Culture

FINDINGS

A preclinical study led by scientists at the UCLA Jonsson Comprehensive Cancer suggests that heating solid tumors during CAR T-cell therapy can enhance the treatment's success.

The researchers found that when a heating technique called photothermal ablation was combined with the infusion of CAR T cells, it suppressed melanoma tumor growth for up to 20 days in mice. Among the mice that were treated with the combination, 33 percent were still tumor free after the 20-day mark.

BACKGROUND

T cells that have been genetically engineered with chimeric antigen receptor, or CAR, have successfully been used to treat many patients with lymphoma and leukemia. But CAR T cell therapy has been less successful for treating solid tumors because the tumors have a protective microenvironment, which makes it harder for the CAR T cells to break into the tumor and keep the T cells activated.

The UCLA scientists decided to test whether combining CAR T therapy with photothermal therapy could overcome that obstacle. Photothermal therapy is a minimally invasive technique that uses heat from laser energy to kill cancer cells; it is already being used to treat a variety of cancers and other medical conditions. The researchers tested a mild hyperthermia about 40 degrees Celsius (about 104 degrees Fahrenheit) to see if it could help enhance the CAR T cells to better attack the tumor.

METHOD

The UCLA-led team tested the technique in mice that were injected with human melanoma tumors. A photothermal agent was injected into the tumors and then irradiated with the laser to heat them. Then, CAR T cells were injected intravenously. Raising the temperature of the laser to about 40 degrees Celsius helped expand blood vessels associated with the tumor, enhancing T cell growth.

IMPACT

By enhancing the power of CAR T cell therapy, the technique could eventually improve the prognosis for people with hard-to-treat solid tumors. The researchers will continue testing the strategy in animals to optimize the heating duration and temperature before determining whether it can be tested on humans.

AUTHORS

Zhen Gu, a professor of bioengineering at the UCLA Samueli School of Engineering, member of the Jonsson Cancer Center and member of the California NanoSystems Institute at UCLA, is the study's co-senior author. The paper's other senior author is Dr. Gianpietro Dotti of the University of North Carolina, Chapel Hill. The first author is Qian Chen, a postdoctoral researcher in Gu's laboratory.

Liposomes are small spherical vesicles with walls comprising two layers of lipids and containing an aqueous core. These artificial structures have been developed for drug delivery or as carriers of active substances in cosmetic products. Another possible application involves the encapsulation of magnetic nanoparticles in liposomes to use them to transmit signals.

This possibility is discussed in an article published by a group of Brazilian researchers supported by São Paulo Research Foundation - FAPESP in Royal Society Open Science.

"Our research belongs to the sphere of basic science but has potential applications in such fields as computational signal transmission, for example. We built a model with two sets of liposomes. One type was nanometric, with a size of about 100 nanometers, and the other was a group of 'giants' measuring 10-20 micrometers," said Iseli Lourenço Nantes Cardoso.

Cardoso is a Full Professor at the Federal University of the ABC (UFABC) in Santo André, Brazil and was co-principal investigator for the study. The other principal investigator was Frank Nelson Crespilho, a professor at the University of São Paulo's São Carlos Chemistry Institute (IQSC-USP).

The nanometric and giant liposomes used in the model were designed to mimic drug carriers and cells, respectively, and to fuse with each other. Instead of delivering drugs, however, the nanometric liposomes transported magnetite nanoparticles with fluorophores (fluorescent molecules) or electrically charged lipids. The fluorophores and charged lipids were used to transmit signals, while the magnetic particles were used to control transmission by means of magnets.

"In the initial situation, the giant vesicles had no fluorophores, charges or magnetite nanoparticles. Upon fusing with the nanometric liposomes, which contained luminous or electrical information, the giant vesicles incorporated this information. They also incorporated the magnetic particles and hence could be drawn by a magnet to the signal-receiving station. This created the possibility of an on/off mechanism. When the magnet moves the vesicle toward the receiving station, we have the 'on' state. When it's in the opposite direction, we have the 'off' mode, and the signal is blocked," Cardoso explained.

"In the case of the light signal, the giant vesicles were conducted by a capillary tube to a fiber-optic connection and from there to a spectrofluorimeter, which recorded the fluorescence spectrum. For the electrical signal, we used a magneto-electrochemical signal transmission system. When the electrically charged molecules are conducted to an electrode by a magnet, a high signal occurs. If the magnet is removed, the signal is very low," he said.

According to the researchers, these devices can be used to perform Boolean logic operations in which the variables and functions have values only of 0 and 1. These would be combined in pairs to create four dyads: 0-0, 0-1, 1-0 and 1-1. The first dyad (0-0) would be the giant vesicle without fluorophores, charges or magnetite particles. With fluorophores but no magnetite, the device produces but does not transmit a light signal (0-1). With magnetite but no fluorophores, the giant vesicle can be transported but does not transmit a light signal (1-0). With both fluorophores and magnetite, it transmits a light signal (1-1).

The study was conducted as part of the Thematic Project "Interfaces in materials: electronic, magnetic, structural and transport properties", for which Professor Adalberto Fazzio is the principal investigator, and demonstrated for the first time that magnetic nanoparticles can be used at the liposome interface to transmit luminous or electrical signals.

RIVERSIDE, Calif. - Kangaroo rats are abundant and seemingly defenseless seed-eating rodents that have to contend with a host of nasty predators, including rattlesnakes -- venomous pit vipers well known for their deadly, lightning-quick strikes. 

Research by a student-led team from UC Riverside, San Diego State University, and UC Davis now shows that desert kangaroo rats frequently foil snakes through a combination of fast reaction times, powerful evasive leaps, and mid-air, ninja-style kicks. 

Video of kangaroo rat defensively kicking a rattlesnake while jumping. More videos below.

Timothy Higham, an associate professor in the Department of Evolution, Ecology and Organismal Biology at UCR, is a coauthor on two papers published today in Functional Ecology and the Biological Journal of the Linnean Society that present detailed analyses of the behaviors and biomechanics of both kangaroo rats and rattlesnakes.

"Both rattlesnakes and kangaroo rats are extreme athletes, with their maximum performance occurring during these interactions," Higham said. "This makes the system excellent for teasing apart the factors that might tip the scale in this arms race." 

The research team documented the interactions between kangaroo rats and rattlesnakes in the wild by using radio telemetry to patiently track the hunting behavior of free-ranging rattlesnakes, and then placing high-speed cameras to record snakes hunting in locations frequented by kangaroo rats. The resultant videos provide the first ever detailed look at the maneuvers that kangaroo rats use to defend themselves against a deadly predator. 

"These lightning-fast and powerful maneuvers, especially when executed in nature, tell us about the effective strategies for escaping high-performing predators," Higham said. "Those that are successful at evading the strike will suggest ways in which the kangaroo rat might be evolving in response to the intricacies of the predatory movements."

A blink of the human eye can last just 150 milliseconds. In contrast, the research team found that the rattlesnakes frequently launched from absolute stillness to reach the kangaroo rats in less than 100 milliseconds. The researchers were surprised to find that the kangaroo rats turned out to be even faster, with typical reaction times around 70 milliseconds.  Their data indicate that some kangaroo rats initiated jumps within just 38 milliseconds of a snake starting its strike. 

"Kangaroo rats that responded quickly were frequently able to jump clear of the snake completely, leaving the serpent biting nothing but dust as the kangaroo rat rocketed 7-8 body lengths into the air," said Rulon Clark, an associate professor of biology at San Diego State University and a coauthor on both research papers. "But in perhaps the most surprising finding of our research, kangaroo rats that did not react quickly enough to avoid the strike had another trick up their sleeves: they often were able to avoid being envenomated by reorienting themselves in mid-air and using their massive haunches and feet to kick the snakes away, ninja-style."  

One video shot by the students on the research team shows a kangaroo rat successfully kicking a snake.  The snake is sent flying through the air and crashing to the ground several feet away while the kangaroo rat bounds off.  Such defensive kicks solved a mystery that had puzzled the team for years: the group's previous research showed that kangaroo rats often emerged from seemingly successful snake bites unscathed, but it was not clear how. The researchers even tested the blood of kangaroo rats to be sure that they weren't physiologically resistant to snake venom, the way some squirrel and opossum species are. 

"Our previous work used lower-speed cameras, and although it seemed as though snakes had successfully struck their prey, the movements of the animals at the moment of impact was too blurry to see details," said Malachi Whitford, a doctoral student at San Diego State University and the lead author on one of the papers.  "In this new work, we used cameras with much higher recording speed and resolution, which helped show in exquisite detail that kangaroo rats not only have record-breaking reaction time, but can also use their long tails to reorient their bodies while jumping, thereby optimally positioning themselves for both defensive kicking and landing on their feet."

Catching prey and avoiding predators are central to the reproductive success of animals.  Kangaroo rats' highly sensitive hearing allows them to hear low-frequency sounds and detect sudden surprise attacks, necessary for avoiding predators. They also have enlarged hindlimb muscles and thick tendons, allowing for the rapid vertical leaps and high accelerations. 

Rattlesnakes are classic ambush predators. They hunt by hiding and remaining nearly motionless for prolonged periods. They strike at prey that gets too close. The prey avoids being struck by initiating a successful evasive maneuver. In the wild, both predator and prey can alter the outcome at multiple stages of an interaction in ways not readily apparent in the lab. 

"Our work, which, to our knowledge, is the first to describe the kinematics of evasive leaps by bipedal rodents avoiding actual attacks from predators, supports the idea that bipedalism may have been favored in kangaroo rats because it allows for the rapid and powerful leaps needed to avoid ambush predators such as vipers and owls," said Grace Freymiller of San Diego State University, the student lead author of the second paper.

Researchers show that how well parents or guardians support millennials' psychological needs prior to their transition to college is an important predictor of their psychological well-being as they adapt to college life.

A new study published in The Journal of Social Psychology has assessed the role of parental relationships in mitigating millennials' worry prior to college transition by meeting their basic psychological needs of autonomy, competence and relatedness. The research discovered that millennials who perceive their parental relationships as supportive of their psychological needs are less likely to worry and adjust better to the transition to college, whereas parenting that feels over involved and controlling predicts less need satisfaction, higher levels of worry and poor psychological well-being.

"Millennial college students are experiencing poorer psychological health than any other previous generation," explained Mr Nathaniel Greene from the University of Missouri, who led the study.

"An early indication of student's well-being is their initial worry about college," he continued, "but understanding what factors might mitigate worry prior to millennials' transition into college is limited in current research."

Specifically, the researchers focused on whether worry, including guilt over academically succeeding family members, could be moderated through the student's parental relationship.

"Millennials have a uniquely close and communicative relationship with their parents," explained Dr Carrie Veronica Smith, who contributed to the study, "so we used the well-established 'Self-Determination Theory' to test if worry would be lower for students who perceive their parental relationships meet their three basic psychological needs: the need to be in control of one's actions (autonomy), the need to feel capable and effective (competence) and the need to feel close and connected to others (relatedness)," she continued.

355 students were surveyed during their two-day orientation visits to a public university in the southeast United States in the summer before their freshman year. Measurements of the participants' demographics, family achievement guilt, basic need satisfaction in the parental relationship, parental bonding and student worry were collected, and the data was subjected to statistical analyses to determine if higher levels of need satisfaction in the parental relationship were related to lower levels of worry and achievement guilt and if these outcomes would differ for first- and continuing-generation students.

Millennials who felt that their parents support their psychological needs reported less worry about their transition to college and lower family achievement guilt. But of the three basic psychological needs, autonomy was the most significant predictor of worry, suggesting that millennials' need to feel in control of their actions may be the most important need in combatting concerns about college. Meanwhile, millennials who felt their parents were over involved and controlling reported less need satisfaction and higher levels of worry and achievement guilt.

"We were surprised to see these results were true for both first- and continuing-generation students because past research has shown first-generation students likely suffer more from family achievement guilt and feelings of disconnection," explained Mr Greene. "But our results nicely highlight the universal importance of these basic needs," he continued.

Overall, the study identifies the importance of psychological need satisfaction in the parental relationship in offsetting millennials' worries about college and relating to their psychological well-being.

"Parents, peers and educators should support millennial students' basic needs for autonomy, competence and relatedness both before and after the transition to college, as they are essential to their overall psychological health" advised Mr Greene.

Tracking animals using DNA signatures are ideally suited to answer the pressing questions required to conserve the world's wildlife, providing benefits over invasive methods such as ear tags and collars, according to a new study by University of Alberta biologists.

Genetic tagging, or the identification and tracking of individual animals using DNA, is a non-invasive method of conducting research that uses samples from shed hair, feathers, feces, or saliva.

"This method provides a toolkit that can answer many of the pressing questions in ecology and conservation and provides a 'one-stop-shop' for getting these answers," explained Clayton Lamb, PhD candidate and Vanier scholar in the Department of Biological Sciences and lead author on the study. "Other methods would generally need to be combined to acquire similar insight. Genetic tagging approaches are complementary to traditional approaches and add a powerful tool to the ecologists' toolkit."

In addition to being non-invasive--in fact, there's no need to handle individual animals at all--there are many benefits to using genetic tagging over other methods. Genetic tagging can cover more ground and is scalable, allowing scientists to examine overall population density or the composition of a single community. It also provides the ability to recognize individual animals with great precision, allowing scientists to research animals that are otherwise difficult to study.

Access to DNA sequencing technology has grown increasingly affordable since the 2000s, thereby increasing access and usability for ecologists and biologists around the globe. And it's a good thing too, as our world continues to change.

"As human pressures on the globe increase, scientists are tasked with identifying drivers of decline and mobilizing this evidence to promote mitigation," said Lamb. "Genetic tagging offers a powerful approach to parameterize such relationships across massive spatial extents, for difficult to sample species, and in a cost-effective and socially-acceptable manner."

The good news is global and local. Keeping inland lakes from turning green means less greenhouse gases entering the atmosphere and contributing to climate change. Healthy drinking water, fishing and recreation opportunities are also increased when waters are not green.

What's wrong with being green? Toxins released by algal blooms can ruin drinking water. When dense algae blooms die, the bacteria that decompose the algae also deplete oxygen in the water. Without oxygen, fish and other animals suffocate. Globally, such green waters are also an important contributor to atmospheric methane -- a greenhouse gas that is up to 34 times more potent than carbon dioxide.

"We estimate that the greening of the world's lakes will increase the emission of methane into the atmosphere by 30 to 90 percent during the next 100 years," said Jake Beaulieu of the United States Environmental Protection Agency and lead author of a paper on lake greening and greenhouse gas emissions published March 26, 2019 in the journal Nature Communications.

According to the authors, three distinct mechanisms are expected to induce increases in lake greening or eutrophication during the next 100 years. First, human populations are expected to increase by 50 percent by 2100. More people means more sewage and more fertilizers that runoff land. At current rates of population growth and climate change, eutrophication in lakes will increase by 25 to 200 percent by 2050 and double or quadruple by 2100.

Second, increased storms and stormwater runoff will increase the nutrient losses from land to inland waters. Third, as the climate warms, lakes will warm. Warmer waters produce more algae. Additionally, the area of the planet covered in water is expected to increase, which will result in more methane-emitting surface waters.

"It is really surprising how much eutrophication could increase in the next 50 to 100 years," said co-author John A. Downing of the University of Minnesota Sea Grant program. "People do four important things that affect eutrophication: they eat, they excrete, they make more people who eat and excrete, and they alter landscapes and climate," said Downing.

Using projected population growth and climate change, the authors simulated the eutrophication of lakes under four different and conservative scenarios of future phosphorus loading from low to high: 80, 130, 170, 200, and 220 percent of current levels.

"We used phosphorus because the relationship between phosphorus and plant or algae growth is well established," said co-author Tonya DelSontro of the University of Geneva. "Currently, the single largest source of atmospheric methane is wetlands. If the phosphorus in lakes triples, then methane emissions from lakes could be twice that of wetlands."

The authors used a statistical model they created in 2018 that correlates methane emissions with lake size and chlorophyll, which is a measure of high algal biomass stimulated by phosphorus. By using global distribution of lake size and total lake area, climatic heating of lakes, future phosphorus concentrations and storm-driven nutrient runoff they were able to estimate future lake methane emissions, which the authors say has not been done before.

The optimistic outcome is that improved nutrient management practices could reverse the greening or eutrophication of lakes and thereby reduce methane emissions. Additionally, local action to improve water quality could have important global consequences.

"In keeping and improving the quality of our fresh water we win twice," said Downing. "Once in the atmosphere and once back down here on Earth."

Scientists at the University of Sheffield and University of Turku are looking at ways to boost captive populations of Asian elephants without relying on taking them from the wild.

Almost a third of Asian elephants are in captivity in countries like India, Myanmar and Thailand, mainly being used in the timber industry to drag logs or for tourism.

Sustaining wild populations is the conservation priority but, with so many individuals in captivity, maintaining sustainable captive populations with high welfare standards is also important for the future of the species.

The sustainability of these elephant populations has always relied on the capture of their wild counterparts, but now they are a protected species their future is uncertain.

In a joint research study, the University of Sheffield and the University of Turku, in Finland, working alongside The Myanma Timber Enterprise (MTE), investigated how trends in elephant capture from the wild influenced birth, death and population growth in 3,500 working elephants over 54 years.

Using birth and death rates from years where wild-capture was reduced the scientists assessed the outlook for captive elephants and found that the population is vulnerable to decline.

The research, published in Proceedings of the Royal Society B, suggests that immediate population declines may be reduced if survival in juvenile elephants is improved.

This could involve improving welfare standards during the training period, as the elephants are separated from their mothers and trained for work around the age of four, which can be stressful for them, and identifying pregnant females earlier and improving their welfare so they can provide for and bond with their calf.

John Jackson, PhD researcher from the University of Sheffield's Department of Animal and Plant Sciences and lead author of the paper, said: "Our model suggests we may see declines in captive elephants for up to 50 years so we must now work to ensure that the captive population is sustainable. With so many Asian elephants in captivity, we must safeguard both captive and wild elephant populations and the people living and working alongside them for the future of the species.

"One hopeful result is that we may see improvements in population growth if we are able to improve the survival of young elephants by just 10 per cent. This shows we can really make a difference by improving welfare for these vulnerable individuals in captivity."

He added: "Many of us have the opportunity to visit captive elephants used in tourism, particularly in Southeast Asia. We all have our part to play to ensure that the welfare of captive elephants is improved and this may have a positive effect on Asian elephants globally."

Professor Virpi Lummaa, from the University of Turku, who led the research, said: "The dependence of captive elephant populations on capture from the wild in the past is truly alarming. The problem with elephants is that they take so long to grow and reproduce and have very complex social lives, making them vulnerable to population declines when disturbed."

The University of Sheffield's Department of Animal and Plant Sciences is a leading department for whole organism biology, with the UK's highest concentration of animal and plant researchers.

It is among the top five animal and plant research centres in the country for research excellence, according to the last Research Excellence Framework in 2014.

Animal and plant scientists at Sheffield study in locations from the Polar Regions to the tropics, at scales from within cells up to entire ecosystems. Their research aims both to understand the fundamental processes that drive biological systems and to solve pressing environmental problems.

People with and without cancer are more likely, over time, to use a more potent form of medical marijuana with increasingly higher amounts of tetrahydrocannabinol (THC), a new study shows.

In a report publishing in the Journal of Palliative Medicine on March 26, researchers say that cancer patients were more likely to favor forms of medical marijuana with higher amounts of THC, which relieves cancer symptoms and the side effects of cancer treatment, including chronic pain, weight loss, and nausea.

By contrast, marijuana formulations higher in cannabidiol (CBD), which has been shown to reduce seizures and inflammation in other studies, were more popular among non-cancer patients, including those with epilepsy and multiple sclerosis, say the study authors.

Cancer patients were also more likely to prefer taking oil droplets containing medical marijuana under the tongue than "vaping".

"Although there is growing patient interest in medical cannabis, there is a scarcity of solid evidence about the benefits, risks, and patterns of use of marijuana products in various disease settings," says study lead investigator Arum Kim, MD, an assistant professor of medicine and rehabilitation medicine at NYU School of Medicine and director of the supportive oncology program at its Perlmutter Cancer Center. "Such information is important for delivering the best care."

Since 1996, 31 states, including New York in 2014, have legalized medical marijuana.

For the study, researchers analyzed data from 11,590 men and women in New York, of whom 1,990 (17.2 percent of the total patient cohort) were cancer patients who purchased and used cannabis products from Columbia Care LLC., a dispensary licensed in New York State, between January 2016 and December 2017.

The researchers caution that their data did not include the type of cancer the purchasers had, how much of what they bought was used, or whether marijuana was used for symptoms unrelated to the cancer. Nevertheless, the patterns of use among cancer patients were distinctly different from those of non-cancer patients.

Specifically, the study found that cancer and non-cancer patients used different dosages of cannabis formulations with dramatically different THC:CBD ratios. The two most common formulations contained THC and CBD, but one had twenty times more THC than CBD, whereas the other had the opposite ratio.

Over the two years of the study, the research team found that all types of patients increased their THC dose by approximately 0.20 milligrams per week.

"Our study provides valuable new information about how cancer patients are using marijuana," says study senior investigator Benjamin Han, MD, MPH, an assistant professor of medicine and population health at NYU School of Medicine. "In the absence of strong clinical research data for medical marijuana, identifying patterns of use offers some sense of how to guide patients who come in with questions for using medical marijuana, and what may or may not help them."

Researchers say they next plan to get more detailed information about how medical marijuana affects patient response to therapy and functional status at different stages of their disease, as well as the risks and side effects of treatment. Furthermore, the profiles of other cannabinoids besides THC and CBD in medical marijuana products warrant further research, according to the study authors.

Joint replacements are among the most common elective surgeries -- but around one in 100 patients suffer post-surgical infections, turning a routine procedure into an expensive and dangerous ordeal. Now, researchers at Stevens Institute of Technology have developed a "self-defensive surface" for these implants that release targeted micro-doses of antibiotics when bacteria approach, potentially sharply reducing infection rates.

The work, led by Matthew Libera, professor of materials science at Stevens, describes a method for coating implant surfaces with a lattice of microgels: flecks, each 100 times smaller than the diameter of a human hair, capable of absorbing certain antibiotics. The microgels' behavior is regulated by electrical charges, and the electrical activity of an approaching microbe causes them to leak antibiotics, preventing infections from taking root.

Microgels could be applied to a wide range of medical devices, including heart valves, tissue scaffolds, and even surgical sutures -- and with the market for hip implants alone forecasted to reach $9.1 billion by 2024, the technology has significant commercial potential. The United States Army, which helped fund the research, is also interested in deploying the technology in field hospitals, where infections currently occur in a quarter of combat injuries.

"The potential impact for patients, and for the healthcare system, is tremendous," said Libera, who chairs the Stevens Conference on Bacteria-Material Interactions. Stevens doctorate candidate Jing Liang and biomedical engineering professor Hongjun Wang collaborated on the study, which appears in the journal Biomaterials.

Post-surgical infections are tough to beat because as microbes colonize surfaces, they form antibiotic-resistant layers called biofilms. Libera and his team disrupt this cycle by killing microbes before they can gain a foothold. "It only takes one bacterium to cause an infection," Libera said. "But if we can prevent infection until healing is complete, then the body can take over."

Unlike conventional treatments that flood the whole body with antibiotics, the Stevens team's approach is highly targeted, releasing tiny amounts of antibiotics to kill individual bacteria. That dramatically reduces the selective pressures that give rise to antibiotic-resistant "superbugs" -- a big improvement over both systemic treatments and local approaches such as blending antibiotics into bone cement, releasing orders of magnitude less antibiotic into the patient's system.

Other self-defensive surfaces currently in development rely on microbes' metabolic byproducts to trigger the release of antibiotics -- a less surefire approach than the Libera's method, which can kill even dormant bacteria. The team's microgels are also remarkably resilient, surviving ethanol sterilization and remaining stable for weeks at a time. Microgels also respond appropriately to human tissue, retaining their antibiotic load until it's needed and promoting healthy bone growth around treated surfaces.

To apply microgels to a medical device such as a knee joint, surgeons could dunk the device in a specially prepared bath for a few seconds; a brief dip in a second bath would then charge the microgels with antibiotics. In theory, surgeons could prepare devices on demand, immediately before implanting them, using antibiotics tailored to a patient's specific risk factors.

So far the approach has been tested in vitro, and the team is still working to fine-tune the microgels and enable them to deliver a wider range of antibiotics. Securing approval from the U.S. Food and Drug Administration will be tricky, given the innovative nature of the technology, but Libera's team is working with industry partners to plan further demonstrations.

A new way of making scaffolding for biological cultures could make it possible to grow cells that are highly uniform in shape and size, and potentially with certain functions. The new approach uses an extremely fine-scale form of 3-D printing, using an electric field to draw fibers one-tenth the width of a human hair.

The system was developed by Filippos Tourlomousis, a postdoc at MIT's Center for Bits and Atoms, and six others at MIT and the Stevens Institute of Technology in New Jersey. The work is being reported in the journal Microsystems and Nanoengineering.

Many functions of a cell can be influenced by its microenvironment, so a scaffold that allows precise control over that environment may open new possibilities for culturing cells with particular characteristics, for research or eventually even medical use.

While ordinary 3-D printing produces filaments as fine as 150 microns (millionths of a meter), Tourlomousis says, it's possible to get fibers down to widths of 10 microns by adding a strong electric field between the nozzle extruding the fiber and the stage on which the structure is being printed. The technique is called melt electrowriting.

"If you take cells and put them on a conventional 3-D-printed surface, it's like a 2-D surface to them," he explains, because the cells themselves are so much smaller. But in a mesh-like structure printed using the electrowriting method, the structure is at the same size scale as the cells themselves, and so their sizes and shapes and the way they form adhesions to the material can be controlled by adjusting the porous microarchitecture of the printed lattice structure.

"By being able to print down to that scale, you produce a real 3-D environment for the cells," Tourlomousis says.

He and the team then used confocal microscopy to observe the cells grown in various configurations of fine fibers, some random, some precisely arranged in meshes of different dimensions. The large number of resulting images were then analyzed and classified using artificial intelligence methods, to correlate the cell types and their variability with the kinds of microenvironment, with different spacings and arrangements of fibers, in which they were grown.

Cells form proteins known as focal adhesions at the places where they attach themselves to the structure. "Focal adhesions are the way the cell communicates with the external environment," Tourlomousis says. "These proteins have measurable features across the cell body allowing us to do metrology. We quantify these features and use them to model and classify quite precisely individual cell shapes."

For a given mesh-like structure, he says, "we show that cells acquire shapes that are directly coupled with the substrate's architecture and with the melt electrowritten substrates," promoting a high degree of uniformity compared to nonwoven, randomly structured substrates. Such uniform cell populations could potentially be useful in biomedical research, he says: "It is widely known that cell shape governs cell function and this work suggests a shape-driven pathway for engineering and quantifying cell responses with great precision," and with great reproducibility.

He says that in recent work, he and his team have shown that certain type of stem cells grown in such 3-D-printed meshes survived without losing their properties for much longer than those grown on a conventional two-dimensional substrate. Thus, there may be medical applications for such structures, perhaps as a way to grow large quantities of human cells with uniform properties that might be used for transplantation or to provide the material for building artificial organs, he says. The material being used for the printing is a polymer melt that has already been approved by the FDA.

The need for tighter control over cell function is a major roadblock for getting tissue engineering products to the clinic. Any steps to tighten specifications on the scaffold, and thereby also tighten the variance in cell phenotype, are much needed by this industry, Tourlomousis says.

The printing system might have other applications as well, Tourlomousis says. For example, it might be possible to print "metamaterials" -- synthetic materials with layered or patterned structures that can produce exotic optical or electronic properties.

A broad-scale study of U.S. forest data suggests a significant - but not simple - relationship between the number of native tree species and the number of nonnative forest pests.

"Invasive insects and diseases pose both ecological and economic threats to our forest ecosystems," says Qinfeng Guo, a research ecologist with the USDA Forest Service Southern Research Station and lead author of an article about the research in Proceedings of the National Academy of Sciences.

One example is the nonnative emerald ash borer, a beetle that has killed hundreds of millions of ash trees across the eastern U.S. Ash trees are popular street and landscaping trees, and the cost to treat, remove, and replace those infected with the beetle is estimated at more than $10 billion.

The study did not find a simple, linear relationship between tree diversity and pest diversity.

"When tree diversity is relatively low, the number of pest species increases with increasing tree diversity. This supports the facilitation hypothesis: greater tree diversity means more ecological niches for pests to exploit," says Guo. "However, when tree diversity continues to increase, we saw a threshold where pest species begin to decrease. This is dilution: high tree diversity usually means fewer individuals of each host tree species in the forest. This can suppress invasion, as certain pest species may no longer have enough resources, either food or habitat, to support their populations."

The study suggests that facilitation and dilution are both occurring in a forest community, but the importance of each shifts with overall tree diversity.

"There's a long standing hypothesis in invasion biology that high biodiversity can help to resist biotic invasions," says Guo. "Past experiments are mostly limited to single species at fine scales. They have shown evidence of dilution or facilitation but rarely both. Our study expands this inquiry and examines 66 important invasive pests found in natural forest ecosystems across the conterminous U.S."

The study examined records of tree species collected across public and private lands by the USDA Forest Service Forest Inventory and Analysis Program (FIA). Scientists combined this dataset with the Alien Forest Pest Explorer, a web tool developed by Northern Research Station co-author Andrew Liebhold. Its database includes spatial records of nonnative forest pests. The researchers focused on 66 of the top nonnative invasive species, including 51 insects and 15 pathogens. Together, these datasets describe where and how many tree species and invasive pest species co-exist.

The researchers looked at other factors, including temperature, precipitation, elevation, and human population density, as a proxy for pest arrival. Although these factors also seem important, tree diversity remains a strong predictor of nonnative pest invasions.

"Diverse plant communities may contain non-hosts as well as species that are natural enemies for potential nonnatives. Both of these can help land managers prevent the establishment of invasive pests - make them work harder to find resources," says Guo.

"There is a lag between a pest's arrival, its impact, and our detection of it. We know which native tree species are hosts for major invasives in the potential pest species pool. We know that the major pathways for pest introduction to new areas include trade or travel that involves moving infested wood materials. One way that we can slow or stop the spread of nonnative pests is by taking early action in prevention and detection. Our work emphasizes the critical importance of conserving native biodiversity in reducing the damages from pest invasions," adds Guo.

The research team also includes Songlin Fei of Purdue University, Kevin Potter of North Carolina State University, Andrew Liebhold of USDA Forest Service, and Jun Wen of Duke University. They hope that their results will inform monitoring efforts and help prioritize areas at greater risk for future pest invasions.

A national-scale study of U.S. forests found strong relationships between the diversity of native tree species and the number of nonnative pests that pose economic and ecological threats to the nation's forests.

"Every few years we get a new exotic insect or disease that comes in and is able to do a number on our native forests," says Kevin Potter, a North Carolina State University research associate professor in the Department of Forestry and Environmental Resources and co-author of an article about the research in Proceedings of the National Academy of Sciences.

"Emerald ash borer is clobbering a number of ash species in the Midwest and increasingly in the South. The chestnut, a magnificent tree that had immense ecosystem value as well as economic value in the South and North, is pretty much gone because of a pathogen. And hemlocks are under attack by the hemlock woolly adelgid from the Northeast along the Appalachian Mountains into the South."

To better understand how nonnative insects and diseases invade U.S. forests, researchers tested conflicting ideas about biodiversity. The first is that having more tree species can facilitate the diversity of pests by providing more places for them to gain a toehold. Another possibility is that tree biodiversity can have protective effects for forests, such as by diluting the pool of host trees and making it harder for pests to become established.

"We found that both facilitation and dilution seem to be happening at the same time," Potter says. "What we found is that native tree biodiversity really is important, but it's important in different ways at different times."

Combining two national county-level data sets, researchers found that relationships between tree diversity and pest diversity follow a hump-shaped curve.

"As you have an increasing number of tree species, you have an increasing number of pest species, up to an inflection point where that relationship changes," Potter says. "Then you have a decreasing number of pest species as the number of host tree species increases."

Overall, counties where forests have 30 to 40 different host tree species tend to have the most nonnative pests. But the effects depend on whether the invader is a specialist that can infest only a single tree species or whether it's a generalist, like the gypsy moth, which can spread to more than 60 different hosts.

"What we see is that forests in the Midwest and up into New England are at the middle part of that hump-shaped curve in terms of the number of host tree species, and those are places where there have been a lot of insect and disease problems," Potter says.

"Out West we have fewer insect and disease pests, but in some cases they still do a lot of damage because the forests are not diverse. If you have a specialist pest come in and knock back one of the major components of your biodiversity, then that can have a greater impact. An example of how that works would be Sudden Oak Death, a disease in California that's affecting oaks there."

Researchers with the U.S. Forest Service, Purdue, NC State, Czech University of Life Sciences and Duke collaborated on the study, which used two large datasets. The U.S. Forest Inventory and Analysis, a national forest census, contains information from 135,000 forested plots across the U.S. where crews regularly measure trees and check environmental conditions. For this study, the FIA data were used to compile counts of tree species for each of 2,098 counties. The Alien Forest Pest Explorer database offers a county-level record of the presence or absence of nonnative insects and diseases, including 66 used for this study.

Researchers also examined other factors that could affect pest invasions, such as human population density and environmental conditions, including precipitation, elevation and average temperature. Tree biodiversity was a better predictor of nonnative pests, Potter says.

Results could help prioritize monitoring efforts for forests most at risk for future pest invasions, he says.

"The unfortunate reality is that a lot of times we don't notice these exotic pests and diseases until they've gotten established and start having an impact on our native species, when it's almost too late."

Many whales take long journeys each year, spending summers feeding in cold waters and moving to warm tropical waters to breed. One theory suggests that these long-distance migrations originated around 5 million years ago, when ocean productivity became increasingly patchy. But patterns of ancient whale migrations have, until recently, been shrouded in mystery. Scientists from the Smithsonian Tropical Research Institute (STRI) and the University of California, Berkeley approached this question with an ingenious technique: barnacles.

"Instead of looking for clues to migration patterns from the whale's bones, we used hitch-hiking whale barnacles instead," said Larry Taylor, STRI visiting scientist and doctoral student at UC Berkeley who led the study.

Barnacles are crustaceans (crabs, lobsters, shrimp) that live stuck in one place in a hard shell. Most glue themselves to rocks, but whale barnacles attach to a whale's skin by sucking the skin in.

"Whale barnacles are usually species specific --one species of barnacle on one type of whale," said Aaron O'Dea, staff scientist at STRI and co-author of the study. "This gives the barnacle several advantages-- a safe surface to live on, a free ride to some of the richest waters in the world and a chance to meet up with others when the whales get together to mate."

As whale barnacles grow, their shells record the conditions by taking up oxygen isotopes from the water. By carefully reading the unique isotope signatures left in the shells, the barnacles can reveal the water bodies the barnacle passed through, helping reconstruct the whale's movements over time.

The study, published in Proceedings of the National Academy of Sciences looked at a number of fossil and modern whale barnacles from the Pacific coast of Panama and California.

"The signals we found in the fossil barnacles showed us quite clearly that ancient humpback and grey whales were undertaking journeys very similar to those that these whales make today," Taylor said. "It seems like the summer-breeding and winter-feeding migrations have been an integral part of the way of life of these whales for hundreds of thousands of years."

"We want to push the technique further back in time and across different whale populations," said Seth Finnegan, co-author from UC Berkeley. "Hunting for fossil whale barnacles is easier than whales, and they provide a wealth of information waiting to be uncovered."

While current therapies for HIV can successfully manage active infection, the virus can survive in tissue reservoirs, including macrophage cells, and remain a persistent problem. Now, Dr. David Russell, William Kaplan Professor of Infection Biology at Cornell University College of Veterinary Medicine, and his research team have pinpointed a novel angle of attack that could selectively eradicate these viral reservoir cells while leaving healthy cells untouched.

In their study published on March 25th in the journal PNAS, Russell's team, lead by first author and postdoctoral fellow Dr. Saikat Boliar, describe how a genetic regulator called SAF helps HIV-infected macrophages avoid cell death. After blocking SAF in HIV-infected cells, the researchers found that these reservoir cells then self-destructed. "We were all surprised by the specificity of the cell death," says Russell. "Only infected cells die while bystander cells, exposed to the same treatment at the same dose, showed no death at all."

While macrophages, immune cells that consume foreign entities in the body, are helpful in fighting off certain microbes, they provide the perfect foxhole for HIV. Some researchers believe these infected macrophages are the reservoirs for persistent HIV infection. "Current HIV drugs work really well on active infection, but it is the tissue reservoirs that are the problem," Russell explains. "These sites of persistent virus are resistant to all current therapies."

Russell, Boliar, and their colleagues wanted to investigate what cellular mechanisms were at play that helped keep infected macrophages alive, and turned their attention to long non-coding RNAs (lncRNAs) -- genetic coding elements that turn genes up or down, but do not translate directly into proteins themselves. "We were interested in long-noncoding RNAs because they are known 'master regulators' of cell pathways, and had not really been looked at systematically in HIV infection," Russell explains.

The team screened a panel of 90 well-characterized lncRNAs in three distinct populations of human macrophages: healthy cells, HIV-infected cells, and 'bystander' cells -- those that had been exposed to HIV, but not infected.

The investigators found that one lncRNA, called SAF, was significantly up-regulated in the HIV-infected macrophages. Previous studies had found that SAF prevented apoptosis, or self-destruction, in cells. Russell and his team suspected SAF was protecting HIV-infected macrophages from dying.

To prove this theory, the team blocked SAF's action using another non-coding RNA called small interfering RNA (siRNA), which effectively degrade targeted RNAs such as SAF. The researchers silenced SAF in the healthy, infected, and bystander macrophage populations; the HIV-infected cells suddenly self-destructed, while the healthy and bystander cells remained unscathed.

"This showed us that when cells are infected with HIV, the virus alters the long non-coding RNAs' expression in that cell," says Russell. This would explain why bystander cells that are exposed to the HIV virions, but not actually infected by them, do not have the same response.

This discovery taps into a novel angle in curing HIV: selectively destroying persistently infected cells--and the Russell team is eager to exploit it for potential therapies.

"We plan to do a drug screen for compounds that drive HIV-infected cells into programmed cell death," says Russell. The team will start by looking for SAF inhibitors, but also will look for other molecules that effectively eradicate reservoir cells through other mechanisms.

PULLMAN, Wash. - A Washington State University researcher says attractive businesswomen are considered less trustworthy, less truthful and more worthy of being fired than less attractive women. This "femme fatale effect," as she and a University of Colorado colleague call it, goes beyond a commonly accepted explanation that attractive women simply aren't seen as fitting in traditionally masculine roles. Rather, the effect taps into more primal feelings of sexual insecurity, jealousy and fear among both men and women.

"Highly attractive women can be perceived as dangerous and that matters when we are assessing things like how much we trust them and whether we believe that what they are saying is truthful," said Leah Sheppard, an assistant professor of management in the WSU Carson College of Business and lead author of a paper in the journal Sex Roles.

The myth of the femme fatale has been around since ancient Greece, when Homer's Odysseus was seduced by the goddess Circe and kept from his wife and home for a year. The ensuing list of man-eaters, vamps and dark-hearted sirens is long, from the smoldering Carmen of George Bizet's opera to the lethal leading ladies of film noir.

Despite decades of feminism and a growing awareness of gender stereotypes, the effect persists.

In fact, said Sheppard, "there's two dueling stereotypes here. You have the 'what is beautiful is good' stereotype, meaning that in general attractive people should fare better across their lifespan. We can say that that's generally true.

"It becomes more nuanced when we look at gender," she added. "For women there are certain contexts in which they don't seem to benefit from their beauty."

Sheppard and Stefanie Johnson, an associate professor at the University of Colorado Boulder's Leeds School of Business, conducted six separate tests to reach their conclusion. They used images drawn from a Google images search for a "professional woman" and had participants in Amazon's Mechanical Turk, an online crowdsourcing platform, rate their attractiveness.

The first four studies asked participants to rate the truthfulness of women and men announcing layoffs in fictional news accounts. Regardless of their title or industry--executive or the traditionally feminine public relations professional, the masculine culture of tech firm or more feminine hospital--the attractive women were consistently considered less truthful than the non-attractive women. Because the results were independent of the women's role or industry, the "best fit" argument failed.

In the fifth study, the researchers used what's called a prime, a suggestion that puts participants into an emotional state that can color their perspective. They asked participants to think and write about a time when they felt secure in a relationship and certain that their romantic partner "was faithful and committed to them alone." This was called the "sexual security" prime. A second "general security" prime had them think and write about a time when they felt very good about themselves.

Those primed to feel sexually secure ended up thinking attractive women were as truthful as less attractive women.

The final study asked if participants thought the woman should be fired, and primed some participants to feel sexually secure, but others to feel sexually insecure. As with the fifth study, the sexually secure participants found both attractive and less attractive women were equally truthful. Participants primed to feel sexually insecure viewed the attractive women as less truthful, and therefore more deserving of termination.

Sheppard sees both evolutionary and social factors at work in the results.

Evolutionarily, women have used their attractiveness to get mates. They see more attractive women as competition and threats to steal their partner. Men, for their part, have been drawn to attractive women but worry that their attractiveness might make them unfaithful. Before the recent advent of the paternity test, they risked raising children that were not their own.

Socially, attractive women can use their looks to get advantages in the workplace, whether they deserve it or not. Both men and other women can find this unfair, said Sheppard, if not deceitful.

Sheppard said the femme fatale effect might be blunted if people were more conscious of the stereotypes they use, but people are often unwilling to acknowledge that they use stereotypes to begin with.

Unfairly or not, she said, much of the burden of addressing the problem falls on attractive women themselves, who she said can attempt to be more transparent.

"They're going to be challenged in terms of building trust," she said. "That's not to say that they can't do it. It's just that trust is probably going to form a bit more slowly."