The pathomechanism of familial hypokalemic periodic paralysis (HypoPP) is a mystery, despite knowledge of the underlying dominant point mutations in the dihydropyridine receptor (DHPR) voltage sensor. In five HypoPP families without DHPR gene defects, we identified two mutations, Arg-672→His and →Gly, in the voltage sensor of domain 2 of a different protein: the skeletal muscle sodium channel α subunit, known to be responsible for hereditary muscle diseases associated with myotonia. Excised skeletal muscle fibers from a patient heterozygous for Arg-672→Gly displayed depolarization and weakness in low-potassium extracellular solution. Slowing and smaller size of action potentials were suggestive of excitability of the wild-type channel population only. Heterologous expression of the two sodium channel mutations revealed a 10-mV left shift of the steady-state fast inactivation curve enhancing inactivation and a sodium current density that was reduced even at potentials at which inactivation was removed. Decreased current and small action potentials suggested a low channel protein density. The alterations are decisive for the pathogenesis of episodic muscle weakness by reducing the number of excitable sodium channels particularly at sustained membrane depolarization. The results prove that SCN4A, the gene encoding the sodium channel α subunit of skeletal muscle is responsible for HypoPP-2 which does not differ clinically from DHPR-HypoPP. HypoPP-2 represents a disease caused by enhanced channel inactivation and current reduction showing no myotonia.

Unmanned aerial vehicles (UAVs) have the potential to revolutionize the way research is conducted in many scientific fields. UAVs can access remote or difficult terrain, collect large amounts of data for lower cost than traditional aerial methods, and facilitate observations of species that are wary of human presence. Currently, despite large regulatory hurdles, UAVs are being deployed by researchers and conservationists to monitor threats to biodiversity, collect frequent aerial imagery, estimate population abundance, and deter poaching. Studies have examined the behavioral responses of wildlife to aircraft (including UAVs), but with the widespread increase in UAV flights, it is critical to understand whether UAVs act as stressors to wildlife and to quantify that impact. Biologger technology allows for the remote monitoring of stress responses in free-roaming individuals, and when linked to locational information, it can be used to determine events or components of an animal's environment that elicit a physiological response not apparent based on behavior alone. We assessed effects of UAV flights on movements and heart rate responses of free-roaming American black bears. We observed consistently strong physiological responses but infrequent behavioral changes. All bears, including an individual denned for hibernation, responded to UAV flights with elevated heart rates, rising as much as 123 beats per minute above the pre-flight baseline. It is important to consider the additional stress on wildlife from UAV flights when developing regulations and best scientific practices.

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Cardiac arrhythmias and conduction disturbances are accompanied by structural remodelling of the specialised cardiomyocytes known collectively as the cardiac conduction system. Here, using contrast enhanced micro-computed tomography, we present, in attitudinally appropriate fashion, the first 3-dimensional representations of the cardiac conduction system within the intact human heart. We show that cardiomyocyte orientation can be extracted from these datasets at spatial resolutions approaching the single cell. These data show that commonly accepted anatomical representations are oversimplified. We have incorporated the high-resolution anatomical data into mathematical simulations of cardiac electrical depolarisation. The data presented should have multidisciplinary impact. Since the rate of depolarisation is dictated by cardiac microstructure, and the precise orientation of the cardiomyocytes, our data should improve the fidelity of mathematical models. By showing the precise 3-dimensional relationships between the cardiac conduction system and surrounding structures, we provide new insights relevant to valvar replacement surgery and ablation therapies. We also offer a practical method for investigation of remodelling in disease, and thus, virtual pathology and archiving. Such data presented as 3D images or 3D printed models, will inform discussions between medical teams and their patients, and aid the education of medical and surgical trainees.