Tech

Amsterdam, NL, June 4, 2020 - Growth factors such as glial cell line-derived neurotrophic factor (GDNF) were initially thought to be exciting new treatments for Parkinson's disease (PD), but trials have been disappointing. A panel of prominent leaders in the field convened to discuss whether there is a future for this approach and what any future PD trial involving GDNF and other GDNF family neurotrophic factors should consider. Their discussions and recommendations are published in the Journal of Parkinson's Disease.

"There is clear evidence that GDNF and related growth factors can restore the dopaminergic nigrostriatal pathway in several animal models of PD," explained lead author Roger A. Barker, PhD, Cambridge Centre for Brain Repair, Department of Clinical Neuroscience and WT-MRC Cambridge Stem Cell Institute, Cambridge, UK. "However, this has yet to translate into a clinically meaningful and robust response in patients."

Growth factors support the development, growth, and survival of cells in the body and brain. The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily PD. Their properties make them an exciting prospect for developing new treatments that could help repair the damage caused in PD.

An international group of experts met to discuss the history and current status of GDNF and related growth factor neurturin (NRTN) therapy for PD, comprehensively reviewing preclinical and clinical studies. Critical evaluation led to conclusions about what has been achieved and what has not been shown using these agents. It was generally agreed that GDNF and NRTN have worked relatively well in neurotoxic animal models of PD, but that their translation to the clinic has so far failed to show a major impact, perhaps highlighting the predictive limitations of toxin animal models being commonly used in the preclinical space in PD to look at disease modifying therapies.

"As to what any trial should look like, there is still much debate as to what primary end-point should be used and at what time point, and input from the patient community on this will be vital going forward," noted co-author Anders Bjorklund, MD, PhD, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.

The workshop participants agreed that the question of whether GDNF has a competitive future in the treatment of PD is still unclear. They offered recommendations about what future trials with GDNF should consider and how they might be designed. For example, compared to the relative complexity of the neurosurgery needed to implant an infusion delivery system and ongoing infusions used in a recent GDNF trial, they felt a viral delivery system using newer modified approaches requiring less complex surgery would be more advantageous. In addition, they indicated that early stage PD patients would most likely benefit from such treatment because this group would have the most neurons and fibers left to rescue, with evidence of fiber loss restricted to the dorsal striatum, where the therapeutic agent could be targeted.

The workshop concluded that future trials with GDNF and related agents should be considered but that much more careful attention is needed to be given to all aspects, including the type of patient enrolled; the form of growth factor given; the dose and volume of agent given; the mode of delivery and length of follow-up along with optimal assessment tools.

At a glance:

Researchers have developed a synthetic microbial system to determine location of origin for objects

DNA-barcoded spores can be sprayed onto goods such as crops, manufactured products, and detected months to years later

The barcoded spores are safe, incapable of growing in the wild, and derived from common and safe microbe strains

Approach can help determine the source of foodborne illnesses

Every year, an estimated 48 million Americans get sick from foodborne illnesses, resulting in some 128,000 hospitalizations and 3,000 deaths, according to the U.S. Centers for Disease Control and Prevention. This public health problem is compounded by billions in economic damage from product recalls, highlighting the need to rapidly and accurately determine the sources of foodborne illnesses.

With the increasing complexity of global supply chains for the myriad foods available to consumers, however, the task of tracing the exact origin of contaminated items can be difficult.

In a novel solution that can help determine the origin of agricultural products and other goods, Harvard Medical School scientists have developed a DNA-barcoded microbial system that can be used to label objects in an inexpensive, scalable and reliable manner.

Reporting in Science on June 4, the research team describes how synthetic microbial spores can be safely introduced onto objects and surfaces at a point of origin, such as a field or manufacturing plant, and be detected and identified months later.

The spores are derived from baker's yeast and a common bacterial strain used in a wide variety of applications, such as probiotic dietary supplements, and designed to be incapable of growing in the wild to prevent adverse ecological effects.

"Spores are in many ways an old-school solution and have been safely sprayed onto agricultural goods as soil inoculants or biological pesticides for decades. We just added a small DNA sequence we can amplify and detect," said study corresponding author Michael Springer, associate professor of systems biology in the Blavatnik Institute at HMS.

"We also worked hard to make sure this system is safe, using commonplace microbial strains and building in multiple levels of control," Springer added. "We hope it can be used to help solve problems that have enormous public health and economic implications."

In recent years, scientists have learned a great deal about the interactions between microbes and their environments. Studies show that microbial communities in homes, on cell phones, on human bodies and more have unique compositions, similar to fingerprints. Attempts to use microbial fingerprints to identify provenance can be time consuming and are not easily scaled, however.

The use of custom-synthesized DNA sequences as barcodes has been shown in principle to be effective for labeling food and other items. To be widely useful, DNA barcodes must be produced cheaply in large volumes, persist on objects in highly variable environments, and able to be reliably and rapidly decoded--hurdles that have thus far not been overcome because DNA is fragile.

Heavy-duty packaging

In their study, Springer and colleagues set out to determine if DNA barcodes packaged within microbial spores, which can be sprayed onto crops and identified months later, could help solve these challenges.

Many microorganisms, including bacteria, yeasts and algae, form spores in response to harsh environmental conditions. Analogous to seeds, spores allow microorganisms to remain dormant for extraordinarily long periods and survive extreme conditions such as high temperatures, drought and UV radiation.

The research team created custom-made DNA sequences that they integrated into the genomes of the spores of two microorganisms--Saccharomyces cerevisiae, also known as baker's yeast, and Bacillus subtilis, a common and widespread bacterium that has numerous commercial uses, including as a dietary probiotic, a soil inoculant and a fermenting agent in certain foods. These spores can be cheaply grown in the lab in large numbers.

The synthetic DNA sequences are short and do not code for any protein product, and are thus biologically inert. Inserted into the genome in tandem, the sequences are designed so that billions of unique barcodes can be created.

The team also ensured that DNA-barcoded spores could not multiply, grow and spread in the wild. They did so by using microbial strains that require specific nutritional supplementation and by deleting genes required for the spores to germinate and grow. Experiments involving from hundreds of millions to more than a trillion of the modified spores confirmed that they are unable to form colonies.

To read the DNA barcodes, the researchers used an inexpensive CRISPR-based tool that can detect the presence of a genetic target rapidly and with high sensitivity. The technology, called SHERLOCK, was developed at the Broad Institute of MIT and Harvard, in a collaboration led by institute members James Collins and Feng Zhang.

"Spores can survive in the wild for an extremely long time and are a great medium for us to incorporate DNA barcodes into," said study co-first author Jason Qian, a graduate student in systems biology at HMS. "Identifying the barcodes is straightforward, using a plate reader and an orange plastic filter on a cell phone camera. We don't envision any challenges for field deployability."

Real world

The team examined the efficacy of their barcoded microbial spore system through a variety of experiments.

They grew plants in the laboratory and sprayed each plant with different barcoded spores. A week after inoculation, a leaf and a soil sample from each pot were harvested. The spores were readily detected, and even when the leaves were mixed together, the team could identify which pot each leaf came from.

When sprayed onto grass outside and exposed to natural weather for several months, spores remained detectable, with minimal spread outside the inoculated region. On environments such as sand, soil, carpet and wood, the spores survived for months with no loss over time, and they were identified after disturbances such as vacuuming, sweeping and simulated wind and rain.

Spores are very likely to persist through the conditions of a real-world supply chain, according to the researchers. As a proof-of-principle, they tested dozens of store-bought produce items for the presence of spores of Bacillus thuringiensis (Bt), a bacterial species that is widely used as a pesticide. They correctly identified all Bt-positive and Bt-negative plants.

In additional experiments, the team built a 100-square-meter (~1000 square feet) indoor sandpit and found that the spread of spores was minimal after months of simulated wind, rain and physical disturbances.

They also confirmed that spores can be transferred onto objects from the environment. Spores were readily identified on the shoes of people who walked through the sandpit, even after walking for several hours on surfaces that were never exposed to the spores. However, the spores could not be detected on these surfaces, suggesting that objects retain the spores without significant spread.

This characteristic, the team noted, could allow spores to be used to determine whether an object has passed through an inoculated area. They tested this by dividing the sandpit into grids, each labeled with up to four different barcoded spores. Individuals and a remote-control car then navigated the sandpit.

They found that they could identify the specific grids that the objects passed through with minimal false positives or negatives, suggesting a possible application as a complementary tool for forensics or law enforcement.

The team also considered potential privacy implications, noting that existing technologies such as UV dyes, cell phone tracking and facial recognition are already widely used but remain controversial.

"As scientists, our charge is to solve scientific challenges, but at the same time we want to make sure that we acknowledge broader societal implications," Springer said. "We believe the barcoded spores are best suited for farming and industrial applications and would be ineffective for human surveillance." Regardless, the use and adoption of this technology should be done with a consideration of ethics and privacy concerns, the study authors said.

The researchers are now exploring ways to improve the system, including engineering potential kill-switch mechanisms into the spores, finding ways to limit propagation and examining if the spores can be used to provide temporal information about location history.

"Outbreaks of harmful foodborne pathogens such as listeria, salmonella and E. coli occur naturally and frequently," Springer said. "Simple, safe synthetic biology tools and knowledge of basic biology allow us to create things that have a lot of potential in solving real world safety issues."

The explosion of mobile electronic devices, electric vehicles, drones and other technologies have driven demand for new lightweight materials that can provide the power to operate them. Researchers from the University of Houston and Texas A&M University have reported a structural supercapacitor electrode made from reduced graphene oxide and aramid nanofiber that is stronger and more versatile than conventional carbon-based electrodes.

The UH research team also demonstrated that modeling based on the material nanoarchitecture can provide a more accurate understanding of ion diffusion and related properties in the composite electrodes than the traditional modeling method, which is known as the porous media model.

"We are proposing that these models based on the nanoarchitecture of the material are more comprehensive, detailed, informative and accurate compared to the porous media model," said Haleh Ardebili, Bill D. Cook Associate Professor of Mechanical Engineering at UH and corresponding author for a paper describing the work, published in ACS Nano.

More accurate modeling methods will help researchers find new and more effective nanoarchitectured materials that can provide longer battery life and higher energy at a lighter weight, she said.

The researchers knew the material tested - reduced graphene oxide and aramid nanofiber, or rGO/ANF - was a good candidate because of its strong electrochemical and mechanical properties. Supercapacitor electrodes are usually made of porous carbon-based materials, which provide efficient electrode performance, Ardebili said.

While the reduced graphene oxide is primarily made of carbon, the aramid nanofiber offers a mechanical strength that increases the electrode's versatility for a variety of applications, including for the military. The work was funded by the U.S. Air Force Office of Scientific Research.

In addition to Ardebili, co-authors include first author Sarah Aderyani and Ali Masoudi, both of UH; and Smit A. Shah, Micah J. Green and Jodie L. Lutkenhaus, all from A&M.

The current paper reflects the researchers' interest in improving modeling for new energy materials. "We wanted to convey that the conventional models out there, which are porous media-based models, may not be accurate enough for designing these new nanoarchitectured materials and investigating these materials for electrodes or other energy storage devices," Ardebili said.

That's because the porous media model generally assumes uniform pore sizes within the material, rather than measuring the varying dimensions and geometric properties of the material.

"What we propose is that yes, the porous media model may be convenient, but it is not necessarily accurate," Ardebili said. "For state-of-the-art devices, we need more accurate models to better understand and design new electrode materials."

ORLANDO, June 4, 2020 - Taking inspiration from nature's nanotech that creates the stunning color of butterfly wings, a University of Central Florida researcher is creating technology to make extremely low-power, ultra-high-definition displays and screens that are easier on the eyes.

The new technology creates digital displays that are lit by surrounding light and are more natural looking than current display technologies that rely on energy-intensive bright lights hidden behind screens. The findings were published Wednesday in the journal Proceedings of the National Academy of Sciences.

"This display is more of a natural look than your current computer or smartphone screens," said Debashis Chanda, an associate professor in UCF's NanoScience Technology Center and principal investigator of the research. "It is like seeing a portrait on the wall at your house. It doesn't have that glare or extra light. It is more like looking at the natural world."

Instead of using bright LED lights located behind a screen to illuminate a display, Chanda's display is lit by reflecting light from the environment. The researcher compared the new viewing experience to switching from eating processed foods to eating natural ones.

"It'll be a step up for people to get used to it," he said. "But this is a way to create displays that are harmonious with how nature displays color and as a result look more natural and don't pump out a huge quantity of light into your eyes."

This is important because staring at brightly lit computer and smartphone displays for prolonged periods of time can cause eye strain, headaches and other health problems.

This new displaying mechanism uses a technique used by many animals, such as butterflies, octopuses, parrots, macaws and beetles, to display color by scattering and reflecting light that hits nanoscale structures on their bodies.

This type of light production is different than pigment colors or dyes, like those used in clothes or paints, that selectively absorb some colors of light and reflect others.

"If we see butterflies, octopuses or many beautiful birds, their color actually originates from nanoscale structures on their feathers, skin or scales," Chanda said. "The protein molecule, the base element, they don't have their own color but when you put them together in an orderly, controlled fashion, it creates all kinds of color. What the butterfly does is simply scatter light back in a way that it creates all this beautiful color without absorbing anything."

The technology, known as plasmonic color displays, can show different colors based on the size, shape and patterns of reflective metallic nanostructures inside the screens. The technology, however, has been limited by problems with displaying the correct color at different angles, fabricating it over large areas and displaying black.

Building upon his previous research, Chanda's group has overcome these challenges by finding a way to make the nanostructures into precise designs to fully control angle-independent scattering of light, resulting in colors that don't depend on viewing angle.

"We discovered a technique where nanoparticles could self-assemble a quasi-random pattern on a pre-designed substrate and then we could optimize that in a very controlled process to create a certain color, like yellow, blue, gold, magenta, white and more, just by changing nanoparticle size, unlike pigment-based colors where different absorbing molecules are needed for different colors," Chanda said.

The self-assembly process used in the study is similar to how the human body controls growth. In the body, enzymes and hormones released at certain times regulate growth. In Chanda's study deposition rate, pressure and temperature control the design and growth of nanostructures, which provides control of the color of light displayed.

"With the mechanism we developed, we can use physical parameters to map back to a particular pattern and subsequently a color," Chanda said.

"However, black color needed a different approach. The scattered light from the nanostructured surface is blocked using a liquid crystal layer in a controlled manner resulting in the first demonstration of black/grey colors in structural color displays," Chanda said.

With the field still emerging, the researcher said it could be a while before displays and consumer products using plasmonic nanostructures are available to the public, but the results of the study are a significant step in that direction.

One of the ways NASA observes tropical cyclones is by using infrared data that provides temperature information and indicates storm strength. The AIRS instrument aboard NASA's Aqua satellite gathered that data and revealed Cristobal has the potential to generate heavy rainfall. That rainfall is now soaking Mexico and portions of Central America as Cristobal meanders.

At 9:35 a.m. EDT on Wednesday, June 3, Tropical Storm Cristobal made landfall in the Mexican state over Campeche, just to the west of Ciudad del Carmen. At the time of landfall, maximum winds were estimated to be 60 mph (95 kph) with higher gusts. Since landfall, Cristobal weakened to a depression, and moved very slowly in a southeasterly direction into northwestern Guatemala. As the storm weakened, it expanded, now heavy rainfall is expected in Mexico, Guatemala, El Salvador, Belize and Honduras.

Damaging and deadly flooding has already been occurring in portions of Mexico and Central America. Cristobal is expected to produce additional extreme rainfall amounts through the end of the week.

Colder Cloud Top Temperatures Indicate Strength

Cloud top temperatures provide information to forecasters about where the strongest storms are located within a tropical cyclone. Tropical cyclones do not always have uniform strength, and some sides are stronger than others. The stronger the storms, the higher they extend into the troposphere, and the colder the cloud temperatures.

NASA provides this infrared data to forecasters at NOAA's National Hurricane Center (NHC) so they can incorporate in their forecasting. That data is reflected in the NHC forecasts of rainfall amounts.

On June 3 at 3:11 p.m. EDT (1911 UTC) NASA's Aqua satellite analyzed Tropical Storm Cristobal using the Atmospheric Infrared Sounder or AIRS instrument. AIRS found coldest cloud top temperatures as cold as or colder than minus 63 degrees Fahrenheit (minus 53 degrees Celsius) south and east of center, over Mexico's Yucatan Peninsula.  NASA research has shown that cloud top temperatures that cold indicate strong storms that have the capability to create heavy rain.

A Look at Extreme Rainfall Potential

NHC forecasters using infrared and other satellite data noted that Cristobal is expected to produce high rain accumulations through Saturday, June 6. NHC noted,"The Mexican states of Campeche, Quintana Roo, Tabasco, and Yucatan are expected to receive an additional 6 to 12 inches, with isolated storm totals of 25 inches.

Mexican states of Veracruz and Oaxaca can expect an additional 5 to 10 inches, while southern Guatemala and parts of Chiapas can expect an additional 15 to 20 inches, and isolated storm total amounts of 35 inches dating back to Saturday, May 30. El Salvador can also expect an additional 10 to 15 inches, with isolated storm total amounts of 35 inches dating back to Saturday, May 30. In Belize and Honduras, an additional 3 to 6 inches with isolated amounts to 10 inches are forecast.

Rainfall in all of these areas may produce life-threatening flash floods and mudslides."

Cristobal on June 4, 2020

NOAA's National Hurricane Center updated Cristobal's status on June 4 at 11 a.m. EDT (1500 UTC) and noted that since it made landfall on June 3, it had weakened to a depression. The center of Tropical Depression Cristobal was located near latitude 17.6 degrees north and longitude 91.0 degrees west. That places the center of Cristobal about 160 miles (260 km) south-southwest of Campeche, Mexico.

The depression is moving toward the east-southeast near 3 mph (6 kph). The estimated minimum central pressure is 998 millibars. Maximum sustained winds have decreased to near 35 mph (55 kph) with higher gusts. Little change in strength is expected through tonight [June 4].  Re-intensification is expected to begin on Friday.

Cristobal's Forecast Path

Forecasters at the NHC said that Cristobal is expected to turn back into the Gulf of Mexico after moving over extreme northwestern Guatemala and eastern Mexico today and tonight. The center is forecast to move back over the southern Gulf of Mexico [June 5] Friday day or Friday night, over the central Gulf of Mexico on Saturday, and approach the northern Gulf of Mexico coast [June 7] Sunday day and Sunday night.

When it fires, a neuron consumes significantly more energy than an equivalent computer operation. And yet, a network of coupled neurons can continuously learn, sense and perform complex tasks at energy levels that are currently unattainable for even state-of-the-art processors.

What does a neuron do to save energy that a contemporary computer processing unit doesn't?

Computer modelling by researchers at Washington University in St. Louis' McKelvey School of Engineering may provide an answer. Using simulated silicon "neurons," they found that energy constraints on a system, coupled with the intrinsic property neurons have to move to the lowest-energy configuration, leads to a dynamic, at-a-distance communication protocol that is both more robust and more energy-efficient than traditional computer processors.

The research, from the lab of Shantanu Chakrabartty, the Clifford W. Murphy Professor in the Preston M. Green Department of Systems & Electrical Engineering, was published last month in the journal Frontiers in Neuroscience.

It's a case of doing more with less.

Ahana Gangopadhyay, a doctoral student in Chakrabartty's lab and a lead author on the paper, has been investigating computer models to study the energy constraints on silicon neurons -- artificially created neurons, connected by wires, that show the same dynamics and behavior as the neurons in our brains.

Like biological neurons, their silicon counterparts also depend on specific electrical conditions to fire, or spike. These spikes are the basis of neuronal communication, zipping back and forth, carrying information from neuron to neuron.

The researchers first looked at the energy constraints on a single neuron. Then a pair. Then, they added more. "We found there's a way to couple them where you can use some of these energy constraints, themselves, to create a virtual communication channel," Chakrabartty said.

A group of neurons operates under a common energy constraint. So, when a single neuron spikes, it necessarily affects the available energy -- not just for the neurons it's directly connected to, but for all others operating under the same energy constraint.

Spiking neurons thus create perturbations in the system, allowing each neuron to "know" which others are spiking, which are responding, and so on. It's as if the neurons were all embedded in a rubber sheet; a single ripple, caused by a spike, would affect them all. And like all physical processes, systems of silicon neurons tend to self-optimize to their least-energetic states while also being affected by the other neurons in the network.

These constraints come together to form a kind of secondary communication network, where additional information can be communicated through the dynamic but synchronized topology of spikes. It's like the rubber sheet vibrating in a synchronized rhythm in response to multiple spikes.

This topology carries with it information that is communicated, not just to the neurons that are physically connected, but to all neurons under the same energy constraint, including ones that are not physically connected.

Under the pressure of these constraints, Chakrabartty said, "They learn to form a network on the fly."

This makes for much more efficient communication than traditional computer processors, which lose most of their energy in the process of linear communication, where neuron A must first send a signal through B in order to communicate with C.

Using these silicon neurons for computer processors gives the best efficiency-to-processing speed tradeoff, Chakrabartty said. It will allow hardware designers to create systems to take advantage of this secondary network, computing not just linearly, but with the ability to perform additional computing on this secondary network of spikes.

The immediate next steps, however, are to create a simulator that can emulate billions of neurons. Then researchers will begin the process of building a physical chip.

Scientists from Nanyang Technological University, Singapore (NTU Singapore), and an international research team have predicted that by 2050, mangroves will not be able to survive rising sea-levels if global carbon emissions are not reduced.

Using sedimentary archives from when the Earth underwent deglaciation up to 10,000 years ago, the researchers estimated the probability of mangrove survival under rates of sea-level rise corresponding to two climate scenarios - low and high carbon emissions.

When rates of sea-level rise exceeded 6 mm per year, corresponding to what is estimated to result under high emissions scenarios for 2050, the researchers found that mangroves very likely (more than 90% probability) stopped growing at the pace required.

In contrast, mangroves can survive by building themselves up vertically when the sea-level rise remains under 5 mm per year, which corresponds to that projected under low emissions scenarios during the 21st century.

The threshold of a 6 mm sea level rise is one that will be "easily surpassed" on tropical coastlines if society does not make concerted efforts to cut carbon emissions, said lead investigator of the study, Professor Neil Saintilan from the Department of Earth and Environmental Sciences at Macquarie University.

Prof Saintilan said, "We know that sea-level rise is inevitable due to climate change, but not much is known about how different rates of sea-level rise affect the growth of mangroves, which is an important ecosystem for the health of the earth."

The team comprising scientists from NTU Singapore, Macquarie University, University of Hong Kong, Rutgers University, and University of Wollongong published their findings on 5 June 2020 in the top academic journal Science.

Co-author Professor Benjamin Horton, who is Chair of the Asian School of the Environment at NTU Singapore said, "In 30 years, if we continue on a high-emissions trajectory, essentially all mangroves, including those in Singapore, will face a high risk of loss."

"This research therefore highlights yet another compelling reason why countries must take urgent action to reduce carbon emissions. Mangroves are amongst the most valuable of natural ecosystems, supporting coastal fisheries and biodiversity, while protecting shorelines from wave and storm attack across the tropics," Prof Horton added.

Why mangroves matter

With roots that rise from under the mud, mangrove stands grow in a process called vertical accretion. This feature is important to their ecosystem as it helps to soak up greenhouse gas emissions (carbon sequestration) at densities far greater than other forests, and provides a buffer between the land and sea - helping protect people from flooding on land.

The study, which covered 78 locations, explored how mangroves responded as the rate of sea-level rise slowed from over 10 mm per year 10,000 years ago to nearly stable conditions 4,000 years later. The drawdown of carbon as mangrove forests expanded over this time contributed to lower greenhouse gas concentrations.

The study found that mangroves will naturally encroach inland if their ability to vertically accrete is hindered. In doing so, mangroves will have to compete with other land-uses and may become squeezed behind coastal protections.

Co-author Assistant Professor Nicole Khan, who is from The University of Hong Kong said, "Most of what we know about the response of mangroves to rising sea level comes from observations over the past several years to decades when rates of rise are slower than projected for later this century. This research offers new insights because we looked deeper into the past when rates of sea-level rise were rapid, reaching those projected under high emissions scenarios.

"Our results underscore the importance of reducing emissions and adopting coastal management and adaptation measures that allow mangroves to naturally expand into low-lying coastal areas to protect these valuable ecosystems."

Sometimes, breaking rules is not a bad thing. Especially when the rules are apparent laws of nature that apply in bulk material, but other forces appear in the nanoscale.

"Nature knows how to go from the small, atomic scale to larger scales," said Melik Demirel, professor of engineering science and mechanics and holder of the Lloyd and Dorothy Foehr Huck Chair in Biomimetic Materials. "Engineers have used mixing rules to enhance properties, but have been limited to a single scale. We've never gone down to the next level of hierarchical engineering. The key challenge is that there are apparent forces at different scales from molecules to bulk."

Composites, by definition, are composed of more than one component. Mixture rules say that, while the ratios of one component to another can vary, there is a limit on the physical properties of the composite. According to Demirel, his team has broken that limit, at least on the nanoscale.

"If you have a conducting polymer composite the amounts of polymer and metal compound are limited by the rule of mixtures," said Demirel. "The rules govern everything about the matrix and filler. We took materials -- a biopolymer and an atomically thin conducting material -- let them organize by self assembly, and broke the rule of mixtures."

The team's materials are composed of a biomimetic polymer based on tandem repeat proteins produced by gene duplication and inspired by the structure of squid ring teeth proteins, and conducting titanium carbide 2D MXene, an only a few-molecules-thick layer of metal. This layered composite self-assembles and the polymer mediates the distance between the metal layers. By using genetic engineering of tandem repeat proteins -- a biopolymer that repeats a conserved sequence -- the researchers can control the inter-layer distance of conducting layers without changing the composite fractions. The researchers' goal is to create self-assembling materials with unprecedented control over their physical properties using synthetic biology.

Because the polymer self-assembles into a cross-linked network, the matrix-to-filler ratios in tiny areas can break the mixture rules, and the electrical properties of the layered material changes. The researchers report the results of their work in a recent issue of ACS Nano.

This biomimetic polymer metal composite can be both flexible and conductive in the proper bulk mixtures. On the microscopic scale, when the structural symmetry is broken, electrical conductivity depends on direction.

"What is unique is that now you can get in-plane electrical conductivity that differs from out-of-plane conductivity," said Demirel.

As long as the current is going along the plane of the 2D material layers, the conductivity is linear, but if the current is directed across the layers, the conductivity becomes nonlinear.

"Now we can make a storage device," said Demirel. "We could also make diodes, switches, regulators and other electronic devices. We want to make materials that are designed with desired properties for building novel functionalities, which are difficult to achieve or previously unattainable."

By analyzing 442 samples from three groups of children and adults with acute myeloid leukemia (AML), researchers have identified new immune classes of the disease that predict the likelihood of drug resistance and positive responses to immunotherapy. Their compendium of immune profiles in AML could enable clinicians to develop targeted and personalized immunotherapy regimens for patients, who must frequently cope with resistance to standard chemotherapies. AML can be difficult to treat because the malignancy has a diverse molecular and immune landscape, and not all patients respond to the same types of interventions. Immunotherapies have been studied as potential treatments for patients who have developed chemotherapy resistance, but clinicians lack the tools to predict which types of patients might respond best to immune modulation. To tackle this information gap, Jayakumar Vadakekolathu and colleagues studied 442 bone marrow samples from three groups of patients with AML (370 total patients). The authors first discovered that most of the samples could be classified into one of two immune subtypes: immune-infiltrated or immune-depleted. By comparing their observations with established disease categories from the European Leukemia-Net research network, the scientists could then predict which patients had the best survival rates and the strongest responses to treatment. One key finding was that patients who showed higher expression of genes associated with the immune molecule IFN-γ were more likely to respond to the experimental immunotherapy flotetuzumab; interestingly, IFN-γ activity also predicted the likelihood of resistance to chemotherapy agents. Vadakekolathu et al. conclude that T cell-targeting therapies should be further evaluated as a new treatment approach for patients with IFN-γ-dominant AML.

A team including researchers from the Department of Chemistry at the University of Tokyo has successfully captured video of single molecules in motion at 1,600 frames per second. This is 100 times faster than previous experiments of this nature. They accomplished this by combining a powerful electron microscope with a highly sensitive camera and advanced image processing. This method could aid many areas of nanoscale research.

When it comes to film and video, the number of images captured or displayed every second is known as the frames per second or fps. If video is captured at high fps but displayed at lower fps, the effect is a smooth slowing down of motion which allows you to perceive otherwise inaccessible details. For reference, films shown at cinemas have usually been displayed at 24 frames per second for well over 100 years. In the last decade or so, special microscopes and cameras have allowed researchers to capture atomic-scale events at about 16 fps. But a new technique has increased this to a staggering 1,600 fps.

"Previously, we successfully captured atomic-scale events in real time," said Project Professor Eiichi Nakamura. "Our transmission electron microscope (TEM) gives incredible spatial resolution, but to see details of small-scale physical and chemical events well, you need high temporal resolution too. This is why we pursued an image capture technique that is much faster than earlier experiments, so we can slow down playback of the events and see them in a whole new way."

Nakamura and his team used a TEM as it has the power to resolve objects smaller than 1 angstrom or one ten-billionth of a meter. They attached an imaging device called a direct electron detection (DED) camera. This camera is highly sensitive and is capable of high frame rates. However, even with this powerful microscope and sensitive camera, there is one enormous hurdle to overcome in order to obtain usable images: Noise.

"To capture high fps, you need an imaging sensor with high sensitivity, and greater sensitivity brings with it a high degree of visual noise. This is an unavoidable fact of electronic engineering," said Project Associate Professor Koji Harano. "To compensate for this noise and achieve greater clarity, we used an image-processing technique called Chambolle total variation denoising. You may not realize, but you have probably seen this algorithm in action as it is widely used to improve image quality of web videos."

The researchers tested their setup by imaging vibrating carbon nanotubes which housed fullerene (C60) molecules resembling faceted soccer balls made from carbon atoms. The imaging setup captured some mechanical behavior never seen before on the nanoscale. Like a pebble in a shaken maraca, the oscillating motion of the C60 molecule is coupled with the oscillation of the carbon nanotube container. This is only visible at high frame rates.

"We were pleasantly surprised that this denoising and image processing revealed the unseen motion of fullerene molecules," said Harano. "However, we still have a serious problem in that the processing takes place after the video is captured. This means the visual feedback from the experiment under the microscope is not yet real-time, but with high-performance computation this might be possible before too long. This could prove to be a very useful tool to those who explore the microscopic world."

Durham, NC - In the search for a cure for Alzheimer's disease, mesenchymal stem cells and their derived extracellular vesicles (MSC-EVs) offer much promise, thanks to their protective and anti-inflammatory properties. The results from a new study done on mice, released today in STEM CELLS Translational Medicine, strengthens this idea by showing for the first time that MSC-EVs delivered by way of the nasal passages reduce inflammation - believed to be a prime factor in Alzheimer's disease. They also trigger actions that guard the brain's neurons against further degenerative effects.

The study, led by Silvia Coco, Ph.D., at the University of Milano-Bicocca in Italy, lays the foundation for future studies that might point the way to a cure for this devastating disease.

Alzheimer's is an irreversible degeneration of the brain that causes disruptions in memory, cognition, personality and other functions that eventually lead to death. Worldwide, 50 million people are believed to be living with Alzheimer's or other dementias, according to a 2018 report by Alzheimer's Disease International, with the cost of care estimated at over US $1 trillion.

While abnormal protein buildups in the brain called amyloid plaques are thought to play a central role in Alzheimer's disease, mounting evidence suggests that inflammation is key to its development, too. This raises the need to target the brain's immune cells as a way to slow down the disease's progression.

MSC-EVs' beneficial effects in regulating inflammation seen in Alzheimer's have already been reported in some different studies on mice. This is due to the ability of MSCs to modulate the body's immune system, which in turn is believed to result from the release of EVs. These nanosized, membrane-bound vesicles transport cargo -- including DNA, RNA, and proteins -- between cells as a form of intercellular communication. They also are thought to rid the cell of damaging substances.

In the earlier studies, MSC-EVs were administered either intravenously or directly into the fluid within the chambers of the brain (cerebral ventricles) over an extended period of weeks or months. That is where this latest study differs. Administration of the MSC-EVs was done through the nasal passages, with dosing occurring over a much shorter period of time. "We believed that the possibility to administer MSC-EVs through a non-invasive route and the demonstration of their anti-inflammatory efficacy might accelerate the chance of exploiting MSC-EVs to treat Alzheimer's disease," Dr. Coco said.

The team conducted their study both in vitro (outside a living organism) and in vivo (within a living organism). They began by collecting MSCs from the bone marrow of healthy human donors and preconditioning them with proteins called cytokines, to increase the MSCs' anti-inflammatory abilities and boost their release of EVs. For the in vitro segment of their study, they added the resulting MSC-EVs to microglia - cells that mediate immune responses in the central nervous system and, as such, are targets in Alzheimer's - isolated from newborn C57BL/6 mice. (These mice are specially bred to be used in studying diseases including Alzheimer's.) The applications were done at intervals of two and 24 hours. The results were then analyzed 48 hours after the final application.

For the in vivo portion of the study, the research team administered two doses of MSC-EVs to a group of 7-month-old female mice with Alzheimer's. The applications were done through the nasal passages, with the second dose occurring just 18 hours after the first. When they assessed the results 21 days later, they found that, just as they had seen with the in vitro experiments, the MSC-EVs had dampened the activation of the microglia cells in the mice brains and increased the density of dendritic spines (structures in the brain that provide cognitive resilience).

"We believe that the striking aspect of our study resides in the fact that the observed effects were achieved by only two intranasal injections of MSC-EVs delivered just hours apart," Dr. Coco said. "This might possibly have occurred because EVs delivered intranasally could reach higher levels than those delivered by other methods."

"Our results strengthen the view that mechanisms of action other than removal of amyloid plaques from the brain should deserve a great attention when treating Alzheimer's," she added. "Undoubtedly, the possibility of obtaining greater effects by repeated intranasal injections has to be considered and will be a matter for future experiments."

"There are several important findings from this study. In the attempt to find a possible cure for Alzheimer's disease, mesenchymal stem cells and their derived extracellular vesicles are being investigated for therapeutic purposes thanks to their protective and anti-inflammatory properties," said Anthony Atala, MD, Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. "The results from this study present an opportunity for potentially effective therapies to be tested by human pilot clinical trials. This work is worthy to progress forward."

Indiscriminate feeding by an alien population of the carnivorous spotted-thighed frog - could severely affect the native biodiversity of southern Australia according to a new study by the University of South Australia.

The invasive amphibian - Litoria cyclorhyncha - which has hitchhiked across the Nullarbor from Western Australia - has now established a community of 1000-plus in Streaky Bay, South Australia, with sightings also confirmed on the Eyre Peninsula and at the Adelaide airport.

This is the first study of the spotted-thighed frog's diet in its invaded range with the findings providing important biological information about the impact of the alien species on natural ecosystems.

Ecology experts, UniSA's Associate Professor Gunnar Keppel and Christine Taylor, say the potential of the spotted-thighed frog spreading to other parts of Australia is very concerning given its destructive eating patterns.

"This frog is an indiscriminate eating machine that will devour just about anything it can fit into its mouth," Taylor says.

"We're talking about a relatively large, predatory tree frog that, as a species is alien to South Australia, and it could have devastating impact on invaded habitats.

"As it eats away at local species, it's impacting the natural ecosystem, which can displace or destroy local food webs, outcompete native birds, reptiles and mammals for resources, and potentially change natural biodiversity."

Biodiversity is the theme of this year's United Nations World Environment Day.

Published in the Australian Journal of Zoology, the study examined the stomach contents of 76 spotted-thighed frogs across three habitats - an artificial wetland, seminatural bushland and an urban setting.

On average, each frog had at least six prey items in its stomach, with prey estimated to include 200 different species, 60 per cent of which were beetles, spiders and insects. Native geckos, young frogs and mice were also identified as prey.

Introduced species can have terrible outcomes for Australia, if not understood well. The infamous introduction of the cane toad in the 1930s as a mechanism to control sugar cane beetles, is just one example. The failure of that initiative continues to ravage Australia's ecology, with the cane toad now listed as a threatening pest under the Environment Protection and Biodiversity Conservation Act.

Assoc Prof Keppel says it is important that people understand how detrimental introduced species can be for whole environments. He warns that if the spread of the spotted-thighed frog is not kept under control they could dominate many ecosystems in south-east Australia, at the expense of the local flora and fauna.

"The spotted-thighed frog is obviously very mobile. Already it's managed to travel more than 2000 kilometres and set up a colony in Streaky Bay. But its considerable tolerance of salinity and potential ability to withstand high temperatures could lead to further geographic spread, and if not controlled, it could extend further eastward into the Murray-Darling Basin," Assoc Prof Keppel says.

"It's vital that we continue to protect Australia's biodiversity. Preventing further dispersal of the spotted-thighed frog is a high conservation priority.

"The state government should consider managing the invasive population of spotted-thighed frogs at Streaky Bay. This should include education programs to inform people about what to do if they find a frog, as well as the feasibility of exterminating the population in South Australia.

"Importantly, if you do see one of these critters in your travels - leave it be. We don't want it hitchhiking any further."

Washington State University researchers have developed a technology that is more than 30 times more sensitive than current lab-based tests in finding early stage cancer biomarkers in blood.

The technology uses an electric field to concentrate and separate cancer biomarkers onto a paper strip. It could someday become a kind of liquid biopsy and could lead to earlier detection of and faster treatments for cancer, a disease that causes more than 9.6 million deaths a year around the world.

Led by Wenji Dong, associate professor in the Gene and Linda Voiland School of Chemical Engineering and Bioengineering, and graduate student Shuang Guo, the researchers were able to detect miniscule levels of the cancer markers in tiny extracellular bubbles called exosomes in as little as 10 minutes. Reporting on their work in the journal, Biosensors and Bioelectronics, the researchers call the work a "significant step" in developing rapid testing and early cancer detection.

Researchers have long sought ways to detect cancer earlier to save more lives. While lab tests to detect tumor biomarkers in blood have been developed, they often can't find early-stage cancer because the cancer markers are at levels too low to detect. Instead, people most often find out they have cancer through invasive biopsies once tumors are established.

In recent years, researchers have discovered that one of the ways cancer cells spread and communicate with other parts of the body is by way of tiny exosome vesicles in blood or other fluids. Ranging in size from 40 to 120 nanometers, or about 1000 times smaller in width than a strand of hair, the exosomes are thought to shuttle molecules from parent cancer cells through the body, entering and then re-programming friendly cells to become cancerous. Cancer cells also secrete more exosome bubbles than regular cells.

"Exosomes provide a unique opportunity as a cancer marker," Dong said.

However, finding the cancer-filled exosomes in blood testing is challenging. They look the same as normal cell exosomes and other extracellular bubbles, and they are at very low levels in the blood in early cancer.

The WSU team for the first time applied a technology that uses an electric field to rapidly isolate, enrich and detect the exosomes taken from a prostate cancer cell line.

The technology was able to concentrate and then separate the cancer-cell exosomes from those from normal cells by way of immune-binding. That is, the researchers captured the target exosomes by using an antibody that is specific to a protein marker on the exosome surface. The researchers were also able to separate out and analyze cancer protein markers within the exosomes.

The technology was 33 times more sensitive than conventional methods that are used in research labs to detect and analyze exosomes.

"This has the potential to become a technique capable of concentrating samples by orders of magnitude in minutes," Dong said.

The researchers demonstrated their technology successfully with a test serum. They are now working to improve it using a greater amount of human blood which, with a confusing mix of hormones, lipids, and other elements floating around, can create a challenging environment for successful testing. The researchers are also working to adjust the power requirements of the technology, so that it can be used portably and more easily in a medical setting.

A technique that has greater sensitivity to assess harmful chemicals adds to the analysis toolkit for cigarette alternatives. This research by KAUST scientists, now published in Tobacco Control, reveals that a tobacco-heating device called "I quit ordinary smoking" (IQOS), emits many more potentially harmful chemicals than those identified by the manufacturer.

The IQOS device operates at a lower temperature than ordinary cigarettes: it heats tobacco sticks to around 300 degrees Celsius, whereas traditional cigarettes burn the tobacco at up to 900 degrees Celsius. It also differs from vaping systems, which heat liquids containing nicotine.

IQOS was developed by Philip Morris International and introduced to the market in 2014. The manufacturer claims it offers a safer alternative to traditional smoking, based on their own and other research. This suggested that IQOS achieves a very significant reduction in toxic exposure compared to regular cigarettes that burn tobacco.

“I wanted to assess the company’s claims,” says Bogdan-Dragoș Ilieș, a Ph.D. student at the KAUST Clean Combustion Research Center. He proposed an independent investigation to his supervisor, Mani Sarathy.

“We brainstormed different approaches to identifying the chemicals released by the heated tobacco sticks,” says Ilies. They realized there were serious limitations with the previously used method, based on offline sampling techniques, because they could not identify potentially significant molecules, such as short-lived and reactive polar carbonyl compounds.

The team devised a real-time gas chromatography mass spectrometry analysis method that collected vapors directly from heated tobacco sticks. Their setup allowed the detection of small molecules that would not persist in the gaseous phase for a sufficiently long-enough time to be detected by previously used procedures. The researchers were nevertheless surprised that they identified as many as 62 compounds, only 10 of which were found in the tests by Philip Morris International.

The additional chemicals found by the researchers included the known toxic compounds diacetyl, 2,3-pentanedione, hydroxymethylfurfural and diethylhexyl phthalate. The latter may be especially significant as it is considered to be potentially carcinogenic.

“It is crucial to monitor and identify any toxic and carcinogenic products released by these new tobacco heating products,” Sarathy comments. He hopes that these findings from KAUST’s independent investigations might lead to collaboration with tobacco companies to identify the health risks of their new products and to learn how to mitigate these risks.

“Our novel approach to identifying chemicals from heating tobacco sticks could also help to improve tobacco legislation around the world,” says Ilieș. “It enlarges the set of analytical techniques available to identify harmful chemicals that were invisible to previous methods.”

Parents with temperamental children should pay special attention to helping them develop good eating habits. These children are more susceptible to developing an unhappy relationship with food, researchers from the Norwegian University of Science and Technology (NTNU) have found.

Temperament is often equated with anger, but it embraces much more. Temperament is the child's fundamental way of dealing with his environment and himself. It can be regarded as a precursor to what is called personality in adults.

Temperament involves how the child thinks, acts and behaves, across situations and over time. For example, does the child become frustrated easily and find it difficult to regulate her emotions, or is she able to regulate her impulses, or complete a task even when tired? Is the child outgoing, curious and exploratory or a little anxious in new situations and with new people?

Parents are of course important in developing good eating habits. Parents do the food shopping, prepare the food and are responsible for the meals. They are also their children's role models and influence their eating habits through the way they relate to food and meals themselves and how they relate to the child's eating. (Example: "You need to eat dinner before you get dessert.") Researchers have shown this in several previous studies (links below).

A new study shows that the child's own characteristics also play a role in the development of eating habits. Researchers investigated the topic as part of the Trondheim Early Secure Study (TESS) project, which is based at NTNU.

When the approximately 800 children were 4, 6, 8 and 10 years old, the researchers asked parents about their children's eating habits and temperament and examined whether temperament could predict how eating habits evolved.

Their findings show that children who are what we often think of as temperamental (e.g., getting frustrated quickly, being more prone to fluctuating moods than others), are particularly vulnerable to developing eating habits that can lead to unhealthy weight gain and difficulties with food and eating.

They resort to emotional eating more over time, are more likely to eat because food is available, even though they may be satiated, and they become pickier eaters over time. Children with this temperament also showed greater emotional undereating later - that is, they were more likely to eat less when they were sad, restless, scared or angry.

It is important to establish good eating habits during childhood because we often bring these habits with us into our teens and adulthood. Good eating habits are important for having a good relationship with food and eating, and to avoid overweight, the researchers say.

Eating habits are not just about what we eat, but also about how we relate to food and eating.

Are you picky or do you love all kinds of food? Do you eat slowly or fast? Do you eat until your plate is empty even though you're actually full? Do you use food as comfort?

These are characteristics of our eating habits that affect what and how much we eat, and therefore also our weight.

Given that temperamental children are extra vulnerable to developing unhealthy eating habits, it is even more important that the parents of these children pay particular attention to supporting healthy eating.

This can be extra challenging for parents of children who have greater moods swings than others. Parents of temperamental children more often have to deal with negative emotions than do parents of children who don't easily become frustrated or angry. It's not surprising that parents of temperamental children more often resort to strategies that may not less than optimal.

A previous study showed that if the child is easily triggered emotionally, parents are more likely to use food to comfort the child. The child learns that food helps when she experiences anger, sadness or other difficult feelings - and thus succumbs to emotional eating more over time.

Even if we parents are not - nor need to be - perfect, we may want to be a little aware of how to help support healthy eating habits in children and how to best meet children's emotions.