One of the drugs, cyclophosphamide, is an outdated chemotherapy drug once used to treat small cell lung cancer. It was displaced in favor of platinum-based drugs in the 1980s. Both kinds of drugs work at first but falter after a few months as the cancer develops resistance. Platinum-based drugs became the standard of care mainly because they cause lesser side effects, but they have not substantially improved prognosis. Today, the typical patient survives less than a year and a half after diagnosis.

In this study, however, researchers showed that small cell lung cancer cells resist cyclophosphamide by activating a specific repair process, and demonstrated that throwing a wrench into the repair process makes the drug much more effective, at least in mice. The findings, available online in Cancer Discovery, suggest a pathway to better therapies for one of the least treatable forms of cancer.

“Small cell lung cancer has one treatment option — platinum-based chemotherapy — and that adds maybe two to six months of life,” said co-senior author Nima Mosammaparast, MD, PhD, an associate professor of pathology & immunology and of medicine at Washington University, and a researcher at Siteman Cancer Centerat Barnes-Jewish Hospital and Washington University School of Medicine. “The problem is that these tumors respond to treatment initially, but then they come back. This has not changed for 30 years. These tumors are just massively resistant to just about everything. So what this study shows is that we can actually combine a new target with an old drug to reduce resistance and potentially make the treatment much better and give these patients a much better chance.”

The study came together fortuitously. Co-senior author Nicolas Reynoird, PhD, a professor at Grenoble Alpes University, studies how internal signaling within cells — and deregulation of such signaling — can lead to cancer progression and drug resistance. A few years ago, his team discovered that a protein called RNF113A may play a role in small cell lung cancer, but the researchers could not determine what the protein does. Meanwhile, Mosammaparast was studying how cells repair injured DNA. In 2017, he published a paper in the journal Nature describing how cancer cells repair a kind of DNA damage known as alkylation damage, the kind caused by cyclophosphamide. The paper noted that RNF113A plays a role in the process. Reynoird essentially cold-called Mosammaparast, and the two teamed up — along with co-senior author Pawel K. Mazur, PhD, an associate professor of experimental radiation oncology at MD Anderson and a longstanding collaborator of Reynoird’s — to investigate how small cell lung cancer cells resist alkylation damage, and whether it’s possible to magnify the effects of alkylating chemotherapy drugs such as cyclophosphamide by interfering with that resistance.

The team discovered that RNF113A is regulated by a protein called SMYD3 that is highly expressed in small cell lung cancer and some other cancers. High levels of SMYD3 are associated with more invasive disease, increased resistance to alkylating chemotherapy and worse prognosis. Healthy lung tissue has very little SMYD3, which led the researchers to think that knocking it down might target cancerous cells while sparing healthy ones.

So they tried it. The researchers created mouse models of human disease by grafting cancerous cells from two people with small cell lung cancer onto separate groups of mice. One set of cells came from a patient who had not yet been treated, so the cells had not had a chance to develop resistance. The other came from a patient who had been treated with and become resistant to standard platinum-based therapy.

All of the mice grew tumors. When the tumors were big enough, the researchers treated the mice with an inhibitor of SMYD3, cyclophosphamide, both or an inactive solution. Inhibiting SMYD3 alone modestly slowed down the growth of the tumors. Cyclophosphamide initially halted the growth of tumors from both patients, but the tumors started to grow again after about two weeks, indicating that they had developed resistance. However, the combination of the two drugs stopped the tumors in their tracks. They did not restart growing for the duration of the experiment.

“We’re talking to a number of other groups about starting a phase 1 clinical trial as soon as possible,” Mosammaparast said. “One of the challenges we will face is convincing doctors to go back to an old drug. But the nice thing about this strategy is that it may work where current therapies have failed. This treatment worked just as well against the tumor from the patient who had already relapsed on platinum-based therapy as it did against the untreated patient. People with small cell lung cancer are in desperate need of better treatments, and I’m very excited about the possibilities here.”

Story Source:

Materials provided by Washington University School of Medicine. Original written by Tamara Bhandari. Note: Content may be edited for style and length.

Antimicrobial resistance has become one of the greatest threats to public health globally. It occurs when bacteria, viruses, fungi and parasites change over time and no longer respond to medicines, making it difficult to treat infections. Because of this, there is a pressing need for the development of new antimicrobial drugs to combat infections.

A new study by scientists from the University of Portsmouth and Naresuan and Pibulsongkram Rajabhat Universities in Thailand explored whether hydroquinine, which is found in the bark of some trees, could inhibit any bacterial strains. Hydroquinine is already known to be an effective agent against malaria in humans, but until now there has been little investigation into its drug-resistant properties.

The findings, published in the Tropical Medicine and Infectious Disease journal, suggest the antimicrobial properties of the organic compound make it a potential candidate for future clinical investigation.

Dr Robert Baldock from the School of Pharmacy and Biomedical Sciences at the University of Portsmouth, said: “Using bacterial killing experiments, we found that hydroquinine was able to kill several microorganisms including the common multidrug-resistant pathogen pseudomonas aeruginosa.

“Characteristically, we also discovered that one of the main mechanisms used by these bacteria to escape killing activity of the drug was upregulated with treatment — indicating a robust response from the bacteria.

“By studying this compound further, our hope is that it may in future offer another line of treatment in combatting bacterial infections.”

Drug-resistant bacteria occur in more than 2.8 million infections and are responsible for 35,000 deaths per year. Common antibiotic-resistant “superbugs” cause diseases including sepsis, urinary tract infections, and pneumonia. Statistics show bloodstream infections with the bacteria — P. aeruginosa are associated with high mortality rates of between 30 and 50%.

The study recommends further investigation into the antimicrobial resistance properties and side effects of hydroquinine.

Dr Jirapas Jongjitwimol from the Department of Medical Technology at Naresuan University added: “Our future research aims to uncover the molecular target of hydroquinine. This would help our understanding of how the compound works against pathogenic bacteria and how it could potentially be used in a clinical setting.”

Story Source:

Materials provided by University of Portsmouth. Note: Content may be edited for style and length.

The findings could have important implications in applied settings such as medical displays, cognitive assistants, and product and environmental design, according to the researchers.

“Since the way we perceive objects determines how we interact with them, it is important to visually process them quickly and with high detail” Sarah Shomstein, a professor of cognitive neuroscience at GW said. “However, the way our eyes perceive and process an object can be different depending on what we know about this object. Our study shows, for the first time, that if we recognize an object as a tool, we perceive it faster but with less detail. If we recognize an object as a non-tool, we perceive it slower but with higher detail.”

To determine how the human brain processes an object visually, Shomstein and Dick Dubbelde, a recent PhD graduate at GW and co-author on the study, showed participants several images of objects that can be easily manipulated by hand such as a coffee mug, snow shovel or screwdriver, and several images of objects that are infrequently manipulated by hand, such as a potted plant, a picture frame or a fire hydrant. For half of the experiment, a small gap could be cut out of the bottom of each object. For the other half of the experiment, the objects could flicker on the screen. The team asked participants to report the presence or absence of a gap or the flicker, which helped the researchers figure out the speed and detail of object processing, and also which regions of the brain were being used to process the object.

Researchers found that objects usually manipulated by your hands are perceived faster than non-manipulable objects, making it easier to see the flickering. Alternatively, objects that we usually do not manipulate are perceived with greater detail than manipulable objects, making it easier to see the small gaps.

“The differences in perception between ‘mugs’ and ‘plants’ in both speed and detail of perception means that these objects are sorted by the visual system for processing in different brain regions,” Dubbelde said. “In other words, your knowledge of the object’s purpose actually determines where in the brain object processing will occur and how well you will perceive it.”

The study also showed that if you interfere with object recognition by making it harder to recognize an object as either manipulable or not manipulable — for example, by turning it upside down — then the differences in the speed and detail perception of the objects disappear.

Shomstein and Dubbelde note that this study could possibly explain individual differences in object perception and underscores that what you know and what your personal experience is with any particular object has direct consequences for perception.

The National Science Foundation (BCS-1921415 and BCS-2022572) supported this work.

Story Source:

Materials provided by George Washington University. Note: Content may be edited for style and length.

The study, done in China, found that teachers in the Chinese equivalent of professional learning communities (PLCs) were more willing to share their knowledge and expertise when they rated their PLC leaders as being higher in humility.

The reason was that humble leaders made teachers feel more empowered to share their knowledge because they felt psychologically safe to take risks, said study co-author Roger Goddard, professor of educational studies at The Ohio State University.

“A little humility on the part of leaders goes a long way in helping groups be more productive and collaborative,” Goddard said.

“When people feel their leader admits mistakes and is open to learning from others, everyone contributes more and makes these groups more effective.”

Goddard conducted the study with Yun Qu of Beijing Normal University in China and Jinjie Zhu, a doctoral student in education at Ohio State. The study was published online recently in the journal Educational Studies.

In the United States and elsewhere, PLCs are designed to facilitate professional development through discussions in which teachers share their best practices and what they have learned through their experiences in the classroom.

“Teachers can feel fairly isolated in the classroom,” Goddard said. “PLCs help teachers build a sense of community and learn from each other about how to improve classroom instruction.”

In China, the equivalent of PLCs are called Teaching Research Groups (TRGs). The leaders of TRGs are experienced teachers who are not traditional administrators, but do serve as supervisors and coordinators and are involved in teacher evaluations, lesson planning and teacher selection.

This study involved 537 teachers from 238 TRGs in a variety of both urban and rural schools in China.

Teachers rated their TRG leaders on three dimensions of humility: their willingness to view themselves accurately, such as admitting when they didn’t know how to do something; their appreciation of others’ strengths; and their teachability, such as being open to other teachers’ advice.

Results showed that teachers who rated their TRG leaders as being higher in humility were more likely to report that they shared their knowledge and expertise in TRG meetings.

“The whole point of these groups is for teachers to share their knowledge, so the fact that humble leaders inspired individuals in their groups to be more willing to do this is very significant,” Goddard said.

The study also found why humble leaders were so effective in helping their teachers share their knowledge.

Results showed that in TRGs with more humble leaders, teachers reported higher levels of psychological safety — they felt they could take risks and knew that others would not act in a way to undermine their efforts.

That feeling of safety led them to feel more psychologically empowered: They felt their jobs had meaning, they had autonomy to do their work, and they felt they were competent and that their work had impact in the school.

So humble leadership led to teachers feeling psychologically safe, which made them feel empowered and ultimately led them to share their experience and knowledge more fully with their colleagues, Goddard said.

“This feeling of teachers that they could safely share their knowledge comes from having a leader who has humility — an openness to learning from others, a willingness to revise opinions, and an appreciation for the strengths of others,” he said.

While this research was done in China, Goddard said he believes the results would be similar in the United States and elsewhere.

“There’s a lot of evidence that suggests trust is a key part of successful organizations. And feeling psychologically safe and empowered to share your knowledge in the workplace is part of building trust, and that’s what humble leaders help create,” he said.

“That is as true in the United States as it is in China.”

In the same way, the results should be applicable outside of education.

“Many of the same principles that make successful organizations cut across cultures and fields. It makes sense that humble leaders will build trust and better relationships that will increase the effectiveness of any groups that have to work together,” Goddard said.

The carbon footprint of timber construction is significantly lower than concrete construction, and timber construction has often been viewed as better for the health of human occupants as well. However, wood panels still use adhesives made from fossil raw materials. They contain formaldehyde, which can be harmful to health, especially for those working in the adhesive manufacturing process. People living in or visiting buildings can also be exposed to toxic formaldehyde from wood panels.

Lignin, on the other hand, comes from wood itself. It binds cellulose and hemicellulose together and gives wood its tough, strong structure. Lignin accounts for about a quarter of the weight of wood and is produced in huge quantities in the pulp and bioprocessing industry. Only two to five percent of the lignin produced is used, and the rest is burned in factories for energy.

Previously, lengthy and chemical-intensive pre-treatments have been necessary to use lignin in formaldehyde-free adhesives. The adhesive developed by Aalto University researchers can use purified kraft lignin and the chemical reaction to make the adhesive takes a few minutes instead of up to 10 hours. No additional heating of the raw material is needed, which reduces energy consumption. The only by-products of the process are salt and sodium hydroxide, or lye.

Monika Österberg, professor at the Aalto University School of Chemical Engineering, stresses that this is an important development for both the environment and industry. ‘Using lignin as a material can reduce carbon dioxide emissions and increase the processing value of forests. This is why research on lignin is an important priority for us at Aalto University.’

Doctoral researcher Alexander Henn explains that glued wood panels such as plywood and chipboard are increasingly used for walls, ceilings and flooring. ‘Therefore, it is important to overcome the disadvantages of wood-based panel adhesives and develop the new innovation into a commercial product. This would enable a shift towards more wood-based construction, as a strong and heat-resistant adhesive made from natural materials makes construction truly ecological and safe.’

The innovation is a major step forward for the forestry and glue industries, as the lignin content of previous adhesives has been relatively low (around 20-50 percent), while the new Aalto University innovation has a lignin content of over 90 percent. The adhesive is strong and non-toxic, and protects surfaces from fire, so it can even be used as a flame retardant.

According to the researchers, lignin can also be used as a raw material for applications such as coatings and composites. Research work will continue in the laboratory, and various commercialization opportunities are likely to be explored in collaboration with LignoSphere Oy, a spin-off from Aalto University.

Story Source:

Materials provided by Aalto University. Original written by Virpi Raski. Note: Content may be edited for style and length.

Dr Kate Quigley, a senior research scientist at the Minderoo Foundation who conducted the research at the Australian Institute of Marine Science, and James Cook University, has developed a new non-destructive method for rapidly and safely scanning coral — cutting down on previously laborious and lengthy surveying techniques.

Inspired by a visit to the dentist, Dr Quigley remarked on the similarities between coral and our teeth — both being calcium-based and requiring measuring tools that can withstand wet surfaces. “One day, I was at the dentist, and they rolled out this new scanning machine. I knew immediately that it was something that could apply to scanning very small corals given corals and teeth actually share many similar properties. The rest is history!”

Coral reefs are among the earth’s most productive ecosystems and provide essential nutritional and protective services to people across the globe. These important ecosystems have suffered serious declines over recent decades — spurring a flurry of research around their basic biology and restoration. Understanding the critical life stage of juvenile coral allows scientists to predict ecosystem changes, the impacts of disturbance and their potential for recovery.

Reconstructing coral 3D models reveals insights into their health and response to pressures like rising temperatures or acidification. Several methods exist to build and assess these 3D models, yet their effectiveness is reduced when constructing measurements at small scales.

Dr Quigley said: “At the moment, it is difficult to accurately measure very small objects in 3D, especially if you are interested in measuring small live animals, like coral, without hurting them.

“During my PhD it would take half a day to produce one scan, and I was interested in scanning hundreds of corals at a time.

“For the first time, this new method will allow scientists to measure thousands of tiny corals fast, accurately and without any negative health impacts on the coral. This has the potential to expand large-scale monitoring of ocean health and for up-scaling coral reef restoration.”

To assess the effectiveness of these dental scanners, namely the ITero Element 5D Flex, Dr Quigley measured juvenile corals at the Australian Institute of Marine Science’s National Sea Simulator. The coral, from the Great Barrier Relief, were temporarily removed from their indoor aquarium and their surface area and volume recorded before being returned to the tanks.

On average it took less than three minutes to scan and build a model of each individual coral compared to over 4 hours with previous methods — a 99% decrease in the time required to carry out such measurements. Dr Quigley recorded equally fast and precise performance when measuring and comparing models of dead skeletons and living coral tissue. Removing the need to sacrifice live animals to take measurements.

Whilst this is a massive step forward in cutting down the time involved in monitoring and studying small marine animals, 3D scans still need to be processed manually, which slows down analysis. Dr Quigley hopes that the next avenue for this research is to try and create an automatic analysis pipeline from scanning to measurement, potentially using AI.

At present, this technology can only be used to perform measurements out of the water. The hardware is not waterproof as the scanner relies on confocal laser technology.

“Potentially the scanner could be made completely waterproof. However, it is unclear how well the laser technology would work completely submerged underwater. We have taken this technology on the boat before and brought up wild and laboratory-reared corals for measurement, so we are getting there!”

Story Source:

Materials provided by British Ecological Society. Note: Content may be edited for style and length.