For example, these microdroplets can reflect incoming sunlight back to outer space, helping to cool a warming planet. Or they can be used to administer drugs to the lungs, especially to treat respiratory ailments.

Thus, the ability to more precisely control how aerosols move is critically important to pharmaceutical sciences and climate research. Aerosol science is also a key aspect of many industries, everything from automobiles to food processing.

Now, scientists have published a study describing a breakthrough device — a new whipping jet aerosol sprayer — that is relatively inexpensive to build and operate.

“We have created a unique, steady-state, gas-focused whipping jet that does not use electricity,” says the lead author Sankar Raju Narayanasamy, PhD, a researcher at Lawrence Livermore National Laboratory, and an affiliate researcher at Berkeley Lab and SLAC National Accelerator Laboratory.

“This development is a significant feat that can have a wide range of applications,” says Narayanasamy, who conducted the research as BioXFEL scholar, a U.S. National Science Foundation-funded research consortium led by University at Buffalo, Hauptman-Woodward Medical Research Institute (HWI) and partner institutions.

Martin Trebbin, PhD, SUNY Empire Innovation assistant professor of chemistry at the University at Buffalo College of Arts and Sciences, is a co-corresponding author of the study.

He says that “fine monodisperse aerosols with controlled sizes are useful in sample environment instrumentation, such as in mass spectrometry, X-ray free-electron lasers (XFELs), and cryo-electron microscopy, which are used to study bio-macromolecules for structural analysis and drug discovery.”

Trebbin, who says that the research is an “important achievement in fluid dynamics and microfluidics,” is a core faculty member of the UB RENEW Institute, and he holds an appointment at the BioXFEL Science and Technology Center.

The technology is described in a study titled “A sui generis whipping instability-based self-sequencing multi-monodisperse 2D Sprays from an anisotropic microfluidic liquid jet device,” which was published Jan. 11 in the Cell Press journal Cell Reports Physical Science.

The study marks a third-generation advancement in liquid jet technology. First came cylindrical liquid jets in 1998, and flat liquid sheet jets followed in 2018.

The new whipping jet is the first of its kind because it produces homogeneous droplets in a two-dimensional profile, says co-corresponding author Hoi-Ying N. Holman, PhD, director of Berkeley Synchrotron Infrared Structural Biology imaging program at Lawrence Berkeley National Laboratory.

In the past 20 years, scientists have tried many ways, such as piezoelectric actuation or local heating, to precisely control the movement of aerosols. Use of those techniques, however, is limited because they tend to alter the specimens that scientists are using the aerosols to study. This is especially true with biological samples.

In the study, researchers discuss the important role that analytical fluid dynamics — a branch of fluid mechanics that uses numerical analysis and data structures to analyze and solve problems involving fluid flows — played in their work.

This includes explaining the “jet diameter, whipping regime and spreading angle” of the devices, says Ramakrishna Vasireddi, PhD, co-first author and a research scientist at SOLEIL, the French synchrotron facility in Paris.

He adds: “The phenomenon is further characterized experimentally by measuring the angle with respect to the flow rate, the distances between droplets, the droplet shapes, and the reproducibility of these parameters.”

In the study, the team also explains how to build such devices, which are relatively inexpensive.

This work was supported by the Cluster of Excellence “The Hamburg Center for Ultrafast Imaging — Structure, Dynamics and Control of Matter at the Atomic Scale” of the Deutsche Forschungsgemeinschaft (DFG). The work was conducted through the Berkeley Synchrotron Infrared Structural Biology (BSISB) Imaging program, which is supported by the U.S. Department of Energy. It was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory.

For the study, published in the journal Ecosphere, scientists analyzed fire severity data from the U.S. Forest Service and Google Earth Engine, across seven major forest types.

They found that in low- and middle-elevation forest types, the average annual area that burned at low-to-moderate severity has decreased from more than 90 percent before 1850 to 60-70 percent today.

At the same time, the area burned annually at high severity has nearly quintupled, rising from less than 10% to 43% today. (High-severity burns are those where more than 95% of aboveground tree biomass is killed by fire.)

Lead author and UC Davis project scientist John N. Williams said this ratio is severely out of balance.

“We’re seeing more ‘bad fire’ and less ‘good fire,” said Williams, who is the coordinator of the California Prescribed Fire Monitoring Program. “Any consolation we’d get from the idea that, ‘At least we’re burning more than we used to,’ isn’t really a consolation because it’s often coming in the form of the wrong kind of fire.”

Good fire, bad fire

Many fire ecologists talk about the need to burn more acreage by putting “good fire” on the ground, such as through prescribed burning, while preventing “bad fire.” In forests like oak woodland, yellow pine and mixed conifer, good fire refers to the low-to-moderate severity burning that the dominant species are adapted to. They are typically ignited by lightning or by people to enrich and restore the land. Many such fires were set by Native Americans before the mid-19th century through the practice of cultural burning.

Before 1850, much more land burned each year in California compared to the present day. The study indicates that gap is beginning to close. Unfortunately, more of what is burning comprises damaging, high-severity fire.

That represents the most concerning result, say the authors: The average area of high-severity burning in the region is now above the best estimates of high-severity burning that took place before Euro-American settlement, even though overall burning in the modern day is still much lower.

“At current or even projected rates of forest management by federal and state agencies, the amount of forest treated or restored is going to be a drop in the bucket compared to the need, and compared to the huge unmanaged areas that are going to burn, often at high severity,” said senior author Hugh Safford, a UC Davis fire ecologist and chief scientist of environmental public benefits corporation Vibrant Planet. “I’m not exaggerating when I say that the very existence of montane conifer forest in California is at risk, especially in the southern part of the state.”

A severe decade

Nine of California’s 10 biggest wildfires occurred within the past decade. The state’s record-breaking 2020 fire year -when nearly 9,900 fires burned 4.3 million acres — was the only year in which the annual area burned exceeded historical levels, but much of that burned at high severity.

The authors say this trend is especially concerning because most of the low- to middle-elevation forest types affected are adapted to low-to-moderate severity burning. Excessively severe fires in these forests can harm landscapes and the habitat and ecosystem services they provide.

Other research carried out by the Safford Lab at UC Davis and its partners has shown that negative effects of severe burning in these forest types are serious and long-lasting to biodiversity, carbon storage, soil biogeochemistry, air quality and forest regeneration.

Getting the right mix

The study’s results highlight the need to better balance fire exclusion with management practices that proactively reduce forest fuels and increase resilience to climate change and other ecological disturbances.

“We need to burn much more each year, but we want the right mix,” Williams said. “The current trend is going in the wrong direction if we want to restore forests and their natural ecological processes.”

The study’s additional coauthors include Nic Enstice of the California Department of Conservation, Zack Steel of the USDA Forest Service Rocky Mountain Research Station, and Alison Paulson of USDA Forest Service Humboldt-Toiyabe National Forest.

However, historically it has been difficult to “read” RNA molecules in their entirety because they are usually thousands of bases long. Instead, researchers have relied on so-called short-read RNA sequencing, which breaks RNA molecules and sequence them in much shorter pieces — somewhere between 200 to 600 bases, depending on the platform and protocol. Computer programs are then used to reconstruct the full sequences of RNA molecules. Short-read RNA sequencing can give highly accurate sequencing data, with a low per-base error rate of approximately 0.1% (meaning one base is incorrectly determined for every 1,000 bases sequenced). Nevertheless, it is limited in the information that it can provide due to the short length of the sequencing reads. In many ways, short-read RNA sequencing is like breaking a large picture into many jigsaw pieces that are all the same shape and size and then trying to piece the picture back together.

Recently, “long-read” platforms that can sequence RNA molecules over 10,000 bases in length end-to-end have become available. These platforms do not require RNA molecules to be broken up before they are sequenced, but they have a much higher per-base error rate, typically between 5% to 20%. This well-known limitation has severely hampered the widespread adoption of long-read RNA sequencing. In particular, the high error rate has made it difficult to determine the validity of novel, previously unknown RNA molecules discovered in a particular condition or disease.

To circumvent this problem, researchers at Children’s Hospital of Philadelphia (CHOP) have developed a new computational tool that can more accurately discover and quantify RNA molecules from these error-prone long-read RNA sequencing data. The tool, called ESPRESSO (Error Statistics PRomoted Evaluator of Splice Site Options), was reported today in Science Advances.

“Long-read RNA sequencing is a powerful technology that will allow us to uncover RNA variation in rare genetic diseases and other conditions, like cancer,” said Yi Xing, PhD, director of the Center for Computational and Genomic Medicine at CHOP and senior author of the study. “We are probably at an inflection point in how we discover and analyze RNA molecules. The transition from short-read to long-read RNA sequencing represents an exciting technological transformation, and computational tools that reliably interpret long-read RNA sequencing data are urgently needed.”

ESPRESSO can accurately discover and quantify different RNA molecules from the same gene — known as RNA isoforms — using error-prone long-read RNA sequencing data alone. To do so, the computational tool compares all long RNA sequencing reads of a given gene to its corresponding genomic DNA, and then uses the error patterns of individual long reads to confidently identify splice junctions — places where the nascent RNA molecule has been cut and joined — as well as their corresponding full-length RNA isoforms. By finding areas of perfect matches between long RNA sequencing reads and genomic DNA, as well as borrowing information across all long RNA sequencing reads of a gene, the tool is able to identify highly reliable splice junctions and RNA isoforms, including those that have not been previously documented in existing databases.

The researchers evaluated the performance of ESPRESSO using simulated data and data on real biological samples. They found that ESPRESSO performs better than multiple currently available tools, both in terms of discovering RNA isoforms and quantifying them. The researchers also generated and analyzed over 1 billion long RNA sequencing reads covering 30 human tissue types and three human cell lines, providing a useful resource for studying human transcriptome variation at the resolution of full-length RNA isoforms.

“ESPRESSO addresses a long-standing problem of long-read RNA sequencing and could usher in new opportunities of discovery,” Dr. Xing said. “We envision that ESPRESSO will be a useful tool for researchers to explore the RNA repertoire of cells in various biomedical and clinical settings.”

This work was supported in part by the Immuno-Oncology Translational Network (IOTN) of the National Cancer Institute’s Cancer Moonshot Initiative (U01CA233074), other National Institutes of Health funding (R01GM088342, R01GM121827, and R56HG012310), along with a National Institutes of Health T32 Training Grant in Computational Genomics (T32HG000046).

Researchers hypothesized that the physical and cognitive demands of orienteering, which integrates exercise with navigation, may stimulate parts of the brain that our ancient ancestors used for hunting and gathering. The brain evolved thousands of years ago to adapt to the harsh environment by creating new neural pathways.

Those same brain functions are not as necessary for survival today due to modern conveniences such as GPS apps and readily available food. Researchers suggest it is a case of “use it or lose it.”

“Modern life may lack the specific cognitive and physical challenges the brain needs to thrive,” says Jennifer Heisz, Canada Research Chair in Brain Health and Aging at McMaster University, who supervised the research. “In the absence of active navigation, we risk losing that neural architecture.”

Heisz points to Alzheimer’s disease, in which losing the ability to find one’s way is among the earliest symptoms, affecting half of all afflicted individuals, even in the mildest stage of the disease.

In the study, published today in the journal PLoS ONE, researchers surveyed healthy adults, ranging in age from 18 to 87 with varying degrees of orienteering expertise (none, intermediate, advanced and elite).

People who participate in orienteering reported better spatial navigation and memory, suggesting that adding elements of wayfinding into regular workouts could be beneficial over the span of a lifetime.

“When it comes to brain training, the physical and cognitive demands of orienteering have the potential to give you more bang for your buck compared to exercising only,” says lead author Emma Waddington, a grad student in the Department of Kinesiology who designed the study and is a coach and member of the national orienteering team.

The goal of orienteering is to navigate by running as quickly as possible over unfamiliar territory, finding a series of checkpoints using only a map and compass. The most skillful athletes must efficiently switch between several mental tasks, making quick decisions while moving across the terrain at a rapid pace.

The sport is unique because it requires active navigation while making quick transitions between parts of the brain that process spatial information in different ways. For example, reading a map depends on a third-person perspective relative to the environment. Orienteers must quickly translate that information relative to their own positions within the environment, in real-time, as they run the course.

It is a skill which GPS systems have engineered out of modern life, say researchers. That may affect not only our ability to navigate but also affect our spatial processing and memory more generally because these cognitive functions rely on overlapping neural structures.

Researchers suggest there are two simple ways to incorporate more orienteering into daily life: turn off the GPS and use a map to find your way when travelling and challenge yourself — spatially — by using a new route for your run, walk or bike ride.

“Orienteering is very much a sport for life. You can often see participants spanning the ages of 6 to 86 years old engaged in orienteering,” says Waddington. “My long-term involvement in this sport has allowed me to understand the process behind learning navigational skills and I have been inspired to research the uniqueness of orienteering and the scientific significance this sport may have on the aging population,” says Waddington.

The new findings, published January 20 in Science Advances, indicate that red sea urchin populations in Southern California may be more vulnerable to climate change than those in Northern California. Although the sea urchins in Southern California are already adapted to warmer conditions, the researchers suspect that further warming of their environment may be more than they can tolerate.

“Red sea urchins from the Southern California population were much more sensitive to environmental changes than those from Northern California, and we think that is likely because they are already closer to some kind of thermal limit,” said senior author Kristy Kroeker, professor of ecology and evolutionary biology at UC Santa Cruz.

First author Emily Donham led the study as a UCSC graduate student and is now a postdoctoral scholar at UC Santa Barbara. “Red sea urchins are an important fishery species along our coast, so understanding how they are likely to be impacted by climate change is very important,” she said.

The study looked at the effects of three key environmental variables in the sea urchins’ coastal habitat: water temperature, dissolved oxygen, and pH (a measure of ocean acidification). Climate change driven by increased carbon dioxide in the atmosphere is warming the oceans and reducing oxygen levels in the water, while increased absorption of carbon dioxide by seawater leads to ocean acidification.

According to Kroeker, most studies looking at the adaptability of species to climate change have focused on one aspect of environmental change, such as warming or ocean acidification. “But all of these species that we are concerned about are embedded in environments with multiple variables that will be affected by climate change,” she said.

Using a network of sensors deployed along the coast, the researchers first characterized the current conditions in Northern and Southern California kelp forests. There are big differences between the coastal waters of Northern and Southern California because of strong seasonal upwelling in the north, which brings to the surface cold deep waters with reduced levels of dissolved oxygen and lower pH (closer to the acidic end of the scale). Coastal upwelling is much weaker in Southern California.

As a result, Northern California sea urchin populations are already exposed to conditions that are more acidic, less oxygenated, and colder than Southern California waters. In the future, however, both regions will experience warmer, more acidic, and less oxygenated waters compared to current conditions.

To study the sensitivity of red sea urchins to these changing conditions, the researchers grew juvenile sea urchins from the two regions in outdoor tanks at UCSC’s Long Marine Laboratory, where they could control the conditions in each tank.

The experiments exposed sea urchins from both populations to the average conditions in each of the two regions for temperature, dissolved oxygen, and pH. The results clearly showed that red sea urchin populations are adapted to their home environments and experience increased mortality when raised in different conditions. Southern California sea urchins fared poorly under Northern California conditions, and vice versa.

The researchers also exposed red sea urchins to the future conditions expected for their home regions based on regional climate projections for the year 2100. These future conditions generally do not overlap with the range of conditions currently measured along the coast.

Although mortality increased in populations from both regions under the projected future conditions, the Northern California sea urchins experienced lower mortality and had better body condition than the Southern California sea urchins.

“Despite the Northern California populations being in more acidic, lower-oxygen conditions in the future, it was the Southern California populations that were much more impacted,” Kroeker said.

This was a surprise, she said, because the Northern California populations are adapted to seasonal changes in which temperature, dissolved oxygen, and pH all decrease in concert, whereas with climate change this tightly coupled variation, or “covariance structure,” will be broken. Dissolved oxygen and pH will decrease further, but temperature will increase.

“It’s breaking down the environmental covariance structure they’re adapted to, so our prediction was that this would make them more vulnerable. But that’s not what we found,” Kroeker said.

The findings suggest that water temperature is a critical environmental variable for red sea urchins. With warmer temperatures to begin with, the coastal waters of Southern California may not have to get much warmer to reach temperatures inhospitable to red sea urchins.

“We should not assume that a species’ vulnerability to climate change is the same across its whole range,” Kroeker said. “Each population is adapted to local conditions, and not all populations are going to respond similarly to global climate change.”

In addition to Donham and Kroeker, the coauthors include Iris Flores, Alexis Hooper, and Evan O’Brien at UC Santa Cruz; Kate Vylet and Jan Freiwald at Reef Check Foundation; and Yuichiro Takeshita at Monterey Bay Aquarium Research Institute. This work was supported by the UC Institute for the Study of Ecological and Evolutionary Climate Impacts (ISEECI) and the California Ocean Protection Council.

In a recent study at the University of Missouri, Emma Teixeiro, an associate professor in the MU School of Medicine, and her team analyzed how immunological memory — the memory the body’s immune system retains after an infection or vaccination that helps protect against reinfection — gets generated and maintained, as well as the role inflammation plays in shaping that immunological memory.

“Our immune system defends us from disease, but it is a very complicated system with many interactions occurring, and if things get dysregulated, it may actually play a role in causing disease,” said Teixeiro, who works in the NextGen Precision Health Institute on MU’s campus. “So, our research focuses on better understanding how these immune responses can be generated and controlled, specifically by looking at the critical role T cells play, as T cells help protect the body from infection and may play a role in attacking cancer.”

Using a mouse model, the researchers created various strains of pathogenic bacteria that increased levels of inflammation through the stimulator of interferon genes — or STING — proteins inside of T cells. While many scientists assumed this increase in inflammation would result in a stronger immune response and therefore stronger immunological memory, Teixeiro and her team found the opposite: immunological memory was reduced.

“Some scientists in the field believe STING activation may be targeted to improve cancer vaccines or immunotherapies, so gaining a basic understanding of all the interacting mechanisms at play is critical to reduce the chances of unintended consequences or harmful side effects,” Teixeiro said. “We want to better understand how to regulate immunological memory, which has implications for potential vaccines or immunotherapies that trigger T cells in a way that hopefully boosts long-term memory, so our bodies are protected from disease over time.”

While her research is fundamental in nature, Teixeiro’s findings have the potential to contribute to the development of more effective treatments to help patients suffering with cancer, chronic obstructive pulmonary disease (COPD), STING-associated vasculopathy with onset in infancy (SAVI), asthma and other chronic inflammatory syndromes.

“The pursuit of knowledge is what drives my curiosity as a scientist,” Teixeiro said. “While there are still more questions to answer, this research is a small step in the right direction, and I am proud to be a part of it.”

“STING controls T cell memory fitness during infection through T cell intrinsic and Indoleamine-pyrrole 2,3-dioxygenase (IDO) dependent mechanisms” was recently published in PNAS. Coauthors on the study include Michael Quaney, Curtis Pritzl, Rebecca Newth, Karin Knudson, Vikas Saxena, Caitlyn Guldenpfennig, Diana Gil, Chris Rae, Peter Lauer, Mark Daniels and Dezzarae Luera.

The team built a new type of fluorescence imaging system that allows them to use light to see how a mouse heart responds to hormones and neurotransmitters in real time. The mice were exposed to noradrenaline, also known as norepinephrine. Noradrenaline is both a neurotransmitter and hormone associated with the body’s “fight or flight” response.

The results reveal that male and female mouse hearts respond uniformly at first after exposure to noradrenaline. However, some areas of the female heart return to normal more quickly than the male heart, which produces differences in the heart’s electrical activity.

“The differences in electrical activity that we observed are called repolarization in the female hearts. Repolarization refers to how the heart resets between each heartbeat and is closely linked to some types of arrhythmias,” said Jessica L. Caldwell, first author of the study. Caldwell is a postdoctoral scholar in the UC Davis School of Medicine Department of Pharmacology.

“We know that there are sex differences in the risk for certain types of arrhythmias. The study reveals a new factor that may contribute to different arrhythmia susceptibility between men and women,” Caldwell said.

Heart disease is the leading cause of death in the U.S.

Heart disease is the leading cause of death for both men and women in the United States. It accounted for about 1 in every 4 male deaths and 1 in every 5 female deaths in 2020. Despite the impact on both sexes, cardiology research has largely been performed on male subjects.

In this study, the researchers were interested in looking at factors that may contribute to arrhythmias. Arrhythmias are a type of heart disorder where the electrical impulses that control heartbeats don’t function properly. They affect somewhere between 1.5% to 5% of the population.

Methods

The novel imaging system uses a mouse, called the CAMPER mouse, that has been genetically modified to emit light during a very specific chemical reaction in the heart — cAMP binding.

The cAMP molecule (an abbreviation of cyclic adenosine 3′,5;-monophosphate) is an intermediate messenger that turns signals from hormones and neurotransmitters, including noradrenaline, into action from heart cells.

The light signals from the CAMPER mouse are transmitted by a biosensor that uses fluorescence resonance energy transfer (FRET). This FRET signal can be picked up at high speed and high resolution by a new imaging system specially designed for hearts. This allows the researchers to record the heart’s reaction to noradrenaline in real time, along with changes in electrical activity.

This new imaging approach revealed the differences in the breakdown of cAMP in female and male mice and the associated differences in electrical activity.

Including female mice leads to discoveries

The researchers had not planned to study sex-based responses, according to Crystal M. Ripplinger, senior author of the study. But the researchers started seeing a pattern of different reactions, which led them to realize the differences were sex-based.

Ripplinger, an electrical and biomedical engineer, is a professor in the Department of Pharmacology.

When she started her lab at the UC Davis School of Medicine over a decade ago, she exclusively used male animals. That was the norm for most research at the time. But several years ago, she began including male and female animals in her studies.

“Sometimes the data between the two sexes is the same. But if the data start to show variation, the first thing we do is look at sex differences. Using both male and female mice has revealed clues into differences we would never have suspected. Researchers are realizing you can’t extrapolate to both sexes from only studying one,” Ripplinger said.

She notes that with the current study, it’s not clear what the differences in cAMP and electrical activity may mean.

“The response in the female mice may be protective — or it may not. But simply documenting that there is a measurable difference in the response to a stress hormone is significant. We are hoping to learn more in future studies,” Ripplinger said.

Additional authors on the study include I-Ju (Eric) Lee, Lena Ngo, Lianguo Wang, Donald M. Bers, Manuel F. Navedo and Julie Bossuyt from UC Davis; Sherif Bahriz from UC Davis and Mansoura University; Bing (Rita) Xu and Yang K. Xiang from UC Davis and VA Northern California.

This work was supported by grants from the National Institutes of Health, the American Heart Association, and the Veterans Administration Merit Grant.