Tech

Chemical 'nose' sniffs critical differences in DNA structures

image: Illustration of the chemical "nose" sensing a G-quadruplex structure.

Image: 
Richard Hooley/UCR

Small changes in the structure of DNA have been implicated in breast cancer and other diseases, but they've been extremely difficult to detect -- until now.

Using what they describe as a "chemical nose," UC Riverside chemists are able to "smell" when bits of DNA are folded in unusual ways. Their work designing and demonstrating this system has been published in the journal Nature Chemistry.

"If a DNA sequence is folded, it could prevent the transcription of a gene linked to that particular piece of DNA," said study author and UCR chemistry professor Wenwan Zhong. "In other words, this could have a positive effect by silencing a gene with the potential to cause cancer or promote tumors."

Conversely, DNA folding could also have a negative effect.

"DNA folds could potentially keep viral proteins from being produced to minimize immune response," Zhong said.

Studying how these folds might impact living beings, either positively or negatively, first requires scientists to detect their presence. To do that, UCR organic chemistry professor Richard Hooley and his colleagues modified a concept that has previously been used to sense other things, such as chemical components in different vintages of wine.

The chemicals in the system could be designed to look for nearly any kind of target molecule. However, the way the "nose" is typically used, it could not detect DNA. Only once Hooley's group added additional, nonstandard components could the nose sniff out its DNA target.

"Humans detect smells by inhaling air containing odor molecules that bind to multiple receptors inside the nose," Hooley explained. "Our system is comparable because we have multiple receptors able to interact with the DNA folds we're looking for."

The chemical nose is composed of three parts: host molecules, fluorescent guest molecules, and DNA, which is the target. When the desired folds are present, the guest glows, alerting scientists to their presence in a sample.

DNA is made of four nucleic acids: guanine, adenine, cytosine and thymine. Most of the time, these acids form a double helix structure resembling a ladder. Guanine-rich regions sometimes fold in a different manner, creating what's called a G-quadruplex.

Parts of the genome that form these quadruplex structures are extremely complex, though UC Riverside researchers have discovered that their folds are known to regulate gene expression, and they play a key role in keeping cells healthy.

For this experiment, the researchers wanted to demonstrate that they could detect one specific type of quadruplex composed of four guanines. Having done so, Zhong said the research team will try to build on their success.

"Now we think we can do more," she said. "There are other three-dimensional structures in DNA, and we want to understand those as well."

The researchers will examine how forces that damage DNA affect the ways they fold. They will also study RNA folding because RNA carries out important functions in a cell.

"RNA has even more complex structures than DNA, and is more difficult to analyze, but understanding its structure has great potential for disease research," Zhong said.

Credit: 
University of California - Riverside

Closing in on state-of-the-art semiconductor solar cells

A synthetic approach that improves absorber layers in perovskite solar cells could help them achieve their full potential and draw closer to the performance of leading gallium arsenide devices.

Solar cells that rely on perovskite thin films to capture sunlight are the fastest growing photovoltaic technology. Cheaper and easier to manufacture and incorporate into devices than conventional semiconductors, lead halide perovskites also effectively absorb visible light and display long charge carrier diffusion lengths -- an indicator of their ability to maintain light-induced electrons and holes separation and facilitate charge transport.

Performance of solar cells hinges on absorber materials with a high-quality crystal structure and a narrow bandgap to maximize sunlight harvesting. This optimal bandgap range spans energies of 1.1 to 1.4 eV, which corresponds to near-infrared wavelengths.

Absorber layers containing polycrystalline lead halide perovskites have provided high-efficiency solar cells. Their performance, however, has been affected by considerable structural disorder and defects. Formamidinium lead triiodide features the smallest bandgap to date, but this bandgap exceeds the optimal range for single-junction devices. One way to reduce the bandgap of perovskites involves forming lead-tin alloys in the absorber, but this introduces crystal defects and instability.

Now, a team from KAUST has developed an approach using a microns-thick absorber layer consisting of perovskite single crystals to minimize the bandgap. The crystals contain a mixture of methylammonium and formamidinium organic cations.

The researchers incorporated the mixed-cation perovskite into unconventional inverted p-i-n solar cells, in which the absorber is sandwiched between an electron transport top layer and a hole transport bottom layer. The resulting solar cells exhibited an efficiency of 22.8 percent, surpassing the best-performing devices using single-crystal methylammonium lead triiodide.

"We had known that mixed-cation single-crystal absorbers could outperform single-cation absorbers due to their lower bandgap and superior optoelectronic qualities. However, this had not been realized before because of challenges in crystal growth and device integration," says Abdullah Alsalloum, a Ph.D. student in Osman Bakr's group.

The external quantum efficiency of the mixed-cation perovskite film, which measures its effectiveness when converting incoming light into charge carriers, shifted toward near-infrared wavelengths from that of polycrystalline formamidinium lead triiodide, consistent with its smaller bandgap. "By utilizing a thicker single-crystal absorber layer, we expanded the absorption range of the film so that it's very close to the optimal range," Alsalloum says.

The team is working on enhancing device performance and stability to get even closer to the top-performing gallium arsenide solar cells. "Future studies include optimizing device interfaces and exploring more favorable device structures," Alsalloum adds.

Credit: 
King Abdullah University of Science & Technology (KAUST)

Aryl hydrocarbon receptor suppresses immunity to oral cancer through immune checkpoint regulation

A new Boston University School of Public Health (BUSPH) study has identified for the first time how the aryl hydrocarbon receptor (AhR), an environmental chemical receptor, drives immunosuppression in oral squamous cell carcinoma (OSCC)--and that its removal from malignant cells can result in tumor rejection.

Published in the journal Proceedings of the National Academy of Sciences, the study findings provide new insight into the biology of cancer immunosuppression, and identify a new target for cancer immunotherapy treatment.

Immune checkpoint inhibitors (immunotherapy drugs) are some of the most important treatments that have emerged for treating many cancers, including OSCC. Targeting immune checkpoint molecules such as PD-1, PD-L1 and CTLA4 has demonstrated that immunosuppression plays a significant role in OSCC pathology. But immune checkpoint inhibitors are only effective for about 30 percent of cancer patients, so there is a critical need for researchers to identify new immunotherapy targets.

"This study illustrates how studying the basic science of common environmental pollutants' suppression of the immune system can result in a hugely impactful new approach to cancer prevention and immunotherapy," says Dr. David Sherr, study lead author and a professor of environmental health at BUSPH. The study was conducted in his lab, the Sherr Lab, located in the Department of Environmental Health at SPH.

Dr. Zhongyan Wang, a postdoctoral fellow at SPH and a co-author of the study, used gene-editing techniques to delete a single gene that encodes the AhR, an environmental chemical receptor, from highly malignant mouse oral cancer cells.

After these minimally altered cancer cells were transplanted into normal mice, Jessica Kenison-White, first author of the study, measured tumor growth and compared the strength and nature of the immune response to the cancer cells with the ineffective immune response to the unaltered cancer cells, using digital gene-expression technologies and laser-based enumeration of immune cells. Kenison-White was a PhD student at Boston University School of Medicine (MED) and a research scientist at the Sherr Lab during the study.

The researchers found that while unaltered tumor cells overwhelmed the mice within 60 days, AhR gene deletion resulted in zero tumor growth.

This lack of growth, they found, was accompanied by a remarkably robust tumor-specific immune response characterized by a profound decrease in expression of immune checkpoint markers, which mediate immune suppression.

The researchers also discovered that the mice transplanted with AhR-negative oral cancer cells in a kind of vaccine protocol were now 100 percent immune to a challenge with unaltered, highly malignant cancer cells.

"We believe that these findings identified a potential master regulator of multiple immune checkpoints--the suppressive components of the immune system that have been individually targeted in recent years with immunotherapeutics in a way that has revolutionized cancer treatment," says Sherr.

"These results strongly suggest that targeting this master immune checkpoint regulator with specific inhibitors may ultimately prove as effective, or more effective, at enhancing anti-cancer immune responses than any single immune checkpoint inhibitor," Sherr says. "We can see how such a novel drug could be used in a cancer prevention, interception, or treatment modality."

Credit: 
Boston University School of Medicine

The micro-environment of breast cancer in three dimensions

image: Penn State researchers 3D bioprinted breast cancer tumors (green) and cultivated their supportive microenvironments (purple) to better understand how they interact with one another. Image:

Image: 
Ozbolat Lab/Penn State

Cancerous tumors thrive on blood, extending their roots deep into the fabric of the tissue of their host. They alter the genetics of surrounding cells and evolve to avoid the protective attacks of immune cells. Now, Penn State researchers have developed a way to study the relationship between solid, difficult-to-treat tumors and the microenvironment they create to support their growth.

The method has the potential to act as a testbed for drugs and other anticancer treatments, according to Ibrahim T. Ozbolat, associate professor of engineering science and mechanics and biomedical engineering, who led the research. The details of the approach were published in Advanced Biology.

Using metastatic triple-negative breast cancer cells -- the most aggressive breast cancer, for which there are few treatments -- and specialized modeling techniques, the researchers cultivated tumor microenvironments.

"We brought together the tumor and its microenvironment and studied how the embedded tumor affects its surrounding matrix," said Madhuri Dey, first author on the paper and a doctoral student in the Department of Chemistry in the Eberly College of Science. "Then we asked if we could get any meaningful genetic information from this composite system."

Typically, researchers examine the genetic information of single cells in a system to understand which signals are being sent and received to encourage specific behaviors. However, Dey said, the individual actions may not reveal every facet of a composite system.

"We looked at the genome of the entire system," Dey said. "The result was a far more representative understanding of how cells talk to each other in the native conditions."

They found that the physiological changes in tumor behavior -- such as growth or movement -- are a direct result of cellular communication in the tumor's microenvironment. Cancer cells communicate with the cells lining blood vessels, called endothelial cells, that also control the exchange of materials between blood and the extracellular environment. Cancer also communicates with the cells that secrete collagen to produce the scaffolding of tissues, called fibroblasts.

"The cancer-endothelial cell crosstalk is equally important as the cancer-fibroblast crosstalk," Dey said, noting that each process can influence the other and change how the cancer grows.

To test their approach, the researchers 3D-bioprinted tumor models called spheroids in a microenvironment to see how distance might influence tumor growth.

"We asked, 'Can proximity increase cancer aggressiveness?' and we found that there is a critical distance," Dey said. "Tumors far apart don't affect each other, but endothelial cells from neighboring tumors can nourish each other and increase how aggressively the cancer spreads."

Next, the researchers plan to use the fabrication method to investigate how immune cells engineered to target cancer cells can be improved to penetrate solid tumors and limit their spread.

"We could also use this as a personalized tool to test treatment effectiveness for individual people -- that's a future goal," Ozbolat said. "There are so many ways in which we can apply this tumor microenvironment model."

Credit: 
Penn State

Snakeskin can inspire to safer buildings

Despite human inventiveness and ingenuity, we still lag far behind the elegant and efficient solutions forged by nature over millions of years of evolution.

This also applies for buildings, where animals and plants, have developed extremely effective digging methods, for example, that are far more energy-efficient than modern tunnelling machines, and even self-repairing foundations that are unusually resistant to erosion and earthquakes (yep, we're talking about roots here).

Researchers from all over the world are therefore seeking inspiration in nature to develop the buildings of the future, and researchers from Aarhus University and University of California Davis have now in collaboration published an article in the scientific journal Acta Geotechnica about constructing foundations inspired by the scales on a snake.

"Previous studies have shown that surface geometry inspired by snakeskin can result in different shear strengths, depending on the load direction. We've taken this knowledge one step further in this research and investigated the interaction between different soil types and these snakeskin surfaces," says Assistant Professor Hans Henning Stutz from the Department of Civil and Architectural Engineering at Aarhus University.

Modern pile foundations are usually made by driving, drilling or pushing piles into the ground to achieve sufficient bearing capacity for a building.

Today, the piles are usually prefabricated with quadratic or circular cross-sections and a load-bearing capacity that is isotropic (identical in all shear directions) due to the mainly symmetrical, smooth profile of the surface.

However, in the study, the researchers experimented with asymmetric micro-structural features on the surface, resembling the scales along the underside of a snake. These so-called ventral scales are elongated in shape, relatively smooth, and have cross-section shaped like an elongated, right-angled triangle.

"By experimenting with 'scales' measuring 0.5 mm in height and 20-60 mm in length, we've achieved - in lab conditions - a significantly increased load-bearing capacity in the media we've examined: more specifically different types of sand. The results of the project show that piles with this surface pattern give 25-50 per cent less resistance during installation compared with the pressure they can subsequently support," says Hans Henning Stutz.

According to the assistant professor, there is still a lot be gained from biology when optimising structures and durable foundations, and he believes that future construction will find much more inspiration in biology.

"Evolution has come up with some quite inspiring solutions during the ages, and there's a lot to be gained in a geotechnical perspective. I'm convinced that in the future we'll see major developments in bio-inspired and very effective solutions, especially in areas such as anchoring, tunnels, and marine constructions," he says.

Credit: 
Aarhus University

Scientists at NREL report new synapse-like phototransistor

Researchers at the U.S. Department of Energy's National Renewable Energy Laboratory (NREL) developed a breakthrough in energy-efficient phototransistors. Such devices could eventually help computers process visual information more like the human brain and be used as sensors in things like self-driving vehicles.

The structures rely on a new type of semiconductor--metal-halide perovskites--which have proven to be highly efficient at converting sunlight into electrical energy and shown tremendous promise in a range of other technologies.

"In general, these perovskite semiconductors are a really unique functional system with potential benefits for a number of different technologies," said Jeffrey Blackburn, a senior scientist at NREL and co-author of a new paper outlining the research. "NREL became interested in this material system for photovoltaics, but they have many properties that could be applied to whole different areas of science."

In this case, the researchers combined perovskite nanocrystals with a network of single-walled carbon nanotubes to create a material combination they thought might have interesting properties for photovoltaics or detectors. When they shined a laser at it, they found a surprising electrical response.

"What normally would happen is that, after absorbing the light, an electrical current would briefly flow for a short period of time," said Joseph Luther, a senior scientist and co-author. "But in this case, the current continued to flow and did not stop for several minutes even when the light was switched off."

Such behavior is referred to as "persistent photoconductivity" and is a form of "optical memory," where the light energy hitting a device can be stored in "memory" as an electrical current. The phenomenon can also mimic synapses in the brain that are used to store memories. Often, however, persistent photoconductivity requires low temperatures and/or high operating voltages, and the current spike would only last for small fractions of a second. In this new discovery, the persistent photoconductivity produces an electrical current at room temperature and flows current for more than an hour after the light is switched off. In addition, only low voltages and low light intensities were found to be needed, highlighting the low energy needed to store memory.

The research is spelled out in the paper, "Low-Energy Room-Temperature Optical Switching in Mixed-Dimensionality Nanoscale Perovskite Heterojunctions," which appears in the journal Science Advances. In addition to Blackburn and Luther, the paper was co-authored by Ji Hao, Young-Hoon Kim, Severin Habisreutinger, Steven Harvey, and Elisa Miller, all from NREL, and by scientists from the University of Wisconsin-Madison and the University of Toledo.

Other scientists have been working toward optical memory and neuromorphic computing, which emulates the way the human brain stores information. The brain uses a "neural network" of neurons that interact with many other neurons across synapses. This highly interconnected network is one of the primary reasons the brain can process information in such an energy-efficient way, so there is a big motivation for scientists to create artificial neural networks that mimic the functions of the brain.

The research provides previously lacking design principles that can be incorporated into optical memory and neuromorphic computing applications. Visual perception accounts for the vast majority of input the brain collects about the world, and these artificial synapses could be integrated into image recognition systems.

"There are many applications where sensor arrays can take in images and apply training and learning algorithms for artificial intelligence and machine-learning-type applications," Blackburn said. "As an example, such systems could potentially improve energy efficiency, performance, and reliability in applications such as self-driving vehicles."

The researchers tried three different types of perovskites--formamidinium lead bromide, cesium lead iodide, and cesium lead bromide--and found each was able to produce a persistent photoconductivity.

"What we made is only one of the simplest devices you could make from combining these two systems, and we demonstrated a simplistic memory-like operation," Blackburn said. "To build a neural network requires integrating an array of these junctions into more complex architectures, where more complex memory applications and image processing applications can be emulated."

The research was supported by the Center for Hybrid Organic-Inorganic Semiconductors for Energy (CHOISE), an Energy Frontier Research Center within the U.S. Department of Energy's Office of Science.

NREL is the U.S. Department of Energy's primary national laboratory for renewable energy and energy efficiency research and development. NREL is operated for the Energy Department by the Alliance for Sustainable Energy, LLC.

Credit: 
DOE/National Renewable Energy Laboratory

Tiny plastic particles in the environment

image: To fear or not to fear? Nanoplastics, electron microscopy image, colored, 150.000x.

Image: 
Empa/ETH

Wherever scientists look, they can spot them: whether in remote mountain lakes, in Arctic sea ice, in the deep-ocean floor or in air samples, even in edible fish - thousands upon thousands of microscopic plastic particles in the micro to millimeter range. This microplastic is now even considered one of the defining features of the Anthropocene, the age of the Earth shaped by modern humans.

Microplastics are formed by weathering and physicochemical or biological degradation processes from macroscopic plastic products, such as the tons of plastic waste in the oceans. It is unlikely that these degradation processes will stop at the micrometer scale. And so there is growing concern about the potential harmful effects nanoplastics could have on various ecosystems. "Numerous media reports suggest, through their sometimes highly emotional coverage, that we are facing a huge problem here," says Empa researcher Bernd Nowack, who has long studied the material flows of synthetic micro- and nanoparticles, for example from textiles or tire abrasion, into the environment. But Nowack says at present this statement can hardly be substantiated by scientific findings: "We don't even know how much nanoplastics there is in the different ecosystems."

Huge gaps in knowledge ...

This is primarily because it is enormously difficult in terms of measurement technology to identify artificial nanoparticles made of plastic in environmental samples with thousands and thousands of (natural) particles of similar size. Appropriate analytical methods would first have to be developed, says Denise Mitrano of ETH Zurich. And then it would be a matter of understanding exactly what risk the tiny plastic particles - some of which differ considerably in their chemical composition - pose to humans and the environment, in other words: how dangerous they ultimately are. Adds Nowack, "So we can't justifiably say we have a serious problem here - but we also can't say we don't."

That's because the smaller particles become, the more likely they are to reach organs and tissues that are inaccessible to larger particles. The blood-brain barrier or placenta, for instance, prevents particles and macromolecules from passing through until they reach a certain size - or rather, smallness - thereby protecting the tissues and organs "behind" them, i.e. the brain and fetus, respectively, from potentially dangerous substances such as viruses and bacteria. "Even if we ingest microplastics, for example through our food, they probably do not enter our bloodstream or our brain, but are simply excreted again," says Peter Wick, head of Empa's Particles-Biology Interactions lab, who studies the interactions of nanoparticles with biological systems. "With nanoplastics, we can't be so sure."

... and great need for research

Because of the enormous gaps in current knowledge, research into nanoplastics must thus be intensified, conclude Mitrano, Wick and Nowack. However, this should be done as systematically and broadly as possible - and with a cool head. After all, emerging pollutants do not always turn out to be as dangerous as originally assumed. "Our society initially adopts a zero-risk attitude toward many things that are new and unknown," Wick says. And that's understandable, he adds, especially in the case of nanoplastics, because, after all, "who wants plastic in their food?"

The solution to the problem, however, is as simple (at least in theory) as it is complex. On the one hand, a large proportion of nanoplastic particles are produced by the degradation of macro- and microplastics. Less plastic in the environment, therefore, reduces the amount of nanoplastics, and here every one of us can help stop polluting the environment with plastic waste. On the other hand, nanoplastics can also be created during the use of plastic products - for example, through abrasion - without the user being able to do anything about it. Indeed, our society is hardly possible without plastic. "The various polymers simply have too many positive properties for that," says Bernd Nowack.

Credit: 
Swiss Federal Laboratories for Materials Science and Technology (EMPA)

Changes in proteins play important role in aging kidneys

Studying protein changes in the kidneys as we age, as well as the transcription of genes into proteins, helps provide a full picture of the age-related processes that take place in these organs, says a study in mice published today in eLife.

Aging causes many changes in the body and in essential organs such as the kidneys, which function less efficiently later in life. Age-related changes in the kidneys have mostly been reported by looking at the transcription of genes - the process by which a segment of DNA is copied into RNA. The current study suggests that this approach, combined with studying changes in proteins, gives us a better understanding of age-related changes in the kidney and may point to new approaches for treating age-related kidney dysfunction.

"Physiological changes in kidney function during aging are well documented, but little is known about the underlying molecular processes that drive this loss of function," explains first author Yuka Takemon, who was a research assistant at the Jackson Laboratory in Bar Harbor, Maine, US, when the study was carried out, and is now a PhD student at the Michael Smith Genome Sciences Centre, University of British Columbia, Canada. "Many previous studies of these physiological changes have looked at the transcription of genes into proteins by measuring messenger RNA (mRNA), but we wanted to see if we could gather more insights by combining this approach with studying protein levels in the kidney."

In their study, Takemon and colleagues looked at age-related changes in kidney function in about 600 genetically diverse mice. They also measured changes in mRNA and proteins in kidney samples from about one-third of the animals.

They discovered an age-related pattern of changes in both mRNA and proteins in the mice that suggests the animals have increasing numbers of immune cells and inflammation in their kidneys, as well as decreased function in their mitochondria, which produce energy for the cells.

However, not all of the changes in proteins corresponded with changes in the mRNA, suggesting that some of the protein changes occur after the transcription of genes into RNA. This could mean that older kidneys become less efficient at building new proteins, or that proteins are broken down more quickly in older kidneys. If further studies confirm this, it could mean that therapies or interventions that promote protein building or slow protein breakdown may be beneficial for treating kidney diseases associated with aging.

"Our study suggests that mRNA measurements alone provide an incomplete picture of molecular changes caused by aging in the kidney," concludes senior author Ron Korstanje, Associate Professor at the Jackson Laboratory. "Studying changes in proteins is also essential to understanding these aging-related processes, and for designing possible new approaches for treating age-related diseases."

Credit: 
eLife

Population-based study shows air pollution exposure contributes to childhood asthma

LONDON, ON - New findings from Ontario have shown that children born in Sarnia have a higher risk of developing asthma compared to neighbouring cities. A research team from Lawson Health Research Institute and Western University, using provincial data from ICES, found that higher air pollution exposure in the first year of life very likely contributed to this higher risk. Their results are published today in CMAJ Open.

Summary of study results:

-Children born in Sarnia in the 1990s and early 2000s were disproportionally at a higher risk of developing asthma in the first few years of life, compared to neighbouring cities.

-Air pollution exposure in the first year was found to be associated with the development of asthma in children.

-Overall rates of new childhood asthma diagnosis in Southwestern Ontario have been decreasing over time in parallel to decreases in air pollution levels.

"It's known that cities in Southwestern Ontario have varied levels of air pollution because of differences in industry and traffic. For example, Sarnia is home to the 'Chemical Valley' where numerous chemical plants and oil refineries are clustered," says Dr. Dhenuka Radhakrishnan, an Adjunct ICES Scientist, formerly working out of ICES Western in London, and Pediatric Respirologist at CHEO. "We wanted to see if children born in three cities - London, Windsor and Sarnia - had a different risk of developing asthma due to the differing air pollution levels in the three regions, even though the people living in these cities are otherwise comparable in many ways."

The researchers followed 114,427 children born in these cities between 1993 and 2009 for 10 years, and found that those in Sarnia were at the highest risk of developing asthma. The researchers found that by the age of 10, nearly 24 per cent of children in Sarnia were diagnosed with asthma, compared to 21 per cent in Windsor and 17 per cent in London. The differences were also present after accounting for many risk factors associated with asthma, such as sex, socioeconomic status and urban versus rural setting. The findings were most apparent in the first two years of life, but persistent beyond the age of six.

"Reassuringly, we found the asthma risk for children has reduced in more recent years as pollution levels have also decreased," adds Dr. Radhakrishnan.

Asthma is the most common chronic disease in Canadian children and has significant impact on quality of life. Asthma is the leading cause of emergency department visits and hospital admissions in this age group.

"It's important to find strategies to prevent asthma development and this study suggests that reducing air pollution exposure, including environmental causes, might reduce the number of children who suffer from asthma," explains Dr. Salimah Shariff, Associate Scientist at Lawson, Adjunct Professor at Western and Scientist at ICES Western.

There is also growing evidence that exposure during pregnancy can influence development of asthma in children. "We need to carefully examine how reducing air pollution exposures within a geographic area translates to reductions in asthma development. Understanding the amount of air pollution that a mother and infant are exposed to, and how this impacts their personal risk, could enable regions to target safer levels for their residents," adds Dr. Shariff.

Wednesday, May 5 is World Asthma Day (WAD). Recognizing symptoms of asthma early is the best a parent can do to improve the health of their child, so they can be diagnosed quickly and start appropriate treatments. If a parent notices their child has wheezing, persistent cough or difficulty with exercise, they are encouraged to bring this to the attention of a health care provider.

Credit: 
Lawson Health Research Institute

Forest fires drive expansion of savannas in the heart of the Amazon

image: Forest destroyed by fire in Middle Negro.The effects of wildfires on plant cover and soil quality

Image: 
Bernardo Monteiro Flores

Agência FAPESP – White-sand savannas are expanding in the heart of the Amazon as a result of recurring forest fires, according to a study published in the journal Ecosystems.

The study was supported by FAPESP, and conducted by Bernardo Monteiro Flores, currently a postdoctoral fellow in ecology at the Federal University of Santa Catarina (UFSC) in Brazil, and Milena Holmgren, a professor in the Department of Environmental Sciences at Wageningen University in the Netherlands.

“The edges of the Amazon Rainforest have long been considered the most vulnerable parts owing to expansion of the agricultural frontier. This degradation of the forest along the so-called ‘deforestation arc’ [a curve that hugs the southeastern edge of the forest] continues to occur and is extremely troubling. However, our study detected the appearance of savannas in the heart of the Amazon a long way away from the agricultural frontier,” Flores told Agência FAPESP.

The authors studied an area of floodplains on the middle Negro River near Barcelos, a town about 400 km upstream of Manaus, the capital of Amazonas state, where areas of white-sand savanna are expanding, although forest ecosystems still predominate. They blame the increasing frequency and severity of wildfires in the wider context of global climate change.

“We mapped 40 years of forest fires using satellite images, and collected detailed information in the field to see whether the burned forest areas were changing,” Flores said. “When we analyzed tree species richness and soil properties at different times in the past, we found that forest fires had killed practically all trees so that the clayey topsoil could be eroded by annual flooding and become increasingly sandy.”

They also found that as burnt floodplain forest naturally recovers, there is a major shift in the type of vegetation, with native herbaceous cover expanding, forest tree species disappearing, and white-sand savanna tree species becoming dominant.

Less resilient

Where do the savanna tree species come from? According to Flores, white-sand savannas are part of the Amazon ecosystem, covering about 11% of the biome. They are ancient savannas and very different from the Cerrado with its outstanding biodiversity, yet even so they are home to many endemic plant species. They are called campinas by the local population. Seen from above, the Amazon is an ocean of forest punctuated by small islands of savanna. The seeds of savanna plants are distributed by water, fish and birds, and are more likely than forest species to germinate when they reach a burnt area with degraded soil, repopulating the area concerned.

“Our research shows native savanna cover is expanding and may continue expanding in the Amazon. Not along the ‘deforestation arc’, where exotic grasses are spreading, but in remote areas throughout the basin where white-sand savannas already exist,” Flores said.

It is important to stress that in the Amazon floodplain forest is far less resilient than upland terra firma forest. It burns more easily, after which its topsoil is washed away and degrades much more rapidly. “Floodplain forest is the ‘Achilles heel’ of the Amazon,” Holmgren said. “We have field evidence that if the climate becomes drier in the Amazon and wildfires become more severe and frequent, floodplain forest will be the first to collapse.”

These two factors – a drier climate, and more severe and frequent fires – are already in play as part of the ongoing climate change crisis. The study shows that wildfires in the middle Negro area during the severe 2015-16 El Niño burned down an area seven times larger than the total area destroyed by fire in the preceding 40 years.

“The additional loss of floodplain forest could result in huge emissions of carbon stored in trees, soil and peatlands, as well as reducing supplies of resources used by local people, such as fish and forest products. The new discoveries reinforce the urgency of defending remote forest areas. For example, a fire management program should be implemented to reduce the spread of wildfires during the dry season,” Flores said.

The article “White-sand savannas expand at the core of the Amazon after forest wildfires” is at: link.springer.com/article/10.1007%2Fs10021-021-00607-x.

Journal

Ecosystems

DOI

10.1007/s10021-021-00607-x

Credit: 
Fundação de Amparo à Pesquisa do Estado de São Paulo

One step closer to efficient cannabis production

image: Micropropagation could make cultivating cannabis a much easier task.

Image: 
Jessica Lubell-Brand

As nurseries and garden centers fill up with spring landscaping plants, home gardeners owe a lot to a technique called micropropagation, which has proven beneficial to many plants - perhaps soon to include cannabis, thanks to work by UConn researchers in the College of Agriculture, Health, and Natural Resources.

Micropropagation is a technique used for growing large quantities of new plants from fewer "parent" plants, yielding clones with the same, predictable qualities. The cannabis (Cannabis sativa) industry, however, has been largely left out of this beneficial technique, because this species of plant is extremely difficult to micropropagate.

Researchers from UConn - including Associate Professor Jessica Lubell-Brand, Ph.D. student Lauren Kurtz, and Professor Mark Brand, in the Department of Plant Science and Landscape Architecture - have worked through some of the challenges of cannabis micropropagation of hemp. Their method was recently published in HortTechnology.

Currently, the commercial cannabis industry relies on other propagation techniques, such as collecting seeds or taking carefully timed cuttings from stock "mother" plants. These methods require a lot of space and maintenance, since multiple specimens of each line of stock plants must be kept in the event of disease outbreak or plant death.

"Micropropagation produces many more clones than other methods. Since it is not relying on seed, the clones are uniform, and they will perform similarly to the parent plant. Plants that come out of tissue culture also have the benefit of being disease-free, they frequently show enhanced vigor, and you can grow a lot more in less space," says Lubell-Brand.

Plants in tissue culture depend on the grower to assume the role of nature to provide the right balance of nutrients and growth hormones in the culture media, to regulate temperature and light -- everything. For some plants, micropropagation is easy to accomplish, where explants placed in the growing medium will multiply readily. For others, like cannabis, the process requires quite a bit of refining to ensure the production of a large number of healthy plants.

"Cannabis does not really want to be in tissue culture. This research is a lot of trying to figure out, What more does the plant need?" says Lubell-Brand.

Realizing the potential to help meet the needs of the rapidly growing medical cannabis industry, the researchers set out to answer this question and decipher the needs of cannabis in tissue culture. The process requires a lot of trial and error, Lubell-Brand explains.

"We start the culture using shoot tips from greenhouse-grown plants. Then we subculture those and if we suspect something is lacking, for instance, that the plant isn't getting what it needs in the media, we experiment with nutrients like calcium, magnesium, phosphorus, and nitrogen to try to increase the length of time that they grow in culture."

Lubell-Brand says one of the issues with hemp micropropagation is hyperhydricity of the shoots: when the shoots get saturated with water, they become brittle, and they don't grow well.

Lubell-Brand explains that by adjusting the media for the first six weeks in culture while also using vented vessels to increase air flow, they were able to avoid hyperhydricity.

"In addition to creating large quantities of clones of the parent plant, micropropagated plants will very likely show enhanced growth vigor compared to conventional stem propagated plants," she says.

In the medical cannabis industry, consistency and reliability in crops is highly sought after, and micropropagation could deliver both. For growers to get started with the micropropagation technique, some equipment is needed, such as an autoclave and a laminar flow bench to ensure a sterile environment. However, for operations already using tissue culture techniques, the equipment is the same, says Lubell-Brand.

Kurtz says the research has been met with some excitement: "Tissue culture is not that well worked-out for cannabis in the literature. People are aware of the complications, problems, and downfalls, so people have been pretty receptive to the paper."

Lubell-Brand says the research is continuing, with Kurtz planning further studies to refine the process, such as determining the optimal timing of rooting and the length of time shoots can remain in culture.

The cultivars the researchers are working with are cannabidol (CBD) cultivars lacking psychoactive amounts of tetrahydrocannabinol (THC), but their micropropagation technique can be applied to THC-dominant cultivars as well. One day, maybe not so far in the future, the majority of cannabis may be micropropagated using tissue culture, though Lubell-Brand says there are still improvements to be made.

"Despite all our efforts, it's still not easy to grow cannabis in tissue culture. However, now we can multiply shoots, root shoots, and transition them from the lab to the greenhouse, which is a step forward."

Credit: 
University of Connecticut

The sensitive brain at rest

You know that raw overwhelm people have been reporting after months of a pandemic, compounded by economic issues and social unrest? Does fatigue and compulsive social media scrolling strike a familiar chord?

Those brittle feelings offer us a glimpse into what regular life can be like for individuals with sensory processing sensitivity (SPS), a biological trait possessed by roughly a third of the population. In a world of constant information overload and stress, it's a characteristic that can result in a variety of behaviors, from emotional outbursts to withdrawal, overwhelm and procrastination.

"Behaviorally, we observe it as being more careful and cautious when approaching new things," said Bianca Acevedo, a researcher in UC Santa Barbara's Department of Psychological & Brain Sciences. "You might see this behavior anywhere, from fruit flies to humans." In a new situation, those with the trait are more likely to hang back and see what happens, she explained.

"Another broad way of thinking about it, that biologists have been using to understand people's individual differences in responses to different things, is that the person with high sensitivity will be more responsive, both for better and for worse," Acevedo continued. So while people with high sensitivity might get more rattled by uncomfortable situations, they might also experience higher levels of creativity, deeper bonds with others and a heightened appreciation of beauty.

The mechanism behind these depths and heights, and extra caution, lies in the way the brains of highly sensitive people process information: They do so more deeply, Acevedo said. And in a paper published in the journal Neuropsychobiology, she and her colleagues continue to home in on where in the brain this deeper processing is occurring.

"One of the novel advancements of this research was that in most of the previous brain imaging studies of sensitivity, we've tended to look at responses to stimuli," Acevedo said. "This was a study where we just examined what the brain at rest does and how being sensitive affects it."

Taking their volunteer subjects to a functional magnetic resonance imaging scanner housed in the basement of UCSB's Psychology Building, the researchers conducted an "empathy task" in which the participants were shown descriptions of happy, sad or neutral events, followed by corresponding emotional faces of their partners and of strangers. The volunteers were asked to count backward by seven from a large number "to wash away the effects of experiencing any kind of emotion," between the facial photo displays.

"Then they were asked to provide some responses to tell us how they felt when they were shown each face image," Acevedo said. After that, the participants were instructed to relax, while their brains were scanned.

"What we found was a pattern that suggested that during this rest, after doing something that was emotionally evocative, their brain showed activity that suggested depth of processing," she said, "and this depth of processing is a cardinal feature of high sensitivity."

Among the most robust signals in the participants who scored with higher levels of SPS was a greater connectivity between the precuneus and the hippocampus, a circuit that is implicated in episodic memory consolidation and spontaneous memory retrieval. The consolidation of memory is important, Acevedo said, in order to prepare an individual for future similar situations and how to respond to them.

Meanwhile, weaker connections were found between the periaqueductal gray and the amygdala, a region important for the modulation of pain and anxiety, as well as between the insula and the hippocampus, a circuit that is thought to be important for emotion processing and stress regulation. These negative connections could be the reason sensitive people report overstimulation and higher anxiety, Acevedo said. The "robust negative connectivity" of the hippocampus and insula in particular suggests "higher order, deliberative consolidation of memory," rather than the habitual, automated responses typically triggered by stressful events.

The results of this paper represent a significant advance in the growing understanding of sensory processing sensitivity, a trait that is present among an estimated 1.4 billion of the global population. The results may also have some clinical relevance for those with mood disorders, such as anxiety, said Acevedo, whose book, "The Highly Sensitive Brain," is a finalist for the 2021 Association of American Publishers Professional and Scholarly Excellence (PROSE) Award in Neuroscience. One way to help with that tension and trouble focusing, whether or not you consider yourself highly sensitive?

"Take a break," Acevedo said. "For all of us, but especially for the highly sensitive, taking a few minutes' break and not necessarily doing anything but relaxing can be beneficial. We've seen it at the behavioral level and the level of the brain."

Credit: 
University of California - Santa Barbara

Soybean cyst nematode is the most damaging soybean pathogen--and it's rapidly spreading

image: Christopher Marett (left) and Gregory Tylka (right)

Image: 
Christopher Marett and Gregory Tylka

The soybean cyst nematode (SCN) is the most damaging pathogen of soybean in the United States and Canada and it is spreading rapidly, according to information compiled by Gregory Tylka and Christopher Marett, nematologists at Iowa State University. SCN was first found in the United States in 1954 and most recent estimates show that SCN results in $1.5 billion in annual yield losses.

"The continuing spread of SCN is alarming, but not surprising," said Tylka. "Anything that moves soil can move the nematode, including wind, water, and farm machinery." In an article published in Plant Health Progress, Tylka and Marett report that SCN was found in 55 new counties in the United States and 24 new counties and rural municipalities in Canada between 2017 and 2020. Most dramatically, New York State, which saw SCN in only one county pre-2017, reported SCN in 29 new counties, and Manitoba reported SCN for the first time in 2017.

The nematode is easily overlooked as it often does not cause obvious aboveground symptoms for several years even as it begins to immediately reduce yields. "Farmers often assume that they do not have SCN because the soybeans don't look sick," said Tylka. "This is an unfortunate mistake because SCN numbers are low when the nematode is first introduced into a field, but those numbers increase steadily if left unmanaged.

Tylka urges all soybean farmers to test their fields by soil sampling before every second or third soybean crop for the presence of SCN even if the pathogen has never been found in their fields before. He also underscores the need for continued investment in basic and applied research on the biology and management of SCN by private industry, government research funding agencies, and soybean checkoff organizations.

To learn more about the alarming spread of SCN, read "Known Distribution of the Soybean Cyst Nematode, Heterodera glycines, in the United States and Canada in 2020" published in the March issue of Plant Health Progress. His research group also strives to reach soybean farmers and those who advise them through the SCN Coalition. Learn more at http://www.TheSCNCoalition.com.

Credit: 
American Phytopathological Society

Addressing the persistent controversies and questions in preterm infant nutrition

image: The Pediatric Academic Societies (PAS) Meeting connects thousands of pediatricians and other health care providers worldwide.

Image: 
PAS

A hot topic symposia session during the Pediatric Academic Societies (PAS) 2021 Virtual Meeting will address the persistent controversies and questions in preterm infant nutrition.

After six years of interdisciplinary expert discussion and critical evidence review, the 2014 vision to develop evidence-informed guidance for the nutritional care of preterm infants has come to fruition. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the Academy of Nutrition and Dietetics (AND) initiated this multiphase process involving expert physician, dietitian, and pharmacology scientists.

The first phase, Pre-B, addressed the existing evidence and research needs for clinical questions within four themes 1) nutrient specifications for preterm infants, 2) clinical and practical issues in enteral feeding of preterm infants, 3) gastrointestinal and surgical issues, and 4) current standards of infant feeding. This phase was published in 2016 by Raiten et al as "Working group reports: evaluation of the evidence to support practice guidelines for nutritional care of preterm infants--the Pre-B Project".

"The National Institutes for Health and the Academy of Nutrition and Dietetics recognized the need for evidence-based practice guidelines for very low birth weight infant nutrition," said Sarah Taylor, MD, MSCR. "They initiated the Pre-B Project to address the lack of guidelines for these infants who were born to early or 'pre' full-term birth. This work included an initial collaborative effort to identify research needs and to determine potential topics for systematic review."

The second phase of this process is a systematic review of the literature led by the AND Evidence Analysis Center and includes an international workgroup of clinical and research experts who will now share the results of this extraordinary multi-disciplinary effort.

Dr. Taylor added: "The second phase was a multidisciplinary expert panel to perform the systematic review and develop evidence-based recommendations. The expert panel focused on enteral nutrition and the systematic review led the panel to evidence-based, specific recommendations for very low birthweight infants to be fed fortified mother's milk supplemented with donor pasteurized human milk when mother's milk is not available. Additionally, the panel formed a specific recommendation for optimal protein supplementation for very low birth weight infants. From this Pre-B Project, the NIH have developed a strategic plan to support research that addresses the multitude of remaining questions for which the current evidence does not provide answers."

"The Academy of Nutrition and Dietetics provides evidence-based guidelines for nutrition throughout the lifespan, but, until the work of this expert panel, did not have guidelines for very low birth weight infants," said Dr. Taylor. "The expert panel was able to develop recommendations for mother's milk, donor human milk and protein intake. Mostly, the expert panel found that the existing literature is quite limited and far greater investigation is needed to determine the optimal composition of very low birth weight nutrition."

The session will focus on clinical questions where the existing evidence conflicts with current clinical nutrition recommendations and where the expert work group experienced more difficulty reaching a consensus. Each presentation also will describe areas where existing data is lacking and therefore research should be prioritized.

Presentations include:

The accomplishments and process of the NICHD Pre-B and the Academy of Nutrition and Dietetics Evidence Analysis Center; presenter: Sharon Groh-Wargo, PhD, RDN - MetroHealth Medical Center

Very low birthweight infant protein needs: recognizing how the evidence differs from experience; presenter: Sarah Taylor, MD, MSCR - Yale University School of Medicine

Energy and specifically fat sources for preterm infants: How is a seemingly basic question so complicated?; presenter: Camilia R. Martin, MD, MS - Harvard Medical School/Beth Israel Deaconess Medical Center

The complex relationship between milk type and very low birthweight preterm infant outcomes; presenter: Ian Griffin, MD, MA - Biomedical Research Institute of New Jersey

Does the evidence support the current clinical definitions of "extrauterine growth restriction" and "postnatal growth failure"?; presenter: Tanis Fenton, PhD, RD - University of Calgary

Dr. Taylor will chair the session, "Addressing the Persistent Controversies and Questions in Preterm Infant Nutrition: Translating the Pre-B Project Into Clinical Practice and a Research Agenda," on Tuesday, May 4 at 2 p.m. EDT. Reporters interested in an interview with the presenters should contact PAS2021@piercom.com.

The PAS Meeting connects thousands of pediatricians and other health care providers worldwide. For more information about the PAS Meeting, please visit http://www.pas-meeting.org.

Credit: 
Pediatric Academic Societies

Your stomach may be the secret to fighting obesity

Scientists believe a stomach-specific protein plays a major role in the progression of obesity, according to new research in Scientific Reports. The study co-authored by an Indiana University School of Medicine researcher, could help with development of therapeutics that would help individuals struggling with achieving and maintaining weight loss.

Researchers focused on Gastrokine-1 (GKN1) -- a protein produced exclusively and abundantly in the stomach. Previous research has suggested GKN1 is resistant to digestion, allowing it to pass into the intestine and interact with microbes in the gut.

In the Scientific Reports study, researchers show that inhibiting GKN1 produced significant differences in weight and levels of body fat in comparison to when the protein was expressed.

"While diet and exercise are critical to maintaining a healthy weight, some individuals struggle with weight loss -- even in cases of bariatric surgery, maintaining weight loss can be a challenge," said David Boone, PhD, associate professor of microbiology and immunology at IU School of Medicine, an adjunct professor in the Department of Biology at the University of Notre Dame and a co-author of the study. "These results are an example of how a better understanding of the gut microbiome and the physiological aspects of obesity -- how our bodies regulate metabolism and accumulate body fat -- could help inform new therapies."

Data from the Centers for Disease Control show adult obesity rates have increased to 42.4 percent in the United States. In addition to increasing an individual's risk of stroke, diabetes, certain cancers and other health issues, obesity can also increase the risk of severe illness due to COVID-19.

Boone and his team conducted a microbiome analysis of mouse models with and without the GKN1 protein expressed. Researchers measured food intake, caloric extraction, blood sugar, insulin and triglyceride levels. They used magnetic resonance imagining to monitor body composition. The team also calculated energy expenditure and observed inflammation levels.

Models without GKN1 weighed less and had lower levels of total body fat and higher percentages of lean mass -- despite consuming the same amount of food. When put on a high-fat diet, models without GKN1 showed a resistance to weight gain, increased body fat and hepatic inflammation, which can lead to liver disease. Researchers also found no evidence of adverse effects such as cancer, diabetes, loss of appetite, malabsorption or inflammation -- and results were consistent in male and female models.

While more research is needed to determine the efficacy of blocking GKN1 to prevent obesity, researchers said if proved as a viable solution, such therapies could reduce the burden on health care systems and help improve quality of life for patients.

Credit: 
Indiana University School of Medicine