Culture

In recent years, a non-invasive biopsy method called liquid biopsy has shown promise as a potential alternative to tissue biopsy, currently the gold standard in cancer detection and diagnosis. A tissue biopsy sample--traditionally collected through a surgical procedure that may require general anesthesia, accompanied by the risk of complications that may occur from any surgery, from pain through to infection and pneumonia --is typically tested for specific genetic variations, also referred to as mutations, which may offer information on a clear optimal treatment for that cancer.

Liquid biopsies, on the other hand, identify the presence of tumor DNA fragments or cells circulating in bodily fluids like blood, urine or saliva - called circulating tumor DNA (ctDNA) - and spares patients from unnecessary harm. Unfortunately, the minute amount of ctDNA in bodily fluids and their short-lived nature remain a challenge for real-life applications.

But biotech researchers at the Tokyo University of Agriculture and Technology (TUAT) have developed a nanopore technique which, in laboratory tests, has shown potential to offer a powerful, quick-and-easy tool for mutation detection.

The findings are published on Aug 9th, 2020, in the peer-reviewed journal Small Methods published by Wiley-VCH.

Nanopore measurements, a third-generation genetic sequencing technology, passes a DNA molecule through a nano-scale hole, or 'pore.' As it transits the pore, the DNA nucleotide bases (adenine [A], cytosine [C], guanine [G], or thymine [T]) cause changes in electrical charge that are specific to each of those bases and which can be catalogued, much like passing sand through a series of sifters. Nanopore tech can also sense the translocation, or exchange of genetic material, of short DNA strands via a blocking of the electric current when the pore is open. In both cases, second-generation measurement run times last anywhere from 4-9 days. But nanopore measurements occur in real time.

The rapid and cheap nanopore technique is often used for whole genome sequencing, but its use for ctDNA analysis remains underdeveloped. Nanopore sequencing is skilled in long read-lengths (>10,000-50,000 nt). Sequencing ctDNA (~150 bp) needs earlier stage processing like giving multiple copies of the original ctDNA to stretch targets. While attempts at approaches using nanopore tech for directly ctDNA detection have been made, and are able to recognize the presence or absence of a single genetic mutation, so far, they have been unable to recognize the position of this mutation.

The TUAT method, based on statistical analysis of the length of time it takes for the genetic code to unzip, and of the blocking of the current, allowing both the presence and position of a mutation to be identified. It has so far only been used on short strips of genetic material, or oligonucleotides, not in real-world liquid biopsies.

"This is still at the proof-of-concept stage, but it is exciting not just because it could permit earlier detection," said Ryuji Kawano, one of the two engineers responsible for devising the new method, "but the technique could be used to assess the degree of metastasis [cancer growth] to how well anticancer drugs are working."

The researchers now hope to work with medical institutions to verify and catalog the location of mutations in ctDNA from a many different cancers in order to develop this method as a simple diagnostic method for a wide range of occurrences of the disease.

Genes that play an important role in allowing SARS-CoV-2 to invade heart cells become more active with age, according to research published today in the Journal of Molecular and Cellular Cardiology. The findings could help explain why age is major risk factor for dying from COVID-19, with people over 70 years at greatest risk, and why the disease can cause heart complications in severe cases, including heart failure and inflammation of the heart.

"When this novel coronavirus first emerged, we expected it to be primarily a respiratory illness, as the virus usually takes hold first in the lungs," said Professor Anthony Davenport from the Department of Medicine. "But as the pandemic has progressed, we've seen more and more COVID-19 patients - particularly older patients - affected by heart problems. This suggests that the virus is capable of invading and damaging heart cells and that something changes as we age to make this possible."

Professor Davenport led an international team of researchers from the University of Cambridge, Maastricht University, KU Leuven and Karolinska Institute to investigate the link between COVID-19 and heart failure. The researchers examined cells known as cardiomyocytes to see how susceptible they were to infection by the coronavirus. Cardiomyocytes make up the heart muscle and are able to contract and relax, enabling the heart to pump blood around the body. Damage to these cells can affect the ability of the heart muscles to perform, leading to heart failure

To cause damage, the virus must first enter the cell. SARS-CoV-2 is a coronavirus - spherical in shape with 'spike' proteins on its surface, which it uses to gain entry. The spike protein binds to ACE2, a protein receptor found on the surface of certain cells. The virus is also able to hijack other proteins and enzymes, including TMPRSS2 and Cathepsins B and L to gain entry.

The researchers compared cardiomyocytes from five young (19-25 year old) males and five older (63-78 year old) males and found that the genes that give the body instructions to make these proteins were all significantly more active in cardiomyocytes from the older males. This suggests that there is likely to be an increase in the corresponding proteins in aged cardiomyocytes.

"As we age, the cells of our heart muscles produce more of the proteins needed by the coronavirus to break into our cells," said Dr Emma Robinson from Maastricht University and KU Leuven. "This makes these cells more vulnerable to damage by the virus and could be one reason why age is a major risk factor in patients infected with SARS-CoV-2."

Some of the proteins encoded by the genes can be inhibited by existing medicines. For example, the anti-inflammatory drug camostat inhibits TMPRSS2 and has been shown to block SARS-CoV-2 entry in cells grown in the laboratory. The study also suggests new targets for medicines that could be developed such as compounds blocking binding of the virus to ACE2 that may be beneficial in protecting the heart.

"The more we learn about the virus and its ability to hijack our cells, the better placed we are to block it, either with existing drugs or by developing new treatments," said Professor Davenport.

WASHINGTON, Aug. 18, 2020 -- Potholes are aggravating to drive over, and they can cause billions of dollars of damage every year to automobile wheels, tires and suspensions. Currently, road crews fill in these holes with hydrocarbon-containing asphalt, but that material can leach out, polluting the environment. Now, scientists report a brand-new way to repair roads that's also eco-friendly -- by using a remnant of wastewater treatment called grit that's usually disposed of in landfills.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

"We had an idea to divert wastewater grit from landfills and turn it into a marketable product," says Zhongzhe Liu, Ph.D., who is presenting the work. "We formulated it into a ceramic mortar that could be used as a patch for pothole repair." The substance, known as grit assisted patch (GAP), is ultimately safer for the environment than hydrocarbon-based asphalt.

But grit, a heavy, unbiodegradable solid, requires processing to become GAP. First, wastewater containing sewage, food scraps and other waste is processed at treatment plants. The result is clean water that is released into waterways, but also solids from the preliminary treatment that are mostly sand and gravel, and this is referred to as grit. Because grit contains pathogens and impurities that make it unsuitable for direct recycling, it is usually taken to a landfill and buried.

Liu, who is at California State University-Bakersfield, and his collaborators were looking for ways to make grit useful, perhaps as a road material. They decided to incorporate it into a chemically bonded phosphate ceramic (CBPC). CBPCs are routinely used to treat hazardous or radioactive waste for disposal, but no one had used this yet on wastewater products.

Because a CBPC contains ingredients that would inactivate microbes, the researchers thought this could be a good way to kill pathogens and end up with a material that could be safely applied to roads. "In the first step of making a CBPC, we mix the wet grit with calcium oxide and magnesium oxide, which form an alkaline grit slurry that prevents the proliferation of pathogens," Liu says. "The second step is to add a weak acid, potassium dihydrogen phosphate, into the pathogen-minimized alkaline slurry to form the grit-CBPC mortar."

Conventional asphalt patch contains bitumen, a sticky, black residue left over after petroleum distillation. The conventional patch contains polycyclic aromatic hydrocarbons (known as PAHs) that are a risk to human health. A grit-formulated patch eliminates this environmental concern because its matrix is composed of calcium and magnesium oxides that are not toxic to people.

So far, the researchers have analyzed GAP performance in the lab, showing it has a compressive strength comparable to asphalt pavement, and they believe its longevity will be superior to that of asphalt-based patches. The group has filed a patent for GAP based on these initial findings. In the meantime, they are working on improving GAP's compressive strength even further, so it could potentially be used for other applications, such as building wheel stops at the end of parking spots.

The next step for getting GAP on the market as a pothole patch is to evaluate its bond strength when in contact with existing pavement and its durability when exposed to environmental extremes. The team is currently working on demonstration-scale experiments to field test GAP on an operational roadway with regular traffic. If necessary, they will explore additives to further improve the mechanical properties and durability of the new material. In addition, they plan to conduct a side-by-side comparison of GAP and conventional patch to gain a thorough understanding of the advantages it provides in terms of carbon footprint and economic benefit.

Jonathan Boreyko, an associate professor in mechanical engineering, has developed an aircraft thermal management technology that stands ready for adaptation into other areas.

The research was published in Advanced Functional Materials on Aug. 18, 2020.

Boreyko was the recipient of a Young Investigator Research Program award in 2016, given by the Air Force Office of Scientific Research. This award funded the development of planar bridging-droplet thermal diodes, a novel approach to thermal management. Boreyko's research has shown this new approach to be both highly efficient and extremely versatile.

"We are hopeful that the one-way heat transfer of our bridging-droplet diode will enable the smart thermal management of electronics, aircraft, and spacecraft," said Boreyko.

Diodes are a special kind of device that allow heat to conduct in only one direction by use of engineered materials. For management of heat, diodes are attractive because they enable the dumping of heat entering one side, while resisting heat on the opposite side. In the case of aircraft (the focus of Boreyko's funding), heat is absorbed from an overheated plane, but resisted from the outside environment.

Boreyko's team created a diode using two copper plates in a sealed environment, separated by a microscopic gap. The first plate is engineered with a wick structure to hold water, while the opposite plate is coated with a water-repelling (hydrophobic) layer. The water on the wicking surface receives heat, causing evaporation into steam. As the steam moves across the narrow gap, it cools and condenses into dew droplets on the hydrophobic side. These dew droplets grow large enough to "bridge" the gap and get sucked back into the wick, starting the process again.

If the source of heat were instead applied the hydrophobic side, no steam can be produced because the water remains trapped in the wick. This is why the device can only conduct heat in one direction.

What does this look like in practice? An object producing heat, like a CPU chip, overheats if this heat is not continually removed. Boreyko's invention is affixed to this heat source. Generated heat is transferred through the conducting plate, into the water. Water turns to steam and moves away from the source of the heat. The hydrophobic, nonconducting side prevents heat from entering via the air or other heat sources that may be near, allowing the diode to manage the heat only from its main subject.

Boreyko's team measured a nearly 100-fold increase in heat conduction when the wicked side was heated, compared to the hydrophobic side. This is a significant improvement to existing thermal diodes. According to Boreyko, current diodes are either not very effective, only conducting a few times more heat in one direction, or require gravity. This new bridging-droplet thermal diode can be used upright, sideways, or even upside-down, and would even work in space where gravity is negligible.

Infectious disease researchers at Fred Hutchinson Cancer Research Center have used a gene editing approach to remove latent herpes simplex virus 1, or HSV-1, also known as oral herpes. In animal models, the findings show at least a 90 percent decrease in the latent virus, enough researchers expect that it will keep the infection from coming back.

The study, published August 18 in Nature Communications, used two sets of genetic scissors to damage the virus's DNA, fine-tuned the delivery vehicle to the infected cells, and targeted the nerve pathways that connect the neck with the face and reach the tissue where the virus lies dormant in individuals with the infection.

"This is the first time that scientists have been able to go in and actually eliminate most of the herpes in a body," said senior author Dr. Keith Jerome, professor in the Vaccine and Infectious Disease Division at Fred Hutch. "We are targeting the root cause of the infection: the infected cells where the virus lies dormant and are the seeds that give rise to repeat infections."

Most research on herpes has focused on suppressing the recurrence of painful symptoms, and Jerome said that his team is taking a completely different approach by focusing on how to cure the disease.

"The big jump here is from doing this in test tubes to doing this in an animal," said Jerome, who also leads the Virology Division at UW Medicine. "I hope this study changes the dialog around herpes research and opens up the idea that we can start thinking about cure, rather than just control of the virus."

Two-thirds of the world population under the age of 50 have HSV-1, according to the World Health Organization. The infection primarily causes cold sores and is lifelong.

In the study, the researchers used two types of genetic scissors to cut the DNA of the herpes virus. They found that when using just one pair of the scissors the virus DNA can be repaired in the infected cell. But by combining two scissors - two sets of gene-cutting proteins called meganucleases that zero in on and cut a segment of herpes DNA - the virus fell apart.

"We use a dual meganuclease that targets two sites on the virus DNA," said first author Martine Aubert, a senior staff scientist at Fred Hutch. "When there are two cuts, the cells seem to say that the virus DNA is too damaged to be repaired and other molecular players come in to remove it from the cell body."

The dual genetic scissors are introduced into the target cells by delivering the gene coding for the gene-cutting proteins with a vector, which is a harmless deactivated virus that can slip into infected cells. The researchers injected the delivery vector into a mouse model of HSV-1 infection, and it finds its way to the target cells after entering the nerve pathways.

The researchers found a 92% reduction in the virus DNA present in the superior cervical ganglia, the nerve tissue where the virus lies dormant. The reductions remained for at least a month after the treatment and is enough the researchers say to keep the virus from reactivating.

The team did other comparisons to fine-tune the gene editing approach:

- Gene cuts with meganucleases were more efficient that with CRISPR/Cas9.

- Refining the vector delivery mechanism, they found the adeno-associated virus (AAV) vector that was the most efficient at getting the gene edits to cells infected with the virus.

The researchers are pursuing a similar strategy for herpes simplex 2, which causes genital herpes. They expect it to take at least 3 years to move toward clinical trials.

"This is a curative approach for both oral and genital HSV infection," Aubert said. "I see it going into clinical trials in the near future."

Respiration is a fundamental process of all living things, allowing them to produce energy, stay healthy, and survive. In cells, respiration involves what are known as "respiratory proteins", e.g. hemoglobin in the blood and myoglobin in muscles.

Respiratory proteins work by binding and releasing small molecules like oxygen, carbon monoxide etc., called ligands. They do this through their "active center", which in many respiratory proteins is a chemical structure called heme porphyrin.

Binding and releasing small molecules causes changes in the heme's molecular and electronic structure. Such a change is the transition from a planar low spin ligated porphyrin form to a domed high spin un-ligated form and vice-versa. This shift is a key step for respiration, ultimately switching hemoglobin between a "relaxed" and "tense" conformation.

Electrons spin around atoms, but also spin around themselves, and can cross over from one spin state to another. The debate about the transition from low-spin planar to a high-spin domed heme has been dominated by two schools of thought: the process is either by thermal relaxation or by a cascade among electron spin states.

Now, a team of scientists led by Majed Chergui at EPFL's School of Basic Sciences have solved the debate. The researchers detached the small molecule from the heme using short, energizing laser pulses. They then used another short, hard X-ray pulse from an X-ray free-electron laser to induce X-ray emission (XES), a very sensitive fingerprint of the spin state of molecules, which monitored the heme's changes as a function of time. They could thus determine that the passage from planar to domed and back is caused by a cascade among spin states.

The study was carried out on nitrosyl-myoglobin, which is myoglobin that has bound a nitric oxide molecule. Nitrosyl-myoglobin plays a crucial role in neurotransmission, regulation of vasodilatation, platelet aggregation, and immune responses.

"The conclusions of our work apply to all heme proteins," says Chergui. "In particular to hemoglobin in its uptake and release of oxygen when we breathe. Although this takes place at the thermal temperatures of the body, breathing is governed by electronic changes in the heme."

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.

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.

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."

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.

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.

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."

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.

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.

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.