How centipedes slay giant prey
Golden head centipede attacks a mouse.
Centipedes are known to subdue large prey by using potent, broad-acting venom. However, venom synthesis requires substantial metabolic investment, and the mechanisms of action of centipede venoms remain unclear. Lei Luo et al. (pp. 1646–1651) report that a golden head centipede (Scolopendra subspinipes mutilans) weighing around 3 g can set upon and subdue a caged laboratory mouse weighing around 45 g within 30 seconds, a single bite of the centipede injecting an estimated 30 µl of crude venom into the mouse. Biochemical analysis of centipede venom uncovered a previously uncharacterized peptide toxin, dubbed Ssm Spooky Toxin (SsTx), which strongly inhibits KCNQ family potassium ion channels, in particular KCNQ4, which controls pulmonary vascular tone and arterial tension. Structural and functional analysis revealed that two interacting pairs of amino acids (K13/D266 and R12/D288) are crucial to the toxin’s effect on KCNQ4. In vivo tests revealed that SsTx is the major vasoconstricting principle in venom, and that the toxin reduces respiratory rate and triggers hippocampal seizures in mice, as well as inducing vessel spasms, acute hypertension, and myocardial ischemia in macaque monkeys. Most of the toxin-induced effects could be reversed by the channel-opening compound retigabine, which is approved for epilepsy treatment. The findings uncover molecular targets of centipede venom and point to an antidote with clinical promise, according to the authors. — P.N.
E-cigarettes and DNA damage
E-cigarette. Image courtesy of Pixabay/lindsayfox.
E-cigarettes deliver nicotine as an aerosol without burning tobacco, and therefore avoid the carcinogenic byproducts of tobacco curing and combustion. E-cigarettes are marketed as a safer alternative to smoking tobacco. Hyun-Wook Lee et al. (pp. E1560–E1569) found that mice exposed to E-cigarette smoke (ECS) had higher levels of DNA damage in heart, lung, and bladder tissues, compared with control mice exposed to filtered air. Mice exposed to ECS also had reduced DNA repair activity and lower levels of certain DNA repair proteins in the lungs relative to control mice. Similar effects were observed in cultured human lung and bladder cells exposed to nicotine and nicotine-derived nitrosamine ketone (NNK), a carcinogenic nicotine derivative. Cultured human cells exposed to nicotine and NNK also had higher rates of mutation and tumorigenic transformation than control cells. The results suggest that nicotine nitrosation can occur in certain human and mouse tissues, and that the resulting products are further metabolized into DNA-damaging compounds. Thus, although ECS has fewer carcinogens than tobacco smoke, E-cigarette smokers might have a higher risk than nonsmokers of developing lung and bladder cancers and heart diseases, according to the authors. — B.D.
Polio eradication and regional conflict
Child receiving polio vaccine. Image courtesy of Wikimedia Commons/USAID.
The global incidence of paralytic polio cases has declined significantly in recent decades. Pakistan is one of the last remaining countries that have yet to stop poliovirus circulation. Insecurity related to regional conflict is often cited as a barrier to eradicating polio, but the claim is based on limited scientific evidence. Amol Verma et al. (pp. 1593–1598) analyzed the number of deaths and injuries related to monthly conflict-related security incidents and health data from 32 districts in northwest Pakistan to study the interplay of insecurity and polio vaccination and incidence. The dataset included 645 paralytic polio cases reported during 2007–2014 and 666 polio vaccination campaigns during 2007–2009. Using statistical modeling, the authors found that high insecurity was linked to reduced vaccinator access and polio vaccination. Campaigns associated with high levels of conflict-related insecurity experienced a 19.7% increase in the number of children inaccessible to vaccinators and a 5.3% decrease in vaccination rates, compared with secure campaigns. Additionally, the incidence of polio was 73% greater in months with high insecurity, compared with secure months. According to the authors, the findings suggest that regional insecurity might stymie polio eradication efforts. — C.S.
Coprolites reveal bird roles in New Zealand ecosystems
Coprolites, which are deposits of ancient dung, provide clues to how species loss affects ecosystems by preserving records of past interactions of extinct and endangered species. Alexander Boast et al. (pp. 1546–1551) sequenced DNA from 23 coprolite samples from four species of giant extinct moa and the endangered kakapo parrot at eight sites on New Zealand’s South Island, ranging in age from 124 to 1,557 years. High-throughput sequencing of the eukaryotic DNA preserved in the coprolites revealed previously unknown aspects of the birds’ dietary behavior, including the consumption of ferns and mosses by moa and the consumption of plant-symbiotic fungi by both moa and kakapo. The detection of fungal DNA suggests that bright-colored plant-symbiotic fungi in New Zealand, now a key component of forest ecosystems, were adapted for dispersal by ground-dwelling birds. The authors also found diverse parasite taxa and species-specific assemblages in the coprolites, suggesting a long history of coevolution and high coextinction between parasite and bird species. According to the authors, the results demonstrate how high-throughput sequencing of coprolites can complement fossil analysis in illuminating the functioning of paleoecosystems. — P.G.
Mechanism of prodrug resistance
The chemotherapy prodrug cytarabine, also known as ara-C, kills cancer cells by interfering with DNA metabolism. Though the drug has been used for decades to treat cancers such as leukemia, lymphoma, and mesothelioma, several aspects of the mechanism of action of this class of drugs remain unclear, including their selectivity for cancer cells and sensitivity for certain cancer types. Therese Triemer et al. (pp. E1366–E1373) describe a traceable mimic of cytarabine that maintains the drug’s biological properties and use super-resolution microscopy to examine its metabolism and mode of action. Produced by converting a single hydroxyl group to azide, the compound exhibits the same biological profile as cytarabine in zebrafish larvae cell cultures. The authors used click chemistry to reveal an apparent contradiction in a hypothesis about how these drugs mediate resistance and sensitivity. The authors report that drug-resistant cells incorporate cytarabine into their genomes in relatively large quantities compared with drug-sensitive cells. According to the authors, the results suggest that normal and drug-resistant cancer cells derive a high degree of stability by efficiently incorporating cytarabine into their DNA, thus causing the formation of reversibly stalled replication forks rather than chain termination and cell death. — T.J.