Culture

The most comprehensive study of the family tree for legumes, the plant family that includes beans, soybeans, peanuts, and many other economically important crop plants, reveals a history of whole-genome duplications. The study also helps to uncover the evolution of genes involved in nitrogen fixation--a key trait likely important in the evolutionary spread and diversification of legumes and vital for their use as "green manure" in agriculture. To reconstruct the family tree, researchers compared the DNA sequence of more than 1500 genes from 463 different legume species, including 391 newly sequenced species, that span the diversity of this large plant family.

A paper describing the study, led by Penn State Professor of Biology Hong Ma, appears in the May 2021 issue of the journal Molecular Plant.

"Legumes make up the third largest family of flowering plants and are incredibly diverse--ranging from tiny herbs to giant trees," said Ma, who is the Huck Distinguished Research Professor of Plant Molecular Biology at Penn State. "They are essential food crops for both humans and livestock, can be used as lumber, and have many other uses. Maybe most importantly, they can 'fix' nitrogen--extracting the vital nutrient from the atmosphere and storing it in nodules on their roots in a symbiotic relationship with soil bacteria--making them important as green manure to improve soil health."

There are over 19,000 species in the legume family divided into six subfamilies and then further divided into narrower and narrower groupings based on their evolutionary relationships. There are 765 genera--the grouping one level above species--of which the team sampled members of 333. To build the family tree, the team analyzed gene sequences from the transcriptomes--the portion of the genome that is expressed as genes--of most of the 463 species and a small number of shallowly sequenced whole genomes from across legume diversity.

"This is the largest study of this kind for a single plant family," said Ma. "We went to great lengths to sample as many species as we could to get a broad representation of the legume family, but it is often difficult to get well-preserved specimens that we can extract DNA or RNA from, especially for species found in remote locations. Having this broad representation of species allowed us to build the most detailed nuclear-gene family tree for legumes to date."

In addition to helping researchers understand the evolution and diversification of legumes, the new legume family tree helps to clarify the relationship between crop plants and their wild relatives. Although the close relatives of important agricultural crops are often known, studying more distant wild cousins could reveal traits that could be exploited to help plants thrive in changing environments and resist diseases or insect pests.

Across the legume family tree, the research team identified strong evidence for 28 separate whole-genome duplication events. Whole-genome duplications, evolutionary events that result in complete duplication of the entire genome, are fairly common among flowering plants and are thought to allow for functional innovation and evolutionary diversification. One of the duplication events that the team identified appears to have occurred in the ancestor of all members of the legume family.

"Because for most of the species in our study we used transcriptomes and do not have entire genome sequences, we consider these as 'proposed' genome duplication events," said Ma. "These kinds of studies are kind of like solving a mystery. If you only have one or a few witnesses it might be difficult to convince a jury of your evidence, but if you have a hundred witnesses who have different perspectives and they all point to the same thing it becomes difficult to dismiss that evidence. In our case, the different species are like our witnesses. The size of our study allowed us to identify events that we might otherwise have dismissed."

The two largest subfamilies account for over 17,000 legume species and include all of the species with the ability to fix nitrogen. Nitrogen is an important plant nutrient--most commercial fertilizers contain a mix of nitrogen, phosphorus and potassium--so the symbiotic relationship between some legumes and the microorganisms that allow them to assimilate nitrogen from the atmosphere using root nodules has spurred their success by allowing them to colonize areas with less fertile soil. The research team also identified clues to the evolution of the genes responsible for this important trait.

"Our data support the idea that nodulation and nitrogen fixation originated a single time early in the history of legumes and other related nitrogen-fixing plants and the whole-genome duplication event at the origin of legumes might have been crucial for the evolution of this process," said Ma. "In addition to this duplication event, we are also able to see gene loss in plants that do not have the ability to nodulate, and evolutionary changes in genes that contributed to their role in nodulation."

Are penalty shots a soccer player's dream or nightmare? What should be an easy shot can become a mammoth task when the hopes and fears of an entire nation rest on a player's shoulders, leading them to choke under pressure. Understanding the brain activity behind choking is the driving force behind a new study in open-access journal Frontiers in Computer Science. The study is the first to measure brain activity during penalty shots in a soccer pitch environment. It finds that people who choked activated areas of the brain involved in long-term thinking, suggesting that they were overthinking the consequences of missing the shot.

Penalty shootouts hold a special fear for many soccer fans. For instance, the English team has suffered some infamous misses over the years and their record at the penalty spot is fairly bleak. Remember Beckham's slip on the penalty spot against Portugal in the 2004 European Cup? He certainly does. Penalties can go either way, which makes them exciting to watch, but they raise some questions about performance under pressure.

"How can it be that football players with a near perfect control over the ball (they can very precisely kick a ball over more than 50 meters) fail to score a penalty kick from only 11 meters?" asks coauthor Max Slutter, an MSc student at the faculty of electrical engineering, mathematics and computer science at the University of Twente, the Netherlands. "Obviously, huge psychological pressure plays a role, but why does this pressure cause a missed penalty? We tried to answer this by measuring the brain activity of football players during the physical execution of a penalty kick."

Slutter and colleagues recruited 22 volunteers to kick penalties and measured their brain activity using a technique called functional near-infrared spectroscopy (fNIRS). fNIRS involves wearing a headset, and can measure brain activity on the move. The study is the first to investigate the neuroscience behind choking under realistic conditions outside a laboratory.

The volunteers attempted to score penalties under different pressure conditions: with an open goal, against a friendly goalkeeper, and in a high-pressure situation where the goalkeeper attempted to distract them and there was a prize at stake.

"We found that players who were able to perform under pressure activated task-relevant areas of the brain," explained Dr Nattapong Thammasan, of the University of Twente. "For example, increased activation of the motor cortex was related to performing under pressure. This seems logical, as movement is one of the most important elements when taking a penalty."

For players who tended to experience more anxiety and miss penalties, another area of the brain was more active - the pre-frontal cortex. This brain region is involved in long-term thinking, suggesting that such players were thinking about the consequences of missing the shot, which impaired their performance.

Strikingly, the researchers believe that the fNIRS technology could assist players to perform better under pressure by letting them know how their brains are behaving. They hypothesize that players could train themselves to activate beneficial brain regions in high-pressure situations.

Excitingly, the technique could also be beneficial for other professions where performance under high pressure is important, such as brain surgery. It may be too late for Beckham, but next-generation brain surgeons could be on the way.

Systemic inequalities mean that low-income households in London are more likely to be exposed to higher levels of indoor air pollution, according to a report by UCL researchers.

The biggest factors are the quality of housing and the characteristics of the surrounding environment, taking location and levels of outdoor air pollution into account - factors beyond occupants' control.

Air pollution exposure is the greatest environmental health threat in the UK, with long-term exposures estimated to cause 28,000-36,000 premature deaths a year.

In the paper, published in Buildings and Cities, researchers used available data and models, assembling evidence to examine five factors explaining why lower socio-economic groups may be exposed to higher levels of indoor air pollution in their homes, focusing on London and the pollutants PM2.5, NOx and CO. These pollutants were selected as they are primarily produced by combustion processes, such as cooking or burning fuel, and are therefore found in most households.

The factors were: housing location and ambient outdoor levels of pollution; housing characteristics including ventilation properties and internal sources of pollution; occupant behaviours; time spent indoors; and underlying health conditions. London was the focus because housing there isn't typically representative of the rest of the country, with a higher proportion of renters and flats as dwellings.

The team used a systems approach highlighting interactions and links between factors to show how they lead to systemic exposure inequalities, with lower income households having limited opportunities to improve their indoor air quality.

Lead author, PhD candidate Lauren Ferguson, (UCL Energy Institute and UCL Institute for Environmental Design & Engineering) said: "This research highlights that exposure to indoor air pollution can lead to health inequalities depending on socio-economic status. Differences in housing quality and characteristics of the surrounding areas mean low-income households are likely to bear a disproportionate risk of elevated exposure to indoor air pollution.

"Poor quality housing can lead to a number of negative health effects and is therefore an area which should be targeted in order to address the growing health inequalities gap in the UK."

Air pollution exposure is associated with health problems such as respiratory and cardiovascular complications, birth defects, childhood asthma cases and sudden infant deaths. Long term exposure to particulate matter (PM) has been linked to adult depression, although this needs more research.

Low socio-economic status (SES) groups are more likely to live in higher density flats and smaller dwellings and areas of London with higher levels of air pollution.

Whilst high density dwellings often have lower ventilation levels which can prevent some outdoor air pollution from getting in, this is not sufficient to offset living in an area of high outdoor pollution. Dwellings with low levels of ventilation prevent indoor air pollution from activities including cooking and smoking from escaping, and are more vulnerable to local pollution from neighbours' cooking or smoking.

Levels of smoking are higher amongst low SES groups, with 25.5% of those in routine and manual occupations smoking regularly, compared with 15.7% in intermediate occupations and 10.2% in managerial and professional occupations. Low SES groups also report longer cooking durations, increasing exposure to pollution.

Low SES groups are more likely to spend less time outdoors, due to a variety of factors including higher levels of unemployment, fewer after-school clubs and little access to green spaces. This raises their susceptibility to developing health conditions from increased exposure to indoor air pollution.

They are at a higher risk of experiencing underlying health conditions, material deprivation and psychological stress, making them more susceptible to air pollution. Material deprivation includes lack of access to healthcare, poor diet - which is strongly linked to income class - and lack of physical activity, which is linked to spending more time indoors due to the factors mentioned above.

The paper builds on previous research in 2020 on how concentrations of indoor domestic air pollution may vary between SES groups. The researchers hope the findings will influence policy decisions regarding air pollution and housing in London, and call for action to improve housing quality, promote and support interventions to reduce exposure to outdoor air pollution and encourage behavioural change to minimise risk factors from smoking and spending large amounts of time indoors.

LUGANO, 7 May, 2021- Findings presented at today's EADV 2021 Spring Symposium suggest that an imbalance in gut microbiota (dysbiosis), could play a significant role in the progression of inflammatory skin disease, Hidradenitis Suppurativa (HS). HS is a painful, long-term skin condition, with a chronic and relapsing nature that significantly impacts patients' quality of life.

Researchers at Hacettepe University collected faecal samples from 15 patients with HS and 15 age and sex matched healthy individuals and analysed regions of the bacterial 16S rRNA gene to investigate differences in their gut microbiota. Researchers found that the relative abundance of three genera of bacteria (known collectively as Firmicutes), unclassified Clostridiales, unclassified Firmicutes and Fusicatenibacter in HS patients were significantly lower than that in controls (p = 0.005, p = 0.029, and p = 0.046, respectively). Reduced amounts of these bacteria are known to disrupt the regulatory balance within the gut and stimulate an inflammatory response.

The human gastrointestinal tract is inhabited with a wide variety of bacterial organisms, known collectively as the gut microbiome.1 Studies have increasingly demonstrated that the gut microbiome and skin are intrinsically connected, offering defence against pathogens in the environment. This relationship is known as the 'gut-skin axis' and has been linked to many inflammatory and autoimmune skin disorders, such as acne and psoriasis. This connection inspired the researchers to characterise the composition of HS patients' intestinal microbiome, hypothesising that imbalance may play a role in the high inflammatory burden of this condition. HS is a multifactorial disease caused by both genetic and environmental factors. Obesity and smoking can significantly exacerbate symptoms, and both of these have an impact on the gut microbiome.

Dr Neslihan Demirel Ogut, Usak University Training and Research Hospital explains, "Our research provides evidence the gut-skin axis is implicated in the progression of this chronic inflammatory skin disorder. While further evidence is required, our research suggests that dietary alteration and personalised probiotic supplementation might also be beneficial for HS patients, particularly since treatment options are limited for these individuals."

Gut microbiota plays a critical role in human health through development of the immune response, controlled by specific pathways and the products of metabolism, known as short-chain fatty acids (SCFA). Bacteria in the gut (such as Firmicutes) produce these SCFAs that ensure a balance between immune cells that stimulate or suppress an inflammatory response is maintained. Any disruption to this balance, as demonstrated by the reduced abundance of these organisms in the gut microbiome of HS patients, may induce an unwanted inflammatory response.

Additional research is required to further understand and explain the connections between the gut microbiota and excessive inflammatory state in HS patients. "As one of the preliminary studies investigating HS, this pioneering research lays the foundation for future research into the management of this debilitating condition. It is an exciting breakthrough in a topic currently at the forefront of scientific research," says Marie-Aleth Richard, EADV Board Member and Professor at the University Hospital of La Timone, Marseille.

PHILADELPHIA-- A gene called GAS2 plays a key role in normal hearing, and its absence causes severe hearing loss, according to a study led by researchers in the Perelman School of Medicine at the University of Pennsylvania.

The researchers, whose findings are published online today in Developmental Cell, discovered that the protein encoded by GAS2 is crucial for maintaining the structural stiffness of support cells in the inner ear that normally help amplify incoming sound waves. They showed that inner ear support cells lacking functional GAS2 lose their amplifier abilities, causing severe hearing impairment in mice. The researchers also identified people who have GAS2 mutations and severe hearing loss.

"Anatomists 150 years ago took pains to draw these support cells with the details of their unique internal structures, but it's only now, with this discovery about GAS2, that we understand the importance of those structures for normal hearing," said study senior author Douglas J. Epstein, PhD, professor of genetics at Penn Medicine.

Two to three of every 1,000 children in the United States are born with hearing loss in one or both ears. About half of these cases are genetic. Although hearing aids and cochlear implants often can help, these devices seldom restore hearing to normal.

One of the main focuses of the Epstein laboratory at Penn Medicine is the study of genes that control the development and function of the inner ear--genes that are often implicated in congenital hearing loss. The inner ear contains a complex, snail-shaped structure, the cochlea, that amplifies the vibrations from sound waves, transduces them into nerve signals, and sends those signals toward the auditory cortex of the brain.

Unraveling the role of Gas2 in hearing

A few years ago, Epstein's team discovered that Gas2, the mouse version of human GAS2, is switched on in embryos by another gene known to be critical for inner ear development. To determine Gas2's role in that development, the team developed a line of mice in which the gene had been knocked out of the genome and called them Gas2-knockout mice.

Alex Rohacek, PhD, a former graduate student in the Epstein lab, was puzzled to observe that the Gas2-knockout mice had inner ears with cells and structures that seemed quite normal. However, the animals, when tested, turned out to be severely hearing-impaired, with deficits at high sound frequencies of up to 50 decibels--equivalent to a loss of 99.999 percent of the normal acoustic energy.

Tingfang Chen, PhD, a postdoctoral fellow and co-first author on the study, determined that Gas2 is normally active within inner-ear support cells called pillar cells and Deiters' cells. In these cells, the protein encoded by the gene binds to flexible, tube-like structures called microtubules in a way that bundles and stabilizes them, effectively stiffening the cells.

With help from the collaborating team of Benjamin L. Prosser, PhD, assistant professor of Physiology at Penn Medicine and an expert on microtubules, the researchers discovered that when pillar cells and Deiters' cells lack Gas2, their microtubule bundles tend to come apart, dramatically reducing the stiffness of the cells.

That turns out to have dire implications for hearing. Within the inner ear, pillar cells and Dieters' cells help form the basic structure of the cochlea and serve as physical supports for cells called outer hair cells. The outer hair cells move in response to incoming acoustical vibrations--essentially to provide a crucial amplification of that sound energy. The experiments revealed that the pillar and Deiters' cells' loss of stiffness, due to the absence of Gas2, severely degrades the sound-amplifying properties of the outer hair cells they support.

"We observed that some of Deiters' cells in the Gas2-knockout mice even buckled under the tension of the rapid movements of the outer hair cells," Epstein said.

The experiments included sophisticated imaging of propagating sound waves in the inner ears of live Gas2-knockout and normal mice, conducted by collaborator John Oghalai, MD, chair and professor of otolaryngology-head and neck surgery at the Keck School of Medicine of USC, and his team.

GAS2 also causes human hearing loss

Curiously, the researchers could find no reports of GAS2-associated congenital hearing loss in the medical literature. Even when they canvassed colleagues around the world who run hearing-loss clinics, they came up empty-handed.

Then one day, Hannie Kremer, PhD, professor and chair of molecular otogenetics at Radboud University Medical Center in the Netherlands, emailed Epstein. She and her team had been studying a Somalian family in which four of the siblings had severe hearing loss from early life. The affected family members had no mutations in known hearing-loss genes--but each carried two mutant copies of GAS2.

The study therefore establishes GAS2 as a very probable new hearing loss gene in humans--the first one known to affect the mechanical properties of inner ear support cells.

The prevalence of hearing loss in people due to GAS2 mutations remains to be determined, but Epstein noted that this type of congenital hearing loss is nevertheless an attractive target for a future gene therapy.

"In many genetic hearing loss conditions, the affected cells are permanently damaged or die, but in this one, the affected cells are intact and conceivably could be restored to normal or near-normal by restoring GAS2 function," he said.

He added that such a gene therapy might be useful not only in more obvious cases of hearing loss in early childhood, but also in cases--perhaps more numerous--in which inherited mutations lead to a slower development of hearing loss in adulthood.

Researchers from University of Southern California, Bocconi University, and Vrije Universitei Amsterdam published a new paper in the Journal of Marketing that explains the six types of judgements consumers make when determining a product's authenticity and how marketers can use this insight to deliver more authentic offerings.

The study, forthcoming in the Journal of Marketing, is titled "The Concept of Authenticity: What it Means to Consumers" and is authored by Joseph Nunes, Andrea Ordanini, and Gaia Giambastiani.

Consumers crave authenticity. Yet marketing itself is typically considered inherently inauthentic. Hence, firms must learn to understand, manage, and excel at rendering authenticity. The critical question is: how? Marketers who wish to deliver authentic consumption experiences would benefit from guidance regarding ways to enhance consumers' assessments of the authenticity of their offerings. The starting point is knowing what consumers mean when they talk about authenticity, a nebulous concept.

Nunes says "When consumers talk about authentic consumption experiences, they really are referencing six types of judgements they make involving: accuracy, connectedness, integrity, legitimacy, originality, and proficiency." Accuracy refers to the seller being transparent and reliable in what is conveyed to consumers. Connectedness describes consumers' feelings of engagement and at times a sense of transformation. Integrity means the source is seen as intrinsically motivated, while acting autonomously and consistently. Legitimacy refers to conformity in terms of adhering to norms, standards, rules, or traditions. Originality refers to a product or service standing out from the mainstream. Finally, proficiency refers to the display of skills, craftsmanship, and/or expertise in the offering.

Knowing that judgments of accuracy, connectedness, integrity, legitimacy, originality, and proficiency are what comprise assessments of authenticity, managers can more efficiently and effectively deduce actionable strategies in terms of positioning. Ordanini continues, "From this research, practitioners can also tell which of these six judgments to emphasize and when in their customer marketing and communications. For example, companies selling hedonic products should see relatively large returns perception-wise from emphasizing proficiency because it matters more for hedonic products than for utilitarian products." The mattress company Tuft & Needle (what is more hedonic than sleep?) illustrates this by focusing on their belief in "quality craftsmanship without the gimmicks" on their website.

Anesthestic drugs act on the brain but most anesthesiologists rely on heart rate, respiratory rate, and movement to infer whether surgery patients remain unconscious to the desired degree. In a new study, a research team based at MIT and Massachusetts General Hospital shows that a straightforward artificial intelligence approach, attuned to the kind of anesthetic being used, can yield algorithms that assess unconsciousness in patients based on brain activity with high accuracy and reliability.

"One of the things that is foremost in the minds of anesthesiologists is 'Do I have somebody who is lying in front of me who may be conscious and I don't realize it?' Being able to reliably maintain unconsciousness in a patient during surgery is fundamental to what we do," said senior author Emery N. Brown, Edward Hood Taplin Professor in The Picower Institute for Learning and Memory and the Institute for Medical Engineering and Science at MIT, and an anesthesiologist at MGH. "This is an important step forward."

More than providing a good readout of unconsciousness, Brown added, the new algorithms offer the potential to allow anesthesiologists to maintain it at the desired level while using less drug than they might administer when depending on less direct, accurate and reliable indicators. That can improve patient's post-operative outcomes, such as delirium.

"We may always have to be a little bit 'overboard'," said Brown, who is also a professor at Harvard Medical School. "But can we do it with sufficient accuracy so that we are not dosing people more than is needed?"

Used to drive an infusion pump, for instance, algorithms could help anesthesiologists precisely throttle drug delivery to optimize a patient's state and the doses they are receiving.

Artificial intelligence, real-world testing

To develop the technology to do so, postdocs John Abel and Marcus Badgeley led the study, published in PLOS ONE [LINK TBD], in which they trained machine learning algorithms on a remarkable data set the lab gathered back in 2013. In that study, 10 healthy volunteers in their 20s underwent anesthesia with the commonly used drug propofol. As the dose was methodically raised using computer controlled delivery, the volunteers were asked to respond to a simple request until they couldn't anymore. Then when they were brought back to consciousness as the dose was later lessened, they became able to respond again. All the while, neural rhythms reflecting their brain activity were recorded with electroencephalogram (EEG) electrodes, providing a direct, real-time link between measured brain activity and exhibited unconsciousness.

In the new work, Abel, Badgeley and the team trained versions of their AI algorithms, based on different underlying statistical methods, on more than 33,000 two-second-long snippets of EEG recordings from seven of the volunteers. This way the algorithms could "learn" the difference between EEG readings predictive of consciousness and unconsciousness under propofol. Then the researchers tested the algorithms in three ways.

First, they checked whether their three most promising algorithms accurately predicted unconsciousness when applied to EEG activity recorded from the other three volunteers of the 2013 study. They did.

Then they used the algorithms to analyze EEG recorded from 27 real surgery patients who received propofol for general anesthesia. Even though the algorithms were now being applied to data gathered from a "noisier" real-world surgical setting where the rhythms were also being measured with different equipment, the algorithms still distinguished unconsciousness with higher accuracy than other studies have shown. The authors even highlight one case in which the algorithms were able to detect a patient's decreasing level of unconsciousness several minutes before the actual attending anesthesiologist did, meaning that if it had been in use during the surgery itself, it could have provided an accurate and helpful early warning.

As a third test, the team applied the algorithms to EEG recordings from 17 surgery patients who were anesthetized with sevoflurane. Though sevoflurane is different from propofol and is inhaled rather than infused, it works in a similar manner, by binding to the same GABA-A receptors on the same key types of brain cells. The team's algorithms again performed with high, though somewhat reduced accuracy, suggesting that their ability to classify unconsciousness carried over reliably to another anesthetic drug that works in a similar way.

The ability to predict unconsciousness across different drugs with the same mechanism of action is key, the authors said. One of the main flaws with current EEG-based systems for monitoring consciousness, they said, is that they don't distinguish among drug classes, even though different categories of anesthesia drugs work in very different ways, producing distinct EEG patterns. They also don't adequately account for known age differences in brain response to anesthesia. These limitations on their accuracy have also limited their clinical use.

In the new study, while the algorithms trained on 20-somethings applied well to cohorts of surgery patients whose average age skewed significantly older and varied more widely, the authors acknowledge that they want to train algorithms distinctly for use with children or seniors. They can also train new algorithms to apply specifically for other kinds of drugs with different mechanisms of action. All together a suite of well trained and attuned algorithms could provide high accuracy that accounts for patient age and the drug in use.

Abel said the team's approach of framing the problem as a matter of predicting consciousness via EEG for a specific class of drugs made the machine learning approach very simple to implement and extend.

"This is a proof of concept showing that now we can go and say let's look at an older population or let's look at a different kind of drug," he said. "Doing this is simple if you set it up the right way."

The resulting algorithms aren't even computationally demanding. The authors noted that for a given 2 seconds of EEG data, the algorithms could make an accurate prediction of consciousness in less than a tenth of a second running on just a standard MacBook Pro computer.

The lab is already building on the findings to refine the algorithms further, Brown said. He said he also wants to expand testing to hundreds more cases to further confirm their performance, and also to determine whether wider distinctions may begin to emerge among the different underlying statistical models the team employed.

Researchers have traced the remaining last steps of the biological pathway that gives oats resistance to the deadly crop disease take-all.

The discovery creates opportunities for new ways of defending wheat and other cereals against the soil-borne root disease.

The research team have already taken the first step in this aim by successfully reconstituting the self-defence system in the model plant Nicotiana benthamiana.

Further experiments to establish the avenacin biosynthetic pathway in wheat's more complex genome, to test if it will provide the same resistance to take-all and other diseases, have already been initiated in collaboration with the National Institute of Botany (NIAB) in Cambridge.

The research by CEPAMS - a collaboration between the John Innes Centre and the Chinese Academy of Sciences - also delivers fresh insights into the mechanisms that shape genome architecture and adaptive evolution in plants.

Avenacins are antimicrobial compounds synthesised in the roots of oats where they offer protection against soil-borne diseases such as take-all. This fungal pathogen causes huge yield losses in wheat and there is no effective means of control.

Wheat and other cereals and grasses do not make these compounds but a better understanding of how they are produced in oat will give crop scientists knowledge they need to create disease resistant lines of wheat using modern technologies.

Earlier experiments had characterised and cloned ten avenacin biosynthetic pathway genes found in the oat genome.

Here, using a genomics-driven approach, with sequencing carried out by Professor Bin Han's group at the Chinese Academy of Sciences, the team elucidated the complete pathway, encoded by 12 genes.

They found that genes are clustered next to each other in the genome like beads on a string and organised along the chromosome approximately in the same order as the biosynthetic pathway - like a recipe written out in order of ingredients.

The avenacin gene cluster is located very close to the end of one arm of chromosome 1 of oat. It is arranged such that the early pathway genes are closer to the end of the chromosome (the telomere) and the late pathway genes are further in.

The team speculate this may be because gene mutations in the late avenacin pathway can result in the accumulation of compounds that negatively affect plant growth while mutations in the early pathway genes do not.

The orientation of these late pathway genes away from the telomere region means the plant is less likely be affected by toxins.

Comparison with the sequenced genomes of other cereals and grasses revealed that the avenacin cluster has formed since the divergence of oats from these other plant species which, the researchers presume, is due to a particular set of selective pressures.

Professor Anne Osbourn, joint corresponding author of the research along with Professor Bin Han said: "Our investigations show that plant genomes are able to shuffle and evolve their genes to enable them to adapt to particular stresses - in this case to soil-borne fungal diseases such as take-all. During this process, winning combinations of genes that provide a selective advantage can be recruited and relocated from around the genome and assembled into a cluster like beads on a string. This clustering will enable the winning gene-set to be passed on from generation to generation and mitigate against incomplete inheritance of the pathway genes with associated deleterious effects."

The study offers the latest example of plant biosynthetic gene clusters for different types of compounds including drugs.

Investigations of how widespread these types of genomic organisations are in the Plant Kingdom hinges on the generation of new genome sequences for a wider variety of plants.

May 7, 2021 - Early in the COVID-19 pandemic, healthcare systems scrambled to modify patient care processes - particularly when it came to strategies aimed at reducing the risk of hospital-related complications. A look at how one hospital applied its learning health system (LHS) framework to respond to a COVID-19-related increase in hospital-acquired pressure injuries (HAPIs) is presented in the May/June Journal for Healthcare Quality (JHQ), the peer-reviewed journal of the National Association for Healthcare Quality (NAHQ). The journal is published in the Lippincott portfolio by Wolters Kluwer.

"Given the significant challenges that pressure injuries may pose to the hospitalized patient, healthcare providers and leaders are faced with the task of HAPI risk mitigation that factors in the unknowns of the COVID pandemic," write Shea Polancich, PhD, RN, and colleagues of University of Alabama at Birmingham. Their experience shows how an LHS approach can support healthcare systems in reducing the risk of HAPIs and other preventable complications, with beneficial effects on patient care and reimbursement.

Using the LHS model improved care delivery - Even during a pandemic

Dr. Polancich and colleagues reviewed electronic health record data of 772 patients who were discharged from their academic medical center from March through July 2020 to gain insights into the prevalence of HAPIs and the efficacy of the organization's 4-year HAPI improvement efforts, based on an LHS model. About 29 percent of patients included in the analysis were diagnosed with COVID-19.

After the start of the pandemic, HAPI numbers began to increase steadily: from 56 cases in March to a peak of 90 cases in May. The researchers believe the increase in HAPIs was related to changes in organizational workflow and processes for evaluating wounds in the early weeks of the pandemic. For example, to reduce COVID-19 exposure and preserve personal protective equipment, the Wound, Ostomy, and Continence (WOC) team used iPads outside patient rooms for remote assessment.

Limited ability to directly observe, touch, and treat patients may have resulted in less-effective management of pressure injuries. Restricted visits by family members or other caregivers - an important set of "eyes and ears" at the patient's bedside - might also have contributed to the increase in HAPIs.

As the nursing leadership team identified opportunities for improvement, workflow and care processes were quickly adapted. Forty-two percent of HAPI cases in COVID patients were potentially related to positioning or devices affecting the face, head, and neck - possibly linked to placing COVID patients in prone position in order to increase aeration of the lungs. The problem was addressed by using silicon adhesive dressings to relieve pressure points in areas above the neck.

With changes in nursing practice and a gradual return to normal hospital operations, HAPI case numbers started to decline in June, reaching a low of 51 events by the end of July. That corresponded to a 45 percent decrease in the total number of HAPIs.

About 37 percent of COVID-19-related HAPIs were stage 3 or above. Hospitals are not eligible to receive full reimbursement from the Centers for Medicare and Medicaid Services for advanced-stage HAPIs - making pressure injuries an important management target.

"Fluctuations and variations in the number of HAPIs during the study period likely occurred due to organizational learning about how to manage patients with COVID 19," the researchers write. By following the LHS model, their hospital was able to identify gaps in patient care in real time and apply the learned information to improve future care delivery. Dr. Polancich and colleagues conclude: "This case study demonstrates the importance of health systems being able to quickly assess and document a problem, deploy resources to fix the problem, as well as evaluate the effectiveness of an intervention."

Today, deliveries via cesarean sections, or c-sections, have become quite common globally. Sometimes, c-sections are a medical necessity when normal deliveries become risky either for the mother or the baby. At other times, it can be a choice. C-sections today have become a considerably safer procedure than it was a few decades ago, but there is need to refine it further.

In a recent study published in Chinese Medical Journal, researchers from China have settled the debate on one important aspect of refining the procedure: the choice of drug to counteract the side effects of the spinal anesthesia required.

C-sections are performed under general anesthesia or spinal anesthesia. With the latter, there can be one key complication: hypotension, or low blood pressure. This can simply make the mother nauseous, or it can have graver consequences such as compromising the fetus. To avoid these problems, medical practitioners typically administer vasopressors, drugs meant to raise the blood pressure to normal levels, as preventatives before giving the spinal anesthesia.

However, a commonly used vasopressor, ephedrine, too can have undesirable effects, some on the fetus, such as increasing fetal heart rate and causing fetal acidosis (a condition in which the proportion of acids in the bodily fluids rises). Studies have also shown that it is slow acting. Recently, an alternative has begun to be employed: norepinephrine. Norepinephrine has shown fewer effects on the heart rate and is faster acting, making it potentially a better alternative to ephedrine. But to date, there are few head to head comparisons of the two.

To understand whether norepinephrine really is the better choice, the team of researchers from China, led by Dr. Zhi-Hong Lu of the Department of Anesthesiology and Perioperative Medicine at the Fourth Military Medical University in Shanghai, conducted a clinical trial.

They enlisted 177 expecting mothers scheduled to undergo c-sections and randomly divided them into groups receiving one of two protocols: norepinephrine infusion for 30 minutes just before spinal anesthesia or a quick dose of ephedrine just before the spinal anesthesia. These are standard protocols for administering these vassopressors.

The team then evaluated various factors like the incidence of hypotension within 30 minutes of spinal anesthesia administration, the conditions of the mother and baby 30 minutes after spinal anesthesia, and the degree of oxygenation in the cerebral region--the uppermost part--of the baby' brain 10 minutes after birth.

They found that fewer mothers who had received norepinephrine suffered from hypotension than those who received ephedrine. Similarly, the frequency of tachycardia, a condition characterized by irregularly fast heartbeats, was lower in mothers given norepinephrine than those administered with ephedrine. The former were also less likely to experience nausea and vomiting.

As for the physical condition of the newborn, including heart rate, effort required for respiration, tone of muscles, stimulation response, and coloration of skin, there weren't significant differences between the two groups. The cord blood gas levels, which indicate metabolic conditions in the newborn, weren't different between the two groups either.

One exception to this trend in newborns, or neonates, was the cerebral oxygenation level. As Dr. Lu has explained, "Neonatal cerebral regional saturations were significantly higher after birth in the norepinephrine group than in the ephedrine group. This indicates that norepinephrine can has potential neonatal benefits as well, which ephedrine does not have. The routine use of this norepinephrine regimen could help reduce neonate neurocognitive complications."

Overall, this study seems to indicate that norepinephrine infusion should be the preferred vasopressor protocol for c-sections. Dr. Lu says, "Further research is required to optimize the regimen to clarify norepinephrine's neonatal benefits and maximizing them. But for now, it appears that its fixed-rate infusion is more effective than the ephedrine protocol for people undergoing elective c-section."

This is the first step to delivering better care at literally the dawn of the future generations.

Children ages two to five who have the most common form of cystic fibrosis (CF), caused by two copies of the F508 gene mutation, have not had any modulator treatments available to them until recently. A new study authored by researchers at Children's Hospital Colorado and published May 6, 2021, in Lancet Respiratory Medicine shows that the CFTR modulator - lumacaftor/ivacaftor - can be safe and well-tolerated for this age range for up to 120 weeks, allowing younger children to begin proactive treatment of CF earlier in their lives.

CF affects more than 70,000 people worldwide and is a chronic, progressive, life-shortening genetic disease caused by an absent or defective protein called the CF transmembrane conductance regulator (CFTR) protein, resulting from mutations in both copies of the CFTR gene. Most people with CF have little to no CFTR protein function. CFTR modulators target the specific defects caused by mutations in the CFTR gene to increase the quantity or function of CFTR protein. Lumacaftor/ivacaftor is the first combination CFTR modulator therapy approved to treat people with CF who have two copies of the most common disease-causing CFTR mutation.

While a prior study found that up to 24 weeks of lumacaftor/ivacaftor was safe and effective, the safety and efficacy of long-term lumacaftor/ivacaftor treatment had not previously been investigated in children under the age of six. During this new study, 57 children between two and five years of age received weight- and age-based doses of lumacaftor/ivacaftor every 12 hours for over 96 weeks with the end results demonstrating that lumacaftor/ivacaftor is safe, effective and can be used for up to 120 weeks of treatment.

"Starting CFTR modulator treatments at a younger age may help to slow and hopefully prevent some of the devastating consequences of CF, such as lung damage, lung function decline and frequent illnesses or hospitalizations," said lead study author Jordana Hoppe, MD, a pediatric pulmonologist with Children's Hospital Colorado and assistant professor of pediatrics at the University of Colorado School of Medicine on the Anschutz Medical Campus. "Prior to the approval of lumacaftor/ivacaftor for children between 2-5 years old, younger patients with two copies of the F508 mutation could only receive symptomatic treatments such as manual chest percussion to clear mucus from the airways, nebulized treatments or antibiotics. The modulator therapy is preventive instead of reactive, targeting the function of the protein to make it work better."

Another key finding demonstrated improvements or an increase in pancreatic function. CF can cause pancreatic insufficiency so that those with the disease must ingest pancreatic enzymes every time they eat to maintain growth and nutrition. These results suggest that for some patients treated with the CFTR modulator therapy, there may be improvement in pancreatic function, possibly resulting in changes to their enzyme dosing.

Additional results included changes in sweat chloride, improved weight gain and growth, and increased lung clearance. It also helps prevent pulmonary exacerbations or respiratory illnesses that require hospitalizations and antibiotic therapy, which has been especially alleviating for families during the COVID-19 pandemic.

"These patients will be transitioned to a more highly effective modulator TRIKAFTA*, but there are certainly benefits to starting modulator therapy at a younger age as the results of this study demonstrated," Hoppe said.

Study visits were conducted in the Colorado Clinical and Translational Sciences Institute (CCTSI) research area at Children's Hospital Colorado. The hospital's Mike McMorris Cystic Fibrosis Research and Care Center is the largest center of its kind in the nation and follows close to 400 children.

"The Colorado Clinical and Translational Sciences Institute (CCTSI) has been a longtime partner with the Mike McMorris Cystic Fibrosis Research and Care Center. Our pediatric Clinical and Translational Research Center and our specialized research nursing staff assist the CF investigators like Dr. Hoppe with conducting CF clinical trials in many ways, including collecting data and obtaining specimens, infusing medications and educating the families and children about research," said Ronald Sokol, MD, director of the CCTSI and vice chair of pediatrics at Children's Hospital Colorado.

*In 2019, researchers at the Children's Hospital Colorado Breathing Institute, one of the largest CF clinical care centers in the U.S., were part of a Therapeutics Development Network that oversaw clinical trials leading to FDA approval of TRIKAFTA, a highly effective CF treatment for people with CF 12 years of age and older. The team was also involved in trials of TRIKAFTA in children ages 6-11 years, which was recently proven efficacious for this patient population and could be soon approved by the FDA for use for kids 6 and older. TRIKAFTA is a combination of three medicines that can improve the CFTR protein function to over 50%, helping approximately 90% of people living with CF.

Ishikawa, Japan - As decarbonization progresses rapidly in the world, fuel cells offer potentially higher electrical efficiency than conventional power-generating systems. Anion exchange membrane fuel cells offer advantages of using non-precious metal catalysts than proton exchange membrane fuel cells. One of the challenges of this next-generation fuel cell is to clarify the hydroxide ion conductivity in the ion conductive polymer around the electrode catalyst. The difficulty of studying the hydroxide ion conductivity at the electrode interface is that the hydroxide ion, which is a carrier, easily reacts with carbon dioxide in the air. To solve this problem, all evaluation devices were improved so that the sample did not come into contacting with air.

In a new study published in ChemSusChem (Accepted Article), researchers from Japan Advanced Institute of Science and Technology (JAIST), namely Associate Professor Yuki Nagao and Ph.D. students Fangfang Wang and Dongjin Wang, succeeded in precisely identifying the hydroxide ion conductivity and the water amount contained in the sample without exposing the thin film sample to air. Fluorene-based cationic polymers were synthesized, and Br- and OH- samples as counter anions were prepared for comparison. It was revealed that the 270-nm-thick thin film containing hydroxide ions exhibits a high hydroxide ion conductivity of 0.05 S cm-1. This ionic conductivity was more than twice as high as the value of the thin film containing Br- ions as shown in Figure 1.

Surprisingly, it was also revealed that the hydroxide ion conductivity of the thin film form containing hydroxide ions was comparable to that of the thick membrane form. This tendency seems to be different from the results reported in proton conductive polymers.

"Developing a better understanding of these properties and their impacts on hydroxide ion conduction will be important for both clarifying hydroxide ion conduction mechanisms and improving fuel cell performance," explains Associate Professor Yuki Nagao from JAIST. New findings seem to be a solid step toward a hydrogen society.

Cells talk to each other to coordinate nutrition, waste removal, energy use, and, in some cases, disease progression. The cells that line the surfaces of organs or specific tissues, called epithelial cells, appear to speak two different languages - one for either side of the cell, according to a new study by researchers based in Japan.

The discovery, published on March 16 in EMBO Reports, could have implications for understanding how cancer spreads and, potentially, for advanced treatments, the team says.

The team, led by Mitsunori Fukuda, professor in the Laboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences at Tohoku University, examined epithelial cells from a kidney model. The cells release particles called exosomes that carry bits of the cells themselves or information about the cells. The proteins and other genetic information in the exosomes can then influence how other cells behave or function. In health, such an information exchange could help the immune system mount a more tailored approach to an invading pathogen. Some diseased cells, such as cancer, can release exosomes that make healthy cells less resistant to invasion.

"Single cells are known to release various kinds of exosomes, but very little is known about the mechanisms by which they are produced and released," Fukuda said. "In this paper, we found that epithelial cells asymmetrically release two distinct types of exosomes with distinct protein compositions."

The researchers developed a purification method to separate out exosomes based on their protein makeup.

"In this paper, we found that epithelial cells asymmetrically release two distinct types of exosomes - apical and basolateral - with distinct protein compositions," said first author Takahide Matsui, assistant professor, Laboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences at Tohoku University.

They found that exosomes released from the apical side of the cell, which faces an external space or lumen, were modulated by ALIX, a protein related to the particle formation inside the cells. Exosomes released from the basolateral side of the cell closest to other tissues and neighboring cells were triggered by ceramide, a fatty molecule. They also found that depleting ALIX and ceramide reduced the number of apical exosomes and basolateral exosomes released, respectively.

Fukuda said that the results could help elucidate the cell-to-cell communication that allows cancer to migrate - and put a stop to it.

"It will be interesting to investigate how cancer cells use two distinct mechanisms of exosome production during cancer progression," Fukuda said. "Since exosomes from cancer cells are involved in their progression, our findings could lead to the discovery of new drugs for treatments for cancers in the future."

Matsui agreed, noting that their research could expand to other realms in health and in disease.

"Our discovery provides an important clue to understanding the generation of different exosomes in many cell types in addition to epithelial cells," Matsui said.

People spend about 80-90% of their time indoors. Compared to outdoor air quality, the indoor air quality is more relevant to people's health. Therefore, understanding the levels, sources and evolution of particulate matter (PM) indoors is important for the accurate evaluation of people's health risks to aerosol exposure.

A research team led by Prof. Yele Sun from the Institute of Atmospheric Physics (IAP) of the Chinese Academy of Sciences deployed a time-of-flight aerosol chemical speciation monitor (ToF-ACSM) to measure time series and mass spectra of non-refractory species in a typical academic office in IAP. The study was published in Indoor Air.

The researchers measured the concentration and chemical composition of indoor PM2.5 for one month along with simultaneous measurements outdoors. They also performed the open-close window and the dampness experiments in order to figure out the mechanism of indoor/outdoor air exchange, and the influence of increased humidity on the indoor PM2.5.

They found that the indoor aerosol species were primarily from outdoor air exchange. "The indoor and outdoor variation trends are similar for most of aerosol species," said Prof. Sun, "However, the chemical compositions of PM2.5 are different. The concentration of organic aerosol from fossil fuel combustion and ammonium nitrate decreases because they evaporate or turn from particle to gas upon indoor transport when the indoor temperature is much higher than the outside in winter."

It is often believed that opening windows to ventilate can improve the indoor air quality. However, according to this newly published study, the PM mass concentration outdoors is significantly higher than that in the office. Elevated natural ventilation will increase PM exposure indoors instead, and this increased exposure might be prolonged when outdoor PM got cleared up. "So it's not a good idea to open windows when the air quality is not good outdoors." Said Prof. Sun.

The team also investigated the effect of air humidifiers, which are widely used to increase the indoor humidity. Prof. Sun said, "The increase of indoor relative humidity could lead to a significant increase in PM2.5 mass concentration, especially for organic aerosol. The increase is likely due to the partitioning of hygroscopic organic species from gas phase to particle phase in indoor air."

"Better understanding of the links between indoor and outdoor air quality will be needed in the future, as well as a more quantitative assessment of human exposure risks indoors," said Sun.

To understand the world, we arrange individual objects, people, and events into different categories or concepts. Concepts such as 'the telephone' consist primarily of visible features, i.e. shape and color, and sounds, such as ringing. In addition, there are actions, i.e. how we use a telephone.

However, the concept of telephone does not only arise in the brain when we have a telephone in front of us. It also appears when the term is merely mentioned. If we read the word "telephone", our brain also calls up the concept of telephone. The same regions in the brain are activated that would be activated if we actually saw, heard, or used a telephone. The brain thus seems to simulate the characteristics of a telephone when its name alone is mentioned.

Until now, however, it was unclear, depending on the situation, whether the entire concept of a telephone is called up or only individual features such as sounds or actions and whether only the brain areas that process the respective feature become active. So, when we think of a telephone, do we always think of all its features or only the part that is needed at the moment? Do we retrieve our sound knowledge when a phone rings, but our action knowledge when we use it?

Researchers at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig have now found the answer: It depends on the situation. If, for example, the study participants thought of the sounds associated with the word "telephone", the corresponding auditory areas in the cerebral cortex were activated, which are also activated during actual hearing. When thinking about using a telephone, the somatomotor areas that underlie the involved movements came into action.

In addition to these sensory-dependent, so-called modality-specific areas, it was found that there are areas that process both sounds and actions together. One of these so-called multimodal areas is the left inferior parietal lobule (IPL). It became active when both features were requested.

The researchers also found out that, in addition to characteristics based on sensory impressions and actions, there must be other criteria by which we understand and classify terms. This became apparent when the participants were only asked to distinguish between real and invented words. Here, a region that was not active for actions or sounds kicked in: the so-called anterior temporal lobe (ATL). The ATL therefore seems to process concepts abstractly or "amodally", completely detached from sensory impressions.

From these findings, the scientists finally developed a hierarchical model to reflect how conceptual knowledge is represented in the human brain. According to this model, information is passed on from one hierarchical level to the next and at the same time becomes more abstract with each step. On the lowest level, therefore, are the modality-specific areas that process individual sensory impressions or actions. These transmit their information to the multimodal regions such as the IPL, which process several linked perceptions simultaneously, such as sounds and actions. The amodal ATL, which represents features detached from sensory impressions, operates at the highest level. The more abstract a feature, the higher the level at which it is processed and the further it is removed from actual sensory impressions.

"We thus show that our concepts of things, people, and events are composed, on the one hand, of the sensory impressions and actions associated with them and, on the other hand, of abstract symbol-like features," explains Philipp Kuhnke, lead author of the study, which was published in the renowned journal Cerebral Cortex. "Which features are activated depends strongly on the respective situation or task" added Kuhnke.

In a follow-up study in Cerebral Cortex, the researchers also found that modality-specific and multimodal regions work together in a situation-dependent manner when we retrieve conceptual features. The multimodal IPL interacted with auditory areas when retrieving sounds, and with somatomotor areas when retrieving actions. This showed that the interaction between modality-specific and multimodal regions determined the behavior of the study participants. The more these regions worked together, the more strongly the participants associated words with actions and sounds.

The scientists investigated these correlations with the help of various word tasks that the participants solved while lying in a functional magnetic resonance imaging (fMRI) scanner. Here, they had to decide whether they strongly associated the named object with sounds or actions. The researchers showed them words from four categories: 1) objects associated with sounds and actions, such as "guitar", 2) objects associated with sounds but not with actions, such as "propeller", 3) objects not associated with sounds but with actions, such as "napkin", and 4) objects associated neither with sounds nor with actions, such as "satellite".