Duchenne muscular dystrophy (DMD), induced by mutations in the gene encoding for the cytoskeletal protein dystrophin, is an inherited disease characterized by progressive muscle weakness. Besides the relatively well characterized skeletal muscle degenerative processes, DMD is also associated with cardiac complications. These include cardiomyopathy development and cardiac arrhythmias. The current understanding of the pathomechanisms in the heart is very limited, but recent research indicates that dysfunctional ion channels in dystrophic cardiomyocytes play a role. The aim of the present study was to characterize abnormalities in L-type calcium channel function in adult dystrophic ventricular cardiomyocytes. By using the whole cell patch-clamp technique, the properties of currents through calcium channels in ventricular cardiomyocytes isolated from the hearts of normal and dystrophic adult mice were compared. Besides the commonly used dystrophin-deficient mdx mouse model for human DMD, we also used mdx-utr mice, which are both dystrophin- and utrophin-deficient. We found that calcium channel currents were significantly increased, and channel inactivation was reduced in dystrophic cardiomyocytes. Both effects enhance the calcium influx during an action potential (AP). Whereas the AP in dystrophic mouse cardiomyocytes was nearly normal, implementation of the enhanced dystrophic calcium conductance in a computer model of a human ventricular cardiomyocyte considerably prolonged the AP. Finally, the described dystrophic calcium channel abnormalities entailed alterations in the electrocardiograms of dystrophic mice. We conclude that gain of function in cardiac L-type calcium channels may disturb the electrophysiology of the dystrophic heart and thereby cause arrhythmias.

Recent Alzheimer's disease (AD) patient studies have focused on retinal analysis, as the retina is the only part of the central nervous system which can be imaged non-invasively by optical methods. However as this is a relatively new approach, the occurrence and role of pathological features such as retinal layer thinning, extracellular amyloid beta (Aβ) accumulation and vascular changes is still debated. Animal models of AD are therefore often used in attempts to understand the disease. In this work, both eyes of 24 APP/PS1 transgenic mice (age: 45-104 weeks) and 15 age-matched wildtype littermates were imaged by a custom-built multi-contrast optical coherence tomography (OCT) system. The system provided a combination of standard reflectivity data, polarization-sensitive data and OCT angiograms. This tri-fold contrast provided qualitative and quantitative information on retinal layer thickness and structure, presence of hyper-reflective foci, phase retardation abnormalities and retinal vasculature. While abnormal structural properties and phase retardation signals were observed in the retinas, the observations were very similar in transgenic and control mice. At the end of the experiment, retinas and brains were harvested from a subset of the mice (14 transgenic, 7 age-matched control) in order to compare the in vivo results to histological analysis, and to quantify the cortical Aβ plaque load. arXiv:1909.08466v2 [physics.med-ph]

The present study examined the kinematic patterns of initial food uptake, food transport, pharyngeal packing and swallowing in the common musk turtle Sternotherus odoratus. These data are supplemented by morphological descriptions of the skull and the hyolingual complex. Although the hyoid is mainly cartilaginous, S. odoratus still use exclusively hydrodynamic mechanisms in prey capture and prey transport. The tongue is relatively small, with weakly developed intrinsic musculature. We propose that the elasticity of the hypoglossum and the hyoid body impacts the capability of S. odoratus to suction feed, but allows these turtles to effectively re-position the food items within the oropharyngeal cavity during transport, manipulation and pharyngeal packing. We standardised conditions in all feeding events by using food items of the same consistence and size, and by always offering the food at the same position at the bottom of the aquarium. Nonetheless, the measured kinematic values varied considerably. The duration of prey capture and prey transport cycles were relatively long in S. odoratus compared to other freshwater turtles studied so far. The initiation of hyoid retraction relative to the onset of jaw opening can be modulated not only in prey capture but also in prey transport cycles. In the common musk turtle, the jaw and hyoid movements apparently have a low level of integration.

Squamous cell carcinoma of the head and neck (HNSCC) is a common malignant tumor in humans and animals. In humans, papillomavirus (PV)-induced HNSCCs have a better prognosis than papillomavirus-unrelated HNSCCs. The ability of tumor cells to switch from epithelial to mesenchymal, endothelial, or therapy-resistant stem-cell-like phenotypes promotes disease progression and metastasis. In equine HNSCC, PV-association and tumor cell phenotype switching are poorly understood. We screened 49 equine HNSCCs for equine PV (EcPV) type 2, 3 and 5 infection. Subsequently, PV-positive versus -negative lesions were analyzed for expression of selected epithelial (keratins, β-catenin), mesenchymal (vimentin), endothelial (COX-2), and stem-cell markers (CD271, CD44) by immunohistochemistry (IHC) and immunofluorescence (IF; keratins/vimentin, CD44/CD271 double-staining) to address tumor cell plasticity in relation to PV infection. Only EcPV2 PCR scored positive for 11/49 equine HNSCCs. IHC and IF from 11 EcPV2-positive and 11 EcPV2-negative tumors revealed epithelial-to-mesenchymal transition events, with vimentin-positive cells ranging between <10 and >50%. CD44- and CD271-staining disclosed the intralesional presence of infiltrative tumor cell fronts and double-positive tumor cell subsets independently of the PV infection status. Our findings are indicative of (partial) epithelial–mesenchymal transition events giving rise to hybrid epithelial/mesenchymal and stem-cell-like tumor cell phenotypes in equine HNSCCs and suggest CD44 and CD271 as potential malignancy markers that merit to be further explored in the horse.

The snake-eyed skink Ablepharus kitaibelii is one of the smallest European lizards, but despite its minute size it is able to feed on comparatively large prey. Here we investigate the diet of A. kitaibelii and the mechanisms that allow the skink to overpower relatively large and even noxious prey. High-speed cinematography showed that A. kitaibelii uses a series of shaking and battering movements to immobilise and kill prey prior to swallowing. During this process, the skinks rises up on the hind limbs and then whacks the prey sidewise on the substrate by twisting the trunk, neck and head laterally. Our analysis showed that the shaking kinematics is very uniform among the investigated specimens. The morphological investigation of the cranio-cervical system revealed that A. kitaibelii possesses a well-developed synovial joint between the odontoid process of the axis, the atlas, and the basioccipital. The odontoid process is cylindrical and slim and together with the atlas and the basioccipital it forms a highly specialised pivot joint for lateral head rotation. We propose that the occipito-atlanto-axial complex of A. kitaibelii represents a functional adaptation for additional stabilisation of the cranio-cervical complex during prey shaking. Digital data from morphological databases showed that specialised joints of this type are very rare, but do also occur in other squamate groups. Thus we hypothesise that specialised cranio-cervical joints have evolved parallel as functional adaptations to different feeding and locomotion patterns. Future studies that link feeding kinematics and locomotion to cranio-cervical morphology might elucidate the function of various specialised occipito-atlanto-axial systems of squamates.