Culture

Low humidity increases COVID risk; another reason to wear a mask

A study focused on the Greater Sydney area during the early epidemic stage of COVID-19 found an association between lower humidity and an increase in community transmission.

Now a second study by the same team confirms the risk.

The study is published today in Transboundary and Emerging Diseases.

The research led by Professor Michael Ward, an epidemiologist in the Sydney School of Veterinary Science at the University of Sydney, and two researchers from our partner institution Fudan University School of Public Health in Shanghai, China, is the second peer-reviewed study of a relationship between weather conditions and COVID-19 in Australia.

“This second study adds to a growing body of evidence that humidity is a key factor in the spread of COVID-19,” Professor Ward said.

Lower humidity can be defined as “dryer air”. The study estimated that for a 1 percent decrease in relative humidity, COVID-19 cases might increase by 7-8 percent.

The estimate is about a 2-fold increase in COVID-19 notifications for a 10 percent drop in relative humidity.

“Dry air appears to favour the spread of COVID-19, meaning time and place become important,” he said. “Accumulating evidence shows that climate is a factor in COVID-19 spread, raising the prospect of seasonal disease outbreaks.”

Why humidity matters

Professor Ward said there are biological reasons why humidity matters in transmission of airborne viruses.

“When the humidity is lower, the air is drier and it makes the aerosols smaller,” he said, adding that aerosols are smaller than droplets. “When you sneeze and cough those smaller infectious aerosols can stay suspended in the air for longer. That increases the exposure for other people. When the air is humid and the aerosols are larger and heavier, they fall and hit surfaces quicker.

“This suggests the need for people to wear a mask, both to prevent infectious aerosols escaping into the air in the case of an infectious individual, and exposure to infectious aerosols in the case of an uninfected individual,” Professor Ward said.

Key findings:

Additional evidence from the Sydney COVID-19 epidemic has confirmed cases to be associated with humidity

Reduced humidity was found in several different regions of Sydney to be consistently linked to increased cases

The same link was not found for other weather factors - rainfall, temperature or wind

Climatic conditions conducive to the spread of COVID-19 present a challenge to public health.

Credit: 
University of Sydney

Escape artists: How vibrio bacteria break out of cells

image: Image of Vibrio parahaemolyticus bacteria trapped in a host cell. A UTSW study found that this foodborne pathogen modifies cholesterol found in a cell's plasma membrane to exit and infect new cells.

Image: 
UT Southwestern Medical Center

DALLAS - Aug. 18, 2020 - As soon as the foodborne pathogen Vibrio parahaemolyticus infects a human intestinal cell, the bacteria are already planning their escape. After all, once it is in and multiplies, the bacterium must find a way out to infect new cells.

Now, UT Southwestern scientists have discovered the surprising route that V. parahaemolyticus takes during this exit - or egress - from cells. The bacteria, they report in the journal eLife, gradually modify cholesterol found in a cell's plasma membrane, eventually weakening the membrane enough so that it can break through.

"The more we understand how bacteria are manipulating host cells at a molecular level, the more we understand how they cause disease," says study leader Kim Orth, Ph.D., professor of molecular biology and biochemistry at UTSW and a Howard Hughes Medical Institute investigator. "Bacteria have many different mechanisms to escape, but this stood out because it's an especially novel one."

Vibrio bacteria are found in warm seawater and humans become infected by eating raw shellfish such as oysters. About a dozen different species of Vibrio can cause human illness; V. parahaemolyticus is the most common in the United States and leads to food poisoning symptoms - diarrhea, cramps, nausea, and vomiting.

About a decade ago, Orth's group first revealed how V. parahaemolyticus infects human intestinal cells. Vibrio, they showed, uses a common bacterial system known as the type 3 secretion system 2 (T3SS2) to invade cells and begin replicating. The T3SS2 is composed of a large complex of proteins that form a needle that can inject molecules into a human cell, coaxing the cell to take in the bacteria and blocking any potential immune response.

"We started to get a good understanding of how this pathogen gets inside cells and maintains an existence," says Orth. "We assumed that it was also using components of the T3SS2 to get out of cells again."

But when Orth and her colleagues started studying the egress of V. parahaemolyticus out of human cells, the T3SS2 didn't seem to play a role. Neither did a number of other known egress mechanisms that bacteria use. Finally, Marcela de Souza Santos - a former assistant professor of molecular biology at UTSW and co-first author of the study - suggested they search V. parahaemolyticus genome for proteins known as lipases, which can break down the fatty molecules that make up cellular membranes.

Orth's team identified a lipase known as VPA0226 and thought they'd found their answer, assuming the lipase digested the membranes of human cells. But they were in for another surprise. When they tracked the activity of the lipase, they discovered that it instead headed for the mitochondria of cells, where it modified membrane cholesterol molecules. Over seven to eight hours, as these cholesterol molecules are modified, the cell membrane becomes weak. By this time, V. parahaemolyticus has multiplied - from one or two bacteria to about 500 - and all the copies can escape through the weakened membrane.

"This is the only report we know of where a bacterium uses this kind of T2SS lipase to egress from a host cell that was invaded in a T3SS2 dependent way," says Suneeta Chimalapati, Ph.D., a research scientist in the Orth lab and co-first author of the study.

To confirm the role of VPA0226, de Souza Santos and Chimalapati tested what happened when V. parahaemolyticus completely lacked the lipase. Indeed, the bacteria successfully invaded human cells and began replicating, but remained stuck inside those initial cells. Eventually, the host cells - crammed full of bacteria - died along with all the V. parahaemolyticus.

The new observation likely won't have any immediate therapeutic implications, the researchers say; V. parahaemolyticus usually resolves on its own without treatment. But it helps shed light on how bacteria evolve egress mechanisms and the importance of looking beyond known secretion systems when thinking about the important molecules used by bacterial pathogens.

"We really had tunnel vision thinking the T3SS2 dominated everything Vibrio did, but this shows how many other tools it has on hand to use for its pathogenesis," says Orth, who holds the Earl A. Forsythe Chair in Biomedical Science and is a W.W. Caruth, Jr. Scholar in Biomedical Research. She was recently elected to the National Academy of Sciences.

Credit: 
UT Southwestern Medical Center

Data omission in key EPA insecticide study shows need for review of industry studies

For nearly 50 years, a statistical omission tantamount to data falsification sat undiscovered in a critical study at the heart of regulating one of the most controversial and widely used pesticides in America.

Chlorpyrifos, an insecticide created in the late 1960s by the Dow Chemical Co., has been linked to serious health problems, especially in children. It has been the subject of many lawsuits and banned in Europe and California. The EPA itself nearly banned the chemical, but in 2017 the Trump administration backtracked and rejected EPA's own recommendation to take chlorpyrifos off the market. The EPA plans to reconsider the chemical's use by 2022.

In February, the largest producer of chlorpyrifos, Corteva Agriscience (which owns Dow), said it would stop making the chemical because of slumping sales, not out of safety concerns. Corteva has kept up a running defense of the chemical.

So, while chlorpyrifos can still be used on some agricultural products, the chemical appears to be approaching the end of its long run.

However, University of Washington researchers report in a new study that decades of exposure to chlorpyrifos and all the political wrangling and lawsuits surrounding it might have been averted if a 1972 study had been adequately reviewed by the EPA, itself newly established in the early 1970s. The EPA also did not re-analyze the study data when new statistical techniques became available a few years later, the UW researchers added.

Lianne Sheppard, a professor of biostatistics and environmental health in the UW School of Public Health and the study's lead author, explained that the 1972 "Coulston study" established erroneously how much of the chemical a human could be exposed to before adverse effects showed up in a body's chemistry.

When Sheppard re-ran the study data using the same longhand statistical analysis as the original, she discovered that key data used in two other level-of-exposure tests in the same study had been left out of the central exposure question -- inexplicably. Consequently, the safe exposure limit, called the "no observed adverse effect level," that the EPA used was wrong.

As the uses for chlorpyrifos expanded in the 1970s and became approved for in-home uses in the 1980s and '90s, the EPA set allowable human exposure levels at the one described as safe in the Coulston study -- .03 mg/kg per day.

"This has huge public health implications," said Sheppard. "This study was the basis of policy for over 15 years and because it concluded that the 'no observed adverse effect level' was more than twice as high as it should have been, the standard was a lot less protective than it should have been."

In the new study, UW researchers stated: "Such an omission of valid data without justification is a form of data falsification that violates all standard codes of ethical research practice and is classified as outright research misconduct. It is tragic that an omission of valid data from the analysis of the Coulston study may have adversely impacted public health."

Sheppard pointed out two other critical problems with this study that made its results more susceptible to producing a higher level of "safe" exposure.

In short, because of how the Coulston study was designed, investigators were not able to compare the test results of the three groups treated with different doses of chlorpyrifos within the same analysis. "This meant that their original analysis was much less powerful than it could have been if it had put all the dose groups together in one analysis," Sheppard said.

Secondly, Sheppard points out, better statistical methods and software tools became available in the 1980s -- well within the window when the EPA was using the Coulston study to set acceptable exposure limits for chlorpyrifos -- and those would have shown that the study did not find a "safe" level of exposure. These 'longitudinal data analysis' tools allow a more direct assessment of how accumulation of the chemical would affect the body's chemistry over time, while also being able to accommodate the poor study design.

Had the Coulston data been put through the more modern technique, as was done by the UW researchers in their new study, EPA's reviewers would have seen that chlorpyrifos' effect on the body's chemistry accumulated over time and that the study had not discovered the "no observed adverse effect level" used by regulators to set safe levels of exposure.

"All kinds of approvals were allowed for uses that never should have been allowed and quite well wouldn't have been allowed if the Coulston study authors had properly reported their results," said Sheppard.

Why the 1972 Coulston study was not thoroughly examined even as the maturing EPA began reviewing these kinds of studies more rigorously through its inaugural 2006 Human Studies Review Board is a mystery, said co-author Richard Fenske, emeritus professor in the UW School of Public Health's Department of Environmental & Occupational Health Sciences.

But when the EPA formally set out to review human-subject studies like the Coulston study, the maker of chlorpyrifos (Dow) specifically removed the study from that process, said Fenske, who was a member of that initial review board.

"You can speculate why they did," said Fenske, "but they formally asked the Human Studies Review Board not to review this study and so it was never reviewed."

Fenske, whose decades-long work involving insecticides includes a 1990 study of chlorpyrifos residue left behind after an in-home spray treatment (finding the treatment could expose children to unsafe levels of the chemical), said that while the Coulston study could be old news now, "it is a cautionary tale that data being submitted for pesticide registration may not have undergone proper review, and that could be happening today."

Sheppard added that "at a minimum," studies funded by companies developing a chemical that's under study must be opened to outside scrutiny. "I'm not sure industry should be doing these studies at all. I don't think the fox should be guarding the hen house."

Credit: 
University of Washington

Smart AI makes all kinds of shapes on its own

image: POSTECH research team develops an artificial neural network system that recommends plastic molding process conditions.

Image: 
POSTECH

Plastic is light, cheap, and can be made into any shape if heated, making it a "gift from the 20th-century god." The key is to maintain its uniform quality but its sensitivity to process conditions makes processing autonomy difficult. It also takes long to change the process once it is set and real-time optimization is deemed impossible due to the difference in actual outcomes.

A research team consisting of Professor Junsuk Rho and doctoral student Chihun Lee of POSTECH's departments of mechanical and chemical engineering and Professor Seungchul Lee, Juwon Na in the MS-PhD integrated program with Professor Seongjin Park in the Department of Mechanical Engineering have together developed a system that recommends process conditions for injection molding by combining artificial neural network (Artificial Neural Network) and a random search. Various shapes can be obtained in real time through using this new system. These research findings were recently published in the journal Advanced Intelligent Systems.

The team trained the relationship between process conditions and final products using artificial intelligence to find the conditions that satisfy the target quality. 3,600 simulations and 476 experiments from 36 different molds were obtained and learned. As a result, the team confirmed that each datum had 15 shapes and five processes as input value and the final weight of the product as the output value.

Based on the weight prediction model trained through transfer learning, a recommender system was developed to find the optimal process conditions by random search. By applying the conditions recommended by the AI model, the average relative error of 0.66% was achieved.

Finally, a GUI (graphical user interface) was developed for the actual injection machines. This allows even non-experts to enter the shape information for any product to establish a process condition that has an error within 1% of the target product weight.

Conventional research predicted the quality of the target product by only changing the process conditions for one specified product. However, this study collected information on the results (weight) of 36 differently shaped products while changing both quantified shapes and process conditions. Therefore, even if a new product is molded, the process conditions can be controlled without having to predict the results or to generate learning data by simply entering the shape of the product. In addition, transfer learning was introduced to obtain both simulation data and the accuracy of experimental data.

Using this newly developed artificial neural network system, even non-experts can obtain uniform results by simply entering the shape and the weight of the final product desired. It is anticipated that such system will enable the implementation of 'unmanned smart factory' in various manufacturing industries by allowing plastic injection processes, machining, 3D printers, and casting, which were previously challenging.

Credit: 
Pohang University of Science & Technology (POSTECH)

Shigella prevents infected cells from sacrificing themselves for the greater good

image: Host cells recognize blockade of caspase-8 apoptosis signaling by bacterial pathogens, and triggers necroptosis as a backup form of host defense. To counteract this cell death crosstalk, Shigella flexneri delivers effectors via the type III secretion system and successfully prevent apoptosis and necroptosis, thereby maintaining its replicative niche.

(i) When Shigella invades and multiplies within epithelial cells, PAMPS and DAMPs are released. Host cells detect these PAMPs and DAMPs, and subsequently trigger apoptosis as host defense to clear bacterial infection. (ii) To counteract this, Shigella delivers OspC1 effector, and directly or indirectly prevents caspase-8 activation and apoptotic cell death. (iii) On the contrary, host cells detect bacterial disturbance of caspase-8 activation, resulting in induction of necroptosis as a backup host defense. (iv) Again, Shigella subsequently delivers OspD3 effector, which targets RIPK1 and RIPK3 for degradation via its protease activity to prevent necroptosis.

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Department of Bacterial Pathogenesis,TMDU

Tokyo, Japan - Enteric pathogens, such as the bacterium Shigella, can cause severe intestinal disease with bloody diarrhea. In a new study, researchers from Tokyo Medical and Dental University (TMDU) discovered a novel molecular survival strategy by which Shigella is able to cause damage to the intestines despite two elaborate protective mechanisms used by host cells.

When bacteria infect the intestines, one of the host's responses is to have its own cells undergo cell death to prevent the pathogen from propagating This sacrifice of infected cells to ensure the overall safety of the host can happen through several mechanisms, two of the most important being apoptosis and necroptosis. While apoptosis results in a non-inflammatory form of programmed cell death through the activation of caspase proteins, necroptosis leads to inflammatory cell death as a form of ultima ratio in a caspase-independent manner. In contrast, during infection with Shigella, cell death is not observed and the resultant survival of the bacteria ensures their proliferation to cause severe inflammatory colitis.

"We know that Shigella are capable of injecting so-called effector proteins to disarm individual protective cell death pathways during the early stage of infection," says the corresponding author of the study Dr. Hiroshi Ashida. "At a later stage of infection, host cells employ a crosstalk between various forms of cell death to ensure that if one failed the other will take over. The goal of our study was to understand the mechanism of the molecular crosstalk between apoptosis and necroptosis, and how Shigella manages to evade both forms of cell death during the late stage of infection."

To achieve their goal, the researchers infected human colon cells with normal Shigella and mutant Shigella lacking various effectors, and found that when OspD3 effector was missing, the colon cells underwent cell death at a higher rate, suggesting that OspD3 is capable of preventing cell death. To understand which form of cell death OspD3 blocks, the researchers investigated the effect of OspD3 on cell death in the presence of RIPK inhibitor, which was able to block the actions of OspD3, suggesting that it blocks necroptosis. To corroborate this finding, the researchers dissected the molecular components of necroptosis and found that OspD3 blocks necroptosis by degrading the proteins RIPK1 and RIPK3.

Having established that Shigella prevents necroptosis through OspD3, the researchers asked what triggers necroptosis during Shigella infection in the first place. Because apoptosis is the first line protection of colon cells during infection, the researchers hypothesized that inhibition of apoptosis triggers necroptosis and thus that both forms of cell death are linked. To test this, they first focused on the protein caspase-8, which activates apoptosis and conversely, activated necroptosis when blocked. The researchers screened a number of Shigella effector proteins and found that OspC1 effector can block caspase-8 and thus apoptosis during Shigella infection. Intriguingly, this concurrently activated the process of necroptosis, demonstrating a molecular crosstalk between apoptosis and necroptosis to ensure cell death and prevent further bacterial multiplication.

"These are striking results that show how colon cells can recognize the blockade of apoptosis and trigger necroptosis as a backup plan for cell death. Our findings provide new insight into the molecular mechanisms by which bacteria disarm the host's protective measures," says Dr. Ashida.

Credit: 
Tokyo Medical and Dental University

Multivitamin, mineral supplement linked to less-severe, shorter-lasting illness symptoms

CORVALLIS, Ore. - Older adults who took a daily multivitamin and mineral supplement with zinc and high amounts of vitamin C in a 12-week study experienced sickness for shorter periods and with less severe symptoms than counterparts in a control group receiving a placebo.

The findings by Oregon State University researchers were published in the journal Nutrients.

The research by scientists at OSU's Linus Pauling Institute involved 42 healthy people ages 55 to 75 and was designed to measure the supplement's effects on certain immune system indicators. It also looked at bloodstream levels of zinc and vitamins C and D while taking the supplement, as these micronutrients are important for proper immune function.

The immune indicators, including white blood cells' ability to kill incoming pathogens, were unaltered in the group receiving the supplement.

The multivitamin group showedimproved vitamin C and zinc status in the blood. Most intriguingly, illness symptoms reported by this group were less severe and went away faster than those experienced by the placebo group.

The same percentage of participants in each group reported symptoms, but days of sickness in the supplement group averaged fewer than three compared to more than six for the placebo group.

"The observed illness differences were striking," said corresponding author Adrian Gombart, professor of biochemistry and biophysics in the OSU College of Science and a principal investigator at the Linus Pauling Institute. "While the study was limited to self-reported illness data and we did not design the study to answer this question, the observed differences suggest that additional larger studies designed for these outcomes are warranted - and, frankly, overdue."

As people get older, the risk of vitamin and mineral deficiencies that contribute to age-related immune system deficiencies rises. Across the United States, Canada and Europe, research suggests more than one-third of older adults are deficient in at least one micronutrient, often more than one.

"That likely contributes to a decline in the immune system, most often characterized by increased levels of inflammation, reduced innate immune function and reduced T-cell function," Gombart said. "Since multiple nutrients support immune function, older adults often benefit from multivitamin and mineral supplements. These are readily available, inexpensive and generally regarded as safe."

The multivitamin supplement used in the study focused on vitamins and minerals typically thought to help immunity. It contained 700 micrograms of vitamin A; 400 international units of vitamin D; 45 milligrams of vitamin E; 6.6 milligrams of vitamin B6; 400 micrograms of folate; 9.6 micrograms of vitamin B12; 1,000 milligrams of vitamin C; 5 milligrams of iron; 0.9 milligrams of copper; 10 milligrams of zinc; and 110 micrograms of selenium.

"Supplementation was associated with significantly increased circulating levels of zinc and vitamin C, and with illness symptoms that were less severe and shorter lasting," Gombart said. "This supports findings that stretch back decades, even to the days of Linus Pauling's work with vitamin C. Our results suggest more and better designed research studies are needed to explore the positive role multivitamin and mineral supplementation might play in bolstering the immune system of older adults."

Credit: 
Oregon State University

New building block in plant wall construction

University of Adelaide researchers as part of a multidisciplinary, international team, have uncovered a new biochemical mechanism fundamental to plant life.

The research, published in The Plant Journal details the discovery of the enzymatic reaction involving carbohydrates present in plant cell walls, which are essential for their structure.

Project leader, Professor Maria Hrmova, said the discovery contributes to important knowledge about how plant cell walls could be formed, structured and re-modelled.

"Plant cell walls perform a number of essential functions, including providing shape to the many different cell types needed to form the tissues and organs of a plant, intercellular communication, and they play a role in plant-microbe interactions, including defence responses against potential pathogens," Professor Hrmova said.

Earlier research into the chemistry and function of the xyloglucan carbohydrates in plants had found that xyloglucan xyloglucosyl transferase enzymes are one of the key accelerants in the re-modelling of cell walls.

It has only been through the development of the methodology used in this study, recombinant technology - which makes it possible to isolate proteins in a pure state - and the availability of defined carbohydrates, that it has been possible to observe the enzymatic reaction which occurs between the xyloglucan and pectin carbohydrates.

"When we were able to closely observe the substrate specificity of barley xyloglucan xyloglucosyl transferases, we discovered a chemical reaction, which results in the production of a hetero-polysaccharide (a carbohydrate composed of chemically distinct components). We could also examine these reactions at the molecular levels to define how these enzymes precisely work," Professor Hrmova said.

"It is one thing to be able to identify the different components of cell walls in plants, but that is not enough, we need to understand how they are formed and what they do, and this method of isolating pure proteins so they can be examined, allowed us to do just that," Professor Hrmova said.

"This discovery is a new building block in our understanding of how the cell wall could be constructed."

"Once you understand how something is made, you can then look at constructing or de-constructing it in different ways," Professor Hrmova said.

"That is why fundamental knowledge on how these enzymes function is so valuable."

The findings could have far-reaching implications for the sustainability of plant-based industries such as agriculture, horticulture, forestry for biofuels production and food and materials processing.

To date the team have characterised four out of 36 xyloglucan xyloglucosyl transferases in barley, so there is still many more to examine, which could lead to further discoveries. Once this work has been completed for barley, the methodology could be applied to examining the cell walls of other crops such as wheat and rice.

"Plants are the world's largest renewable resource - plants feed the world and they also produce energy in the form of biofuels," Professor Hrmova said.

The knowledge could allow for the bioengineering of similar proteins involved in plant cell wall re-modelling to create higher quality foods and to learn how to de-construct plant cell walls to obtain biofuels.

Credit: 
University of Adelaide

Low-dose real-time X-ray imaging with nontoxic double perovskite scintillators

image: a, Photographs of Cs2Ag0.6Na0.4In0.85Bi0.15Cl6 single crystals and powder under X-ray illumination. b, Proposed mechanism of X-ray scintillation in a lead-free halide double perovskite scintillator. c, Stokes shift of Cs2Ag0.6Na0.4In1-yBiyCl6 with different Bi3+ contents. d, RL spectra of Cs2Ag0.6Na0.4In0.85Bi0.15Cl6, LuAG:Ce and CsI:Tl wafers. e, Attenuation efficiency and light yield of Cs2Ag0.6Na0.4In1-yBiyCl6 versus Bi3+ content. f, Afterglow curves of Cs2Ag0.6Na0.4In0.85Bi0.15Cl6 and CsI:Tl.

Image: 
Wenjuan Zhu, Wenbo Ma, Yirong Su, Zeng Chen, Xinya Chen, Yaoguang Ma, Lizhong Bai, Wenge Xiao, Tianyu Liu, Haiming Zhu, Xiaofeng Liu, Huafeng Liu, Xu Liu, and Yang (Michael) Yang

X-ray imaging has been actively utilized in the fields of industrial material inspection, medical diagnosis and scientific research. The key component to detect X-ray is the scintillator which can convert X-ray photons to visible photons and then be detected by a photodiode array. Despite of decades of intensive research of scintillators, the performances of conventional scintillators are still far from ideal. While the emerging lead halide perovskite starts to show very promising characters, there are still several unpleasant factors such as strong self-absorption, relatively low light yield and lead toxicity that limit their practical application.

In a new paper published in Light Science & Application, a team of researchers, led by Professor Yang Yang from State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, China, and co-workers have developed a nontoxic Cs2Ag0.6Na0.4In0.85Bi0.15Cl6 double perovskite scintillator, which exhibits not only a high light yield but also long-term stability under continuous thermal treatment and X-ray irradiation. Given the high light output and fast light decay of this scintillator, static X-ray imaging was attained under an extremely low dose of ~1 μGyair, and dynamic X-ray imaging of finger bending without a ghosting effect was demonstrated under a low dose rate of 47.2 μGyair s-1. These results reveal the huge potential in exploring scintillators beyond lead halide perovskites, not only for avoiding toxic elements but also for achieving higher performance.

Scintillators are capable of converting X-ray photons into visible photons. The plausible mechanism of X-ray scintillation can be described as follows: The radiation energy is first absorbed by the heavy atoms of the scintillators mainly through the photoelectric effect and inelastic Compton scattering, ejecting massive hot electrons; then, these electrons thermalize on an ultrafast timescale and are captured by luminescent centres. These scientists summarize the design principles of scintillator:

"We design the scintillator according to the following three principles:(1) Introduce heavy atom (Bi3+) to improve X-ray absorption efficiency; (2) Weaken self-absorption and improve photoluminescence quantum yield to optimize light out; (3) Reduce afterglow and shorten light decay time to increase the signal-to-noise ratio (SNR) of X-ray imaging."

"The realization of high-resolution X-ray image under an extreme low X-ray dose demonstrate that the X-ray dose requirement for medical X-ray imaging can be significantly reduced in the future." They added.

"The presented scintillators can be used in X-ray computed tomography (CT) and dynamic X-ray imaging, which is important to understand many biological processes and is also useful for online monitoring of industrial process." The scientists forecast.

Credit: 
Light Publishing Center, Changchun Institute of Optics, Fine Mechanics And Physics, CAS

New links found between diabetes blood markers and Alzheimer's disease pathology

image: New links found between diabetes blood markers and Alzheimer's disease pathology.

Image: 
UEF / Raija Törrönen

A new study published in the Journal of Alzheimer's Disease provides insight into the association of blood markers of diabetes with brain beta-amyloid accumulation among older people at risk of dementia. The results suggest a link between Alzheimer's pathology, lower levels of insulin and lower insulin resistance.

The deposition of beta-amyloid plaques in the brain is known to be one of the key elements of Alzheimer's disease and can begin years or even decades before the disease progresses to the dementia stage. Amyloid accumulation in the brain can be detected by PET scans.

Type 2 diabetes is a known risk factor for cognitive impairment and Alzheimer's disease, but the underlying mechanisms are still unknown. Autopsy studies have found that diabetes is associated with small vessel pathology typical of vascular dementia, but not specifically of Alzheimer's disease. Insulin resistance, an indicator of a pre-diabetic state, has been associated with amyloid accumulation in cognitively normal middle-aged and late middle-aged individuals, but not in the older age groups.

In the present study, researchers from the University of Eastern Finland investigated the association of blood markers of diabetes with beta-amyloid accumulation detected in PET scans in older people at risk of dementia. The study population included 41 participants from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). FINGER has investigated the cognitive benefits of a multidomain lifestyle intervention for people over 60, who are at risk of cognitive decline.

Results from the study indicate slightly better insulin homeostasis in amyloid positive older individuals at risk of dementia. The findings contrast with earlier findings, possibly due to the fact that this study population was at high risk of cognitive decline.

"The results could also suggest that in people with diabetes and vascular pathology, less amyloid accumulation in the brain may be needed to trigger the onset of Alzheimer's dementia," Associate Professor Alina Solomon from the University of Eastern Finland says.

"Interestingly, no association was found for amyloid deposition with fasting glucose levels or HbA1c, which measures the average level of blood sugar."

This new study adds to the growing amount of data on the associations of insulin resistance and diabetes with Alzheimer's disease pathology.

Due to its promising results, the FINGER study has expanded around the globe as part of the World Wide FINGERS research network, which has been setup to help execute lifestyle interventions for, and research into, cognitive impairment and dementia prevention. In the future, this will enable the replication of the results obtained in this study with larger populations and help gain further insight into the connections between diabetes and Alzheimer's disease.

Credit: 
University of Eastern Finland

Flexible and protected

video: This is a simulation of four spike proteins (red, orange, blue and grey) of the SARS-CoV-2 virus. The proteins and lipids are shown in surface representation. The protective glycan chains are shown in green.

The spike protein is at the centre of vaccine development because it triggers an immune response in humans. A group of German scientists, including members of EMBL in Heidelberg, the Max Planck Institute of Biophysics, the Paul-Ehrlich-Institut, and Goethe University Frankfurt have focused on the surface structure of the virus to gain insights they can use for the development of vaccines and of effective therapeutics to treat infected patients.

Image: 
Sören von Bülow, Mateusz Sikora, Gerhard Hummer/MPI of Biophysics

At the start of a COVID-19 infection, the coronavirus SARS-CoV-2 docks onto human cells using the spike-like proteins on its surface. The spike protein is at the centre of vaccine development because it triggers an immune response in humans. A group of German scientists, including members of the European Molecular Biology Laboratory (EMBL) in Heidelberg, the Max Planck Institute of Biophysics, the Paul-Ehrlich-Institut, and Goethe University Frankfurt have focused on the surface structure of the virus to gain insights they can use for the development of vaccines and of effective therapeutics to treat infected patients.

The team combined cryo-electron tomography, subtomogram averaging, and molecular dynamics simulations to analyse the molecular structure of the spike protein in its natural environment, on intact virions, and with near-atomic resolution. Using EMBL's state-of-the-art cryo-electron microscopy imaging facility, 266 cryotomograms of about 1000 different viruses were generated, each carrying an average of 40 spikes on its surface. Subtomogram averaging and image processing, combined with molecular dynamics simulations, finally provided the important and novel structural information on these spikes.

The results were surprising: the data showed that the globular portion of the spike protein, which contains the receptor-binding region and the machinery required for fusion with the target cell, is connected to a flexible stalk. "The upper spherical part of the spike has a structure that is well reproduced by recombinant proteins used for vaccine development," explains Martin Beck, EMBL group leader and a director of the Max Planck Institute (MPI) of Biophysics. "However, our findings about the stalk, which fixes the globular part of the spike protein to the virus surface, were new."

"The stalk was expected to be quite rigid," adds Gerhard Hummer, from the MPI of Biophysics and the Institute of Biophysics at Goethe University Frankfurt. "But in our computer models and in the actual images, we discovered that the stalks are extremely flexible." By combining molecular dynamics simulations and cryo-electron tomography, the team identified the three joints - hip, knee and ankle - that give the stalk its flexibility.

"Like a balloon on a string, the spikes appear to move on the surface of the virus and thus are able to search for the receptor for docking to the target cell," explains Jacomine Krijnse Locker, group leader at the Paul-Ehrlich-Institut. To prevent infection, these spikes are targeted by antibodies. However, the images and models also showed that the entire spike protein, including the stalk, is covered with chains of glycans - sugar-like molecules. These chains provide a kind of protective coat that hides the spikes from neutralising antibodies: another important finding on the way to effective vaccines and medicines.

Credit: 
European Molecular Biology Laboratory

Scan for arterial plaque is better at predicting heart attack than stroke

image: This chart shows the risk of heart attack (red) versus stroke (blue) at different coronary artery calcium (CAC) levels. Having a CAC score within the highest category was strongly associated with risk for heart attack in the study.

Image: 
UT Southwestern Medical Center

DALLAS - Aug. 18, 2020 - The amount of calcified plaque in the heart's arteries is a better predictor of future heart attacks than of strokes, with similar findings across sex and racial groups, according to new research from UT Southwestern.

The study, published today in Circulation: Cardiovascular Imaging, is the first to examine the predictive value of recently recommended coronary artery calcium (CAC) score categories for heart attacks and strokes. Using two population-based, multiethnic cohorts, the researchers evaluated how well the amount of calcium detected by a CT scan of the heart predicted whether white, Black, and Hispanic men and women would have a stroke or a heart attack in the next 10 years.

Calcium is part of the fatty plaque that builds up in arteries supplying blood to the heart and brain and can lead to blockages, causing heart attacks or strokes. As plaque becomes more calcified and hardens, it becomes more visible on a heart CT scan.

"In our study, there was a twofold greater risk of heart attack than stroke at CAC levels at or above 100," a score indicating moderate to high levels of calcified plaque, says Parag Joshi, M.D., a cardiologist and assistant professor of internal medicine at UT Southwestern and senior author of the study. "That held true for Black, white, and Hispanic men and women."

Women and Black individuals generally have higher stroke risk, Joshi says.

"In fact, while the calcium score may not be a strong predictor of stroke risk for most, for some reason it did well in predicting strokes in Black participants," says Anurag Mehta, M.D., the first author of the study, formerly at UT Southwestern and now at Emory University School of Medicine.

The findings could help guide health care providers as they decide how aggressively to treat patients with risk factors such as high cholesterol and blood pressure but who have never had a major cardiovascular event.

In 2018, the American Heart Association and the American College of Cardiology issued joint cholesterol management guidelines that recommend using the CAC score as an aid when deciding whether to prescribe a cholesterol lowering statin drug in situations where the decision - based on the routine risk assessment using systolic blood pressure, cholesterol level, etc. - is uncertain.

Joshi's study evaluated data from more than 7,000 participants in two large studies - the Multi-Ethnic Study of Atherosclerosis (MESA) funded by the National Institutes of Health, and the Dallas Heart Study at UT Southwestern.

The authors divided study participants by the AHA/ACC calcium risk categories - 0, 1-99, and 100 or above - to evaluate how useful the calcium scores would have been in predicting heart attacks and strokes. It also subdivided the participants by sex and race (Black, white, and Hispanic) to calculate the risk levels for the different groups.

For participants with a calcium score of zero, there was a similarly low risk of either a stroke or a heart attack in the coming 10 years - less than 2 percent for either event among all study participant categories, according to the study.

The risk level for both heart attacks and strokes rose a bit for those with scores of 1-99, yet still remained below 6 percent - increasing about equally for both and across most demographic groups. At this level, women did have a greater increase in the risk for stroke than for heart attack, whereas men had higher heart attack risk than stroke.

Greater differences were found when the CAC scores rose to 100 or above, with heart attack risk twice as high as stroke risk for the entire study population. While 10-year heart attack risk jumped above 12 percent for men and over 14 percent for Hispanic individuals, heart attack risk for women was approximately 8 percent, according to the study.

Meanwhile, stroke risk remained below 8 percent across all groups, although women, Black, and Hispanic people had higher risk than men and white participants.

For doctors and patients, the findings could help tilt the scales either toward or away from using statin drugs to lower cholesterol in cases where the decision is not clear-cut from factors such as age, sex, cholesterol, systolic blood pressure, and smoking history.

Patients are sometimes reluctant to begin what is likely to become a lifelong drug therapy, Joshi says. "If you think your patient should be on a statin and your patient doesn't want to take it, this can be a good arbitrator of that," he says. "Our findings also highlight some of the nuance between heart attack risk and stroke risk and how our patients might consider those two risks in their decision making."

Credit: 
UT Southwestern Medical Center

Russian chemists proposed a new design of flow batteries

image: The setup for testing the cell of vanadium redox flow battery. MEA is mounted on a tripod above the peristaltic pump. The tanks are filled with vanadium electrolyte (before the start of charging process).

Image: 
Image courtesy of study authors.

In 2020 China plans to launch the largest battery complex in the world with a capacity of 800 MW*h (approximately this amount of energy per year is consumed by a household with 200 apartments). This complex is based not on the usual lithium-ion or lead-acid batteries, but on the redox flow battery where the electricity is stored in the form of chemical energy of solutions - electrolytes. Battery consists of two tanks in which electrolytes are stored and membrane-electrode assembly (MEA) - solutions are supplied to MEA by pumps where they undergo electrochemical reactions which provide charging and discharging of the battery.

Due to this setup, redox flow batteries, unlike many other energy storage devices, enable independent scaling of power and capacity of the battery, which are determined by the size of MEA and electrolyte volume, respectively. In addition, redox flow batteries exhibit minimal self-discharge over extended periods and their electrolytes do not degrade even after tens of thousands of operating cycles, making them promising candidates for storing large amounts of energy in the smart power grids. For example, they can store excess electricity generated by photovoltaic solar cells during daylight and generate back-up electricity at night or in cloudy weather.

"Flow batteries are being actively integrated into the power grids of China, Germany and other countries, on one hand, and on the other hand, are continued to be developed and refined in laboratories", comments one of the authors of the work, researcher at the NTI Competence Center at IPCP RAS, Dmitry Konev. "We have proposed a completely new design of MEA, which will facilitate the research process and greatly reduce entrance threshold for new research groups into this area. In the future, this will help to achieve significant progress and will bring distributed energy resources from niche positioning to very high level of commercialization, including in Russia".

Sandwich with laser filling

The MEA is the heart of the flow battery. It looks like a sandwich of different sheets materials, divided into two symmetrical parts supplied with its own electrolyte. When the battery is connected to a power supply, the one electrolyte is oxidized, while another is reducing and so the battery is charging. After that, the power source can be disconnected and replaced with energy consumer - the electrolytes will undergo reverse processes and the battery will begin to discharge.

An important part of the MEA is the flow field plates, sandwich layers through which the electrolyte is pumped to the electrodes where the electrolytes are oxidized or reduced. The performance of the battery, i.e. power and efficiency, depend strongly on how well the flow fields are organized. Therefore, researchers often select different types of fields to optimize battery performance, but now this is a very labor-intensive task: flow fields are milled in dense graphite plates, which is time-consuming procedure. Russian researchers have proposed a different approach.

"We form flow fields by using several thin layers of flexible graphite materials: the necessary patterns in them are cutted by a laser and then these layers are superimposed on each other to get the required field", says the first author of the work, researcher at Mendeleev Univeristy, Roman Pichugov. "The procedure to create flow fields takes only a few minutes, which is much less than traditional milling of graphite. Plus, cheaper materials are used, and as a result, there is more scope for variation and selection of flow fields."

From cell to stack

Flow batteries can operate with different types of electrolytes. The most common (including those that are installed in China and are being introduced in other countries) utilize vanadium electrolytes, namely solutions of vanadium salts. Exactly on this electrolyte Russian scientists tested their cell design. They sorted out various types of flow fields, varied the electrolyte flow rate and obtained results that on a qualitative level coincide with the best world studies and on a quantitative level even slightly surpass them: the power of tested MEA slightly exceeded the power of similar cells on graphite.

Thus, the new design of MEA is greatly simplifying laboratory test and in the future can be used in real energy storage systems for distributed power grids. Now Russian scientists in collaboration with InEnergy LLC are developing and testing a vanadium flow battery composed of 10 such cells with a total power of 20 watts. The construction of the cell itself and the stack of 10 cells are protected by patents, the last of which belongs to ADARM company, created by the employees of MUCTR. In addition, scientists develop other types of flow batteries utilizing different electrolytes on the basis of the proposed design of MEA.

Credit: 
Mendeleev University

Insect wings inspire new ways to fight superbugs

image: Common whitetail dragonfly.

Image: 
Public domain image by Christopher Johnson (Insects Unlocked, University of Texas at Austin)

Scientists have revealed how nanomaterials inspired by insect wings are able to destroy bacteria on contact.

The wings of cicadas and dragonflies are natural bacteria killers, a phenomenon that has spurred researchers searching for ways to defeat drug-resistant superbugs.

New anti-bacterial surfaces are being developed, featuring different nanopatterns that mimic the deadly action of insect wings, but scientists are only beginning to unravel the mysteries of how they work.

In a review published in Nature Reviews Microbiology, researchers have detailed exactly how these patterns destroy bacteria - stretching, slicing or tearing them apart.

Watch and embed the video

Lead author, RMIT University's Distinguished Professor Elena Ivanova, said finding non-chemical ways of killing bacteria was critical, with more than 700,000 people dying each year due to drug-resistant bacterial infection.

"Bacterial resistance to antibiotics is one of the greatest threats to global health and routine treatment of infection is becoming increasingly difficult," Ivanova said.

"When we look to nature for ideas, we find insects have evolved highly effective anti-bacterial systems.

"If we can understand exactly how insect-inspired nanopatterns kill bacteria, we can be more precise in engineering these shapes to improve their effectiveness against infections.

"Our ultimate goal is to develop low-cost and scaleable anti-bacterial surfaces for use in implants and in hospitals, to deliver powerful new weapons in the fight against deadly superbugs."

Bacteria-killing surfaces

The wings of cicadas and dragonflies are covered in tiny nanopillars, which were the first nanopatterns developed by scientists aiming to imitate their bactericidal effects.

Since then, they've also precisely engineered other nanoshapes like sheets and wires, all designed to physically damage bacteria cells.

Bacteria that land on these nanostructures find themselves pulled, stretched or sliced apart, rupturing the bacterial cell membrane and eventually killing them.

The new review for the first time categorises the different ways these surface nanopatterns deliver the necessary mechanical forces to burst the cell membrane.

"Our synthetic biomimetic nanostructures vary substantially in their anti-bacterial performance and it's not always clear why," Ivanova said.

"We have also struggled to work out the optimal shape and dimensions of a particular nanopattern, to maximise its lethal power.

"While the synthetic surfaces we've been developing take nature to the next level, even looking at dragonflies, for example, we see that different species have wings that are better at killing some bacteria than others.

"When we examine the wings at the nanoscale, we see differences in the density, height and diameter of the nanopillars that cover the surfaces of these wings, so we know that getting the nanostructures right is key."

Ivanova said producing nanostructured surfaces in large volumes cost-effectively, so they could be used in medical or industrial applications, remained a challenge.

But recent advancements in nanofabrication technologies have shown promise for opening a new era of biomedical antimicrobial nanotechnology, she said.

Credit: 
RMIT University

Airing commercials after political ads actually helps sell nonpolitical products

BLOOMINGTON, Ind. -- About $7 billion reportedly will be spent this fall on television and digital commercials from political campaigns and political action committees, filling the airwaves with political ads many viewers dislike. Companies running ads immediately afterward have been concerned about the potential of a negative spillover effect on how they and their products and services are perceived.

But new research from the Indiana University Kelley School of Business finds that the opposite is true. Contrary to mainstream thought, political ads instead yield positive spillover effects for nonpolitical advertisers.

And this happens regardless of whether the political ad is an attack ad or not, who the ad supports, and whether it's sponsored by a candidate, political party or PAC. Political advertising accounts for nearly 10 percent of all U.S. television ad revenue.

The findings are in the article, "Impact of Political Television Advertisements on Viewers' Response to Subsequent Advertisements ," -- accepted for publication in Marketing Science -- by Beth Fossen, assistant professor of marketing; Girish Mallapragada, associate professor of marketing and Weimer Faculty Fellow; and doctoral candidate Anwesha De, all from the Kelley School of Business.

"Our investigations provide insights into the previously unexplored ad-to-ad spillover effects and, more broadly, provides insights into how political messages influence consumers," Fossen said. "Nonpolitical ads that follow political ads benefit through a reduction in audience decline and an increase in positive post-ad chatter."

Using data for 849 national prime-time ads during the 2016 U.S. general election, the researchers found that ads airing after a political commercial saw an 89 percent reduction in audience decline and a 3 percent increase in post-ad chatter online.

Their findings remained consistent when examining the effect by TV network and political party affiliation.

"It seems reasonable to assume that Fox News viewers are more likely to be positively stimulated by pro-Republican ads than viewers of other channels," researchers wrote. "However, evidence from our data suggests that the positive spillover from pro-Republican ads is not higher and is nearly lower on Fox News viewership decline than when pro-Republican ads air on other channels."

They found a similar trend when it came to advertising on MSNBC, whose viewers frequently identify with the Democratic Party and progressive causes.

Mallapragada said the findings show that television networks and stations can leverage the positive spillover effects on subsequent ads by implementing differential pricing and systematic ad sequencing.

Prevailing belief in the business industry has suggested that political ads on television hurt the effectiveness of subsequent ads. To illustrate this concern, during the 2020 Super Bowl, game broadcaster Fox isolated political ads from other paying advertisers in their own ad breaks, a decision that cost the network millions in ad revenue, because it ran nonpaid show promos alongside the political ads instead of commercials from paying advertisers.

"The insights from this research enable advertisers to advocate for the inclusion of ad positioning in ad buys and, specifically, negotiate that their ads follow political ads," he said. "Our results may also encourage advertisers outside of the television context to experiment with advertising next to political content, an experimentation that may be especially beneficial for online advertisers given that they commonly blacklist political topics to avoid having their ads appear near political content."

Credit: 
Indiana University

The tropics are expanding, and climate change is the primary culprit

WASHINGTON--Earth's tropics are expanding poleward and that expansion is driven by human-caused changes to the ocean, according to new research.

The tropics wrap around Earth's middle like a warm, wet belt. This part of the globe gets the most direct sunlight throughout the year and is characterized by high average temperatures and heavy rainfall. In contrast to the tropics' lush interior, however, this region's edges are hot and parched.

Scientists have noticed for the past 15 years that these arid bands are expanding toward the poles into regions like the Mediterranean, southern Australia and southern California. Interestingly, these dry areas have expanded more in the Southern Hemisphere than the Northern Hemisphere and researchers have struggled to pinpoint exactly what is driving the trend.

A new study in AGU's ,Journal of Geophysical Research: Atmospheres argues that the failure to agree on an exact mechanism has been, in part, because most researchers have been looking in the wrong place. The new study found tropical expansion is driven primarily by ocean warming caused by climate change rather than direct changes to the atmosphere. A bigger shift is happening in the Southern Hemisphere because it has more ocean surface area, according to the new study.

Tropical expansion could have profound economic and social implications: the process could shift storm paths and cause more severe wildfires and droughts in places like California and Australia that are already water-stressed.

The new findings provide the clearest evidence yet that tropical expansion is in fact primarily driven by climate change, according to the study authors. While natural long-term climate fluctuations contribute to the observed trends, these variations alone cannot explain the extent to which expansion has already occurred.

This means, the authors argue, that climate change might have already significantly contributed to tropical expansion, especially in the ocean-dominated Southern Hemisphere.

"We demonstrate that the enhanced subtropical ocean warming is independent from the natural climate oscillations," said Hu Yang, a climate scientist at the Alfred Wegner Institute in Bremerhaven, Germany and lead author of the new study. "This is a result of global warming."

A disconcerting phenomenon

A 2006 paper published in the journal Science announced a troubling finding: in some parts of the world, the tropics were expanding. Researchers have attempted to figure out the culprit ever since that paper was published. Scientists estimate from satellite observations that this widening is happening at a rate of 0.25 to 0.5 degrees latitude per decade. But without pinpointing a root cause, they cannot accurately model how quickly the expansion will occur in the future or what regions it will impact.

Some researchers have suggested greenhouse gas emissions, ozone depletion and aerosols in the atmosphere are driving the expansion. But climate models using these variables to explain the expansion consistently underestimate the speed of the shift and do not account for why expansion is happening in some regions but not others. This has led some researchers to theorize that tropical expansion can simply be explained by natural oscillations in Earth's climate. But natural variation does not quite fit the patterns scientists have already observed.

Ocean versus atmosphere

Yang and colleagues began to take notice of tropical expansion in 2015, when analyzing ocean currents that carry warm water toward the poles. This got them thinking: what if tropical expansion was driven not by changes in the atmosphere, but changes in the ocean?

Because the ocean and atmosphere are highly connected systems, it is often difficult to tell which is driving the other, Yang said. In the new study, Yang and his colleagues analyzed water temperatures in the major ocean gyres, large circular ocean currents that carry warm water toward the poles and cold water toward the equator. They used satellite observations of sea surface temperature between 1982, the year observations began, and 2018, and compared these observations to data on the expanding tropics that stretches back to 1979.

They found excess heat building up in the subtropical oceans since global warming began in the mid-1800s has driven tropical edges and ocean gyres toward the poles. When the researchers compared movement of the ocean gyres to tropical expansion, they found the two phenomena matched: tropical expansion was happening in places where the ocean gyres were moving poleward.

"I actually am really impressed with this paper," said Kristopher Karnauskas, associate professor in the Department of Atmospheric and Oceanic Sciences at the University of Colorado Boulder who was not connected to the new study. "There really aren't a lot of papers out there that really investigate the role of the ocean in the tropical expansion problem."

Credit: 
American Geophysical Union