Culture

Decoded genome of little-known disease offers hope for citrus

image: Progression of citrus yellow vein disease, from left to right.

Image: 
Gerardo Uribe/UCR

Scientists are hoping the RNA of an obscure infection can one day be used like a Trojan horse to deliver life-saving treatments to citrus trees.

The infection, citrus yellow vein disease, was discovered 64 years ago in Riverside and has never been seen elsewhere in the world. Decades later, UC Riverside researchers have finally unraveled the associated pathogen's genetic codes -- a significant step toward harnessing its unique properties.

A paper describing this work was published recently in the journal Frontiers in Microbiology. It opens the door to testing whether this apparently benign infection could be used as a vehicle to transport antibacterial and antiviral agents into citrus plants' vascular systems, where infections usually take place.

Citrus crops face a highly uncertain future due to Huanglongbing, also known as citrus greening disease. In the past decade, the disease has caused a 72% decline in oranges used for juice, and a 21% decrease in the American fresh citrus fruit market. Growers in other parts of the world are similarly affected, and it continues to spread unabated.

Though there are promising treatments and disease-resistant hybrids being developed for Huanglongbing, none are yet commercially available.

Cells use RNA to convert the information stored in DNA into proteins that carry out different functions. Yellow vein disease is associated with small, independently mobile RNA, called iRNA, which spreads through a plant's vascular system. This spreading mechanism could be a new way to send treatments for Huanglongbing or other diseases into plants.

The story of this promising research starts in 1957 with Lewis Weathers, a UC Riverside plant pathology professor.

"He found four limequat trees with beautiful, bright veins on their leaves, almost fluorescent yellow," said Georgios Vidalakis, a plant pathology professor at UCR, UC-ANR cooperative extension specialist, and principal investigator on the new paper.

"That color was recognized as a disease, and samples of it were deposited at the Citrus Clonal Protection Program disease bank where it was waiting for us to study decades later," Vidalakis said.

Based on Weathers' experiments, it did not appear as though the disease is carried by any animal or other microorganism, Vidalakis said.

"We think it was introduced into the limequats in a single event, and once those plants were destroyed, it never spread to other citrus in California."

Researchers have learned, however, how the disease spread between cells in infected plants. The iRNA disguises itself with plant proteins that lets it pass through cellular connective tissue. This ability to travel inside citrus trees may allow the iRNA to send protective molecules into noncitrus plants as well, including grapes, olives, and cacao.

Yellow vein disease iRNA is also surprisingly small, even for a microscopic organism. Plant viruses typically have four to 10 genes on an average, each with at least one function. The iRNA of this disease has only one functional gene.

"The iRNA is amazing because it's able to manipulate plant cells to help it replicate, despite having only one functional gene," explained Kiran Gadhave, a UCR microbiologist, corresponding author of the paper, and lead researcher of the iRNA project. "In addition to its potential therapeutic value, it's just a scientific curiosity. This is as small as it gets."

Though they believe the pathogen to be benign, the research team is doing additional testing to make sure it won't affect fruit quality or quantity, tree height, or any other markers of health. Symptoms in greenhouse-grown trees were mild. Now this is being tested in a field trial in the living laboratory at the UCR Agricultural Experiment Station AgOps.

"The support of the Citrus Research Board and our close collaborations with the University of Maryland and Silvec Biologics are proving to be crucial in taking this technology from lab to the farm," Gadhave said.

One day, iRNA could be used alongside gene editing technologies like CRISPR, in which cells are trained to recognize and destroy nucleic acids from invading plant pathogens. There are challenges with both methods that need to be overcome first, like managing unintended effects, costs, and efficient delivery.

"The common limitations of both approaches can be overcome by matching their strengths, the same way we integrate different disease management solutions," Gadhave said.

Credit: 
University of California - Riverside

Bacteria hijack latent phage of competitor

image: As virus particles, phages infect bacteria in order to ensure their own progress.

Image: 
© Thomas Böttcher

This targeted control of phages provides entirely new biotechnological and therapeutic approaches, e.g. for phage therapies. The results produced in the context of an ERC grant have been published in the Journal of the American Chemical Society.

The human body and its microbiota harbour a large amount of phages. These infect bacteria as virus particles to ensure their own survival. One of their strategies is to integrate into the bacterial genome and multiply via bacterial cell division. However, external signal molecules can trigger the phages' sudden awakening from their dormant stage. Once activated, they destroy their host, the bacterium, and thus release their newly produced viral particles. With a prestigious ERC Consolidator Grant of the European Research Council, Thomas Böttcher investigates the switch from the sleeping (lysogenic) to the activated (lytic) lifestyle of phages.

Warfare between microbes

"We already know that phages decisively influence the population dynamics of bacteria and that microorganisms compete by using chemical weapons," says Thomas Böttcher, Professor of Microbial Biochemistry of the Faculty of Chemistry and the Centre of Microbiology and Environmental Systems Science. "We now wanted to investigate whether, in the complex microbial ecosystems, there are also microbes that specifically activate phages in order to use them against their competitors."

Indeed, the researchers could show that the bacterium Pseudomonas aeruginosa produces large amounts of a signal molecule that triggers the conversion of a phage, residing in a strain of the species Staphylococcus aureus, from a quiet companion into a deadly parasite.

Highly selective phage activation

"We were completely surprised to find that the chemical compound pyocyanin, which we were able to isolate and synthesise, only specifically activated one of several phages of Staphylococcus aureus. Pyocyanin is therefore a highly selective agent," says co-author Magdalena Jancheva.

The drug mitomycin C induces DNA damage in bacterial cells and causes phages to leave their dying host, but according to Thomas Böttcher, "it activates all phages in the bacteria in a non-selective manner". The researchers also observed that pyocyanin releases even more phages in Staphylococcus aureus than mitomycin C, pyocyanin therefore had an "remarkably strong effect".

Discovery provides new perspectives

The bacterial species Pseudomonas aeruginosa and Staphylococcus aureus occupy the same ecological niche in the human body. As pathogens, they frequently occur in the lungs of patients with cystic fibrosis, a congenital metabolic disease. Staphylococcus bacteria dominate at a young age, while Pseudomonas bacteria become more prevalent with increasing age.

The current study demonstrates the efficiency of activation of latent phages by chemical signaling agents in the battle for space and resources between bacterial strains. It provides the first evidence that chemical signaling agents can exhibit selectivity for specific phages in a polylysogenic bacterial strain. Here, the activated phage (phiMBL3) revealed a previously unknown molecular switch through which the signaling agent acts.

"Certain signaling molecules could make it possible to combat pathogens via phage activation - they could thus be used to initiate internal phage therapy," Thomas Böttcher states. At the same time, the phages' molecular switches, which selectively trigger the production of viral particles through a signaling molecule such as pyocyanin, could also serve as a new tool for biotechnology or synthetic biology. "Our findings open up a wide field in which we want to move forward", the researchers conclude.

Credit: 
University of Vienna

New method eliminates interference of nicotine in detection of methamphetamine

image: The ion mobility spectra of Methamphetamine, nicotine, and their mixture without (left) and with doped pyridine (right)

Image: 
XIA Lei

Recently, a research group led by CHU Yannan and HUANG Chaoqun from the Institute of Health & Medical Technology of the Hefei Institutes of Physical Science (HFIPS) developed an effective method for on-site detection of methamphetamine (MA) in the presence of nicotine by a homemade ion mobility spectrometry. Relevant results were published in Analytical and Bioanalytical Chemistry.

MA is a highly addictive stimulant that affects the central nervous system. The on-site rapid detection of trace amounts of MA and screening illicit drugs in clandestine laboratories are important for drug enforcement agencies and the forensic community in general. However, detecting MA in the presence of nicotine by the frequently used ion mobility spectrometry method is difficult.

In this research, the researchers optimized the temperature of the drift tube and the concentration of the pyridine. It was shown that the best temperature of the drift tube to distinguish MA from nicotine was about 100 ?, when the concentration of doped pyridine was 18 ppm.

The new instrument developed by the team proved effective. "We used pyridine as a dopant," said Prof. HUANG, who conducted this research, "the doped pyridine can eliminate the interference of nicotine, resolve the overlapping spectral peaks of MA and nicotine, and offer a high selectivity and a low limit of detection (LOD) when detecting MA from nicotine."

Further experiment proved that no matter how high the nicotine content was, the interference of nicotine could always be eliminated in the detection of MA using the new method.

These promising results provide a practical method for on-site detection of MA.

Credit: 
Hefei Institutes of Physical Science, Chinese Academy of Sciences

Improved climate resilience through better seasonal forecasts

image: Dam on the Upper Atbara river in Sudan. Precise seasonal precipitation forecasts enable optimized operation. (Photo: Harald Kunstmann/KIT)

Image: 
Harald Kunstmann/KIT

Lack of water, floods, or crop losses: As a result of climate change, pronounced periods of drought and rainfall are occurring more frequently and more intensively all around the world, causing human suffering and major economic damage. The more precise seasonal forecasts for the coming months are, the more effectively these consequences can be mitigated. A research team from Karlsruhe Institute of Technology (KIT) has now been able to improve global forecasts using statistical methods so that they can be used on the regional level. The researchers describe the new approach and the economic benefits of seasonal forecasts in the journals Earth System Science Data and Scientific Reports.

One of the consequences of global warming relates to more frequent and more intense periods of drought or precipitation which are now causing major problems worldwide - for example in the supply of food, energy, or drinking water. Improved seasonal meteorological forecasts can be very helpful here: "If we are able to predict rainfall amounts and temperatures more accurately for the weeks and months to come, local decision makers can, e.g., more proactively plan and manage reservoirs or seed selection for the planting season. In this way, they can reduce damage and losses," says Professor Harald Kunstmann who works at the Institute of Meteorology and Climate Research - Atmospheric Environmental Research (IMK-IFU), KIT Campus Alpin, in Garmisch-Partenkirchen and at the University of Augsburg. Using statistical methods, he and his team have now been able to derive local forecasts from global climate models that are significantly more precise than the seasonal forecasts available to date. The researchers developed this method within the framework of an international project called "Seasonal Water Resource Management in Arid Regions" (SaWaM for short), which was funded by the German Federal Ministry of Education and Research (BMBF) and has now been completed.

Regionalized Global Forecasts with Local Relevance

Until now, only global climate models have been available in most cases when it comes to deliver regional forecasts over an average period of weeks or months. "For high-resolution seasonal forecasts, however, these models in their basic form are actually not suitable at all," explains Dr. Christof Lorenz from the Campus Alpin of KIT, who is a co-developer of the new method. The reasons for this are, among others, inconsistencies between forecasts that use different start times and deviations from climatological reference data due to model errors. "Thanks to the statistical correction and regionalization procedures we developed, we can now derive seasonal forecasts that are many times more accurate," says Lorenz. In the regions studied, such as Sudan, Ethiopia, Iran, northeastern Brazil, Ecuador, Peru, and West Africa, the new method enabled the researchers to predict abnormal heat and drought periods up to seven months in advance - with better results than ever before.

Thanks to their extreme precision for preparing seasonal forecasts, the new methods can now be put to practical use. "In particular, by providing early warning of wet or dry periods with an above-average extent, the improved forecast allows to initiate local measures to minimize damage in due time," explains Tanja Portele, a participating climate researcher who works at the Campus Alpin of KIT and at the University of Augsburg. The scientists were able to demonstrate the economic relevance of their approach by using climate data from several decades. "We've shown that seasonal drought forecasts when used in practice can save up to 70 percent of the costs, which would have been theoretically possible with a computationally determined best practice." For the large Upper Atbara Dam in Sudan, the scientists performed an exemplary quantification of the exact savings potential for a drought year. It amounts to $ 16 million.

KIT Methods in Use Worldwide

The new methods for more accurate seasonal forecasting are particularly important for semi-arid regions where the rainy season is limited to a few months of the year. "Here, the water usually has to be stored in reservoirs," Kunstmann says. "For its use, conflicting goals might arise between agriculture, the energy sector, and drinking water supply." Therefore, weather services and official institutions from Sudan and Iran have already adopted the new statistical methods from KIT in order to be able to base their local actions on sound knowledge. Moreover, even for regions that were rarely affected in the past, seasonal forecasts with higher precision are becoming increasingly relevant due to climate change. "So the method will also be used for drought forecasts in Germany in the future," the climate researcher adds.

Credit: 
Karlsruher Institut für Technologie (KIT)

Model shows sharp decrease in HIV incidence in England

The annual number of new HIV infections among men who have sex with men (MSM) in England is likely to have fallen dramatically, from 2,770 in 2013 to 854 in 2018, showing elimination of HIV transmission by 2030 to be within reach - suggests work by researchers from the MRC Biostatistics Unit at the University of Cambridge and Public Health England (PHE), published in The Lancet HIV.

To manage the HIV epidemic among MSM in England, enhanced testing and earlier treatment strategies were scaled-up between 2011 and 2015 and supplemented from 2015 by pre-exposure prophylaxis (PrEP). The researchers examined the effect of these interventions on the number of new infections and investigated whether the United Nations (UN) targets for HIV control and elimination of HIV transmission by 2030 might be within reach among MSM in England.

A complexity in this assessment is that HIV infections are not observed. Routine surveillance collects data on new HIV diagnoses, but trends in new diagnoses alone can be misleading as they can represent infections that occurred many years previously and depend on the testing behaviour of infected individuals.

To estimate new HIV infections among adult MSM (age 15 years and above) over a 10-year period between 2009 and 2018, the researchers used a novel statistical model that used data on HIV and AIDS diagnoses routinely collected via the national HIV and AIDS Reporting System in England, and knowledge on the progression of HIV. Estimated trends in new infections were then extrapolated to understand the likelihood of achieving the UN elimination target defined as less than one newly acquired infection per 10,000 MSM per year, by 2030.

The peak in the number of new HIV infections in MSM in England is estimated to have occurred between 2012 and 2013, followed by a steep decrease from 2,770 new infections in 2013 to 1,740 in 2015, and a further steadier decrease from 2016, down to 854. The decline was consistent across all age groups but was particularly marked in MSM aged 25-34 years, and slowest in those aged 45 years or older. Importantly, this decrease began before the widespread roll-out of PrEP in 2016, indicating the success of testing and treatment as infection prevention measures among MSM in England.

Through extrapolation, the researchers calculated a 40% likelihood of England reaching the UN elimination target by 2030 and identified relevant age-specific targeting of further prevention efforts (i.e., to MSM aged ?45 years) to increase this likelihood.

Senior author, Professor Daniela De Angelis, Deputy Director of the MRC Biostatistics Unit, University of Cambridge, said:

"This is very good news and suggests that prevention measures adopted in England from 2011 have been effective. With the rollout of PrEP, England looks on course to meet the goal of zero transmissions by 2030. Our study also shows the value of regular estimation of HIV incidence to recognise and respond appropriately to changes in the current downward trend. The challenge now is to achieve these reductions in all groups at risk for HIV acquisition."

Valerie Delpech, Head of National HIV Surveillance at Public Health England, said:

"We have made good progress towards ending HIV transmission by 2030 in England. Frequent HIV testing and the use of PrEP amongst people most at risk of HIV, together with prompt treatment among those diagnosed, are key to ending HIV transmission by 2030.

"You can benefit from life-saving HIV treatments if you are diagnosed with HIV and it also means you cannot pass the virus on.

"HIV and STI tests are still available through sexual health clinics during the COVID pandemic. Many clinics offer online testing throughout the year - people can order tests on clinic websites, take them in the privacy of their own home, return by post and receive results via text, phone call or post."

Credit: 
University of Cambridge

Botany: Scent of death attracts coffin flies to pipevine flowers

image: Unlike other Aristolochia species with their showy flowers, A. microstoma has inconspicuous brownish flowers that are horizontal, partially buried or close to the ground under leaf litter or stones. The flowers emit an unpleasant, carrion-like odor to attract and trap pollinators.

Image: 
Thomas Rupp et al.

Plants use numerous mechanisms for their pollination. Now botanists have discovered a particularly sophisticated system among pipevines that is based purely on deception.

The flowers of the Greek plant Aristolochia microstoma emit a foul, musty scent that seems to mimic the smell of decaying insects. The fly pollinators from the genus Megaselia likely get attracted to this odor while searching for arthropod corpses to potentially mate over and lay their eggs. Then, when entering the tube of an Aristolochia flower, the flies are guided by downward-pointing hairs into a small chamber, which holds the female and male floral organs. Trapped inside, they deposit pollen they carry onto the stigma, before the stamens ripen and release pollen on the body of the flies. When the hairs that block the entrance to the chamber wither, the pollinators can escape, and a new cycle can begin.

"Here we show that the flowers of A. microstoma emit a highly unusual mix of volatiles that includes alkylpyrazines, which are otherwise rarely produced by flowering plants. Our data suggest that this is the only plant species known so far to deceive pollinators attracted to the smell of dead and rotting arthropods, rather than vertebrate carrion," says corresponding author Prof Stefan Dötterl, the head of the plant ecology group and the Botanical Garden at the Paris-Lodron University of Salzburg, Austria.

Between 4-6% of flowering plants are deceptive: they use odor, color, and / or tactile signals to advertise a reward to pollinators, such as nectar, pollen, or mating and breeding sites, but do not actually give this reward. The deception works because pollinators are poor at distinguishing between the reward and the mimic. Deceptive pollination is typical of many orchids, but has also independently evolved many times in other plants, including the genus Aristolochia.

"Aristolochia contains over 550 species spread around the world, especially in tropical and subtropical areas. Aristolochia species are mostly woody vines and herbaceous perennial plants with spectacular, complex flowers that temporarily imprison their visitors for pollination purposes", explains Prof Christoph Neinhuis, co-author of the study, who cultivates one of the largest Aristolochia collection worldwide at the Botanical Garden of TU Dresden.

"Many Aristolochia are known to attract flies with floral scents, for example mimicking the smell of carrion or feces of mammals, decaying plants, or fungi," says Thomas Rupp, first author of the study. "But our curiosity was piqued by A. microstoma, a small herb known only from Greece: unlike other Aristolochia with their colorful, showy flowers, A. microstoma has inconspicuous brownish flowers that lie horizontally - close to the ground or partly buried, among leaf litter or between rocks."

"A. microstoma flowers emit a simple but highly unusual mix of scents that includes 2,5-dimethylpyrazine, a molecule that does not occur in vertebrate carcasses or feces, but in dead beetles. The unpleasant, carrion-like scent can be noticed by people even at a short distance," concludes botanist Prof. Stefan Wanke from TU Dresden.

Credit: 
Technische Universität Dresden

Researchers' algorithm to make CRISPR gene editing more precise

It eventually became a Nobel prize-winning revolution when researchers first engineered CRISPR as a gene editing technology for bacterial, plant, animal and human cells. The potential of the technology is great and span from curing genetically disposed diseases to applications in agricultural and industrial biotechnology, but there are challenges.

One such challenge consists of selecting a so-called gRNA molecule which should be designed to guide the Cas9 protein to the right location in the DNA where it will make a cut in relation to the gene editing.

"Typically, there are multiple possible gRNAs and they are not all equally efficient. Therefore, the challenge is to select the few that work with high efficiency and that is precisely what our new method does," says Yonglun Luo, Associate Professor Department of Biomedicine at Aarhus University.

The new method is developed from the researchers' new data and implementation of an algorithm, which gives a prediction on what gRNAs that work most efficiently.

"By combining our own data with publicly available data and including knowledge on the molecular interactions between gRNA, DNA and the CRISPR-Cas9 protein, we have succeeded in developing a better method," says Jan Gorodkin, professor at the Department of Veterinary and Animal Sciences at the University of Copenhagen.

Data, deep learning molecular interactions

Jan Gorodkin's research group with Giulia Corsi and Christian Anthon have collaborated with Yonglun Luo's research group in order to achieve the new results. The experimental part of the study was conducted by Luo's group while Gorodkin's group spearheaded the computer modelling.

"In our study, we have quantified the efficiency of gRNA molecules for more than 10.000 different sites. The work was achieved using a massive, high throughput library-based method, which would not be possible with traditional methods," says Yonglun Luo.

The researchers took their starting point concerning data generation in the concept of having a virus express gRNA and a synthetic target site in one cell at a time. The synthetic target sites have exactly the same DNA sequences as the corresponding target sites in the genome. Thus, these synthetic target sites are used as so-call surrogate target sites to capture the CRISPR-Cas9 editing efficiency. Together with colleagues from Lars Bolund Institute of Regenerative Medicine in BGI-Research and Harvard Medical School, they generated high quality CRISPR-Cas9 activity for over 10,000 gRNAs.

With this dataset of gRNAs with known efficiencies from low to high, the researchers were able to construct a model that could predict efficiencies of gRNAs which has not been seen before.

"In order to train an algorithm to become precise, one has to have a large dataset. With our library of viruses, we have obtained data that constitutes the perfect starting point for training our deep learning algorithm to predict the efficiency of gRNAs for gene editing. Our new method is more precise than other methods currently available," says Jan Gorodkin.

Credit: 
University of Copenhagen - The Faculty of Health and Medical Sciences

New way to 3D-print custom medical devices to boost performance and bacterial resistance

image: Centre for Additive Manufacturing (CfAM).

Image: 
University of Nottingham

Using a new 3D printing process, University of Nottingham researchers have discovered how to tailor-make artificial body parts and other medical devices with built-in functionality that offers better shape and durability, while cutting the risk of bacterial infection at the same time.

Study lead, Dr Yinfeng He, from the Centre for Additive Manufacturing, said: "Most mass-produced medical devices fail to completely meet the unique and complex needs of their users. Similarly, single-material 3D printing methods have design limitations that cannot produce a bespoke device with multiple biological or mechanical functions.

"But for the first time, using a computer-aided, multi-material 3D-print technique, we demonstrate it is possible to combine complex functions within one customised healthcare device to enhance patient wellbeing."

The hope is that the innovative design process can be applied to 3D-print any medical device that needs customisable shapes and functions. For example, the method could be adapted to create a highly-bespoke one-piece prosthetic limb or joint to replace a lost finger or leg that can fit the patient perfectly to improve their comfort and the prosthetic's durability; or to print customised pills containing multiple drugs - known as polypills - optimised to release into the body in a pre-designed therapeutic sequence.

Meanwhile, the aging population is increasing in the world, leading to a higher demand for medical devices in the future. Using this technique could improve the health and wellbeing of older people and ease the financial burden on the government.

How it works

For this study, the researchers applied a computer algorithm to design and manufacture - pixel by pixel - 3D-printed objects made up of two polymer materials of differing stiffness that also prevent the build-up of bacterial biofilm. By optimising the stiffness in this way, they successfully achieved custom-shaped and -sized parts that offer the required flexibility and strength.

Current artificial finger joint replacements, for example, use both silicone and metal parts that offer the wearer a standardised level of dexterity, while still being rigid enough to implant into bone. However, as a demonstrator for the study, the team were able to 3D-print a finger joint offering these dual requirements in one device, while also being able to customise its size and strength to meet individual patient requirements.

Excitingly, with an added level of design control, the team were able to perform their new style of 3D-printing with multi-materials that are intrinsically bacteria-resistant and bio-functional, allowing them to be implanted and combat infection (which can occur during and after surgery) without the use of added antibiotic drugs.

The team also used a new high-resolution characterisation technique (3D orbitSIMS) to 3D-map the chemistry of the print structures and to test the bonding between them throughout the part. This identified that - at very small scales - the two materials were intermingling at their interfaces; a sign of good bonding which means better device is less likely to break.

The study was carried out by the Centre for Additive Manufacturing (CfAM) and funded by the Engineering and Physical Sciences Research Council. The complete findings are published in Advanced Science, in a paper entitled: 'Exploiting generative design for 3D printing of bacterial biofilm resistant composite devices'.

Prior to commercialising the technique, the researchers plan to broaden its potential uses by testing it on more advanced materials with extra functionalities such as controlling immune responses and promoting stem cell attachment.

Credit: 
University of Nottingham

RUDN University chemist proposed eco-friendly synthesis of fluorescent compounds for medicine

image: RUDN and Shahid Beheshti University(SBU) chemist proposed an eco-friendly method for the synthesis of pyrrole and pyrazole derivatives with a wide range of applications in medicine: from antidepressants to anticancer. Moreover, the synthesized compounds possess interesting fluorescence features, and the bioactive scaffolds might attract great interest in the fields of clinical diagnostics and biomedical research in the future.

Image: 
RUDN University

RUDN and Shahid Beheshti University(SBU) chemist proposed an eco-friendly method for the synthesis of pyrrole and pyrazole derivatives with a wide range of applications in medicine: from antidepressants to anticancer. Moreover, the synthesized compounds possess interesting fluorescence features, and the bioactive scaffolds might attract great interest in the fields of clinical diagnostics and biomedical research in the future. The results are published in the Organic & Biomolecular Chemistry.

Heterocyclic compounds expose remarkable chemistry with significant applications in medicinal and organic chemistry, industry, and pharmaceutical. These compounds are widely found in many natural products such as vitamins, hormones, antibiotics, alkaloids, herbicides, pigments, and dyes. Besides, a wide variety of heterocyclic rings is originated from the scaffolds of various drugs and bioactive molecules. Among them, pyrrole and pyrazole are heterocycles with a wide biological activity. They are part of drugs for the treatment of cancer, headaches and depression, relieving inflammation and a number of other diseases. Some of them demonstrate fluorescent properties, and therefore they can be used for clinical diagnosis, for example, cancer. However, the synthesis of compounds with these heterocycles remains non eco-friendly and expensive. It needs high temperatures and hazardous compounds. The RUDN and SBU chemist and his colleagues from Tehran-Iran suggested a safer and cheaper way to create pyrrole and pyrazole derivatives.

"Pyrroles and pyrazoles represent one of the most active classes of compounds, possessing a wide range of biological activities. It includes anti-inflammatory, antidepressant, antitubercular activity, they are also active against microbes, fungi and bacteria. That is not the complete list. Still, it is a powerful challenge to design an ideal synthetic protocol for this type of biologically active compound using environmentally friendly and step-economic methods and less hazardous reagents under mild reaction conditions", Dr. Ahmad Shaabani from RUDN and SBU.

The chemists have obtained compounds of pyrazole and pyrrole derivatives by the "one-pot" method, when all the stages of synthesis take place in a single reactor. Thus, scientists do not need to waste time and reagents on the isolation and purification of intermediate compounds. In total, four types of substances participate in the reaction: aminopyrazole, aldehyde, dimethyl acetylenedicarboxylate, isocyanide. They convert in a domino reaction, when all the steps occur one after the other without additional compounds. The reaction occurs at a low temperature -- 45? -- under ultrasound irradiation in the presence of p-toluenesulfonic acid as a catalyst.

By changing the combinations of the four reactants, the chemists obtained 22 compounds. It turned out that most of them have fluorescent features -- they glow blue under the ultraviolet light. The most intense fluorescence was associated with the presence of bromine derivatives in the cyclic fragments of the obtained substances.

"This eco-friendly, mild condition and atom-economical process generated two C-N and two C-C bonds and formed two five-membered heterocycles connected to each other. We believe that these new classes of fluorescent compounds may be of excellent interest in biomedical applications and clinical diagnostics in the future".

Credit: 
RUDN University

As a decade of ecosystem restoration kicks off, don't forget the people

image: Scientists warn that restoration action is at risk of failure if it doesn't address social and political considerations.

Image: 
Alliance of Bioversity International and CIAT/E.Hermanowicz

With the start of the United Nations' Decade on Ecosystem Restoration, which runs through 2030, a tremendous amount of money and effort will be put into re-growing forests, making over-exploited farmland productive, and reviving damaged marine environments. This is a good, and vital, initiative. Without quick action to clean up the fallout of humanity's scorched-earth economic systems, goals on hunger, biodiversity and climate will be unattainable.

But in examining restoration projects already underway across the globe, a group of scientists has found that restoration action is at risk of failure if it doesn't make social and political considerations at the center of efforts.

"Biophysical considerations are usually central to restoration efforts," said Marlène Elias, a CGIAR gender researcher at the Alliance of Bioversity International and CIAT. "While there's usually a peripheral nod at other issues, there generally isn't substantial engagement with the social, human and political dimensions of restoration."

The research is part of a special edition of Ecological Restoration titled "Restoration by Whom, for Whom," published in June 2021. The eleven papers include a successful kelp restoration project on Canada's West Coast, centered on the worldviews, ethics, and values of the Haida First Nation, with co-authors from the Haida First Nation. There is a study of a lake restoration project in Bangalore, India, where the lake ecosystem was "successfully" restored but the main beneficiaries were well-heeled urban residents at the exclusion of more vulnerable local communities who used to depend on the lake to fish, water their livestock, and more. Another group of authors reflect on inclusiveness in restoration based on their experience developing a mangrove restoration project with local communities.

Other research included work onfarmer-managed natural regeneration in Ghana, on-farm experiments and payments for ecosystem services in Kenya, a government-led tree planting initiative in Vietnam and the use of an adapted Restoration Opportunities Assessment Methodology in India. The remaining papers provide perspectives on multi-stakeholder engagement and restoration approaches that offer entry points for inclusive restoration.

Authors include scientists from the CGIAR's International Food Policy Research Institute, International Water Management Institute, and World Agroforestry, as well as from universities, Indigenous communities, NGOs, governments, the World Resources Institute, and other organizations from around the globe.

"Restoration projects need to be more inclusive," Elias said. "If you're looking at major goals like restoring millions of square kilometers of land, planting a trillion trees, or rehabilitating marine ecosystems, you're almost certainly not going to have success unless you put people at the center of the work."

A feminist political ecology of restoration

In the collection's introductory paper, Elias and the special issue's co-guest editors, Deepa Joshi and Ruth Meinzen-Dick, delve into "feminist political ecology" (FPE) and what this means in the context of ecological restoration. Meinzen-Dick said that one reason that social and political issues are often left out of restoration projects is because they're "messy." Top-down, one-size-fits all "solutions" tend to fail because land-rights issues, complicated relations among stakeholders, divergent worldviews and value systems, and potentially unequal distributions of benefits and costs are not addressed at the outset. While many oft-disenfranchised groups are left out of restoration plans, rural women face some of the most significant constraints in top-down restoration projects.

"Our aim is to prompt critical reflection that can open new avenues for meaningful engagement with issues of power and justice in restoration, to challenge the assumptions and discourses that (re)produce the status quo, and suggest ways forward for more political, inclusive agendas," Joshi writes.

The FPE approach focuses on three main pillars: gendered power relations, historical awareness and scale integration. The first refers to the inter-relations and inequalities on the basis of gender and other factors of social differentiation that shape rights to resources, decision-making, labor, and more that critically influence natural resource management.

Historical awareness means recognizing that current patterns of resource use and management can't be understood within considering the historical social, economic, political, and ecological contexts within which they are embedded. Scale integration refers to the fact that local resource management strategies are a function of factors (such as institutions) that go far beyond the local scale, such as international agendas, national policies, markets and commodity prices.

"We conclude that much needs to change to address the systemic fault lines that create exclusions in restoration policies and practice, and to legitimize the plural voices, values, meanings and situated knowledges of what makes the environment or nature in order to sustainably transform degraded landscapes," they write.

None of this undermines the importance of applied ecological science in restoration initiatives: the understanding of ecosystem function, interactions between diverse species ranging from fungi to trees, and the importance of biodiversity in restoration are all key to successful restoration.

"But the dominance of the natural sciences over the social sciences in the field of restoration results in a framing of restoration as a primarily technical issue, rather than as a socio-ecological issue with multiple, intricately intertwined dimensions," Elias said. "Ecological outcomes cannot be sustained without addressing social inclusion and equity. The point of restoration is not only to enhance ecosystem services, but to ensure the ecological, social, economic, cultural, and other functions that landscapes under restoration provide to improve human wellbeing."

Credit: 
The Alliance of Bioversity International and the International Center for Tropical Agriculture

Institutional environments trap disabled geoscientists between a rock and a workplace

Inaccessible workplaces, normative departmental cultures and 'ableist' academic systems have all contributed to the continued underrepresentation and exclusion of disabled researchers in the Geosciences, according to an article published today (Thursday 8 June) in Nature Geosciences.

The article argues that changes to both working spaces and attitudes are urgently needed if institutions are to attract, safeguard and retain people with disabilities.

Anya Lawrence, a disabled early career researcher in the University of Birmingham's School of Geography, Earth and Environmental Science and author of the piece says:

"Disabled geoscientists like myself face barrier after barrier on a daily basis just to get by in academia. My aim, in writing this article, was to capture some of the shared difficulties that disabled geoscientists experience, particularly struggles that may be less obvious or less apparent at a surficial level, but are significant nonetheless. For example, I think it may come as a surprise to some that traditional workplace cultures like communal coffee breaks can actually be a source of exclusion for those with disabilities. Likewise, 'feeling sorry' and showing pity for disabled colleagues could seem well-meaning but just serves to reinforce negative stereotypes towards disability."

The article makes a series of suggestions about how those with disabilities can be attracted, supported and retained in academic geosciences such as university leaders taking advice from outside agencies with experience in embedding inclusion in the workplace, along with making visible commitments to disability-hiring initiatives.

Anya adds: "I think lots of examples of best practice are already out there in other sectors. It's a case of whether people across the various different levels of the academic hierarchy from those in the highest leadership roles to the academics 'on the ground' and doing the research in Geoscience departments, are committed to creating respectful cultures and welcoming spaces for disabled scholars."

"Although I have encountered many hurdles myself, I am very fortunate in that I have an amazingly supportive supervisor and head of school and also my parents who everyday face the challenge of caring for a disabled child with nothing but great courage and selflessness. I realise that so many disabled researchers just don't have this kind of close support network and are quite isolated and alone in academia."

Another potential initiative outlined in the article is increased collaborative research involving mixed groups of disabled and non-disabled geoscientists.

"Collaborating with other geoscientists without disabilities or with different disabilities to me has been really beneficial not only at a personal level but for the research itself," says Anya. "By working with people who have different opinions, life experiences and areas of expertise from myself I have learnt so much; I have been prompted to try new methods and analytical techniques, publish my findings in outlets I hadn't even heard of and think critically about my research at every stage of the process - all of which wouldn't have been possible had I kept going it alone."

"It's also just nice to feel included and valued- working with people who appreciate my involvement and view disability as being different, not deficient, means the world to me. To this end I would like to thank the editors of Nature Geoscience, especially Dr James Super and Dr Simon Harold for being sensitive and deeply respectful in their communication and, most of all, for inviting someone with lived experience of disability to contribute to the discussion on disability in the geosciences!"

Credit: 
University of Birmingham

Cells construct living composite polymers for biomedical applications

image: 'Swarmbots,' living cells engineered to produce monomer molecules, grow until they sense their population density has reached a certain level, whereupon they burst open, allowing the monomers to mingle and self-assemble into a composite polymer.

Image: 
Zhuojun Dai

DURHAM, N.C. - Biomedical engineers at Duke University have demonstrated that a class of interwoven composite materials called semi-interpenetrating polymer networks (sIPNs) can be produced by living cells. The approach could make these versatile materials more biologically compatible for biomedical applications such as time-delayed drug delivery systems.

The research appears online on June 8 in the journal Nature Communications.

The concept of sIPNs has been around for more than 100 years and has been used in automotive parts, medical devices, molding compounds and engineering plastics. The general idea is for one or more polymers to assemble around another polymer scaffold in such a way that they become interlocked. Even though the polymers are not chemically bonded, they cannot be pulled apart and form a new material with properties greater than the simple sum of its parts.

Traditional methods for manufacturing sIPNs typically involve producing the constituent parts called monomers and mixing them together in the right chemical conditions to control their assembly into large networks in a process called polymerization.

"When it works, it's a fantastic platform that can incorporate different functionalities into the self-assembled layer for biomedical or environmental applications," said Lingchong You, professor of biomedical engineering at Duke. "But the process is often not as biocompatible as you might want. So we thought why not use living cells to synthesize the second layer to make it as biocompatible as possible?"

In the new paper, Zhuojun Dai, a former postdoc in the You lab who is now an associate professor at the Shenzhen Institute of Synthetic Biology, uses a platform that the lab has been developing for several years called "swarmbots" to do just that.

The swarmbots are living cells that are programmed to produce biological molecules within their walls and then explode once their population reaches a certain density. In this case, they're programmed to produce monomers called elastin-like polypeptides (ELPs) fused to functional features called SpyTag and SpyCatcher. These two molecular structures form a lock-and-key system, allowing the ELPs to self-assemble into a polymer chain when mixed. As they grow, these polymers entangle themselves with the polymeric microcapsules containing the cells to form sIPNs.

Each monomer can contain multiple SpyTags or SpyCatchers and can also be fused to proteins that generate a readout or have specific functions. It's sort of like making a chain-link fence out of many tiny charm bracelets that have room for clasps and charms.

The researchers first program the cells to fill this accessorizable feature with a fluorescent protein to prove that the system can lock them into place. After that successful demonstration, they turn their attention to engineering a useful drug delivery system with their new invention.

"You could replace the fluorescent marker with anything that has a function you want to feature," said You. "We decided to touch on antibiotics because it's one of the other focuses of our lab."

Beta-lactam antibiotics, such as penicillin and its derivatives, are some of the most commonly used antibiotics in the world. They're also often overused and can have negative effects such as destroying the natural microbiome that lives within our guts.

To demonstrate one way in which their new cell-built sIPNs could be useful, the researchers fill the accessorizable spot with beta-lactamase, which can degrade beta-lactam antibiotics. By injecting the newly functionalized sIPNs into mice, the researchers showed the platform could slowly release the otherwise short-lived protective molecule to help the mice's gut microbiomes ward off negative side effects from the antibiotics.

"Nobody has used living cells as a factory to produce monomers in real-time for sIPNs before," said You. "The proof-of-principle demonstration shows that, not only can we fabricate these types of functional materials with live cells, but they can exhibit medically relevant functions."

Credit: 
Duke University

Humans are ready to take advantage of benevolent AI

Humans expect that AI is Benevolent and trustworthy. A new study reveals that at the same time humans are unwilling to cooperate and compromise with machines. They even exploit them.

Picture yourself driving on a narrow road in the near future when suddenly another car emerges from a bend ahead. It is a self-driving car with no passengers inside. Will you push forth and assert your right of way, or give way to let it pass? At present, most of us behave kindly in such situations involving oth-er humans. Will we show that same kindness towards autonomous vehicles?

Using methods from behavioural game theory, an international team of researchers at LMU and the University of London have conducted large-scale online studies to see whether people would behave as cooperatively with artificial intelligence (AI) systems as they do with fellow humans.

Cooperation holds a society together. It often requires us to compromise with others and to accept the risk that they let us down. Traffic is a good example. We lose a bit of time when we let other people pass in front of us and are outraged when others fail to reciprocate our kindness. Will we do the same with machines?

Exploiting the machine without guilt

The study which is published in the journal iScience found that, upon first encounter, people have the same level of trust toward AI as for human: most expect to meet someone who is ready to cooperate.

The difference comes afterwards. People are much less ready to reciprocate with AI, and instead exploit its benevolence to their own benefit. Going back to the traffic example, a human driver would give way to another human but not to a self-driving car.

The study identifies this unwillingness to compromise with machines as a new challenge to the future of human-AI interactions.

"We put people in the shoes of someone who interacts with an artificial agent for the first time, as it could happen on the road," explains Dr. Jurgis Karpus, a behavioural game theorist and a philosopher at LMU Munich and the first author of the study. "We modelled different types of social encounters and found a consistent pattern. People expected artificial agents to be as cooperate as fellow humans. However, they did not return their benevolence as much and exploited the AI more than humans."

With perspectives from game theory, cognitive science, and philosophy, the researchers found that 'al-gorithm exploitation' is a robust phenomenon. They replicated their findings across nine experiments with nearly 2,000 human participants.

Each experiment examines different kinds of social interactions and allows the human to decide whether to compromise and cooperate or act selfishly. Expectations of the other players were also measured. In a well-known game, the Prisoner's Dilemma, people must trust that the other characters will not let them down. They embraced risk with humans and AI alike, but betrayed the trust of the AI much more often, to gain more money.

"Cooperation is sustained by a mutual bet: I trust you will be kind to me, and you trust I will be kind to you. The biggest worry in our field is that people will not trust machines. But we show that they do!" notes Prof. Bahador Bahrami, a social neuroscientist at the LMU, and one of the senior researchers in the study. "They are fine with letting the machine down, though, and that is the big difference. People even do not report much guilt when they do," he adds.

Benevolent AI can backfire

Biased and unethical AI has made many headlines--from the 2020 exams fiasco in the United Kingdom to justice systems--but this new research brings up a novel caution. The industry and legislators strive to ensure that artificial intelligence is benevolent. But benevolence may backfire.

If people think that AI is programmed to be benevolent towards them, they will be less tempted to co-operate. Some of the accidents involving self-driving cars may already show real-life examples: drivers recognize an autonomous vehicle on the road, and expect it to give way. The self-driving vehicle meanwhile expects for normal compromises between drivers to hold.

"Algorithm exploitation has further consequences down the line. If humans are reluctant to let a polite self-driving car join from a side road, should the self-driving car be less polite and more aggressive in order to be useful?" asks Jurgis Karpus.

"Benevolent and trustworthy AI is a buzzword that everyone is excited about. But fixing the AI is not the whole story. If we realize that the robot in front of us will be cooperative no matter what, we will use it to our selfish interest," says Professor Ophelia Deroy, a philosopher and senior author on the study, who also works with Norway's Peace Research Institute Oslo on the ethical implications of inte-grating autonomous robot soldiers along with human soldiers. "Compromises are the oil that make soci-ety work. For each of us, it looks only like a small act of self-interest. For society as a whole, it could have much bigger repercussions. If no one lets autonomous cars join the traffic, they will create their own traffic jams on the side, and not make transport easier".

Credit: 
Ludwig-Maximilians-Universität München

Investing in an HEPA air purifier might not be a bad idea

image: Ahmad Sedaghat, M.D., Ph.D., shown at the University of Cincinnati Gardner Neuroscience Institute.

Image: 
Colleen Kelley/University of Cincinnati

As COVID-19 restrictions ease nationwide and more people host indoor gatherings, investing in a high efficiency particulate air (HEPA) purifier might not be a bad idea, says a University of Cincinnati College of Medicine researcher.

Several published studies evaluating aerosols and submicron particles similar in size to the SARS-CoV-2 virion have shown that portable HEPA purifiers are able to significantly reduce airborne COVID-19 particles, says Ahmad Sedaghat, MD, PhD, director of the UC Division of Rhinology, Allergy and Anterior Skull Base Surgery.

Sedaghat identified the medical literature showing published studies on the effectiveness of HEPA purifiers. His review is available online in the scholarly journal of the American Academy of Otolaryngology-Head and Neck Surgery Foundation.

Air purifiers could benefit hospitals and physician offices where aerosol-generating procedures occur, but they are also useful for reducing COVID transmission anywhere that large groups of individuals congregate.

"One of the issues with COVID-19, is when physicians perform an aersol-generating medical procedure any asymptomatic COVID-19 positive patient may release SARS-CoV-2 laden aersols into the air," explains Sedaghat. "Guidance from the Centers for Disease Control indicates that we can rely on our HVAC systems to slowly decontaminate the air during an hour timeframe. Studies in the medical literature are showing us that we can use portable air purifiers to do a better and faster job of decominating these airborne particles to keep our patients and staff safe."

"Air purifiers with HEPA filters can be used as very effective means to decontaminate the air above and beyond what many HVAC systems may offer," says Sedaghat who also published studies documenting COVID-19 infection leading to reduced taste and smell in patients and possibly attacking the central nervous system.

"If people are walking around coughing or sneezing because it is allergy season and by chance they happen to be one of these asymptomatic carriers of COVID-19, there is a danger of transmission in individuals not vaccinated," says Sedaghat. "People are catching the disease from asymptomatic carriers."

"The results of this study can be applied to our daily lives outside of a physician's office," says Sedaghat. "If you want to host larger gatherings you should consider putting the air purifiers into your living room to help decontaminate anything that is released into the air. HEPA based air purifiers work the best. HEPA based air purifiers decontaminate these airborne particles much faster and more effectively than non HEPA filters."

"They aren't terribly expensive and you can buy these at any home improvement or department store to help decontaminate air borne coronavirus," says Sedaghat. "This may be more important for controlling the spread of COVID-19 for people who are still not vaccinated."

Air purifiers offer added protection but UC researchers also found that better-fitting facemasks greatly improve protection against COVID-19 as well.

Credit: 
University of Cincinnati

LSU Health New Orleans study reports compound blocks SARS-CoV-2 and protects lung cells

New Orleans, LA - Research conducted at LSU Health New Orleans Neuroscience Center of Excellence reports that Elovanoids, bioactive chemical messengers made from omega-3 very-long-chain polyunsaturated fatty acids discovered by the Bazan lab in 2017, may block the virus that causes COVID-19 from entering cells and protect the air cells (alveoli) of the lung. Their findings are published online in Scientific Reports, available here.

"Because the compounds are protective against damage in the brain and retina of the eye and the COVID-19 virus clearly damages the lung, the experiment tested if the compounds would also protect the lung," notes Nicolas Bazan, MD, PhD, Director of the LSU Health New Orleans Neuroscience Center and senior author of the paper.

The research team tested Elovanoids (ELVs) on infected lung tissue from a 78-year-old man in petri dish cultures. They found that ELVs not only reduced the ability of the SARS-CoV-2 spike protein to bind to receptors and enter cells, but they also triggered the production of protective, anti-inflammatory proteins that counteract lung damage.

The scientists report that ELVs decreased the production of ACE2. ACE2 is a protein on the surface of many cell types. ACE2 receptors act like locks on cells, and the SARS-CoV-2 spike proteins act like keys that open the locks letting the virus enter cells to multiply rapidly. They also demonstrated for the first time that alveolar cells are endowed with pathways for the biosynthesis of ELVs.

"Since SARS-CoV-2 affects nasal mucosa, the GI tract, the eye, and the nervous system, uncovering the protective potential of ELVs expands the scope of our observations beyond the lung," adds Dr. Bazan. "Our results provide a foundation for interventions to modify disease risk, progression, and protection of the lung from COVID-19 or other pathologies (including some types of pneumonia)."

Credit: 
Louisiana State University Health Sciences Center