Comprehensive ECG reference intervals in C57BL/6N substrains provide a generalizable guide for cardiac electrophysiology studies in mice.

Reference ranges provide a powerful tool for diagnostic decision-making in clinical medicine and are enormously valuable for understanding normality in pre-clinical scientific research that uses in vivo models. As yet, there are no published reference ranges for electrocardiography (ECG) in the laboratory mouse. The first mouse-specific reference ranges for the assessment of electrical conduction are reported herein generated from an ECG dataset of unprecedented scale. International Mouse Phenotyping Consortium data from over 26,000 conscious or anesthetized C57BL/6N wildtype control mice were stratified by sex and age to develop robust ECG reference ranges. Interesting findings include that heart rate and key elements from the ECG waveform (RR-, PR-, ST-, QT-interval, QT corrected, and QRS complex) demonstrate minimal sexual dimorphism. As expected, anesthesia induces a decrease in heart rate and was shown for both inhalation (isoflurane) and injectable (tribromoethanol) anesthesia. In the absence of pharmacological, environmental, or genetic challenges, we did not observe major age-related ECG changes in C57BL/6N-inbred mice as the differences in the reference ranges of 12-week-old compared to 62-week-old mice were negligible. The generalizability of the C57BL/6N substrain reference ranges was demonstrated by comparison with ECG data from a wide range of non-IMPC studies. The close overlap in data from a wide range of mouse strains suggests that the C57BL/6N-based reference ranges can be used as a robust and comprehensive indicator of normality. We report a unique ECG reference resource of fundamental importance for any experimental study of cardiac function in mice.

Perturbation of fatty acid composition, pigments, and growth indices of Chlorella vulgaris in response to silver ions and nanoparticles: A new holistic understanding of hidden ecotoxicological aspect of pollutants.

This study assesses and compares the influence of silver nanoparticles (AgNPs) and silver nitrate (AgNO3) on the fatty acid composition, pigments, and growth indices of Chlorella vulgaris. Toxicity testing was carried at the estimated and/or above predicted environmental concentrations of AgNPs and AgNO3. AgNO3 treatments impaired the population growth of C. vulgaris about 2-183 times more than the respective AgNPs ones. The pigments displayed a concentration-dependent decrease in response to both forms of silver; however, AgNO3 displayed higher severity to the pigments than AgNPs. In exposure to 10 µg L-1 AgNO3, the contents of chlorophyll a, chlorophyll b, total chlorophyll, and carotenoid, respectively, demonstrated a reduction of about 5, 3, 4, and 4 times when compared with the same respective concentration of AgNPs. Total amounts of saturated (∑SFA), monounsaturated (∑MUFA), and polyunsaturated (∑PUFA) fatty acids as well as the ratio of unsaturated to saturated ones (Unsat./Sat.) displayed somewhat similar-concentration responses. ∑SFA exhibited a hormesis response, and ∑MUFA, ∑PUFA, and Unsat./Sat. did a decreasing trend with increasing concentration of AgNPs and AgNO3. Myristoleic acid, nervonic acid, and eicosadienoic acid revealed the highest sensitivity. Pearson analysis illustrated the highest correlation among myristoleic acid, eicosenoic acid, and nervonic acid as well as among palmitic acid, stearic acid, palmitoleic acid, and oleic acid. Taken together, AgNPs and the released ions could disrupt physiological health state of microalgae through perturbation in the fatty acid composition (especially MUFAs and PUFAs) and other macromolecules. These types of bioperturbations could change the good health state of aquatic ecosystems.