Tech

With outbreaks of infectious diseases making headlines around the world, scientists are under pressure to understand the drivers that influence the transmission of pathogens in order to better predict and control disease outbreaks.

A new research study led by Professor Kathleen Alexander of the College of Natural Resources and Environment explores the ways that landscapes can influence animal behavior, fostering dynamics that either encourage or limit the spread of infectious diseases.

By observing banded mongoose populations across a range of environments in Botswana, researchers were able to gain insight into the manner in which land type and animal behavior interact to influence the spread of a novel tuberculosis pathogen that is transmitted through olfactory communication behaviors.

The study, published in the journal Frontiers in Ecology and Evolution, was funded with an award from the National Science Foundation's Evolution and Ecology of Infectious Diseases program.

"Banded mongoose use scent marking to communicate information to other individuals, a central fitness behavior in this and many other species," explained Alexander, faculty member in the Department of Fish and Wildlife Conservation and an affiliate of the Fralin Life Sciences Institute. "Scent marks are deposited into the environment and contain odor signals that convey information from one mongoose to another."

"The novel tuberculosis pathogen we've discovered has essentially hijacked mongoose communication pathways: as they communicate information with other mongoose, they can also transmit the tuberculosis pathogen," she continued.

Working through the Chobe Research Institute and Centre for the Conservation of African Resources: Animals, Communities, and Land Use (CARACAL) that she co-established in northern Botswana, Alexander and former graduate student Carol Anne Nichols utilized radio collars and camera traps with remote sensors in den sites to monitor mongoose behaviors. In this way, the researchers could observe mongoose without influencing their behavior and were able to study them in protected park landscapes, urban environments, and other locations with varying characteristics. The result was a comprehensive data set of mongoose behavioral interactions across a range of landscape types.

"What we found is that land type significantly influences the interaction of vigilance -- watching out for predators or competitors -- with scent marking behavior," Alexander said. "This has the potential to change pathogen transmission and, where scent marking is elevated, create superspreading landscapes."

"When the mongoose were in Chobe National Park, for example, they had to be vigilant against predators," explained Nichols, who earned her master's in fisheries and wildlife sciences from Virginia Tech in 2018. "They were less likely to participate in scent marking or communicating with other mongoose. If you're running from a predator, you're not stopping to leave a message for other animals. You're running for your life."

But at tourism lodges, vigilance in mongoose was largely associated with the detection of other mongoose that might move in to take advantage of food and denning opportunities. Here, there was an increase in olfactory communication behaviors. In these environments, predators that might injure or kill mongoose were largely excluded.

Alexander notes that these insights demonstrate the importance of understanding complex land-behavior interactions when trying to predict disease distribution and transmission dynamics.

"Banded mongoose are social animals and live in territories, which is what makes this particular transmission method and these findings so interesting," Alexander explained. "By utilizing olfactory communication behaviors, the pathogen can circumvent territorial boundaries because individuals from adjacent territories will come and smell the scent marks. But, as we found here, it matters where an animal lives and how it behaves in that environment.

"Infectious diseases will continue to emerge as we have seen again with the novel coronavirus," she added. "Our results suggest an urgency in understanding how landscape types influence animal behavior and how these interactions might increase or decrease the potential for disease to be transmitted between animals and humans."

Researchers at the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan have identified a new mechanism that helps animals to develop with precise and constant form.

The reproducibility of form, shape, and characteristic appearance is a key feature of our development that is made possible because their instructions are coded in our DNA. What is perplexing, however, is how this reproducibility is achieved despite genetic variation and developmental "noise" resulting from environmental, physical and chemical fluctuations. Recent work in fruit flies has suggested that "noise-cancelling" mechanisms in the embryo rely on a detailed and highly reproducible genetic "blueprint" with specific instructions down to the single-cell level.

Now, in research published in Developmental Cell, an international team led by Yu-Chiun Wang at RIKEN BDR asked whether this blueprint is sufficient to explain developmental consistency, or whether it is helped by alternative noise-cancelling mechanisms. Their findings indicate a previously overlooked role for the mechanical forces that sculpt the embryo, as they turn out to be the noise-producing culprit as well as the key to ensuring precision - a true double-edged sword!

In their work, the team investigated a structure called the cephalic furrow in the fruit fly embryo, in which the surface of the embryo folds along a straight line in an origami-like fashion. To make this fold, the cells deploy a molecule called myosin to exert mechanical forces that shorten the cells making up the fold. What was surprising, however, was that on average 20% of the cells did not receive the instructions to become part of the cephalic furrow. It turned out that the information of where to make a fold was precise, but the reading of this information was unexpectedly sloppy. As a result, myosin distribution was highly variable, resulting in a discrepancy between the blueprint information and cell behavior. "These results were very puzzling as generations of developmental biologists were in awe of how the genetic blueprint could instruct machine-like precision of development," says Wang.

To find out how the embryo folds along a straight crease as in an origami despite this "noise", the researchers looked more broadly across the tissue and realized that myosin is polarized along the direction parallel to the forming crease. They hypothesized that, powered by myosin, the cell membranes pull on each other, creating a form of mechanical communication that allows a straightened ribbon-like structure to emerge out of a fuzzy zone of stochastic membrane contraction. It appeared that this myosin-dotted ribbon is the crease of the developing cephalic furrow.

To show that this was indeed the case, the scientists cut the ribbon used a sharply focused laser beam to inactivate myosin in a small number of cells. They found that the cephalic furrow developed a kink, indicating that the straightness of the folding requires an intact ribbon of contractile membranes. Computer simulations also confirmed that tissue folding based on polarized contractile forces indeed can overcome the noise in contractile forces.

The conclusion of this study is that the constancy of animal form requires more than just the deterministic process of genetic inheritance and genetic networks, but also relies on the stochastic and emergent behaviors of mechanical forces. "This work taught us that constancy in biology stems not only from its regulatory complexity, but also from the unique noise-and-self-correction principle of self-organization. This is a missing chapter in developmental biology textbooks," Wang says. Wang also thinks that by the same token, pathological processes that involve growth, reorganization and changing cell and tissue shapes, such as tumor formation and cancer metastasis, must also contain an element of mechanical self-organization, alongside the well-known factor of genetic susceptibility. "The cephalic furrow is a very pronounced structure," he continues, "yet it forms and disappears about one hour after its initiation. This mysterious, beautiful and yet ephemeral structure of "epithelial origami" continues to mesmerize us and teach us things that we haven't yet understood about animal development."

PLYMOUTH MEETING, PA [March 12, 2020] -- New research from the American Cancer Society in the March 2020 issue of JNCCN--Journal of the National Comprehensive Cancer Network finds that younger cancer survivors are more likely to experience significant financial strain for daily living necessities, such as food, housing, and monthly bills, even years after diagnosis. Among survivors between ages 18 and 39, 20.4% expressed high levels of worry about paying monthly bills compared to 12.9% of individuals without a history of cancer. Likewise, 6.3% of cancer survivors in that age group reported being unable to afford balanced meals, versus 3.4% of those without a cancer history. The findings were less consistent for survivors in the 40-64 age group, and the disparities disappeared for those 65-and-older.

"This could be because younger cancer survivors are not able to maintain their jobs due to health conditions, and therefore lose their health insurance coverage," explained lead researcher Zhiyuan Zheng, PhD, American Cancer Society, who also worked with researchers from UCLA and The Center for Health Research at Kaiser Permanente on this study. "At the same time, they may have substantial other financial obligations, such as student loans, mortgage obligations, and child-rearing responsibilities. Younger cancer survivors may have had fewer opportunities to accumulate wealth, and for millennials specifically, I think they are living in an economic environment with low interest rates and low saving rates, combined with the rapidly increasing costs of cancer care, they face significant challenges in paying large out-of-pocket costs."

"For survivorship planning, we should address the needs of patients with younger age, lower family income, and a higher number of comorbid conditions, and develop both clinical and health policy interventions to reduce the impact of cancer on nonmedical financial burden and food insecurity in the United States," Dr. Zheng continued.

For this study, the researchers used the 2013-2017 National Health Interview Survey (NHIS), a cross-sectional household survey from the National Center for Health Statistics within the Centers for Disease Control and Prevention. Their sample included 12,141 cancer survivors--defined as those who reported every being diagnosed with cancer or any malignancy by a doctor or other health professional, excluding nonmelanoma skin cancer--(771 age 18-39; 4,269 age 40-64; and 7,101 age 65 and older) and 143,664 individuals without a cancer history (53,262 age 18-29; 60,141 age 40-64; and 30,261 age 65 and older). They sorted financial concerns into categories related to retirement, standard of living, monthly bills, and housing costs. They also assigned a point system to the responses "very worried," "moderately worried," "not too worried," and "not worried at all," in order to quantify the impact these types of concerns were having on the different age groups and cancer-survival groups. They similarly scored food insecurity based on "worry about food running out," "food not lasting," and "unable to afford balanced meals."

The adjusted analyses found that 26.4% of cancer survivors age 18-39 reported severe financial worry, and 12.6% reported severe food insecurity. For the 40-64 year-old cohort, 22.2% reported severe financial worry, and 6.8% severe food insecurity. Among those 65-and-older, 6.9% reported severe financial worry, and 2.3% had severe food insecurity.

"Young adult survivors are more vulnerable to financial instability for many reasons related to the tasks of young adult development, such as early career disruptions, the need for increased child care, costs of fertility treatment, or unexpected costs of medical care," commented Karen M. Fasciano, PsyD, Dana-Farber Cancer Institute, an expert on cancer survivorship and young adults who was not involved in this research. "In addition, the psychological impact of being a cancer survivor as a young adult is greater than for older adults and includes being exposed to uncertainty at an age earlier than most peers. When a negative event has happened one time, it follows that a young person is primed to worry about future uncertainty in life domains including financial and food security."

The researchers call for additional study evaluating the relative impact of different financial hardships on long-term outcomes for cancer survivors. They also highlighted some policies they consider promising steps toward addressing these concerns.

"Congress passed the Deferment for Active Cancer Treatment Act of 2018, which allows patients with cancer to postpone payments on public student loans while they are actively receiving cancer treatment," said Dr. Zheng. "In addition, the Centers for Medicare & Medicaid Services has also expanded Medicare Advantage coverage to allow insurers to include healthy groceries, rides to medical appointments, and home delivered meals in their new benefits for qualified younger people with disabilities. These efforts, plus some state-level Medicaid policies, may provide much-needed help for cancer survivors."

To read the entire study, visit JNCCN.org. Complimentary access to "Worry About Daily Financial Needs and Food Insecurity Among Cancer Survivors in the United States" is available until June 10, 2020.

Colloidal quantum dot (CQD) solar cells have attracted considerable attention due to the advantages of being flexible and lightweight. Besides, they are much easier to manufacture, compared with that of commercial silicon solar cells in use today. A novel technology, capable of maximizing the performance of the existing CQD solar cells has been developed, recently.

A research team, led by Professor Sung-Yeon Jang in the School of Energy and Chemical Engineering at UNIST has developed high?efficiency, solution?processed, hybrid series, tandem photovoltaic devices featuring CQDs and organic bulk heterojunction (BHJ) photoactive materials. The absorption of the organic back?cell effectively compensated the optical loss in the CQD front?cell, which improved the overall photon harvesting.

Quantum dots (QDs) are semiconductor particles with sizes smaller than a few nanometres. As they display interesting phenomena, such as size dependent emission wavelength, the absorption spectra of the solar cell can be quite changeable. In other words, the advantage of QDs is that it shows light absorption in the near-infrared (NIR) region, which other photoactive layers cannot. However, there are some ares in the NIR region where light absorption does not occur, even with QDs.

In the work, researchers developed high-efficiency CQD/organic hybrid series tandem photovoltaic devices, featuring CQDs and organic BHJs as photoactive materials to compensate for the external quantum efficiency (EQE) loss in the NIR region. The NIR?absorbing organic BHJ devices were employed as the back sub?cells to harvest the transmitted NIR photons from the CQD front sub?cells.

In addition, the team optimized the short?circuit current density balance of each sub?cell, and thus created a near ideal series connection using an intermediate layer to achieve a power conversion efficiency (PCE) that is superior to that of each single?junction device. Indeed, the PCE (12.82% ) of the hybrid tandem device was the highest among the reported CQDPVs, including single?junction devices and tandem devices, according to the research team. Besides, researchers also noted that "This study suggests a potential route to improve the performance of CQDPVs by proper hybridization with NIR?absorbing photoactive materials."

Furthermore, the new hybrid tandem solar cells are manufactured at room temperature and use a solution process for easy manufacturing. As a result, this solar cell is affordable, more economical, and having less cost as compared to silicon solar cells. Their lower manufacturing costs also gives them a clear advantage mass production.

"The hybrid tandem device exhibited almost negligible degradation after air storage for 3 months," says Professor Jang. "Moreover, this study suggested the potential to achieve PCE > 15% in hybrid tandem devices by reduction of energy loss in CQDPVs and enhancement of NIR absorption in OPVs."

Nanoengineers at the University of California San Diego developed a safety feature that prevents lithium metal batteries from rapidly heating up and catching fire in case of an internal short circuit.

The team made a clever tweak to the part of the battery called the separator, which serves as a barrier between the anode and cathode, so that it slows down the flow of energy (and thus heat) that builds up inside the battery when it short circuits.

The researchers, led by UC San Diego nanoengineering professor Ping Liu and his Ph.D. student Matthew Gonzalez, detail their work in a paper published in Advanced Materials.

"We're not trying to stop battery failure from happening. We're making it much safer so that when it does fail, the battery doesn't catastrophically catch on fire or explode," said Gonzalez, who is the paper's first author.

Lithium metal batteries fail because of the growth of needle-like structures called dendrites on the anode after repeated charging. Over time, dendrites grow long enough to pierce through the separator and create a bridge between the anode and cathode, causing an internal short circuit. When that happens, the flow of electrons between the two electrodes gets out of control, causing the battery to instantly overheat and stop working.

The separator that the UC San Diego team developed essentially softens this blow. One side is covered by a thin, partially conductive web of carbon nanotubes that intercepts any dendrites that form. When a dendrite punctures the separator and hits this web, electrons now have a pathway through which they can slowly drain out rather than rush straight towards the cathode all at once.

Gonzalez compared the new battery separator to a spillway at a dam.

"When a dam starts to fail, a spillway is opened up to let some of the water trickle out in a controlled fashion so that when the dam does break and spill out, there's not a lot of water left to cause a flood," he said. "That's the idea with our separator. We are draining out the charge much, much slower and prevent a 'flood' of electrons to the cathode. When a dendrite gets intercepted by the separator's conductive layer, the battery can begin to self-discharge so that when the battery does short, there's not enough energy left to be dangerous."

Other battery research efforts focus on building separators out of materials that are strong enough to block dendrites from breaking through. But a problem with this approach is that it just prolongs the inevitable, Gonzalez said. These separators still need to have pores that let ions flow through in order for the battery to work. As a consequence, when the dendrites eventually make it through, the short circuit will be even worse.

Rather than block dendrites, the UC San Diego team sought to mitigate their effects.

In tests, lithium metal batteries equipped with the new separator showed signs of gradual failure over 20 to 30 cycles. Meanwhile, batteries with a normal (and slightly thicker) separator experienced abrupt failure in a single cycle.

"In a real use case scenario, you wouldn't have any advance warning that the battery is going to fail. It could be fine one second, then catch on fire or short out completely the next. It's unpredictable," Gonzalez said. "But with our separator, you would get advance warning that the battery is getting a little bit worse, a little bit worse, a little bit worse, each time you charge it."

While this study focused on lithium metal batteries, the researchers say the separator can also work in lithium ion and other battery chemistries. The team will be working on optimizing the separator for commercial use. A provisional patent has been filed by UC San Diego.

The group headed by Dr. Julia Brailovskaia published their results in the journal "Computers in Human Behavior" from 6. March 2020.

On average a good hour of Facebook every day

The research team recruited 286 people for the study who were on Facebook for an average of at least 25 minutes a day. The average usage time per day was a good hour. The researchers subdivided the test persons into two groups: the control group comprised of 146 people used Facebook as usual. The other 140 people reduced their Facebook usage by 20 minutes a day for two weeks, which is about one third of the average usage time.

All participants were tested prior to the study, one week into it, at the end of the two-week experiment, and finally one month and three months later. Using online questionnaires, the research team surveyed the way they used Facebook, their well-being and their lifestyle.

Not necessary to give it up altogether

The results showed: participants in the group that had reduced their Facebook usage time used the platform less, both actively and passively. "This is significant, because passive use in particular leads to people comparing themselves with others and thus experiencing envy and a reduction in psychological well-being," says Julia Brailovskaia. Participants who reduced their Facebook usage time, moreover, smoked fewer cigarettes than before, were more active physically and showed fewer depressive symptoms than the control group. Their life satisfaction increased. "After the two-week period of Facebook detox, these effects, i.e. the improvement of well-being and a healthier lifestyle, lasted until the final checks three months after the experiment," points out Julia Brailovskaia.

According to the researchers this is an indication that simply reducing the amount of time spent on Facebook every day could be enough to prevent addictive behavior, increase well-being and support a healthier lifestyle. "It's not necessary to give up the platform altogether," concludes Julia Brailovskaia.

UPTON, NY—A team of scientists led by the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory and Lawrence Berkeley National Laboratory has captured in real time how lithium ions move in lithium titanate (LTO), a fast-charging battery electrode material made of lithium, titanium, and oxygen. They discovered that distorted arrangements of lithium and surrounding atoms in LTO “intermediates” (structures of LTO with a lithium concentration in between that of its initial and end states) provide an “express lane” for the transport of lithium ions. Their discovery, reported in the Feb. 28 issue of Science, could provide insights into designing improved battery materials for the rapid charging of electric vehicles and portable consumer electronics such as cell phones and laptops.

“Consider that it only takes a few minutes to fill up the gas tank of a car but a few hours to charge the battery of an electric vehicle,” said co-corresponding author Feng Wang, a materials scientist in Brookhaven Lab’s Interdisciplinary Sciences Department.  “Figuring out how to make lithium ions move faster in electrode materials is a big deal, as it may help us build better batteries with greatly reduced charging time.”

Lithium-ion batteries work by shuffling lithium ions between a positive and negative electrode (cathode and anode) through a chemical medium called an electrolyte. Graphite is commonly employed as the anode in state-of-the-art lithium-ion batteries, but for fast-charging applications, LTO is an appealing alternative. LTO can accommodate lithium ions rapidly, without suffering from lithium plating (the deposition of lithium on the electrode surface instead of internally).

As LTO accommodates lithium, it transforms from its original phase (Li4Ti5O12) to an end phase (Li7Ti5O12), both of which have poor lithium conductivity. Thus, scientists have been puzzled as to how LTO can be a fast-charging electrode. Reconciling this seeming paradox requires knowledge of how lithium ions diffuse in intermediate structures of LTO (those with a lithium concentration in between that of Li4Ti5O12 and Li7Ti5O12), rather than a static picture derived solely from the initial and end phases. But performing such characterization is a nontrivial task. Lithium ions are light, making them elusive to traditional electron- or x-ray-based probing techniques—especially when the ions are shuffling rapidly within active materials, such as LTO nanoparticles in an operating battery electrode.

In this study, the scientists were able to track the migration of lithium ions in LTO nanoparticles in real time by designing an electrochemical cell to operate inside a transmission electron microscope (TEM). This electrochemical cell enabled the team to conduct electron energy-loss spectroscopy (EELS) during battery charge and discharge. In EELS, the change in energy of electrons after they have interacted with a sample is measured to reveal information about the sample’s local chemical states. In addition to being highly sensitive to lithium ions, EELS, when carried out inside a TEM, provides the high resolution in both space and time needed to capture ion transport in nanoparticles.

“The team tackled a multifold challenge in developing the electrochemically functional cell—making the cell cycle like a regular battery while ensuring it was small enough to fit into the millimeter-sized sample space of the TEM column,’’ said co-author and senior scientist Yimei Zhu, who leads the Electron Microscopy and Nanostructure Group in Brookhaven’s Condensed Matter Physics and Materials Science (CMPMS) Division. “To measure the EELS signals from the lithium, a very thin sample is needed, beyond what is normally required for the transparency of probing electrons in TEMs.”

The resulting EELS spectra contained information about the occupancy and local environment of lithium at various states of LTO as charge and discharge progressed. To decipher the information, scientists from the Computational and Experimental Design of Emerging Materials Research (CEDER) group at Berkeley and the Center for Functional Nanomaterials (CFN) at Brookhaven simulated the spectra. On the basis of these simulations, they determined the arrangements of atoms from among thousands of possibilities. To determine the impact of the local structure on ion transport, the CEDER group calculated the energy barriers of lithium-ion migration in LTO, using methods based on quantum mechanics.

“Computational modeling was very important to understand how lithium can move so fast through this material,” said co-corresponding author and CEDER group leader Gerbrand Ceder, Chancellor’s Professor in the Department of Materials Science and Engineering at UC Berkeley and a senior faculty scientist in the Materials Science Division at Berkeley Lab. “As the material takes up lithium, the atomic arrangement becomes very complex and difficult to conceptualize with simple transport ideas. Computations were able to confirm that the crowding of lithium ions together makes them highly mobile.”

“An important aspect of this work was the combination of experiment and simulation, as simulations can help us to interpret experimental data and develop a mechanistic understanding,” said co-author Deyu Lu, a physicist in the CFN Theory and Computation Group. “The expertise in computational spectroscopy we have been developing at CFN over the years plays an important role in this collaborative user project in identifying key spectral fingerprints in EELS and unraveling their physical origin in atomic structures and their electronic properties.”

The team’s analysis revealed that LTO has metastable intermediate configurations in which the atoms are locally not in their usual arrangement. These local “polyhedral” distortions lower the energy barriers, providing a pathway through which lithium ions can quickly travel.

“Unlike gas freely flowing into your car’s gas tank, which is essentially an empty container, lithium needs to “fight” its way into LTO, which is not a completely open structure,” explained Wang. “To get lithium in, LTO transforms from one structure to another. Typically, such a two-phase transformation takes time, limiting the fast-charging capability. However, in this case, lithium is accommodated more quickly than expected because local distortions in the atomic structure of LTO create more open space through which lithium can easily pass. These highly conductive pathways happen at the abundant boundaries existing between the two phases.”

Next, the scientists will explore the limitations of LTO—such as heat generation and capacity loss associated with cycling at high rates—for real applications. By examining how LTO behaves after repeatedly absorbing and releasing lithium at varying cycling rates, they hope to find remedies for these issues. This knowledge will inform the development of practically viable electrode materials for fast-charging batteries.

“The cross-institutional efforts combining in situ spectroscopy, electrochemistry, computation, and theory in this work set a model for conducting future research,” said Zhu.

“We look forward to examining transport behaviors in fast-charging electrodes more closely by fitting our newly developed electrochemical cell to the powerful electron and x-ray microscopes at Brookhaven’s CFN and National Synchrotron Light Source II (NSLS-II),” said Wang. “By leveraging these state-of-the-art tools, we will be able to gain a complete view of lithium transport in the local and bulk structures of the samples during cycling in real time and under real-world reaction conditions.”

The scientists carried out the experimental work using TEM facilities in Brookhaven’s CMPMS Division and the theoretical work using computational resources of Brookhaven’s Scientific Data and Computing Center (part of the Computational Science Initiative). Both CFN and NSLS-II are DOE Office of Science User Facilities. The research was supported by the Laboratory Directed Research and Development program at Brookhaven; DOE’s Office of Energy Efficiency and Renewable Energy (EERE), Vehicle Technologies Office (VTO), under the Advanced Battery Materials Research program; DOE’s Offices of Basic Energy Sciences and EERE VTO; and the National Science Foundation.

Brookhaven National Laboratory is supported by the U.S. Department of Energy’s Office of Science. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit https://energy.gov/science.

Follow @BrookhavenLab on Twitter or find us on Facebook.

Related Links

Scientific paper: "Kinetic pathways of ionic transport in fast-charging lithium titanate"
Brookhaven Lab news release: "Surprising Discovery Could Lead to Better Batteries"
Brookhaven Lab feature story: "Toyota to Use Brookhaven Lab's Center for Functional Nanomaterials to Advance Vehicle Battery Tech"
Brookhaven Lab news release: "Scientists Capture Lithium-Ion Batteries in Nanoscale Action"

Journal

Science

DOI

10.1126/science.aax3520

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Non-small cell lung cancer (NSCLC) is the most commonly diagnosed cancer, and the leading cause of cancer death worldwide. More than half of NSCLC patients die after developing metastases. There are no tests currently that would allow doctors to identify patients where more aggressive therapy could reduce mortality. Researchers at Tulane University have identified a protein on tumor-derived extracellular vesicles that indicates if a NSCLC tumor is likely to metastasize, according to a new study in Science Advances.

The protein could be used as a biomarker to develop a rapid, minimally invasive test to catch these cancers early when they are more treatable, said study author Tony Hu, Weatherhead Presidential Chair in Biotechnology Innovation at Tulane University School of Medicine.

"The goal of any cancer diagnosis and treatment is to catch it early," says Hu. "This information could help diagnose patients who are at high risk for having their cancer metastasize, and treatment could be tailored to account for that. Not all patients have the same type of tumor, and if you can target therapy to address a particular tumor, you can improve outcomes."

Most patients with NCSLC aren't diagnosed until their primary tumor has metastasized to other parts of the body. However, patients even patients diagnosed with non-metastatic NSCLC tumors of the same stage can often have very different treatment outcomes. A marker that could identify which patients are likely to develop metastatic NSCLC, would aid in selecting those patients who should receive different treatment approaches to reduce their risk of metastasis and improve odds for long-term survival. However, no biomarkers identified to date have adequate sensitivity, specificity, or reproducibility for this purpose and most require tumor samples that require invasive procedures that are not suitable for repeated analyses.

All cells shed extracellular vesicles, small membrane particles that carry proteins, RNA and other molecules. These vesicles can bind to and transfer their contents to specific cell types to change the behavior of these cells. Extracellular vesicles shed by cancer cells can alter the environment of both adjacent and distant cells to establish metastatic niches that promote the invasion and growth of circulating tumor cells. Study researchers evaluated proteins carried by extracellular vesicles shed by NSCLC cells to determine which might serve as markers for metastatic NSCLC cells. Hu and his team identified a protein that was highly expressed on extracellular vesicles of metastatic but not nonmetastatic NSCLC cells. This could predict which NSCLC patients were at increased risk for metastasis when its expression was analyzed on extracellular vesicles isolated from their blood.

The next goal of Hu's team is to incorporate the biomarker profiling with their well-developed nanoplasmonic detection assay for a rapid clinical translation.

The world's first minimally-invasive tricuspid valve replacement was performed at St. Michael's Hospital of Unity Health Toronto by Drs. Neil Fam, Mark Peterson and Geraldine Ong.

The 76-year-old male patient who underwent the procedure - a catheter-based tricuspid valve replacement through the femoral vein in his leg - reported a significant improvement in his health within 48 hours of the procedure, which was performed on May 23, 2019.

The team used the EVOQUE tricuspid valve replacement system (Edwards Lifesciences, Irvine, CA). Tricuspid valve replacement procedures are typically performed either through open heart surgery or a thoracotomy, an incision through the patient's ribs. Those surgical methods are effective but due to their more invasive nature, they pose a greater risk of complications for older patients.

"Doing tricuspid valve replacements through the femoral approach is a game changer as it opens up treatment options for patients with heart failure who are too sick to undergo surgery, or are not good candidates for tricuspid clipping. Going through the femoral vein means the risk of complications is dramatically lower," explained Dr. Fam, an interventional cardiologist and the Director of Interventional Cardiology and Cardiac Catheterization Labs at St. Michael's.

Prior to the procedure, the patient explained that low-effort tasks such as getting out of the car or making the short walk from the bedroom to the bathroom proved too difficult. After the procedure, he could resume these tasks and many other daily activities with great ease.

Since the world-first procedure, the St. Michael's Structural Heart team has performed multiple tricuspid valve replacement procedures using the femoral approach, with the other patients reporting similarly significant improvements in their health.

The EVOQUE heart valve was first used for mitral valve replacement. Just over two years ago, Dr. Fam approached Edwards to discuss if EVOQUE might be effective for tricuspid valve replacements as well, and this led to a great partnership that brought this idea to reality.

For the past five years, St. Michael's has been a world leader in transcatheter tricuspid valve interventions, in which tricuspid valves are repaired using MitraClip and PASCAL repair systems. However, some patients' tricuspid valves were irreparable and the challenge was to develop a safe and effective procedure to entirely replace the tricuspid valve. The early results with EVOQUE tricuspid valve replacement are very encouraging and further studies are planned.

This world first has just been published in the Journal of the American College of Cardiology: Cardiovascular Interventions, with further publications planned.

Oxford, March 11, 2020 - In a new retrospective study, researchers found that the use of immunosuppressive therapy does not increase the occurrence or recurrence of vulvar or vaginal cancer in women with inflammatory bowel disease (IBD). However, earlier onset of cancer was reported, and lymphomas were found in some patients, which is very rare in the genital tract. Their results appear in Digestive and Liver Disease, published by Elsevier.

Immunosuppressive drugs are the cornerstone for treatment of IBD, but they have been associated with an increased risk of certain cancers including lymphoma and urinary tract cancer. A team of researchers in The Netherlands and the Dutch Workgroup on IBD and Vulvovaginal Neoplasia investigated whether the use of these drugs also increases the risk of vulvar and vaginal cancer.

The researchers retrieved histopathological data of all IBD patients with vulvovaginal malignancies from the nationwide network and registry of histopathology and cytopathology reports in the Netherlands (PALGA) over a 24-year period, from 1991 to 2015. Medical histories for these patients were obtained from their treating physicians, including demographics, medication history, HPV status, smoking, and use of immunosuppressive drugs.

The rate of vaginal and vulvar carcinoma or pre-stage neoplasia in IBD patients did not differ significantly from that of the general population, the researchers found. In addition, in patients with IBD the use of immunosuppressive drugs did not increase the rate of these diseases. However, IBD patients who were treated with immunosuppressive therapy were, on average, 11 years younger than other IBD patients when their vaginal or vulvar cancer was diagnosed. Sixty-seven percent of the women with vulvovaginal cancers had Crohn's disease versus 33 percent with ulcerative colitis.

"A high percentage of HPV-related tumors might explain the younger age at diagnosis. HPV is strongly associated with higher rates of vaginal cancer in the general population, and other research suggests that IBD patients are at an increased risk for other cancers including cervical cancer," explained investigator Maxine D. Rouvroye, MD, PhD Candidate, Amsterdam UMC, Vrije Universiteit Amsterdam, Gastroenterology and Hepatology, Amsterdam Gastroenterology & Metabolism, Amsterdam, The Netherlands. "Unfortunately, our data on HPV status are incomplete, as HPV status was analyzed in very few cases."

In a commentary accompanying the article, Vito Annese, MD, Valiant Clinic & American Hospital, Dubai, United Arab Emirates, noted, "These malignancies are clearly more frequent in Crohn's disease patients, were frequently very advanced at the time of diagnosis, and sometimes atypical. Although the authors did not find evidence for more advanced screening yet, it is cautious to recommend yearly gynecological surveillance starting at 40, especially in patients with Crohn's disease who are under immunosuppressive therapy."

A new Simon Fraser University-led study looking at the effects that glacier retreat will have on western North American Pacific salmon predicts that while some salmon populations may struggle, others may benefit.

The research, published today in the journal BioScience, examined the multiple ways in which salmon might be affected by climate-change driven glacier retreat over the coming decades. The researchers predict that in southern watersheds the loss of cold glacier meltwater during summer months could lead to low water flows and warmer water temperatures, both challenges for adult and young salmon.

However, in more northern watersheds, glacier retreat may create new salmon habitat.

Eighty-five per cent of major salmon watersheds or regions in western North America currently have at least some glacier coverage. Glaciers in this region are expected to lose up to eighty per cent of their ice volume by the year 2100, with significant implications for salmon habitat availability, water flows, and water temperatures.

SFU PhD candidate Kara Pitman, the study's lead author, says, "In regions where the landscape is still dominated by glaciers, such as in south-central Alaska, massive glaciers are currently peeling back from low-lying valleys, creating new rivers and lakes that young salmon can use as they develop," Pitman says.

"Salmon evolved over millennia in rivers that were dynamic and ever-changing," she says. "If given enough time, salmon are well-adapted to cope with the landscape changes associated with glacier retreat."

Unfortunately, dwindling glacier ice is just one of many sources of rapid change in salmon ecosystems. The authors caution that glacier retreat is adding one more pressure on salmon systems that are already stressed by climate change, habitat destruction, and hatchery practices that erode salmon biodiversity.

SFU professor and co-author Jonathan Moore says this study highlights the need for forward-looking perspectives on salmon conservation and management. "In this era of rapid global change, there is an urgent need to protect and manage for the future of salmon and their ecosystems, not just the present," Moore says.

Conserving natural habitat around strawberry fields can help protect growers' yields, their bottom line and the environment with no detectable threat to food safety, indicates a study led by the University of California, Davis.

In the study, published in the journal Ecological Applications, researchers conducted grower surveys and experiments at 20 strawberry farms stretching between Santa Cruz, Watsonville, and Salinas on California's Central Coast--a region that produces 43 percent of the nation's strawberries.

"Our results indicate that strawberry farmers are better off with natural habitat around their farms than without it," said lead author Elissa Olimpi, a postdoctoral researcher in the lab of Daniel Karp, assistant professor with the UC Davis Wildlife, Fish and Conservation Biology department.

CONSERVING HABITAT SAVES GROWERS MONEY

The study's models indicate that adding natural habitat can decrease crop damage costs by 23 percent. Removing natural habitat can increase costs up to a whopping 76 percent.

Critically, farms with more natural habitat showed no evidence of higher fecal contamination on or surrounding strawberry plants. Also, while bird feces were regularly encountered on the ground, only 2 of 10,000 berries examined showed signs of direct fecal contamination. Those berries would be removed from food production during the hand-harvesting process.

"We found no evidence that conserving habitat presented a food safety risk," Olimpi said.

FOOD SAFETY AND NATURAL HABITAT

The results run contrary to market-driven farm management practices that encourage habitat removal to decrease bird fecal contamination and crop damage. Natural habitat includes forests, grasslands, wetlands, and shrubs.

Those measures were developed in response to a deadly outbreak of E. coli in 2006 that was traced to spinach grown in the region. Since then, private food safety protocols and public regulations were designed to help avert further foodborne illness crises. Yet some requirements may compromise environmental and social sustainability, as a 2019 study by Olimpi describes.

Between 2006 and 2009, roughly 13 percent of the riparian habitat along the Salinas River was removed in response to food safety reforms, notes a 2013 study.

MUTING THE NEGATIVE

The study notes that wild birds did create crop damage in some cases, particularly at the edges of farms. And while they help control insects, some of those are beneficial insects. But overall, the presence of natural habitat muted the effects of birds on farms and associated damage costs.

In other words, says Olimpi: "No matter your crop damage, birds will be more beneficial when you have natural habitat. We think the natural habitat is providing what they need, so the strawberry field isn't this oasis for them."

The work is part of a larger research goal to explore how agricultural landscapes can both support and benefit from biodiversity and ecological communities.

"The future of many species hinges on them being able to survive in working landscapes," Olimpi said. "If we can find those opportunities in agriculture where we can enhance biodiversity and production, that's the golden ticket."

Using data from the Dark Energy Survey (DES), researchers have found more than 300 trans-Neptunian objects (TNOs), minor planets located in the far reaches of the solar system, including more than 100 new discoveries. Published in The Astrophysical Journal Supplement Series, the study also describes a new approach for finding similar types of objects and could aid future searches for the hypothetical Planet Nine and other undiscovered planets. The work was led by graduate student Pedro Bernardinelli and professors Gary Bernstein and Masao Sako.

The goal of DES, which completed six years of data collection in January, is to understand the nature of dark energy by collecting high-precision images of the southern sky. While DES wasn't specifically designed with TNOs in mind, its breadth and depth of coverage made it particularly adept at finding new objects beyond Neptune. "The number of TNOs you can find depends on how much of the sky you look at and what's the faintest thing you can find," says Bernstein.

Because DES was designed to study galaxies and supernovas, the researchers had to develop a new way to track movement. Dedicated TNO surveys take measurements as frequently as every hour or two, which allows researchers to more easily track their movements. "Dedicated TNO surveys have a way of seeing the object move, and it's easy to track them down," says Bernardinelli. "One of the key things we did in this paper was figure out a way to recover those movements."

Using the first four years of DES data, Bernardinelli started with a dataset of 7 billion "dots," all of the possible objects detected by the software that were above the image's background levels. He then removed any objects that were present on multiple nights--things like stars, galaxies, and supernova--to build a "transient" list of 22 million objects before commencing a massive game of "connect the dots," looking for nearby pairs or triplets of detected objects to help determine where the object would appear on subsequent nights.

With the 7 billion dots whittled down to a list of around 400 candidates that were seen over at least six nights of observation, the researchers then had to verify their results. "We have this list of candidates, and then we have to make sure that our candidates are actually real things," Bernardinelli says.

To filter their list of candidates down to actual TNOs, the researchers went back to the original dataset to see if they could find more images of the object in question. "Say we found something on six different nights," Bernstein says. "For TNOs that are there, we actually pointed at them for 25 different nights. That means there's images where that object should be, but it didn't make it through the first step of being called a dot."

Bernardinelli developed a way to stack multiple images to create a sharper view, which helped confirm whether a detected object was a real TNO. They also verified that their method was able to spot known TNOs in the areas of the sky being studied and that they were able to spot fake objects that were injected into the analysis. "The most difficult part was trying to make sure that we were finding what we were supposed to find," says Bernardinelli.

After many months of method-development and analysis, the researchers found 316 TNOs, including 245 discoveries made by DES and 139 new objects that were not previously published. With only 3,000 objects currently known, this DES catalog represents 10% of all known TNOs. Pluto, the best-known TNO, is 40 times farther away from the sun than Earth is, and the TNOs found using the DES data range from 30 to 90 times Earth's distance from the sun. Some of these objects are on extremely long-distance orbits that will carry them far beyond Pluto.

Now that DES is complete, the researchers are rerunning their analysis on the entire DES dataset, this time with a lower threshold for object detection at the first filtering stage. This means that there's an even greater potential for finding new TNOs, possibly as many as 500, based on the researchers' estimates, in the near future.

The method developed by Bernardinelli can also be used to search for TNOs in upcoming astronomy surveys, including the new Vera C. Rubin Observatory. This observatory will survey the entire southern sky and will be able to detect even fainter and more distant objects than DES. "Many of the programs we've developed can be easily applied to any other large datasets, such as what the Rubin Observatory will produce," says Bernardinelli.

This catalog of TNOs will also be a useful scientific tool for research about the solar system. Because DES collects a wide spectrum of data on each detected object, researchers can attempt to figure out where the TNO originated from, since objects that form more closely to the Sun have are expected to have different colors than those that originated in more distant and colder locations. And, by studying the orbits of these objects, researchers might be one step closer to finding Planet Nine, a hypothesized Neptune-sized planet that's thought to exist beyond Pluto.

"There are lots of ideas about giant planets that used to be in the solar system and aren't there anymore, or planets that are far away and massive but too faint for us to have noticed yet," says Bernstein. "Making the catalog is the fun discovery part. Then when you create this resource; you can compare what you did find to what somebody's theory said you should find."

Permanent magnets akin to those used on refrigerators could speed the development of fusion energy - the same energy produced by the sun and stars.

In principle, such magnets can greatly simplify the design and production of twisty fusion facilities called stellarators, according to scientists at the U.S. Department of Energy's (DOE) Princeton Plasma Physics Laboratory (PPPL) and the Max Planck Institute for Plasma Physics in Greifswald, Germany. PPPL founder Lyman Spitzer Jr. invented the stellarator in the early 1950s.

Most stellarators use a set of complex twisted coils that spiral like stripes on a candy cane to produce magnetic fields that shape and control the plasma that fuels fusion reactions. Refrigerator-like permanent magnets could produce the hard part of these essential fields, the researchers say, allowing simple, non-twisted coils to produce the remaining part in place of the complex coils.

Twisted coils most expensive

"The twisted coils are the most expensive and complicated part of the stellarator and have to be manufactured to very great precision in a very complicated form," said physicist Per Helander, head of the Stellarator Theory Division at Max Planck and lead author of a paper describing the research (link is external) in Physical Review Letters (PRL). "We are trying to ease the requirement on the coils by using permanent magnets."

Simplifying stellarators, which run without the risk of damaging disruptions that more widely used tokamak fusion devices face, can hold great appeal. "I am extremely excited about the use of permanent magnets to shape the plasma in stellarators," said Steve Cowley, PPPL director and a coauthor of the paper. "It leads to much simpler engineering design."

Fusion, the power that drives the sun and stars, combines light elements in the form of plasma -- the hot, charged state of matter composed of free electrons and atomic nuclei -- that generates massive amounts of energy. Scientists around the world are using tokamaks, stellarators, and other facilities in the effort to create and control fusion on Earth for a virtually inexhaustible supply of safe and clean power to generate electricity.

The novel idea for permanent magnets is an offshoot of a science fair project that Jonathan Zarnstorff, the son of PPPL Chief Scientist Michael Zarnstorff, a coauthor of the paper, put together in junior high school. Jonathan wanted to build a rail gun, a device that usually uses high-voltage current to generate a magnetic field that can fire a projectile. But the high-voltage current would be dangerous to use in a classroom.

Father and son solution

The solution that father and son arrived at was to use neodymium, or rare earth, permanent magnets to safely produce the magnetic field. Rare earth magnets have surprising and useful properties. They generate quite powerful fields for the magnets' small size, and these are "hard" fields that are almost unaffected by other fields nearby. These magnets could thus provide what physicists call the "poloidal" part of a spiraling stellarator field, while simple round coils could provide the "toroidal" part that makes up the rest of the field. "I'd thought about that over the years but had no time to develop the idea," Zarnstorff said. The notion finally came to fruition during discussions with Cowley and physicist Cary Forest of the University of Wisconsin-Madison.

Permanent magnets are always "on" in sharp contrast to the standard electromagnetic coils that stellarators and tokamaks use. Such coils create magnetic fields when an electric current runs through them -- current that requires power supplies that permanent magnets do not need. Other advantages of the use of permanent magnets to simplify stellarator coils include:

Lower cost than hand-crafted electromagnets;

Creation of ample space between the simplified coils to facilitate maintenance;

Ability to reposition the magnets to create a variety of shapes for the magnetic fields;

Reduced engineering and manufacturing risks.

Permanent magnets have disadvantages, too. "You can't turn them off," Helander said, which means they can pull in anything they can attract within range. They also produce limited maximum field strength, he said. Nonetheless, such magnets "can be great for creating experiments on the way to a reactor," he added, "and stronger permanent magnets may become available."

New set of tools

For Zarnstorff, permanent magnets are "a strategy and a new set of tools, and we have to figure out how to use them." He now plans several uses. First will come construction of a table-top stellarator with permanent magnets installed. Further ahead he hopes PPPL could produce the world's first simple optimized stellarator, one designed to meet specific performance goals. That facility could be upgraded to increase its field strength, in preparation for continued development of the simplified machine. Eventually, a stellarator including permanent magnets might produce energy to generate electricity for all humankind.

TAMPA, Fla (March 11, 2020) -- Bridging integrator 1, known as BIN1, is the second most common risk factor for late-onset Alzheimer's disease, according to genome-wide studies of genetic variants. Yet, scientists know little about what this protein does in the brain.

Now a new preclinical study has discovered that a lack of BIN1 leads to a defect in the transmission of neurotransmitters that activate the brain cell communication allowing us to think, remember and behave. Led by Gopal Thinakaran, PhD, of the University of South Florida Health (USF Health) Morsani College of Medicine and colleagues at the University of Chicago, the study was published March 10 in Cell Reports.

Approximately 40% of people with Alzheimer's disease have one of three variations in the BIN1 gene - a glitch in a single DNA building block (nucleotide) that heightens their risk for the neurodegenerative disease, said the paper's senior author Dr. Thinakaran, a professor of molecular medicine at the USF Health Byrd Alzheimer's Center and associate dean for neuroscience research at the Morsani College of Medicine.

"Our findings that BIN1 localizes right at the point of presynaptic communication and may be precisely regulating neurotransmitter vesicle release brings us much closer to understanding how BIN1 could exert its function as a common risk factor for Alzheimer's disease," Dr. Thinakaran said. "We suspect it helps control how efficiently neurons communicate and may have a profound impact on memory consolidation - the process that transforms recent learned experiences into long-term memory."

The research team created a mouse model in which the BIN1 gene was selectively inactivated, or knocked out, to characterize the protein's normal function in the brain. In particular, they used advanced cell and molecular biology techniques to investigate the role of BIN1 in regulating synapses associated with learning and memory.

To frame the study results, it helps to know that a healthy human brain contains tens of billions of brain cells (neurons) that process and transmit chemical messages (neurotransmitters) across a tiny gap between neurons called a synapse. In the Alzheimer's disease brain, this synaptic communication is destroyed, progressively killing neurons and ultimately causing a steep decline in memory as well as other signs of dementia. Individuals most susceptible to developing full-blown Alzheimer's in later life are those who lose the most synapses, Dr. Thinakaran said.

Among the Cell Reports study highlights:

Loss of BIN1 expression in neurons leads to impaired spatial learning and memory. That is, the deficit alters how effectively information about surrounding environmental space is acquired, stored, organized and used. The BIN1 knockout mice had significantly more difficulty than controls in finding the hidden platform in a Morris water maze.

Further analysis distinguished that BIN1 primarily locates on neurons that send neurotransmitters across the synapse (presynaptic sites) rather than residing on those neurons that receive the neurotransmitter messages (postsynaptic sites). Synaptic transmission in the hippocampus, a brain region associated primarily with memory, showed deterioration in the release of neurotransmitters from vesicles. Vesicles are bubble-like carriers that transfer neurotransmitters from presynaptic to postsynaptic neurons.

The BIN1 deficiency was associated with reduced density of synapses and a decrease in the number of synaptic clusters in the knockout mice compared to controls.

3-D electron microscopy reconstruction of the synapses showed a significant accumulation of docked and reserve pools of synaptic vesicles in the BIN1 knockout mice. That indicates slower (less successful) release of neurotransmitters from their vesicles, the researchers suggest.

The study authors conclude that altogether their work highlights a non-redundant role for neuronal BIN1 in presynaptic regulation and "opens new paths for the future investigation of the precise role of BIN1 as a risk factor in Alzheimer's disease pathophysiology."