Enhanced vision may have enabled evolutionary shift from water to land
Enlarged eyes may have aided vertebrates’ shift from water to land.
The origin of limbs in the evolutionary foray of vertebrates from water to land has long claimed researchers’ interest, but the role of vision in this momentous transition, which began around 385 million years ago, has been little explored. Malcolm MacIver et al. (pp. E2375–E2384) assembled 1,000 time-constrained evolutionary trees for 59 fossil animals that bookend the transition and boast reasonably well-preserved skulls and eye sockets. Analysis of relative eye socket sizes measured from published records revealed that the mean absolute eye socket size—and, by inference, eye size—nearly tripled during the time interval that separates lobe-finned fishes from tetrapods with digit-bearing limbs. Further, the placement of eyes changed from the piscine lateral position to bony ridges atop the head, long before limbs evolved from fins. Computational simulations of the animals’ visual environments and performance suggest that the enlarged eyes improved the animals’ ability to see through the transparent medium of air while they lounged in water like crocodiles, eyes poised above the water line. The gain in eye size in turn provisioned a millionfold increase in visually monitored space and a greatly expanded smorgasbord of shore-bound invertebrate prey. According to the authors, such a boost in long-distance vision may have set the stage for the evolution of limbs as well as neural circuits required for a fully terrestrial mode of life. — P.N.
Continuous monitoring of organoid behavior
Modular multisensor integrated multiorgan-on-a-chip platform.
Organ-on-a-chip systems are miniaturized, microfluidic 3D devices designed to model the physiological environment of organs. While the devices hold potential for use in drug screening, challenges remain in integrating monitoring systems needed to study an organ’s response to drug effects. Yu Shrike Zhang et al. (pp. E2293–E2302) developed an automated modular design platform that operates a multiorgan-on-a-chip system capable of continually monitoring various biochemical and biophysical parameters in a dual-organoid setup that models the human liver and heart. The system incorporates a microfluidic breadboard to control the routing of fluids, and uses physical biosensors to monitor the extracellular environment and electrochemical biosensors to measure biomarkers. Furthermore, miniature microscopes attached to the organoid modules help observe organoid morphology. To test the multiorgan-on-a-chip system, the authors used cultured human cells to generate healthy liver and heart as well as cancerous liver and heart organoids, which were exposed to acetaminophen or the chemotherapeutic drug, doxorubicin, respectively. In addition to providing measurements on acidity, temperature, and oxygen levels, the system allowed for long-term monitoring of drug-induced toxicity in healthy organoids for up to 5 days and cancerous organoids for up to 24 hours. According to the authors, the technology might provide a platform to improve the performance of current organ-on-a-chip models. — C.S.
Biomarker for cancerous cell subtypes
Tumor from a patient with TNBC: red, pan-cytokeratin; green, alpha smooth muscle actin; and blue, vimentin.
Cancerous cells exist in developmental states similar to epithelial and mesenchymal tissues and often exhibit phenotypic heterogeneity, which can affect tumor development. Researchers have made limited progress in parsing carcinoma cell heterogeneity, such as that observed in mesenchymal phenotypes related to triple-negative breast cancer (TNBC), into distinct cellular subtypes. Brian Bierie et al. (pp. E2337–E2346) used a prognostic biomarker to examine heterogeneity in mesenchymal-like TNBC cells. The biomarker, a cell surface protein called integrin-β4 (ITGB4), was derived from mammary epithelial cells, and tested in 10 human TNBC cell lines as well as tumors removed from individuals with TNBC. Following cellular and genetic analyses, the authors found that ITGB4 was expressed more abundantly in epithelial TNBC cells than in mesenchymal TNBC cells. In tumors from individuals with TNBC who had received chemotherapy, the authors found that tumors that exhibited high levels of ITGB4 RNA were associated with a decreased probability of 5-year relapse-free survival. Moreover, the authors found that the protein ZEB1, involved in activating epithelial-to-mesenchymal transition programs, can repress ITGB4 expression, and that ZEB1 and ITGB4 modulate histopathological phenotypes of tumors derived from mesenchymal TNBC cells, suggesting that ITGB4 could be used to identify subtypes of mesenchymal carcinoma cells in TNBC. According to the authors, the results could help improve the prognosis for high-risk individuals with TNBC. — C.S.
Tortuous mode of action of pit viper toxin
Brazilian lancehead pit viper. Image courtesy of Texas A&M University, Kingsville, Office of Marketing and Communications.
Toxins in venomous snakes, spiders, and cone snails elicit pain through blunt and precise mechanisms, such as enzyme-mediated disgorgement of cellular contents and stimulation or inhibition of receptors and ion channels in pain-sensing neurons. Using laboratory cultures of sensory neurons to screen for toxins in snake venoms, Chuchu Zhang et al. (pp. E2524–E2532) uncovered a novel toxin in the venom of the Brazilian lancehead pit viper (Bothrops moojeni), a pestilential scourge in Latin America whose painful bites are accompanied by tissue inflammation. Named BomoTx, the toxin structurally resembles the phospholipase A2 enzyme but lacks its catalytic activity. Electrophysiological experiments revealed that rather than directly damaging nerves the toxin triggers calcium release in a group of sensory neurons, prying open conduits called pannexin hemichannels, through which the metabolite ATP sluices into the space surrounding cells. Once released, ATP stimulates pain-sensing P2X receptors on a neighboring group of neurons, triggering acute pain and mechanical hypersensitivity when the toxin was injected into the hind paws of mice. Further, the toxin’s ATP-mediated action on nonneural cells triggered paw swelling and edema. The findings illustrate how BomoTx triggers symptoms that mark the bite of Bothrops, which claims a large fraction of snake-related injuries and fatalities in Latin America, according to the authors. — P.N.