Culture

WINSTON-SALEM, N.C., - July 30, 2020 - The scientists who developed the first 3D multicellular brain organoid with a functional blood brain barrier now report that the model could be a promising platform to screen drugs that could work to control inflammation, which is at the center of many neurological conditions, like ischemic stroke.

Wake Forest Institute for Regenerative Medicine (WFIRM) scientists first published in 2018 that they had developed the 3D brain organoid - the first engineered tissue equivalent to closely resemble normal human brain anatomy containing all six major cell types found in normal organs including neurons and immune cells. They reported that the organoids promoted the formation of a fully cell-based, natural and functional barrier - the blood brain barrier - that mimics normal human anatomy. The blood brain barrier (BBB) is a semipermeable membrane that separates the circulating blood from the brain, protecting it from foreign substances that could cause injury.

"It is well known that inflammation is at the center of many neurological conditions," said Goodwell Nzou, PhD., a co-author of the study. "Our results here implicate inflammation as one of the causes of blood brain barrier dysfunction. These organoids can help us gain understanding of some of the brain physiological changes that happen as the result of a stroke."

For this study, the 3D brain organoid was used to model the effects of oxygen deprivation and inflammation on blood brain barrier function to better understand what is happening in a human brain during an ischemic stroke. The team evaluated the expression levels of proteins critical in BBB maintenance, basement membrane proteins, tight junction proteins, and BBB transport proteins, finding significant changes that may contribute to BBB dysfunction. The research shows how the BBB becomes leaky and allows blood-born components to easily cross the barrier.

"The work demonstrates how important this model is to further understanding of disease mechanisms at the BBB, the passage of drugs through the barrier, and the effects of drugs once they cross the barrier," said Anthony Atala, MD, senior author and director of WFIRM. "We can also optimize the model for personalized medicine. An organoid containing patient derived cells to identify therapeutic targets that are specific to the individual could be tested with different drugs to determine efficacy which will result in better outcomes for patients."

Winter cover crops benefit soil health and can suppress weeds in subsequent row crops but may also lead to lower yields. Some farmers and agronomists speculate that allelopathic chemicals released by cover crops may be the cause for some of the observed yield reductions, but cause-and-effect relationships are rarely established. We know that allelopathic cover crops inhibit weed seed germination and early growth, but do they also impact row crops?

In an article recently published in Agricultural & Environmental Letters, a publication of the American Society of Agronomy, Crop Science Society of America and Soil Science Society of America, researchers reviewed literature documenting effects of allelopathic winter cover crops on four row crops. Studies that used known allelochemicals in the lab or measured allelochemicals in the field were included.

Only seven studies met the criteria for inclusion and six of them were lab studies. Corn and wheat germination and root length were sometimes impacted by allelopathic chemicals from cereal rye and other cover crops, but soybean was unaffected. One field study reported reduced cotton performance due to allelopathic cover crops.

We could not establish clear cause-and-effect relationships for row crops grown in the field due to the limited number of studies. However, with the increase in cover crop acreage and constantly evolving management practices, research to identify risk factors for allelopathic impacts and how to avoid them is needed.

Australian researchers have shown how viruses can be used to save lives, developing the potential use of bacteriophages in bandages to treat life-threatening golden staph infections which may not respond to traditional antibiotics.

Targeting multidrug-resistant Staphylococcus aureus ('golden staph') in diabetic foot ulcers, Flinders University microbiology researchers have joined infectious diseases and pharmaceutical partners to show the usefulness of a possible 'phage cocktail' therapy on wound infections.

A phage (or bacteriophage) is a virus capable of infecting a bacterial cell and is capable of being used in a range of medical applications including as a therapy against 'superbugs'.

Bacteriophages (phages, viruses that infect bacteria) represent an alternative or adjunct therapy to antibiotics, with S aureus a common and particularly virulent pathogen often found to be resistant and limited for antimicrobial treatment options.

"Diabetic foot ulcers are very dangerous and when infected can lead to amputation and even death," says Flinders University Associate Professor Peter Speck, who is Secretary of the Australasian Virology Society.

"The next step in our research is to bind phages to a dressing to make a truly antibacterial dressing, with specific activity against golden staph. The technology exists to make such a dressing, with a big advantage being that bound phages remain viable for a year even when stored at room temperature, making this approach ideal for use in hospitals and clinics - even in rural and remote settings."

Co-author on a new paper in BMC Microbiology, Flinders PhD Legesse Garedew Kifelew says the results of the sound treatment in mice were very promising.

"This study demonstrates that phage therapy could be a potential alternative in combating antibiotic-resisant bacterial infections," says Mr Kifelew, who works in infectious disease management at the Queen Elizabeth Hospital and has ties to St Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.

"The phages effectively decreased the bacterial load and significantly improved wound healing in in multi-drug resistant S aureus infection - similar or superior to the currently prescribed antibiotic treatment," he says.

With diabetes on the rise, the global burden of diabetic foot ulcers (DFUs) is also affecting up to 26.1 million people each year, with these ulcers the cause of almost 90% of limb amputations. The five-year mortality rate following foot amputation due to DFUs has been estimated at up to 74%.

Based on 2015 prevalence data from the International Diabetes Federation, it is estimated that foot ulcers develop in 9.1 million to 26.1 million people with diabetes annually worldwide.

In the US, the annual cost of managing DFU infections is estimated at an additional US$9-13 billion over the cost of diabetes itself. In England, it is estimated that the annual cost of managing DFUs exceeds the total cost of breast, prostate and lung cancers combined.

Whale-watching season is delighting the viewing public along the east Australian coast but while it’s a boon for the tourism industry, for the majestic humpback whale it’s potentially a time of less optimal health.

UNSW Sydney researchers collected and analysed samples of whale blow – similar to mucus from a human nose – and found “significantly less” microbial diversity and richness on the return leg of the whales’ migration, indicating the whales were likely in poorer health than when their journey began.

Microbial diversity accounts for the wide array of microorganisms – the smallest forms of life.

Lead author Dr Catharina Vendl, UNSW Science researcher, said the study, published in Scientific Reports this week, provided the first evidence whales’ airway microbiota was a potential indicator of a whale’s overall health.

East Australian humpback whales complete, on average, an arduous 8000-kilometre round trip between Antarctica and Queensland from May to November each year, fasting for most of their journey.

“The physical strains of the humpback’s migration likely affected the microbial communities in the whales’ airways – so, our findings are key to further developing the analysis of airway microbiota as a non-invasive method for monitoring the immune function and overall health of whales and dolphins,” Dr Vendl said.

“People enjoy whale-watching season, but with it comes reports of whales becoming stranded. Although humpback whale stranding events occur naturally and regularly to injured and young whales, it is crucial to monitor the population health of this iconic species to ensure its long-term survival.

“Humpback whales do not only play an essential role in their marine ecosystem but also represent an important economic resource, because whale watching is a booming industry in many Australian cities and around the world.”

Humpback whales were almost hunted to extinction. The last whaling station in NSW, at Byron Bay, closed in 1962 because so few whales could be found.

Humpback whales are now protected throughout Australia, and in NSW are listed as a vulnerable species under the Biodiversity Conservation Act 2016.

Dr Vendl, who has a background in veterinary science, said it was amazing the east and west Australian humpback whale populations had recovered well in the years since whaling stopped.

“So, these whale populations are not endangered, but that doesn't necessarily mean things will stay that way,” she said.

Collecting whale ‘snot’

Dr Vendl said it was important to find a non-invasive method to study whale health, because many whale populations around the world were endangered – yet scientists still knew fairly little about whales’ physiology.

“Many whale species are at or near the top of their food chain – so, a whale’s general health can be a good indicator of the health of their marine ecosystem,” she said.

“Humpback whales mostly live on tiny creatures called krill, but because there is less of this preferred food along the east Australian coast and it’s such a huge effort for them to open their mouths to feed, they rely on energy stored in their blubber.

“Fasting is therefore a major physiological strain during the whales’ migration.”

Dr Vendl collected airway mucus from 20 whales in Hervey Bay, Queensland, during the humpback’s return leg to Antarctica when the whales were several months into their migration in August 2017.

The researchers then analysed and compared the whales’ blow microbiota to samples Macquarie University scientists collected near Sydney in May and June 2017, for a separate study, when the whales were at the start of their migration.

UNSW Science Professor Tracey Rogers pioneered the technique the UNSW researchers used to examine the whales’ airway microbial communities, more than a decade ago.

Dr Vendl said researchers wanted to determine if there was a significant difference between the microbial communities of the whales at the start of and later on in their migration.

“I used two methods to collect the whales’ blow while working from a boat. For one method, I flew a waterproof drone over the whales which carried a petri dish,” she said.

“It was pure luck waiting for the whales to exhale at the same time the drone was within range for droplets from their blow to settle on the petri dish.

“My second technique was a 4.6-metre long telescopic pole with petri dishes attached to the end. In Hervey Bay, the whales are curious and approach boats.

“So, I held the pole out and waited until the whales exhaled and then collected their samples that way.”

Migration pressure link to potential poor health

The study found the whales’ respiratory microbiota was severely depleted in diversity and richness the longer they fasted during their migration.

Dr Vendl said such changes often reflected a compromised state of health in the airways of humans.

“We concluded the physical strains of the migration, likely in addition to the exposure to marine pollutants, compromise the whales’ immune systems and consequently cause a shift in the whales’ airway microbiota.

“Our findings are the first to provide good evidence of a connection between the whales’ airway bacterial communities, their physiology and immune function – something that has been established in humans.”

Dr Vendl said a high level of bacterial variety and richness in respiratory microbiota was a sign of healthy airways in humans.

“I researched literature in human medicine: when you have a respiratory disease in a person, it also means the bacterial communities in their airways have changed and are usually depleted,” she said.

“We had no idea if we would find a similar pattern in whales, but we at least showed the initial evidence for that occurring.”

New potential for non-invasive methods

Dr Vendl said she hoped her research would lead to further study in non-invasive techniques to monitor whale health in populations around the world.

“Our findings showed the first evidence of a link between whales’ respiratory microbiota and their overall health, but more research needs to be done,” she said.

“Analysing whale blow to assess and monitor whale health opens up more possibilities for the use of non-invasive techniques, such as photogrammetry – where you fly a drone to film and measure whales to determine how much blubber they have and things like that.

“Other methods were outside the scope of my PhD, but it’s important for researchers to experiment with and refine new techniques to assess their effectiveness in helping whale conservation.”

Find the study in Scientific Reports: https://doi.org/10.1038/s41598-020-69602-x

Journal

Scientific Reports

DOI

10.1038/s41598-020-69602-x

A review paper by Monash Biomedicine Discovery Institute (BDI), published in the high-impact journal Nature Reviews Microbiology, casts light on organelles, the internal compartments in bacterial cells that house and support functions essential for their survival and growth.

The BDI's Professor Trevor Lithgow and Associate Professor Chris Greening, experts in bacterial cell biology and physiology, were invited to review the available scientific literature worldwide to consolidate the latest knowledge of organelles.

"There was an age-old truism until recently that bacteria were simply a bag of enzymes, the simplest type of cells," Professor Lithgow said. "New developments in nanoscale imaging have shown that internal compartments - organelles - make them very complex," he said.

Cryoelectron microscopy and super-resolution microscopy have allowed scientists to fathom the workings of bacterial organelles, which typically have a diameter 10,000 times smaller than a pinhead. The BDI has been at the forefront in Australia in adopting and developing the use of these technologies, Professor Lithgow said.

"It's been a rewarding experience doing this scholarly review and being able to showcase the broad swathe of work that demonstrates the complexity of bacterial cells," he said.

Organelles enable bacteria to do extraordinary things. They help bacteria photosynthesise in dimly lit environments, break down toxic compounds like rocket fuel or even orientate themselves relative to the Earth's magnetic field by lining up magnetic iron particles. Some bacteria use gas collected within organelles to control buoyancy to let them rise or go deeper in water, allowing optimal access to light and nutrients for growth and division.

Exploring and understanding the intricacies of bacterial cells is not only important for scientific knowledge, but also for biotechnological applications and for addressing global issues of human health.

"Organelles enable many bacteria to perform functions useful for us, from supporting basic ecosystem function to enabling all sorts of biotechnological advances. But a few pathogens use organelles to cause disease," Associate Professor Greening said. "The deadly pathogen that causes tuberculosis, for example, scavenges fatty molecules from our own bodies and stores them as energy reserves in organelles, helping the pathogen to persist for years in our lungs, compromising treatment and making the emergence of drug resistance likely."

Countering drug-resistant infections are key 21st century problems for humans, Professor Lithgow said. "In these times of COVID-19 the death tolls we're seeing for viral infections are terrible, but the projection is that by 2050 at least 22,000 Australians (and 10 million people worldwide) will die every year due to infections caused by drug-resistant bacteria," he said.

Robots working in abattoirs, sky-high vertical farms, more gene-edited foods in our supermarkets and automated farming systems could all help guarantee food supply in the next pandemic.

University of Queensland Professor Robert Henry said the technologies had all been in various stages of planning prior to COVID-19, but food producers would now be moving much faster to prepare for the next pandemic.

"Food processing facilities like meat works have had to close due to a staff member being infected with the coronavirus, and all food processing industries where you have workers in small confined spaces are similarly at risk," Professor Henry said.

Professor Henry, who is the Director of the Queensland Alliance for Agriculture and Food Innovation (QAAFI), said roboticised abattoirs and automated harvesting and production facilities would also reduce the risk of transmission of pathogens among workers but also the spread of viruses via the food itself.

"COVID does not seem to be transmissible from an infected human touching food but a future pandemic virus might be transmitted this way, so automating the food supply chain reduces this risk.

"It also minimises reliance on human workers that are not available due to migration restrictions and border closures."

Professor Henry said protected cropping, including vertical farms - or growing food in vertically stacked layers similar to a skyscraper building - would optimise plant growth and enable control over climate variations, chemical inputs and water resources.

"There will have to be policies that drive consumer acceptance of gene edited foods, which some consumers consider as GMOs.

"Advanced technologies need to be adopted globally, in each region, to deliver local food production capability that could provide secure sources of food in future pandemics.

"We will need to design crops to suit automated systems - for example for fruit to grow in places where it can be harvested robotically."

Professor Henry said the ongoing COVID-19 pandemic made it difficult to fully assess the impact on agriculture and food supply.

He said despite growing stocks of foods such as cereals, it was estimated the number of people facing a food crisis will grow from 135 million to 265 million by the end of 2020.

"It may seem to those of us in Western countries that the only impact on food supply has been a rush on pasta and rice in the supermarket and home-baking but the loss of income caused by the pandemic has hit some countries in Africa hard.

'We are in a situation where we have food surpluses while there has been a doubling in the number of people who can't afford to eat - and the situation is likely to get worse."
Professor Henry said increased investment in agricultural research and development would support enhanced food security.

Have you ever wondered why stars twinkle? It's because turbulence in the Earth's atmosphere makes light emitted from the star wobble as it completes its lightyears-long journey to the lenses in our eyes and telescopes.

But now scientists from international research institutions including UNSW Sydney have found the best place on Earth where - with the help of technology - we can view distant stars as they really appear, without the distorting twinkle.

And it happens to be situated due south of Australia's Davis Station in Antarctica, on a plateau 4000 metres above sea-level called Dome A.

In research published today in the journal Nature, scientists showed that the conditions at the plateau lend themselves perfectly to viewing stars from Earth with greatly reduced interference from atmospheric turbulence.

According to UNSW Science's Professor Michael Ashley, who was part of Chinese-led research team of scientists that designed, built and set up a small telescope system at Dome A, the findings represent a fantastic opportunity to obtain better observations of the universe from ground-based telescopes.

"After a decade of indirect evidence and theoretical reasoning, we finally have direct observational proof of the extraordinarily good conditions at Dome A," says Prof Ashley, an astronomer with UNSW's School of Physics.

"Dome A is the highest point in the central plateau region of Antarctica, and the atmosphere is extremely stable here, much more so than anywhere else on Earth. The result is that the twinkling of the stars is greatly reduced, and the star images are much sharper and brighter."

The telescope that was installed at Dome A - the KunLun Differential Image Motion Monitor - was 25cm in aperture and placed on an eight metre platform. The height of the platform was crucial because it raised the telescope above the steep temperature gradients near the ice.

As Prof Ashley explains, turbulent eddies build up when wind moves across a changing topography such as mountains, hills and valleys.

"This causes the atmospheric turbulence which bends the starlight around so by the time it hits the ground, it's all over the place and you get these blurry images."

BOUNDARY LAYERS

But, he says, Dome A in Antarctica is a plateau that is almost dead flat for many hundreds of kilometres in every direction, making its atmosphere very stable. It's also at an altitude of more than 4000 meters - much higher than Mount Kosciuszko.

"There is this very slow wind that blows across the plateau which is so smooth that it doesn't generate much turbulence," Prof Ashley says.

"What little turbulence there is we see restricted to a very low 'boundary layer' - the area between the ice and the rest of the atmosphere.

"We measured the boundary layer thickness at Dome A using a radar technique about a decade ago and it's about 14 meters, on average, but it fluctuates - it goes down to almost nothing, and it goes up to maybe 30 metres."

The team found that by setting up their telescope on an 8-metre platform, it protruded past the boundary layer about a third of the time. Last year between April 11 and August 4 the telescope took photos every minute, and obtained 45,930 images taken when the boundary layer was lower than the 8-metre platform, it reported in Nature.

Prof Ashley says it was very challenging to finally obtain the readings and images that confirmed Dome A to be the premier location on earth to see into the depths of the cosmos.

"It was very difficult because the observations have to be made in mid-winter with no humans present. UNSW played a crucial role in designing and building the infrastructure that was used - the power supply system, computers, satellite communications - which was managed by remote control."

GROUND VS SATELLITE TELESCOPES

But if the atmosphere plays such havoc with our instruments on Earth, wouldn't a satellite - such as the Hubble Telescope, launched back in 1990 - be ideal for such a job?

Prof Ashley says there are a couple of good reasons why a ground telescope set up at Dome A would be the better option. Beyond the obvious savings in dollars, there are also savings in time.

"Satellites are a lot more expensive," Prof Ashley says, "we're talking maybe factors of 10 to 100 times the cost. But another advantage of making Earth-based observations is you can always add the latest technology to your telescope on the ground. Whereas in space, everything is delayed. And you can't easily use a lot of modern integrated circuits because they're not radiation hardened. So you end up with space lagging the technology on the ground by 10 years or more."

Another advantage of using a telescope at Dome A rather than anywhere else on the planet is that smaller and fainter stars are suddenly much more observable thanks to the better resolution.

"Basically this means that for a given size telescope, you're going to get a lot better images at Dome A. So rather than build a big telescope on a non-Antarctic site, you could build a smaller one and get the same performance, so it's cheaper."

POLAR NIGHTS

There is also a strategic advantage in the location of Dome A - which is 900km from the South Pole - over other areas on Earth at more hospitable latitudes. Being so far from the equator, polar nights of 24 hours or more of darkness in mid-winter open up a much wider window to view stars.

"If you were to observe a star in say, Sydney, from when it rises to when it sets, you can only observe it for maybe eight hours a night," Prof Ashley says.

"Whereas in wintertime at Dome A you can observe a star continuously. And for some projects like searching for planets around other stars, the fact that you can observe them continuously means you can find planets around them much more effectively."

Looking ahead, Prof Ashley says he would like to continue the research with UNSW's Chinese partners, and notes that China has an impressive and growing record in Antarctic scientific research. But he wonders whether Australia recognises the great potential that Dome A represents in space research.

"Dome A is a superb site for astronomical observations, and we should make every effort to participate in an international project to put a large telescope there to take advantage of the conditions.

"With Antarctica being so close to Australia, it is a tremendous opportunity," he says.

In a breakthrough new study, scientists and engineers at the University of Minnesota have electrically transformed the abundant and low-cost non-magnetic material iron sulfide, also known as "fool's gold" or pyrite, into a magnetic material.

This is the first time scientists have ever electrically transformed an entirely non-magnetic material into a magnetic one, and it could be the first step in creating valuable new magnetic materials for more energy-efficient computer memory devices.

The research is published in Science Advances, a peer-reviewed scientific journal published by the American Association for the Advancement of Science (AAAS).

"Most people knowledgeable in magnetism would probably say it was impossible to electrically transform a non-magnetic material into a magnetic one. When we looked a little deeper, however, we saw a potential route, and made it happen," said Chris Leighton, the lead researcher on the study and a University of Minnesota Distinguished McKnight University Professor in the Department of Chemical Engineering and Materials Science.

Leighton and his colleagues, including Eray Aydil at New York University and Laura Gagliardi (chemistry) at the University of Minnesota, have been studying iron sulfide, or 'fool's gold,' for more than a decade for possible use in solar cells. Sulfur in particular is a highly abundant and low-cost byproduct of petroleum production. Unfortunately, scientists and engineers haven't found a way to make the material efficient enough to realize low-cost, earth-abundant solar cells.

"We really went back to the iron sulfide material to try to figure out the fundamental roadblocks to cheap, non-toxic solar cells," Leighton said. "Meanwhile, my group was also working in the emerging field of magnetoionics where we try to use electrical voltages to control magnetic properties of materials for potential applications in magnetic data storage devices. At some point we realized we should be combining these two research directions, and it paid off."

Leighton said their goal was to manipulate the magnetic properties of materials with a voltage alone, with very little electrical current, which is important to make magnetic devices more energy-efficient. Progress to date had included turning on and off ferromagnetism, the most technologically important form of magnetism, in other types of magnetic materials. Iron sulfide, however, offered the prospect of potentially electrically inducing ferromagnetism in an entirely non-magnetic material.

In the study, the researchers used a technique called electrolyte gating. They took the non-magnetic iron sulfide material and put it in a device in contact with an ionic solution, or electrolyte, comparable to Gatorade. They then applied as little as 1 volt (less voltage than a household battery), moved positively charged molecules to the interface between the electrolyte and the iron sulfide, and induced magnetism. Importantly, they were able to turn off the voltage and return the material to its non-magnetic state, meaning that they can reversibly switch the magnetism on and off.

"We were pretty surprised it worked," Leighton said. "By applying the voltage, we essentially pour electrons into the material. It turns out that if you get high enough concentrations of electrons, the material wants to spontaneously become ferromagnetic, which we were able to understand with theory. This has lots of potential. Having done it with iron sulfide, we guess we can do it with other materials as well."

Leighton said they would never have imagined trying this approach if it wasn't for his team's research studying iron sulfide for solar cells and the work on magnetoionics.

"It was the perfect convergence of two areas of research," he said.

Leighton said the next step is to continue research to replicate the process at higher temperatures, which the team's preliminary data suggest should certainly be possible. They also hope to try the process with other materials and to demonstrate potential for real devices.

Planter performance is a critical component when laying the foundation for a successful crop season. Environmental and soil conditions can significantly impact crop germination and emergence and help or hinder development of an adequate crop stand early in the season. Adjusting specific planter components and settings to match current field conditions can ensure maximized emergence and increase yield in most cases.

The key planter parameters used to maximize crop emergence include uniform and high-stand establishment, consistent seed depth at planting, and accurate seed placement. To identify the best setting for each parameter, Wesley Porter, an Extension Precision Ag and Irrigation Specialist at the University of Georgia, conducted cotton depth and downforce research, in which he tested three downforce settings, three preplant irrigation applications, three seeding depths, and two seed sizes.

Porter found that wetter field conditions and deeper depths reduced emergence on the whole but using a larger seed produced a slight increase in emergence. Additionally, hill-drop planting was found to overcome some inadequate field conditions, and in some cases, plants were able to compensate for the lack of stand establishment. Overall, Porter found that environmental conditions are a critical factor in successful planting and recommends that growers monitor these conditions and adjust planter depth and downforce accordingly.

Porter explains the research in detail in the webcast "Importance of Planter Depth and Downforce in Cotton Production" and offers more advice to cotton growers. This 28-minute presentation is available through the "Focus on Cotton" resource on the Plant Management Network. This resource contains more than 100 webcasts, along with presentations from a number of conferences, on a broad range of aspects of cotton crop management: agronomic practices, diseases, harvest and ginning, insects, irrigation, nematodes, precision agriculture, soil health and crop fertility, and weeds. These webcasts are available to readers open access (without a subscription).

What The Study Did: Mood homeostasis (the ability to stabilize your mood with mood-modifying activities) before and during the COVID-19 lockdown among Dutch students was investigated in this observational study.

Authors: Guy M. Goodwin, M.D., of Warneford Hospital in Oxford, United Kingdom, is the corresponding author.

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

(doi:10.1001/jamapsychiatry.2020.2389)

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

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

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamapsychiatry/fullarticle/10.1001/jamapsychiatry.2020.2389?guestAccessKey=886fcf5f-9796-4c90-9c0c-255542380ad7&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=072920

Journal

JAMA Psychiatry

What The Study Did: Researchers identified surgical specialties with the lowest percentage of female resident physicians and looked at the changes over a decade in the percentage of women in different specialties.

Authors: Christopher L. Bennett, M.D., M.A., of Brigham and Women's Hospital and Harvard Medical School in Boston, is the corresponding author.

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

(doi:10.1001/jamasurg.2020.2171)

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

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

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamasurgery/fullarticle/10.1001/jamasurg.2020.2171?guestAccessKey=1822af79-8196-450c-9616-3054af0f32a2&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=072920

Journal

JAMA Surgery

Research at the Centro Nacional de Investigadores Cardiovasculares (CNIC) has identified the mechanism of competition between distinct mitochondrial genomes coexisting in the same cell. The study, published today in Science Advances, examines why the simultaneous presence of more than one variant of mitochondrial DNA (mtDNA) in a cell is rejected in most cells, which select a single mtDNA variant whose identity depends on the tissue.

The study was coordinated by Dr José Antonio Enríquez, head of the Functional Genetics of the Oxidative Phosphorylation System laboratory at the CNIC. Mitochondrial DNA is genetic material passed exclusively from mother to offspring. The research team found that the selection between mtDNAs present in the same cell depends on their impact on cell metabolism and can be influenced by differences in gene function, the action of drugs, or dietary changes. These factors together determine the preference for a particular mtDNA variant.

The study is the result of more than 5 years of research and collaborations with several laboratories across Europe. The results show that cells can detect the presence of mitochondria with distinct mtDNA genomes and select the variant more suited to the metabolic needs of the specific cell type. This explains how the selected mtDNA variant can differ between cell types.

"The study establishes that the selection of a mtDNA variant depends on the cell type and not the tissue, as was thought previously," explained Dr Ana Victoria Lechuga-Vieco, first author on the study. "The preference of a cell for a specific mitochondrial variant depends on the cell's metabolic program and on several nuclear genes that have subtle effects on metabolism and the control of mitochondrial quality. We have shown that this mechanism is a process of functional selection."

Mitochondria are organelles present in the cytoplasm of most eukaryotic cells. Mitochondria provide most of the available energy in the cell by generating ATP (adenosine triphosphate)--the main source of energy in living organisms--in the respiratory chain. Mitochondria have their own DNA, which accounts for just 0.2% of the genetic information in humans and encodes 37 genes.

"The coexistence of more than one mtDNA variant in the same cell is more common than expected in humans and can be the result of new treatments for mitochondrial diseases and new medical technologies involving mitochondrial donation. This situation is defined technically as heteroplasmy. Understanding the implications of heteroplasmy is of vital importance for evaluating the safety of the procedures that cause it," explained Dr Enríquez.

Dr Ana Latorre-Pellicer, coauthor on the article and currently an investigator at the University of Zaragoza, underlined that the new study "provides the first description of the presence of more than once mitochondrial genome at the cellular level, as well as defining the mechanism of competition between distinct mitochondrial genomes within the same cell."

The research was conducted using mice with distinct mitochondrial genomes coexisting in individual cells. This model system allowed the team to determine how cells select one mitochondrial variant to avoid the presence of more than one type of mtDNA and to study the complexity of the communication between cell nuclei and mitochondria.

Moreover, the researchers add, the study has identified molecular targets for the development of tools to control mtDNA selection and cell metabolism in order to prevent the accidental generation of heteroplasmy through new medical procedures. These new technologies include the transplantation of healthy mitochondria to prevent mitochondrial diseases, injection of mitochondria into oocytes to increase fertility, and the proposed transfer of mitochondria in cell therapies to treat diverse diseases, including cardiovascular, lung, and neurological diseases.

MINNEAPOLIS - Even after all of their symptoms are gone, people who have had a concussion take longer to regain complex reaction times, the kind you need in most real-life driving situations on the road, according to a preliminary study released today that will be presented at the American Academy of Neurology's Sports Concussion Virtual Conference from July 31 to August 1, 2020. The preliminary results could have implications for how quickly experts recommend drivers get back behind the wheel after a concussion.

"People who have concussions often have slower reaction times as a result, and do more poorly on tests of thinking skills after their injury than their peers without concussions," said Julianne D. Schmidt, Ph.D., ATC, of the University of Georgia in Athens. "Our study suggests that complicated driving skills, the kind involving split-second reaction times that could mean the difference between life and death, are the ones that may take the longest to regain after you have a concussion--even when all of your symptoms have resolved."

The study involved 28 college students with valid drivers' licenses and an average age of 20, including 14 with concussions and 14 without. Ten of the 14 concussed students experienced concussions while playing sports. All college students were matched by age, sex, and driving experience. Participants completed both a simulated driving reaction time test and a computerized neurocognitive test within 48 hours of their concussion symptoms resolving, which occurred an average of 16 days after the injury.

The driving reaction time test consisted of two simulated driving scenarios. The first scenario involved a stoplight reaction time simulation in which the stoplight changed from green to yellow and participants had to rapidly choose to brake or accelerate. The second scenario involved a child running in front of a vehicle and participants needed to brake or swerve to avoid collision.

The computerized test consisted of four measures of reaction time including simple, complex, and Stroop reaction time, which is the lag that occurs when you are asked to select a word like "blue" that is printed in a different color.

The drivers who had concussions demonstrated slower computerized complex reaction times than those who did not have concussions by an average of 0.06 seconds. When reacting to a change in stoplight color, it took those with concussions 0.24 seconds longer to react, or the equivalent of 15.6 feet in stopping distance, compared to those without concussions. During the driving simulation involving a child running in front of a car, it took those with concussions 0.06 seconds longer to react, or the equivalent of 3.3 feet in stopping distance, compared to those without concussions. Slower reaction time is a strong predictor of crash risk, and these additional split seconds and feet needed to change the vehicle's movement could be critical for avoiding an accident. Interestingly, only the computerized complex and Stroop reaction times moderately related to the driving stoplight reaction time, and no other relationships were observed, suggesting computerized reaction time measures are not a perfect replacement for measuring real-life driving reaction times.

"Overall, after the symptoms of the drivers with concussions resolved, their reaction times were similar to drivers who didn't have concussions. However, when we looked specifically at stoplight reaction time, we saw lingering deficits in the drivers who had concussions," Schmidt said. "This could mean traditional reaction time tests aren't the best measure of driving responsiveness and readiness. And that could have important public safety implications, considering more than three million people have sports-related concussions in the United States each year."

Not all humans are morning people. Neither, according to a new study, are all sperm whales - at least when it comes to foraging for food.

The research, led by the University of East Anglia (UEA), has revealed the daily habits of the endangered Mediterranean sperm whale. Unmanned underwater gliders equipped with acoustic monitors recorded the sperm whale sounds, or 'clicks', over several months and 1000s of kilometres of ocean.

Sperm whales are highly vocal, producing distinct types of clicks for both echolocation and social interaction purposes. The study, published today in the Endangered Species Research, focused on the extremely powerful and highly directional 'usual clicks' produced while foraging.

The recordings confirmed the whales' widespread presence in the north-western Mediterranean Sea and identified a possible hotspot for sperm whale habitat in the Gulf of Lion, where a higher rate of clicks was found. This could indicate a higher number of whales, but could also be for behavioural reasons.

In addition, continuous day and night monitoring during winter months suggests different foraging strategies between different areas. In the Ligurian Sea, mobile and scattered individual whales forage at all times of day. In the Sea of Sardinia usual clicks were also detected at all times of the day.

However, in the Gulf of Lion larger groups target intense oceanographic features in the open ocean, such as fronts and mixing events, with acoustic activity showing a clear 24-hour pattern and decreased foraging effort at dawn. This could suggest they may have modified their usual foraging pattern of eating at any time to adapt to local prey availability. It provides a clue regarding sperm whale diet in this area and may be what makes it attractive to them.

There are fewer than 2500 mature individual Mediterranean sperm whales and threats to them include being caught as bycatch in fishing nets and, as recently the case off the Italian coast, entanglement in illegal fishing gear. Other dangers are ship strike and ingestion of marine debris, to disturbance by human-made noise and whale watching activities.

The study involved researchers from UEA and the Centre for Environment, Fisheries & Aquaculture Science (CEFAS), the Scottish Association for Marine Science (SAMS), University of Gothenburg and Sorbonne University.

Lead author Pierre Cauchy, a postgraduate researcher at UEA's Centre for Ocean and Atmospheric Sciences (COAS) and CEFAS, said their findings would help conservation efforts: "Information on the ecology of the Mediterranean sperm whale subpopulation remains sparse and does not meet the needs of conservation managers and policy makers.

"Increasing observation efforts, particularly in winter months, will help us better understand habitat use, and identify key seasonal habitats to allow appropriate management of shipping and fishing activities."

He added: "The clear daily pattern identified in our results appear to suggest that the sperm whales are adapting their foraging strategy to local prey behaviour. The findings also indicate a geographical pattern to their daily behaviour in the winter season."

The whales spend a substantial amount of their time foraging - when in a foraging cycle, they produce usual clicks 60 per cent of the time. As such, they provide a reliable indicator of sperm whale presence and foraging activity, and their specific features allow them to be identified and detected up to a distance of four to 20 km.

The study involved analysing sounds recorded by passive acoustic monitoring (PAM) sensors, previously successfully used for weather observation, on gliders deployed by the team to collect oceanographic data during winter 2012-2013 and June 2014, covering 3200 km.

Prof Karen Heywood, also of COAS, said the study demonstrated the possibilities of using existing glider missions to monitor the Mediterranean sperm whale over the winter months, for which there is a lack of crucial data for conservation.

"Our ability to successfully observe sperm whale distribution in different geographic areas of the north-western Mediterranean Sea, across the slopes and the open ocean, highlighted the complexity of sperm whale behaviour, foraging strategy and habitat use," she said.

"This study shows that the addition of PAM sensors to existing oceanographic glider missions offers the opportunity for sustained long-term observation, which would significantly improve sperm whale population monitoring and behaviour description, as well as identification of key habitat and potentially harmful interaction with human activities."

Co-author Dr Denise Risch, a marine mammal ecologist at SAMS, added: "We need to understand the Mediterranean sperm whale population better in order to work towards their conservation by eliminating threats.

"This is also true for other marine mammal species globally, and gliders allow us to go into new areas, which we wouldn't have any observations from otherwise, and also at times of year when we are not usually monitoring."

Scientists around the world have access to a rich trove of information through the Encyclopedia of DNA Elements (ENCODE)--annotated versions of the human and mouse genomes that are vital for interpreting their genetic codes. In the July 29, 2020 issue of the journal Nature, an international consortium of approximately 500 scientists reports on the completion of Phase 3 of an ongoing project, an achievement 20 years in the making that will help reveal how genetic variation shapes human health and disease.

[Watch "ENCODE: Encyclopedia Of DNA Elements": https://www.youtube.com/watch?v=Y3V2thsJ1Wc]

Funded by the National Human Genome Research Institute, ENCODE launched in 2003, soon after the human genome was first sequenced. Its researchers are developing a comprehensive catalog of the human and mouse genomes' functional elements--dense arrays of protein-coding genes, non-coding genes, and regulatory elements. Thousands of researchers worldwide have taken advantage of ENCODE data, using it to shed light on cancer biology, cardiovascular disease, human genetics, and other topics.

"When the first draft of the human genome was completed . . . it became immediately clear that while we had the primary sequence of the genome, or we had a draft of it . . . we needed to have an annotation for the genome," says Cold Spring Harbor Laboratory Professor Thomas Gingeras, whose team has been contributing to the ENCODE project since its inception. "We knew where the genes were located. Where the regulatory mechanisms and loci were located was significantly underdeveloped."

In Phase 3, researchers took advantage of the latest genetic technologies to glean data from biological specimens and deeply investigate the regulatory regions outside of genes, where most of the genome's person-to-person variation lies. Their data identifies some 900,000 candidate regulatory elements from the human genome and more than 300,000 from the mouse, which can be explored through ENCODE's new online browser.

Gingeras's team is investigating genome elements that instruct cells about how and when to transcribe DNA sequences into RNA. In a companion publication to the ENCODE report, a team led by Gingeras and collaborator Roderic Guigó at the Centre for Genomic Regulation detail work identifying molecular fingerprints that can be used to identify five groups of human cells. "Our work redefines, based on gene expression, the basic histological types in which tissues have been traditionally classified," Guigó says.

Those findings are now available through the ENCODE database. Meanwhile, the project has begun its fourth phase, employing new technologies and investigating additional cell types. Gingeras notes:

"This encyclopedia is a living resource. It has a beginning but really no end. It will continue to be improved, and grown, as time goes on."