A Look Inside-Histopathological Examinations of Different Tail Tip Lesions in Dairy Cows.

Feedlot cattle are frequently affected by inflammation and necrosis of the tail tips, resulting in impeded animal welfare and economic losses. In a recent study, it was demonstrated that dairy cows are also affected by different lesions of the tail tip, including alopecia, annular constrictions, crusting, scaling and swelling. Despite the frequent occurrence of these lesions, the underlying etiology and pathomechanisms are unclear to date. To gain insight into this malady, we histopathologically examined 16 tail tips of slaughtered dairy cows, representing the entire range of different lesions. While macroscopically alopecic areas were characterized by the formation of granulation tissue in the dermis with an inconspicuous epidermis, we found not only dermal granulation tissue but also purulent-necrotizing inflammation with the breakdown of the basement membrane in encrusted lesions. Interestingly, in some cases, we found areas of coagulation necrosis of the epidermal and dermal layers in the crusts. Tails with macroscopical scaling were affected by ortho- and/or parakeratotic hyperkeratosis, and, in tails with macroscopical swelling, we observed a low-protein edema of the central longitudinal connective tissue of the tail. We conclude that the observed lesions might be caused by ischemia of the skin in the distal parts of the tail.

Gaining masculine power through guns? The impact of masculinity threat on attitudes toward guns.

Gun violence is a serious problem in the United States and elsewhere and more so among men than women. We conducted an experiment to examine if men whose masculinity was threatened are more attracted to guns than non-threatened men, presumably to compensate for the threat. After completing a gender knowledge test, men (N = 168) randomly received either false masculinity threatening (experimental condition) or masculinity affirming (control condition) feedback. Subsequently, we measured men's attitudes toward guns and their choice of a gun-range voucher. Men whose masculinity was threatened (vs. affirmed) showed more positive attitudes toward guns and were more likely to choose the voucher. Both effects were statistically significant when the whole sample was analyzed and when very strict exclusion criteria were applied. However, when data exclusions were based on a suspicion check, effects were statistically significant only when a covariate was included (i.e., social dominance orientation, patriotism, or experience with guns). We discuss reasons for this mixed evidence, including the possibility that suspicion regarding the masculinity feedback could itself be a compensatory reaction to threat.

Long-term survival of monolithic tooth-supported lithium disilicate crowns fabricated using a chairside approach: 15-year results.

OBJECTIVES: To investigate the clinical performance of chairside fabricated tooth-supported posterior single crowns from lithium disilicate ceramic. MATERIALS AND METHODS: Thirty-four crowns (IPS e.max CAD, Ivoclar Vivadent, Schaan, Liechtenstein) were inserted between 2006 and 2007 and again evaluated after 15 years. Survival and success rates were calculated according to Kaplan-Meier, and the quality of the crowns was evaluated by using modified United States Public Health (USPHS) criteria. RESULTS: Twenty-two crowns were available for recall; six patients were defined as dropouts. The mean observation period was 15.2 years (± 0.2). Six failures occurred (1 technical/5 biological) resulting in a survival rate of 80.1%. The success rate was 64.2%. The roughness of the crowns increased (p = 0.021) and the majority of adhesive gaps were discolored (p = 0.001) in comparison to baseline. The color, tooth, and crown integrity remained stable over the follow-up period (p ≥ 0.317). CONCLUSION: The fabrication of tooth-supported lithium disilicate crowns using a chairside approach yielded acceptable long-term survival and success rates. Due to discoloration, the long-term use of dual-cure self-adhesive resin cements might result in unpleasing esthetic results. CLINICAL RELEVANCE: The performance of posterior lithium disilicate single crowns revealed excellent to good clinical quality and an acceptable number of events after 15 years of clinical service.

Bovine Peripheral Blood Derived Lymphocyte Proteome and Secretome Show Divergent Reaction of Bovine Immune Phenotypes after Stimulation with Pokeweed Mitogen.

We recently identified a deviant bovine immune phenotype characterized by hyperproliferation of lymphocytes after polyclonal stimulation. This phenotype was first discovered in dams that responded to PregSure BVD vaccination by producing pathological antibodies, triggering the fatal disease "bovine neonatal pancytopenia" in calves. The aim of the study was to gain deeper insights into molecular processes occurring in lymphocytes of immune phenotypes and the effect on their secretome after immune stimulation. Two discovery proteomic experiments were performed with unstimulated and Pokeweed Mitogen (PWM) stimulated lymphocytes, using label-free LC-MS/MS. In lymphocytes, 2447 proteins were quantified, and 1204 proteins were quantified in the secretome. Quantitative proteome analysis of immune deviant and control samples after PWM stimulation revealed clear differences. The increase in abundance of IL17A, IL17F, IL8, CCL5, LRRC59, and CLIC4 was higher in controls through mitogenic stimulation. In contrast, the abundance of IFNγ, IL2, IL2RA, CD83, and CD200 increased significantly more in immune deviant lymphocytes. Additional pathway enrichment analysis of differentially secreted proteins also yielded fundamental differences between the immune phenotypes. Our study provides a comprehensive dataset, which gives novel insights into proteome changes of lymphocytes from different bovine immune phenotypes. These differences point to the development of diverse immune responses of bovine immune phenotypes after immune stimulation.

Proteomic Phenotyping of Stimulated Müller Cells Uncovers Profound Pro-Inflammatory Signaling and Antigen-Presenting Capacity.

Müller cells are the main macroglial cells of the retina exerting a wealth of functions to maintain retinal homoeostasis. Upon pathological changes in the retina, they become gliotic with both protective and detrimental consequences. Accumulating data also provide evidence for a pivotal role of Müller cells in the pathogenesis of diabetic retinopathy (DR). While microglial cells, the resident immune cells of the retina are considered as main players in inflammatory processes associated with DR, the implication of activated Müller cells in chronic retinal inflammation remains to be elucidated. In order to assess the signaling capacity of Müller cells and their role in retinal inflammation, we performed in-depth proteomic analysis of Müller cell proteomes and secretomes after stimulation with INFγ, TNFα, IL-4, IL-6, IL-10, VEGF, TGFß1, TGFß2 and TGFß3. We used both, primary porcine Müller cells and the human Müller cell line MIO-M1 for our hypothesis generating approach. Our results point towards an intense signaling capacity of Müller cells, which reacted in a highly discriminating manner upon treatment with different cytokines. Stimulation of Müller cells resulted in a primarily pro-inflammatory phenotype with secretion of cytokines and components of the complement system. Furthermore, we observed evidence for mitochondrial dysfunction, implying oxidative stress after treatment with the various cytokines. Finally, both MIO-M1 cells and primary porcine Müller cells showed several characteristics of atypical antigen-presenting cells, as they are capable of inducing MHC class I and MHC class II with co-stimulatory molecules. In line with this, they express proteins associated with formation and maturation of phagosomes. Thus, our findings underline the importance of Müller cell signaling in the inflamed retina, indicating an active role in chronic retinal inflammation.

Cell Surface Profiling of Retinal Müller Glial Cells Reveals Association to Immune Pathways after LPS Stimulation.

Retinal Müller glial cells (RMG) are involved in virtually every retinal disease; however, the role of these glial cells in neuroinflammation is still poorly understood. Since cell surface proteins play a decisive role in immune system signaling pathways, this study aimed at characterizing the changes of the cell surface proteome of RMG after incubation with prototype immune system stimulant lipopolysaccharide (LPS). While mass spectrometric analysis of the human Müller glia cell line MIO-M1 revealed 507 cell surface proteins in total, with 18 proteins significantly more abundant after stimulation (ratio ≥ 2), the surfaceome of primary RMG comprised 1425 proteins, among them 79 proteins with significantly higher abundance in the stimulated state. Pathway analysis revealed notable association with immune system pathways such as "antigen presentation", "immunoregulatory interactions between a lymphoid and a non-lymphoid cell" and "cell migration". We could demonstrate a higher abundance of proteins that are usually ascribed to antigen-presenting cells (APCs) and function to interact with T-cells, suggesting that activated RMG might act as atypical APCs in the course of ocular neuroinflammation. Our data provide a detailed description of the unstimulated and stimulated RMG surfaceome and offer fundamental insights regarding the capacity of RMG to actively participate in neuroinflammation in the retina.

NEU1 is more abundant in uveitic retina with concomitant desialylation of retinal cells.

Desialylation of cell surface glycoproteins carried out by sialidases affects various immunological processes. However, the role of neuraminidase 1 (NEU1), one of the four mammalian sialidases, in inflammation and autoimmune disease is not completely unraveled to date. In this study, we analyzed the retinal expression of NEU1 in equine recurrent uveitis (ERU), a spontaneous animal model for autoimmune uveitis. Mass spectrometry revealed significantly higher abundance of NEU1 in retinal Müller glial cells (RMG) of ERU-diseased horses compared to healthy controls. Immunohistochemistry uncovered NEU1 expression along the whole Müller cell body in healthy and uveitic states and confirmed higher abundance in inflamed retina. Müller glial cells are the principal macroglial cells of the retina and play a crucial role in uveitis pathogenesis. To determine whether higher expression levels of NEU1 in uveitic RMG correlate with the desialylation of retinal cells, we performed lectin-binding assays with sialic acid-specific lectins. Through these experiments, we could demonstrate a profound loss of both α2-3- and α2-6-linked terminal sialic acids in uveitis. Hence, we hypothesize that the higher abundance of NEU1 in uveitic RMG plays an important role in the pathogenesis of uveitis by desialylation of retinal cells. As RMG become activated in the course of uveitis and actively promote inflammation, we propose that NEU1 might represent a novel activation marker for inflammatory RMG. Our data provide novel insights in the expression and implication of NEU1 in inflammation and autoimmune disease.