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Background: Clopidogrel is commonly prescribed to cats with perceived increased risk of thromboembolic events, but little information exists regarding its antiplatelet effects. ObjectiveTo determine effects of clopidogrel on platelet responsiveness in cats with or without the A31P mutation in the MYBPC3 gene. A secondary aim was to characterize variability in feline platelet responses to clopidogrel. AnimalsFourteen healthy cats from a Maine Coon/outbred mixed Domestic cat colony: 8 cats homozygous for A31P mutation in the MYPBC3 gene and 6 wild-type cats without the A31P mutation. MethodsEx vivo study. All cats received clopidogrel (18.75 mg PO q24h) for 14 days. Before and after clopidogrel treatment, adenosine diphosphate (ADP)-induced P-selectin expression was evaluated. ADP- and thrombin-induced platelet aggregation was measured by optical aggregometry (OA). Platelet pVASP and ADP receptor response index (ARRI) were measured by Western blot analysis. ResultsPlatelet activation from cats with the A31P mutation was significantly (P = .0095) increased [35.55% (18.58-48.55) to 58.90% (24.85-69.90)], in response to ADP. Clopidogrel treatment attenuated ADP-induced P-selectin expression and platelet aggregation. ADP- and PGE(1)-treated platelets had a similar level of pVASP as PGE(1)-treated platelets after clopidogrel treatment. Clopidogrel administration resulted in significantly lower ARRI [24.13% (12.46-35.50) to 11.30% (-7.383 to 23.27)] (P = .017). Two of 13 cats were nonresponders based on OA and flow cytometry. Conclusion and Clinical ImportanceClopidogrel is effective at attenuating platelet activation and aggregation in some cats. Cats with A31P mutation had increased platelet activation relative to the variable response seen in wild-type cats.

Thesis advisor: Thomas N. Seyfried / Sandhoff Disease (SD) is an autosomal recessive neurodegenerative disease caused by a mutation in the Hexb gene for the β-subunit of β-hexosaminidase A, resulting in the inability to catabolize ganglioside GM2 within the lysosomes. SD presents with an accumulation of GM2 and its asialo derivative GA2 primarily in the CNS. Myelin-enriched glycolipids, cerebrosides and sulfatides, are also decreased in SD corresponding with dysmyelination. At present, no treatment exists for SD. Previous studies have shown the therapeutic benefit of using adeno-associated virus (AAV) vector-mediated gene therapy in the treatment of SD in murine and feline models. In this study, CNS tissue was evaluated from SD cats (4-6 week old) treated with bilateral injections of AAVrh8 expressing feline β-hexosaminidase α and β into the thalamus and deep cerebellar nuclei (Thal/DCN) or into the thalamus combined with intracerebroventricular injections (Thal/ICV). Both groups of treated animals had previously shown improved quality of life and absence of whole-body tremors. The activity of β-hexosaminidase was significantly elevated whereas the content of GM2 and GA2 was significantly decreased in tissue samples taken from the cerebral cortex, cerebellum, thalamus, and cervical intumescence. Treatment also increased levels of myelin-enriched cerebrosides and sulfatides in the cortex and thalamus. This study demonstrates the therapeutic benefits of AAV treatment for feline SD and suggests a similar potential for human SD patients. / Thesis (MS) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

Ctenocephalides felis is a major pest of companion animals worldwide. This project aimed to generate novel genetic resources for C. felis and develop tools to aid drug-target identification and validation. Sample handling methods were assessed and candidate reference genes validated, to ensure quality of RNA samples and reliable gene expression normalisation. Piercing C. felis samples prior to storage in RNAlater ensured RNA integrity was maintained over time. Glyceraldehyde 3-phosphate dehydrogenase , 60S ribosomal protein L19 and elongation factor-1α were demonstrated as stable reference genes across all comparisons tested. A C. felis transcriptome encompassing multiple developmental stages, sexes and tissues was sequenced and de novo assemblies produced with two assemblers, Trinity and Oases. Each assembly contained >100000 contigs. Annotation of the assemblies generated functional insight, such as top BLAST hits, GO annotations and signal peptide predictions. The Trinity assembly was deemed the highest quality and searched for genes of interest, involved in development. Expression analysis of selected transcripts across stadia gave insight into developmental processes, and demonstrated the utility of the transcriptome. This study was the first to demonstrate that C. felis can mount an RNAi response upon exposure to dsRNA. Knockdown of glutathione S-transferase σ (GSTσ), was demonstrated in adult C. felis: ≈80 % knockdown following microinjection of dsGSTσ; ≈64 % knockdown after soaking in dsGSTσ; ≈96 % knockdown after continuous feeding on dsGSTσ. RNAi machinery was identified in C. felis. siRNAi pathway components, Dicer 2 and Argonaute 2, were upregulated following dsRNA exposure. Dicer 2 was knocked-down by soaking in dsDicer2, although results of an “RNAi of RNAi” experiment were inconclusive. Transcripts encoding machinery putatively involved in dsRNA uptake and breakdown were also identified. Through these studies, this project has generated novel insights into C. felis biology and opened up new avenues for research.

A telephone questionnaire was developed to collect information on pet owners, cat ownership patterns, and people's opinions about homeless pets. A 7-day observation log was also developed to gather information about free-roaming cats in Caldwell, TX. The objectives of this research were: (1) to evaluate the reliability of the telephone questionnaire, (2) to assess general cat ownership patterns, (3) to evaluate attachment level of pet owners to their pets, (4) to determine general opinions about free-roaming cats, (5) to determine if demographics were associated with opinions about free-roaming cat and dog problems and (6) to investigate free-roaming cat activity in a community. Telephone questionnaire information collected from 100 subjects was tested for reliability. Reliability was fair to good for cat level questions (sex, age, breed, length of time owned, indoor/outdoor status, litter, number of vet visits, vaccinated). Reliability was good for questions concerning subjects' knowledge of cat and dog behavior and levels of attachment to their pets. Reliability was excellent for all household level (demographic) variables. Reliability was moderate for questions regarding subjects' opinions about homeless animals. Telephone questionnaire responses collected from 441 subjects were checked for associations using exploratory logistic and linear regression models. A cat's role as a pet, vaccination status, and the length of time owned were associated with a cat's sterilization status. A cat's role as a pet was associated with the cat's indoor/outdoor status. Household size, education level and ethnicity of the owner were associated with cat ownership. Having children was associated with a negative opinion about homeless cats. Education level was associated with subjects' knowledge about dog and cat behavior. Gender, household size, and knowledge score were associated with subjects' attachment to their pets. Descriptive information on free-roaming cat activity was collected from 21 subjects using the 7-day observation log. Subjects made 382 cat sightings during the study period. Slightly more cat sightings were made during the morning than in the evening and afternoon. Most cats were spotted in neighborhoods and were resting or eating. Most of these cats that were eating were seen during the morning or evening hours.

We studied the effects of varying perturbation magnitude and direction on the postural control process of the central nervous system (CNS) caused by perturbation, before and after sensory loss. The electromyogram (EMG) response to a postural perturbation can be composed by a weighted sum of the center of mass (CoM) kinematics. We extended an existing CoM feedback model which predicted EMG of one muscle for unidirectional perturbations; we used recorded data of bidirectional perturbations, which caused muscle activity in anterior as well as posterior muscles. Modeling the CNS as two delayed feedback controllers, we reconstructed the EMGs of two antagonistic muscles simultaneously that were recorded during postural perturbation experiments on cats. Minimizing the error between predicted and recorded EMG and CoM kinematics, we were able to identify controller gains that would result in the best prediction of the recorded EMGs. We hypothesized that the weights on the CoM kinematics remained constant independent of variations in perturbation magnitude or reversed perturbation direction. We applied our model to data from bidirectional perturbations with varying magnitude, with which the cats were perturbed for a short time in one direction and a longer time in the opposite direction. The gains showed small variation for EMG predictions following long perturbations; however, the prediction of EMG following the initial displacement resulted in large gain variations. We showed that these variations were caused by our optimization methods, which was not able to consistently identify controller gains for short initial movements. Using the weights identified for unidirectional perturbations, we were able to predict muscle activity for both directions with the same gains. This suggests that the weights of the CoM kinematics for each muscle did not change for varying perturbation magnitude. We conclude that varying EMG shapes were induced solely by the variation of the CoM kinematics. We repeated the investigations on data that was recorded from cats suffering from sensory loss and found reduced CoM acceleration feedback.

A telephone questionnaire was developed to collect information on pet owners, cat ownership patterns, and people's opinions about homeless pets. A 7-day observation log was also developed to gather information about free-roaming cats in Caldwell, TX. The objectives of this research were: (1) to evaluate the reliability of the telephone questionnaire, (2) to assess general cat ownership patterns, (3) to evaluate attachment level of pet owners to their pets, (4) to determine general opinions about free-roaming cats, (5) to determine if demographics were associated with opinions about free-roaming cat and dog problems and (6) to investigate free-roaming cat activity in a community. Telephone questionnaire information collected from 100 subjects was tested for reliability. Reliability was fair to good for cat level questions (sex, age, breed, length of time owned, indoor/outdoor status, litter, number of vet visits, vaccinated). Reliability was good for questions concerning subjects' knowledge of cat and dog behavior and levels of attachment to their pets. Reliability was excellent for all household level (demographic) variables. Reliability was moderate for questions regarding subjects' opinions about homeless animals. Telephone questionnaire responses collected from 441 subjects were checked for associations using exploratory logistic and linear regression models. A cat's role as a pet, vaccination status, and the length of time owned were associated with a cat's sterilization status. A cat's role as a pet was associated with the cat's indoor/outdoor status. Household size, education level and ethnicity of the owner were associated with cat ownership. Having children was associated with a negative opinion about homeless cats. Education level was associated with subjects' knowledge about dog and cat behavior. Gender, household size, and knowledge score were associated with subjects' attachment to their pets. Descriptive information on free-roaming cat activity was collected from 21 subjects using the 7-day observation log. Subjects made 382 cat sightings during the study period. Slightly more cat sightings were made during the morning than in the evening and afternoon. Most cats were spotted in neighborhoods and were resting or eating. Most of these cats that were eating were seen during the morning or evening hours.

caT, a Petri net-based hypertext system, supports the modeling of user characteristics, contextual information, as well as the policies that govern the operation of a digital library within the infrastructure that presents its contents. Traditionally, users have created caT networks from scratch, thus limiting their use to small collections. In this research, we introduce TcAT, a new authoring tool that supports features for component-based authoring, with a view to enable the creation of large caT nets that can represent complex, real-life spaces such as libraries and museums. TcAT supports graphical, template-based creation of nets as well as a textual language for easy manipulation of large structures. It implements composition operations from Petri net theory to select, categorize, and modify existing net fragments as building blocks for composing larger networks. Authors may switch modes between visual and textual authoring at will, thus combining the strengths of expressing large nets textually and selecting net fragments via point-and-click interaction. A user evaluation of the new authoring mechanisms suggests that this is a promising tool for improving the efficiency of experienced users as well as that of novice users, who are unfamiliar with the Petri net formalism.

Zugl.: München, Techn. Univ., Diss., 2008