Tech

Presented a program capable of detecting neurodegeneration biomarkers through magnetic

image: This tool is able to identify single-person neurodegeneration before the symptom's appearance, which could significate a more effective and personalized medicine.

Image: 
Bellvitge Biomedical Research Institute (IDIBELL)

Magnetic resonance imaging is the most sensitive and reliable technique for diagnosing and monitoring neurodegenerative diseases. Through the images obtained, we can make a complete anatomical analysis of the brain and detect atrophy in specific regions. However, the inspection of the images is usually visual, which means that certain signs of neurodegeneration, invisible to the human eye, are not detected until the damage is already advanced.

Dr. Estela Cámara from Bellvitge Biomedical Research Institute (IDIBELL) and Psychology Faculty and the Neuroscience Institute of the University of Barcelona (UBNeuro), together with Alicia Palomar, has designed a computer program that allows the quantitative analysis of magnetic resonance images easily, quickly and adaptable to any brain affection. This program, called SeSBAT (Single Subject Brain Analysis Toolbox), integrates different image analysis protocols that can measure the volume of specific regions of the brain or perform a general exploration of it, being able to detect small changes, invisible to the eye, but that could predict the risk of developing a degenerative disease.

SeSBAT opens the door to the identification of new biomarkers that would help to improve the early detection and monitoring of neurodegenerative diseases. Since it is a quantitative analysis, it is capable of identifying anatomical modifications of the brain that take place before the appearance of symptoms.

With this type of integrated analysis, data can be extracted from a single individual, avoiding the inter-individual variability of working with groups. This allows the individualized monitoring of a patient over time, which would be very useful to determine the efficacy of certain drugs in clinical trials or to monitor people at risk of developing a neurodegenerative disease.

Dr. Cámara's team has tested the accuracy of this new tool in magnetic resonance imaging of patients with Huntington's neurodegenerative disease. The results, published in the journal Frontiers in Systems Neuroscience, show how this tool is able to identify those patients who are in the early stages of the disease, and even those who have not yet presented the first symptoms.

Dr. Cámara states that it is a very versatile program that could be adapted and personalized for each type of neurodegenerative disease or project. The Cámara's group opens the doors to new collaborations with groups interested in applying this technology to their projects. Similarly, a tool like this could easily be applied to routine clinical practice, allowing a much deeper analysis of MRI images and more accurate management of patients with neurodegenerative diseases.

Credit: 
IDIBELL-Bellvitge Biomedical Research Institute

Airdropping sensors from moths

video: University of Washington researchers have created a sensor system that can ride aboard a small drone or an insect, such as a moth, until it gets to its destination.

Image: 
University of Washington

There are many places in this world that are hard for researchers to study, mainly because it's too dangerous for people to get there.

Now University of Washington researchers have created one potential solution: A 98 milligram sensor system -- about one tenth the weight of a jellybean, or less than one hundredth of an ounce -- that can ride aboard a small drone or an insect, such as a moth, until it gets to its destination. Then, when a researcher sends a Bluetooth command, the sensor is released from its perch and can fall up to 72 feet -- from about the sixth floor of a building -- and land without breaking. Once on the ground, the sensor can collect data, such as temperature or humidity, for almost three years.

The team presented this research Sept. 24 at MobiCom 2020.

"We have seen examples of how the military drops food and essential supplies from helicopters in disaster zones. We were inspired by this and asked the question: Can we use a similar method to map out conditions in regions that are too small or too dangerous for a person to go to?" said senior author Shyam Gollakota, a UW associate professor in the Paul G. Allen School of Computer Science & Engineering. "This is the first time anyone has shown that sensors can be released from tiny drones or insects such as moths, which can traverse through narrow spaces better than any drone and sustain much longer flights."

While industrial-sized drones use grippers to carry their payloads, the sensor is held on the drone or insect using a magnetic pin surrounded by a thin coil of wire. To release the sensor, a researcher on the ground sends a wireless command that creates a current through the coil to generate a magnetic field. The magnetic field makes the magnetic pin pop out of place and sends the sensor on its way.

The sensor was designed with its battery, the heaviest part, in one corner. As the sensor falls, it begins rotating around the corner with the battery, generating additional drag force and slowing its descent. That, combined with the sensor's low weight, keeps its maximum fall speed at around 11 miles per hour, allowing the sensor to hit the ground safely.

The researchers envision using this system to create a sensor network within a study area. For example, researchers could use drones or insects to scatter sensors across a forest or farm that they want to monitor.

Once a mechanism is developed to recover sensors after their batteries have died, the team expects their system could be used in a wide variety of locations, including environmentally sensitive areas. The researchers plan to replace the battery with a solar cell and automate sensor deployment in industrial settings.

Credit: 
University of Washington

Hearts harvested from pigs may soon help solve chronic shortages of these donor organs

BOSTON - The goal of harvesting hearts from pigs to solve the chronic shortage of these donor organs appears to be in reach, according to a new scientific review by researchers at Massachusetts General Hospital (MGH). This analysis, published in the journal Circulation, describes how recent breakthroughs in genetic engineering and drug development led to the recent successful transplantation of pig hearts into baboons by a team in Germany. This pioneering cardiac xenotransplantation--implanting a heart from one species into another--could help prolong and save countless human lives.

A heart transplant is often the only hope of survival for patients with severe heart failure and certain other cardiac conditions that don't respond to other treatments. In 2019, surgeons in the United States performed 3,552 heart transplants, according to the United Network for Organ Sharing. A patient in need of a new heart typically waits more than six months for a donor organ to become available, and often much longer. For many, the wait is too long.

Lead author Richard N. Pierson III, MD, an investigator in MGH's Division of Cardiac Surgery, and his coauthors discuss the scientific breakthroughs that have overcome obstacles to cardiac xenotransplantation. For example, the immune systems of baboons and other primates (including, presumably, humans) recognize pig hearts as "foreign" and attack them, leading to organ rejection. In response, scientists have used genetic engineering techniques to produce pigs whose organs lack certain carbohydrates that are the principal targets of the immune system.

Genetic engineering has also helped solve another problem with cardiac xenotransplantation. Early experiments found that incompatibility between proteins in human blood and proteins on the lining of pig blood vessels could cause blood clots. Pierson and his colleagues have contributed to efforts to develop and test pigs that are engineered to carry genes responsible for producing a human version of a protein called thrombomodulin, which keeps clotting under control.

Innovation in drug development has also made cardiac xenotransplantation possible. Transplant recipients must take drugs that suppress the immune system to prevent organ rejection. "But those drugs don't work when you put a pig organ into a baboon," says Pierson, suggesting that conventional immune suppression wouldn't work in humans, either. To solve this problem, Pierson collaborated with other researchers to develop monoclonal antibodies that block "costimulatory" molecules known as CD40 and CD154. These monoclonal antibodies prevent human or baboon immune cells from attacking pig organs much more effectively than conventional immunosuppressants.

Finally, the Circulation review addresses the question of whether transplanting animal organs into humans could transmit infectious diseases, a concern heightened by the current coronavirus pandemic. "That looks quite unlikely," says Pierson. "The culmination of a lot of research and hard work by our group and others over the last 35 years is that it now looks as though pig-to-human heart transplantation is feasible." He predicts that the first humans could receive transplanted pig hearts as soon as the end of 2021.

Credit: 
Massachusetts General Hospital

Researchers find consistent mercury levels in arctic seals

image: A study published in Environmental Toxicology and Chemistry spanning 45 years of testing indicates that mercury concentrations in ringed seals from the Canadian Arctic have remained stable, showing very limited declines over time.

Image: 
Magali Houde

Ringed seals and other Arctic marine mammals are important in the diet of Arctic Indigenous peoples. A study spanning 45 years of testing indicates that mercury concentrations in ringed seals from the Canadian Arctic have remained stable, showing very limited declines over time.

The authors of the Environmental Toxicology and Chemistry study noted that different climate parameters may have affected mercury accumulation in seals.

"Ringed seal is an important species for contaminants surveillance and monitoring across the Arctic. With the collaboration and support of Inuit communities, we've been able to study contaminants in seals for decades in Canada," said corresponding author Magali Houde, PhD, of Environment and Climate Change Canada. "Levels of mercury have not changed much in ringed seals through time. Our result suggest that climate factors could be influencing the accumulation of mercury in seals."

October 12th is Indigenous Peoples' Day in the United States.

Credit: 
Wiley

Discovery of a new key player in long-term memory

A McGill-led multi-institutional research team has discovered that during memory consolidation, there are at least two distinct processes taking place in two different brain networks - the excitatory and inhibitory networks. The excitatory neurons are involved in creating a memory trace, and the inhibitory neurons block out background noise and allow long-term learning to take place.

The team, led by McGill University Professors Nahum Sonenberg and Arkady Khoutorsky, Université de Montréal Professor Jean-Claude Lacaille, and University of Haifa Professor Kobi Rosenblum, senior authors on the paper published today in Nature, also found that each neuronal system can be selectively manipulated to control long-term memory. The research, which answers a long-standing question about which neuronal subtypes are involved in memory consolidation, has potential implications for novel targets for medication for disorders such as Alzheimer's disease and autism, which involve altered memory processes.

Looking for the neurons involved in memory consolidation

How do short-term memories (which last just a few hours) transform into long-term memories (which may last years)? It's been known for decades that this process, called memory consolidation, requires the synthesis of new proteins in brain cells. But until now, it hasn't been known which subtypes of neurons were involved in the process.

To identify which neuronal networks are essential in memory consolidation, the researchers used transgenic mice to manipulate a particular molecular pathway, eIF2α, in specific types of neurons. This pathway had already been shown to play a key role in controlling the formation of long-term memories and regulating protein synthesis in neurons. Moreover, earlier research had identified eIF2α as pivotal for both neurodevelopmental and neurodegenerative diseases.

Excitatory and inhibitory systems both play a role in memory consolidation

"We found that stimulation of protein synthesis via eIF2α in excitatory neurons of the hippocampus was sufficient to enhance memory formation and modification of synapses, the sites of communication between neurons", says Dr. Kobi Rosenblum.

However, interestingly, "we also found that stimulation of protein synthesis via eIF2α in a specific class of inhibitory neurons, somatostatin interneurons, was also sufficient to augment long-term memory by tuning the plasticity of neuronal connections", says Dr. Jean-Claude Lacaille.

"It is fascinating to be able to show that these new players - inhibitory neurons - have an important role in memory consolidation," added Dr. Vijendra Sharma, a research associate in Prof. Sonenberg's lab and the first author on the paper. "It had been assumed, until now, that eIF2α pathway regulates memory via excitatory neurons."

"These new findings identify protein synthesis in inhibitory neurons, and specifically somatostatin cells, as a novel target for possible therapeutic interventions in disorders such as Alzheimer's disease and autism," concluded Dr. Nahum Sonenberg. "We hope that this will help in the design of both preventative and post-diagnosis treatments for those who suffer from disorders involving memory deficits."

Credit: 
McGill University

Amniotic fluid may yield new, better treatment for ischemic stroke

image: Neuroprotective effects of human amniotic fluid stem cell-secretome in an I/R model.

Image: 
AlphaMed Press

Durham, NC - A study released today in STEM CELLS Translational Medicine points the way to a possible new avenue of treatment for ischemic stroke. The study, led by Annamaria Cimini, Ph.D., of the University of L'Aquila, and Liborio Stuppia, M.D., of D'Annunzio University, Italy, reveals how the secretome of amniotic fluid stem cells can restore neuronal plasticity (the brain's capacity to change and adapt), improve cognition, and replace neurons damaged or lost due to an ischemic stroke.

Their finding may lead to a more broadly applicable stroke therapy that is not hindered by a narrow treatment window or pre-existing conditions.

Each year, 5.5 million people across the world die from stroke, and more than 116 million years of healthy life are lost due to stroke-related death and disabilities, according to the World Stroke Organization. Most strokes - an estimated 87 percent - are the ischemic type, which occur when a vessel supplying blood to the brain becomes obstructed.

The most effective treatment currently in use is a clot-busting drug known as a tissue plasminogen activator (t-PA). However, to be effective the t-PA must be given within three hours after the onset of stroke symptoms, and even then the cure rate is just one in 10 patients. t-PAs also have their own risks, especially for people who have a history of bleeding problems, uncontrolled high blood pressure, or recent surgery or trauma.

"Thrombolytic therapy itself can lead to brain injuries, namely cerebral ischemia/reperfusion (I/R) injury. I/R injury is one of the major reasons for disability, high morbidity, and mortality worldwide," Dr. Cimini said. (Reperfusion refers to the act of restoring the flow of blood to an organ or tissue, typically after a heart attack or stroke.)

In the search for better treatment options, stem cells have emerged as a possible candidate due to their regenerative abilities. Human amniotic fluid stem cells (hAFSCs) in particular are interesting, as adult stem cells - even after reprogramming - might pass along any pre-existing genetic conditions, thus representing a limitation in their application.

On the other hand, hAFSCs offer a clean therapeutic slate. A novel class of pluripotent stem cells with intermediate characteristics between embryonic and adult stem cells, hAFSCs are able to safely differentiate into all types of tissue. Furthermore, ethical issues related to their use are minimal, as they are collected during routine amniocentesis, third-trimester amnio-reduction or Cesarean section.

The growing interest in hAFSCs over the past decade has led researchers to also investigate the cells' secretome - which encompasses the complete set of proteins expressed by cells and secreted into the extracellular space - and its potential neuroprotective mechanisms.

In their current study, the Cimini- Stuppia team wanted to determine which signal transduction pathways might be activated by hAFSC-derived secretome during a stroke. (Signal transduction is how signals are transferred through a cell via proteins - a process necessary for healing.) They also wanted to analyze miRNA expression in the conditioned medium. miRNAs found in exosomes are key regulators of the immune response that affect maturation, proliferation, differentiation and activation of immune cells, as well as antibody secretion and release of inflammatory mediators.

"Thus, exosomes offer an alternative therapeutic approach as a substitute for cell transplantation," Dr. Cimini said.

The team began by first devising an in vitro stroke model. To do this, they deprived hAFSCs of oxygen and glucose for a three hour period after testing several different time windows - at three hours, the cells showed a reduction in viability of about 50 percent. Then, 24 hours later, they treated the oxygen/glucose depleted cells with several different percentages of hAFSC-conditioned medium.

"When we examined the results, we found that the hAFSC-derived secretome had activated pro-survival pathways, as well as pathways that halted apoptosis (programmed cell death). Furthermore, microRNA analysis in the exosomal component revealed an abundance of miRNAs involved in protecting neurons and controlling neuronal cell death," Dr. Stuppia reported.

"In light of the data obtained, we believe that the use of conditioned medium and, in particular, exosomes may represent a suitable treatment for I/R injury," he concluded.

"These early pre-clinical results are certainly encouraging and demonstrate the need to further pursue human amniotic fluid stem cells-derived secretome as a regenerative cell therapy," said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. "These outcomes suggest a potential approach that could change the outcome for millions of patients who suffer a stroke."

Credit: 
AlphaMed Press

Taking the STING out of MND

image: Almost all patients with MND have evidence of TDP-43 (red) being in the wrong place inside motor neuron cells. Mitochondria (blue) provide power to motor neurons, but if invaded by TDP-43, they leak out their DNA (green) which triggers a virus sensor called STING. Drugs targeting STING prevent inflammation and keep MND patient motor neurons alive longer in laboratory tests.

Image: 
Image courtesy of the Walter and Eliza Hall Institute of Medical Research

Melbourne researchers are working towards a potential treatment to slow the progression of motor neuron disease (MND), offering hope to people with this debilitating and incurable illness.

The research team have uncovered how inflammation in MND is triggered. Pinpointing the molecules involved in this pathway could be a first step towards a new treatment for MND.

They found that by blocking an immune sensor called STING, they could dramatically prevent inflammation from MND patient cells, paving the way for a new class of drugs to be developed for people with neurodegenerative disorders, such as MND.

The discovery, published today in Cell, was led by Walter and Eliza Hall Institute researchers Associate Professor Seth Masters and Dr Alan Yu, with colleagues from the University of Melbourne and Hudson Institute.

At a glance

Researchers have uncovered the primary immune pathway that is activated by a protein that accumulates in patients with MND

By blocking the STING immune sensor, researchers were able to prevent inflammation from patient motor neurons, and thus promote motor neuron survival

The discovery is a first step towards a treatment therapy for MND

Halting the inflammatory response

MND is an incurable condition in which the nerve cells controlling the muscles that enable us to move, speak, swallow and breathe, fail to work. One in 10,000 Australians will be diagnosed with MND in their lifetime and the average life expectancy from diagnosis is just two years.

Most people suffering from MND have an accumulation of a protein called TDP-43 within cells of the central nervous system. This build-up is associated with an inflammatory response that precedes major symptoms of MND.

Institute researchers investigated how the disease-causing inflammation is triggered in MND, said Associate Professor Masters. "This unexpectedly identified that an immune sensor called STING is activated downstream of TDP-43. Fortuitously, our team had already studied the role of STING in other inflammatory diseases and are now working out how to block it."

The team then used new inhibitors - drug-like compounds - to block different components of this inflammatory pathway.

"Using cells from patients with MND that we can turn into motor neurons in a dish, we showed that blocking STING dramatically prevented inflammation and kept the cells alive longer. This is an exciting first step before taking these inhibitors into the clinic for treatment for MND.

Vital first step towards a treatment

Associate Professor Masters said his research had also established activation of STING in people who had passed away due to MND.

"We are now aiming to validate a biomarker of the pathway earlier in the disease progression. Once this neuroinflammatory biomarker is validated, we will better understand which patients will benefit the most from treatments targeting the pathway," he said.

"With this knowledge, there is the potential to develop a treatment for patients with MND.

"Interestingly, our preclinical models suggest that although the anti-inflammatory drugs that inhibit STING did not prevent disease onset, they did slow the degenerative progression of disease."

Hope for people with MND and other neurodegenerative disorders

Associate Professor Masters said this discovery offered hope for people diagnosed with the debilitating condition.

"We are hopeful this research could lead to a treatment for people with established MND, who currently have very few treatment options and a life expectancy post diagnosis of just two to five years," he said.

"While it isn't a cure, we hope it might extend life expectancy and dramatically improve the quality of life for people diagnosed with MND."

Associate Professor Masters said a future treatment might also be effective in slowing the progression of other neurodegenerative disorders.

"We are hoping to develop a new class of drugs that would act as STING inhibitors to stop the progression of neurodegenerative disorders, such as MND, Frontotemporal Dementia and Parkinson's disease."

Credit: 
Walter and Eliza Hall Institute

New findings pave the way to environmentally friendly supercapacitors

image: Harald Fitzek, Christian Prehal and Qamar Abbas (from left) at the SAXS facility SAXSpoint 2.0 (Anton Paar GmbH): With their work at Graz University of Technology, the researchers are providing new insights into hybrid supercapacitors.

Image: 
© Lunghammer - TU Graz

Limited safety, sustainability and recyclability are key drawbacks of today's lithium-ion battery technology, along with restricted availability of starting materials (e.g. cobalt). In the search for alternative electrochemical energy storage systems for use in e-mobility and for storing energy from renewable sources, a combination of battery and capacitor is very promising: the "hybrid supercapacitor". It can be charged and discharged as quickly as a capacitor and can store almost as much energy as conventional batteries. In comparison to the latter, it can be charged and discharged much faster and much more frequently: while a lithium-ion battery achieves a service life of a few thousand cycles, a supercapacitor manages around one million charging cycles.

System made of carbon and salt water

A particularly sustainable, but so far quite unexplored variant of such a hybrid supercapacitor consists of carbon and aqueous sodium iodide (NaI) electrolyte, with a positive battery electrode and a negative supercapacitor electrode. Researchers at Graz University of Technology have now investigated in more detail how exactly the electrochemical energy storage in this supercapacitor works and what happens in the nanometer-sized pores of the carbon electrode, and have recently published their promising results in the scientific journal Nature Communications. "The system we are looking at in detail consists of nanoporous carbon electrodes and an aqueous sodium iodide electrolyte, in other words salt water. This makes this system particularly environmentally friendly, cost-effective, incombustible and easy to recycle," explains Christian Prehal. He is the first author of the study and has recently moved from the Institute of Chemistry and Technology of Materials at TU Graz to ETH Zurich.

Unexpectedly higher energy storage capacity

With the aid of small-angle X-ray scattering and Raman spectroscopy, the researchers were able to show for the first time that solid iodine nanoparticles are formed in the carbon nanopores of the battery electrode during charging, which dissolve again during discharge. This corrects the previously suspected reaction mechanism and has far-reaching consequences, as Christian Prehal explains: "The degree of filling of the nanopores with solid iodine determines how much energy can be stored in the electrode. This enables the energy storage capacity of the iodine carbon electrodes to reach unexpectedly high values by storing all chemical energy in the solid iodine particles." This new fundamental knowledge opens the way to hybrid supercapacitors or battery electrodes with incomparably higher energy density and extremely fast charging and discharging processes. Such hybrid capacitors have been very successfully investigated and further developed for several years by Qamar Abbas, currently a Lise Meitner FWF scholarship holder at the Institute of Chemistry and Technology of Materials and another main author of the study.

With targeted improvements, hybrid supercapacitors can now be put to use as a safe, non-flammable, cost-effective and sustainable alternative for stationary storage of electrical energy. This can be an attractive option especially for the storage of energy from photovoltaic cells in private households, for example.

New investigation method for electrochemical energy storage systems

The researchers achieved another breakthrough with regard to the investigation methods used. In Raman spectroscopy, the interaction of light with matter is used to gain insight into the structure or properties of a material. Small-angle X-ray scattering (SAXS) makes structural changes during electrochemical reactions visible. Both methods took place in operando, i.e. live during the charging and discharging of a specially developed electrochemical cell. "Both operando Raman spectroscopy and operando SAXS were performed for the first time on a hybrid supercapacitor with aqueous NaI electrolyte at the Institute of Electron Microscopy and Nanoanalysis (FELMI) and in the soft matter application lab at Graz University of Technology. For the operando SAXS investigation, we have developed a special measuring cell for batteries and electrochemical energy storage devices," explains Prehal. The results of the work show that operando SAXS is ideally suited to follow structural changes in a supercapacitor or battery on the nanometer scale and directly "live" during charging and discharging. This new investigation method could therefore be widely used in future in the field of electrochemical energy storage.

Credit: 
Graz University of Technology

Microneedles for therapeutic gene delivery

image: Microneedles for therapeutic gene delivery

Image: 
Khademhosseini Lab

(LOS ANGELES) - There is great potential in gene therapy for treating certain types of cancer and genetic defects, immunological diseases, wounds and infections. The therapies work by delivering genes into the patients' cells, which then produce therapeutic proteins to treat the affliction.

When determining the method of delivery for these genes, there are advantages to choosing a local, rather than systemic delivery of the genetic material. With systemic delivery, there is the possibility of unwanted tissue accumulation or of the genetic material becoming unstable. It is also advantageous to target the skin as a site for local delivery, as it is easily accessible and contains fluid and lymph vessels, as well as immune cells upon which the genetic material can act to initiate treatment.

Despite these advantages, it is still difficult to deliver genes into the skin. An ideal gene delivery approach must be able to deliver the genetic material without producing inflammation or toxicity in the body and should be able to penetrate the skin layer effectively.

A collaborative team, which includes a group from the Terasaki Institute for Biomedical Innovation, has recently published an approach based on microneedles that meets these challenges. These microneedles are made of a biocompatible material mixed with nanoparticles containing therapeutic genes. This mixture can be molded into a microneedle patch array for application to the skin. The microneedles are biodegradable, so once they have penetrated the skin, they will release the nanoparticles upon needle degradation. Moreover, the timing and sustainability of this release can be controlled by adjustments in the biomaterial preparation.

The team conducted extensive tests to optimize the release and performance of the gene-containing nanoparticles, and they also validated the efficacy of the genes. "This biodegradable microneedle patch with gene-delivering nanoparticles is an effective and minimally-invasive vehicle for local therapeutic gene delivery," said Terasaki Institute Fellow Wujin Sun, Ph.D., who is an author of the publication. "This platform can be utilized for applications such as vaccinations, protein supplementation or gene editing."

The development of these microneedles illustrates the potential for similar gene delivery systems that can be customized according to the therapeutic genes chosen. This new technology can provide a more effective way to treat skin and other cancers, skin-related cosmetic needs or diseases such as psoriasis and muscular dystrophy. It can even be used as a method for vaccine delivery against such diseases as skin or breast cancer, influenza or COVID-19.

"The ability to enable local therapeutic gene delivery using this microneedle system is a notable achievement," said Terasaki Institute Director and CEO Ali Khademhosseini, Ph.D., who is the senior author of the paper. "It opens the possibilities for a variety of clinical applications and synergizes with a number of platforms at the Terasaki Institute, which aims to leverage our ability to find personalized solutions for patients.

Credit: 
Terasaki Institute for Biomedical Innovation

UMD researchers develop tools to sharpen 3D view of large RNA molecules

image: University of Maryland researchers developed a method to expand the scope of nuclear magnetic resonance (NMR) spectroscopy. In the example above, the researchers were able to create a 3D image revealing the site on a piece of hepatitis RNA where small molecules such as a drug could bind (shown in green).

Image: 
Kwaku Dayie/University of Maryland

University of Maryland scientists have developed a method to determine the structures of large RNA molecules at high resolution. The method overcomes a challenge that has limited 3D analysis and imaging of RNA to only small molecules and pieces of RNA for the past 50 years.

The new method, which expands the scope of nuclear magnetic resonance (NMR) spectroscopy, will enable researchers to understand the shape and structure of RNA molecules and learn how they interact with other molecules. The insights provided by this technology could lead to targeted RNA therapeutic treatments for disease. The research paper on this work was published in the journal Science Advances on October 7, 2020.

"The field of nuclear magnetic resonance spectroscopy has been stuck looking at things that are small, say 35 RNA building blocks or nucleotides. But most of the interesting things that are biologically and medically relevant are much bigger, 100 nucleotides or more," said Kwaku Dayie, a professor of chemistry and biochemistry at UMD and senior author of the paper. "So, being able to break down the log jam and look at things that are big is very exciting. It will allow us to peek into these molecules and see what is going on in a way we haven't been able to do before."

In NMR spectroscopy, scientists direct radio waves at a molecule, exciting the atoms and "lighting up" the molecule. By measuring changes in the magnetic field around the excited atoms--the nuclear magnetic resonance--scientists can reconstruct characteristics such as the shape, structure and motion of the molecule. The data this produces can then be used to generate images, much like MRI images seen in medicine.

Ordinarily, NMR signals from the many atoms in a biological molecule such as RNA overlap with each other, making analysis very difficult. However, in the 1970s, scientists learned to biochemically engineer RNA molecules to work better with NMR by replacing the hydrogen atoms with magnetically active fluorine atoms. In relatively small molecules of RNA consisting of 35 or fewer nucleotides, the fluorine atoms light up readily when hit with radio waves and remain excited long enough for high-resolution analysis. But as RNA molecules get larger, the fluorine atoms light up only briefly, then quickly lose their signal. This has prevented high-resolution 3D analysis of larger RNA molecules.

Previous work by others had shown that fluorine continued to produce a strong signal when it was next to a carbon atom containing six protons and seven neutrons (C-13). So, Dayie and his team developed a relatively easy method to change the naturally occurring C-12 in RNA (which has 6 protons and 6 neutrons) to C-13 and install a fluorine atom (F-19) directly next to it.

Dayie and his team first demonstrated that their method could produce data and images equal to current methods by applying it to pieces of RNA from HIV containing 30 nucleotides, which had been previously imaged. They then applied their method to pieces of Hepatitis B RNA containing 61 nucleotides--nearly double the size of previous NMR spectroscopy possible for RNA.

Their method enabled the researchers to identify sites on the hepatitis B RNA where small molecules bind and interact with the RNA. That could be useful for understanding the effect of potential therapeutic drugs. The next step for the researchers is to analyze even larger RNA molecules.

"This work allows us to expand what can be brought into focus," Dayie said. "Our calculations tell us that, in theory, we can look at really big things, like a part of the ribosome, which is the molecular machine that synthesizes proteins inside cells."

By understanding the shape and structure of a molecule, scientists can better understand its function and how it interacts with its environment. What's more, this technology will enable scientists to see the 3D structure as it changes, because RNA molecules in particular change shape frequently. This knowledge is key to developing therapeutics that narrowly target disease-specific molecules without affecting healthy cell functions.

"The hope is that if researchers know the nooks and crannies in a molecule that is dysfunctional, then they can design drugs that fill the nooks and crannies to take it out of commission," Dayie said. "And if we can follow these molecules as they change shape and structure, then their response to potential drugs will be a little bit more predictable, and designing drugs that are effective can be more efficient."

Credit: 
University of Maryland

Data tool helps users manage water resources, protect infrastructure

River systems are essential resources for everything from drinking water supply to power generation - but these systems are also hydrologically complex, and it is not always clear how water flow data from various monitoring points relates to any specific piece of infrastructure. Researchers from Cornell University and North Carolina State University have now developed a tool that draws from multiple databases to give water resource managers and infrastructure users the information they need to make informed decisions about water use on river networks.

"A streamgage tells you what the water level is at a specific point in the river - but that's not really enough information," says Sankar Arumugam, co-author of a paper on the work and a professor of civil engineering at NC State. "If you are an infrastructure operator, what you really need to know is how long it will take for that water-level information to be relevant to your infrastructure. How far away is the streamgage from your water intake along the river path, not just as the crow flies? How closely connected are those two things, hydrologically?"

"This information is important for managing water systems efficiently, for ensuring that infrastructure - such as power plants - are able to continue operating, and for protecting the infrastructure," says Sudarshana Mukhopadhyay, first author of the paper and currently a postdoctoral researcher at Cornell University. "The information is particularly important during extreme conditions, such as flooding or drought.

"All of that data already exists, it's just scattered across separate databases. We've developed an algorithm that efficiently pulls all of that information into one place and accounts for how the streamgages and the various infrastructure sites are hydrologically connected over a large watershed," says Mukhopadhyay, who worked on the research as a Ph.D. student at NC State.

To demonstrate the tool's utility, the researchers used the algorithm to create a connectivity network demonstrating the interconnectedness of about 1,400 reservoirs and 1,600 streamgages in the upper and lower Colorado River basins.

For this network, the algorithm used data from three sources: topographic information from the U.S. Geological Survey's (USGS) National Hydrographic Dataset; streamgages from the USGS National Water Information System; and reservoir data from the National Inventory of Dams.

"This is a tool that can be used by power plant operators, reservoir operators, water resource managers - really it's for anyone who draws water from the river system," Mukhopadhyay says. "It can inform them about river conditions both upstream and downstream, and help them make decisions about where they should draw water from the system."

The researchers have also made a template publicly available, allowing anyone to develop similar connectivity networks for other watersheds.

"It should be fairly easy for water resources professionals," Mukhopadhyay says.

"We are currently working on a national version, which we think will help us better understand all of the ways that river basins connect infrastructures across the country," Arumugam says.

Credit: 
North Carolina State University

Beat the heat: Novel passive cooling device for surfaces and enclosed spaces

image: The bottom layer of the Janus emitter absorbs the heat inside the vehicle and emits it through the top layer to the atmosphere (indicated in blue), causing a temperature drop. The right image shows an experimental model that simulates a vehicle.

Image: 
Young Min Song/GIST

If you have ever stepped into a car parked under the sun, you would be familiar with how hot it can get on the inside. This occurs because although sunlight can pass through the transparent windows, the thermal radiation re-emitted by the interior cannot, thereby creating a "greenhouse effect" and heating the inside of the car to temperatures as high as 82°C. Elderly people and children are at a particularly high risk of suffering heatstroke or hyperthermia at such temperatures.

This heat from a parked vehicle can be released by either spending energy in active cooling, which is not sustainable, or opening a window, which is not ideal on rainy days or when driving on a highway. Fortunately, scientists from Gwangju Institute of Science and Technology (GIST), Korea, have developed a new type of passive cooling technology to solve this issue.

In a new study, published in Science Advances, they present a device called "Janus emitter," or JET. Named after the two-faced Greek god Janus, the JET comprises a stack of patterned quartz, silver, and polydimethylsiloxane thin layers. Each face of the JET has unique properties for passively cooling enclosed spaces. The bottom side absorbs a broad spectrum of thermal radiation from inside the enclosure and, through a quantum phenomenon called "spoof surface plasmon polaritons," re-emits this energy to the atmosphere on the top side in a selective frequency range that maximizes emissivity. Prof Young Ming Song, who led this study, explains, "The 'Janus' thermal radiation characteristics of the JET allow it to function as a heat channel that efficiently draws heat from the enclosure and sends it outside."

The JET requires no electricity at all and no conscious effort from the user, which makes it a sustainable way of keeping the temperature of stationary vehicles, building interiors, and solar cells low. Excited about the results, Dr Song concludes, "Our work is the first to address passive radiative cooling for enclosed spaces, and we hope it creates a ripple effect that bolsters research in this field."

Indeed, as this novel technology takes off, staying cool doesn't have to be so hard anymore!

Credit: 
GIST (Gwangju Institute of Science and Technology)

NASA finds dry air sapping Tropical Storm Norbert's strength

image: On Oct. 7 at 4:30 a.m. EDT (0830 UTC), the MODIS instrument aboard NASA's Aqua satellite gathered temperature information about Norbert's cloud tops. MODIS found a limited area of powerful thunderstorms (red) around the center where temperatures were as cold as or colder than minus 70 degrees Fahrenheit (minus 56.6 Celsius). Dry air around it was sapping other thunderstorms from developing.

Image: 
NASA/NRL

Infrared imagery from NASA's Aqua satellite revealed that dry air is eroding Tropical Storm Norbert, located off the coast of southwestern Mexico.

Infrared Data Reveals Dry Air Effects

On Oct. 7 at 4:30 a.m. EDT (0830 UTC), the Moderate Resolution Imaging Spectroradiometer or MODIS instrument aboard NASA's Aqua satellite gathered temperature information about Norbert's cloud tops. Infrared data provides temperature information, and the strongest thunderstorms that reach high into the atmosphere have the coldest cloud top temperatures.

Dry air suppresses the development of thunderstorms that need warm, moist air to form. Dry air saps the moisture. Tropical cyclones consist of hundreds of thunderstorms. When their development is limited by environmental factors, they have difficulty strengthening and often weaken. The MODIS image showed fragmentation of thunderstorms around Norbert's center as dry air affected development.

MODIS found that Norbert has weakened as entrainment of dry air has disrupted the compact system. The National Hurricane Center reported that Norbert's center was partially exposed overnight, but recent infrared imagery shows a new burst of deep convection near the center. MODIS identified that burst of strong thunderstorms in infrared light, where temperatures were as cold as or colder than minus 70 degrees Fahrenheit (minus 56.6 Celsius). Cloud top temperatures that cold indicate strong storms with the potential to generate heavy rainfall.

Norbert's Status on Oct. 7

At 5 a.m. EDT (0900 UTC), the center of Tropical Storm Norbert was located near latitude 14.0 degrees north and longitude 107.1 degrees west. Norbert is drifting toward the southwest near 1 mph (2 kph). The storm is forecast to meander or remain nearly stationary over the next couple of days.

Satellite-derived wind data indicate that maximum sustained winds have decreased to near 40 mph (65 kph) with higher gusts. Some fluctuations in strength will be possible during the next few days. The estimated minimum central pressure is 1005 millibars.

Norbert's Future

Forecasters at the National Hurricane Center noted the forecast for Norbert over the next couple of days is challenging. "The intensity forecast for Norbert remains tricky given its small circulation and the presence of dry air in the surrounding environment. Sea-surface temperatures are more than sufficient for at least modest strengthening, but the question will be whether Norbert can survive the increased southeasterly shear that the SHIPS [computer forecast model] guidance calls for during the next 24-48 hours."

NASA Researches Tropical Cyclones

For more than five decades, NASA has used the vantage point of space to understand and explore our home planet, improve lives and safeguard our future. NASA brings together technology, science, and unique global Earth observations to provide societal benefits and strengthen our nation. Advancing knowledge of our home planet contributes directly to America's leadership in space and scientific exploration.

For updated forecasts, visit: http://www.nhc.noaa.gov

By Rob Gutro
NASA's Goddard Space Flight Center

Credit: 
NASA/Goddard Space Flight Center

NASA analyzes rainfall around Typhoon Chan-hom's ragged eye

image: On Oct. 7 at 2 a.m. EDT (0600 UTC), NASA's IMERG estimated Typhoon Chan-hom was generating as much as (30 mm/1.18 inches of rain (dark pink) around the center of circulation. Rainfall throughout most of the storm was occurring between 5 and 15 mm (0.2 to 0.6 inches/yellow and green colors) per hour. The rainfall data was overlaid on infrared imagery from NOAA's GOES-16 satellite.

Image: 
NASA/NOAA/NRL

A NASA satellite rainfall product that incorporates data from satellites and observations found heavy rainfall occurring throughout Typhoon Chan-hom and the heaviest rainfall in the eyewall. Chan-hom is expected to bring rainfall to Japan on its track through the Northwestern Pacific Ocean.

Chan-hom's Status on Sept. 18

At 5 a.m. EDT (0900 UTC), the center of Typhoon Chan-hom was located near latitude 26.2 degrees north and longitude 134.4 degrees east. It was centered 378 nautical miles east of Kadena Air Base, Okinawa Island, Japan, moving toward the northwest. Maximum sustained winds are near 65 knots (75 mph/120 kph) with higher gusts.

Estimating Chan-hom's Rainfall Rates from Space

NASA's Integrated Multi-satellitE Retrievals for GPM or IMERG, which is a NASA satellite rainfall product, estimated on Oct. 7 at 2 a.m. EDT (0600 UTC), Chan-hom was generating as much as 30 mm (1.18 inches) of rain per hour falling in the ragged eyewall that surrounds the eye. Rainfall throughout most of the storm was estimated as falling at a rate between 5 and 15 mm (0.2 to 0.6 inches) per hour. At the U.S. Naval Laboratory in Washington, D.C., the IMERG rainfall data was overlaid on infrared imagery from NOAA's GOES-16 satellite to provide a full extent of the storm.

In addition to the rainfall calculation within the typhoon, animated enhanced infrared satellite imagery revealed a consolidating system with a ragged eye. Microwave imagery indicates improved banding of thunderstorms wrapping tightly into a microwave eye feature.

Warnings for heavy rainfall are in effect for Kyushu, the southernmost big island of Japan. Watches were posted for much of Japan's southeastern and east central coasts.

What Does IMERG Do?

This near-real time rainfall estimate comes from the NASA's IMERG, which combines observations from a fleet of satellites, in near-real time, to provide near-global estimates of precipitation every 30 minutes. By combining NASA precipitation estimates with other data sources, we can gain a greater understanding of major storms that affect our planet.

Instead, what the IMERG does is "morph" high-quality satellite observations along the direction of the steering winds to deliver information about rain at times and places where such satellite overflights did not occur. Information morphing is particularly important over the majority of the world's surface that lacks ground-radar coverage. Basically, IMERG fills in the blanks between weather observation stations.

Chan-hom's Forecast

Forecasters at the Joint Typhoon Warning Center (JTWC) expect Chan-hom to track northwestward to northward through the next two days and closer to Japan. Chan-hom is forecast to make a slow track paralleling the coast of Japan from Oct. 8 through the 11, when it is expected to affect Tokyo before heading out to open waters.

JTWC expects Chan-hom to continue weakening over the next several days and begin transitioning to an extra-tropical storm.

NASA Researches Tropical Cyclones

Hurricanes/tropical cyclones are the most powerful weather events on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

For more than five decades, NASA has used the vantage point of space to understand and explore our home planet, improve lives and safeguard our future. NASA brings together technology, science, and unique global Earth observations to provide societal benefits and strengthen our nation. Advancing knowledge of our home planet contributes directly to America's leadership in space and scientific exploration.

For more information about NASA's IMERG, visit: https://pmm.nasa.gov/gpm/imerg-global-image

For updated warnings from the Japan Meteorological Agency, visit: https://www.jma.go.jp/en/warn/

By Rob Gutro
NASA's Goddard Space Flight Center

Credit: 
NASA/Goddard Space Flight Center

High-speed photos shine a light on how metals fail

image: An alloy sample being stretched in front of the laser-high speed camera set up

Image: 
Aalto University

How things deform and break is important for engineers, as it helps them choose and design what materials they're going to use for building things. Researchers at Aalto University and Tampere University have stretched metal alloy samples to their breaking point and filmed it using ultra-fast cameras to study what happens. Their discoveries have the potential to open up a whole new line of research in the study of materials deformation.

When materials get stretched a bit, they expand, and when the stretching stops, they return to their original size. However, if a material gets stretched a lot, they no longer return back to their original size. This over-stretching is referred to as "plastic" deformation. Materials that have begun to be plastically deformed behave differently when they're stretched even more, and eventually snap in two. Some materials - including the lightweight aluminium alloys used in high tech applications like cars and aircraft - start to deform unpredictably when they become plastically deformed. The specific problem the researchers were interested in solving is called the Portevin-Le Chatelier (PLC) effect, where bands of deformation in the material move as it gets stretched. The movement of these bands causes the unpredictable deformation, and researchers wanted to develop a better understanding of how they moved, to be able to better predict how these materials would deform. 'There were models for how these materials deformed,' said Professor Mikko Alava, the leader of the research group at Aalto, 'but until now, they weren't very useful.'

To develop the new model, the researchers used very high-speed cameras, illuminated using laser light, to photograph the samples. Once they gathered this data, they were able to see what theoretical models fit the data. They found that a model for the behavior of magnets, called the ABBM model, could be used to predict the behavior of the materials as they deformed really well. The ABBM model is well established in materials science for describing the change of magnetization in magnets. 'The art of the theory of this work was realizing which parameters of the material aligned with the parameters in an evolved version of the ABBM model,' said Professor Alava, 'and then by gathering the large quantity of data that we did, we were able to show how the model could be used to predict deformation in these materials.' The results are being published in Science Advances.

'Until now the time resolution of the experiments has not been sufficient for comparison with this type of model.' said Tero Mäkinen, doctoral candidate with the major responsibility for study. 'The movement of the deformation bands has been studied previously, particularly in the material science community, but one really needs to see the fine detail to be able to show that the bands behave - in some sense - similarly to magnets.'

'It is quite remarkable that two phenomena which are apparently so different -- change of magnetization in magnets and propagation of deformation bands in alloys -- can be described with the same, simple statistical physics model,' says Associate Professor Lasse Laurson from Tampere University, who participated in the study.

The research has been a long time coming 'I first came up with the general idea around 2015,' explains Professor Alava, but now that the model has been shown to apply to the PLC effect in aluminium alloys, the group are interested in testing if it applies to a wider range of metal alloys. 'There are several different types of PLC bands that can exist in materials, we've shown it for one type, and now we want to see if it applies to all of them.'

Credit: 
Aalto University