The beetle’s extraordinary arsenal has been held up by some as a proof of God’s existence: how on earth, creationists argue, could such a complex, multistep defense mechanism evolve by chance? Now researchers at Stevens Institute of Technology in Hoboken, N.J. show how the bombardier beetle concocts its deadly explosives and in the process, learn how evolution gave rise to the beetle’s remarkable firepower.

“We explain for the first time how these incredible beetles biosynthesize chemicals to create fuel for their explosions,” said Athula Attygalle, a research professor of chemistry and lead author of the work, which appears today in the July 2020 issue of the Science of Nature. “It’s a fascinating story that nobody has been able to tell before.”

To trace the workings of the beetle’s internal chemistry set, Attygalle and colleagues at University of California, Berkeley used deuterium, a rare hydrogen isotope, to tag specially synthesized chemical blends. The team led by Kipling Will then either injected the deuterium-labeled chemicals into the beetles’ internal fluids, or mixed them with dog food and fed them to the beetles over a period of several days.

Attygalle’s team sedated the bugs by popping them in the freezer, then gently tugged at their legs, annoying the sleepy insects until they launched their defensive sprays onto carefully placed filter papers. The team also dissected some beetles, using human hairs to tie closed the tiny ducts linking their chemical reservoirs and reaction chambers, and sampling the raw chemicals used to generate explosions.

Using mass spectrometers, Attygalle checked the samples sent to Stevens for deuterium-labeled products, enabling him to figure out exactly which chemicals the beetles had incorporated into their bomb-making kits. “People have been speculating about this for at least 50 years, but at last we have a clear answer,” Attygalle said. “It turns out that the beetles’ biochemistry is even more intricate than we’d thought.”

Previously, researchers had assumed that two toxic, benzene-like chemicals called benzoquinones found in the beetles’ spray were metabolized from hydroquinone, a toxic chemical that in humans can cause cancer or genetic damage. The team at Stevens showed that in fact just one of the beetle’s benzoquinones derived from hydroquinone, with the other springing from a completely separate precursor: m-cresol, a toxin found in coal tar.

It’s fascinating that the beetles can safely metabolize such toxic chemicals, Attygalle said. In future studies, he hopes to follow the beetles’ chemical supply chain further upstream, to learn how the precursors are biosynthesized from naturally available substances.

The team’s findings also show that the beetles’ explosives rely on chemical pathways found in many other creepy-crawlies. Other animals such as millipedes also use benzoquinones to discourage predators, although they lack the bombardier’s ability to detonate their chemical defenses. Evolutionarily distant creatures such as spiders and millipedes use similar strategies, too, suggesting that multiple organisms have independently evolved ways to biosynthesize the chemicals.

That’s a reminder that the bombardier beetle, though remarkable, is part of a rich and completely natural evolutionary tapestry, Attygalle said. “By studying the similarities and differences between beetles’ chemistry, we can see more clearly how they and other species fit together into the evolutionary tree,” he explained. “Beetles are incredibly diverse, and they all have amazing chemical stories to tell.”

Every year, dozens and even hundreds of “cold-stunned” turtles are treated at the Aquarium’s Quincy Animal Care Center for a variety of life-threatening medical conditions that result from weeks of hypothermia and the inability to feed during stranding season. Typically, the stranding season begins in early November and runs through early January when New England water temperatures quickly turn cold and the turtles get stuck on the north side of Cape Cod. The turtles are then rescued and rehabilitated for two to eight months. When the time comes to be released back into the wild, the turtles must enter the ocean at beaches with appropriate water temperatures, often requiring transportation to southeastern states by climate controlled SUV or van. These transports may take up to 24 hours, and can induce a stress response.

“As for humans, traveling many hours over long distances can be stressful for turtles. We wanted to characterize the degree of the stress response and document whether the turtles were still in good condition after such a long trip,” said Dr. Charles Innis, Director of Animal Health at the New England Aquarium.

Until now, the full impact of the transport process was unclear. In this new study, led by Dr. Kathleen Hunt of George Mason University and published in the journal Integrated Organismal Biology, all turtles had stranded in a cold-stunned state along the shore of Cape Cod Bay between October and December of 2011-2017 and were rehabilitated at the Aquarium’s Animal Care Center for six to eight months. During trips to release the turtles back into the wild, scientists studied the responses of Kemp’s ridley and loggerhead turtles before and after vehicle transport for under six hours, 12 hours, 18 hours, and 24 hours, gathering blood samples.

The researchers found that transport induced a physiological stress response for both sea turtle species. The duration of those transports significantly affected the stress responses, with both species showing more pronounced changes on longer journeys. Importantly, despite the findings, both turtle species in the study remained in good clinical condition based on evaluation of vital signs and blood data, even after 24-hour transport. Nonetheless, the researchers suggest that minimizing transport time, when possible, may help to ensure that rehabilitated turtles are released into the ocean under the best possible conditions.

“Results of this study will be used to ensure that sea turtle transports are conducted under controlled environments and at safe durations,” said Connie Merigo, Marine Animal Rescue Department Manager. “This study will be helpful to the global community of sea turtle rehabilitators, veterinarians, researchers and biologists.”

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In a study published in the journal PLOS ONE, honeybee researchers in OSU’s College of Agricultural Sciences found detrimental effects in bees exposed to Transform and Sivanto, which are both registered for use in the United States and were developed to be more compatible with bee health.

The western honeybee is the major pollinator of fruit, nut, vegetable and seed crops that depend on bee pollination for high quality and yield.

Coupled with other stressors such as varroa mites, viruses and poor nutrition, effects from these pesticides can render honeybees incapable of performing their tasks smoothly. Beekeepers and some environmental groups have raised concerns in recent years about these insecticides and potential negative effects on bees.

According to the researchers, this is the first study to investigate “sub-lethal” effects of sulfoxaflor, the active ingredient in Transform, and flupyradifurone, the active ingredient in Sivanto. Sub-lethal effects mean that the bees don’t die immediately, but experience physiological stress resulting in shortened lifespan.

In the case of Transform, the bees’ lives were severely shortened. A majority of the honeybees exposed to Transform died within six hours of being exposed, confirming the severe toxicity of the pesticide to bees when exposed directly to field application rates recommended on the label, the researchers said.

Study lead author Priyadarshini Chakrabarti Basu, a postdoctoral research associate in the Honey Bee Lab in OSU’s College of Agricultural Sciences, emphasized that the researchers aren’t calling for Sivanto or Transform to be taken off the market.

“We are suggesting that more information be put on the labels of these products, and that more studies need to be conducted to understand sublethal effects of chronic exposure,” Basu said.

Sivanto and Transform are used on crops to kill aphids, leaf hoppers and whiteflies, among other pests. Many of these same crops attract bees for pollination. There are some restrictions on their use. For example, Transform can’t be applied to crops in bloom, for example.

Honeybees might be exposed indirectly through pesticide drift, said study co-author Ramesh Sagili, associate professor of apiculture and honeybee Extension specialist in OSU’s College of Agricultural Sciences.

“The average life span of a worker honeybee is five to six weeks in spring and summer, so if you are reducing its life span by five to 10 days, that’s a huge problem,” Sagili said. “Reduced longevity resulting from oxidative stress could negatively affect colony population and ultimately compromise colony fitness.”

For the study, the researchers conducted two contact exposure experiments: a six-hour study and a 10-day study in May 2019. The honeybees were obtained from six healthy colonies at the OSU apiaries. In each experiment, groups of 150 bees were placed in three cages. One group was exposed to Transform, a second to Sivanto and the third was a control group that wasn’t exposed to either pesticide.

Honeybee mortality, sugar syrup and water consumption, and physiological responses were assessed in bees exposed to Sivanto and Transform and compared to bees in a control group. Mortality in each cage was recorded every hour for the six-hour experiment and daily for the 10-day experiment.

While Sivanto was not directly lethal to honeybees following contact exposure, the 10-day survival results revealed that field-application rates of Sivanto reduced adult survival and caused increased oxidative stress and apoptosis in the honey bee tissues. This suggests that even though Sivanto is apparently less toxic than Transform, it might also reduce honeybee longevity and impart physiological stress, according to the study authors.

Co-authors on the study included graduate student Emily Carlson and faculty research assistant Hannah Lucas, who both conduct research in the Honey Bee Lab; and Andony Melathopoulos, assistant professor and pollinator health Extension specialist.

As detailed in a paper published online today by The Lancet Oncology, patients with high-grade serous ovarian cancer (HGSOC) who were treated with the drug, berzosertib, and chemotherapy lived substantially longer before their disease began to worsen than did those treated with chemotherapy alone. The findings may set the stage for testing berzosertib — an inhibitor of the ATR protein — in a range of other cancers, investigators say.

“Our results in his phase 2 trial suggest that ATR inhibition in combination with chemotherapy has the potential to offer significant benefit to patients with chemotherapy-resistant HGSOC and, potentially, other tumor types where ATR plays a key role,” says the study’s lead author, Panagiotis Konstantinopoulos, MD, PhD, director of translational research, Gynecologic Oncology, at Dana-Farber.

Berzosertib is designed to take advantage of one of the most glaring vulnerabilities of some cancer cells. Like a tractor run non-stop, a tumor cell, driven by a constant imperative to proliferate, is apt to need frequent repairs. In a tumor cell, that involves fixing broken strands of DNA.

HGSOC, like other types of cancer, relies heavily on the ATR protein in making those repairs. That reliance becomes even greater when these cancers are treated with chemotherapy, which disrupts cells’ ability to copy their DNA.

“The unbridled growth of cancer cells places enormous stress on the process of DNA replication,” Konstantinopoulos explains. “ATR helps them survive that stress: its job is to coordinate the halting of the cell cycle to check if the DNA is intact or needs repair. Drugs that inhibit ATR — that deprive tumor cells of such repair — have the potential to be particularly effective in some cancers.”

In the study, investigators at 11 cancer centers around the country enrolled 70 patients with HGSOC that was resistant to platinum-based chemotherapy. Half the participants were randomly assigned to receive the standard chemotherapy agent gemcitabine alone and half received gemcitabine in combination with berzosertib.

The estimated median progression-free survival of patients receiving gemcitabine alone — the period in which their disease was in retreat or stable — was 14.7 weeks. For those receiving gemcitabine and berzosertib, it was 22.9 weeks. Among patients with the most platinum resistant tumors (i.e. those who had progressed within 3 months from prior platinum-based chemotherapy), the difference was even greater: 9 weeks for gemcitabine versus 27.7 weeks for gemcitabine and berzosertib.

Side effects were similar in the two groups. Those receiving the combination therapy, however, had a higher rate of thrombocytopenia, or low blood platelet levels.

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Materials provided by Dana-Farber Cancer Institute. Note: Content may be edited for style and length.