Hyperostotic tympanic bone spicules in domestic and wild animal species

Hyperostotic tympanic bone spicules (HTBS), or "mucoperiosteal exostoses" (ME, syn.) are small, globular (>= 1 mm in diameter), mostly stalked and drumstick-like, bony structures, which arise from the inner wall of the tympanic bulla and project into the middle ear cavity. HTBS present as mineral densities inside the tympanic bulla on radiographs or computed tomographic (CT) images. They have previously been referred to as "otoliths" and were thought to represent mineral concretions secondary to otitis media. Recently, it was shown that HTBS actually consist of regularly composed bone tissue, covered by normal middle ear mucosa. So far, HTBS have only extensively been described in dogs, where they occur with a prevalence of up to >45%. A recent study detected ME, most likely representing HTBS, in the tympanic cavities of skeletonised skull bones of African lions. To estimate the occurrence of HTBS in other mammal species, the middle ears of adult animals of 78 different domestic, wild, and zoo species undergoing routine necropsy at the Institute of Veterinary Pathology of the LMU Munich, Germany were examined in the present study. HTBS were found in the tympanic bullae of carnivorous species, such as canids (wolf, fox), and in several large felid species (lion, tiger, leopard, cheetah). In contrast, HTBS were not present in domestic cats (more than to 200 cases), small carnivorous species such as mustelids, nor in any primate, ungulate, ruminant, pig, insectivore, or rodent species. The detectability of HTBS by CT of the tympanic bullae of large felids was demonstrated in an African lion. Histologically, HTBS consisted of mature lamellar bone, covered by periosteum and a partially ciliated, flat epithelium, regularly without any apparent inflammatory alterations. The present study demonstrates that HTBS may frequently occur in large felids and in different canid species. These findings should be taken into account when examining the middle ear, or interpreting bulla radiographs/CT-images of the respective species. However, the factors triggering the development of HTBS remain to be identified

Synthesis of Ozone at Atmospheric Pressure by a Quenched Induction-Coupled Plasma Torch

The technical feasibility of using an induction-coupled plasma (ICP) torch to synthesize ozone at atmospheric pressure is explored. Ozone concentrations up to ~250 ppm were produced using a thermal plasma reactor system based on an ICP torch operating at 2.5 MHz and ~11 kVA with an argon/oxygen mixture as the plasma-forming gas. A gaseous oxygen quench formed ozone by rapid mixing of molecular oxygen with atomic oxygen produced by the torch. The ozone concentration in the reaction chamber was measured by Fourier Transform infrared (FTIR) spectroscopy over a wide range of experimental configurations. The geometry of the quench gas flow, the quench flow velocity, and the quench flow rate played important roles in determining the ozone concentration. The ozone concentration was sensitive to the torch RF power, but was insensitive to the torch gas flow rates. These observations are interpreted within the framework of a simple model of ozone synthesis

Early disruption of photoreceptor cell architecture and loss of vision in a humanized pig model of usher syndromes

Usher syndrome (USH) is the most common form of monogenic deaf‐blindness. Loss of vision is untreatable and there are no suitable animal models for testing therapeutic strategies of the ocular constituent of USH, so far. By introducing a human mutation into the harmonin‐encoding USH1C gene in pigs, we generated the first translational animal model for USH type 1 with characteristic hearing defect, vestibular dysfunction, and visual impairment. Changes in photoreceptor architecture, quantitative motion analysis, and electroretinography were characteristics of the reduced retinal virtue in USH1C pigs. Fibroblasts from USH1C pigs or USH1C patients showed significantly elongated primary cilia, confirming USH as a true and general ciliopathy. Primary cells also proved their capacity for assessing the therapeutic potential of CRISPR/Cas‐mediated gene repair or gene therapy in vitro. AAV‐based delivery of harmonin into the eye of USH1C pigs indicated therapeutic efficacy in vivo

Early disruption of photoreceptor cell architecture and loss of vision in a humanized pig model of usher syndromes

Usher syndrome (USH) is the most common form of monogenic deaf-blindness. Loss of vision is untreatable and there are no suitable animal models for testing therapeutic strategies of the ocular constituent of USH, so far. By introducing a human mutation into the harmonin-encoding USH1C gene in pigs, we generated the first translational animal model for USH type 1 with characteristic hearing defect, vestibular dysfunction, and visual impairment. Changes in photoreceptor architecture, quantitative motion analysis, and electroretinography were characteristics of the reduced retinal virtue in USH1C pigs. Fibroblasts from USH1C pigs or USH1C patients showed significantly elongated primary cilia, confirming USH as a true and general ciliopathy. Primary cells also proved their capacity for assessing the therapeutic potential of CRISPR/Cas-mediated gene repair or gene therapy in vitro. AAV-based delivery of harmonin into the eye of USH1C pigs indicated therapeutic efficacy in vivo

Recovery after inadvertent intramedullary microchip implantation at C1–C2 in a kitten.

Case summary: A 15-week-old male British Shorthair cat was presented for peracute paralysis immediately after microchip implantation. Neurological examination revealed a non-ambulatory tetraparesis and left thoracic limb plegia localised to C1–C5 spinal cord segments. CT of the cervical spine showed a diagonally orientated metallic foreign body (microchip transponder, 10 mm in length) within the vertebral canal at the level of C1–C2, resulting in a penetrating spinal cord injury. Based on concerns about further iatrogenic spinal cord injury through surgery, medical management was chosen. Despite the severe clinical signs, the kitten returned to ambulation within 6 days of the injury, with controlled urination and defecation. Continuous neurological improvement was seen for up to 6 weeks after the injury at which point a mild-to-moderate ambulatory tetraparesis and ataxia remained, with an overall good quality of life. Follow-up CT at the age of 13 months revealed a relative cranial displacement and rotation of the microchip towards the foramen magnum, while the cat’s neurological status was unchanged. Relevance and novel information: This case demonstrated a cervical penetrating spinal cord injury in a growing cat caused by a microchip, which was successfully managed with medical treatment, suggesting that this might be an option for patients at risk of severe surgery-related complications or where owners reject surgery

Autochthonous Taenia crassiceps infection in a ring-tailed lemur (Lemur catta) in the Salzburg Zoo.

Captive primates are susceptible to infection with cestodes of the family of Taeniidae. This report describes the infection of a five-year-old female ring tailed-lemur (Lemur catta) in Salzburg Zoo (Salzburg, Austria) with Taenia crassiceps. Necropsy revealed extensive amounts of organized and free cysts in the thoracic cavity, completely encasing and compressing the lungs and the heart. Infection probably occurred by oral uptake of Taenia crassiceps eggs from faeces of red fox (Vulpes vulpes) within the zoo or in the surrounding park, where the lemurs roam freely. Two foxes shot in the vicinity of the zoo were confirmed to have an intestinal infection with Taenia crassiceps. The simultaneous detection of Taenia crassiceps tapeworms in a natural definite host (fox) and of their metacestodes in an accidental intermediate host provides evidence of an autochthonous infection. Compared to other zoo primates, ring-tailed lemurs (Lemur catta) seem to be highly susceptible to infection with Taenia crassiceps. Therapy and preventive methods are discussed

Progressive muscle proteome changes in a clinically relevant pig model of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is caused by genetic deficiency of dystrophin and characterized by massive structural and functional changes of skeletal muscle tissue, leading to terminal muscle failure. We recently generated a novel genetically engineered pig model reflecting pathological hallmarks of human DMD better than the widely used mdx mouse. To get insight into the hierarchy of molecular derangements during DMD progression, we performed a proteome analysis of biceps femoris muscle samples from 2-day-old and 3-month-old DMD and wild-type (WT) pigs. The extent of proteome changes in DMD vs. WT muscle increased markedly with age, reflecting progression of the pathological changes. In 3-month-old DMD muscle, proteins related to muscle repair such as vimentin, nestin, desmin and tenascin C were found to be increased, whereas a large number of respiratory chain proteins were decreased in abundance in DMD muscle, indicating serious disturbances in aerobic energy production and a reduction of functional muscle tissue. The combination of proteome data for fiber type specific myosin heavy chain proteins and immunohistochemistry showed preferential degeneration of fast-twitch fiber types in DMD muscle. The stage-specific proteome changes detected in this large animal model of clinically severe muscular dystrophy provide novel molecular readouts for future treatment trials

Unraveling ERBB network dynamics upon betacellulin signaling in pancreatic ductal adenocarcinoma in mice.

Pancreatic ductal adenocarcinoma (PDAC) will soon belong to the top three cancer killers. The only approved specific PDAC therapy targets the epidermal growth factor receptor (EGFR). Although EGFR is a crucial player in PDAC development, EGFR-based therapy is disappointing. In this study, we evaluated the role of the EGFR ligand betacellulin (BTC) in PDAC. The expression of BTC was investigated in human pancreatic cancer specimen. Then, we generated a BTC knockout mouse model by CRISPR/Cas9 technology and a BTC overexpression model. Both models were crossed with the Ptf1a(Cre/+);KRAS(G12D/+) (KC) mouse model (B-/-KC or BKC, respectively). In addition, EGFR, ERBB2, and ERBB4 were investigated by the pancreas-specific deletion of each receptor using the Cre-loxP system. Tumor initiation and progression were analyzed in all mouse lines, and the underlying molecular biology of PDAC was investigated at different time points. BTC is expressed in human and murine PDAC. B-/-KC mice showed a decelerated PDAC progression, associated with decreased EGFR activation. BKC mice developed severe PDAC with a poor survival rate. The dramatically increased BTC-mediated tumor burden was EGFR-dependent, but also ERBB4 and ERBB2 were involved in PDAC development or progression, as depletion of EGFR, ERBB2, or ERBB4 significantly improved the survival rate of BTC-mediated PDAC. BTC increases PDAC tumor burden dramatically by enhanced RAS activation. EGFR signaling, ERBB2 signaling, and ERBB4 signaling are involved in accelerated PDAC development mediated by BTC indicating that targeting the whole ERBB family, instead of a single receptor, is a promising strategy for the development of future PDAC therapies

Proliferative kidney disease and proliferative darkening syndrome are linked with brown trout (<em>Salmo trutta fario</em>) mortalities in the pre-alpine Isar River.

For many years, brown trout (Salmo trutta fario) mortalities within the pre-alpine Isar River in Germany were reported by the Bavarian Fisheries Association (Landesfischereiverband Bayern e.V.) and local recreational anglers during August and September. Moribund fish seemed to be affected by proliferative darkening syndrome (PDS). In addition, proliferative kidney disease (PKD) caused by Tetracapsuloides bryosalmonae was discussed. To investigate this phenomenon, the present field study monitored brown trout mortalities by daily river inspection in 2017 and 2018. Moribund brown trout (n = 31) were collected and examined using histology, immunohistochemistry, qPCR, and quantitative stereology. Our investigations identified 29 (93.5%) brown trout affected by PKD. Four brown trout (12.9%) displayed combined hepatic and splenic lesions fitting the pathology of PDS. The piscine orthoreovirus 3, suspected as causative agent of PDS, was not detectable in any of the samples. Quantitative stereological analysis of the kidneys revealed a significant increase of the renal tissue volumes with interstitial inflammation and hematopoietic hyperplasia in PKD-affected fish as compared to healthy brown trout. The identified T. bryosalmonae strain was classified as part of the North American clade by phylogenetical analysis. This study highlights PKD and PDS as contributing factors to recurrent autumnal brown trout mortalities