danrad, Carl Sabottke, Claude Pirtle, and Eric Wallace in Diagnostic Radiology; and Dr. Jason Mussell in Cell Biology and Anatomy. Dr. Catherine Batte in the Department of Physics & Astronomy at Louisiana State University also contributed.

The authors conclude, "Our hope is that this investigation can aid in the promotion of active learning and lecture participation as well as to explore metrics for gauging diagnostic performance and pattern recognition in image-based curricula both within the classroom and in remote teaching formats. A larger sample size and more intricate study designs, for example, with the adjunct of eye tracking, may support the burgeoning role that handheld devices and imaged-based social media applications like Snapchat can play in learning at all levels of education especially in the context emergency radiology."

Credit: 
Louisiana State University Health Sciences Center

Evaluating the effectiveness of travel bans

With the reopening of flights during the summer holiday season in Europe, many countries have started to see an increase in COVID-19 infections. A new IIASA-led study sheds light on how COVID-19 spreads regionally and between countries, as well as on how effective governmental measures to curb the spread of the pandemic have been to date.

The current COVID-19 pandemic has prompted countries around the world to institute travel bans restricting the influx of visitors from especially countries where the spread of the virus is still rampant. Such restrictions, as well as other measures put in place by governments to curb the spread of COVID-19, have been heavily criticized in both political and public debate, prompting many to wonder how effective current measures aimed at reducing the spread of the pandemic really are. To address this uncertainty, IIASA researchers examined how the virus is spread regionally as well as between countries, and how this develops over time. The study's surprising results have been published in Letters in Spatial and Resource Sciences.

According to the authors, the majority of studies about transmission of COVID-19 tend to focus on specific countries. This study however, explored a much wider cross-section of countries and used approaches more commonly applied to estimate regional transmission of economic quantities (such as GDP or trade). The main questions that the researchers wanted to address were, on the one hand, whether governmental measures have actively been reducing the cross-border transmission of COVID-19 cases and, on the other hand, which channels were the main sources of transmission across national borders.

"Back in January this year, the virus was often seen as a Chinese and later an Italian problem. Due to the rapid spread of COVID-19 across the globe, however, almost all Western countries reacted by employing measures to contain or delay the spread of the virus," explains study lead author Tamás Krisztin, a researcher in the IIASA Ecosystems Services and Management Program. "It is important to model daily infection counts across countries to assess the effectiveness of government measures such as border closures and flight suspensions, and also to estimate scenarios of what the infection rate would look like if such measures were not taken."

The results indicate that cross-country transmission processes, specifically via international flight connections, played a particularly important role in the early stages of the virus' spread and that the shutdown of international airports and border closures were indeed important policies to prevent further spillovers across countries. It appears that governments, who took early action to reduce cross-border air passenger traffic, did in fact do the right thing to prevent the spread of infection. The research also supports anecdotal evidence that countries that delayed closing their borders to air traffic have higher infection rates.

Also interesting to note is the fact that the spread between countries could mostly be explained by international flight connections between them, rather than shared borders (land-travel transmission). The researchers point out that this could also explain why Austria was relatively more affected by the virus than, for instance, neighboring countries in Eastern Europe, even though they share land borders with Austria.

"In the face of decreasing public appetite for travel restrictions, and understandable concern over the economic consequences of drastic lockdown measures, we want to support and strengthen the decisions taken by European and most other governments in this regard. The policies they introduced appear to have played a particular role in reducing COVID-19 cases, flattening the curve, relieving stress on the healthcare system and, ultimately, saving lives," says Krisztin.

The researchers caution that as governments reopen cross-border air traffic, they should carefully evaluate where they allow flights to, and which regions they accept flights from. The scale of this traffic should also be carefully calibrated and continually monitored. The study clearly demonstrates that cross-border air traffic is a very important channel for spread of COVID-19, and as opposed to land travel where the spread is geographically limited, air traffic allows the virus to jump countries and continents in a very short time.

Credit: 
International Institute for Applied Systems Analysis

Diverse amyloid structures and dynamics revealed by high-speed atomic force microscopy

image: High-speed atomic force microscopy enables visualizing and analyzing fibril formation of variants of a single protein.

Image: 
Kanazawa University

In the human body, proteins sometimes occur in fibrillar aggregates called amyloids. Although certain amyloids are known to have a biological function, amyloid formation is often associated with pathologies, including Alzheimer's and Parkinson's diseases. Understanding how exactly amyloid fibrils form is crucial for gaining insights into the development of such diseases and for advancing with treatment approaches. Now, Takahiro Watanabe-Nakayama from Kanazawa University, Kenjiro Ono from Showa University, and colleagues have investigated the formation process of particular amyloid fibrils using a technique enabling visualization of growth over time. The scientists specifically looked at the effect of cross-seeding ('mixing') different proteins forming aggregates, and found variations in elongation rates and the structures of the fibrils.

The researchers studied alpha-synuclein, a protein abundant in the human brain. They looked at what happened when letting wild-type alpha-synuclein molecules -- the natural, most abundant variant -- form aggregates, and also how aggregation is different when introducing (cross-seeding) mutant variants associated with Parkinson's disease. In addition, the scientists examined the influence of the pH level of the microenvironment in which fibril growth takes place.

By means of high-speed atomic-force microscopy (HS-AFM), Watanabe-Nakayama, Ono and colleagues could record fibril aggregation at nanometer resolution and high video rate for various cases. First, the scientists looked at the growth of single variant types (self-seeding). They found that mutants produced more aggregates, or that they aggregated faster at neutral pH than the wild-type variants. Another observation was that elongation was faster at lower pH (5.8, i.e. acidic) than at higher pH (7.4, i.e. basic).

For cross-seeding, different scenarios can occur. Fibril growth can be accelerated or slowed down, or even stopped. The morphology of the original seed can be preserved, but it also happens that the structure of the resulting fibril is different -- typical structural forms are 'straight' or 'spiral'. The researchers checked that fibril structure and dynamics as observed with HS-AFM correspond to the processes in solution by means of fluorescence experiments; similar conclusions were obtained.

The findings of Watanabe-Nakayama, Ono and colleagues are relevant for better understanding amyloid-related diseases. Quoting the researchers: "Cross-seeding combined with variations in elongation rates has the effect of increasing the structural diversity of the resulting assemblies. This diversity may be reflected in distinct neurotoxic effects for various [protein] assemblies."

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Kanazawa University

Children's National Hospital case report sounds the alarm for antibiotic resistance

WASHINGTON-(August, 3, 2020)- A recent meningitis case treated at Children's National Hospital raises serious concerns about a rise in antibiotic resistance in the common bacterium that caused it, researchers from the hospital write in a case report. Their findings, published online August 3 in the Journal of the Pediatric Infectious Disease Society, could change laboratory and clinical practice across the U.S. and potentially around the globe.

Neisseria meningitidis is the leading cause of bacterial meningitis in adolescents and an important cause of disease in younger children as well, say case report authors Gillian Taormina,D.O., a third year fellow in Pediatric Infectious Diseases at Children's National, who was on service for this recent case, and Joseph Campos, Ph.D., D(ABMM), FAAM, director of the Microbiology Laboratory and the Infectious Diseases Molecular Diagnostics Laboratory at Children's National. As standard clinical practice in the U.S., they explain, patients who are thought to have this infection are typically treated first with the broad spectrum antibiotic ceftriaxone while they wait for a microbiology lab to identify the causative organism from blood or cerebrospinal fluid samples. Once the organism is identified as N meningitidis, patients are typically treated with penicillin or ampicillin, antibiotics with a narrower spectrum of activity that's less likely to lead to ceftriaxone resistance. Family members and other close contacts are often prophylactically treated with an antibiotic called ciprofloxacin.

Because N. meningitidis has historically been sensitive to these antibiotics, most laboratories do not perform tests to confirm drug susceptibility, Dr. Campos says. But the protocol at Children's National is to screen these isolates for penicillin and ampicillin resistance with a rapid 5-minute test. The isolate from Dr. Taormina's five-month-old patient -- a previously healthy infant from Maryland who came to the Children's National emergency room after six days of fever and congestion -- yielded surprising results: N. meningitidis grown from the patient's blood was positive for beta-lactamase, an enzyme that destroys the active component in the family of antibiotics that includes penicillin and ampicillin. This isolate was also found resistant to ciprofloxacin.

"The lab used a rapid test, and after just a few minutes, it was positive," Dr. Campos says. "We did it again to make sure it was accurate, and the results were reproducible. That's when we knew we needed to share this finding with the public health authorities."

Dr. Campos, Dr. Taormina and their colleagues sent samples of the antibiotic-resistant bacteria first to the Washington, D.C. Public Health Laboratory and the Maryland Department of Health, and later to the Centers for Disease Control and Prevention (CDC). When the CDC asked other state laboratories to send their own N. meningitidis samples to be tested, 33 were positive for beta-lactamase. And like the bacterium isolated from Dr. Taormina's patient, 11 of these were also resistant to ciprofloxacin.

"These bacteria wouldn't have been susceptible to the common antibiotics that we would normally use for this infection," Dr. Taormina says, "so it's entirely possible that the infections caused by these bacteria could have been treated inappropriately if doctors used the standard protocol."

Dr. Taormina says that her patient cleared his infection after staying on ceftriaxone, the original antibiotic he'd been prescribed, for the recommended seven days. His six family members and close contacts were prophylactically treated with rifampin instead of ciprofloxacin.

Although this case had a positive outcome, Dr. Campos says it raises the alarm for other N. meningitidis infections in the U.S., where antibiotic resistance is a growing concern. The danger is even higher in other countries, where the vaccine that children in the U.S. commonly receive for N. meningitidis at age 11 isn't available.

In the meantime, Drs. Taormina and Campos say their case highlights the need for the appropriate use of antibiotics, known as antibiotic stewardship, which is only possible with close partnerships between infectious disease doctors and microbiology laboratories.

"Our lab and the infectious diseases service at Children's National interact every day on cases like this to make sure we're doing the best job we can in diagnosing and managing infections," says Dr. Campos. "We're a team."

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Children's National Hospital

Boycotts or buycotts? The role of corporate activism

Researchers from Texas Christian University, University of Arizona, University of Oregon, and Portland State University published a new paper in the Journal of Marketing that examines the effect of corporate activism on financial and other types of performance to empower managers with insights they can use to chart their company's course in today's marketplace.

The study, forthcoming in the Journal of Marketing, is titled "Corporate Sociopolitical Activism and Firm Value" and is authored by Yashoda Bhagwat, Nooshin L. Warren, Joshua T. Beck, George F. Watson IV.

In 2014, a group of concerned mothers demanded that Chipotle prohibit guns in its restaurants. The company agreed and uproar ensued among a divided customer base as strong opinions opposing and favoring the policy translated into boycotts and buycotts. Chipotle is not alone in its controversy. Other examples include when Nike famously took a stand in support of Black Lives Matter, Delta cut ties with the NRA, Target publicly supported transgender rights, Amazon stopped selling confederate flags, and J.C. Penney supported LGBTQ+ families. Corporations have historically avoided contentious issues, but many are now responding to growing expectations that they become advocates.

These activities are called Corporate Sociopolitical Activism (CSA), defined as a firm's public demonstration (statements and/or actions) of support for--or opposition to--one side of a partisan sociopolitical issue. CSA reflects a shift. For decades, corporations have strived to be socially responsible (known as "CSR"), which involves broadly favored activities such as donating to charity or limiting pollution. Also, firms have lobbied to change laws in ways that favor their operations (known as corporate political activity [CPA]). Now some firms are going beyond these traditional, performance-enhancing activities to engage in CSA with unknown outcomes.

The researchers investigate how customer and investor responses to CSA affect firm performance. Bhagwat explains that "We argue that CSA publicly signals a firm's sociopolitical values and increases uncertainty among investors for at least two reasons. First, CSA may deviate from the political values of key stakeholders--customers, employees, and state government legislators. Second, CSA signals a shift in a firm's strategic commitments. Firms focusing more on sociopolitical issues may divert resources (money, time, attention) from other more profit-oriented activities." Thus, CSA has a negative effect overall on a firm's stock return. However, the effect of CSA varies highly and can even be positive.

To better understand the range of CSA outcomes, the study examines several contingency factors. First, it tested the extent to which CSA deviates from the political values of its stakeholders. Results indicate that highly misaligned CSA that deviates from the values of customers, employees, and state lawmakers results in a 2% stock decline, on average. Alternatively, highly aligned CSA can increase stock returns by nearly 1%, on average.

Second, it examined how the implementation of CSA signals a firm's commitment to activism. Warren says that "The more strategically committed a firm seems to be, the more uncertain investors become. CSA that takes the form of an action (vs. a statement), is delivered by the CEO (vs. another executive), is motivated purely on moral terms (vs. rationalized as being good for business), or is conducted alone (vs. in a coalition with multiple other firms) signals stronger commitment and, ultimately, a more negative impact on a firm's near-term stock price."

Importantly, the study also examines the impact of CSA on next-quarter and next-year sales growth. Findings are generally consistent with the stock return results and demonstrate the high potential of CSA. When CSA is aligned across stakeholders, it can result in an 8% increase in next-quarter sales growth and a 12% increase in next-year sales growth. This is presumably because well-aligned CSA works to strengthen relationships with customers, employees, and state lawmakers who fundamentally agree with the firm's stance.

The researchers advise managers navigating these unchartered waters to: (1) pick CSA they feel confident supporting and that aligns with the values of key stakeholders; (2) prepare for a short-term stock drop, realizing that activism has the potential to hurt or enhance stock price and sales growth; and (3) persuade stakeholders that CSA serves the interests of society and the company because customers will reward CSA they believe in.

Customers should be aware that their values matter and play a key role in whether activism is successful for firms. Investors should recognize sociopolitical activism as a new firm activity and that while it may risk backlash, it may also lead to tangible positive financial outcomes, particularly when aligned with customers.

Credit: 
American Marketing Association

Is less more? How consumers view sustainability claims

Researchers from City University of Hong Kong, Hong Kong Baptist University, and The Chinese University of Hong Kong published a new paper in the Journal of Marketing that offers consumer insights to guide marketing teams' communication of products' negatively framed attributes.

The study forthcoming in the Journal of Marketing is titled "When Less is More: How Mindset Influences Consumers' Responses to Products with Reduced Negative Attributes" and is authored by Vincent Chi Wong, Lei Su, and Howard Pong-Yuen Lam.

As companies embrace sustainability and circular economy concepts, they are transforming products and services to reduce negative impacts. By so doing, they can help preserve the environment for future generations, burnish their corporate social responsibility credentials, and, ideally, drive sales with values-based consumers. But is it true that sustainability claims increase sales?

The study challenges this common intuition and finds that a marketing claim of reducing negative product properties may be interpreted by consumers in one of two ways: 1) view the claim as improving the product relative to its previous state; or 2) draw attention to a negative product feature that might otherwise have been overlooked. Moreover, whether such claims have positive or negative influence depends on whether consumers interpret such claims through an incremental or entity mindset. Consumers with an incremental mindset (i.e., the tendency to think of attributes as malleable) take a trend-based view of a reduction in negative attributes, which results in improved product evaluations. In contrast, consumers with an entity mindset (i.e., attributes are unlikely to change) view these claims negatively.

The researchers first manipulated consumers' mindsets by exposing them to marketing materials such as advertising slogans, promotional direct mail, and spokespersons' quotes. Results show that activating consumers' incremental (vs. entity) mindset leads to more favorable evaluations for luncheon meat with sodium nitrite reduced by 30%, for frozen mussels with reduced microplastic content, and for antidiabetic drugs with reduced side effects. In other studies, the researchers measured consumers' chronic incremental and entity mindsets and show that those with a dominant incremental (vs. entity) mindset preferred stereo speakers with 50% less non-recyclable materials, bottled water with plastic materials reduced by 35%, and yogurt with 50% reduced sugar. Ironically, communicating a reduced negative attribute leads to poorer sales compared to no communication for consumers with an entity mindset.

The findings have managerial marketing implications. Wong explains, "Our research provides new techniques in marketers' toolbox to activate more easily consumers' incremental versus entity mindsets as a controllable variable. In addition, companies intuitively expect that promoting a reduction in negative attributes should benefit sales as opposed to doing nothing. Our findings imply that communicating a reduced negative attribute might have unintended consequences if consumers approach it with the wrong mindset." Accordingly, marketers should estimate the potential risks of such communications and carry out such communication strategically (along with properly activating consumers' mindset).

Su adds that, "Marketers may also strategically induce these mindsets to fight against competitors." To entice consumers from a competitor's product that claims a reduction of a negative attribute, marketers may activate an entity mindset using advertising slogans (e.g., De Beers' "A diamond is forever"). Moreover, slogans for significant social events can also temporarily prime different mindsets (e.g., Barack Obama's "Change we can believe in" likely activated an incremental mindset). Marketers can strategically leverage such social events as opportunities to promote products containing reduced negative attributes. "Importantly, individuals in Western countries (e.g., Americans) typically hold entity beliefs whereas those in Eastern countries (e.g., Chinese) typically hold incremental beliefs by default. Thus, promotion strategies for products with reduced negative attributes need to be customized across cultures," says Lam. Similarly, consumers' incremental versus entity mindset can be traced to demographic, geographic, or political ideology information. Marketers need to consider these factors when promoting products with a reduced negative attribute.

Credit: 
American Marketing Association

Food menu fit for pandemic times

image: Lead researcher Associate Professor Mehta, from the Caring Futures Institute at Flinders University, South Australia.

Image: 
Flinders University

In the midst of a global pandemic, eating well in a sustainable way is more important now than ever, Flinders University experts say.

'Eating local' and growing your own fruit and vegetables can save money, provide families and local producers with vital income - and also improve health and immunity.

“The COVID-19 pandemic provides many good reasons to eat in healthier and more sustainable ways,” says Flinders University researcher Associate Professor Kaye Mehta.

“Gardening or being part of a community gardening or local food swap group lifts social connection, reduces anxiety and stress, and improves mental health by nurturing plants out in the fresh air.”

In a new study, the researchers warn the Australian diet is not sustainable, with high rates of eating meat, excessive packaging and food waste and unhealthy consumption levels.

But how much time do people spend weighing up food decisions for their nutritional content, environmental sustainability and fairness, ask Flinders University nutrition and public health experts in a new paper in the Health Promotion Journal of Australia.

“At the supermarket and when you eat out, do you investigate where the food comes from? In an ideal world, food supply would not only be healthy but also be environmentally and socially sustainable,” Associate Professor Mehta says.

“Our dietary choices are made within a complex, powerful and unsustainable food system which contributes to rising problems of food insecurity, malnutrition, chronic disease, climate change, loss of biodiversity, and unfair food trade practices,” she says in the new study of food literacy awareness at Flinders University.

The researchers put these questions to the test by running a two-week online course examining aspects of the food system, including:

The links between food production and greenhouse gas emissions

The environmental effects of ‘food miles', or distance travelled by the produce

Power, profits and fair prices for farmers

The association between the industrial food system and current public health nutrition problems, and more.

The 47 participants of the online course – all staff and students of Flinders University – found their understanding of the food system and their attitudes towards food purchases changed to consider social and environmental sustainability, as well as health.

“Food choices that help the environment will also be healthier because people will eat more locally produced vegetables and fruits, less meat and less processed foods,” says dietitian-nutritionist Associate Professor Mehta, from the Flinders University Caring Futures Institute.

The study – the culmination of almost a decade of research into ‘food literacy’ and the effects of our food system – shows how much more can be done to improve our food supply and personal food decisions so that every bite we take considers the food’s origins and cumulative impact on the planet.

Lead researcher Associate Professor Mehta, from the Caring Futures Institute at Flinders University, says “food system literacy has not been a focus of food and nutrition

Education, in spite of growing public interest in sustainable eating”.

“Food system literacy is an opportunity for people to make better food choices that are good for their health as well as the environment and farmers.”

Credit: 
Flinders University