POSTMODERN ALCHEMY; SPAGYRICS

A minty-fresh solution: Using a menthol-like compound to activate plant immune mechanisms

A menthol-like compound was found to boost the expression of genes that protect crop species from pest-related damage

TOKYO UNIVERSITY OF SCIENCE

Research News

 

IMAGE: REDUCTION OF INSECT-CAUSED LEAF DAMAGE BY MENT-VAL EXPOSURE view more 

CREDIT: TOKYO UNIVERSITY OF SCIENCE

Although plants may look fairly inactive to casual observers, research into plant biology has shown that plants can send each other signals concerning threats in their local environments. These signals take the form of airborne chemicals, called volatile organic compounds (VOCs), released from one plant and detected by another, and plant biologists have found that a diverse class of chemicals called terpenoids play a major role as airborne danger signals.

Past studies have shown that soybean and lima bean plants both release terpenoid signals that activate defense-related genes in neighboring plants of the same species, and this chemically induced gene activation can help the plants protect themselves from threats like herbivorous pests.

In recent years, scientists have realized that the capacity of these chemical signals to boost plant defense mechanisms could make them useful pest control tools for agriculture and horticulture. One such scientist is Prof. Gen-ichiro Arimura of the Tokyo University of Science, Japan. Prof. Arimura notes that "the development of agricultural technology to date has been largely reliant on the use of pesticides and chemical fertilizers, which has resulted in environmental pollution and the destruction of ecosystems." As a greener alternative to pesticides, terpenoid signaling molecules may help farmers continue their production of vital foodstuffs while lessening the associated environmental costs.

In pursuit of this goal, Prof. Arimura and his colleagues chose to investigate the terpenoid compound menthol, which is derived from mint leaves and can activate plant immune systems. The aim of this project, which the researchers describe in an article recently published in the journal Plant Molecular Biology, was to develop compounds that are structurally similar to menthol but improve upon menthol's ability to activate plant immune systems. The researchers therefore experimented with chemically modifying menthol by attaching amino acids, which are a structurally diverse set of compounds that living cells use to construct proteins. In total, the researchers synthesized six different menthol derivatives with attached amino acids.

The researchers then tested the resulting menthol derivatives to see whether the modified compounds could outperform unmodified menthol at activating plant defense mechanisms. To do this, they treated soybean leaves with either menthol or one of the six menthol derivatives to see which of the derivatives, if any, could outclass menthol itself at boosting the expression levels of two defense-related soybean genes after 24 hours of exposure. The found that only one of the modified compounds bested menthol, and this compound is called valine menthyl ester, or "ment-Val" for short.

The researchers found that spraying soybean leaves once with a ment-Val solution boosted expression of the defense-related genes for three days, and a second spraying on the fourth day worked to boost the expression of those genes again. These findings suggest that ment-Val could provide sustainable pest control for farmers growing soybeans. Further experiments showed that ment-Val also increased the expression of defense-related genes in other crops, including peas, tobacco, lettuce, and corn. Ment-Val also proved to be quite stable under various conditions, which suggests that farmers would probably not lose the compound to degradation during storage.

Overall, these results suggest that ment-Val could be extremely useful as an alternative to the chemical pesticides that so many farmers rely on. Prof. Arimura notes that spraying ment-Val may be an effective way "to reduce pest damage to soybeans and other crops." He has applied for a patent on ment-Val's use as a crop protection agent, and he predicts that the commercialization of ment-Val "will generate billions of yen in economic benefits through its usage by companies operating in the fields of horticulture and agriculture." He also notes that ment-Val's anti-inflammatory properties could make it useful for human medicine.

The future is certainly going to be exciting for research into menthol derivatives like ment-Val!

CAPTION

A recent study found that a compound derived from menthol, which in turn comes from mint leaves, may help farmers reduce pest-related crop losses without having to rely on chemical pesticides

CREDIT

Travis Colbert on Unsplash

About The Tokyo University of Science

Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japan's development in science through inculcating the love for science in researchers, technicians, and educators.

With a mission of "Creating science and technology for the harmonious development of nature, human beings, and society", TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today's most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field.

Website: https://www.tus.ac.jp/en/mediarelations/

About Professor Gen-ichiro Arimura from Tokyo University of Science

Dr Gen-ichiro Arimura is a Professor in the Department of Biological Science and Technology within the Faculty of Advanced Engineering at TUS, Japan. After completing his postgraduate education at the Hiroshima University Graduate School, he worked in the field of plant biology for several years before moving to TUS in 2013. A senior and well-respected researcher, he has more than 110 publications to his credit. His key research interests include plant biotechnology, ecology, and biochemistry.

Funding information

This work was funded by the Japan Society for the Promotion of Science; the Japanese Ministry of Education, Culture, Sports, Science and Technology; the Japan Science and Technology Agency; the Fuji Foundation for Protein Research; and the Nagase Science and Technology Foundation.

A pioneering study: Plant roots act like a drill

Plant roots screw themselves into the ground - just like a drill penetrating a wall

TEL-AVIV UNIVERSITY

VIDEO: SINGLE-NUCLEI TRACKING ANALYSIS IN RESPONSE TO CELL-TYPE-SPECIFIC AUXIN INDUCTION. RED: 35S:H2B-RFP (MARKING NUCLEI). GREEN: DR5:VENUS (AUXIN RESPONSE MARKER). view more 

CREDIT: TEL AVIV UNIVERSITY

In an interdisciplinary research project carried out at Tel Aviv University, researchers from the School of Plant Sciences affiliated with the George S. Wise Faculty of Life Sciences collaborated with their colleagues from the Sackler Faculty of Medicine in order to study the course of plant root growth. The plant researchers were aided by a computational model constructed by cancer researchers studying cancer cells, which they adapted for use with plant root cells.

The fascinating and groundbreaking findings: For the first time in the world, it has been demonstrated, at the resolution of a single cell, that the root grows with a screwing motion - just like a drill penetrating a wall. In the wake of this study, the cancer researchers conjecture that cancer cells, too, are assisted by a spiral motion in order to penetrate healthy tissue in the environment of the tumor, or to create metastases in various organs of the body.

The research was led by Prof. Eilon Shani from the School of Plant Sciences and Food Security and Prof. Ilan Tsarfaty from the Department of Clinical Microbiology and Immunology at Tel Aviv University, and was conducted in collaboration with researchers from the USA, Austria and China. The article was published in March 2021 in the acclaimed journal Nature Communications.

The researchers in Prof. Shani's group, led by Dr. Yangjie Hu, used as a model the plant known as Arabidopsis. They marked the nuclei of the root cells with a fluorescent protein and observed the growing process and movement of the cells at the root tip through a powerful microscope - approximately 1000 cells in each movie. Furthermore, in order to examine what causes and controls the movement, they focused on a known hormone named auxin, which regulates growth in plants. They built a genetic system that enables activation of auxin production (like a switch) in a number of selected cells-types, and then monitored the influence of the on/off mechanism, in four dimensions - the three spatial dimensions and the dimension of time. After each instance of auxin biosynthesis, each of the thousand cells was video recorded for a period of 6 to 24 hours, thus an enormous amount of data accumulated.

CAPTION

Tracking cell-type-specific auxin-dependent root skewing. Green: DR5:VENUS (auxin response marker). Credit to Lukas Hoermayer (IST Friml lab)

CREDIT

Tel Aviv University

For the next stage, the researchers were aided by the computational tools provided by Prof. Tsarfaty, which had been developed in his laboratory for the purpose of monitoring the development of cancerous growths. They used these tools to analyze the imaging data obtained in the study. Thus they were actually able, for the first time, to observe with their own eyes the corkscrew movement of the root, as well as to precisely quantify and chart some 30 root growth parameters relating to time and space - including acceleration, length, changes in cell structure, coordination between cells during the growth process and velocity - for each one of the thousand cells at the root tip. Using fluorescent reporters, the findings even allowed them to precisely assess the movement and the influence of the auxin on the root, and the way in which it controls the growth process.

Prof. Shani: "Plants present special challenges to researchers. For example, half of the plant (the hidden half), namely, the root system, is buried beneath the ground. The computational tools that were developed for cancer research have enabled us, for the first time, to precisely measure and quantify the kinetics of growth and to reveal the mechanisms that control it at the resolution of a single cell. By this they have significantly advanced plant research, an area of utmost importance for society - both from an environmental point of view and in terms of agriculture and feeding the population."

CAPTION

Single-cell nuclei tracking of the root meristem and elongation zones.

CREDIT

Tel Aviv University

Prof. Shani adds: "In the course of our study we discovered a fascinating phenomenon that had not been previously observed 'live': we saw that the cells at the root tip move in a spiral motion, like a drill penetrating the earth. We also recognized that the hormone auxin controls the screwing process of the root tip. We learned and measured the directions of the auxin hormone's movement, passing from one cell to another in the root, in order to control the growth of the root and the corkscrew motion."

Prof. Tsarfaty adds: "This was a synergetic collaboration that benefited and enlightened both parties. In plants, processes take place much more rapidly, and therefore constitute an excellent model for us. In consequence of the findings provided by this plant study, we are presently examining the possibility of a similar screw-like motion in cancer cells and in metastases, in the course of their penetration into adjacent healthy tissues."

Cloth face coverings can be as effective as surgical masks at protecting against COVID-19

UNIVERSITY OF SURREY

Research News

 

Researchers from the Universities of Bristol and Surrey have found that well-fitting, three-layered cloth masks can be as effective at reducing the transmission of COVID-19 as surgical masks.

At the height of the COVID-19 pandemic, 139 countries mandated the use of face coverings in public space such as supermarkets and public transports. The World Health Organization also advises the use of face coverings and offers guidance on their effective features. Face coverings suppress the onward transmission of COVID-19 through exhalation and protect the wearer on inhalation.

In a paper published by the Physics of Fluids journal, the researchers detail how they looked at how liquid droplets are captured and filtered out in cloth masks by reviewing and modelling filtration processes, including inertial impaction.

Inertial impaction does not filter as a sieve or colander does - it works by forcing the air in your breath to twist and turn inside the mask so much that the droplets can't follow the path of the air. Instead, the droplets crash into fibres inside the mask to prevent inhalation.

The team found that, under ideal conditions and dependent on the fit, three-layered cloth masks can perform similarly to surgical masks for filtering droplets - with both reducing exposure by around 50 to 75 per cent. For example, if an infected person and a healthy individual are both wearing masks, scientists believe this could result in up to 94 per cent less exposure.

Dr Richard Sear, co-author of the study and Leader of the Soft Matter Group at the University of Surrey, said:

"While wearing a simple and relatively inexpensive cloth face mask cannot eliminate the risk of contracting COVID-19, measurements and our theoretical model suggests they are highly effective in reducing transmission. We hope that our work inspires mask designs to be optimised in the future and we hope it helps to remind people of the importance of continuing to wear masks while COVID-19 remains present in the community."

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Job changes following breast cancer are frequent in some cases

Study by the University of Bonn: Around ten percent of patients mention involuntary job changes

UNIVERSITY OF BONN

Research News

 

Breast cancer diagnosis: Around 88 percent of patients survive the dangerous disease in the first five years. Work is important for getting back to normality. Researchers from the University of Bonn and the German Cancer Society investigated how satisfied former patients are with their occupational development over a period of five to six years since diagnosis. About half experienced at least one job change during the study period. Around ten percent of those affected even report involuntary changes. The researchers conclude that there is a need for long-term support measures for patients. The study is now published in the Journal of Cancer Survivorship.

Breast cancer is the most commonly occurring cancer in women. Almost 70,000 cases are diagnosed every year in Germany alone. Studies show that the five-year survival rate is 88 percent. "Returning to work is important; it provides a sense of normality and meaning after a crisis caused by cancer," explains sociologist Kati Hiltrop from the Center for Health Communication and Health Services Research at University Hospital Bonn (UKB). But a breast cancer diagnosis and successful treatment are often followed by long-term difficulties such as fatigue syndrome, which means a feeling of persistent tiredness, exhaustion and listlessness. Other after-effects of chemotherapy and the fear that the cancer will return can also limit productivity.

How do breast cancer patients succeed in returning to work? "There are numerous studies on this. Our long-term study now focuses on the post-return phase from the patient's perspective," says Hiltrop. Together with the head of the research center, Prof. Dr. Nicole Ernstmann, who is also a member of the Transdisciplinary Research Area "Life and Health" at the University of Bonn, and the German Cancer Society, the sociologist investigated how a total of 184 former breast cancer patients fared after returning to work over a period of five to six years after diagnosis.

From the perspective of breast cancer patients

The study focused on how satisfied the patients were with their occupational development since diagnosis. About half experienced at least one job change during the study period. "The main finding is that we found no relationship between the number of job changes and satisfaction, but that greater involuntariness of change was associated with lower satisfaction," Hiltrop says. "The results suggest that the quality of change matters more than the quantity." About 16 percent of job changes did not happen by choice. These changes included, for example, increased workload or retirement. The results suggest that the former breast cancer patients have difficulties in meeting the job requirements in the long term after their return, resulting in changes at work.

The research team's findings show what can contribute to satisfaction at work. "Providing a welcoming work environment and showing patients understanding and support can facilitate a satisfactory return to work," Hiltrop explains. This can help avoid involuntary job changes that are perceived as particularly drastic. The researchers conclude from the results that a satisfactory return to work and, in particular, remaining at work requires long-term support, for example because chemotherapies and aftercare have to be continued, there is a fear of a recurrence of the tumor, or fatigue symptoms have to be managed.

The current study is a follow-up study of the project "Strengthening patient competence: Breast cancer patients' information and training needs" (PIAT), which surveyed approximately 1000 breast cancer patients. The researchers interviewed the PIAT participants again 5-6 years after diagnosis. At four measurement points, surveys and interviews were used to explore the subjective assessment of health status, how often job changes occurred, and how fulfilling the job was. Socioeconomic data, such as age, number of children, and education, were also surveyed. Satisfaction with occupational development was associated with higher age, better perceived health status, and lower levels of involuntariness of job changes.

"Open communication with managers and colleagues about expectations and what can be accomplished is very important," explains Hiltrop. In addition, handling the situation more flexibly, can increase the likelihood that patients will be satisfied when they return to work.

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Financial support and participating institutions

The study involved the University Hospital Bonn, the German Cancer Society, the Federal Centre for Health Education, the Institute of Medical Sociology, Health Services Research, and Rehabilitation Science at the University of Cologne, and the Carl von Ossietzky University of Oldenburg. The German Statutory Pension Insurance Scheme and the Federal Ministry of Health funded the projects.

Publication: Kati Hiltrop, Paula Heidkamp, Clara Breidenbach, Christoph Kowalski, Anna Enders, Holger Pfaff, Lena Ansmann, Franziska Geiser and Nicole Ernstmann: Involuntariness of job changes is related to less satisfaction with occupational development in long-term breast cancer survivors, Journal of Cancer Survivorship, DOI: http://dx.doi.org/10.1007/s11764-021-01035-5

Virtual reality could help improve balance in older people

UNIVERSITY OF BATH

Research News

VIDEO: RESEARCHERS AT THE UNIVERSITY OF BATH INVESTIGATING HOW VIRTUAL REALITY (VR) CAN HELP IMPROVE BALANCE BELIEVE THIS TECHNOLOGY COULD BE A VALUABLE TOOL IN THE PREVENTION OF FALLS. HTTPS://WWW.BATH.AC.UK/ANNOUNCEMENTS/VIRTUAL-REALITY-COULD-HELP-IMPROVE-BALANCE-IN-OLDER-PEOPLE/... view more 

CREDIT: UNIVERSITY OF BATH

Researchers at the University of Bath investigating how virtual reality (VR) can help improve balance believe this technology could be a valuable tool in the prevention of falls.

As people grow older, losing balance and falling becomes more common, which increases the risk of injury and affects the person's independence.

Falls are the leading cause of non-fatal injuries in over 65-yearolds and account for over 4 million bed days per year in England alone, at an estimated cost of £2 billion.

Humans use three ways of keeping their balance: vision, proprioceptive (physical feedback from muscles and joints) and vestibular system (feedback from semi-circular canals in the ear). Of these, vision is the most important.

Traditional ways of assessing balance include patient surveys and physical tests such as using a treadmill or testing agility when performing specific movements or exercises.

However, the accuracy of these tests can be affected by age, sex and motivation, and the movements measured aren't necessarily reflective of real-life scenarios.

Therefore, several research studies have explored the use of VR to help assess balance and even help train users to improve their balance.

Dr Pooya Soltani, from the University of Bath, and Renato Andrade, from Clínica do Dragão, Espregueira-Mendes Sports Centre - FIFA Medical Centre of Excellence, Porto (Portugal), reviewed data from 19 separate studies to investigate the validity, reliability, safety, feasibility and efficacy of using head-mounted display systems for assessing and training balance in older adults.

Their results, published in the scientific journal Frontiers in Sports and Active Living, found that VR was effective in assessing balance and could be useful for fall prevention and for improving postural control and gait patterns.

They found these systems also have the capacity to differentiate healthy and balance-impaired individuals.

Dr Soltani, Studio Engineer at CAMERA, the University of Bath's motion capture research centre, said: "Traditional tests for measuring balance can be inaccurate and sometimes unsafe - for example if the patient is on a treadmill that stops suddenly.

"It may also be difficult to replicate real life situations in a lab. But using VR opens up a huge range of possible scenarios that are more natural and relevant to the real world.

"For example, patients could be asked to cross a busy street and these scenes can be adapted easily to help them gradually improve their balance and build up confidence in their movement.

"Alternatively, VR could be used more like a video game where patients navigate virtually through a maze whilst doing additional cognitive tasks, like solving mathematical problems.

"VR gives us the flexibility to add disorientating effects or resize and remove elements, to test how well participants maintain their balance."

The researchers found that during VR versions of traditional balance tests, older adults generally acquired a cautious behaviour and took more time to complete the tasks. However, they tended to find them more enjoyable which could help encourage participants to stick to a rehabilitation programme.

Dr Soltani said: "Our review shows this technology has great potential, however there is a lot of work to do before it can be used widely in rehabilitation.

"We need to check parameters such as altering frame rate, find which scenarios are most effective, and also reduce the problems some users experience with motion sickness when using VR."

Whilst Covid19 has temporarily delayed plans to test the technology on volunteers, the researchers are now looking to recruit PhD students to define protocols and develop a robust system that can be tested by users later in the year.

CAPTION

Dr Soltani fits a VR headset to a volunteer

Research could enable biotechnology advances: medicine, protective equipment, sensors

U.S. ARMY RESEARCH LABORATORY

Research News

 

IMAGE: NEW ARMY-FUNDED SYNTHETIC BIOLOGIC RESEARCH MANIPULATE MICRO-COMPARTMENTS IN CELLS, POTENTIALLY ENABLING BIO-MANUFACTURING ADVANCES FOR MEDICINE, PROTECTIVE EQUIPMENT, AND ENGINEERING APPLICATIONS. view more 

CREDIT: COURTESY MONICA OLVERA DE LA CRUZ, NORTHWESTERN UNIVERSITY

RESEARCH TRIANGLE PARK, N.C. -- New Army-funded synthetic biology research manipulated micro-compartments in cells, potentially enabling bio-manufacturing advances for medicine, protective equipment and engineering applications.

Bad bacteria can survive in extremely hostile environments -- including inside the highly acidic human stomach--thanks to their ability to sequester toxins into tiny compartments.

In a new study, published in ACS Central Science, Northwestern University researchers controlled protein assembly and built these micro-compartments into different shapes and sizes, including long tubes and polyhedrons. Because this work illuminates how biological units, such as viruses and organelles, develop, it also could inform new ways to design medicine, synthetic cells and nano-reactors that are essential for nanotechnology.

"These results are an exciting step forward in our ability to design complex protein-based compartments," said Dr. Stephanie McElhinny, program manager at the U.S. Army Combat Capabilities Development Command, known as DEVCOM, Army Research Laboratory. "Being able to control the size and shape of these compartments could enable sophisticated bio-manufacturing schemes that are customized to support efficient production of complex molecules and multi-functional materials that could provide the future Army with enhanced uniforms, protective equipment and environmental sensors."

Further down the road, these insights potentially could lead to new antibiotics that target micro-compartments of pathogens while sparing good bacteria.

Researchers control protein assembly and build cell micro-compartments into different shapes and sizes that could lead to bio-inspired building blocks for various engineering applications.

"By carefully designing proteins to have specific mutations, we were able to control assembly of the proteins that form bacterial micro-compartments," said Dr. Monica Olvera de la Cruz, professor of materials science and engineering and chemistry at Northwestern who led the theoretical computation. "We used this also to predict other possible formations that have not yet been observed in nature."

Many cells use compartmentalization to ensure that various biochemical processes can occur simultaneously without interfering with one another. Made of proteins, these micro-compartments are a key to survival for a wide variety of bacterial species.

"Based on previous observations, we have known that the geometry of micro-compartments can be altered," said Dr. Danielle Tullman-Ercek, associate professor of chemical and biological engineering at Northwestern who led the experimental work. "But our work provides the first clues into how to alter them to achieve specific shapes and sizes."

To study these crucial compartments, the Northwestern team turned to Salmonella enterica, which rely on micro-compartments to break down the waste products of good bacteria in the gut. When the researchers genetically manipulated a protein isolated from Salmonella, they noticed the micro-compartments formed long tubes.

"We saw these weird, extended structures," Tullman-Ercek said. "It looked like they used the varying building blocks to form different shapes with different properties."

By coupling the mechanical properties of the compartment with the chemicals inside the compartment, Olvera de la Cruz and her team used theoretical computation to predict how different mutations led to different shapes and sizes. When six-sided proteins assembled together, they formed long tubes. When five-sided proteins assembled together, they formed soccer ball-shaped icosahedrons. The team also predicted that proteins could assemble into a triangular samosa shape, resembling the fried, South Asian snack.

Understanding this process could lead to bio-inspired building blocks for various engineering applications that require components of varying shapes and sizes.

"It's like building with Legos," Tullman-Ercek said. "It's not desirable to use the same shape block over and over again; we need different shapes. Learning from bacteria can help us build new and better structures at this microscopic scale."

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In addition to the U.S. Army, the Department of Energy, the National Science Foundation and the Sherman Fairchild Foundation supported this research.

Visit the laboratory's Media Center to discover more Army science and technology stories

DEVCOM Army Research Laboratory is an element of the U.S. Army Combat Capabilities Development Command. As the Army's corporate research laboratory, ARL is operationalizing science to achieve transformational overmatch. Through collaboration across the command's core technical competencies, DEVCOM leads in the discovery, development and delivery of the technology-based capabilities required to make Soldiers more successful at winning the nation's wars and come home safely. DEVCOM is a major subordinate command of the Army Futures Command.

CAPTION

Researchers control protein assembly and build cell microcompartments into different shapes and sizes that could lead to bio-inspired building blocks for various engineering applications

CREDIT

Monica Olvera de la Cruz, Northwestern University

Scientists create first-of-its-kind 3D organoid model of the human pancreas

New research platform will shed light on the early stages of pancreatic cancer and could open the door to life-saving screening

BETH ISRAEL DEACONESS MEDICAL CENTER

Research News

 

Boston - This year, more than 60,000 adults in the United States will be diagnosed with pancreatic cancer and, statistically, as few as 10 percent will survive five years after diagnosis, according to the American Cancer Society. Because pancreatic cancer is hidden deep within the body and often symptomless, it's frequently diagnosed after the disease has progressed too far for surgical intervention and/or has spread throughout the body. Research indicates that earlier detection of pancreatic tumors could quadruple survival rates; however, no validated and reliable tests for early detection of pancreatic cancer currently exist.

Now, researchers at the Cancer Research Institute at Beth Israel Deaconess Medical Center (BIDMC) have successfully created the first three-dimensional (3D) organoid models of the pancreas from human stem cells. Unlike previous platforms for the study of pancreatic cancer, this first-of-its-kind organoid model includes both the acinar and ductal structures that play a critical role in the majority of pancreatic cancers. The new research platform -- which is not expected to guide patient care at this time -- will shed new light on the origins and development of pancreatic cancer, as well as reveal potential means for discovering markers of early diagnosis and monitoring the disease. The team's report appears in Cell Stem Cell.

"We thought, if we had a way to use human pancreatic cells to forward engineer cancer, we could begin to understand the earliest steps in the development of this disease," said corresponding author Senthil Muthuswamy, PhD, Director of Cell Biology at the Cancer Research Institute at BIDMC. "This model could also serve as a platform to potentially discover biomarkers -- measurable changes linked to disease -- that we hope to use in the clinic to monitor cancer development."

The pancreas is a hormone-secreting organ consisting of ducts and acinar cell, structures. Researchers suspect that the most common kind of pancreatic cancer (pancreatic ductal adenocarcinoma, or PDAC) arises in the cells lining acinar and ductal structures. However, until now, scientists have not been able to successfully grow and maintain human acinar structures in the lab challenging their ability to test the hypothesis in a model.

To coerce the stem cells down the path to becoming ductal and acinar cells, Ling Huang, Instructor or Medicine at BIDMC in the Muthuswamy laboratory collaborated with Doug Melton's laboratory at Harvard University and methodically tested various combinations of cell growth media used for different lengths of time. The culmination of five-plus years' of work, presented in the study represents the first time researchers successfully generated human acinar cells in culture and maintained them long enough to be able to use them in experiments.

"It's like a cooking recipe -- a complex recipe, with no precedent," said Muthuswamy, who is also Associate Professor Medicine, Harvard Medical School. "Only when you use all the right ingredients in the right proportions and do them in the correct sequence do you get the cells becoming the acinar cells."

Next, Huang and Ridhdhi Desai, a Research Fellow at BIDMC, used the two separate lineages of ductal and acinar organoids, engineered to include gene mutations known to be associated with pancreatic cancer. When the organoids were later implanted into mice, the different lineages behaved in distinct, predictable ways. For example, one mutation caused seven out of 10 of the mice transplanted with acinar-like organoids to develop cellular changes analogous to early pancreatic cancer in humans.

"Understanding the mechanisms that regulate these events will provide important insights into the events regulating the initiation of pancreatic cancer," said Muthuswamy, who stressed that direct use of this acinar organoid technology for patients who have cancer today may be limited. "The idea is to see if we can identify biomarkers to benefit future patients -- including by screening those at high risk for pancreatic cancer, so we can catch it before it's too late."

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Co-authors also included Dipikaa Akshinthala, Christine Maria Lim, Raul Gonzalez, Lakshmi B Muthuswamy of BIDMC; Daniel N. Conrad and Zev Gartner of University of California San Francisco; Nayara Carvalho Leite of Harvard University.

This work was supported by Institutional startup funds and UO1 (CA224193); F32 fellowship (F32GM115201); seed grant from Hirschberg Foundation for Pancreatic Cancer Research; and R01 from NIGMS (R01GM135462).

The authors declare no competing interests.

About Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www.bidmc.org.

Beth Israel Deaconess Medical Center is a part of Beth Israel Lahey Health, a health care system that brings together academic medical centers and teaching hospitals, community and specialty hospitals, more than 4,000 physicians and 35,000 employees in a shared mission to expand access to great care and advance the science and practice of medicine through groundbreaking research and education.

New frontier for 3D printing developed state-of-the-art soft materials able to self-heal

Research by the MP4MNT (Materials and Processing for Micro and Nanotechnologies) team of the Politecnico di Torino published in the journal Nature Communication

POLITECNICO DI TORINO

Research News

 

The scientific community is focusing its research into the multiple applications of Hydrogels, polymeric materials which contains a large amount of water, that have the potential to reproduce the features of biological tissues. This aspect is particularly significant in the field of regenerative medicine, which since a long time has already recognised and been using the characteristics of these materials. In order to be used effectively to replace organic tissues, hydrogels must meet two essential requirements: possessing great geometric complexity and, after suffering of a damage, being able to self-heal independently, exactly like living tissues.

The development of these materials may now be easier, and cheaper, thanks to the use of 3D printing: the researchers in the MP4MNT (Materials and Processing for Micro and Nanotechnologies) team of the Department of Applied Science and Technology of the Politecnico di Torino, coordinated by Professor Fabrizio Pirri, have demonstrated, for the first time, the possibility of manufacturing hydrogels with complex architectures capable of self-healing following a laceration, thanks to 3D printing activated by light. The research was published by the prestigious journal Nature Communication in an article entitled "3D-printed self-healing hydrogels via Digital Light Processing" (DOI 10.1038/s41467-021-22802-z).

Up to now, hydrogels either with self-healing properties or modellable in complex architectures using 3D printing, had already been created in the laboratory, but in the present case, the discovered solution encompasses both features: architectural complexity and the ability to self-heal following damage. In addition, the hydrogel was created using materials available on the market, processed using a commercial printer, thus making the approach proposed extremely flexible and potentially applicable anywhere, opening new possibilities for development both in the biomedical and soft-robotics fields.

The research was carried out in the context of the HYDROPRINT3D doctoral project, funded by the Compagnia di San Paolo, in the frame of "Joint Research Projects with Top Universities" initiative, by the PhD student Matteo Caprioli, under the supervision of the DISAT researcher Ignazio Roppolo, in collaboration with Professor Magdassi's research group of the Hebrew University of Jerusalem (Israel).

"Since many years", Ignazio Roppolo recounts, "in the MP4MNT group, a research unit coordinated by Dr Annalisa Chiappone and I is specifically devoted to development of new materials that can be processed using 3D printing activated by light. 3D printing is able to offer a synergistic effect between the design of the object and the intrinsic properties of materials, making possible to obtain manufactured items with unique features. From our perspective, we need to take advantage of this synergy to best develop the capabilities of 3D printing, so that this can truly become an element of our everyday life. And this research falls right in line with this philosophy".

This research represents a first step towards the development of highly complex devices, which can exploit both the complex geometries and the intrinsic self-healing properties in various application fields. In particular, once the biocompatibility studies underway at the interdepartmental laboratory PolitoBIOMed Lab of the Politecnico have been refined, it will be possible to use these objects both for basic research into cellular mechanisms and for applications in the field of regenerative medicine.

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Processed diets might promote chronic infections that can lead to disorders such as diabetes

GEORGIA STATE UNIVERSITY

Research News

ATLANTA--Processed diets, which are low in fiber, may initially reduce the incidence of foodborne infectious diseases such as E. coli infections, but might also increase the incidence of diseases characterized by low-grade chronic infection and inflammation such as diabetes, according to researchers in the Institute for Biomedical Sciences at Georgia State University.

This study used mice to investigate how changing from a grain-based diet to a highly processed, high-fat Western style diet impacts infection with the pathogen Citrobacter rodentium, which resembles Escherichia coli (E. coli) infections in humans. The findings are published in the journal PLOS Pathogens.

Gut microbiota, the microorganisms living in the intestine, provide a number of benefits, such as protecting a host from infection by bacterial pathogens. These microorganisms are influenced by a variety of environmental factors, especially diet, and rely heavily on complex carbohydrates such as fiber.

The Western-style diet, which contains high amounts of processed foods, red meat, high-fat dairy products, high-sugar foods and pre-packaged foods, lacks fiber, which is needed to support gut microbiota. Changes in dietary habits, especially a lack of fiber, are believed to have contributed to increased prevalence of chronic inflammatory diseases such as inflammatory bowel disease, metabolic syndrome and cancer.

In this study, the researchers found switching mice from a standard grain-based rodent chow to a high-fat, low-fiber Western-style diet resulted in a rapid reduction in the number of gut bacteria. Mice fed the Western-style diet were frequently unable to clear the pathogen Citrobacter rodentium from the colon. They were also prone to developing chronic infection when re-challenged by this pathogen.

The researchers conclude the Western-style diet reduces the numbers of gut bacteria and promotes encroachment of microbiota into the intestine, potentially influencing immune system readiness and the body's defense against pathogenic bacteria.

"We observed that feeding mice a Western-style diet, rather than standard rodent grain-based chow, altered the dynamics of Citrobacter infection, reducing initial colonization and inflammation, which was surprising. However, mice consuming the Western-style diet frequently developed persistent infection that was associated with low-grade inflammation and insulin resistance," said Dr. Andrew Gewirtz, senior co-author of the study and professor in the Institute for Biomedical Sciences. "These studies demonstrate potential of altering microbiota and their metabolites by diet to impact the course and consequence of infection following exposure to a gut pathogen."

"We speculate that reshaping gut microbiota by nutrients that promote beneficial bacteria that out-compete pathogens may be a means of broadly promoting health," said Dr. Jun Zou, senior co-author of the study and assistant professor in the Institute for Biomedical Sciences at Georgia State.

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Additional co-authors of the study include Junqing An, Xu Zhao, Yanling Wang and Juan Noriega.

The study was funded by the National Institutes of Health and the American Diabetes Association.

To read the study, visit https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009497.

 

Using nanobodies to block a tick-borne bacterial infection

In cells and mice, tiny molecules stop bacteria from hijacking cells

OHIO STATE UNIVERSITY

Research News

 

COLUMBUS, Ohio - Tiny molecules called nanobodies, which can be designed to mimic antibody structures and functions, may be the key to blocking a tick-borne bacterial infection that remains out of reach of almost all antibiotics, new research suggests.

The infection is called human monocytic ehrlichiosis, and is one of the most prevalent and potentially life-threatening tick-borne diseases in the United States. The disease initially causes flu-like symptoms common to many illnesses, and in rare cases can be fatal if left untreated.

Most antibiotics can't build up in high enough concentrations to kill the infection-causing bacteria, Ehrlichia chaffeensis, because the microbes live in and multiply inside human immune cells. Commonly known bacterial pathogens like Streptococcus and E. coli do their infectious damage outside of hosts' cells.

Ohio State University researchers created nanobodies intended to target a protein that makes E. chaffeensis bacteria particularly infectious. A series of experiments in cell cultures and mice showed that one specific nanobody they created in the lab could inhibit infection by blocking three ways the protein enables the bacteria to hijack immune cells.

"If multiple mechanisms are blocked, that's better than just stopping one function, and it gives us more confidence that these nanobodies will really work," said study lead author Yasuko Rikihisa, professor of veterinary biosciences at Ohio State.

The study provided support for the feasibility of nanobody-based ehrlichiosis treatment, but much more research is needed before a treatment would be available for humans. There is a certain urgency to coming up with an alternative to the antibiotic doxycycline, the only treatment available. The broad-spectrum antibiotic is unsafe for pregnant women and children, and it can cause severe side effects.

"With only a single antibiotic available as a treatment for this infection, if antibiotic resistance were to develop in these bacteria, there is no treatment left. It's very scary," Rikihisa said.

The research is published this week in Proceedings of the National Academy of Sciences.

The bacteria that cause ehrlichiosis are part of a family called obligatory intracellular bacteria. E. chaffeensis not only requires internal access to a cell to live, but also blocks host cells' ability to program their own death with a function called apoptosis - which would kill the bacteria.

"Infected cells normally would commit suicide by apoptosis to kill the bacteria inside. But these bacteria block apoptosis and keep the cell alive so they can multiply hundreds of times very rapidly and then kill the host cell," Rikihisa said.

A longtime specialist in the Rickettsiales family of bacteria to which E. chaffeensis belongs, Rikihisa developed the precise culture conditions that enabled growing these bacteria in the lab in the 1980s, which led to her dozens of discoveries explaining how they work. Among those findings was identification of proteins that help E. chaffeensis block immune cells' programmed cell death.

The researchers synthesized one of those proteins, called Etf-1, to make a vaccine-style agent that they used to immunize a llama with the help of Jeffrey Lakritz, professor of veterinary preventive medicine at Ohio State. Camels, llamas and alpacas are known to produce single-chain antibodies that include a large antigen binding site on the tip.

The team snipped apart segments of that binding site to create a library of nanobodies with potential to function as antibodies that recognize and attach to the Etf-1 protein and stop E. chaffeensis infection.

"They function similarly to our own antibodies, but they're tiny, tiny nano-antibodies," Rikihisa said. "Because they are small, they get into nooks and crannies and recognize antigens much more effectively.

"Big antibodies cannot fit inside a cell. And we don't need to rely on nanobodies to block extracellular bacteria because they are outside and accessible to ordinary antibodies binding to them."

After screening the candidates for their effectiveness, the researchers landed on a single nanobody that attached to Etf-1 in cell cultures and inhibited three of its functions. By making the nanobodies in the fluid inside E. coli cells, Rikihisa said her lab could produce them at an industrial scale if needed - packing millions of them into a small drop.

She collaborated with co-author Dehua Pei, professor of chemistry and biochemistry at Ohio State, to combine the tiny molecules with a cell-penetrating peptide that enabled the nanobodies to be safely delivered to mouse cells.

Mice with compromised immune systems were inoculated with a highly virulent strain of E. chaffeensis and given intracellular nanobody treatments one and two days after infection. Compared to mice that received control treatments, mice that received the most effective nanobody showed significantly lower levels of bacteria two weeks after infection.

With this study providing the proof of principle that nanobodies can inhibit E. chaffeensis infection by targeting a single protein, Rikihisa said there are multiple additional targets that could provide even more protection with nanobodies delivered alone or in combination. She also said the concept is broadly applicable to other intracellular diseases.

"Cancers and neurodegenerative diseases work in our cells, so if we want to block an abnormal process or abnormal molecule, this approach may work," she said.

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This study was supported by the National Institutes of Health.

Additional co-authors, all from Ohio State, include Wenqing Zhang, Mingqun Lin, Qi Yan, Khemraj Budachetri, Libo Hou, Ashweta Sahni, Hongyan Liu and Nien-Ching Han.

Contact: Yasuko Rikihisa, Rikihisa.1@osu.edu

Written by Emily Caldwell, Caldwell.151@osu.edu