Tech

Remote islands: Stepping stones to understanding evolution

image: The scientists used Winkler traps to extract the trap-jaw ants out of leaf litter into flasks of ethanol.

Image: 
OIST

For millions of years, remote islands have been hotbeds of biodiversity, where unique species have flourished. Scientists have proposed different theories to explain how animals and plants colonize and evolve on islands but testing ideas for processes happening over long time scales has always been a challenge.

Recently, cutting-edge techniques in DNA sequencing, 3D imaging, and computation have opened up opportunities for investigating historical processes. In a new study published in Evolution, researchers from the Okinawa Institute of Science and Technology Graduate University (OIST) and collaborators from the University of the Ryukyus investigated evolutionary and ecological changes in ants in the South Pacific archipelago of Fiji to examine a controversial theory for how evolution occurs on islands.

"Islands like Fiji, which are small and remote, act as perfect natural laboratories to study the interplay between ecological and evolutionary processes," said Dr. Cong Liu, first author and former PhD student from the OIST Biodiversity and Biocomplexity Unit. "But until recently, there haven't been many studies on ants."

The team focused on Strumigenys trap-jaw ants, the genus with the greatest number of ant species in Fiji. They collected many specimens of trap-jaw ants during an expedition to Fiji in 2007.

The researchers set out to examine how well the changes in appearance and distribution observed in trap-jaw ants over time fit with a theory called the taxon cycle hypothesis, which describes how species colonize and evolve on islands. According to this theory, species pass through a predictable "life cycle" of colonization, geographic range expansion, decline, and (sometimes) extinction, with this cycle then restarted by a new colonizer.

Cracking the colonization stage

The scientists extracted and sequenced DNA from Strumigenys species endemic to the Fijian archipelago - in other words, they are only found in these islands. The team also included samples of the trap-jaw ants more regionally and globally distributed relatives. Based on the DNA sequences, the scientists constructed an evolutionary tree, showing how closely related all the species were.

"We discovered that all 14 of the trap-jaw ant species endemic to Fiji were descended from a single original colonizer, rather than from multiple colonizers," Dr. Liu explained.

These results contradict what would be expected by the taxon cycle hypothesis, which predicts that later colonizers arrive and kickstart new taxon cycles of radiation and decline.

"There are a few reasons why repeated colonizations may not have occurred," said Dr. Liu. He explained that the first trap-jaw colonizers could have diversified and occupied all the niches, closing the door to any newcomers. Or perhaps, he added, the Fijian archipelago is so remote that additional colonizers never arrived.

Revealing the radiation stage

According to the taxon cycle hypothesis, a species first colonizes an island, and then undergoes a huge expansion in range, specializing to the available niches in each habitat.

When the scientists looked at the distribution of the 14 trap-jaw species endemic to Fiji, they found that soon after colonization, the initial lineage split in two, with one giving rise to species living in lowland habitats, and one giving rise to species in upland habitats.

The scientists then measured key morphological features of the ants to determine whether they established their niches through adaptive radiation. "Adaptive radiation often occurs on islands, with the most iconic example being Darwin's finches," said Dr. Liu. "This sudden explosion in abundance, diversity and appearance is often due to a greater number of empty niches that the ants can adapt to, due to a lack of competitors or predators."

The scientists used micro-CT scanners to create 3D models of each Fijian ant species. They also measured the size of the ants' bodies, jaws (mandibles) and eyes.

"We saw a clear diversification of form that is associated with the niches they are occupying, which was clearly a result of adaptive radiation," said Dr. Liu. In general, the ants in the upland lineage evolved larger bodies, allowing them to catch larger prey. These ants also developed shorter mandibles, defining how they hunt.

Delving into the decline stage

The taxon cycle hypothesis predicts that over time, as species adapt to increasingly specialized niches, their population size and the range of their habitat declines. These predictions only held true for the Fijian trap-jaw ants in the upland habitats.

The team found that the populations of upland species of ants had shrunk in numbers over time and had greater genetic differences between populations, suggesting that they were less able to disperse and breed across the Fijian archipelago.

This loss of competitive ability increases the vulnerability of these older, more specialized ants, which are currently threatened by deforestation - a major environmental issue in Fiji. "Because these endemic species only occupy a small geographical area and only have a limited ability to disperse, deforestation can quickly lead to extinction of these species," said Dr. Liu.

The team now plans to apply their approach, which combines population genomics, phylogenetics and morphological studies, to all ant species on Fiji.

It's still not clear how closely data from the trap jaw ants aligns with the taxon cycle hypothesis, said Dr. Liu. This study, as well as one published last year that examined the Pheidole genus of Fijian ants, "only provided partial support" for the hypothesis, he said. "More data is needed to determine whether evolution on these islands does follow these predictable stages, or whether it is a more random process that differs each time."

Credit: 
Okinawa Institute of Science and Technology (OIST) Graduate University

Study suggests new approach to improve radiation therapy resistance in glioblastoma

Many modern cancer drugs target a specific genetic mutation that is driving a particular cancer's runaway growth and division -- such as the HER-2 protein in some breast cancers or EGFR in certain lung cancers.

But this strategy hasn't worked well against glioblastoma, an aggressive form of brain cancer, which is known for having multiple mutations that differ from region to region and cell to cell within a single tumor.

Now research led by the University of Michigan Rogel Cancer Center has hit upon a new approach: Make radiation therapy more effective for glioblastoma patients by targeting a critical metabolic pathway and disrupting its ability to repair the DNA damage caused by the radiation.

As it turns out, the Food and Drug Administration has already approved a drug that can inhibit this pathway, which makes biological building blocks known as purines. Starting with an existing drug lowers the barriers to launch a clinical trial to test the strategy's effectiveness in glioblastoma patients, the researchers note. The team's findings appear in Nature Communications.

"Radiation therapy is a key treatment for nearly every patient with glioblastoma, and resistance to radiation leads to a recurrence of the cancer. So, finding new ways to overcome this resistance could help improve outcomes for many patients," says senior study author Daniel Wahl, M.D, Ph.D., a radiation oncologist and researcher at Michigan Medicine. "And because of the variety of genetic alterations seen in glioblastoma, we wanted to find a way to overcome this resistance that would work across genotypes."

New treatments for glioblastoma are sorely needed. Fewer than 5% of glioblastoma patients live more than five years after being diagnosed, and recurrence after a first round of treatment is almost inevitable.

Wahl and co-author Yoshie Umemura, M.D., an assistant professor of neurology, are launching a research study in human patients based on the team's research, which will start enrolling patients soon.

Why are some cells resistant to radiation?

"What's the relationship between glioblastoma metabolism and resistance to radiation therapy? -- that's the central question we started with," Wahl says. "Our measurements allowed us to ask which metabolites correlate with radiation resistance? That is, if cells live after radiation treatment, do they have more of any particular metabolites?"

They began by examining the characteristics of 23 glioblastoma cell lines, Wahl explains, looking at the metabolites produced by each cell line and measuring how resistant each was to radiation.

The group found that the cell lines that were more resistant to radiation treatment also had higher levels of purines -- biological compounds that are known as the building blocks of DNA and RNA, and that can also activate signaling pathways.

"This was very exciting because lots of different genetic mutations that occur in glioblastoma lead to this purine pathway being activated," Wahl says.

This suggested that they might be able to target the downstream effect of multiple genetic mutations.

"We hypothesized that targeting this metabolic activity might work across tumor cells with different types of mutations -- instead of just whatever fraction of cells has that one particular genetic aberration you might go after with a mutation-targeting therapy."

Once the researchers discovered the correlation between high levels of purines and radiation resistance, they set out to demonstrate whether the metabolic changes actually caused the radiation to be less effective.

"We gave cells more purines. It made them more resistant," Wahl says. "We took away purines. It made them more sensitive to radiation. And we found it was doing this by affecting the cells' ability to repair radiation-induced DNA damage."

Moving from the lab toward the clinic

To better understand whether targeting purine metabolism might help overcome resistance to radiation therapy in patients, the team used mouse models of glioblastoma with tumors grown from human patients' cells.

They gave the mice a drug called mycophenolate mofetil, or MMF, which blocks purine biosynthesis and which has been approved for the treatment of organ transplant rejection since 2000.

Tumor growth was moderately slowed down in mice who received radiation therapy alone or MMF alone, but almost totally halted in the mice who received both, Wahl explains. The benefits of MMF were similar whether animal tumors were grown in the brains of the mice or elsewhere in their bodies, demonstrating the drug's ability to effectively penetrate the blood-brain barrier -- which is critical for treating brain cancer patients.

"Since the FDA has already found the drug to be safe enough to use in patients for one purpose, it makes it easier to set up a clinical trial aimed at a second disease," he says.

Ultimately, Wahl adds, the research was made possible by the collaborative, multidisciplinary environment at U-M -- where clinicians and researchers with expertise in glioblastoma can team up with others who specialize in cancer metabolism, data modeling and launching new clinical trials.

"None of this happens without all these different teams sharing knowledge, models, methods and enthusiasm for making a difference in the lives of patients," he says.

Credit: 
Michigan Medicine - University of Michigan

Two for the price of one

image: Using an iridium catalyst bound to a bipyridonate ligand, researchers were able to synthesize dicarboxylic acids from aqueous diols, with the added benefit of generating hydrogen as a byproduct

Image: 
Kyoto University

Kyoto, Japan -- Every year, the chemical industry makes trillions of dollars synthesizing the countless chemical compounds we use every day.

From pharmaceuticals for keeping you healthy to polyester woven into your shirt, industrial processes turn simple chemicals into complex, valuable compounds. Researchers in turn work constantly to develop new substances as well as safer and more efficient methods of production.

In a paper published in ChemSusChem, researchers from Kyoto University's Graduate School of Human and Environmental Studies describe how they have significantly improved the process that leads to polymers and plasticizers. And as an added bonus, their method generates hydrogen as a byproduct.

"We use renewable chemical compounds collectively known as diols to dramatically change the synthesis of dicarboxylic acids," explains corresponding author Ken-ichi Fujita, "These are needed to produce polymers, plasticizers, and lubricants."

Existing production methods, based on the oxidation of hydrocarbons using toxic oxidants, generate harmful waste products. Knowledge of this motivated the team to work on a new method of synthesis, changing the initial compound along with the catalyst.

"We began by looking at liquid solutions of diols, which are more renewable than starting materials previously used," continues Fujita.

"Then we needed to find a catalyst, and we settled on using iridium bound to a bipyridonate ligand."

The team were pleased to find that combining the diols with the new catalyst generated dicarboxylic acids with greater efficiency and significantly more yield, as well as four equivalents of hydrogen for every unit of diols.

Developing more efficient and safer methods of compound production is vital for industrial organic chemistry, and for the global environment.

"It is a pleasant surprise to see how efficient our new process is," concludes Fujita. "We hope to continue to improve safety and efficiency as we discover alternative chemical processes that are valuable to all humanity."

Credit: 
Kyoto University

New method lets scientists peer deeper into ocean

image: Senior Research Scientist Barney Balch collects ocean optics data during a research cruise in the Gulf of Maine. Balch is part of a team of researchers that has established a new approach to detect algae and measure key ocean properties using light, based on their research in the Gulf of Maine and beyond.

Image: 
Bigelow Laboratory for Ocean Sciences

Researchers have advanced a new way to see into the ocean’s depths, establishing an approach to detect algae and measure key properties using light. A paper published in Applied Optics reports using a laser-based tool, lidar, to collect these measurements far deeper than has been typically possible using satellites.

“Traditional satellite remote sensing approaches can collect a wide range of information about the upper ocean, but satellites typically can’t ‘see’ deeper than the top five or 10 meters of the sea,” said Barney Balch, a senior research scientist at Bigelow Laboratory for Ocean Sciences and an author of the paper. “Harnessing a tool that lets us look so much deeper into the ocean is like having a new set of eyes.”

Lidar uses light emitted by lasers to gain information about particles in seawater, much as animals like bats and dolphins use sound to echolocate targets. By sending out pulses of light and timing how long it takes the beams to hit something and bounce back, lidar senses reflective particles like algae in the water.

Lead study author Brian Collister used a shipboard lidar system to detect algae and learn about conditions deeper in the ocean than satellites can measure. The research team on this 2018 cruise was composed of scientists from Old Dominion University and Bigelow Laboratory for Ocean Sciences.

“The lidar approach has the potential to fill some important gaps in our ability to measure ocean biology from space,” said Collister, a PhD student at Old Dominion University. “This technique will shed new light on the distribution of biology in the upper oceans, and allow us to better understand their role in Earth’s climate.”

In the Gulf of Maine, the team used lidar to detect and measure particles of the mineral calcium carbonate, gathering information about a bloom of coccolithophores. These algae surround themselves with calcium carbonate plates, which are white in color and highly reflective. The plates scatter light in a unique way, fundamentally changing how the light waves are oriented – and creating an identifiable signature that the lidar system can recognize.

Balch’s research team has studied the Gulf of Maine for over two decades through the Gulf of Maine North Atlantic Time Series. Their experience in finding and identifying algae in this ecosystem provided key background information for testing the lidar system in what turned out to be the largest coccolithophore bloom observed in the region in 30 years.

“This cruise allowed us an ideal opportunity to try the lidar system out with the ability to sample the water and know exactly what species were in it,” Balch said. “Lidar has been used in the ocean for decades, but few, if any, studies have been done inside a confirmed coccolithophore bloom, which profoundly changes how light behaves in the environment.”

Coccolithophores thrive around the global ocean and exert a huge level of control on the biogeochemical cycles that shape the planet. Studying them is key to understanding global ocean dynamics, but field research is always costly. The team established that using lidar could potentially allow researchers to remotely estimate coccolithophore populations without stopping the ship to collect water samples – increasing their ability to collect valuable data, thus also conserving precious ship-time funds.

The research team also tested this approach in ocean environments that included the clear depths of the Sargasso Sea and the turbid waters off the coast of New York City. They found it to be effective across these diverse environments. Lidar systems can probe the ocean up to three times deeper than passive satellite remote sensing techniques that rely on the sun. Further research may establish approaches that allow lidar measurements to be taken by satellites, as well.

“It’s a huge deal that we are learning to reliably identify particles in the ocean from a lidar system positioned above the water,” said Richard Zimmerman, a study author and professor at Old Dominion University. “This is a significant advance, and it could revolutionize our ability to characterize and model marine ecosystems.”

This work was supported by the National Aeronautics and Space Administration, the National Science Foundation, and the Virginia SpaceGrant Consortium.

Journal

Applied Optics

DOI

10.1364/AO.389845

Credit: 
Bigelow Laboratory for Ocean Sciences

NASA finds Post-Tropical Low Douglas crossing a line   

image: On July 30 at 0105 UTC (July 29 at 9:05 p.m. EDT), the MODIS instrument that flies aboard NASA's Aqua satellite gathered infrared data on Douglas that confirmed wind shear was adversely affecting the storm. Persistent southerly vertical wind shear pushed strongest storms (yellow) north of the center where cloud top temperatures are as cold as minus 50 degrees Fahrenheit (minus 45.5 Celsius).

Image: 
NASA/NRL

The strong wind shear that weakened Douglas to a tropical storm early on July 29 has further weakened it to a post-tropical low-pressure area. NASA's Aqua satellite provided an infrared view of those remnants, headed across the International Date Line in the Pacific Ocean.

NASA's Aqua Satellite Shows a Post-tropical System 

NASA's Aqua satellite uses infrared light to analyze the strength of storms by providing temperature information about the system's clouds. The strongest thunderstorms that reach high into the atmosphere have the coldest cloud top temperatures.

On July 30 at  0105 UTC  (July 29 at 9:05 p.m. EDT), the Moderate Resolution Imaging Spectroradiometer or MODIS instrument that flies aboard NASA's Aqua satellite gathered infrared data on Douglas that confirmed wind shear had reduced the storm to a post-tropical low pressure area. The wind shear pushed the coldest cloud tops northeast of the center. Those storms had cloud top temperatures as cold as minus 50 degrees Fahrenheit (minus 45.5 Celsius).

What is a Post-tropical Cyclone?

NOAA's National Hurricane Center defines a post-tropical cyclone as a former tropical cyclone. This generic term describes a cyclone that no longer possesses sufficient tropical characteristics to be considered a tropical cyclone. Post-tropical cyclones can continue carrying heavy rains and high winds. Note that former tropical cyclones that have become fully extratropical... as well as remnant lows...are two classes of post-tropical cyclones.

Douglas Ready to Cross a Line

NOAA's Central Pacific Hurricane Center (CPHC) issued the final advisory on Douglas on July 29 at 11 a.m. EDT (5 a.m. HST/1500 UTC). Douglas had degenerated into a post-tropical low-pressure area about 1,135 miles (1,830 km) west-northwest of Honolulu, Hawaii. It was centered near latitude 24.7 degrees north and longitude 175.4 degrees west. The post-tropical cyclone is moving toward the west near 23 mph (37 kph). Maximum sustained winds are near 35 mph (55 kph) with higher gusts.

Douglas' remnants were expected to cross the International Date Line early on July 30, and it is expected to dissipate shortly after the crossing.

Established in 1884, the International Date Line passes through the mid-Pacific Ocean and generally follows a 180 degrees longitude north-south line on the Earth. East of the Date Line lies the central Pacific Ocean. West of the dateline is the western Pacific Ocean.

NASA Researches Tropical Cyclones

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

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

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

Credit: 
NASA/Goddard Space Flight Center

'Drawn-on-skin' electronics offer breakthrough in wearable monitors

image: A new form of electronics known as "drawn-on-skin electronics" allows multifunctional sensors and circuits to be drawn on the skin with an ink pen.

Image: 
University of Houston

A team of researchers led by Cunjiang Yu, Bill D. Cook Associate Professor of Mechanical Engineering at the University of Houston, has developed a new form of electronics known as "drawn-on-skin electronics," allowing multifunctional sensors and circuits to be drawn on the skin with an ink pen.

The advance, the researchers report in Nature Communications, allows for the collection of more precise, motion artifact-free health data, solving the long-standing problem of collecting precise biological data through a wearable device when the subject is in motion.

The imprecision may not be important when your FitBit registers 4,000 steps instead of 4,200, but sensors designed to check heart function, temperature and other physical signals must be accurate if they are to be used for diagnostics and treatment.

The drawn-on-skin electronics are able to seamlessly collect data, regardless of the wearer's movements.

They also offer other advantages, including simple fabrication techniques that don't require dedicated equipment.

"It is applied like you would use a pen to write on a piece of paper," said Yu. "We prepare several electronic materials and then use pens to dispense them. Coming out, it is liquid. But like ink on paper, it dries very quickly."

Wearable bioelectronics - in the form of soft, flexible patches attached to the skin - have become an important way to monitor, prevent and treat illness and injury by tracking physiological information from the wearer. But even the most flexible wearables are limited by motion artifacts, or the difficulty that arises in collecting data when the sensor doesn't move precisely with the skin.

The drawn-on-skin electronics can be customized to collect different types of information, and Yu said it is expected to be especially useful in situations where it's not possible to access sophisticated equipment, including on a battleground.

The electronics are able to track muscle signals, heart rate, temperature and skin hydration, among other physical data, he said. The researchers also reported that the drawn-on-skin electronics have demonstrated the ability to accelerate healing of wounds.

In addition to Yu, researchers involved in the project include Faheem Ershad, Anish Thukral, Phillip Comeaux, Yuntao Lu, Hyunseok Shim, Kyoseung Sim, Nam-In Kim, Zhoulyu Rao, Ross Guevara, Luis Contreras, Fengjiao Pan, Yongcao Zhang, Ying-Shi Guan, Pinyi Yang, Xu Wang and Peng Wang, all from the University of Houston, and Jiping Yue and Xiaoyang Wu from the University of Chicago.

The drawn-on-skin electronics are actually comprised of three inks, serving as a conductor, semiconductor and dielectric.

"Electronic inks, including conductors, semiconductors, and dielectrics, are drawn on-demand in a freeform manner to develop devices, such as transistors, strain sensors, temperature sensors, heaters, skin hydration sensors, and electrophysiological sensors," the researchers wrote.

Credit: 
University of Houston

American Cancer Society updates guideline for cervical cancer screening

An updated cervical cancer screening guideline from the American Cancer Society reflects the rapidly changing landscape of cervical cancer prevention in the United States, calling for less and more simplified screening. The guideline appears in the ACS's flagship journal, CA: A Cancer Journal for Clinicians.

The updated guideline recommends that individuals with a cervix initiate cervical cancer screening at age 25, continuing through age 65, and that primary human papillomavirus (HPV) testing (HPV testing without the Pap test) every 5 years be the preferred method of testing.

The guideline says using HPV testing in combination with a Pap test (called cotesting) every 5 years or Pap tests alone every 3 years are acceptable options for now, as not all labs have transitioned to primary HPV testing.

"These streamlined recommendations can improve compliance and reduce potential harms," said Debbie Saslow PhD, managing director, HPV & GYN Cancers for the American Cancer Society. "They are made possible by some important developments that have allowed us to transform our approach to cervical cancer screening, primarily a deeper understanding of the role of HPV and the development of tools to address it."

Virtually all cases of cervical cancer are caused by infection with high-risk strains of HPV. Evidence shows the HPV test is more accurate than the Pap test and can be done less often; one HPV test every five years is more effective than a Pap test every three years, and even every year as was recommended in the 1980's and 1990's, in reducing the risk of cervical cancer. A negative HPV test is linked to a very low cervical cancer risk. In addition, a vaccine for HPV has been in use for nearly 15 years, and more women of screening age are now vaccinated and protected from the majority of cervical cancers.

The previous ACS guideline, released in 2012, called for screening starting at age 21. Since then, HPV vaccination rates have improved in the United States. Data suggest vaccination has led to a drop in rates of precancerous cervical changes, the precursors to cancer. In addition, cervical cancer incidence is low in this age group. Cancer registry data from 2011 to 2015 indicates an estimated 108 cases of invasive cervical cancer in women 20 to 24 years in the U.S. each year, a number that is expected to continue to fall as vaccine use increases. There are also potential harms related to the treatment of precancerous cells identified by screening including preterm birth, and screening has not been shown to lower the rate of cancer in women in this age group. Also, most HPV infections in women in this age group become undetectable in 1-2 years. Those factors led the ACS to move the recommended age to initiate cervical cancer screening to 25.

"We estimate that compared with the currently recommended strategy of cytology (Pap testing) alone beginning at age 21 and switching to cotesting at age 30 years, starting with primary HPV testing at age 25 will prevent 13% more cervical cancers and 7% more cervical cancer deaths," said Dr. Saslow. "Our model showed we could do that with a 9% increase in follow-up procedures, but with 45% fewer tests required overall."

American Cancer Society screening guidelines are created by the Guideline Development Group (GDG), 11 clinicians and population health care professionals and 1 patient advocate appointed by the ACS Board of Directors to create all of its cancer screening guidelines. To avoid professional conflicts of interest, the GDG considers content specific input and the opinions of expert clinical specialists but is responsible for supervising the review of the evidence and transforming the evidence into writing the guidelines.

The full guideline:

The ACS recommends that individuals with a cervix initiate cervical cancer screening at age 25 and undergo primary HPV testing every 5 years through age 65 (preferred). If primary HPV testing is not available, individuals aged 25-65 years should be screened with cotesting (HPV testing in combination with cytology) every 5 years or cytology alone every 3 years (acceptable). (Strong recommendation)

Cotesting or cytology testing alone are included as acceptable options for cervical cancer screening because access to an HPV test that has been approved by the FDA for primary screening may be limited in some settings. As the US makes the transition to primary HPV testing, the use of cotesting or cytology alone for cervical cancer screening will not be included in future guidelines.

The ACS recommends that individuals with a cervix who are older than age 65 years, who have no history of CIN2+ within the past 25 years, and who have documented adequate negative prior screening in the 10-year period prior to age 65, discontinue cervical cancer screening with any modality. (Qualified recommendation)

Adequate negative prior screening is currently defined as 2 consecutive, negative primary HPV tests or 2 negative cotests or 3 negative cytology tests within the past 10 years, with the most recent test occurring within the past 5 years. These criteria do not apply to persons who are currently under surveillance for abnormal screening results.

If sufficient documentation of prior screening meeting criteria for screening cessation is not available, individuals with a cervix who are older than age 65 years, without conditions limiting life expectancy, should be screened until criteria are met.

Cervical cancer screening may be discontinued in individuals of any age with limited life expectancy.

Credit: 
American Cancer Society

Headline news: Botox injections may lessen depression

Botox, a medication derived from a bacterial toxin, is commonly injected to ease wrinkles, migraines, muscle spasms, excessive sweating and incontinence. Forehead injection of the medication is also currently being tested in clinical trials for its ability to treat depression.

Researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego have mined the U.S. Food and Drug Administration (FDA)'s Adverse Effect Reporting System (FAERS) database to see what nearly 40,000 people reported happened to them after treatment with Botox for a variety of reasons.

In the study, published July 30, 2020 in Scientific Reports, the team discovered that people who received Botox injections -- at six different sites, not just in the forehead -- reported depression significantly less often than patients undergoing different treatments for the same conditions.

"For years, clinicians have observed that Botox injected for cosmetic reasons seems to ease depression for their patients," said Ruben Abagyan, PhD, professor of pharmacy. "It's been thought that easing severe frown lines in forehead region disrupts a feedback loop that reinforces negative emotions. But we've found here that the mechanism may be more complex, because it doesn't really matter where the Botox is injected."

Abagyan led the study with Tigran Makunts, PharmD, who was a pharmacy student at the time and is now a research fellow at the FDA, and Marc Axel Wollmer, MD, a psychiatrist and researcher in Germany who has led past clinical studies in which Botox was found to alleviate depression.

The FAERS database contains more than 13 million voluntary reports of adverse effects people experienced while taking a medication. Abagyan and team have found they can also use the database to look at absence of a health complaint when a person takes a medication, if compared to a control group. In this case, they searched for the absence of depression.

The team focused on nearly 40,000 FAERS reports of people experiencing adverse events after Botox treatment. The reports cover Botox treatment for eight different reasons and injection sites, including forehead, neck, limbs and bladder. Then the team applied a mathematical algorithm to look for statistically significant differences between Botox users and patients who received different treatments for the same conditions.

Here's what they found: Depression was reported 40 to 88 percent less often by Botox-treated patients for six of the eight conditions and injection sites.

"This finding is exciting because it supports a new treatment to affect mood and fight depression, one of the common and dangerous mental illnesses -- and it's based on a very large body of statistical data, rather than limited-scale observations," Makunts said.

To be clear, the data used in this study was not collected for the purpose of exploring the association between Botox use and depression exclusively. In addition, the FAERS data represents only the subset of Botox users who experienced negative side effects. While the team excluded reports in which a person was also taking antidepressants, the use of other prescription and over-the-counter medications could have been underreported in some cases.

The clinical trial underway are directly testing Botox treatment for people with depression, a gold standard approach for gathering insights on the relationship between a medication and a health condition. Since that trial is only testing forehead injection of Botox, Abagyan says additional clinical trials may be necessary to work out the best site and dose to administer the medication specifically for the treatment of depression.

Likewise, more research is needed to determine the mechanism by which Botox acts as an antidepressant, Abagyan says. He and collaborators hypothesize a few possibilities worth investigating: Botox could be transported to the regions of the central nervous systems involved in mood and emotions. Or, since Botox is commonly used to treat chronic conditions that may contribute to depression, its success in relieving the underlying problem may indirectly also relieve depression.

The World Health Organization estimates that more than 264 million worldwide experience depression. Depression is frequently treated with psychotherapy, selective serotonin reuptake inhibitors, dopamine-norepinephrine reuptake inhibitors and/or serotonin-norepinephrine reuptake inhibitors. Yet these approaches are ineffective for nearly one-third of patients. That's why clinicians and researchers are exploring other therapeutic options, including electroconvulsive therapy, transcranial magnetic stimulation, ketamine infusions and, more recently, Botox forehead injections.

Credit: 
University of California - San Diego

NIH researchers discover new set of channels connecting malaria parasite and blood cells

image: Diagram of the two membrane channels between the malaria parasite vacuole and the red blood cell.

Image: 
National Institutes of Health

WHAT:

Researchers at the National Institutes of Health and other institutions have discovered another set of pore-like holes, or channels, traversing the membrane-bound sac that encloses the deadliest malaria parasite as it infects red blood cells. The channels enable the transport of lipids--fat-like molecules--between the blood cell and parasite, Plasmodium falciparum. The parasite draws lipids from the cell to sustain its growth and may also secrete other types of lipids to hijack cell functions to meet its needs.

The finding follows an earlier discovery of another set of channels through the membrane enabling the two-way flow of proteins and non-fatty nutrients between the parasite and red blood cells. Together, the discoveries raise the possibility of treatments that block the flow of nutrients to starve the parasite.

The research team was led by Joshua Zimmerberg, M.D., Ph.D., a senior investigator in the Section on Integrative Biophysics at NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The study appears in Nature Communications.

In 2018, there were 228 million cases of malaria worldwide, leading to more than 400,000 deaths, 67% of which were among children under 5, according to the World Health Organization. In the current study, researchers determined that the channels through the sac, or vacuole, that encloses the parasite are made of Niemann-Pick C1-related protein (PfNCR1). The PfNCR1 channels are restricted to locations where the vacuole membrane touches the parasite's membrane. The channels the team discovered in the previous study are formed by exported protein 2 (EXP2). Areas of the vacuole membrane containing EXP2 are located far from the parasite's membrane, at an average distance of 20 to 40 nanometers. The researchers believe that the parasite may use this variation in distance to separate the two transport systems.

Credit: 
NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development

Keep safe and cool in the pool: Novel chip sensor makes swimming pools safer

image: The new chip will remove the arduous task of manually testing swimming pools, avoids overuse of pool chemicals, and reduces the risk of infection from incorrect pool chemistry.

Image: 
University of SA

A new microchip that enables continuous monitoring of pH and chlorine levels in swimming pools will vastly improve water safety and hygiene for more than 2.7 million Australians as new research shows it can deliver consistent and accurate pool chemistry for reliable pool management.

Developed by the University of South Australia using world-class fabrication capabilities, in partnership with electronics research and manufacturing company Tekelek Australia, the new 'lab-on-a-chip' technology, makes monitoring swimming pools more affordable, more reliable, and easy to install - even on existing pools.

UniSA researcher and micro/nanofabrication expert, Associate Professor Craig Priest, says the microfluidic chip could be a vital addition to Australian swimming pools, particularly as COVID-19 makes people more aware of the importance of pool hygiene.

"Pool chemistry keeps swimmers safe from viruses and bacteria, yet getting it right takes a lot of effort," Assoc Prof Priest says.

"Backyard swimming pool management would be a lot easier with a continuous and automated water quality sensor that can reliably measure accurate chlorine and pH levels all summer.

"The sensor that we've developed is essentially a 'lab-on-a-chip' - a network of microscopic pipes running through a credit card-sized chip.

"The chip quickly and continuously does all the work of a chemistry laboratory using tiny amounts of chemical, without leaving the poolside.

"For pool owners, this removes the arduous task of manually testing swimming pools and avoids overuse of pool chemicals, which saves time, money and, most importantly, the risk of infection from incorrect pool chemistry."

In Australia, 2.7 million people (13 per cent of the population) live in a house with a swimming pool. Currently, existing pool monitoring systems - either wireless swimming pool sensors with expensive hardware or labour-intensive manual testing kits such as those purchased at hardware stores - are used to monitor the safety of chemicals in pools.

But, as Assoc Prof Priest says, asking pool owners to be backyard chemists could turn summer fun into a health hazard.

"Many of the domestic pools samples showed flaws in manual pool testing," Assoc Prof Priest says.

"One family's swimming pool was seriously overdosed with chlorine, yet they had no idea.

"Having just bought their home, they did a quick water check at the local pool shop and were told that there was 'enough' chlorine in the water but didn't show that there was actually too much.

"A few weeks later, the chlorine levels dropped to zero, which not only highlighted a problem with the chlorinator, but also showed how quickly pool chemistry can become unsafe."

The research tested samples from 12 swimming pools (nine domestic, two public and one outdoor public) with measures taken on multiple occasions. Every sample had its own ambient situation - frequent public use, high leaf matter, different chlorination methods - ensuring realistic sensor challenges.

An over-dosage of chlorine can cause adverse health effects to the skin, eyes, and immune system, while under-dosage creates risks of infection for swimmers.

Research partner, Stephen Thornton, Tekelek Australia says the new microchip has mass potential for both private and public swimming pools.

"Right now, the need to stay healthy is paramount for us all, and while we generally feel safe in our own backyard, we must remember that all swimming pools need to be accurately and efficiently monitored to ensure water safety," Thornton says.

"Partnering with UniSA has meant that we've been able to develop a product that truly meets the needs of the market, while also ensuring public health and safety."

The research team is currently in the final stages of developing the microchip with industry and hopes to have it on the market soon.

Credit: 
University of South Australia

Peering into the secrets of phages to see how they kill bacterial superbugs

image: Artistic representation of the flagellotropic YSD1 bacteriophage based on cryo-electron microscopy reconstructions. The virus' host Salmonella Typhi is a flagellated bacteria responsible for typhoid fever. It is shown at a smaller scale in the background.

Image: 
F. Coulibaly & J.M. Hardy

A research collaboration involving Monash University has made an exciting discovery that may eventually lead to targeted treatments to combat drug-resistant bacterial infections, one of the greatest threats to global health.

The study, led by Monash Biomedicine Discovery Institute's Associate Professor Fasséli Coulibaly and Professor Trevor Lithgow is published in Nature Communications. It outlines the use of high-resolution imaging to uncover how viruses known as phages can attack and kill Salmonella Typhi, the causative agent of typhoid, providing scientists with a new understanding of how they can be used in the ongoing fight against antimicrobial resistance (AMR).

The study was a collaboration between researchers at the Monash Biomedicine Discovery Institute (BDI), the Monash University Centre to Impact AMR and the University of Cambridge.

What they saw was an incredible "choreography" by the phages as they assembled the main components of their particles: a head filled with the viral DNA and a tail used to infect the bacteria.

"We saw how the building blocks of the particle interlock in an intricate choreography. At a molecular level, arms swing out and curl around each other forming a continuous chain that braces the head of the phage," Associate Professor Coulibaly said.

"This rigid chainmail provides further protection to the DNA of the phage. Surprisingly, the tail on the other hand remains flexible. It's able to bend and not break as it captures the bacteria and ultimately injects them with the phage DNA."

Phages are a class of viruses that infect bacteria, and each phage is specific for the species of bacteria it can kill. Phages can be purified to a point of being FDA-approved for treatment of people with bacterial infections, and documented success has been had in the USA, Europe and, recently, Australia.

At Monash University, the Centre to Impact AMR is grappling with these issues and is looking at the types of phages needed for new, "phage therapies" to treat bacterial infections.

"This finding will help us overcome one of the most critical hurdles in phage therapies which is a precise understanding of how phage work, in order to predict in advance and select with accuracy the best phage for each patient infection," Professor Lithgow said.

"It could help move phage therapies from compassionate use, where all other treatment options have been exhausted, to more widespread clinical use."

Antimicrobial resistance (AMR) is one of the biggest threats to global health, food security and economic development. It is a pressing health and humanitarian crisis in Asia, that is increasing in severity globally.

AMR affects all aspects of society and is driven by many interconnected factors including antibiotic overuse, and the rapidly adaptive nature of bacteria to evolve into drug-resistant forms. At-risk groups for AMR infections are many, and include COVID-19 patients on respirators, mothers and children during childbirth, surgery patients, people with cancer and chronic disease and the elderly.

The first authors of this study Dr Joshua Hardy and Dr Rhys Dunstan used the Ramaciotti centre for cryo-electron microscopy at Monash University, the Monash molecular crystallisation facility, and the Australian Synchrotron for the structure determination.

Credit: 
Monash University

Scientists make quantum technology smaller

A way of shrinking the devices used in quantum sensing systems has been developed by researchers at the UK Quantum Technology Hub Sensors and Timing, which is led by the University of Birmingham.

Sensing devices have a huge number of industrial uses, from carrying out ground surveys to monitoring volcanoes. Scientists working on ways to improve the capabilities of these sensors are now using quantum technologies, based on cold atoms, to improve their sensitivity.

Machines developed in laboratories using quantum technology, however, are cumbersome and difficult to transport, making current designs unsuitable for most industrial uses.

The team of researchers has used a new approach that will enable quantum sensors to shrink to a fraction of their current size. The research was conducted by an international team led by University of Birmingham and SUSTech in China in collaboration with Paderborn University in Germany. Their results are published in Science Advances.

The quantum technology currently used in sensing devices works by finely controlling laser beams to engineer and manipulate atoms at super-cold temperatures. To manage this, the atoms have to be contained within a vacuum-sealed chamber where they can be cooled to the desired temperatures.

A key challenge in miniaturising the instruments is in reducing the space required by the laser beams, which typically need to be arranged in three pairs, set at angles. The lasers cool the atoms by firing photons against the moving atom, lowering its momentum and therefore cooling it down.

The new findings show how a new technique can be used to reduce the space needed for the laser delivery system. The method uses devices called optical metasurfaces - manufactured structures that can be used to control light.

A metasurface optical chip can be designed to diffract a single beam into five separate, well-balanced and uniform beams that are used to supercool the atoms. This single chip can replace the complex optical devices that currently make up the cooling system.

Metasurface photonic devices have inspired a range of novel research activities in the past few years and this is the first time researchers have been able to demonstrate its potential in cold atom quantum devices.

Dr Yu-Hung Lien, lead author of the study, says: "The mission of the UK Quantum Technology Hub is to deliver technologies that can be adopted and used by industry. Designing devices that are small enough to be portable or which can fit into industrial processes and practices is vital. This new approach represents a significant step forward in this approach."

The team have succeeded in producing an optical chip that measures just 0.5mm across, resulting in a platform for future sensing devices measuring about 30cm cubed. The next step will be to optimise the size and the performance of the platform to produce the maximum sensitivity for each application.

Credit: 
University of Birmingham

Reopening K-12 schools during COVID-19 pandemic

What The Viewpoint Says: This article summarizes recommendations made in a National Academies of Sciences, Engineering, and Medicine report about how to safely reopen and operate elementary and secondary schools for the 2020-2021 school year, which emphasizes the need for partnerships with public health officials and community leaders, and for transparent communication of risks and rewards that will result from every policy decision.

Authors: Kenne A. Dibner, Ph.D., of the National Academies of Sciences, Engineering and Medicine in Washington, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2020.14745)

Editor's Note: The article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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Media advisory: The full Viewpoint and other related articles are attached to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2020.14745?guestAccessKey=8b99722f-c78a-4632-968e-e84154ec719c&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=072920

Credit: 
JAMA Network

Trying to listen to the signal from neurons

image: Local-differential recording of neuronal activities (top) Fabricated coaxial needle-electrode (bottom)

Image: 
COPYRIGHT (C) TOYOHASHI UNIVERSITY OF TECHNOLOGY. ALL RIGHTS RESERVED.

Overview

Associate Professor Takeshi Kawano, Department of Electrical and Electronic Information Engineering, Toyohashi University of Technology (TUT) and the research team at the Electronics-Inspired Interdisciplinary Research Institute (EIIRIS) have developed a coaxial cable-inspired needle-electrode with the diameter of less than 10 μm, using crystal growth of semiconducting material of silicon. The microscale coaxial needle-electrode has two electrodes in the needle, enabling differential recordings to be made at very close distances, a task that had previously been difficult with conventional electrode devices. In addition, the microscale electrode reduces tissue damage compared to conventional electrodes. These advantages of the coaxial electrode enable high-quality recording of neuronal signals that could not be realized with conventional ways, and it is expected that the coaxial needle-electrode can be used as a new way of electrophysiology in the field of neuroscience.

Details

Neuronal signals can be detected by penetrating a fine electrode into the brain tissue. They are a very important technology for electrophysiological recording in the brain tissue, and by taking the advantage of high spatial resolution it is possible to gain detailed information about neuronal activity. For example, in brain-machine interface (BMI) technology--a technique that allows a patient to move their prosthetic arm or leg using signals from their brain--the technology used to implant the electrodes in the patient's brain and record the neuronal signals with high spatial resolution is very important. It is also important to maintain a high signal-to-noise ratio when recording the signals. Electrical signals from neurons are extremely small, on the order of tens of μV (1/100,000 of 1 V), and the quality of the signal deteriorates due to noise propagating in the tissue space. This means that electrode devices must have high spatial resolution and be highly resistant to noise. Furthermore, an electrode geometry of 10 μm or less is required in order to avoid damage to the brain tissue.

To solve these challenges relating to the electrodes, the research team used the vapor-liquid-solid (VLS) growth method--a silicon growth technology--to develop a needle-like electrode device having closely positioned two electrodes in the

Development Background

Shinnosuke Idogawa, a PhD student at TUT and the lead author, commented, "In order to achieve the proposed local-differential recording, we proposed a coaxial cable-inspired microneedle-electrode. This coaxial electrode enables to dramatically reduce the electrode spacing to 6 μm compared to, for example, around 200 μm electrode spacing where conventional needle electrodes are arranged side by side. Furthermore, by performing local-differential recording with these two electrodes, we were able to reduce noise during the recording. In addition, because of the tiny needle electrode with the diameter of less than 10 μm, we are able to reduce tissue damage compared to conventional electrodes with diameters of 50 μm or more. Consequently, we have developed an electrode device that can record neuronal signals with high-quality and low invasiveness.

Future Outlook

The research team believes it will be necessary to verify whether the proposed coaxial electrode can give stable recordings over a long period of time, and to evaluate tissue damage. Through this work, the research team are aiming to realize high-quality neuronal signal acquisition that has never been achieved before, and hope that the electrode device technology will be used not only for basic research in neuroscience but also for medical applications, including BMI technology and treatments of various brain diseases.

Credit: 
Toyohashi University of Technology (TUT)

Study provides new insight on colorectal cancer growth

A new study by researchers at the University of Kentucky identifies a novel function of the enzyme spermine synthase (SMS) to facilitate colorectal cancer growth.

SMS is an enzyme that produces spermine from spermidine, which has been shown to be important for cell growth. However, excessive accumulation of spermidine can have harmful effects on cell viability. How cancer cells maintain a relatively high level of spermidine but below the toxic threshold to facilitate tumor growth is not well understood.

A group led by the Markey Cancer Center researcher Qing-Bai She, a professor in the UK College of Medicine's Department of Pharmacology and Nutritional Sciences, discovered that SMS is overexpressed in colorectal cancers and plays an important role in balancing cellular spermidine levels that are a necessary adaptation for colorectal cancer growth.

The group further revealed a link between the signaling of SMS and the oncogene MYC, a gene that plays a role in many cancer types, to maintain colorectal cancer cell survival. The study showed that combined inhibition of SMS and MYC signaling induced cancer cell death and tumor regression, which could be a promising strategy for colorectal cancer therapy.

"Our findings provide an in-depth understanding of how the polyamine metabolic pathway interacts with oncogenic signaling pathways in tumorigenesis and highlight the unmet need of clinically effective SMS inhibitors for the targeted therapy," said She.

Credit: 
University of Kentucky