Culture

Scientists isolated a molecule, extracted from the leaves of the European chestnut tree, with the power to neutralize dangerous, drug-resistant staph bacteria. Frontiers in Pharmacology published the finding, led by scientists at Emory University.

The researchers dubbed the molecule Castaneroxy A, after the genus of the European chestnut, Castanea. The use of chestnut leaves in traditional folk remedies in rural Italy inspired the research.

"We were able to isolate this molecule, new to science, that occurs only in very tiny quantities in the chestnut leaves," says Cassandra Quave, senior author of the paper and associate professor in Emory's Center for the Study of Human Health and the School of Medicine's Department of Dermatology. "We also showed how it disarms Methicillin-resistant Staphylococcus aureus by knocking out the bacteria's ability to produce toxins."

Methicillin-resistant Staphylococcus aureus (MRSA) causes infections that are difficult to treat due to its resistance to antibiotics. It is one of the most serious infectious disease concerns worldwide, labeled as a "serious threat" by the Centers for the Disease Control and Prevention. In the United States alone, nearly 3 million antibiotic-resistant infections occur in the U.S. each year, killing more than 35,000 people.

Antibiotics work by killing staph bacteria, which can lead to greater resistance among those few bacteria that survive, spawning "super bugs." The Quave lab has identified compounds from the Brazilian peppertree, in addition to the European chestnut tree, that simply neutralize the harmful effects of MRSA, allowing cells and tissue to naturally heal from an infection without boosting resistance.

"We're trying to fill the pipeline for antimicrobial drug discovery with compounds that work differently from traditional antibiotics," Quave says. "We urgently need these new strategies." She notes that antimicrobial infections kill an estimated 700,000 globally each year, and that number is expected to grow exponentially if new methods of treatment are not found.

First author of the Frontiers in Pharmacology paper is Akram Salam, who did the research as a PhD student in the Quave lab through Emory's Molecular Systems and Pharmacology Graduate Program.

Quave is a medical ethnobotanist, researching traditional plant remedies to find promising leads for new drugs. Although many major drugs are plant-based, from aspirin (the bark of the willow tree) to Taxol (the bark of the Pacific yew tree), Quave is one of the few ethnobotanists with a focus on antibiotic resistance.

The story behind the current paper began more than a decade ago, when Quave and her colleagues researched written reports and conducted hundreds of field interviews among people in rural southern Italy. That pointed them to the European, or sweet, chestnut tree, native to Southern Europe and Asia Minor. "In Italian traditional medicine, a compress of the boiled leaves is applied to the skin to treat burns, rashes and infected wounds," Quave says.

Quave took specimens back to her lab for analysis. By 2015, her lab published the finding that an extract from the leaves disarms even the hyper-virulent MRSA strains capable of causing serious infections in healthy athletes. Experiments also showed the extract did not disturb normal, healthy bacteria on skin cells.

Finally, the researchers demonstrated how the extract works, by inhibiting the ability of MRSA bacteria to communicate with one another, a process known as quorum sensing. MRSA uses this sensing signaling system to make toxins and ramp up its virulence.

For the current paper, the researchers wanted to isolate these active ingredients from the plant extract. The process is painstaking when done manually, because plant extracts typically contain hundreds of different chemicals. Each chemical must be separated out and then tested for efficacy. Large scale fraction collectors, coupled to high-performance liquid chromatographic systems, automate this separation process, but they can cost tens of thousands of dollars and did not have all the features the Quave lab needed.

Marco Caputo, a research specialist in the lab, solved the problem. Using a software device from a child's toy, the LEGO MINDSTORMS robot creator, a few LEGO bricks, and some components from a hardware store, Caputo built an automated liquid separator customized to the lab's needs for $500. The lab members dubbed the invention the LEGO MINDSTORMS Fraction Collector. They published instructions for how to build it in a journal so that other researchers can tap the simple, but effective, technology.

The Quave lab first separated out a group of molecules from the plant extract, cycloartane triterpenoids, and showed for the first time that this group actively blocks the virulence of MRSA. The researchers then dove deeper, separating out the single, most active molecule from this group, now known as Castaneroxy A.

"Our homemade piece of equipment really helped accelerate the pace of our discovery," Quave says. "We were able to isolate this molecule and derive pure crystals of it, even though it only makes up a mere .0019 percent of the chestnut leaves."

Tests on mouse skin infected with MRSA, conducted in the lab of co-author Alexander Horswill at the University of Colorado, confirmed the molecule's efficacy at shutting down MRSA's virulence, enabling the skin to heal more rapidly.

Co-author John Bacsa, director of Emory Department of Chemistry's X-ray Crystallography Center, characterized the crystal shape of Castaneroxy A. Understanding the three-dimensional configuration of the crystal is important for future studies to refine and optimize the molecule as a potential therapeutic.

"We're laying the groundwork for new strategies to fight bacterial infections at the clinical level," Quave says. "Instead of being overly concerned about treating the pathogen, we're focusing on ways to better treat the patient. Our goal is not to kill the microbes but to find ways to weaken them so that the immune system or antibiotics are better able to clear out an infection."

Photobombs - when something or someone unexpectedly enters a camera's field of sight during the taking of a photograph - happen every day. Sometimes it is a friend, other times a stranger or perhaps a bird. Rarely, however, is it a whole planet. Yet, this is exactly what happened while CHEOPS, the Swiss-led space telescope, was taking pictures of a planetary system 50 light-years away.

A planet like no other

The planetary system is located in the constellation Lupus (latin for Wolf), around a star called Nu2 Lupi, visible to the naked eye (but not from Switzerland). In 2019, Swiss astronomers announced the detection of three exoplanets around this bright, Sun-like star. The three exoplanets have masses between those of Earth and Neptune (17 times the Earth) and take 12, 28 and 107 days to circle their parent star. "What makes these exoplanets really outstanding is that we can see them passing just in front of their star; they're said to 'transit'", says Yann Alibert, professor of astrophysics at the University of Bern and co-author of the study which has been published in Nature Astronomy. "We knew that already for the two inner planets, which led us to point CHEOPS to the system in the first place. However, the third planet is quite far away from the star, no one was expected to see its transit!", Alibert adds. In fact, the farther away the planet is from its star, the less likely it is to transit.

This proved a game changer, as it is the first time an exoplanet with a revolution period of over 100 days - which corresponds to a distance from the star somewhere between that of Mercury and Venus from the Sun - has been spotted transiting a star that is bright enough to be visible to the naked eye.

"Due to its relatively long period, the amount of stellar radiation reaching the planet is mild in comparison to many other discovered exoplanets. The less radiation a planet receives, the less it changes over time. Therefore, a planet with a long period could have retained more information about its origin", says David Ehrenreich, professor at the University of Geneva and mission scientist of CHEOPS, who co-signed the study. But so far, the few such exoplanets astronomers had found orbited faint stars. In other words: little of their light reaches Earth and therefore makes them difficult to study. Not this time: "Since its bright host star is quite close to us, it is easier to study. This makes it a golden target for future study with no known equivalent", Ehrenreich adds.

Further insights from other telescopes

The high-precision measurements of CHEOPS reveal the third planet, called nu2 Lupi d, to be about 2.5 times the size of Earth and almost 9 times its mass. By combining these measurements with archival data from other observatories and numerical models developed by the University of Bern, Laetitia Delrez, a visiting researcher at the University of Geneva and lead-author of the study, was able to accurately characterize the density and composition the planet and its neighbors. "The innermost planet is mainly rocky, while the outer two appear to be enshrouded in envelopes of hydrogen and helium gases beneath which they hold large amounts of water", Delrez explains. Far more water, in fact, than the Earth has: a quarter of each planet's mass is made up of water, compared to less than 0.1% for Earth. This water, however, is not liquid, instead taking the form of high-pressure ice or high-temperature steam, making the planets uninhabitable. But these insights could only be the beginning.

"Now that we discovered that all three planets transit and have precisely measured their properties, the next step is to study them with bigger and more powerful instruments than CHEOPS, like the Hubble Space Telescope or its successor, the James Webb Space Telescope. They could reveal further details, such as the composition of the atmosphere" says Ehrenreich. Given its overall properties and orbit, planet d is going to become the poster-child of exoplanets with a mild-temperature atmosphere around a star similar to the Sun.

Annapolis, MD; June 28, 2021—Drones keep getting smaller and smaller, while their potential applications keep getting bigger and bigger. And now unmanned aircraft systems are taking on some of the world’s biggest small problems: insect pests.

From crop-munching caterpillars to disease-transmitting mosquitoes, insects that threaten crops, ecosystems, and public health are increasingly being targeted with new pest-management strategies that deploy unmanned aircraft systems (UAS, or drones) for detection and control. And a variety of these applications are featured in a new special collection published this week in the Journal of Economic Entomology.

“Ten years ago, there was not much happening in the space in terms of entomologists deploying UAS for pest management,” says Nathan Moses-Gonzales, CEO of M3 Agriculture Technologies, who compiled the research collection alongside Michael Brewer, Ph.D., professor of field crops entomology with AgriLife Research at Texas A&M University. But, in the time since, technological advances have opened the doors for creative collaborations between entomologists and drone developers, Moses-Gonzales says. “The evolution of UAS technology in entomology has been fascinating to watch.”

The collection in the Journal of Economic Entomology, featuring both newly released and recently published research, gathers examples illustrating both the progress and potential of drone technology in insect pest management settings. Case studies include:

Locating and sampling standing water for mosquito larvae and improving accuracy of insecticide applications targeting mosquito larvae and adults.
Applying precise amounts of pheromones via drone over cranberry beds to disrupt the mating of cranberry fruitworms (Acrobasis vaccinii) and blackheaded fireworms (Rhopobota naevana).

Photographing tree canopies from above via drone in winter to survey for presence of cocoons of the moth Monema flavescens and prevent defoliation in the subsequent summer.
Delivering and releasing predator and parasitoid insects via drone to target the European corn borer (Ostrinia nubilalis) and the eastern spruce budworm (Choristoneura fumiferana).
Using drones to release sterile Mexican fruit flies (Anastrepha ludens) and codling moths (Cydia pomonella) to suppress wild populations of the pests—a modern improvement on the classic sterile insect technique.

Several articles in the collection also explore potential future applications for drone technology in insect pest management, including aerial spectral imagery of crops and plants to assess signs of pest damage, enhanced deployment of traps and monitoring systems to detect insects in hard-to-reach locations, and more.

“Our special collection speaks to the uniqueness of these partnerships and demonstrates the vital role entomologists play in bringing concepts to reality through methods development and field testing,” Moses-Gonzales says.

Of course, continued research, development, and experimentation will refine drone technology in the pest management context, and research in related fields such as automation and artificial intelligence will be critical, as well. Moses-Gonzales and Brewer say they see a bright future for this multidisciplinary field.

“Here, we hope that the Journal of Economic Entomology will serve as a venue that not only supports rigorous research but also details the development of new and novel tools for use in pest management,” Moses-Gonzales says.

The year 2020 was a period of economic hardship and significant change in a wide range of sectors for most countries. A team of authors from HSE University has explored how Russia will recover from this crisis and which industries will be affected by the economic recovery. Their study was published in the journal Voprosy ekonomiki.

Last year, the global economy experienced a crisis due to the coronavirus pandemic, with output falling by 3.5% compared to 2019. Russia's decline from the coronavirus measures was more moderate than in many developed countries (industrial production fell by 3.1% in 2020) and much less severe than in past crises (7.8% in 2009 and 5.3% in 1998). Recovery following those crises took different trajectories -- in the early 2000s the Russian economy showed very high growth rates, while the 2008-2009 crisis was followed by stagnation. Experts are now attempting to predict which scenario the recovery will mimic in the coming years and how sustainable growth will be.

The authors of the paper analysed the sources that shaped economic growth in Russia from 1995 to 2016. To do so, they compared the contribution of various production factors to economic growth in different industries, labour productivity and resource efficiency. Separately, the authors sought to distinguish between intensive growth (due to lower specific labour and capital costs) and extensive growth (due to the new resources).

Economists have used the term Total Factor Productivity (TFP), which characterizes the efficiency of production and use of resources (other than capital and labour) and determines the growth generated by lower factor inputs per unit of output. For example, in 2002-2007, almost all productivity growth was achieved through an increase in TFP (5.5 p.p. out of 6 per cent), while in 2011-2016 productivity rose (through capital inputs) but TFP declined, indicating less sustainable economic growth after the 2008-2009 crisis.

In Russia, this approach tends to be applied to the economy as a whole rather than to individual industries. In this case, differences in productivity across industries and labour reallocation between industries are not taken into account; this can affect conclusions about the degree of intensity and sustainability of growth. To avoid this problem, researchers have used the KLEMS indicator system, which allows individual industries' contribution to economic growth to be assessed and compared, as well as productivity growth and resource efficiency to be measured.

There are two sources of productivity growth: intra-industry (technology development, improvements in labour quality, capital inflows) and that which is due to structural shifts (reallocation of workers between sectors). Total labour productivity growth between 1995 and 2016 was 2.9%, three-quarters of which came from intra-industry sources. During the period of rapid TFP growth (2002-2007), the largest contributors were construction, trade and telecommunications, the expanded mining complex (EMC - mining, including oil and gas, fuel production and wholesale trade), finance, and business services. In 2011-2016, only finance and agriculture remained on the plus side, while the EMC saw the biggest drop, which also had a significant effect on overall economic growth.

The remaining quarter of the productivity increase comes from the reallocation of labour. The main direction is from goods to services: from agriculture and manufacturing to construction, trade, telecommunications and finance. At the same time, agricultural productivity remains very low (it is highest in EMC and finance), so reallocation of workers increases average productivity in the economy.

In making their forecast, the researchers have assumed that main pre-COVID proximate sources of growth remain the same. In this scenario, the calculations show that the largest contribution to economic growth is to be expected from the contribution of capital formation to the EMC. In terms of possible growth stimulating policy the most promising issue seems to be some efforts to make EMC more efficient. Additional growth under these conditions can be provided primarily through measures to improve production efficiency and exports of natural resources; these measures should be based on further analysis of the reasons for the decline in EMC efficiency, which started well before the pandemic. Such causes can be both objective (e.g., worsening production conditions), as well as subjective and able to be corrected (e.g., imperfect transportation tariffs for petroleum products). Reducing the Russian economy's dependence on the state of the EMC requires economic diversification and reducing the share of the EMC. Despite the fact that the need to reduce the share of the EMC has been discussed for decades, the share of the EMC in value added has remained unchanged since 1995, holding steady at 20-25%.

'For now, I assume the situation will be similar to the early 2010s -- a boom period in China, a build-up of commodity exports in resource-exporting countries, including Russia, increased investment in the Russian mining complex and associated infrastructure. As a consequence, we will see a tangible contribution to growth through capital intensity in natural resource extraction and export activities. We should see this in the dynamics of investment in oil and gas extraction, infrastructure, mining and processing of metal ores, and corresponding export positions,' said Ilya Voskoboynikov https://www.hse.ru/en/org/persons/503434, Assistant Professor in the Faculty of Economic Sciences and director of the Centre for Productivity Studies at HSE and one of the authors of the study, in sharing his forecast. 'A noticeable recovery in other areas will indicate the possible emergence of other sources of growth.'

LAWRENCE -- Despite facing cultural and political pushback, the evidence remains clear: Face masks made a difference in Kansas.

"These had a huge effect in counties that had a mask mandate," said Donna Ginther, the Roy A. Roberts Distinguished Professor of Economics and director of the Institute for Policy & Social Research at the University of Kansas. "Our research found that masks reduced cases, hospitalizations and deaths in counties that adopted them by around 60% across the board."

Ginther's article "Association of Mask Mandates and COVID-19 Case Rates, Hospitalizations and Deaths in Kansas" examines the effect of masks on the state's 105 counties. It appears in JAMA Network Open, a journal published by the American Medical Association.

Kansas boasts the fifth-highest total of counties among all the states. Executive Order No. 20-52 that took effect in July of 2020 was initially adopted by only 15 counties, with 68 others not adopting the order through October. A second mandate in November was embraced by an additional 40 counties.

"We thought masks would matter for certain cases, but the effect size for hospitalizations and deaths being the same rate was pretty astonishing," Ginther said.

Co-written with Carlos Zambrana, an associate researcher at the Institute for Policy & Social Research, Ginther estimated masks saved about 500 lives in adoptive counties. And, yet, other counties often refused to adopt the mandate, citing personal freedoms and lack of scientific evidence as reasons.

"There's no way to run a clinical trial on masks because you'd have to observe people using them all the time, and we can't observe everyone's behavior. This type of observational study is the best we can do," Ginther said.

"But in terms of personal freedom, I would say that wearing a mask is a public good. There's a negative externality to not wearing one, and you could get infected or infect others. In a pandemic, where close to 600,000 people have died, this is a low-cost preventative measure that preserves life."

Data for her study was corralled from several sources. She used the daily total number of cases per county from The New York Times COVID-19 data in the U.S. GitHub repository. The state information came from the list of county official actions compiled by the Kansas Health Institute. Linear regression difference-in-difference models were then employed, with cases regressed on an indicator variable that started 21 days after the mandate to allow for changes in mask-wearing behavior, an indicator for no coronavirus cases and the number of days since the first recorded case.

"We are required to wear seatbelts in the state to save lives. We get driver's licenses to save lives. We have vaccine mandates for children going to school to prevent the spread of infectious disease. These are all public health measures that we follow. At some point, the government steps in and says, 'These are the right things to do to save lives,'" she said.

Aside from the health implications of ignoring a mask mandate, there are also economic ones.

"COVID-19 costs money," she said. "It slows down economic activity. It drains money for hospitalizations. We show that if you prevent COVID, you save the health care system money."

Now in her 18th year at KU, Ginther believes "Association of Mask Mandates" demonstrates the importance of nonmedical interventions for preventing the spread of respiratory diseases.

She said, "Given everything that's happening around the world, this may not be the last pandemic in our lifetime. Just think about places like India that don't have access to the vaccine. If you're wanting to slow the spread, knowing that a mask works and is a cost-effective approach to public health is really important."

In the context of recent debate over the FDA's approval of aducanumab, it's refreshing to learn about a model of Alzheimer's neurodegeneration that doesn't start with the pathogenic proteins amyloid or Tau.

A new paper in Alzheimer's & Dementia from Emory neuroscientist Shan Ping Yu and colleagues focuses on an unusual member of the family of NMDA receptors, signaling molecules that are critical for learning and memory. Their findings contain leads for additional research on Alzheimer's, including drugs that are already FDA-approved that could be used preventively, and genes to look at for risk factors.

"It's not just another rodent model of Alzheimer's," Yu says. "We are emphasizing a different set of mechanisms leading to neurodegeneration."

Those mechanisms include alterations in calcium and neuronal hyperactivity, which occur first in this mouse model, rather than standard models that have clumps of amyloid or Tau as the primary drivers.

For the last several years, Yu and his laboratory have been studying the NMDA receptor subunit GluN3A in the context of stroke and also brain development. According to their research, GluN3A acts like a control rod in a nuclear reactor, cooling down signaling in the brain so that things don't overheat. It's an inhibitory part of a receptor assembly that is usually stimulatory.

Yu says GluN3A's role in the adult brain is understudied, because it is generally thought to fade away after early development. Mice that are missing the gene for GluN3A get a benefit earlier in life, in that they have enhanced memory and spatial learning. But later on, the missing gene's function catches up, and the mice develop several features of Alzheimer's, including olfactory deficits, cognitive decline, neurodegeneration and neuroinflammation, and eventually amyloid/tau pathology.

"We show that virtually all clinical symptoms and pathophysiology spontaneously developed in the GluN3A knockout mouse in an age-dependent manner," Yu says.

Yu says he was originally motivated to examine GluN3A's role in neurodegeneration because the GluN3A-knockout mice develop the early symptom of olfactory dysfunction, which is commonly seen in Alzheimer's and Parkinson's patients. In the current paper, Yu and colleagues show that loss of GluN3A leads to elevated calcium levels, normally tightly regulated, and what they call "degenerative excitotoxicity".

This is distinct from the excitotoxicity that is harmful in traumatic brain injury or stroke - milder and more chronic. They connect the hyperactivity and inflammation to the "calcium hypothesis" for Alzheimer's - a well-established idea that dysregulated calcium drives neurodegeneration. Yu says that their discovery of the role of GluN3A relates more to the early stages of the disease, before amyloid plaque formation.

Looking forward, the findings on GluN3A have implications for additional investigation. First, the NMDA receptor inhibitor memantine is FDA-approved for Alzheimer's, but it is generally thought only to have an effect on symptoms. Yu's lab showed that they could prevent some (but not all) deficits by treating GluN3A-mutant mice with memantine. Maybe memantine or a similar drug could play a preventive role if given to people with mild cognitive impairment or early Alzheimer's? Second, genetic variations in GluN3A has barely been studied in Alzheimer's, and studies on other neuropsychiatric conditions suggest that a significant percentage of people carry mutations or deletions affecting GluN3A gene function.

Middle ear infections, also known as otitis media, affect more than 80% of the children in the U.S. In a new study, researchers have designed a miniaturized 3D-printed device to inactivate Pseudomonas aeruginosa, a common bacterium that causes the infection.

The device--a microplasma jet array--generates plasma, which is composed of charged particles and reactive molecules that have been previously shown to inactivate various pathogens. "This is the first time anyone has tried treating middle ear infections using plasma technology," said Jungeun Won, a graduate student in the Boppart lab. "Usually, the treatment involves using antibiotics or surgical intervention."

The problem with using antibiotics is two-fold. First, antibiotics are ineffective in more than 30% of the patients with acute infections. Second, their use can lead to increased antibiotic resistance because the bacteria form biofilms--aggregates that attach to the surface of the ear.

"Biofilms are very dense, making it difficult for the antibiotics to penetrate," said Helen Nguyen (IGOH), an Ivan Racheff Professor in Civil and Environmental Engineering. "Our idea was that if we could disrupt the structure of the biofilm, we could increase the penetration of the antibiotics."

The researchers tested the microplasma jet array by building a model of the middle ear. They used an excised rat eardrum and tested the antimicrobial effects of the microplasma on the bacteria that were located behind the eardrum.

"We used different duration times for the treatment and found that 15 minutes and longer was effective in inactivating the bacteria," Won said. "We also monitored the tissue to see if we had created any holes or ruptures, but we didn't find any obvious physical damage."

"We think that the microplasma disrupts the biofilm by disturbing the bacterial cell membrane," Nguyen said. "So far, we only have indirect measurements supporting our idea, but we will look into it in the future."

Although the thickness of the rat eardrum is 30% lower than that of a human, which is about the width of a hair strand, the results suggest that the microplasma treatment could be used to treat middle ear infections in humans.

"Middle ear infections and the over-prescription of antibiotics to treat these are major clinical challenges that are in need of new treatment technologies and solutions," said Stephen Boppart, Grainger Distinguished Chair in Engineering, who is also a medical doctor.

The researchers are now designing a smaller, earbud-shaped jet array for treatments that will allow longer exposure times. They will also test the devices on animal models using biofilms of the other bacteria that cause middle ear infections, including, but not limited to, Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, to test whether the treatment is also effective with these bacteria. Additionally, the researchers will closely monitor the tissues of the middle ear to ensure that there is no structural and functional tissue damage from the plasma technology.

New Brunswick, N.J. (June 28, 2021) - A Rutgers-led study sheds new light on the evolution of photosynthesis in plants and algae, which could help to improve crop production.

The paper appears in the journal New Phytologist.

The scientists reviewed research on the photosynthetic amoeba Paulinella, which is a model to explore a fundamental question about eukaryote evolution: why was there a single origin of algae and plants? That is, why did photosynthesis by primary plastid endosymbiosis not originate multiple times in the tree of life?

Photosynthesis is the process by which plants and other organisms use sunlight to synthesize foods from carbon dioxide and water, which generates oxygen as a byproduct.

Endosymbiosis is a relationship between two organisms wherein one cell resides inside the other. This interaction, when stable and beneficial for the "host" cell, can result in massive genetic innovation. Despite its critical evolutionary role, there is limited knowledge about how endosymbiosis is initially established.

Primary plastid endosymbiosis, which evolved about 1.5 billion years ago, is the process in which a eukaryote -- which are organisms such as plants and algae whose cells have a membrane-bound nucleus and tiny organs called organelles -- engulfs a prokaryote, which are organisms such as bacteria that lack a membrane-enclosed nucleus. The plastid is a membrane-bound organelle within the cells of plants and algae.

"It turns out that photosynthesis results in enormous risks because it produces harmful chemicals and heat as byproducts that can damage the host cell," said senior author Debashish Bhattacharya, a Distinguished Professor in the Department of Biochemistry and Microbiology at Rutgers University-New Brunswick. "Therefore, creating a novel organelle is a highly complex process that makes it fleetingly rare in evolution. Paulinella, which is the only known case of an independent plastid primary endosymbiosis other than in algae and plants, offers many clues to this process that helps explain why it is so rare."

The origin of photosynthesis in algae and plants changed our planet by providing a major source of oxygen and supporting many ecosystems, due to their primary production, of fixed carbon (sugars and lipids). Understanding how this critical process happened will help us potentially engineer it in synthetic systems as well as to improve crop production.

"Because Paulinella is an independent origin of photosynthesis, it provides key clues to how this process occurs and what costs it imposes on the host cell," said lead author Timothy G. Stephens, a postdoctoral researcher at Rutgers. "The genome of Paulinella contains many independently evolved genes involved in photosynthesis and dealing with the associated stresses that can potentially be engineered in algae and plants could help to improve their ability to withstand stresses such as high light levels or salt stress."

AMES, Iowa - During the course of a criminal investigation, it is common for investigators to interview individuals who are exhausted and have had little sleep. While unavoidable in some cases, a new Iowa State University study found sleep disruption or deprivation may limit the amount of information provided during an interview.

The study, published in the academic journal SLEEP, is one of the first to look at how sleep affects behavior during interrogations or interviews. Zlatan Krizan, an ISU professor of psychology, says while beliefs about the impact of sleep on interrogation subjects have existed for decades, he and co-authors, ISU professor Christian Meissner and graduate student Anthony Miller, found little direct scientific evidence related to its effectiveness. Krizan says the findings from their study have implications for suspect interviews as well as the countless interviews investigators conduct with victims of and witnesses to crimes.

"This is the first evidence to really hit on the efficacy of sleep loss as a tactic to elicit more information," Krizan said.

To test the effect of sleep deprivation or disruption, the research team interviewed sleep-restricted and well-rested individuals about past criminal activity and then compared the quantity and quality of their responses (more detail about study design below). The results show sleep-restricted participants provided 7% less information about the crime, in terms of who, what, when, why, where or how.

"Think about how many interviews and pieces of information are collected in the course of a homicide investigation," Krizan said. "If investigators are interviewing individuals who are sleep deprived, across 10 people they're missing five pieces of critical information that they could use to corroborate or cross check with other information."

Findings related to the quality or precision of the information showed a similar pattern, although they did not reach statistical significance. Several additional findings suggested lack of sleep hampered motivation and made it more difficult to remember details.

Sleep loss common

In the paper, the researchers referenced anecdotal reports of investigators waking up suspects in order to conduct an interview. Given the circumstances surrounding most crimes, Krizan says it is not unusual for suspects, victims or witnesses to be fatigued or functioning on just a few hours of sleep when they are interviewed.

To reflect these interview conditions, researchers randomly assigned the 143 participants to a sleep-restricted or control group. Those in the sleep-restricted group were instructed to go to bed two hours later than normal and wake up two hours earlier to remove up to eight hours of sleep over two days. To monitor compliance, participants wore a watch to track their sleep and wake patterns.

For the interview, participants were asked to disclose past criminal activity based on a list of 20 crimes that ranged from transporting fireworks and trespassing to shoplifting and driving under the influence. They were then questioned about the most severe crime - underage drinking, experimenting with illegal drugs and driving under the influence were the most common.

Meissner, a professor of psychology who studies interrogation techniques, says additional research is needed to determine how sleep loss affected behavior.

"People who had less sleep were not as motivated to recall information or found doing so required more effort to recall information," Meissner said. "These patterns suggest that increased fatigue due to sleep loss may be an important factor in disclosure."

The researchers acknowledged that study participants did not face the threat of any legal consequence as a suspect would in a criminal case. However, they likely experienced other barriers, such as feelings of guilt or shame, similar to many suspects, victims or witnesses involved in a crime. The researchers say this is another area to explore with future studies.

One of the key mutations seen in the 'Alpha variant' of SARS-CoV-2 - the deletion of two amino acids, H69/V70 - enables the virus to overcome chinks in its armour as it evolves, say an international team of scientists.

SARS-CoV-2 is a coronavirus, so named because spike proteins on its surface give it the appearance of a crown ('corona'). The spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. The virus manipulates the host cell's machinery to allow the virus to replicate and spread.

As SARS-CoV-2 divides and replicates, errors in its genetic makeup cause it to mutate. Some mutations make the virus more transmissible or more infectious, some help it evade the immune response, potentially making vaccines less effective, while others have little effect.

Towards the end of 2020, Cambridge scientists observed SARS-CoV-2 mutating in the case of an immunocompromised patient treated with convalescent plasma. In particular, they saw the emergence of a key mutation - the deletion of two amino acids, H69/V70, in the spike protein. This deletion was later found in B1.1.7, the variant that led to the UK being forced once again into strict lockdown in December (now referred to as the 'Alpha variant').

Now, in research published in the journal Cell Reports, researchers show that the deletion H69/V70 is present in more than 600,000 SARS-CoV-2 genome sequences worldwide, and has seen global expansion, particularly across much of Europe, Africa and Asia.

The research was led by scientists at the University of Cambridge, MRC-University of Glasgow Centre for Virus Research, The Pirbright Institute, MRC Laboratory of Molecular Biology, and Vir Biotechnology.

Professor Ravi Gupta from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the University of Cambridge, the study's senior author, said: "Although we first saw this mutation in an immunocompromised patient and then in the Kent - now 'Alpha' - variant, when we looked at samples from around the world, we saw that this mutation has occurred and spread multiple times independently."

Working under secure conditions, Professor Gupta and colleagues used a 'pseudotype virus' - a harmless virus that displays SARS-CoV-2 spike proteins with the H69/V70 deletion - to understand how the spike protein interacts with host cells and what makes this mutation so important.

When they tested this virus against blood sera taken from fifteen individuals who had recovered from infection, they found that the deletion did not allow the virus to 'escape' neutralising antibodies made after being vaccinated or after previous infection. Instead, the team found that the deletion makes the virus twice as infective - that is, at breaking into the host's cells - as a virus that dominated global infections during the latter half of 2020. This was because virus particles carrying the deletion had a greater number of mature spike proteins on their surface. This allows the virus to then replicate efficiently even when it has other mutations that might otherwise hinder the virus.

"When viruses replicate, any mutations they acquire can act as a double-edged sword: a mutation that enables the virus to evade the immune system might, for example, affect how well it is able to replicate," said Professor Gupta.

"What we saw with the H69/V70 deletion was that in some cases, the deletion helped the virus compensate for the negative effects that came with other mutations which allowed the virus to escape the immune response. In other words, the deletion allowed these variants to have their cake and eat it - they were both better at escaping immunity and more infectious."

Dr Dalan Bailey from The Pirbright Institute, who co-led the research, added: "In evolutionary terms, when a virus develops a weakness, it can lead to its demise, but the H69/V70 deletion means that the virus is able to mutate further than it otherwise would. This is likely to explain why these deletions are now so widespread."

Bo Meng from the Department of Medicine at the University of Cambridge, first author on the paper, said: "Understanding the significance of key mutations is important because it enables us to predict how a new variant might behave in humans when it is first identified. This means we can implement public health and containment strategies early on."

Below please find link(s) to new coronavirus-related content published today in Annals of Internal Medicine. All coronavirus-related content published in Annals of Internal Medicine is free to the public. A complete collection is available at https://annals.org/aim/pages/coronavirus-content.

1. ACTIV Therapeutics-Clinical Working Group describe development and launch of nine master protocols for evaluating therapeutic agents for COVID-19

Free full text: https://www.acpjournals.org/doi/10.7326/M21-1269

Members of the ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) workgroup, a partnership of experts representing government, industry, and academia, describe how nine master protocols for evaluating therapeutic agents for COVID-19 were designed, developed, and launched, and lessons learned that may be useful in meeting the challenges of a future pandemic. Their commentary is published in Annals of Internal Medicine.

The Therapeutics-Clinical Working Group (TX-Clinical WG) within ACTIV, which is coordinated by the Foundation for the NIH, was created to develop a systematic review process for identification and prioritization of therapeutic candidates and to create master protocols for efficient, flexible, rigorous assessment of safety and efficacy of selected candidates. This is important because a master protocol uses a single trial infrastructure, trial design, and protocol to evaluate 1 or more drugs in 1 or more diseases for efficient and accelerated drug development. The protocols clearly define research objectives for candidates being studied and all candidates are evaluated against a control rather than each other. The protocols call for randomization, shared controls, adequate power to detect moderately sized treatment effects with respect to primary end points, early stopping rules if a trial proves futile, design adaptations, graduation rules, and end point alignment. Currently, the protocols are being used to evaluate existing and new drugs to treat patients in four clinical population categories: critically ill/ventilated; hospitalized/moderately ill; outpatient; and prevention.

The authors detail several trials currently underway using the master protocols and the lessons learned so far. Their hope is that this initiative will help to lessen the mortality and morbidity of COVID-19 and that the process developed may inform responses to future pandemics.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. To speak with the corresponding author, Stacey Adam, PhD, please contact Katherine Thompson at kthompson@fnih.org.

Also new in Annals:

Moral Injury

Venktesh R. Ramnath, MD

On Being A Doctor

Free full text: https://www.acpjournals.org/doi/10.7326/M21-0997

ANN ARBOR, Mich. -- As their infants and toddlers grow, many parents may wonder if their children are walking, talking and socializing when they're supposed to be.

In fact, nearly a quarter of parents have suspected their child might be delayed in their development, a new national poll finds - but they may not always share these concerns with a doctor.

Among parents who worried that their child was behind in hitting milestones, nearly one in five did not seek advice from a healthcare or childcare provider, according to the University of Michigan C.S. Mott Children's Hospital National Poll on Children's Health.

"Parents may be unsure whether their child is progressing appropriately for their age and are on track with peers," says co-poll director and Mott pediatrician Gary L. Freed, M.D., M.P.H. "While most do seek a professional's advice, some parents may turn to potentially less reliable sources, like friends or online content."

The majority of parents felt confident in knowing when children should achieve most of their developmental milestones, according to the nationally-representative report based on responses from 779 parents with at least one child five or under.

And more than 80% of those who suspected their child was behind asked for advice from either healthcare providers (63%) or childcare providers (24%).

Still, another 18% only looked up information online, asked family or friends or sought advice on social media. Parents who have worried their child might be delayed are also more likely to learn about milestones from the internet than parents who haven't had these concerns.

"When parents seek advice from friends, family or social media, they may hear inaccurate or outdated information about what's expected during different stages of development," Freed says.

One in three parents also said they've compared their children to a friend's child and a similar number said they compared siblings. Dads were more likely than moms to have compared their child to friends' children (41% vs 28%) or to other children in their family (32% vs. 25%.)

Freed notes that while most milestones typically take place during predictable windows, there's a range of normal for gaining certain skills like walking, talking or laughing.

"It's important for parents to keep in mind that child development is a process that unfolds over time. Each child is unique," he says. "Some children might reach certain milestones earlier or later than same-age peers. This doesn't necessarily mean that one child is advanced or that another is delayed."

Sometimes parents aren't the first to notice potential developmental concerns in their child, according to the poll, with some hearing about it from family members (9%), healthcare providers (9%) or friends (4%).

But if parents have any questions about a child's physical, social/emotional, communication, and cognitive skills, they should ask an expert, Freed says. Healthcare providers will check on a child's progress during well-child visits asking about such developments as rolling over, smiling at a parent, babbling or responding to facial expressions.

For some children, such as those born premature, expectations about the timing of developmental milestones will also need to be adjusted, Freed notes.

"Checking and monitoring developmental milestones can be helpful in detecting delays or problems early and assessing whether children need additional support," Freed says.

"For many parents, well child visits are the best time to discuss age appropriate milestones and to learn what to be looking for by the next checkup."

Arlington, Va., June 28, 2021 - Designed initially for entertainment purposes, escape rooms are proving their value as medical training tools as demonstrated by the Central Texas Veterans Health Care System. Staff there have used the concept for a flu pandemic escape room and is reporting increased staff handwashing and acceptance of flu vaccines as a result.

The escape room is the brainchild of Gracia Boseman, RN, MPH, and Kristy Causey, MSN, RN, who are presenting their findings today at the Association for Professionals in Infection Control and Epidemiology's (APIC's), 48th Annual Conference, being held virtually.

In 2017, Boseman and Causey aimed to boost staff attendance, especially among non-clinical staff, of voluntary infection prevention and control education at the health care system, which includes hospitals and clinics surrounding Austin, Waco, and Temple. Seizing on the popularity of The Walking Dead and the fact it was almost Halloween, the team hit upon the idea for a zombie-themed High Consequence Infectious Disease (HCID) escape room to entice staff into the sessions.

Not only was their escape room a runaway hit, but the concept proved to be prescient as it preceded the coronavirus pandemic by three years.

"The escape room was successful beyond our wildest expectations," said Boseman, who added that self-reported behavioral changes among participants include an increase in handwashing by 61% and personal protective equipment (PPE) use by 21%. "Staff also became acutely aware that contaminated surfaces play a role in disease transmission as they carry viruses and bacteria, and the importance of wearing PPE -- knowledge that would prove invaluable during the COVID-19 pandemic."

Participants were given a pandemic, novel flu scenario and asked to select appropriate PPE prior to entering the room. Once inside, participants had to work as a team to find all the clues in the short amount of time.

"The more senses we engage, the more people learn and the higher the level of retention, so we designed a hands-on, immersive training environment," explained Causey. "We set up different types of specimen collection kits including viral transport medium and bacterial swabs, and participants had to pick the correct swab. We also placed whitening laundry detergent on surfaces to show where germs were and how they transfer from one surface to the other."

Attendance at voluntary education increased from an average of 20 clinical attendees per training to 189 clinical and non-clinical attendees. Non-clinical staff included clerks, facilities and engineering staff, and environmental services workers. The team reported employee lines before they opened, took walk-ins during their lunch breaks, outfitted a bus to take the escape room to outlying clinics, and repeated the escape room for infection prevention training in 2018 and 2019.

Planned trainings for 2020 were cancelled due to COVID. However, during the COVID-19 pandemic, Boseman and Causey noted that hospital employees who had attended the trainings were more actively engaged in preparation for the pandemic. Ultimately, the Central Texas Veterans Health Care System trained more than 1,100 employees over three years using the escape room.

"Engaging healthcare staff in the basics of infection prevention and control is a cornerstone of patient safety," said 2021 APIC President Ann Marie Pettis, BSN, RN, CIC, FAPIC. "This team proves that when learning is fun, we can achieve better health outcomes, and that's a win for everyone."

The Central Texas Veterans Healthcare System has provided consultative input to a half-dozen other Veteran health care systems interested in replicating the escape room as part of their infection prevention training and other simulation training.

Sophia Antipolis - 28 June 2021: A study in more than 200,000 individuals has found that patients with heart failure are more likely to develop cancer compared to their peers without heart failure. The research is presented today at Heart Failure 2021, an online scientific congress of the European Society of Cardiology (ESC),1 and published in ESC Heart Failure, a journal of the ESC.2

"This was an observational study and the results do not prove that heart failure causes cancer," said author Dr. Mark Luedde of the Christian-Albrechts-University of Kiel and Cardiology Joint Practice Bremerhaven, Germany. "However, the findings do suggest that heart failure patients may benefit from cancer prevention measures."

Heart failure affects around 65 million people worldwide.3 Some patients with cancer develop heart failure as a consequence of cancer treatment.4 More recently it has also emerged that heart failure patients may have an elevated incidence of cancer during the course of their heart disease, but most studies have been small.5-8

The current study investigated the association between heart failure and new cancer development in a large cohort. The study used information from the nationally representative Disease Analyser database, which covers 1,274 general practices in Germany.

A total of 100,124 patients with heart failure and 100,124 individuals without heart failure were
included in the analysis. Heart failure patients and those without heart failure were individually matched by sex, age, obesity, diabetes, and consultation frequency. No participants had cancer at the start of the study. Statistical models were used to examine the association between heart failure and the incidence of cancer over 10 years.

The average age of the study population was 72.6 years and 54% were women. During the 10 year observation period, the incidence of cancer was significantly higher among heart failure patients (25.7%) compared to those without heart failure (16.2%). In women, the incidence of cancer was 28.6% in patients with heart failure and 18.8% in those without heart failure. In men the corresponding rates were 23.2% and 13.8%.

Heart failure was significantly associated with the incidence of cancer, with a hazard ratio of 1.76. The hazard ratios for women and men were 1.85 and 1.69, respectively.

Significant associations were found between heart failure and all cancer types assessed. The greatest increase in risk was observed for cancer of the lip, oral cavity, and pharynx, with a hazard ratio of 2.10, followed by respiratory organ cancer, with a hazard ratio of 1.91. The hazard ratios for other sites were 1.86 for female genital organ cancer, 1.83 for skin tumours, 1.77 for lymphoid and haematopoietic tissue cancer, 1.75 for digestive tract cancer, 1.67 for breast cancer, 1.64 for genitourinary tract cancer, and 1.52 for male genital organ cancer.

Dr. Luedde said: "Our results allow us to speculate that there may be a causal relationship between heart failure and an increased rate of cancer. This is biologically plausible, as there is experimental evidence that factors secreted by the failing heart may stimulate tumour growth."7

He continued: "While heart failure and cancer share common risk factors such as obesity and diabetes, these were accounted for in the analysis by matching. It should be noted that our database does not include information on smoking, alcohol consumption or physical activity, so we were unable to match for these in the analysis."

Dr. Luedde concluded: "It is common practice for cancer patients who have received heart-damaging drugs to be monitored for heart failure. Conversely, evidence is accumulating to indicate that heart failure patients could benefit from intensive monitoring for cancer development - for example through screening. Considering the high incidence of both

Oncotarget published "The presence of polymorphisms in genes controlling neurotransmitter metabolism and disease prognosis in patients with prostate cancer: a possible link with schizophrenia" reported that polymorphisms of neurotransmitter metabolism genes were studied in patients with prostate cancer (PC) characterized by either reduced or extended serum prostate-specific antigen doubling time corresponding to unfavorable and favorable disease prognosis respectively.

The following gene polymorphisms known to be associated with neuropsychiatric disorders were investigated:

A. The STin2 VNTR in the serotonin transporter SLC6A4 gene;

B. The 30-bp VNTR in the monoamine oxidase A MAOA gene;

C. The Val158Met polymorphism in the catechol-ortho-methyltransferase COMT gene;

D. The promoter region C-521T polymorphism and the 48 VNTR in the third exon of the dopamine receptor DRD4 gene.

The STin2 12R/10R variant of the SLC6A4 gene and the -521T/T homozygosity of the DRD4 gene tended to be overrepresented in PC patients with unfavorable disease prognosis.

These gene variants are regarded as protective against schizophrenia, and the observed trend may be directly related to a reduced PC risk described for schizophrenia patients.

These results warrant further investigation of the potential role of neurotransmitter metabolism gene polymorphisms in PC pathogenesis.

Dr. Vladimir N. Anisimov from The Petrov National Medical Research Center of Oncology said, "The importance of complex networks of heterotypic interactions between multiple distinct cell types (both malignant and normal) and regulatory circuits has now become widely recognized."

The importance of complex networks of heterotypic interactions between multiple distinct cell types (both malignant and normal) and regulatory circuits has now become widely recognized.

The traditional tumor-centric view focused exclusively on malignant cell populations has largely been replaced with a concept of tumor microenvironment, the latter being regarded as a "dynamic interaction arena in which tumor cells interact with the extracellular matrix, resident and recruited cells, and soluble factors".

Although there is a general consensus that chronic stress and depression tend to result in an impairment of the immune responses and might facilitate cancer initiation and progression, while the risk of developing some cancers appears to be decreased in patients with schizophrenia.

Pancreatic Cancer is not only the second most common cancer in men, but this is also a condition characterized by a wide variation of severity that ranges from indolent to highly aggressive disease.

The latter feature of PC makes tumor growth monitoring a very important prerequisite for successful disease management, and repeated measurement of the concentration of a blood biomarker of PC, prostate-specific antigen, is generally accepted as an important prognostic tool for routinely monitoring patients with this condition.

It was noted above that psychiatric disorders may be associated with a seriously altered PC risk, but little is known about possible influences of patients' genetic background both on this phenomenon and on disease prognosis when PC is already present.

The Anisimov Research Team concluded in their Oncotarget Research Output that oncological conditions are known to occur less frequently in schizophrenia patients, and this phenomenon primarily affects men, being especially pronounced for PC.

Interestingly, PC has recently emerged as a cancer, development of which strongly depends on neurogenic regulatory pathways provided by nerves growing as an important TME component.

Furthermore, neurotransmitters, such as serotonin and dopamine, are now regarded as major factors modulating neoplastic growth through influences on angiogenesis and neoplastic cell proliferation.

The results presented in this paper indicate that the presence of certain polymorphic variants of the SLC6A4 and DRD4 genes related to serotonin and dopamine signaling pathways respectively appears to correlate with PC prognosis.

Further larger studies are needed for clarifying the role of neurotransmitter metabolism gene polymorphisms in PC pathogenesis.