Treatment of naturally acquired demodectic mange with amitraz in two harbour seals (Phoca vitulina)

Two male harbour seals (Phoca vitulina; 33 and 35 years old, respectively), housed since 2002 at a zoo for exhibition purposes, developed severe, multifocal and diffuse skin lesions. Skin scrapings and microscopy for parasites as well as pure cultures for bacteria and dermatophytes were carried out to identify the aetiological agent. Skin scrapings showed that lesions appearing on the seals were caused by an infestation of Demodex mites, which is uncommon in marine mammals, and were not due to other causative agents (parasites, bacteria or dermatophytes). Treatment with amitraz (0.01%) once a week for three weeks and with ampicillin (10 mg/kg SID per os) for six days eliminated the mites and resolved the clinical signs of demodectic mange in the harbour seals. The purpose of this report is to describe the successful treatment of naturally acquired demodectic mange with amitraz in harbour seals

KITENIN increases invasion and migration of mouse squamous cancer cells and promotes pulmonary metastasis in a mouse squamous tumor model

AbstractKAI1 C-terminal interacting tetraspanin (KITENIN) is reported to promote metastasis in mouse colon cancer models. We investigated the role of KITENIN on the progression of squamous cell carcinoma (SCC). In a preliminary clinical study using resected tissues from head and neck SCC patients, KITENIN was highly expressed in tumors and metastatic lymph nodes, while KAI1 was more increased in adjacent mucosa than in tumor. KITENIN-transfected mouse squamous cancer (SCC VII/KITENIN) cells showed significantly higher invasion, migration, and proliferation than empty vector-transfected cells. In syngeneic mouse squamous tumor models, more increased tumor volume and enhanced lung metastasis were found in SCC VII/KITENIN cells-injected mice. Thus, KITENIN increases invasion and migration of squamous cancer cells and thereby promotes distant metastasis in mouse squamous tumor models

Comprehensive MicroRNAome Analysis of the Relationship Between Alzheimer Disease and Cancer in Double-Knockout Mice

Purpose Presenilins are functionally important components of γ-secretase, which cleaves a number of transmembrane proteins. Manipulations of PSEN1 and PSEN2 have been separately studied in Alzheimer disease (AD) and cancer because both involve substrates of γ-secretase. However, numerous clinical studies have reported an inverse correlation between AD and cancer. Interestingly, AD is a neurodegenerative disorder, whereas cancer is characterized by the proliferation of malignant cells. However, this inverse correlation in the PSEN double-knockout (PSEN dKO) mouse model of AD has been not elucidated, although doing so would shed light onto the relationship between AD and cancer. Methods To investigate the inverse relationship of AD and cancer under conditions of PSEN loss, we used the hippocampus of 7-month-old and 18-month-old PSEN dKO mice for a microRNA (miRNA) microarray analysis, and explored the tumorsuppressive or oncogenic role of differentially-expressed miRNAs. Results The total number of miRNAs that showed changes in expression level was greater at 18 months of age than at 7 months. Most of the putative target genes of the differentially-expressed miRNAs involved Cancer pathways. Conclusions Based on literature reviews, many of the miRNAs involved in Cancer pathways were found to be known tumorsuppressive miRNAs, and their target genes were known or putative oncogenes. In conclusion, the expression levels of known tumor-suppressive miRNAs increased at 7 and 18 months, in the PSEN dKO mouse model of AD, supporting the negative correlation between AD and cancer

ATAD5 suppresses centrosome over-duplication by regulating UAF1 and ID1

Centrosomes are the primary microtubule-organizing centers that are important for mitotic spindle assembly. Centrosome amplification is commonly observed in human cancer cells and contributes to genomic instability. However, it is not clear how centrosome duplication is dysregulated in cancer cells. Here, we report that ATAD5, a replisome protein that unloads PCNA from chromatin as a replication factor C-like complex (RLC), plays an important role in regulating centrosome duplication. ATAD5 is present at the centrosome, specifically at the base of the mother and daughter centrioles that undergo duplication. UAF1, which interacts with ATAD5 and regulates PCNA deubiquitination as a complex with ubiquitin-specific protease 1, is also localized at the centrosome. Depletion of ATAD5 or UAF1 increases cells with over-duplicated centrosome whereas ATAD5 overexpression reduces such cells. Consistently, the proportion of cells showing the multipolar mode of chromosome segregation is increased among ATAD5-depleted cells. The localization and function of ATAD5 at the centrosomes do not require other RLC subunits. UAF1 interacts and co-localizes with ID1, a protein that increases centrosome amplification upon overexpression. ATAD5 depletion reduces interactions between UAF1 and ID1 and increases ID1 signal at the centrosome, providing a mechanistic framework for understanding the role of ATAD5 in centrosome duplication

Outer membrane protein a of Salmonella enterica serovar Typhimurium activates dendritic cells and enhances Th1 polarization

<p>Abstract</p> <p>Background</p> <p>Typhoid, which is caused by <it>Salmonella enterica </it>serovar Typhimurium, remains a major health concern worldwide. Multidrug-resistant strains of <it>Salmonella </it>have emerged which exhibit increased survivability and virulence, thus leading to increased morbidity. However, little is known about the protective immune response against this microorganism. The outer membrane protein (Omp)A of bacteria plays an important role in pathogenesis.</p> <p>Results</p> <p>We purified OmpA from <it>S. enterica </it>serovar Typhimurium (OmpA-sal) and characterized the role of OmpA-sal in promoting adaptive and innate immune responses. OmpA-sal functionally activated bone marrow-derived dendritic cells by augmenting expression of CD80, CD86, and major histocompatibility complex classes I and II. Interestingly, OmpA-sal induced production of interferon-γ from T cells in mixed lymphocyte reactions, thus indicating Th1-polarizing capacity. The expression of surface markers and cytokine production in dendritic cells was mediated by the TLR4 signaling pathway in a TLR4 Knock-out system.</p> <p>Conclusions</p> <p>Our findings suggest that OmpA-sal modulates the adaptive immune responses to <it>S. enterica </it>serovar Typhimurium by activating dendritic cells and driving Th1 polarization, which are important properties to consider in the development of effective <it>S. enterica </it>serovar Typhimurium vaccines and immunotherapy adjuvant.</p

Safety and Efficacy of Second-Generation Everolimus-Eluting Xience V Stents Versus Zotarolimus-Eluting Resolute Stents in Real-World Practice Patient-Related and Stent-Related Outcomes From the Multicenter Prospective EXCELLENT and RESOLUTE-Korea Registries

ObjectivesThis study sought to compare the safety and efficacy of the Xience V/Promus everolimus-eluting stent (EES) (Abbott Vascular, Temecula, California) with the Endeavor Resolute zotarolimus-eluting stent (ZES-R) (Medtronic Cardiovascular, Santa Rosa, California) in “all-comer” cohorts.BackgroundOnly 2 randomized controlled trials have compared these stents.MethodsThe EXCELLENT (Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting) and RESOLUTE-Korea registries prospectively enrolled 3,056 patients treated with the EES and 1,998 patients treated with the ZES-R, respectively, without exclusions. Stent-related composite outcomes (target lesion failure [TLF]) and patient-related composite outcomes were compared in crude and propensity score-matched analyses.ResultsOf 5,054 patients, 3,830 (75.8%) had off-label indication (2,217 treated with EES and 1,613 treated with ZES-R). The stent-related outcome (82 [2.7%] vs. 58 [2.9%], p = 0.662) and the patient-related outcome (225 [7.4%] vs. 153 [7.7%], p = 0.702) did not differ between EES and ZES-R, respectively, at 1 year, which was corroborated by similar results from the propensity score-matched cohort. The rate of definite or probable stent thrombosis (18 [0.6%] vs. 7 [0.4%], p = 0.306) also was similar. In multivariate analysis, off-label indication was the strongest predictor of TLF (adjusted hazard ratio: 2.882; 95% confidence interval: 1.226 to 6.779; p = 0.015).ConclusionsIn this robust real-world registry with unrestricted use of EES and ZES-R, both stents showed comparable safety and efficacy at 1-year follow-up. Overall incidences of TLF and definite stent thrombosis were low, even in the patients with off-label indication, suggesting excellent safety and efficacy of both types of second-generation drug-eluting stents

An Essential Regulatory Role of Downstream of Kinase-1 in the Ovalbumin-Induced Murine Model of Asthma

The downstream of kinase (DOK)-1 is involved in the protein tyrosine kinase (PTK) pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases