Heavens

A new technique may help scientists study the body's immune response to intestinal parasite infections one gut cell at a time, according to a study published today in eLife.

Intestinal parasites are a serious threat to both humans and livestock in large parts of Africa, South America and Asia. The findings, originally posted as a preprint on bioRxiv*, may help scientists understand how adult parasites evade the immune system and to test ways to boost the immune response to fight these infections.

A parasite's larvae may infect humans and other organisms through contaminated food or by penetrating bare skin. Once the parasites grow into adults inside the body, the immune system has a hard time getting rid of them and scientists have found it challenging to study immune cells in infected tissues.

"One big problem has been the difficulty to extract immune cells from an infected gut, as the infection causes very strong local reactions such as intense cellular slime production to try and flush the worms out," says senior author Johannes Mayer, PhD, Research Fellow at the Malaghan Institute of Medical Research in Wellington, New Zealand.

Mayer and colleagues tested many different ways to extract immune cells from the guts of mice infected with an intestinal parasite called Heligmosomoides polygyrus bakeri. Most of their attempts failed, but they eventually developed a technique that isolated millions of immune cells from the infected animals' guts. The technique involves three washes with EDTA, an agent to remove the mucus, lasting for 10 minutes. This is followed by 30 minutes in a solution of enzymes that help break down the tissue into individual cells, and then cell filtration.

"This allowed us to study the individual immune cells for the first time," explains lead author Laura Ferrer-Font, PhD, Staff Scientist at the Malaghan Institute of Medical Research. "We used a new technology called spectral flow cytometry to look at many different types of immune cells all at the same time, and identified various changes that take place throughout the course of parasitic infection."

The team also verified that the immune changes they saw in the cells were representative of the immune changes that occurred in the tissue taken from the infected animals, ensuring that the cell-extraction process did not skew their findings.

"Now that we have found a way to extract immune cells from parasite-infected guts, we can start to answer important questions about the immune response," Mayer concludes. "This technique will enable scientists to use powerful tools like single-cell RNA sequencing to study the immune response in different hosts. It might also help those studying inflammatory bowel disorders or food allergies to extract single cells from the gut for further investigation."

Polymers are long molecules made from periodically connected molecular building blocks called monomers. Some polymers occur naturally in the shape of closed rings - for example as plasmids, cyclic DNA strands in bacteria, or for sufficiently long protein chains. Imagine immersing such objects into a solvent constrained between two parallel plates. We talk about shearing the system when we pull these plates in anti-parallel directions.

Under shear, polymers feature different dynamic modes: "Tumbling" means their swaying and flipping, comparable to the motion of a coin that has been tossed into the air. "Tank-Treading" means the rotation of a polymer ring, comparable to a rolling coin or a bicycle chain. In addition to these modes, rings under shear experience stretching in flow direction, comparable to a stretched rubber band. Like said rubber band, the stretched polymer is under tension. Rotation-, stretching- and alignment behavior were assumed to be the only shear effects on ring polymers - until now.

New movement mode discovered

When simulating these ring polymers, the authors of the study discovered a completely new phase - the so-called "inflation phase". Above a certain shear velocity, they observed a swelling not only in flow direction, but also in the orthogonal one: the stretched ring "opened". Furthermore, the ring stabilized itself, tilted in space with respect to the imposed flow. The formerly typical flipping and tumbling were almost completely suppressed. Polymers of a different topological form, such as linear chains, stars and microgels, do not feature any such behavior. When the scientists increased the shear rate further, eventually tumbling set in again, and the polymer aligned with the flow as expected.

The effect becomes even more pronounced when looking at knotted ring polymers. This is best visualized by tying a knot onto a string and then connecting both ends. The knot can then no longer be untied without cutting the string open. Such a knot is pulled tight under shear. In the context of the inflation phase, the scientists found the tight knot serves as a kind of additional stabilization anchor and suppresses tank-treading as well as tumbling.

Polymers can self-stabilize

The team owes their discovery to a simulation method called Multi-Particle Collision Dynamics, which accounts for local vortices and streams. In the specific case of ring polymers under shear, solvent particles are reflected from the stretched ends and the body of the ring. This leads to the collision of two opposite streams of reflected solvent particles in flow direction near the polymer's center-of-mass. The resulting stream escapes to the sides which causes the ring to open and therefore the observed swelling not only in flow- but also vorticity direction - that is the direction orthogonal to the flow, but parallel to the sheared plates. The resulting flow field relative to the imposed shear is also responsible for the polymer's self-stabilization.

The observed effect shows the importance of considering hydrodynamic interactions and fluctuations for analyzing the behavior of ring-shaped polymers. The new findings are predicted to be employed in future studies on separation methods for rings of different sizes and polymers of different topological forms.

Lithium batteries are found everywhere: They power smart phones, laptops, and electric bicycles and cars by storing energy in a very small space. This compact design is usually achieved by winding the thin sandwich of battery electrodes into a cylindrical form. This is because the electrodes must nevertheless have large surfaces to facilitate high capacity and rapid charging

An international team of researchers from the Helmholtz-Zentrum Berlin and University College London has now investigated the electrode surfaces during charging and discharging using for the first time a combination of two complementary tomography methods. Employing X-ray tomography at the European Synchrotron Radiation Facility (ESRF) in Grenoble, they were able to analyse the microstructure of the electrodes and detect deformations and discontinuities that develop during the charging cycles.

"Neutron tomography, on the other hand, made it possible to directly observe the migration of lithium ions and also to determine how the distribution of the electrolyte in the battery cell changes over time", explains Dr. Ingo Manke, tomography expert at HZB. The neutron tomography data were obtained mainly at the HZB BER II neutron source at the CONRAD instrument, one of the best tomography stations worldwide.

Additional data were obtained at the neutron source of the Institut Laue-Langevin (ILL, Grenoble), where with the help of the HZB team of experts a first neutron imaging station is currently being set up. Following the shutdown of BER II in December 2019, the CONRAD instrument will be transferred to ILL so that it will be available for research in the future.

A new mathematical method developed at the Zuse-Institut in Berlin then enabled physicists to virtually unwind the battery electrodes - because the cylindrical windings of the battery are difficult to examine quantitatively. Only after mathematical analysis and the virtual unwinding could conclusions be drawn about processes at the individual sections of the winding.

"The algorithm was originally meant for virtually unrolling papyrus scrolls", explains Manke. "But it can also be used to find out exactly what happens in compact densely wound batteries."

Dr. Tobias Arlt of HZB continues: "This is the first time we have applied the algorithm to a typical commercially available lithium battery. We modified and improved the algorithm in several feedback steps in collaboration with computer scientists of the Zuse-Institut".

Characteristic problems with wound batteries were able to be investigated using this method. For example, the inner windings exhibited completely different electrochemical activity (and thus Lithium capacity) than the outer windings. In addition, the upper and lower parts of the battery each behaved very differently. The neutron data also showed areas where a lack of electrolyte developed, which severely limited the functioning of the respective electrode section. It could also be shown that the anode is not equally well loaded and unloaded with lithium everywhere.

"The process we have developed gives us a unique tool for looking inside a battery during operation and analysing where and why performance losses occur. This allows us to develop specific strategies for improving the design of wound batteries", concludes Manke.

Boulder, Colo., USA: Recent seafloor drilling has revealed that the “hidden continent

” of Zealandia—a region of continental crust twice the size of India
submerged beneath the southwest Pacific Ocean—experienced dramatic
elevation changes between about 50 million and 35 million years ago. New
findings from this expedition, published today in Geology, propose
this topographic upheaval may have been due to a widespread reactivation of
ancient faults linked to formation of the western Pacific’s infamous Ring of Fire.

Since the 1970s the prevailing scientific wisdom has been that Zealandia’s
unusually low profile is due to the thinning of its crust as it separated
from Gondwana, the ancient supercontinent that included Antarctica and
Australia, around 85 million years ago. After these tectonic fireworks,
says

Rupert Sutherland, a geophysicist at New Zealand’s Victoria University of Wellington and the
paper’s lead author, this model has Zealandia “doing nothing but gently
cooling and subsiding.”

But fossils in the drillcores collected in 2017 by

International Ocean Discovery Program Expedition 371

indicate that during the early Cenozoic, portions of northern Zealandia
rose 1-2 kilometers while other sections subsided about the same amount
before the entire continent sank another kilometer deep underwater. The
timing of these topographic transformations, say Sutherland and his
co-authors, coincides with a global reorganization of tectonic plates
evidenced by the bend in the Emperor-Hawaii seamount chain, the
reorientation of numerous mid-ocean ridges, and the onset of subduction—and
the related volcanism and seismicity—in a belt that still encircles much of
the western Pacific.

Although subduction drives Earth’s plate tectonic cycle, says Sutherland,
scientists don’t yet understand how it starts. The drilling expedition to
Zealandia may offer new insights into this fundamental process. “One of the
amazing things about our observations,” says Sutherland, “is that they
reveal the early signs of the Ring of Fire were almost simultaneous
throughout the western Pacific.” Because this timing predates the global
tectonic plate reorganization, he says, scientists need to find an
explanation for how subduction began across such a broad area in such a
short time.

Sutherland and his co-authors propose a new mechanism: a ‘subduction
rupture event,’ which they argue is similar to a massive, super-slow
earthquake. The researchers believe the event resurrected ancient
subduction faults that had lain dormant for many millions of years.

“We don’t know where or why,” says Sutherland, “but something happened that
locally induced movement, and when the fault started to slip, like in an
earthquake the motion rapidly spread sideways onto adjacent parts of the
fault system and then around the western Pacific.” But unlike an
earthquake, Sutherland says, the subduction rupture event may have taken
more than a million years to unfold. “Ultimately,” he says, “Zealandia’s
sedimentary record should help us determine how and why this event happened
and what the consequences were for animals, plants, and global climate.”

The process has no modern analogue, according to Sutherland, and because
the subduction rupture event is linked to a time of rapid, global plate
tectonic change, other instances of such change in the geologic record may
imply that comparable events have occurred in the past. “Geologists
generally assume that understanding the present is the key to understanding
the past,” he says. “But at least in this instance, this may not hold.”

FEATURED ARTICLE

Continental-scale geographic change across Zealandia during Paleogene
subduction initiation

Contact author Rupert Sutherland: rupert.sutherland@vuw.ac.nz;

https://pubs.geoscienceworld.org/gsa/geology/article/doi/10.1130/G47008.1/581016/Continental-scale-geographic-change-across (open access)

Overview video:
https://www.youtube.com/watch?v=6qCQAvAXLOU&feature=share

Related article:

https://theconversation.com/expedition-reveals-the-violent-birth-of-earths-hidden-continent-zealandia-forged-in-a-ring-of-fire-130860

GEOLOGY articles are online at
http://geology.geoscienceworld.org/content/early/recent. Representatives of
the media may obtain complimentary articles by contacting Kea Giles at the
e-mail address above. Please discuss articles of interest with the authors
before publishing stories on their work, and please make reference to
GEOLOGY in articles published. Non-media requests for articles may be
directed to GSA Sales and Service, gsaservice@geosociety.org.

Journal

Geology

PROVIDENCE, R.I. [Brown University] -- When entrances to caves and mines -- essential roosting places for bats -- are blocked to prevent people from going inside, the gates often include a pipe to allow bats to access their roosts. However, many of the pipes have been constructed with corrugated rings for added strength.

Through field observations, biologist Patricia E. Brown discovered that some bat species will abandon roosts with entrances constructed with these corrugated rings. Now, new research helps to explain why -- the corrugations create unusual acoustic effects that interfere with bats' echolocation and prevent them from navigating properly.

"From a conservation point of view, anything that interferes with the use of individual roosts by bats, particularly species whose populations are threatened, deserves attention to see if it might be mitigated," said James Simmons, a Brown University professor of biology and lead author of the new study published in Scientific Reports this month.

In the study, bats attempted to navigate through two different scenarios in a custom-built flight room: a narrow corridor surrounded by vertically hanging plastic chains to model vegetation, and a tunnel of round plastic hula hoops to model the pattern of raised rings along a corrugated pipe.

The bats were able to successfully navigate through the chain corridor 99 percent of the time, but their success rate dropped to 49 percent when they flew through the hoop tunnel. Flights were considered failures when the bats collided with a chain or hoop, or when they exited the tunnel prior to reaching the end.

The researchers also compared the bats' echolocation patterns during the flights through the hoop tunnel and chain corridor. Past research indicates that bats emit different timing patterns of their sonar sounds when they perform difficult tasks compared to simpler tasks, and this was also the case for the bats in the study. For example, during their flights through the hoop tunnel, the bats emitted more rapid sound pulses, which suggests that the hoop tunnel was cognitively more challenging for them.

Taken together, the results indicate that spaces containing raised rings, like hoops and corrugations, create significant difficulties for bats. This is likely because sound bounces off the rings in confusing ways, which creates the illusion that obstacles are always present in the tunnel, just in front of the bat. These "phantom objects" cause the bats to become disoriented, as they're unable to perceive that the path ahead is clear.

Two of the four bats in the study were able to navigate more effectively through the hoop tunnel with practice, which suggests that raised rings may impair the navigational abilities of some individuals more than others, and that abilities may improve over time.

Going forward, resource managers could try addressing this issue by spraying concrete over the corrugations inside pipes, thereby reducing acoustic distortions and allowing bats to navigate more easily. However, the researchers said further research must be done to explore this issue.

"The corrugations in pipes are similar to the hoops but not identical," Simmons said. "Getting a significant length of corrugated pipe into our flight room is challenging, so one of the next steps might be to survey yet more mines and caves with corrugated pipe entrances to see how commonly they're abandoned by bats. The other step is to find a colony of bats in a mine and give them two entrances -- with corrugated and smooth pipes -- to see if they prefer one to the other. Some of the mines already studied have multiple entrances with different types of gates, and this comparison originally prompted our experiments with the hoops."

Typical examples include paralysis due to a spinal cord injury and visual field atrophy or even complete blindness due to optic nerve atrophy in glaucoma patients. Therefore, in-depth study of the basic biological processes that affect axon regeneration is particularly important for human health. Traditional research on axon regeneration has focused on the cytoskeleton, with a few studies exploring cell membranes. However, because the nervous system is rich in lipids, and the axon regeneration process requires a large amount of lipids to participate in the formation of cell membranes, related research is of great significance. The role of neuronal lipid metabolism on axon regeneration is a mystery that is still waiting to be solved.

The latest study by Prof. LIU Kai, Cheng Associate Professor at The Hong Kong University of Science and Technology's Division of Life Science, started from the direction of lipid metabolism. For the first time, it was found that regulating the glycerolipid metabolism of neurons can promote the regeneration of axons of central neurons after injury.

Researchers first knocked down key genes that are involved in fatty acid metabolism, cholesterol synthesis, and the glycerol phosphate pathway in dorsal root ganglion (DRG) neurons, which were cultured in vitro. After item-by-item testing, it was found that knocking down a gene called lipin1 can significantly promote DRG neurite growth. This indicates that lipid metabolism in neurons has an important effect on the axon regeneration process.

Lipin1 is a key enzyme of the glycerol phosphate pathway because it can catalyze the conversion of phosphatidic acid to diglyceride, which is a substrate for the synthesis of various phospholipids and triglycerides. Triglycerides are the main energy storage substance in mammals, and phospholipids containing phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are the main components of cell membranes.

Lipin1 has two main functions: participating in the synthesis of diglycerides and regulating gene expression in the nucleus. To determine which function is related to axon regeneration, researchers have overexpressed the lipin1 gene with a phosphatase function mutation and nuclear localization sequence deletion in the retinal ganglion cells with lipin1 depletion. They found that its phosphatase function is the main factor affecting axon regeneration.

Researchers also tested the effects of lipin1 elimination on neuronal lipid metabolism to explore which components affect axon regeneration. Their measurements showed the following: cholesterol and fatty acid content in neurons did not change significantly after lipin1 elimination; triglyceride content was significantly reduced; and the PC and PE levels had significantly increased. This suggests that lipin1 may cause neurons to synthesize triglycerides rather than phospholipids. What effect do triglycerides and phospholipids have on axon regeneration? Experiments have revealed that skewing glycerolipid metabolism toward storage triglycerides impedes axon regrowth in injured neurons, while directing it toward phospholipid synthesis promotes the axon regeneration. Therefore, the inhibition of triglyceride synthesis or an increase in phospholipid synthesis can promote axonal regeneration.

The current state of this research was aptly summarized by Professor Liu: "This research provides a new direction for the study of the axon regeneration in the central nervous system. The results provide a new explanation for the difference between the regeneration capacity of the central and peripheral nervous systems, and it may provide new translational targets for CNS injury."

Specialized stringy fluids flow through the human joints and help constitute substances such as mucus. These fluids contain long, flexible molecules like polymers or proteins, giving them the ability to stretch and absorb shock.

However, scientists have yet to fully understand how these enigmatic fluids interact with small-scale biological structures. Structures of particular interest are cilia - tiny hair-like projections attached to the cell membrane, which undulate to perform functions such as clearing contaminants out of airways. These fluid-structure interactions are important for understanding precisely how cilia move to perform their biological duties. However, these interactions occur on such a small scale that they have been difficult to study experimentally.

Now, researchers in the Micro/Bio/Nanofluidics Unit at the Okinawa Institute of Science and Technology Graduate University (OIST) have identified some key features of how these so-called viscoelastic fluids flow around cilia. Viscoelastic fluids are viscous, like molasses, as well as stretchy. The study, published in Small, suggests that it is the fluids' elasticity that drives the patterned movement of the cilia, the researchers say.

Entering the world of the very small

To set up their experiment, the scientists hollowed out microchannels in fused silica glass. These channels contained either one or two flexible cylindrical posts attached to one side of the channel, which represented cilia.

The scientists then used syringe pumps to propel a viscoelastic solution through the glass microchannels at a precisely controlled speed. The experimental fluid contained wormlike micelles (also called living polymers), which are micron-sized flexible structures that mimic the movement of biological molecules present in human body fluids.

The researchers took a series of measurements, using three separate high-powered microscopes with different optical techniques to capture the behavior and properties of the fluid as it interacted with the posts.

First, the scientists used a method called micro-particle image velocimetry to record the velocity of the fluid as it flowed around the posts. They observed that the fluid preferentially moved around one side of the posts, leaving virtually stationary fluid on the other side. At certain flow speeds, however, the fluid on the stationary side began flowing in a jerky motion.

As fluid moved, the post began oscillating. "An important aspect of the study was our ability to carefully track the resulting oscillations of the posts as a function of time using high-speed video microscopy", said Dr. Simon Haward, the group leader of the unit.

Using a method called high-speed polarized light microscopy they were also able to trace the regions around the cylindrical posts where the worm-like micelles stretched elastically, and to correlate the amount of stretching with the position of the posts.

While interacting with the fluid, two posts located near one another began to oscillate in almost perfect synchrony, suggesting that the fluid elasticity is mediating the synchronous beating of a cell's cilia, the researchers say.

"The synchronous time-dynamics of the posts are completely imparted by the fluid itself," said Dr Cameron Hopkins, the first author of the study. "However, this only happens under specific conditions. If we increase the flow rate and thus the influence of the fluid's elasticity, then we lose the regularity of the oscillations and it becomes erratic."

Developing new biological models

Moving forward, the scientists hope to study how changing the flexibility and distances between the cylindrical posts will affect their behavior. Hopkins and his colleagues also hope to repeat the experiment in a larger system with up to twenty cylindrical posts to emulate an array of cilia.

"Our current experimental setup is an idealized geometry -- of course, real biological systems are much more complicated," said Professor Amy Shen, the head of the Micro/Bio/Nanofluidics Unit. "This current model is a stepping-stone to something more complex and more biologically relevant."

The researchers hope that further research will help illuminate the physics of the very small - and perhaps provide insight into the dynamic movements occurring within our very cells.

Access to firearms and other lethal methods of suicide during periods of risk can make it more likely that a suicide attempt will end in death. Yet many patients with suicidal thoughts or behaviors receive no counseling about this from healthcare providers, and many have questions about options for firearm or medication storage.

To address the issue, clinicians and researchers at the University of Colorado School of Medicine at the Anschutz Medical Campus partnered with Grit Digital Health. The team created Lock to Live, a web resource to help suicidal adults - and family, friends or providers - make decisions about reducing access to firearms, medications, and other potential suicide methods.

The self-administered online tool guides a person through detailed questions on storage factors and personal preferences. It then displays storage or disposal options for firearms and medications, including logistical considerations like cost and legal issues.

A pilot trial for Lock to Live was completed at three large emergency departments in Colorado to test the feasibility and acceptability of the tool for adults with suicidal thoughts or behavior. The results were published today in the Journal of Medical Internet Research.

"Efforts in healthcare settings, like providing this tool to change how dangerous items are stored, can make a big difference for people in crisis," said Emmy Betz, MD, MPH, associate professor of emergency medicine at the University of Colorado School of Medicine and director of the project. "This isn't about gun control. It's about helping people take action to keep themselves and their loved ones safe during tough times."

Over ten months, 49 adult patients were enrolled in the trial, with 33 randomized to the Lock to Live intervention group and 16 to the control group. The results include:

Interest in the Lock to Live resource was very high among adults with acute suicide risk. Almost all reported they would recommend it to someone in the same situation.

Participants overwhelmingly found the tool to be useful, informative, and respectful of their values with regard to firearm ownership.

Seventy three percent wanted a print-out of the storage recommendations.

Additionally, the tool proved to be feasible for use in a clinical setting. There were no issues accessing the content via tablet in the emergency department and it didn't interrupt the patient experience, taking only six minutes to complete.

"Lock to Live is an exciting new tool. We don't know yet if it changes behavior or home storage, but other ongoing studies should help answer that question. Its web format has the potential for rapid and widespread dissemination and integration into suicide prevention efforts," said Deborah Azrael, PhD, Director of Research, Harvard Injury Control Research Center, Harvard School of Public Health and co-investigator on the study.

Cigarette butts pile up in parks, beaches, streets and bus stops, places where all types of littering are frowned upon. Best estimates are that over five trillion butts are generated by smokers each year worldwide, and concern about their environmental impact has prompted studies of how they affect water and wildlife habitats. But despite their prevalence, almost no one has studied the airborne emissions coming off these tiny bits of trash.

When Dustin Poppendieck was asked to evaluate them, he was skeptical. As a measurement scientist at the National Institute of Standards and Technology (NIST) he realized there was no standard way of analyzing the amounts of chemicals swirling in the air around cigarettes hours and days after they'd been put out, and he was intrigued. But he also thought there might not be enough chemicals present to make the measurements meaningful.

What his team found, however, was that a used butt -- one that is cold to the touch -- can in one day give off the equivalent of up to 14% of the nicotine that an actively burning cigarette emits.

"I was absolutely surprised," said Poppendieck. "The numbers are significant and could have important impacts when butts are disposed of indoors or in cars." The NIST measurements were performed under an interagency agreement with the Food and Drug Administration as part of its analysis of the overall impact of cigarette smoking on people's lives.

For a long time, most of the health impacts of smoking were misunderstood and often underestimated, in part because the emissions of cigarettes had not been fully assessed. Measurements and epidemiological studies over the last 50 years have improved our understanding of the health impacts of tobacco. We now know a good deal about how cigarette smoking affects smokers' own bodies as they inhale and exhale, referred to as mainstream smoking. Work has also been done to establish the health effects of secondhand smoke, which is the emissions from the end of a cigarette, pipe or cigar, and the smoke that is exhaled by smokers.

More recently, research has also examined thirdhand exposure, which comes from the chemical residue that stays on surfaces such as walls, furniture, hair, clothing and toys after a cigarette has been extinguished. Like mainstream smoking and secondhand smoke, thirdhand exposure can increase the risk of cancers and cause numerous other health problems, especially in the still-developing bodies and brains of infants and children.

The overall goal of the recent NIST study was to quantify the emissions from extinguished cigarettes and discover what happens to those emissions when the butts are left in different environments.

Poppendieck's team measured eight of the hundreds of chemicals typically emitted from cigarettes, including four that are on the FDA list of harmful and potentially harmful constituents.

They also measured triacetin, a plasticizer often used to make filters stiff. Filters were added to cigarettes in the 1950s. While they do collect part of what comes off a burning cigarette, they don't fully negate the exposure from inhaling tobacco smoke. Filters provide a kind of handle for cigarette users who want to avoid burning their lips or fingers, wasting tobacco, or having to pull stray tobacco bits off their tongues. Triacetin can make up as much as 10% of a filter, and its low volatility means it doesn't evaporate quickly at normal temperatures, so it could be a good indicator of long-term emissions from a butt, Poppendieck explained.

The question that Poppendieck and his team considered, therefore, was not the impact of filters on smokers themselves. Rather, they focused on emissions from discarded butts, which are largely just used filters.

"If you have ever sat on a park bench when somebody next to you smoked, then they got up and left their cigarette butt behind, that odor you were smelling is indicative of what we are trying to capture and measure," Poppendieck said. "Anyone with a good sense of smell knows it's there."

The team had to "smoke" over 2,100 cigarettes, although the scientists didn't actually light up and inhale. Instead Poppendieck's team built a "smoking machine" that uses robotic movements to simulate what humans do when they light up. The machine was made to move air through each cigarette in the same way, to remove some potential variables associated with the behavior of actual smokers.

Extinguished cigarettes were placed in a walk-in, stainless steel chamber in order to characterize airborne emissions.

The team also tried to determine if environmental differences in temperature, humidity and saturation in water would change those emission rates.

Most of the chemicals from the extinguished butts were emitted in the first 24 hours, Poppendieck noted. However, nicotine and triacetin concentrations were still about 50% of the initial level five days later.

The team also found that butts emitted these chemicals at higher rates when the air temperature was higher.

"The nicotine coming from a butt over seven days could be comparable to the nicotine emitted from mainstream and sidestream [second- or thirdhand] smoke during active smoking," Poppendieck said. This means if you don't empty an ashtray in your home for a week, the amount of nicotine exposure to nonsmokers could be double current estimates.

Figuring out what to call these newly discovered and measured emissions has been challenging. In the lab, Poppendieck and his team refer to them loosely as "after smoke" or just butt emissions.

No matter what terminology is used, the research team wants people to know that the chemicals remain long after the cigarette goes out. People have been asked to not throw their cigarettes out car windows, because it takes years for the butts to degrade. Poppendieck wants people to also know they can put used butts in sealable metal or glass jars with sand instead of leaving them out in the open.

"You might think that by never smoking in your car when kids are present, you are protecting the nonsmokers or children around you," Poppendieck said. "But if the ashtray in your hot car is full of butts that are emitting these chemicals, exposure is happening."

As a non-regulatory agency of the U.S. Department of Commerce, NIST promotes U.S. innovation and industrial competitiveness by advancing measurement science, standards and technology in ways that enhance economic security and improve our quality of life. More information about NIST can be found at http://www.nist.gov

Working with lead isotopes taken from tooth enamel of prehistoric animals, researchers at the University of Arkansas have developed a new method for assessing the geographic origins of ancient humans.

John Samuelsen, doctoral candidate in anthropology and research assistant at the Arkansas Archeological Survey, analyzed linear patterning of lead isotopes on teeth from a 600- to 800-year-old skull and mandible cemetery at the Crenshaw site in southwest Arkansas. The new method allowed the researchers to compare the ancient human teeth to those of prehistoric animals, as well as rocks and soil samples, taken from the same area.

The research, sponsored in part by the National Science Foundation, was published in the Journal of Archaeological Science.

The Crenshaw site along the Red River is a culturally significant multiple-mound ceremonial center of the Caddo Indians. Previous studies have yielded conflicting interpretations of what the human skulls and mandibles reflect. Some research suggests the remains belonged to victims of violence who came from outside the region, while other research suggests the remains represent a local Caddo Indian burial practice of their own ancestors.

Samuelsen emphasized that a full evaluation of the human remains will be addressed in a future study, but he and Potra found that teeth of five of the 352 individuals tested with the new method contained isotopic signatures consistent with those found in the teeth of prehistoric animals from several sites in the area. Moreover, their isotopic signatures were inconsistent with isotopes from humans and animals from other regions.

"While our focus in this article is to establish a method for using lead isotopes to evaluate ancient human geographic origins," Samuelsen said, "this does suggest that at least these five individuals were from southwest Arkansas."

Lead is a toxic trace metal that affects the health of biological organisms, but it is useful for determining geographic origins. Its isotopic content within human and animal tooth enamel, via food chain pathways, reflects the geology of the region in which an organism grew up. While the lead isotopes from animal teeth were successful at identifying local human remains, versus those from other geographical areas, those isotopes taken from nearby rocks were far too variable to be useful for the same purpose, Samuelsen said. Rock analysis was done by Adriana Potra, associate professor of geosciences, who co-authored the paper.

A major research concern with lead isotope studies is modern, human-caused lead contamination found on soil, rocks and human and animal remains. If modern lead from gas, mines or industrial sources has contaminated the remains, then the lead isotopes will not reflect their original locations. Even if they are uncontaminated by modern lead, the natural soil contains lead that can affect the results similarly. For these reasons, the researchers' study used three different methods to assess contamination and provided recommendations for future research.

With these concerns in mind, the researchers performed isotopic work within the metal-free, modular Radiogenic Isotope Laboratory, a "room inside a room" clean lab at the University of Arkansas. The isotopic and trace element data were collected at the Trace Element and Radiogenic Isotope Laboratory, with help from Erik Pollock, scientific research technician in the Department of Biological Sciences, and Barry Shaulis, research associate in the Department of Geosciences. High accuracy isotopic data were collected on a multi-collector, inductively coupled plasma mass spectrometer. Drilling of teeth was performed with a Leica M80 binocular microscope, housed by Celina Suarez, associate professor of geosciences.

The research project is supervised by George Sabo, director of the Arkansas Archeological Survey. Sabo is Samuelsen's graduate advisor. The research was funded by the Department of Anthropology and the Arkansas Archeological Society, in addition to the National Science Foundation. The study is being conducted in collaboration with the Caddo Nation of Oklahoma to help answer questions the tribe has about the cultural affiliation and origin of the remains.

JUPITER, Fla. --Jan. 20, 2020--The move toward targeted anti-cancer treatments has produced better outcomes with fewer side-effects for many breast cancer patients. But so far, advances in precision medicine haven't reached people diagnosed with so-called triple-negative breast cancer.

An innovative compound developed in the lab of Scripps Research chemist Matthew D. Disney, PhD, offers a new potential route to intervene. Published the week of Jan. 20 in the Proceedings of the National Academy of Sciences, the Disney team's paper describes a compound that, in mice, awakened cancer cells' self-destruct system, killing the cancer cells and stopping their spread, while leaving healthy cells untouched.

While most drugs work by binding to proteins, Disney's compound first latches onto an uncommon target, a molecule called a microRNA precursor, involved in silencing gene transcription. Next it recruits and activates the cell's own disposal system to destroy it. MicroRNA-21 has been called an oncogenic RNA because of its role in metastasis. An abundance of it predicts lower survival in people with triple-negative breast cancer.

Triple-negative breast cancer lacks the traits that would make it sensitive to precision anti-cancer drugs currently available. Between 10 and 15 percent of people with breast cancer receive this diagnosis, as their tumors test negative for estrogen and progesterone sensitivity, as well as HER2 protein production, leaving traditional chemotherapy as the first-line treatment.

"Breast cancer affects one in eight women in their lifetime. Unfortunately, there are no precision medicines for triple-negative breast cancer patients. And often times, these cancers become metastatic--they spread. This metastasis can result in death," Disney says. "We asked ourselves if we could develop a compound that can target genes that cause cancer metastasis and direct triple-negative breast cancer cells to self-destruct."

Disney says a tool he developed in 2014 to identify druggable RNA structures and compounds that would bind to them, called Inforna, revealed the needle in the proverbial haystack, a compound that bound selectively to microRNA-21.

Disney's team combined the optimized compound with a second molecule that recruits and activates an RNA-cutting enzyme, one that is part of our immune system. In this way, the compound enabled destruction of the microRNA-21 target.

Disney has dubbed this precision target-and-destroy system "RIBOTAC," short for "ribonuclease-targeting chimeras." The tool represents a sort of gene-expression editor, precisely deleting disease-linked sequence from RNA.

The Disney team spent considerable effort studying whether the compound Inforna identified was selective, that is, whether it targeted microRNA-21 without producing unintended off-target effects. They searched for significant changes in the breast cancer cells' protein production and found a favorable result.

Matthew Costales, PhD, one of Disney's graduate students, was the paper's first author. Costales says a variety of cell-based and mouse tests produced expected results.

"Generally, proteins involved in genome stability were upregulated while oncogenes were downregulated, consistent with what would occur upon knockdown of microRNA-21," Costales says. "Overall, this translated to a robust decrease in the spread of breast cancer to the lung in a mouse model."

In addition to triple-negative breast cancer, the team found the compound broadly decreased invasiveness in melanoma and lung cancer cell lines that showed aberrant microRNA-21 activity. It had no apparent effect on healthy breast tissue.

Disney says these are early days for a treatment approach that defies convention. Traditional drugs work by binding to proteins because they are structurally more complex than RNA, which has only four bases. The chemistry strategies his team employs overcome that barrier, Disney says.

"It is clear from this study that compounds targeting RNA can be as selective as compounds that target proteins, even those that are designed to destroy toxic sequence," Disney adds. "We anticipate the developing small molecules that target RNAs for destruction will be applied broadly going forward."

Ever since it was proposed that atoms are building blocks of the world, scientists have been trying to understand how and why they bond to each other. Be it a molecule (which is a group of atoms joined together in a particular fashion), or a block of material or a whole living organism, ultimately, everything is controlled by the way atoms bond, and the way bonds break.

The challenge is that lengths of chemical bonds are between 0.1 - 0.3 nm, about half a million times smaller than the width of a human hair, making direct imaging of bonding between a pair of atoms difficult. Advanced microscopy methods, such as atomic force microscopy (AFM) or scanning tunnelling microscopy (STM), can resolve atomic positions and measure bond lengths directly, but filming chemical bonds to break or to form, with spatiotemporal continuity, in real time, still remains one of the greatest challenges of science.

This challenge has been met by a research team from the UK and Germany led by Professor Ute Kaiser, head of the Electron Microscopy of Materials Science in the University of Ulm, and Professor Andrei Khlobystov in the School of Chemistry at the University of Nottingham they have published 'Imaging an unsupported metal-metal bond in dirhenium molecules at the atomic scale' in Science Advances, a journal of the American Association for the Advancement of Science covering all aspects of scientific endeavour.

Atoms in a nano test tube

This group of researchers are known for their pioneering use of transmission electron microscopy (TEM) to film 'movies' of chemical reactions at the single-molecule level, and dynamics of tiny clusters of metal atoms in nanocatalysts utilise carbon nanotubes - atomically thin hollow cylinders of carbon with diameters at the molecular scale (1-2 nm) as miniature test tubes for atoms.

Professor Andrei Khlobystov, said: "Nanotubes help us to catch atoms or molecules, and to position them exactly where we want. In this case we trapped a pair of rhenium (Re) atoms bonded together to form Re2. Because rhenium has a high atomic number it is easier to see in TEM than lighter elements, allowing us to identify each metal atom as a dark dot."

Professor Ute Kaiser, added: "As we imaged these diatomic molecules by the state of the art chromatic and spherical aberration corrected SALVE TEM, we observed the atomic-scale dynamics of Re2 adsorbed on the graphitic lattice of the nanotube and discovered that the bond length changes in Re2 in a series of discrete steps."

A dual use of electron beam

The group have rich track record of using electron beam as a tool for dual-purpose: precise imaging of atomic positions and activation of chemical reactions due to energy transferred from fast electrons of the electron beam to the atoms. The "two-in-one" trick with TEM allowed these researchers to record movies of molecules reacting in the past, and now they were able to film two atoms bonded together in Re2 'walking' along the nanotube in a continuous video. Dr Kecheng Cao, Research Assistant at Ulm University who discovered this phenomenon and performed the imaging experiments, said: 'It was surprisingly clear how the two atoms move in pairs, clearly indicating a bond between them. Importantly, as Re2 moves down the nanotube, the bond length changes, indicating that the bond becomes stronger or weaker depending on the environment around the atoms.'

Breaking the bond

After a period of time, atoms of Re2 exhibited vibrations distorting their circular shapes onto ellipses and stretching the bond. As the bond length reached a value exceeding the sum of atomic radii, the bond snapped and vibration ceased, indicating that the atoms became independent of one another. A little later the atoms joined together again, reforming a Re2 molecule.

Dr Stephen Skowron, Postdoctoral Research Assistant at University of Nottingham who carried out the calculations for Re2 bonding, said: 'Bonds between metal atoms are very important in chemistry, particularly for understanding magnetic, electronic, or catalytic properties of materials. What makes it challenging is that transition metals, such as Re, can form bonds of different order, from single to quintuple bonds. In this TEM experiment we observed that the two rhenium atoms are bonded mainly through a quadruple bond, providing new fundamental insights into transition metal chemistry'.

Electron microscope as a new analytical tool for chemists

Andrei Khlobystov, said: 'To our knowledge, this is the first time when bond evolution, breaking and formation was recorded on film at the atomic scale. Electron microscopy is already becoming an analytical tool for determining structures of molecules, particularly with the advance of the cryogenic TEM recognised by 2017 Nobel Prize in Chemistry. We are now pushing the frontiers of molecule imaging beyond simple structural analysis, and towards understanding dynamics of individual molecules in real time.' The team believe that one day in future electron microscopy may become a general method for studying chemical reactions, similar to spectroscopic methods widely used in chemistry labs.

Astronomers at the National Astronomical Observatory of Japan (NAOJ) have analyzed the paths of two objects heading out of the Solar System forever and determined that they also most likely originated from outside of the Solar System. These results improve our understanding of the outer Solar System and beyond.

Not all comets follow closed orbits around the Sun. Some fly through the Solar System at high speed before heading out to interstellar space, never to return. Although it is simple to calculate where these comets are going, determining where they came from is more difficult.

There are two possible scenarios. In the first scenario, a comet is originally in a stable orbit far from the Sun, but gravitational interactions with a passing object pull the comet out of its orbit. The comet then falls into the inner Solar System where it can be observed before being flung out into interstellar space. In the second scenario, a comet originates someplace very far away, perhaps a different planetary system, and as it flies through interstellar space, by random chance it passes through the Solar System once before continuing on its way.

Arika Higuchi and Eiichiro Kokubo at NAOJ calculated the types of trajectories which would typically be expected in each scenario. The team then compared their calculations to observations of two unusual outbound objects, 1I/'Oumuamua discovered in 2017 and 2I/Borisov discovered in 2019. They found that the interstellar origin scenario provides the better match for the paths of both objects.

The team also showed that it is possible for gas-giant-sized bodies passing close to the Solar System to destabilize long-orbit comets and set them on paths similar to the paths of these two objects. Survey observations have not uncovered any gas-giant-sized bodies which can be linked to these two outbound objects, but further study, both theoretical and observational, of small interstellar objects is needed to better determine the origins of these objects.

Nine sources of extremely high-energy gamma rays comprise a new catalog compiled by researchers with the High-Altitude Water Cherenkov (HAWC) Gamma-Ray Observatory. All produce gamma rays with energies over 56 trillion electron volts (TeV) and three emit gamma rays extending to 100 TeV and beyond, making these the highest-energy sources ever observed in our galaxy. The catalog helps to explain where the particles originate and how they are accelerated to such extremes.

"The Earth is constantly being bombarded with charged particles called cosmic rays, but because they are charged, they bend in magnetic fields and don't point back to their sources. We rely on gamma rays, which are produced close to the sources of the cosmic rays, to narrow down their origins," said Kelly Malone, an astrophysicist in the Neutron Science and Technology group at Los Alamos National Laboratory and a member of the HAWC scientific collaboration. "There are still many unanswered questions about cosmic-ray origins and acceleration. High energy gamma rays are produced near cosmic-ray sites and can be used to probe cosmic-ray acceleration. However, there is some ambiguity in using gamma rays to study this, as high-energy gamma rays can also be produced via other mechanisms, such as lower-energy photons scattering off of electrons, which commonly occurs near pulsars."

For an affiliated video about the research, see Newly Discovered Gamma Ray Sources Have the Highest Energy Ever Recorded

The newly cataloged astrophysical gamma-ray sources have energies about 10 times higher than can be produced using experimental particle colliders on Earth. While higher-energy astrophysical particles have been previously detected, this is the first time specific galactic sources have been pinpointed. All of the sources have extremely energetic pulsars (highly magnetized rotating neutron stars) nearby. The number of sources detected may indicate that ultra-high-energy emission is a generic feature of powerful particle winds coming from pulsars embedded in interstellar gas clouds known as nebulae, and that more detections will be forthcoming.

The HAWC Gamma-Ray Observatory consists of an array of water-filled tanks sitting high on the slopes of the Sierra Negra volcano in Puebla, Mexico, where the atmosphere is thin and offers better conditions for observing gamma rays. When these gamma rays strike molecules in the atmosphere they produce showers of energetic particles. Although nothing can travel faster than the speed of light in a vacuum, light moves more slowly through water. As a result, some particles in cosmic ray showers travel faster than light in the water inside the HAWC detector tanks. The faster-than-light particles, in turn, produce characteristic flashes of light called Cherenkov radiation. By recording the Cherenkov flashes in the HAWC water tanks, researchers can reconstruct the sources of the particle showers to learn about the particles that caused them in the first place.

The HAWC collaborators plan to continue searching for the sources of high-energy cosmic rays. By combining their data with measurements from other types of observatories such as neutrino, x-ray, radio and optical telescopes, they hope to disentangle the astrophysical mechanisms that produce the cosmic rays that continuously rain down on our planet.

Washington, DC-- A long-sought-after class of "superdiamond" carbon-based materials with tunable mechanical and electronic properties was predicted and synthesized by Carnegie's Li Zhu and Timothy Strobel. Their work is published by Science Advances.

Carbon is the fourth-most-abundant element in the universe and is fundamental to life as we know it. It is unrivaled in its ability to form stable structures, both alone and with other elements.

A material's properties are determined by how its atoms are bonded and the structural arrangements that these bonds create. For carbon-based materials, the type of bonding makes the difference between the hardness of diamond, which has three-dimensional "sp3" bonds, and the softness of graphite, which has two-dimensional "sp2" bonds, for example.

Despite the enormous diversity of carbon compounds, only a handful of three-dimensionally, sp3-bonded carbon-based materials are known, including diamond. The three-dimensional bonding structure makes these materials very attractive for many practical applications due to a range of properties including strength, hardness, and thermal conductivity.

"Aside from diamond and some of its analogs that incorporate additional elements, almost no other extended sp3 carbon materials have been created, despite numerous predictions of potentially synthesizable structures with this kind of bonding," Strobel explained. "Following a chemical principle that indicates adding boron into the structure will enhance its stability, we examined another 3D-bonded class of carbon materials called clathrates, which have a lattice structure of cages that trap other types of atoms or molecules."

Clathrates comprised of other elements and molecules are common and have been synthesized or found in nature. However, carbon-based clathrates have not been synthesized until now, despite long-standing predictions of their existence. Researchers attempted to create them for more than 50 years.

Strobel, Zhu, and their team--Carnegie's Gustav M. Borstad, Hanyu Liu, Piotr A. Gu?ka, Michael Guerette, Juli-Anna Dolyniuk, Yue Meng, and Ronald Cohen, as well as Eran Greenberg and Vitali Prakapenka from the University of Chicago and Brian L. Chaloux and Albert Epshteyn from the U.S. Naval Research Laboratory--approached the problem through a combined computational and experimental approach.

"We used advanced structure searching tools to predict the first thermodynamically stable carbon-based clathrate and then synthesized the clathrate structure, which is comprised of carbon-boron cages that trap strontium atoms, under high-pressure and high-temperature conditions," Zhu said.

The result is a 3D, carbon-based framework with diamond-like bonding that is recoverable to ambient conditions. But unlike diamond, the strontium atoms trapped in the cages make the material metallic--meaning it conducts electricity--with potential for superconductivity at notably high temperature.

What's more, the properties of the clathrate can change depending on the types of guest atoms within the cages.

"The trapped guest atoms interact strongly with the host cages," Strobel remarked. "Depending on the specific guest atoms present, the clathrate can be tuned from a semiconductor to a superconductor, all while maintaining robust, diamond-like bonds. Given the large number of possible substitutions, we envision an entirely new class of carbon-based materials with highly tunable properties."

"For anyone who is into--or whose kids are into--Pokémon, this carbon-based clathrate structure is like the Eevee of materials," joked Zhu. "Depending which element it captures, it has different abilities."