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We developed an organoid culture system derived from the airways of the bat species Carollia perspicillata . Using this cell system, we showed that the airway epithelium of these bats is highly susceptible to infection by influenza viruses of other mammalian species and thus is not a barrier for interspecies transmission.

ZusammenfassungDer Beitrag rückt die Hypothese in den Fokus, dass die Fachkräfte der Sozialen Arbeit im Zuge der sozialpolitischen Wende hin zum aktivierenden Sozialstaat vermehrt durch punitive Einstellungen gekennzeichnet sind. In diesem Kontext verfolgt diese Studie das Ziel, empirisch zu beforschen, wie häufig und warum punitive Einstellungen unter angehenden Fachkräften der Sozialen Arbeit und in der Allgemeinbevölkerung mit soziodemografisch ähnlicher sozialer Lage vorkommen. Die Ergebnisse untermauern die Hypothese punitiver Einstellungen in der Sozialen Arbeit nur teilweise. Zwar zeigen sich unter angehenden Fachkräften der Sozialen Arbeit durchaus punitive Einstellungen, insgesamt treten sie im Vergleich zur entsprechenden Referenzgruppe der Allgemeinbevölkerung jedoch seltener und weniger stark auf. Die Befunde stellen zudem die politische Einstellung und die soziale Herkunft als Determinanten punitiver Einstellungen heraus.

The human grading system is currently applied to canine meningioma, although it has not been validated in dogs. The present study focused on standardising the human grading system applied to canine meningioma. Four veterinary neuropathologists graded 186 canine meningiomas as follows: Grade I tumour, with4 mitoses/2.37 mm

Chronic asymptomatic orchitis (CAO) is a common cause of acquired non-obstructive azoospermia in dogs. To understand the impact and mode of action of apoptosis, we investigated TUNEL, Bax, Bcl-2, Fas/Fas ligand, and caspase 3/8/9 in testicular biopsies of CAO-affected dogs and compared the results to undisturbed spermatogenesis in healthy males (CG). TUNEL+ cells were significantly increased in CAO, correlating with the disturbance of spermatogenesis. Bcl-2, Bax (p < 0.01 each), caspase 9 (p < 0.05), Fas, caspase 8 (p < 0.01 each), and caspase 3 (p < 0.05) were significantly increased at the mRNA level, whereas FasL expression was downregulated. Cleaved caspase 3 staining was sporadic in CAO but not in CG. Sertoli cells, some peritubular (CAO/CG) and interstitial immune cells (CAO) stained Bcl-2+, with significantly more immunopositive cells in both compartments in CAO compared to CG. Bcl-2 and CD20 co-expressing B lymphocytes were encountered interstitially and in CAO occasionally also found intratubally, underlining their contribution to the maintenance of CAO. Our results support the crucial role of the intrinsic and extrinsic apoptotic pathways in the pathophysiology of canine CAO. Autoprotective Bcl-2 expression in Sertoli cells and B lymphocytes seems to be functional, however, thereby also maintaining and promoting the disease by immune cell activation.

A high prevalence of AA-amyloidosis was identified in a breeding colony of northern tree shrews ( Tupaia belangeri) in a retrospective analysis, with amyloid deposits in different organs being found in 26/36 individuals (72%). Amyloid deposits, confirmed by Congo red staining, were detected in kidneys, intestines, skin, and lymph nodes, characteristic of systemic amyloidosis. Immunohistochemically, the deposited amyloid was intensely positive with anti-AA-antibody (clone mc4), suggesting AA-amyloidosis. The kidneys were predominantly affected (80%), where amyloid deposits ranged from mild to severe and was predominantly located in the renal medulla. In addition, many kidneys contained numerous cysts with atrophy of the renal parenchyma. There was no significant association between concurrent neoplastic or inflammatory processes and amyloidosis. The lack of distinctive predisposing factors suggests a general susceptibility of captive T. belangeri to develop amyloidosis. Clinical and laboratory findings of a female individual with pronounced kidney alterations were indicative of renal failure. The observed tissue tropism with pronounced kidney alterations, corresponding renal dysfunction, and an overall high prevalence suggests amyloidosis as an important disease in captive tree shrews.

Myeloid-derived suppressor cells (MDSCs) are a compendium of immature myeloid cells that exhibit potent T-cell suppressive capacity and expand during pathological conditions such as cancer and chronic infections. Although well-characterized in cancer, the physiology of MDSCs in the infection setting remains enigmatic. Here, we integrated single-cell RNA sequencing (scRNA-seq) and functional metabolic profiling to gain deeper insights into the factors governing the generation and maintenance of MDSCs in chronic Staphylococcus aureus infection. We found that MDSCs originate not only in the bone marrow but also at extramedullary sites in S. aureus-infected mice. scRNA-seq showed that infection-driven MDSCs encompass a spectrum of myeloid precursors in different stages of differentiation, ranging from promyelocytes to mature neutrophils. Furthermore, the scRNA-seq analysis has also uncovered valuable phenotypic markers to distinguish mature myeloid cells from immature MDSCs. Metabolic profiling indicates that MDSCs exhibit high glycolytic activity and high glucose consumption rates, which are required for undergoing terminal maturation. However, rapid glucose consumption by MDSCs added to infection-induced perturbations in the glucose supplies in infected mice hinders the terminal maturation of MDSCs and promotes their accumulation in an immature stage. In a proof-of-concept in vivo experiment, we demonstrate the beneficial effect of increasing glucose availability in promoting MDSC terminal differentiation in infected mice. Our results provide valuable information of how metabolic alterations induced by infection influence reprogramming and differentiation of MDSCs.

A 9-year-old female, neutered European shorthair cat was presented with acute vomiting, obvious jaundice and painful enlargement of the abdomen. Icteric skin and mucous membranes in addition to severe bilirubinaemia (mainly direct bilirubin) and a large increase in liver enzyme activities were the main findings at the initial examination. Radio- and ultrasonographic evaluation revealed a massive fluid-filled structure caudal to the liver displacing abdominal organs, in particular the stomach. As this structure with a diameter of 8-10 cm occupied considerable space in the cranioventral abdomen, a detailed ultrasonographic examination of the liver and the gallbladder, and determination of the structure's association with a particular abdominal organ was initially impossible. Via ultrasound-assisted puncture under general anaesthesia 300 ml of an almost clear fluid could be aspirated. Cytological examination revealed a cyst content-like fluid with cell detritus.Further ultrasonographic and computed tomographic diagnostics followed by abdominal laparotomy finally enabled diagnosis of a cystic dilatation of the entire common bile duct and accumulation of white bile. Histopathological examination after euthanasia (requested by the owner) identified lymphoplasmacytic cholangitis and necrosis of the duodenal papilla. The massive dilatation of the common bile duct complicated its definite diagnosis by diagnostic imaging methods. It was most likely caused by a longer-standing obstruction of the bile flow by lymphoplasmacytic cholangitis with necrosis and granulation tissue formation in the area of the duodenal papilla. An interesting but initially misleading feature was the presence of white bile. The etiology of this extremely rare condition remains obscure but in the described case a manifestation of impaired hepatocyte function secondary to biliary stasis is suspected to be the cause.Eine 9 Jahre alte, kastrierte Europäisch-Kurzhaar-Katze wurde mit akutem Vomitus, Ikterus und schmerzhaftem, umfangsvermehrtem Abdomen vorgestellt. Die auffälligsten Befunde der Erstuntersuchung umfassten hochgradig ikterische Schleimhäute, ausgeprägte Bilirubinämie (vorrangig direktes Bilirubin) und hochgradig erhöhte Leberenzymaktivitäten. Röntgen- und Ultraschalluntersuchungen ergaben eine große flüssigkeitsgefüllte Struktur kaudal der Leber mit Verdrängung der abdominalen Organe, insbesondere des Magens. Durch das Ausmaß der Struktur (8–10 cm Durchmesser) waren eine ausführliche sonografische Untersuchung von Leber und Gallenblase sowie eine Bestimmung der Organzugehörigkeit dieser Struktur nicht möglich. Bei der ultraschallgeführten Punktion unter Vollnarkose konnten 300 ml einer nahezu klaren Flüssigkeit gewonnen werden, die zytologisch einer zysteninhaltähnlichen Flüssigkeit mit Zelldetritus entsprach. Weitere sonografische und computertomografische Untersuchungen in Verbindung mit einer diagnostischen Laparotomie führten zur Diagnose einer zystischen Dilatation des gesamten gemeinsamen Gallengangs mit Vorliegen von weißer Galle. Die Katze wurde auf Besitzerwunsch euthanasiert. Die histopathologische Untersuchung ergab eine lymphoplasmazytäre Cholangitis und eine Nekrose der Duodenalpapille. Die massive Erweiterung des gemeinsamen Gallengangs erschwerte bei diesem Tier die eindeutige Diagnose durch bildgebende Verfahren. Deren Ursache war höchstwahrscheinlich eine länger andauernde Abflussstörung der Galle durch eine lymphoplasmazelluläre Cholangitis mit Nekrose und Granulationsgewebsbildung im Bereich der Duodenalpapille. Eine interessante, jedoch initial irreführende Besonderheit war das Vorliegen der weißen Galle. Die Entstehung dieses äußerst seltenen Merkmals ist weitestgehend unbekannt. Im beschriebenen Fall stellt die beeinträchtigte Funktion der Hepatozyten sekundär zum Gallestau die wahrscheinlichste Ursache dar.

A relevant number of coronavirus disease 2019 (COVID-19) survivors suffers from post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (PASC). Current evidence suggests a dysregulated alveolar regeneration in COVID-19 as a possible explanation for respiratory PASC symptoms, a phenomenon which deserves further investigation in a suitable animal model. This study investigates morphological, phenotypical and transcriptomic features of alveolar regeneration in SARS-CoV-2 infected Syrian golden hamsters. We demonstrate that CK8+alveolar differentiation intermediate (ADI) cells occur following SARS-CoV-2-induced diffuse alveolar damage. A subset of ADI cells shows nuclear accumulation of TP53 at 6- and 14-days post infection (dpi), indicating a prolonged arrest in the ADI state. Transcriptome data show the expression of gene signatures driving ADI cell senescence, epithelial-mesenchymal transition, and angiogenesis. Moreover, we show that multipotent CK14+airway basal cell progenitors migrate out of terminal bronchioles, aiding alveolar regeneration. At 14 dpi, presence of ADI cells, peribronchiolar proliferates, M2-type macrophages, and sub-pleural fibrosis is observed, indicating incomplete alveolar restoration. The results demonstrate that the hamster model reliably phenocopies indicators of a dysregulated alveolar regeneration of COVID-19 patients. The results provide important information on a translational COVID-19 model, which is crucial for its application in future research addressing pathomechanisms of PASC and in testing of prophylactic and therapeutic approaches for this syndrome.

Canine distemper virus (CDV), a morbillivirus within the family Paramyxoviridae, is a highly contagious infectious agent causing a multisystemic, devastating disease in a broad range of host species, characterized by severe immunosuppression, encephalitis and pneumonia. The present study aimed at investigating pulmonary immune responses of CDV-infected dogs in situ using immunohistochemistry and whole transcriptome analyses by bulk RNA sequencing. Spatiotemporal analysis of phenotypic changes revealed pulmonary immune responses primarily driven by MHC-II+, Iba-1+ and CD204+ innate immune cells during acute and subacute infection phases, which paralleled pathologic lesion development and coincided with high viral loads in CDV-infected lungs. CD20+ B cell numbers initially declined, followed by lymphoid repopulation in the advanced disease phase. Transcriptome analysis demonstrated an increased expression of transcripts related to innate immunity, antiviral defense mechanisms, type I interferon responses and regulation of cell death in the lung of CDV-infected dogs. Molecular analyses also revealed disturbed cytokine responses with a pro-inflammatory M1 macrophage polarization and impaired mucociliary defense in CDV-infected lungs. The exploratory study provides detailed data on CDV-related pulmonary immune responses, expanding the list of immunologic parameters potentially leading to viral elimination and virus-induced pulmonary immunopathology in canine distemper.