Culture

Study suggests reporting of sexually transmitted infections may be impacted by COVID-19

image: Artist illustrations of the microbes behind the three sexually transmitted infections for which reporting and tracking have been impacted by the clinical focus on COVID-19, according to a study by Johns Hopkins Medicine.

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Graphic created by M.E. Newman, Johns Hopkins Medicine, using bacterial illustrations from the U.S. Centers for Disease Control and Prevention

With the health care community heavily focused on COVID-19 since the first quarter of 2020, there have been concerns that reporting of other diseases -- and the resulting data that enables them to be more effectively treated and controlled -- may have been impacted. For example, little is known about how the pandemic may have affected the reporting of sexually transmitted infections (STIs).

To address that issue, researchers at Johns Hopkins Medicine recently analyzed the number of reported cases of STIs within the United States during the first 40 weeks of 2020 and compared the counts with those recorded for the same period in 2019. And because the COVID-19 outbreak was first declared a U.S. national emergency on March 13, 2020 -- near the end of week 11 -- the researchers used that as the starting point for comparing reported STI cases in 2020 with the number of COVID-19 cases documented in weeks 12 through 40 of 2020.

Their findings were reported online Nov. 1, 2020, in the journal Sexually Transmitted Infections.

For their study, the researchers obtained numbers of cases for COVID-19 and three STIs -- chlamydia, gonorrhea and syphilis -- from the National Notifiable Diseases Surveillance System managed by the U.S. Centers for Disease Control and Prevention (CDC).

Comparing weekly incident case counts in 2020 from weeks 1 through 11 with weeks 12 through 40, the researchers found decreases for two of the STIs -- 20.2% for chlamydia and 3.0% for gonorrhea -- while there was a 5.5% rise in reports of syphilis cases. Comparing cumulative year-to-date case reporting data at week 40 in 2019 with the same time period in 2020, the researchers found decreases in chlamydia (18.2%) and syphilis (6.9%) but no significant change in gonorrhea numbers (a 0.06% decrease).

When compared with the number of cases reported each week for COVID-19 during weeks 12 through 40 of 2020, the weekly numbers for the three STIs appeared to inversely rise or fall for the most part with the coronavirus counts. In other words, periods of heavy COVID-19 case reporting seemed to coincide with fewer STIs being counted.

Additionally, the Johns Hopkins Medicine team showed that the reported case numbers for 42 of the 44 nationally notifiable diseases tracked by the CDC decreased from 2019 to 2020 for weeks 1 through 40. The researchers say that this possibly indicates the observed effect may impact infectious diseases other than STIs.

"It isn't clear whether or not the decreases seen in reported cases of chlamydia, and to a lesser extent, gonorrhea and syphilis, were because COVID-mediated physical distancing was preventing transmission or, more likely, that there was a decrease in testing and reporting of cases, with fewer people seeking medical attention for STI symptoms during the pandemic," says Matthew Crane, a medical student at the Johns Hopkins University School of Medicine and lead author of the study.

Based on their findings, the researchers believe there is a critical need for innovative strategies -- such as patient-collected and mailed specimens -- to counter any impacts in case reporting during a pandemic.

Credit: 
Johns Hopkins Medicine

Urban land and aerosols amplify hazardous weather, steer storms toward cities

image: Intensified convection is just one way urban land and anthropogenically produced aerosols may shape hazardous weather. Longer-lasting rainfall and larger hail are other potential byproducts of the interactions between cityscapes and storms, according to new research from PNNL scientists.

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(Photo by 12019 | Pixabay.com)

RICHLAND, Wash.--Urban landscapes and human-made aerosols--particles suspended in the atmosphere--have the potential to not only make gusts stronger and hail larger; they can also start storms sooner and even pull them toward cities, according to new research exploring the impact of urban development on hazardous weather, led by scientists at the U.S. Department of Energy's Pacific Northwest National Laboratory.

By modeling two thunderstorms--one near Houston, Texas, and another in Kansas City, Missouri.--atmospheric scientist Jiwen Fan teased out the separate and synergistic effects that urban landscapes and human-caused aerosols can have on storms, rain and hail.

In the case of the Kansas City storm, urban land and aerosols worked together to amplify the frequency of large hail by roughly 20 percent. In Houston, an otherwise gentler thunderstorm saw amplified, longer-lasting rainfall that developed sooner, among other changes.

Fan shared her findings at the American Geophysical Union's 2020 fall meeting, on Tuesday, Dec. 1, and answered questions virtually on Tuesday, Dec. 15.

"The novelty of our study is that we consider both urban land and aerosols together," said Fan, "instead of their separate impacts."

In previous work, researchers have shown that urban land shapes weather, both through its topographical nature and the heat it produces. Cities are often warmer than their surroundings, because buildings not only absorb and retain the sun's heat differently than trees and agricultural land, but also block wind flow.

Yet many studies focus primarily on how cities and aerosols change precipitation and temperature, or only examine the influence of those factors separately, rather than their joint effect.

Simulated storms reveal changes in hazardous weather

Fan modeled two very different types of storms: Kansas City's violent, rotating, hail-filled thunderstorm, and Houston's gentler, sea breeze-induced thunderstorm. She simulated multiple versions of the same storms, with and without cities and aerosols present, to isolate the effects of these two distinct factors.

In Houston, afternoon showers swelled as urban land and aerosols worked synergistically to amplify rainfall. Compared to simulations without cities, rain drenched Houston roughly a half-hour sooner, increasing its total by an extra 1.5 millimeters. Sea breeze winds blew stronger as well, whipped up by the influence of urban land.

When cooler, denser air from the sea breeze flowed toward Houston, it brought moisture with it and clashed with warmer, lighter city air. The two mixed upon meeting, creating stronger convection compared to simulations without urban land.

Houston's thunderstorm clouds began as warm clouds with only liquid drops, but the strengthened sea breeze caused a quickened transition to mixed-phase clouds, named for their simultaneous mixture of water vapor, ice particles and supercooled water droplets. Even after the sea breeze trickled off, said Fan, residual heat from the city continued feeding storm convection well through the night, causing longer-lasting rain. Contrast that with Fan's simulation where the city was removed, showing a weaker sea breeze and a storm that dissipated sooner.

Aerosols played a larger role in enhancing precipitation than urban land in Houston. As mixed-phase clouds formed and convection grew stronger, numerous ultrafine particles were transformed into cloud droplets. This transformation enhanced the conversion of water vapor into cloud condensates, thereby increasing latent heating and further strengthening the storm.

In the case of the Kansas City storm, heat from the city was carried downwind, where it met the already formed storm at the northern urban-rural boundary. When warmer, drier air met with cooler, moister rural air, it intensified convergence, creating turbulent mixing and a more violent storm that moved toward urban land.

In contrast with Houston's thunderstorm, Kansas City's aerosols did not influence storm initiation or propagation, nor did they, on their own, greatly influence hail. But, when simulated alongside urban land, the two amplified hail, synergistically producing a more hazardous hailstorm. Because of this relationship, said Fan, it's important to consider both urban land and aerosols when exploring the impact cities have on weather and associated hazards.

Hail alone inflicts billions of dollars of damage in the U.S. and, according to the National Oceanic and Atmospheric Administration, it is possible for especially large hailstones to fall at over fhail100 miles per hour.

Accounting for aerosols

Urban land and aerosols shape weather differently, according to Fan, depending on other environmental conditions, like whether air is already polluted.

"The aerosol effect really depends on the background concentration," said Fan. "If the environment is already polluted, adding more aerosols doesn't seem to affect much. But if you're already in clean a condition and you add aerosols, it may produce a large impact."

Houston's busy shipping channel and nearby oil refineries, three of which are in its metro area, regularly discharge aerosols into the atmosphere, said Fan. Humidity, too, she added, can amplify the aerosol effect.

Fan hopes her work may lead to more accurate predictions of hazardous weather, mitigating the death and damage dealt by storms. She plans to more deeply explore how sprawling urbanization will shape severe storms in future climate scenarios.

Credit: 
DOE/Pacific Northwest National Laboratory

Male bats with high testosterone levels have large forearm crusts when females are fertile

video: Mariana Muñoz-Romo talks about her research.

Image: 
Ana Endara, STRI

Males may put a lot of effort into attracting females. Male peacocks flaunt eye-catching trains, but male bats, because they are active at night, may rely on females' sense of smell to draw them in. Three years ago, Victoria Flores, a predoctoral fellow at the Smithsonian Tropical Research Institute (STRI) in Panama, discovered that male fringed-lipped bats often have a sweet-smelling, crusty substance on their forearms. Because only males had crusts and primarily exhibited these crusts during the putative reproductive season, Flores speculated that crusts might play a role in mating. Now Mariana Muñoz-Romo, postdoctoral fellow at STRI and National Geographic Explorer, and her colleagues have evidence to prove it.

To make the crust, males scratch their whole body with the claws on their hind feet, nibble on their claws and then spit a sticky yellow substance onto their forearms. Females do not do this.

"It is one thing to assume that because only males have a particular feature, it must have to do with mating, but when we measured the size of the smelly crusts on males' forearms, quantified their testosterone levels and the size of their testes, we found that all of these factors are related," Muñoz-Romo said. "Males with the highest testosterone levels and the largest testes have the largest crusts on their forearms, which makes us pretty sure that this trait is associated with reproduction."

Muñoz-Romo measured testosterone levels in plasma samples from wild bats at INDICASAT, Panama's Institute for Science and Technology. She also looked at the time of year when the males have enlarged crusts and whether it corresponds to the time when females are fertile, another signal that crusts and mating go arm in arm.

"There are actually very few studies that measure testosterone levels, female fertility and one of these male-only traits in mammals, and to the best of our knowledge this is the first study like this in bats," Muñoz-Romo said.

One of the reasons why studies of this kind are so rare is that it can be difficult to tell if females are in estrus. In this case, researchers sampled vaginal cells to find out if females were fertile. Most baby fringe-lipped bats are born at the end of Panama's dry season in May. Most of the males had enlarged crusts about five months earlier, during the mating season.

Testosterone is the most important male hormone, and in humans it is often associated with natural body odors. "Our results suggest that crust size is indeed determined by testosterone levels--males with higher levels of testosterone and larger testes produce bigger crusts," said Rachel Page, STRI staff scientist and co-author of the study. "All of these factors combined suggest that odorous crusts play a critical role in courtship and mating."

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Smithsonian Tropical Research Institute

Researchers turn DNA detectives to aid rhino poaching prosecutions with forensic evidence

video: Tista Ghosh sampling DNA from rhino dung_Video by Parikshit Kakati

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Parikshit Kakati

The project is part of the Rhino DNA Indexing System (RhODIS- India) conservation program. This database has been created to build a DNA catalogue of the existing Indian greater one-horned rhinoceros, Rhinoceros unicornis, to tackle rhino poaching and assist conservation efforts for this vulnerable species.

Inspired by a similar program in South Africa, PhD student and senior research fellow Tista Ghosh, along with Dr Samrat Mondol (WII) and Amit Sharma (WWF India), collected dung from 749 rhinoceros to gather vital genetic information. By analysing dung for traces of population specific genetic signals, a genetic baseline was created for rhinoceros across India and 406 unique individuals were identified.

Microsatellite markers are present in nuclear DNA, similar to a fingerprint, where each individual has its own unique genetic signature. The use of 14 markers helps to identify individuals from dung data based on unique individual rhino's signature.

By comparing seized rhino horn samples to these specific genetic signals, the researchers could trace the rhino back to its breeding population, thus identifying trade routes and pinpointing poaching hotspots, which are notoriously difficult for traditional law enforcement to track.

"Having an allele frequency map aids in pinpointing the location of the orphan seized rhino sample to its breeding population based on genetic signatures", commented Tista Ghosh.

The forensics team at WII were also able to match a suspected poached carcass from a protected area to a seized horn found elsewhere along the trade route in India. Occasionally, they had as little to work with as blood-stained soil, pebbles or a bullet to perform DNA profiling.

These results display the powerful abilities which this microsatellite panel has for tackling wildlife crime and providing valuable insights to the forest department. Furthermore, individual DNA matching assists in court prosecutions by providing concrete scientific evidence regarding the poaching of wild rhino, native to India.

On the significance of this method, Tista said: "Many times the seized rhino body parts are found after a long time of poaching incidences as a result of which it becomes difficult to pinpoint the location of the crime. Thus, it is important to locate such networks and have law enforcement resulting in breaking the chain of trading."

India's current population of greater one-horned rhinoceros' is relatively small, at approximately 3,500 rhino individuals. Using statistical probabilities, the team calculated that 14 microsatellite markers were sufficient to be able to do individual matching across the whole range of the population.

In addition, the researchers are keen to collaborate with Nepal field teams to extend this work to the second strong hold of greater one-horned rhinoceros.

However, in the field of wildlife forensics, there are severe limitations due to the poor quality of samples, and circumstances when data could not be generated using microsatellite only. In those scenarios Tista said, of these exciting developments, "We are planning to do a mitochondrial DNA screening to look for park/state specific genetic markers and combine that data with our existing database to avoid such situations."

Further the RhODIS-India marker panel is still in the process of developing an 'allelic ladder' (reference point) for comparisons with other laboratories. When this becomes available, this will foster greater collaboration between the global wildlife forensics community. In order to increase the size of the database, plans are already in place to carry out wider sampling across the Indian rhino's range.

Tista Ghosh's talk will be available on-demand from the 14th - 18th of December 2020 at the Festival of Ecology. The selection procedure of a 14-microsatellite panel and its application in curbing rhino poaching in India is currently under review in a peer reviewed scientific journal. This online conference will bring together 1,400 ecologists from than 50 countries to discuss the most recent breakthroughs in ecology.

Credit: 
British Ecological Society

An avocado a day keeps your gut microbes happy

image: Adding avocado to your meal improves gut health, a new University of Illinois study shows.

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College of ACES, University of Illinois.

URBANA, Ill. - Eating avocado as part of your daily diet can help improve gut health, a new study from University of Illinois shows. Avocados are a healthy food that is high in dietary fiber and monounsaturated fat. However, it was not clear how avocados impact the microbes in the gastrointestinal system or "gut."

"We know eating avocados helps you feel full and reduces blood cholesterol concentration, but we did not know how it influences the gut microbes, and the metabolites the microbes produce," says Sharon Thompson, graduate student in the Division of Nutritional Sciences at U of I and lead author on the paper, published in the Journal of Nutrition.

The researchers found that people who ate avocado every day as part of a meal had a greater abundance of gut microbes that break down fiber and produce metabolites that support gut health. They also had greater microbial diversity compared to people who did not receive the avocado meals in the study.

"Microbial metabolites are compounds the microbes produce that influence health," Thompson says. "Avocado consumption reduced bile acids and increased short chain fatty acids. These changes correlate with beneficial health outcomes."

The study included 163 adults between 25 and 45 years of age with overweight or obesity - defined as a BMI of at least 25 kg/m2 - but otherwise healthy. They received one meal per day to consume as a replacement for either breakfast, lunch, or dinner. One group consumed an avocado with each meal, while the control group consumed a similar meal but without the avocado. The participants provided blood, urine, and fecal samples throughout the 12-week study. They also reported how much of the provided meals they consumed, and every four weeks recorded everything they ate.

While other research on avocado consumption has focused on weight loss, participants in this study were not advised to restrict or change what they ate. Instead they consumed their normal diets with the exception of replacing one meal per day with the meal the researchers provided.

The purpose of this study was to explore the effects of avocado consumption on the gastrointestinal microbiota, says Hannah Holscher, assistant professor of nutrition in the Department of Food Science and Human Nutrition at U of I and senior author of the study.

"Our goal was to test the hypothesis that the fats and the fiber in avocados positively affect the gut microbiota. We also wanted to explore the relationships between gut microbes and health outcomes," Holscher says.

Avocados are rich in fat; however, the researchers found that while the avocado group consumed slightly more calories than the control group, slightly more fat was excreted in their stool.

"Greater fat excretion means the research participants were absorbing less energy from the foods that they were eating. This was likely because of reductions in bile acids, which are molecules our digestion system secretes that allow us to absorb fat. We found that the amount of bile acids in stool was lower and the amount of fat in the stool was higher in the avocado group," Holscher explains.

Different types of fats have differential effects on the microbiome. The fats in avocados are monounsaturated, which are heart-healthy fats.

Soluble fiber content is also very important, Holscher notes. A medium avocado provides around 12 grams of fiber, which goes a long way toward meeting the recommended amount of 28 to 34 grams of fiber per day.

"Less than 5% of Americans eat enough fiber. Most people consume around 12 to 16 grams of fiber per day. Thus, incorporating avocados in your diet can help get you closer to meeting the fiber recommendation," she notes.

Eating fiber isn't just good for us; it's important for the microbiome, too, Holscher states. "We can't break down dietary fibers, but certain gut microbes can. When we consume dietary fiber, it's a win-win for gut microbes and for us."

Holscher's research lab specializes in dietary modulation of the microbiome and its connections to health. "Just like we think about heart-healthy meals, we need to also be thinking about gut healthy meals and how to feed the microbiota," she explains.

Avocado is an energy-dense food, but it is also nutrient dense, and it contains important micronutrients that Americans don't eat enough of, like potassium and fiber.

"It's just a really nicely packaged fruit that contains nutrients that are important for health. Our work shows we can add benefits to gut health to that list," Holscher says.

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University of Illinois College of Agricultural, Consumer and Environmental Sciences

Gene therapy for placental insufficiency moves toward the clinic

image: journal in the field and provides all-inclusive access to the critical pillars of human gene therapy: research, methods, and clinical applications.

Image: 
Mary Ann Liebert, Inc., publishers

New Rochelle, NY, December 15, 2020--A new study identified an adenovirus gene therapy vector carrying a VEGF isoform. It can improve uterine blood flow in placental insufficiency, as reported in the peer-reviewed journal Human Gene Therapy. Click here to read the full-text article free on the Human Gene Therapy website through January 15, 2021.

Reduced uterine blood flow and lack of bioavailable VEGF due to placental insufficiency is a major cause of severe fetal growth restriction (FGR). This is untreatable and causes serious neonatal morbidity and death.

Anna David, UCL Institute for Women's Health, and colleagues tested different VEGF isoforms on endothelial cells from four species, including from human umbilical vein. The results support the use of the best performing VEGF isoform "in a human clinical trial for FGR caused by placental insufficiency."

"The placenta is one of the most critical and uniquely physiologically adapted structures in human anatomy. The work by Dr. David and her group moves forward an important new gene therapy approach to restoring the vascular integrity of the placenta when it is impaired and thereby protecting fetal health," according to Editor-in-Chief of Human Gene Therapy Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School.

Credit: 
Mary Ann Liebert, Inc./Genetic Engineering News

A first-in-human clinical trial shows microbubbles augments radiation in liver cancer patients

PHILADELPHIA - Primary liver cancer is on the rise worldwide, largely due to an increase in hepatitis C infections and chronic liver disease. Liver cancer is also hard to treat - it kills 750,000 people a year worldwide, making it the second deadliest type of cancer behind lung cancer. Current treatments include a targeted radiation therapy delivered with the help of radiation-emitting glass beads. New research shows that this treatment can be augmented by infusing microbubbles - small gas bubbles surrounded by a lipid shell - into the liver, and popping those bubbles by ultrasound, in a first-in-human pilot clinical trial of the combination. The findings of this study were published in Radiology on December 8th.

"This approach has shown to be effective in preclinical studies using animal models of other solid tumors like bladder, prostate, and breast cancer," says John Eisenbrey, PhD, associate professor of radiology and lead author of the study. "This is the first work to demonstrate this approach is safe and shows promise in humans with liver cancer, which is very exciting."

About 15-25% of patients with advanced disease are recommended a treatment called trans-arterial radioembolization, whereby radioactive glass beads are inserted into blood vessels the liver, and the radiation emitted provides a therapeutic dose to the tumor, destroying it. However, the extent to which the radiation can penetrate liver tissue is limited, and tumor response is highly dependent on distance from the radioactive beads. By combining microbubbles with TARE, the synergistic approach reduces the dose of radiation needed to kill blood vessels in the tumor and increases the effectiveness of treatment.

"The microbubbles themselves are found in commercially available ultrasound contrast agents," says Colette Shaw, MD, associate professor and interventional radiologist, and the lead clinical author of the study. "The procedure to get the microbubbles into the tumor involves similar techniques used to access blood vessels."

When the microbubbles are hit with the ultrasound wave, they start to vibrate and if the wave is strong enough, they burst. The sheer energy of these tiny explosions causes physical and chemical damage to the blood vessels of the tumors, making them more sensitive to radiation. By targeting the ultrasound to exactly where the tumors are, the researchers can burst or destroy the bubbles right where the radiation beads are and achieve highly localized sensitization

The pilot study enrolled 28 patients who were randomly assigned to two treatment groups - trans-arterial radioembolization alone (TARE) or radioembolization and ultrasound-triggered destruction of microbubbles (TARE+UTMD). The team first evaluated the safety profile of the microbubbles - they observed no changes in vital signs like body temperature, blood pressure, and heart rate in patients receiving UTMD. Importantly, UTMD did not compromise liver function, and there were no additional side effects of the combined approach.

The researchers looked at 10 tumors in the TARE only group, and 15 tumors in the TARE+UTMD group, and evaluated tumor response to each treatment. 93% of tumors showed partial to complete response to the TARE+UTMD approach, while only 50% showed a response in the TARE alone group.

The team also found that patients receiving the combined therapy were also more likely to receive a liver transplant, which offers the best chance for long term survival for patients with cirrhosis and liver cancer. These patients also lived longer, and required fewer retreatments compared to those receiving TARE alone.

"Even at this early stage, we've been able to show a significant improvement in tumor outcomes with this combined therapy," says Dr. Shaw. "Looking ahead, we are enrolling more patients to demonstrate key benchmarks in the promise of this approach."

"Our findings are really setting the stage for a whole range of studies to be done in humans," says Dr. Eisenbrey. "This approach could be effective in treating metastatic liver tumors, but also other types of primary cancer. The bubbles themselves can also be engineered to deliver chemotherapy or oxygen as they burst. This is really the tip of the iceberg."

This work was supported by NIH R01 CA238241. The ultrasound scanner used in this study was provided by Siemens Healthineers for research purposes. The authors report no conflict of interest.

Credit: 
Thomas Jefferson University

Balancing climate and development goals

That is the key finding in a new study published today in Environmental Research Letters by scientists from the Carnegie Institution for Science, USA and the University of Waterloo, Canada.

The study explores the climate consequences that would emerge should developing countries reach a specific per-capita GDP level before they start to focus their efforts on reducing carbon emissions. Using historical records of CO2 emissions combined with gross domestic product (GDP) and population data from the World Bank, scientists Lei Duan and Ken Caldeira from the Carnegie Institution for Science with Juan Moreno-Cruz from the University of Waterloo, created a wide range of future scenarios in which CO2 emissions increase according to historical trends and then start to decline only when countries reach a specified income level.

Lei Duan from the Carnegie Institution for Science said: "Decarbonisation is not often the priority for less developed countries, at least not compared to ensuring economic growth and provision of energy services. As these countries work their way towards prosperity, they need to strike a balance between climate and development goals. But if developing countries wait to adopt measures to reduce their CO2 emissions, we need to know what the climate implications of that would be."

The study found that if countries were to begin to decarbonise when per-capita GDP exceeded $10,000, there would be less than 0.3°C of additional warming. If countries above that GDP level reduce emissions at a rate of 2% each year, the delay in decarbonisation from developing countries would represent only an estimated 6% between 2020 and 2100 to total cumulative CO2 emissions.

Juan Moreno-Cruz from the University of Waterloo said: "Over half the world's population currently lives in countries below an income threshold of $10,000, yet our study shows that a lack of participation in decarbonisation amongst these countries would have relatively little impact on the global temperature change."

However, the paper warns that lock-ins into long-term emission emitting technologies must be avoided.
"The challenge is to make sure fossil fuel investments made today do not create an infrastructure or political constituency that would make a low-carbon future infeasible." Ken Caldeira from the Carnegie Institution for Science explains. "The risk is that less-developed countries become addicted to fossil-fuelled development and find the habit hard to kick as they become more wealthy. Near-term energy system investments must address near-term needs, but must take place in the context of the longer-term development of a modern low carbon-emission economy."

Lei Duan goes on to say: "We recognise that all countries need to work together to achieve the Paris agreement ambitions of holding temperature rises to no more than 2°C above pre-industrial levels, with an aspiration of a 1.5C limit. But this study shows, across a wide range of scenarios and assumptions, that the greater impact will come from middle and high income countries' decarbonisation."

Credit: 
IOP Publishing

Do tumors stiff-arm the immune system?

image: Immune cells need to be close enough to a tumor (within 150 Å) for a synapse to form and for them to undergo activation. Tumors use the extended form of complement receptor 3 (CR3) and the "I belong" tag iC3b to keep immune cells at a distance. The stiff-arm fend off protects the cancer cell from attack. In contrast, therapeutics can enhance synapse formation and tumor killing by increasing the "I don't belong" C3d tag levels in the contact zone, locking in the flexed CR3 conformation. The iC3b and C3d tags are different breakdown products of the Component Protein C3.

Image: 
Alan Herbert

In a paper just published in the Journal for the Immunotherapy of Cancer (doi:10.1136/jitc-2020-001712), Dr Herbert, Head of Discovery at InsideOutBio, asks whether cancer cells stiff-arm immune cells just like rugby players push off defenders from the other team. He describes the nanoscale machinery used by tumors to fend off the immune system. The molecules involved are capable of flexing and extending as needed, just like a rugby player's arm. The tumor's stiff-arm tactic limits the effectiveness of current immunotherapeutics, such as checkpoint inhibitors. These treatments only work once the initial tackle is made, allowing the defender to recover the ball and go on to score.

Cancer cells make many abnormal proteins. The tumors they form should be easy for the immune system to find and destroy. Yet the cancer cells carry on uninterrupted. The mechanism they use to fend off immune cells is based on a defense system that reaches right back to the dawn of multi-cellular organisms. The system tags normal cells that belong differently from those that should not be there. It originally evolved as a defense against bacteria and disease-causing viruses. It is based on a set of more than 30 proteins, referred to as the complement system, which has been studied by scientists for the last 130 years. The complement system places an "I belong" tag on normal cells to prevent the immune system from attacking them. Cancer cells exploit this mechanism to fend off the immune system. They do so by producing the "I belong" tag in excess. They need to "Super-Self" themselves to hide all the abnormal proteins they have on their surface. They are then able to run past the immune cell defenders without being tackled.

The "I belong" tag (called iC3b in the paper) is much larger in size that the "I don't belong" tag (called C3d in the paper) that identifies unwanted cells. Both tags are made from the same complement protein (called Complement C3 in the paper). Host cells are able to process C3 to produce the "I belong" iC3b tag by inhibiting production of the "don't belong" C3d tag. They have a set of proteins on their surface designed to prevent C3d tag formation. Bacteria and other foreign cells lack these proteins and end up covered with the C3d tag, leading to their destruction by immune cells. Surprisingly, the receptor (called CR3 in the paper) for the "I belong" and is the same as the one for the "I don't belong" tags. How then does the immune system know which tag is which? This is the question Dr. Herbert addresses in the paper.

It turns out that the CR3 receptor can change conformation just like an arm can be either flexed or extended. The receptor CR3 binds the "I belong" tag most strongly when it is extended. It prevents immune cells from attacking by pushing them away, the molecular equivalent to a stiff-arm. In contrast, the receptor binds the "don't belong" tag when it is flexed, drawing the immune cells close enough to engage. The defenders can then check for abnormal proteins. If they find any that "don't belong," they then respond to eliminate the threat. To avoid facing sudden death, tumors overproduce the "I belong" tag so that they appear normal rather than dangerous.

Cancer cells have many different strategies for coating their surface with "I belong" tags. These tags enable the tumors to escape attack, preventing an anti-tumor immune response from developing and long-term immunity from forming. Tumors can overproduce all the components necessary to load their surface with the "I belong" tag. Alternatively, they can capture the "I belong" tag from their immediate surroundings. In one example, tumors take advantage of bacteria that grow inside them. The bacteria initiate complement activation. The tumors then need produce only those proteins necessary to coat their surface with the "I belong" iC3b tag. In return, the lack of immune response also enables the bacteria to survive.

The complement system was first characterized by its ability to work with antibodies to eliminate disease-causing bacteria. Many talented scientists have worked over the last 130 years to characterize its many components with many features now revealed at atomic resolution. This work led to an understanding of how gene mutations that impair the "I belong" tagging process cause inflammatory diseases like glomerulonephritis and auto-immune hemolytic anemias, as well as the development of new therapeutics to treat these disorders. The work in the current paper builds on these findings to explain how this ancient system for self-nonself discrimination is exploited by tumors to ensure their survival. While the new insights are surprising after such a long and storied history, it does suggest that on occasions, an old dog may still have some new tricks to show you.

Credit: 
InsideOutBio

Study: Surge of teen vaping levels off, but remains high as of early 2020

Findings released today from the most recent Monitoring the Future (MTF) survey of substance use behaviors and related attitudes among teens in the United States indicate that levels of nicotine and marijuana vaping did not increase from 2019 to early 2020, although they remain high. The annual MTF survey is conducted by the University of Michigan's Institute for Social Research, Ann Arbor, and is funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.

In the four years since the survey began including questions on nicotine and marijuana vaping, use of these substances among teens have increased to markedly high levels. From 2017 to 2019, the percentage of teenagers who said they vaped nicotine in the past 12 months roughly doubled for eighth graders from 7.5% to 16.5%, for 10th graders from 15.8% to 30.7%, and for 12th graders from 18.8% to 35.3%. In 2020, the rates held steady at a respective 16.6%, 30.7%, and 34.5%. However, somewhat encouragingly, daily, or near daily (20 occasions in the past 30 days), nicotine vaping declined among 10th and 12th graders from 2019 to 2020, by close to half--from 6.8% to 3.6% in 10th grade and from 11.6% to 5.3% in 12th grade.

"The rapid rise of teen nicotine vaping in recent years has been unprecedented and deeply concerning since we know that nicotine is highly addictive and can be delivered at high doses by vaping devices, which may also contain other toxic chemicals that may be harmful when inhaled," said NIDA Director Nora D. Volkow, M.D. "It is encouraging to see a leveling off of this trend though the rates still remain very high."

Past-year vaping of marijuana also remained steady in 2020, with 8.1% of eighth graders, 19.1% of 10th graders, and 22.1% of 12th graders reporting past-year use, following a two-fold increase over the past two years. Additionally, daily marijuana vaping significantly decreased by more than half from 2019, to 1.1% among 10th graders and 1.5% among 12th graders in 2020.

Survey results also showed that reported use of JUUL vaping devices (also known as e-cigarettes), which contain nicotine and were previously the most popular brand among teens, significantly decreased from 2019 to 2020 among the older two grades. In 10th graders, past 12-month use of JUUL vaping devices decreased from 28.7% in 2019 to 20% in 2020 and in 12th graders, it decreased from 28.4% in 2019 to 22.7% in 2020.

The MTF survey is given annually to students in eighth, 10th, and 12th grade who self-report their substance use behaviors over various prevalence periods: daily, past 30 days, past 12 months and lifetime. The survey also documents students' perception of harm, disapproval of use, and perceived availability of drugs. The survey results are released the same year the data are collected.

From February 11 through March 14, 2020, the MTF survey investigators collected 11,821 surveys in 112 schools before data collection stopped prematurely due to the COVID-19 pandemic. While the completed surveys from early 2020 represent about 25% of the sample size of a typical year's data collection, the results were gathered from a broad geographic and representative sample, so the data were statistically weighted to provide national numbers. Estimates from MTF may differ from other government surveys due to differences in study population, questionnaire language and other factors. Study investigators are working with schools to deploy the survey in early 2021 to gather data that will reflect substance use during the COVID-19 pandemic and related periods of social distancing.

MTF researchers also conducted an in-depth analysis of a subset of the 2020 MTF data, combining 10th and 12th graders into a sample of 8,660 high schoolers, which was published today in JAMA Pediatrics. The percentage of combined 10th and 12th graders who said they vaped nicotine in the past 30 days, past 12 months, or over the course of their lifetime were similar from 2019 to 2020, at 22%, 32%, and 41% respectively. Similarly, in this group, daily, or near daily, nicotine vaping declined from 9% to 7% from 2019 to 2020. Overall, investigators concluded nicotine vaping for participants in these two grades remained steady despite decreases in use of previously popular brands like JUUL because teens moved to use of other vaping device brands, such as disposable, single use vaping devices. This and other data on trends in vaping brands used, perceived availability of vaping devices, and perceived risk of vaping from this subset of teens were published today in the same study.

Other highlights:

The use of marijuana (in all forms, including smoking and vaping), the most commonly used illicit drug by adolescents, did not significantly change in any of the three grades for lifetime use, past 12-month use, past 30-day use, and daily use from 2019-2020.

Alcohol use has not significantly changed over the past five years. However, across all grades, alcohol use in the past 12 months has leveled off from its historical gradual decline.

Past year non-medical use of amphetamines among eighth graders increased from 3.5% in 2017 to 5.3% in 2020. However, 10th and 12th graders reported recent lows in past year use at 4.3% for both grades and significant 5-year declines.

Among eighth graders, past 12-month use of inhalants has increased among eighth graders from 3.8% in 2016 to 6.1% in 2020, a 64% proportional increase, unlike 12th graders, who reported an all-time low use of inhalants.

Cigarette smoking in the last 30 days did not significantly change from 2019 to 2020. In all three grades, prevalence has dropped at least four-fold since the mid-1990s and is at or near historic lows.

Past year use of over-the-counter cough medicine among eighth graders has gradually increased over the past five years, from 1.6% in 2015 to 4.6% in 2020, its highest rate since 2006.

The percent of students reporting past year use of other drugs remains relatively low among 12th graders: 3.9% for LSD; 2.4% for synthetic cannabinoids; 2.9% for cocaine; 1.8% for MDMA (ecstasy); 1.4% for methamphetamine; and 0.3% for heroin.

Credit: 
NIH/National Institute on Drug Abuse

Poverty linked to higher risk of Covid-19 death, study suggests

People in Scotland's poorest areas are more likely to be affected by severe Covid-19 - and to die from the disease - than those in more affluent districts, according to a study of critical care units.

The first nationwide study of its kind found patients from the most economically disadvantaged areas had a higher chance of critical care admission, and that intensive care units there were more likely to be over capacity.

Researchers say the study highlights the need for extra support to be given to critical care units in poorer areas, and for more to be done to tackle health inequalities.

Researchers from the Universities of Edinburgh and Glasgow gauged how living in an area of socioeconomic poverty - measured by the Scottish Index of Multiple Deprivation - was linked to severe Covid-19 using anonymous health records.

They also accessed hospital data to assess the impact of the pandemic on critical care units at all of Scotland's hospitals.

They found that 735 patients with Covid-19 were admitted to critical care units across Scotland between March and June 2020. Of those, around one quarter of admissions were from the most deprived quintile compared with 13 per cent from the least deprived quintile.

Death rates after 30 days were significantly higher in patients from the most deprived places in Scotland compared with the least deprived, after accounting for other factors such as age and sex.

Hospitals in the most deprived health board areas were also more likely to have higher peak in demand for intensive care beds, and to be operating over their normal capacity for longer.

Doctors say that the findings highlight the need for greater resources in these areas to tackle coronavirus.
The study is published in the journal The Lancet Regional Health - Europe and was carried out in collaboration with the Scottish Intensive Care Society Audit Group.

Lead researcher Dr Nazir Lone, Senior Clinical Lecturer in Critical Care at the University of Edinburgh and Honorary Consultant in Critical Care at NHS Lothian, said, "A number of factors could be driving this link between poverty and severe disease, including poor housing, increased use of public transport and financial pressures to continue working. The most deprived communities, and the hospitals that serve them, will need extra support as the pandemic continues."

Dr Joanne McPeake, co-author of the study from the University of Glasgow, said: "While we move through this pandemic, it is increasingly important to understand how this virus affects different groups in order for informed decisions to be taken on mitigating risks. This data will help inform how we support different communities in both the short and long-term, in order to adequately ensure that socioeconomic inequalities are not exacerbated further."

Credit: 
University of Edinburgh

Purdue researchers uncover blind spots at the intersection of AI and neuroscience

image: Purdue University researchers are doing work at the intersection of artificial intelligence and neuroscience. In this photo, a research participant is wearing an EEG cap with electrodes.

Image: 
Chris Adam/Purdue University

WEST LAFAYETTE, Ind. - Is it possible to read a person's mind by analyzing the electric signals from the brain? The answer may be much more complex than most people think.

Purdue University researchers - working at the intersection of artificial intelligence and neuroscience - say a prominent dataset used to try to answer this question is confounded, and therefore many eye-popping findings that were based on this dataset and received high-profile recognition are false after all.

The Purdue team performed extensive tests over more than one year on the dataset, which looked at the brain activity of individuals taking part in a study where they looked at a series of images. Each individual wore a cap with dozens of electrodes while they viewed the images.

The Purdue team's work is published in IEEE Transactions on Pattern Analysis and Machine Intelligence. The team received funding from the National Science Foundation.

"This measurement technique, known as electroencephalography or EEG, can provide information about brain activity that could, in principle, be used to read minds," said Jeffrey Mark Siskind, professor of electrical and computer engineering in Purdue's College of Engineering. "The problem is that they used EEG in a way that the dataset itself was contaminated. The study was conducted without randomizing the order of images, so the researchers were able to tell what image was being seen just by reading the timing and order information contained in EEG, instead of solving the real problem of decoding visual perception from the brain waves."

The Purdue researchers originally began questioning the dataset when they could not obtain similar outcomes from their own tests. That's when they started analyzing the previous results and determined that a lack of randomization contaminated the dataset.

"This is one of the challenges of working in cross-disciplinary research areas," said Hari Bharadwaj, an assistant professor with a joint appointment in Purdue's College of Engineering and College of Health and Human Sciences. "Important scientific questions often demand cross-disciplinary work. The catch is that, sometimes, researchers trained in one field are not aware of the common pitfalls that can occur when applying their ideas to another. In this case, the prior work seems to have suffered from a disconnect between AI/machine-learning scientists, and pitfalls that are well-known to neuroscientists."

The Purdue team reviewed publications that used the dataset for tasks such as object classification, transfer learning and generation of images depicting human perception and thought using brain-derived representations measured through electroencephalograms (EEGs)

"The question of whether someone can read another person's mind through electric brain activity is very valid," said Ronnie Wilbur, a professor with a joint appointment in Purdue's College of Health and Human Sciences and College of Liberal Arts. "Our research shows that a better approach is needed."

Credit: 
Purdue University

Researchers use origami to solve space travel challenge

image: The researchers have developed an origami-inspired, folded plastic fuel bladder that doesn't crack at super cold temperatures and could someday be used to store and pump fuel.

Image: 
WSU

PULLMAN, Wash. -- WSU researchers have used the ancient Japanese art of paper folding to possibly solve a key challenge for outer space travel - how to store and move fuel to rocket engines.

The researchers have developed an origami-inspired, folded plastic fuel bladder that doesn't crack at super cold temperatures and could someday be used to store and pump fuel. Led by graduate student Kjell Westra and Jake Leachman, associate professor in the School of Mechanical and Materials Engineering, the researchers have published their work in the journal, Cryogenics.

The challenge of fuels management has been an important limiting factor in space travel, largely restricting space travel to either shorter trips for large amounts of cargo or to small satellites for long duration missions. In the early days of the U.S. space program in the 1960s and 1970s, researchers tried to develop round balloons to store and pump liquid hydrogen fuel. They failed. Every bladder would shatter or leak as they tried to squeeze it at the required very cold temperatures for the liquid fuels. The heartiest designs only lasted five cycles.

The researchers abandoned the effort and instead came to rely on less ideal propellant management devices. Current systems use metal plates and the principle of surface tension to manage liquid fuels, but the systems are slow and can only dribble out fuels in small quantities, so the size of fuel tanks and missions are limited.

"Folks have been trying to make bags for rocket fuel for a long time," Leachman said. "We currently don't do large, long-duration trips because we can't store fuel long enough in space."

Through a literature search, Westra came upon a paper in which researchers developed some origami-based bellows. Researchers started studying origami in the 1980s and 1990s with the idea of making use of its complex shapes and interesting mechanical behavior. The origami folds spread out stresses on the material, making it less likely to tear. Using a thin, Mylar plastic sheet, Westra and collaborators in the Hydrogen Properties for Energy Research laboratory decided to apply the design he saw to develop a fuel bladder.

"The best solutions are the ones that are already ready-made and that you can then transfer to what you're working on," Westra said.

Having never tried origami before, he said it took a couple tries and a few hours with a Youtube video to figure out how to fold the bellows. Once he folded it, he tested it in liquid nitrogen at about 77 degrees Kelvin. The researchers found that the bladder can be squeezed at least 100 times without breaking or leaking under cold conditions. They've since demonstrated the bellows numerous times, and it still doesn't have holes in it.

"We think we've solved a key problem that was holding everybody back," Leachman said. "We're kind of excited about that."

The researchers are now beginning to conduct more rigorous testing. They plan to do testing with liquid hydrogen, assessing how well they can store and expel fuel and comparing the flow rates of their bladder with current systems. Westra recently received a NASA graduate fellowship to continue the project.

"Kjell's success is a perfect example of great WSU students studying what's out there and then being in the right place at the right time to make it happen," Leachman said.

Credit: 
Washington State University

COVID-19 preprint data rapidly influenced critical care practice

image: Rapid translation of preprint data influenced use of dexamethasone influenced care of COVID-19 patients in Australia.

Image: 
ATS

Dec. 15, 2020-- In a new research letter published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine, researchers examine whether preprint data on the use of the corticosteroid dexamethasone influenced clinical practice in treating COVID-19 critical care patients throughout Australia.

Preprints are scientific papers that are posted online rapidly, before peer review. Preprint services have been increasingly used by researchers since the beginning of the COVID-19 pandemic, in order to disseminate their findings quickly, prior to peer-review publication.

In "Rapid Translation of COVID-19 Preprint Data into Critical Care Practice," Andrew A. Udy, PhD, professor and deputy director, Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia, and colleagues looked at findings from the RECOVERY trial and whether the study's recommendations were adopted after their preprint posting.

The RECOVERY clinical trial tested the efficacy of dexamethasone in hospitalized patients with clinically suspected or confirmed infection with SARS-CoV-2, the virus that causes COVID-19. The study demonstrated a reduction in COVID-related 30-day mortality, especially in patients receiving mechanical ventilation or oxygen. Prior to preprint publication of these results, the Australian and New Zealand Intensive Care Society (ANZICS) Guidelines recommended against the routine use of corticosteroids.

"Our study demonstrated widespread, wholesale adoption of corticosteroid therapy for critically ill patients with COVID-19," said Prof. Udy. "This occurred almost immediately after preprint release of the RECOVERY trial results. This intervention was rapidly translated into bedside clinical care, prior to peer-reviewed publication in an established medical journal."

Dr. Udy and colleagues came to these conclusions after studying the SPRINT-SARI Australia database, which covers nearly all confirmed COVID-19 patients admitted to the ICU throughout the country. They compared corticosteroid use in adult COVID patients in the database before the study's June 22, 2020 preprint, after the preprint, and then after July 17, 2020 journal publication. They calculated the percentage of patients receiving corticosteroids per week, and used statistical methodologies to make comparisons across time periods.

"To our knowledge, this is the first report to quantify the impact of a preprint release on clinical practice across an entire country," the authors state. They found that the preprint led to significant practice change, with little additional change after peer-reviewed publication.

Dr. Udy notes that a number of factors may have influenced this change, including: (1) the high-quality nature of the clinical trial; (2) clinicians' urgent desire to provide some form of disease-modifying therapy to address the effects of a global potentially deadly viral pandemic; (3) the widespread availability of dexamethasone, which has been used broadly in medicine for decades, and (4) established clinical familiarity with this drug and its known side effects.

Dr. Udy cautions that not all clinical interventions disseminated via preprint may have the same risk profile, and the external validity of research findings should always be considered before widespread clinical implementation.

"Preprint publication relies on close inspection of the study findings, and we can only hope that with higher risk interventions, or those with a more questionable risk-benefit profile, such widespread adoption would not be so rapid."

Credit: 
American Thoracic Society

Proteins enable crop-infecting fungi to 'smell' food

image: Neurospora crassa eating plant biomass.

Image: 
Vincent Wu/JGI

New research shows the same proteins that enable human senses such as smell also allow certain fungi to sense something they can eat.

The UC Riverside study offers new avenues for protecting people from starvation due to pathogenic fungus-induced food shortages. Understanding how fungi sense and digest plants can also help scientists engineer fungal strains that are more efficient at producing biofuels.

Newly published by the American Society for Microbiology journal mBio, the study details how fungi react to cellulose, the main component of plant cell walls. Humans and other animals lack the enzymes to digest cellulose, but fungi can convert it into glucose, a sugar that makes an excellent biofuel feedstock.

Key to this conversion process are G proteins, which send signals from a cell's outer membrane into its nucleus.

"These proteins get information about what's outside the cell into what is essentially the brain of the cell, the nucleus, which in turn instructs the cell to produce a cocktail of cellulose-digesting enzymes," said study author and biochemistry doctoral student Logan Collier.

To determine whether G proteins play a role in the ability of fungi to sense nearby cellulose, the researchers modified strains of a fungus called Neurospora crassa. Once the G proteins were mutated, Neurospora no longer had the ability to "see" that it was on cellulose.

Neurospora is a filamentous fungus, which means it's made of thin tubes that extend and form a mesh as it grows. It plays a critical role in the environment, recycling carbon by consuming decaying plant matter and converting it into glucose.

It is also closely related to pathogenic fungi that kill crops such as tomatoes and wheat. One related species also causes rice blast, which destroys enough rice to feed about 80 million people annually. Knowing how to interfere with G protein signaling in the fungus so it cannot detect its "food" could be crucial to stopping these kinds of infections.

"No one has previously examined every member of the signaling pathway, creating a model for how every all of the G proteins work together," said Katherine Borkovich, a UC Riverside microbiology and plant pathology professor, who led the study.

Moving forward, the research team would also like to apply what they've learned to biofuel production.

"It does appear from our study that there are ways to modify the fungus to produce extra cellulose-digesting enzymes, which would make them more efficient at breaking down biofuel feedstocks," Collier said. Based on renewable sources like plants, biofuels can play a valuable role in reducing dependence on fossil fuels.

Credit: 
University of California - Riverside