The Borrelia telomere resolvase, ResT, forms the unusual hairpin telomeres of the linear Borrelia replicons in a process referred to as telomere resolution. Telomere resolution is a DNA cleavage and rejoining reaction that proceeds from a replicated telomere intermediate in a reaction with mechanistic similarities to that catalyzed by type IB topoisomerases. Previous reports have implicated the hairpin-binding module, at the end of the N-terminal domain of ResT, in distorting the DNA between the scissile phosphates so as to promote DNA cleavage and hairpin formation by the catalytic domain. We report that unwinding the DNA between the scissile phosphates, prior to DNA cleavage, is a key cold-sensitive step in telomere resolution. Through the analysis of ResT mutants, rescued by substrate modifications that mimic DNA unwinding between the cleavage sites, we show that formation and/or stabilization of an underwound pre-cleavage intermediate depends upon cooperation of the hairpin-binding module and catalytic domain. The phenotype of the mutants argues that the pre-cleavage intermediate promotes strand ejection to favor the forward reaction and that subsequent hairpin capture is a reversible reaction step. These reaction features are proposed to promote hairpin formation over strand resealing while allowing reversal back to substrate of aborted reactions.
Objectives The aim of this study was to evaluate changes in the conjunctival microbiota of shelter-housed cats with time, upper respiratory disease (URD) and famciclovir administration. Methods Cats were assigned to treatment groups on shelter entry. Healthy cats or cats with URD received ~30 mg/kg or ~90 mg/kg of famciclovir or placebo PO q12h for 7 days, or were untreated. Swabs were collected from ventral conjunctival fornices prior to (day 1) and immediately after (day 8) the treatment period. Microbiota analysis was conducted on 124 randomly selected swabs from healthy (56 swabs) or URD-affected (68 swabs) cats. Following DNA extraction and amplification of the V4 region of the 16S rRNA gene, sequences were assembled into operational taxonomic units (OTUs). Over-represented OTUs (as determined by linear discriminate analysis effect size), alpha and beta diversity, and median relative abundance of known feline ocular surface pathogens were assessed for the entire population and in 10 clinically relevant subpopulations of cats. Results Bacteria from 33 phyla and 70 genera were identified. Considering all cats, median relative abundance of Mycoplasma increased from day 1 to day 8, while Proteobacteria decreased. Community membership and structure (beta diversity) differed between days 1 and 8 for all famciclovir-treated cats (regardless of health status or dose) and healthy or URD-affected cats (regardless of famciclovir dose). Differences in taxonomic diversity within a sample (alpha diversity) between day 1 and day 8 were not detected in any subpopulations. Conclusions and relevance Within 1 week of shelter entry, there were significant changes in community structure and membership of the feline conjunctival microbiota, with a shift towards over-representation of feline ocular surface pathogens. Although famciclovir may impact beta diversity of the feline conjunctival microbiota, absence of change in alpha diversity suggests minimal shift in individual cats.
Objectives The aim of this retrospective case-control study was to report the efficacy of subcutaneous triamcinolone as part of a regimen for feline eosinophilic keratoconjunctivitis (FEK). Methods Records and clinical photographs were reviewed and lesions semi-quantitatively graded for cats with cytologically confirmed FEK. Clinical data were compared between a study population of nine cats (11 eyes) treated with, and a reference population of seven cats (eight eyes) treated without, a median 0.11 mg/kg (range 0.10–0.20 mg/kg) of triamcinolone acetonide subcutaneously. Results Breed, sex, age and prevalence of corneal ulceration at presentation; corneal disease severity before and at the initiation of immunomodulation; and duration of antiviral treatment before immunomodulation did not differ significantly between populations ( P ⩾0.059). Corneal plaques resolved in five cats each from the study and reference populations ( P = 0.366). Median (range) time from immunomodulation to corneal plaque resolution did not significantly differ ( P = 0.246) between the study (median 14 days; range 8–38 days) and reference (median 28 days, range 14–46 days) populations. No adverse reactions were attributed to triamcinolone administration, and all corneal ulcers in the study population re-epithelialized within 14 days (range 8–38 days) following triamcinolone injection. Time to corneal ulcer re-epithelialization following triamcinolone injection varied minimally in those receiving antivirals prior to (8 or 30 days until re-epithelialization), simultaneously with (38 days) or after (14 or 24 days) triamcinolone. Conclusions and relevance In otherwise healthy cats with FEK, subcutaneous administration of triamcinolone appears to be well tolerated and as efficacious as conventional topical immunomodulatory therapies. It may be especially useful in ulcerated eyes where topical immunomodulation is contraindicated.
Objective To assess correlations between clinical and cytological features of feline eosinophilic keratoconjunctivitis at the time of cytological diagnosis. Animals Studied Fifteen client‐owned, domestic breed cats (18 eyes) examined between 2007 and 2019. Procedures An electronic search and medical record review of cats diagnosed with feline eosinophilic keratitis or keratoconjunctivitis (FEK) based on clinical examination findings and eosinophils detected on corneal cytology were conducted. Clinical severity was graded using a modified version of a previously validated semiquantitative preclinical ocular toxicology scoring (SPOTS) system. Clinical grades were assigned following review of clinical images and medical record descriptions, and cytological grades were assigned following review of archived corneal cytology slides. Correlations were analyzed for significance using Spearman's rank correlation coefficient. Results Higher total corneal scores correlated with higher total conjunctival scores, but not with total fluorescein scores. Small lymphocyte scores correlated negatively with scores for collagen degeneration or mineralization. Globule leukocytes, a unique cell type not previously described in ocular cytology, were identified in 4 of 18 cytological samples. Higher globule leukocyte scores were correlated with higher scores for mast cells or plasma cells. Specimens with lower eosinophil scores had higher globule leukocyte scores. Conclusions Large variability was detected in the cytological characteristics and clinical features of FEK‐affected cats. This is the first report of globule leukocytes being identified in ocular cytology from any species. The role of globule leukocytes in the etiopathogenesis and progression of FEK remains unknown and warrants further investigation.
Neoplasms metastatic to the eye are infrequently reported in dogs. 1,2 For example, ocular metastases were identified in only 11.6% of dogs with metastatic or multicentric neoplasms diagnosed on necropsy, with the uveal tract being the most commonly affected ocular site. 3 Metastasis to or multicentric neoplasia affecting the uveal tract has been reported in dogs with lymphoma, 1-4 hemangiosarcoma, 1,3 histiocytic sarcoma, 2 malignant oral melanoma, 1 transmissible
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