Culture

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".

To infect its host plant maize, the fungal parasite Ustilago maydis uses a complex of seven proteins. Numerous findings reveal an essential role of the complex in causing disease and suggest a widespread occurence in fungal plant pathogens.

Each year, fungal plant pathogens such as rusts, rice blast and mildews destroy huge amounts of cereal crops that could feed millions of people. Many of these fungi are biotrophic pathogens: Instead of killing their host plants, they manipulate host cells to assure that these sustain fungal growth. Among these pathogens, the corn smut fungus Ustilago maydis has emerged as a model for basic research on biotrophic fungi.

During the infection, U. maydis releases an entire cocktail of so-called effectors which function either in the interaction zone between fungus and host or are delivered to plant cells. Effector proteins suppress plant immunity, alter plant biosynthesis pathways and re-initiate cell division in leaf tissue, leading to prominent tumor-like structures from which the fungus spreads its spores. At present, the mechanism how effectors of plant-pathogenic fungi end up in plant cells remains a mystery.

Over many years, researchers around Regine Kahmann at the Max Planck Institute for Terrestrial Microbiology have worked on elucidating the molecular function of effectors. In the present study they have identified five fungal effectors plus two transmembrane proteins, which form a stable protein complex. If only one of these seven proteins is missing, the infection process stops entirely. Such a strong contribution to virulence is highly unusual for effectors which individually usually have only a modest contribution to virulence. Mutants lacking complex members fail to downregulate host immunity, suggesting an involvement of the complex in effector delivery. Localization experiments in part conducted with collaboration partners in the US and at the Philipps-Universität in Marburg revealed that complex proteins reside in structures extending from the fungus into host cells.

Essential for infection

These and other findings together with the observation that the expression of the complex is co-regulated with the infection process point towards a central, if not universal role of the protein complex. "We consider it likely that the effector complex in fact acts as a transmembrane structure that helps pathogens to deliver effector proteins into host cells", says Regine Kahmann. "Such devices are well known from bacteria, but not from fungi so far."

However, direct proof is tough to come by. "This would require to show that certain effectors fail to enter the plant cell when the complex is missing, something we cannot really prove at the moment since mutants lacking the complex are immediately attacked by the plant immune system and die after entering the plant" says Nicole Ludwig, lead author of the study that was published in the journal Nature Microbiology. "We hope that in the near future the already achieved reconstitution of the complex will pave the way to study its atomic structure and presumed function in effector delivery."

But there is also an applied aspect associated with the essential role of the complex, as Regine Kahmann points out. "Because the complex is indispensable for infection, it is an attractive target for stopping the disease by developing new fungicides". First steps towards this goal have already been taken by setting up a high throughput screen in collaboration of the Max Planck researchers in Marburg with the Compound Management and Screening Center (COMAS) at the MPI for Molecular Physiology in Dortmund. The screen resulted in several candidate compounds, of which the most promising ones could successfully inhibit disease symptoms not only of U. maydis but also disease caused by a rust fungus. Supported by Max Planck Innovation a patent was recently filed at the European Patent Office, illustrating the transfer of basic research to potential applications in agriculture.

May 7, 2021 - Among collegiate football players and other athletes, Black athletes recognize fewer concussion-related symptoms than their White counterparts, reports a study in the May/June issue of the Journal of Head Trauma Rehabilitation (JHTR). The official journal of the Brain Injury Association of America, JHTR is published in the Lippincott portfolio by Wolters Kluwer.

"Despite NCAA concussion education requirements for athletes, Black collegiate-athletes were found to have lower concussion symptom knowledge than White collegiate-athletes," according to the new research by Jessica Wallace, PhD, MPH, LAT, ATC, of University of Alabama, Tuscaloosa, and colleagues. The study also finds racial differences in the sources of concussion symptom knowledge.

Need for 'equitable strategies' to communicate concussion information

In the study, 768 collegiate athletes - about 83 percent White and 17 percent Black - completed a standard assessment of concussion symptom knowledge. Participants included 196 football players, of whom 59 percent were White and 41 percent were Black.

Scores on the concussion symptom knowledge questionnaire were compared for Black and White athletes, with adjustment for other characteristics. The athletes were also asked about their sources of information about concussion symptoms.

"Black athletes were more likely to have lower concussion symptom knowledge scores than White athletes," according to the authors. The difference was small: average scores on the 34-point questionnaire were 27.7 for White athletes and 25.9 for Black athletes. However, the between-group difference remained statistically significant after adjustment for other factors. The findings were similar for football players compared to all athletes.

Concussion symptom knowledge varied for a range of sleep, mood, physical, and cognitive symptoms of concussion. In particular, Black athletes were less likely to correctly recognize the symptoms of feeling like "in a fog," nausea or vomiting, and feeling more irritable/angry.

Most athletes identified athletic trainers as a main source of concussion information. White athletes were somewhat more likely to mention other school-based professionals (such as teachers or nurses), online medical sources, or the National Collegiate Athletic Association (NCAA). Black athletes were more likely to cite referees as a source of concussion information.

Basic knowledge of concussion symptoms is fundamental to prompt recognition and reporting of concussions. Studies have suggested that 50 to 80 percent of concussions may go unreported.

In previous studies, Dr. Wallace and colleagues reported racial disparities in concussion knowledge among high school and youth athletes. Concussion knowledge was lowest for athletes attending schools of lower socioeconomic status and without access to athletic trainers.

These differences in concussion knowledge may extend to the college level, the new study suggests. The disparity may be related to historic and systemic bias/discrimination and inequitable access to healthcare and other resources, or to racial distrust in medical resources and healthcare overall. "All of these contributing factors of inequity and disparity at the community level, youth sports level, and high school sports level could impact exposure and/or receptiveness to concussion education materials that may ultimately explain the lower concussion symptom knowledge of Black collegiate-athletes," Dr. Wallace and coauthors write.

The researchers emphasize the need for strategies to ensure equitable access to concussion education and prevention that do not perpetuate disparity: "Moving forward, a conscious attempt is needed to redevelop concussion education initiatives as racially, culturally, and linguistically inclusive, addressing the needs of all collegiate athletes equally and equitably."

The NCAA provides educational resources on concussion: https://www.ncaa.org/sport-science-institute/concussion-educational-resources.

Click here to read "Assessing Differences in Concussion Symptom Knowledge and Sources of Information Among Black and White Collegiate-Athletes."
DOI: 10.1097/HTR.0000000000000672

RNA-based drugs have the potential to change the standard of care for many diseases, making personalized medicine a reality. This rapidly expanding class of therapeutics are cost-effective, fairly easy to manufacture, and able to go where no drug has gone before, reaching previously undruggable pathways.

Mostly.

So far, these promising drugs haven't been very useful in getting through to the well-protected brain to treat tumors or other maladies.

Now a multi-institutional team of researchers, led by Costas Arvanitis at the Georgia Institute of Technology and Emory University, has figured out a way: using ultrasound and RNA-loaded nanoparticles to get through the protective blood-brain barrier and deliver potent medicine to brain tumors.

"We're able to make this drug more available to the brain and we're seeing a substantial increase in tumor cell death, which is huge," said Arvanitis, assistant professor in the Wallace H, Coulter Department of Biomedical Engineering (BME) and Georgia Tech's George W. Woodruff School of Mechanical Engineering (ME).

Arvanitis, whose collaborators include researchers and clinicians from Emory's School of Medicine and the University of Cincinnati College of Medicine, is the corresponding author of a new paper published in the journal Science Advances that describes the team's development of a next-generation, tunable delivery system for RNA-based therapy in brain tumors.

"Our results were very positive, but if you think I'm excited, you haven't talked to oncologists - they're 10 times as excited," Arvanitis said.

The roots of this project go back to when he and the paper's lead author, ME grad student Yutong Guo, arrived at Georgia Tech in August 2016.

"From the start, I was very interested in the application of ultrasonics in treating brain disease," said Arvanitis, who linked up with Emory physician Tobey MacDonald, director of the Pediatric Neuro-Oncology Program at the Aflac Cancer and Blood Disorders Center, and one of the paper's co-authors. "Our main question was, can we use ultrasound to deliver drugs to tumors? Because that is a major challenge."

RNA drugs have two major weaknesses: limited circulation time and limited uptake by cells. To overcome these challenges, the drugs are packaged in robust nanocarriers, typically 100 nm in size, to improve their bioavailability. Still, these nanocarriers have typically been too large to penetrate the blood-brain barrier, the tightly-connected and selective endothelial cells surrounding blood vessels in the brain, until now a locked door to RNA drugs.

But now, Arvanitis and his colleagues have discovered a safe way to get the drug safely across.

Using mouse models, the team deployed a modified version of ultrasound, the diagnostic imaging technique that uses sound waves to create images of internal body structures, such as tendons, blood vessels, organs and, in the case of pregnant women, babies in utero. The researchers combined this technology with microbubbles -- tiny gas pockets in the bloodstream, designed as vascular contrast agents for imaging -- which vibrate in response to ultrasound waves, changing the permeability of blood vessels.

"Focusing multiple beams of ultrasound energy onto a cancerous spot caused the microbubbles' vibrations to actually stretch, pull, or shear the tight junctions of endothelial tissue that make up the blood-brain barrier, creating an opening for drugs to get through," Guo said.

It's a technique that biomedical ultrasound researchers have been refining for more than a decade, and recent clinical trials have demonstrated its safety. But there hasn't been much evidence for selective and effective delivery of nanoparticles and their payloads directly into brain tumor cells. But even when blood borne drugs succeed in penetrating the blood-brain barrier, if they are not taken up by the cancer cell, the job isn't complete.

Arvanitis and his team packaged siRNA, a drug that can block the expression of genes that drive tumor growth, in lipid-polymer hybrid nanoparticles, and combined that with the focused ultrasound technique in pediatric and adult preclinical brain cancer models. Using single-cell image analysis, they demonstrated a more than 10-fold improvement in delivery of the drug, reducing harmful protein production and increasing tumor cell death in preclinical models of medulloblastoma, the most common malignant brain tumor in children.

"This is completely tunable," Arvanitis said. "We can fine tune the ultrasound pressure to attain a desired level of vibration and by extension drug delivery. It's non-invasive, because we are applying sound from outside the brain, and it's very localized, because we can focus the ultrasound to a very small region of the brain."

Current standard treatments for brain tumors come with potentially awful side effects, Arvanitis said, "however, this technology can provide treatment with minimal side effects, which is very exciting. Now we are moving forward to try and identify what components are missing to translate this technology to the clinic."

Some meat eaters feel disgusted by meat, according to a new study.

University of Exeter scientists showed food pictures to more than 700 people, including omnivores (who eat meat and other foods), flexitarians (who try to eat less meat) and vegetarians.

About 7% of meat eaters (15% of flexitarians and 3% of omnivores) had a "fairly strong disgust response" to images of meat dishes commonly eaten in the UK, like roast chicken or bacon.

As a group, omnivores rated meat images about twice as disgusting on average as pictures of carbohydrate-rich foods like bread, chips and rice.

Based on the findings, the researchers say harnessing the "yuk factor" may be more effective than relying on willpower for anyone who wants to eat less meat.

"We were surprised to find that so many people are grossed out by meat - even people who eat meat all the time," said Elisa Becker, of the University of Exeter.

"Our results don't explain why these people eat meat, but it's possible that habits, family and cultural traditions all play a part.

"Meat consumption is increasingly seen as unsustainable, unhealthy and unethical, and many people want to eat less meat.

"If you're trying to cut down your meat intake, sheer willpower may not be enough - but harnessing the 'yuk factor' could be the way to go."

The study's 711 participants - 402 omnivores, 203 flexitarians and 106 vegetarians - each completed a survey and took a rapid-response task (measuring instinctive reactions) to test their levels of "meat disgust".

"Meat liking" was also measured. About 75% of omnivores - and more than 20% of vegetarians - showed a fairly strong liking for meat.

To be classified as having "fairly strong" meat disgust, participants had to rate six meat images closer to "very much" than "not at all" on a sliding scale of disgust, and also had to show evidence of meat disgust on the rapid-response task.

Among flexitarians - the only group attempting to reduce their meat intake - meat disgust was a better predictor than self-control (measured in a separate questionnaire) of reduced meat-eating.

Meat disgust was also associated with reduced intake over the following six months.

"We hope that this information can help us develop new interventions to help people reduce their meat intake," said Professor Natalia Lawrence, of the University of Exeter.

"Not everyone wants to reduce their meat consumption - but for those who do, we are working on computer tasks that might help them harness the power of disgust in a fun way.

"It's important to note that our study does not establish causation - so further research is needed to find out whether meat disgust causes people to eat less meat, or whether avoiding meat allows these negative emotional responses to develop or be expressed."

Becker added: "It's interesting to note that almost all of us experience meat disgust from time to time - for example when we see unfamiliar meats or dishes made from parts of animals we don't usually eat, like squirrel meat or beef heart.

"Humans may have evolved a degree of meat disgust because eating spoilt meat can be much more dangerous than eating a carrot that's a bit off."

Depressive symptoms are more common in teenage girls than in their male peers. However, boys' mental health appears to be affected more if they suffer from obesity. Irrespective of gender, bullying is a considerably greater risk factor than overweight for developing depressive symptoms. These conclusions are drawn by researchers at Uppsala University who monitored adolescents for six years in a questionnaire study, now published in the Journal of Public Health.

Peer-review/Observational study/People

"The purpose of our study was to investigate the connection between body mass index (BMI) and depressive symptoms, and to take a close look at whether being subjected to bullying affects this relationship over time. We also wanted to investigate whether any gender differences existed," says Sofia Kanders, a PhD student at Uppsala University's Department of Neuroscience.

In the study young people, born in Västmanland County, replied to questions about their height, weight and depressive symptoms on three separate occasions (2012, 2015 and 2018). The respondents' mean age was 14.4 years on the first occasion and 19.9 years on the last.

Based on BMI, the adolescents were divided into three groups: those with normal weight, overweight and obesity respectively. They were also grouped according to the extent of their depressive symptoms.

Overall, regardless of their weight, the girls stated more frequently that they had depressive symptoms. In 2012, 17 per cent of the girls and 6 per cent of the boys did so. By 2015, the proportions of adolescents with these symptoms had risen to 32 per cent for the girls and 13 per cent for the boys. The corresponding figures for 2018 were 34 and 19 per cent respectively.

A higher BMI did not, as far as the researchers could see, affect the girls' mental well-being to any great extent. Among the boys, however, the pattern observed was entirely different.

"When we analysed girls and boys separately, we saw that for boys with obesity in 2012, the risk for having depressive symptoms in 2015 was, statistically, five times higher than for normal-weight boys. In the girls we found no such connection," Kanders says.

The study has been unable to answer the question of what causes this gender difference, and the researchers think more research is needed in this area.

The young respondents were also asked about bullying -- for example, to state whether, in the past year, they had been physically exposed to blows and kicks, teased or excluded, subjected to cyberbullying (abusive texting or other electronic or web bullying), or bullied by an adult at school.

In every analysis, exposure to bullying was associated with a higher risk of depressive symptoms. This connection was also evident six years later, especially in overweight boys. The researchers believe that these results seem to indicate a gender difference in how BMI and bullying together drive development of future depressive symptoms.

"One key conclusion and take-home message from our study is that bullying can affect mental illness for a long time to come, which therefore makes preventive measures against bullying in schools extremely important," Kanders says.

Nearly four-fifths of 16- and 17-year-olds have encountered pornographic content on the Internet

Pornography is a multibillion-dollar business. Pornographic content is virtually ubiquitous on the Internet, and surveys suggest that 25% of all searches lead to explicit content. Given the size of the market, it's not surprising that young people are drawn to such sites, which are only a couple of clicks away.

Professor Neil Thurman of the Department of Media and Communication (IfKW) at Ludwig-Maximilians-Universitaet (LMU) in Munich, in collaboration with statistician Fabian Obster (Universität der Bundeswehr München), has carried out a study on the use of pornographic sites by young people. Based on a survey involving a sample of 1000 British adolescents, the survey also provides pointers for regulators and legislators in Germany.

Overall, 78% of users between the ages of 16 and 17 reported that they had encountered pornography on the Internet. Moreover, many of them stated that they visited dedicated pornographic websites frequently. Those who participated in the survey admitted that, on average, they had last visited such sites 6 days prior to filling in the questionnaire. And many respondents said they watched porno videos and viewed picture galleries on that very day. Analysis of the responses indicated that adolescents spent an average of 2 hours per month on commercial pornographic websites, almost always accessed on their smartphones or tablets. The survey also revealed that young consumers are also turning to social media portals for access to explicit material. Adolescent users of online pornography are more likely to be male.

Well acquainted with VPNs and the Tor browser

In Germany, the UK, France and Canada, efforts are now underway to regulate access to legal online pornography, and in some cases measures have already been implemented. These include provisions for mandatory age verification prior to the admission of users to such websites. But, according to Thurman's survey, around half of the respondents had used VPNs or the Tor browser. Both tools anonymize connection data, thus allowing country-specific restrictions to be circumvented.

"At present, the online pornography market is highly concentrated. It is dominated by a few global firms. Indeed, only a handful of websites account for the majority of consumption," Thurman says. In the context of measures to protect minors, he therefore suggests that, in additional to country-specific measures, there should also be pressure placed on the major global publishers of pornography, to encourage them to introduce effective age restrictions in all the markets in which they operate. In addition, similar regulations should be applied, as is already happening in the UK, to social-media platforms.

Great reed warblers normally migrate by night during its month-long migration from northern Europe to Sub-Saharan Africa. However, researchers have now discovered that during the few occasions when it continues to fly during daytime, it flies at extremely high altitudes (up to 6300 meters). One possible explanation for this unexpected and consistent behaviour could be that the birds want to avoid overheating. The study is published in Science.

Most of the many millions of songbirds that migrate every year between Europe and Africa fly by night and spend the daytime hours resting and eating. Some species, which normally only fly by night, occasionally fly for over 24 consecutive hours to avoid having to stop in inhospitable locations with insufficient access to food, such as deserts and seas. The great reed warbler, Acrocephalus arundinaceus, is such a species. During its month-long migration, it can fly for up to 34 consecutive hours without landing.

A research team from Lund University in Sweden, University of Copenhagen and the Nature Research Centre in Vilnius has used unique data loggers developed at Lund University to study these long migratory flights almost minute by minute. The researchers used the data loggers, weighing no more than 1.2 grams, to track 14 great reed warblers which were captured during the summer at Lake Kvismaren, close to Örebro in Central Sweden.

The data loggers collected data over a full year, thereby providing the researchers with valuable information. As the great reed warblers migrated to and from Africa, the data loggers continuously stored information about altitude, activity and the sun's ascend and descend. The altitude measurements were recorded once per hour and every five minutes the data loggers saved information about whether the birds were flying, looking for food on the ground or resting.

Based on this information, the researchers calculated that the great reed warblers flew at an average altitude of 2400 metres at night. On the few occasions on which the birds flew for more than one consecutive night, they climbed 3000 metres at dawn to fly at an average altitude of 5400 metres during the day. They remained cruising at that altitude until dusk, when they dived 3-4000 metres and continued their flight at an altitude of around 2000 metres the following night.

Sissel Sjöberg and Dennis Hasselquist at Lund University led the study, and the results came as a surprise to them and their colleagues. They describe the great reed warblers' behaviour as very consistent, indicating that the birds may have to fly at more than twice their night-time altitude to manage migrating during daylight hours at all.

There is no definitive explanation as yet. However, the research team rules out the previously predominant explanations for choice of altitudes in migratory birds: winds and air temperature.

"At altitudes over 2000 metres, winds and air temperatures do not change merely going from day to night or vice versa", says Sissel Sjöberg.

Nor are there any high mountains along the migration route that could push the birds up to extreme altitudes. Two possible explanations could be that during daytime, the great reed warblers see further from a great height and that they can avoid birds of prey. But the researchers also suggest another explanation: the birds climb to more than double the altitude during the day to avoid becoming overheated when they are exposed to the additional effect of the sun's heat radiation.

"It is colder higher up in the air and when the birds rise to 5400 metres, they reach a layer of air with a temperature of around minus 9 degrees centigrade. That is 22 degrees colder than the altitude at which the birds fly during the night", says Sissel Sjöberg.

"The wings of migratory songbirds beat several times per second, so they are working extremely hard, which makes their bodies very warm regardless of whether they are flying by day or by night. But if they fly by day, they are also exposed to the heat from the sun's radiation; that is what we suggest they are compensating for when they climb to a much colder layer of air at daytime. It is likely that they would not manage to fly by day without becoming overheated if they did not climb to these extreme altitudes", says Dennis Hasselquist.

The researchers are continuing to study the great reed warblers. In time, they hope to find answers to the question of why the birds behave in this way, which might also help to explain why most birds that migrate to the tropics during the winter fly almost entirely by night, whereas they are active during the day and sleep at night for the rest of the year.