Helicases perform vital roles in the cell by unwinding D N A to make it accessible for the essential processes of replication, transcription and repair. In Caenorhabditis elegans, the DOG- 1 helicase-like protein is required for polyG/polyC-tract (G/C-tract) maintenance, as dog-l animals have a mutator phenotype characterized by deletions that initiate in G/C-tracts. DOG-1 may unwind secondary structures that form in polyguanine D N A during lagging strand replication. In order to more completely understand the role of dog-1, genetic interactors were identified, dog-1 functionally interacts with the him-6/BLM helicase. Absence of recombinational repair-implicated proteins in the dog-1 background, including HIM-6/BLM, RAD-51, BRD-1/BARD1 and HIM-9/XPF, as well as the trans-lesion synthesis polymerases polKMD po/7 increased the frequency of animals with G/C-tract deletions, indicating that these pathways are important mechanisms for repair at G/C-tracts in the absence of DOG-1. These data support the hypothesis that persisting D N A secondary structures can cause replication fork stalling, which can be resolved by deletion-free or deletion-prone mechanisms. DOG-1 has highest sequence identity to human BR1P1/FANCJ, which is mutated in patients from the Fanconi Anemia (FA) subgroup J. D N A damage sensitivity experiments indicated that, like chicken F A N C J cells, dog-1 mutants were not significantly sensitive to DNA damage from X-ray or UV-irradiation, but were extremely hypersensitive to the D N A interstrand cross-linking agent UVA-activated trimethylpsoralen. Thus, DOG-1 appears to have a conserved role in cross-link repair and is the C. elegans F A N C J homolog. Characterization of the dog-1/FANCJ-relatsd helicase, Jrh-1, revealed that mutants for this putative helicase are moderately sensitive to cross-linking agents, dog-1 jrh-1 double mutants displayed a synthetic lethal phenotype characterized by excessive recombination intermediates and mitotic catastrophe in the germline. However, absence of JRH-1 did not have any effect on G/C-tract deletions, indicating that JRH-1 does not have a redundant function with DOG-1 at G/C-tracts. Absence of JRH-1 reduced the fitness of eTl and nTl translocation hétérozygotes, but not translocation homozygotes, jrh-1 was synthetically lethal with him-6/BLM and with the endonuclease mus-81, suggesting a possible role for JRH-1 in regulating the balance between different types of repair.

No description available.

Thesis (doctoral)--Rijksuniversiteit te Utrecht, 1959. / Includes bibliographical references (p. 94-96).

Thesis (doctoral)--Rijksuniversiteit te Utrecht, 1959. / Includes bibliographical references (p. 94-96).

The influence of dog education on their behaviour in maturity was described and documented in this diploma thesis. The dog handling and relationship to other members of family and to other dogs were studied. Questionnaire investigation was made in the area of Trhové Sviny town. It was found, that not only the time of removing the puppies from their mother, but also the way of the care for the dog before the removing play important and primary role. The way and the degree of social cognition by the new owner and the knowledge in field of ethology and in dog communication signals of the new owner are important as well.

Helicases perform vital roles in the cell by unwinding D N A to make it accessible for the essential processes of replication, transcription and repair. In Caenorhabditis elegans, the DOG- 1 helicase-like protein is required for polyG/polyC-tract (G/C-tract) maintenance, as dog-l animals have a mutator phenotype characterized by deletions that initiate in G/C-tracts. DOG-1 may unwind secondary structures that form in polyguanine D N A during lagging strand replication. In order to more completely understand the role of dog-1, genetic interactors were identified, dog-1 functionally interacts with the him-6/BLM helicase. Absence of recombinational repair-implicated proteins in the dog-1 background, including HIM-6/BLM, RAD-51, BRD-1/BARD1 and HIM-9/XPF, as well as the trans-lesion synthesis polymerases polKMD po/7 increased the frequency of animals with G/C-tract deletions, indicating that these pathways are important mechanisms for repair at G/C-tracts in the absence of DOG-1. These data support the hypothesis that persisting D N A secondary structures can cause replication fork stalling, which can be resolved by deletion-free or deletion-prone mechanisms. DOG-1 has highest sequence identity to human BR1P1/FANCJ, which is mutated in patients from the Fanconi Anemia (FA) subgroup J. D N A damage sensitivity experiments indicated that, like chicken F A N C J cells, dog-1 mutants were not significantly sensitive to DNA damage from X-ray or UV-irradiation, but were extremely hypersensitive to the D N A interstrand cross-linking agent UVA-activated trimethylpsoralen. Thus, DOG-1 appears to have a conserved role in cross-link repair and is the C. elegans F A N C J homolog. Characterization of the dog-1/FANCJ-relatsd helicase, Jrh-1, revealed that mutants for this putative helicase are moderately sensitive to cross-linking agents, dog-1 jrh-1 double mutants displayed a synthetic lethal phenotype characterized by excessive recombination intermediates and mitotic catastrophe in the germline. However, absence of JRH-1 did not have any effect on G/C-tract deletions, indicating that JRH-1 does not have a redundant function with DOG-1 at G/C-tracts. Absence of JRH-1 reduced the fitness of eTl and nTl translocation hétérozygotes, but not translocation homozygotes, jrh-1 was synthetically lethal with him-6/BLM and with the endonuclease mus-81, suggesting a possible role for JRH-1 in regulating the balance between different types of repair. / Medicine, Faculty of / Medical Genetics, Department of / Graduate

Aggressive behavior in dogs poses public health and animal welfare concerns, however the biological mechanisms regulating dog aggression are not well understood. We investigated the relationships between endogenous plasma oxytocin (OT) and vasopressin (AVP)-neuropeptides that have been linked to affiliative and aggressive behavior in other mammalian species-and aggression in domestic dogs. We first validated enzyme-linked immunosorbent assays (ELISAs) for the measurement of free (unbound) and total (free + bound) OT and AVP in dog plasma. In Experiment 1 we evaluated behavioral and neuroendocrine differences between a population of pet dogs with a history of chronic aggression toward conspecifics and a matched control group. Dogs with a history of aggression exhibited more aggressive behavior during simulated encounters with conspecifics, and had lower free, but higher total plasma AVP than matched controls, but there were no group differences for OT. In Experiment 2 we compared OT and AVP concentrations between pet dogs and a population of assistance dogs that have been bred for affiliative and non-aggressive temperaments, and investigated neuroendocrine predictors of individual differences in social behavior within the assistance dog population. Compared to pet dogs, assistance dogs had higher free and total OT, but there were no differences in either measure for AVP. Within the assistance dog population, dogs who behaved more aggressively toward a threatening stranger had higher total AVP than dogs who did not. Collectively these data suggest that endogenous OT and AVP may play critical roles in shaping dog social behavior, including aspects of both affiliation and aggression.

Master of Science in Biomedical Sciences / Department of Clinical Sciences / Walter C. Renberg / OBJECTIVE: The purpose of the study reported here was to evaluate pharmacokinetics of cefazolin in dogs receiving a single IV injection of cefazolin (22 mg/kg) and dogs receiving simultaneous IV and IM injections of cefazolin (total dose, 44 mg/kg). METHODS: Twelve purpose-bred Beagles (6/group) were assigned to receive a single injection of cefazolin (22 mg/kg, IV) or simultaneous injections (22 mg/kg, IV, and 22 mg/kg, IM). Interstitial fluid was collected over a 5-hour period using ultrafiltration probes for pharmacokinetic analysis. RESULTS: Mean cefazolin concentration in the interstitial fluid at 1, 1.5, 2, 3, 4, and 5 hours after injection was 39.6, 29.1, 21.1, 10.3, 6.4, and 2.7 μg/mL, respectively, for the IV group and 38.3, 53.3, 46.4, 31.7, 19.1, and 8.9 μg/mL, respectively, for the IV + IM group. The mean area under the concentration-time curve extrapolated to infinity, maximum concentration, half life and time to the maximum concentration was 74.99 and 154.16 h•μg/mL, 37.3 and 51.5 μg/mL, 0.96 and 1.11 hours, 1.28 and 1.65 hours, respectively, for the IV and IV + IM groups. CONCLUSIONS AND CLINICAL RELEVANCE: Cefazolin concentrations in interstitial fluid of dogs were maintained at > 4 μg/mL for 4 hours after a single IV injection and for 5 hours after simultaneous IV and IM injections. Based on these results, simultaneous administration of cefazolin IV + IM 30 to 60 minutes before surgery should provide interstitial fluid concentrations effective against the most common commensal organisms (Staphylococcus spp and Streptococcus spp) on the skin of dogs for surgical procedures lasting ≤ 4 hours.

Canine-mediated rabies is a serious zoonosis responsible for at least 55,000 human deaths every year, primarily in less developed communities in Asia and Africa where domestic dogs are free-roaming. The disease can be effectively controlled through vaccinating at least 45% of the dogs in a population; however the impact of vaccinations on disease incidence may be affected by dynamic demographic and immunological processes. Specifically, the contribution of these processes, and their regulatory factors, to vaccination coverage and rabies transmission has not been comprehensively estimated. To improve rabies control, through field interventions and epidemiological modelling, more information regarding the effect of these processes, and their regulatory factors, on population and disease dynamics and vaccinal responses was needed. This required a multifaceted approach, using techniques from the fields of population ecology, vaccine-immunology, social science and epidemiological modelling. Demographic data were collected from four populations of free-roaming domestic dogs, two in South Africa and two in Indonesia where rabies is endemic. Longitudinal, individual-level data were obtained by direct observation and surveys, and community-level data by participatory methods. Longitudinal, serological data were collected from three cohorts within the populations. Epidemiological models were based on epidemic theory and empirical data from this current study and previous studies. A wide array of data were generated relevant to planning rabies control programmes, however of particular importance was evidence regarding positive and negative the impacts of human factors on population and disease dynamics. Nearly all of the dogs were owned, despite being free-roaming, and were accessible for vaccination through their owners; and population size was regulated through human demand for dogs and a substantial fraction of dogs was acquired from outside the communities. These translocated dogs may contribute to the spread of rabies, necessitating widespread and sustained vaccination programmes. Considerable differences in the handleability of dogs between locations and, thus ease of vaccine delivery, may also be attributable to differences in human-dog interactions. Finally, a critical review of the literature, and evaluation of epidemiological models, suggests that human interference in the transmission processes may reduce the incidence of rabies and vaccination threshold. This study has provided specific evidence that human behaviours are likely to be critically important in relation to the transmission and control of canine-mediated rabies ? and is the first to properly identify this. Further detailed studies are required to explore these behaviours and how they vary culturally and geographically. In addition, the results highlight the critical role that demographic processes more generally, as well as immunological decay, play in influencing the long term success of rabies vaccination programmes. Overall, this research has provided valuable support for planning rabies control programmes and for parameterisation of epidemiological models of infectious diseases, including rabies.

Stress in dogs can contribute to behavioural problems which may lead to rehoming or euthanasia of the dog. The aim of this study was to investigate how dog characteristics correlated to stress, whether it is possible to detect behavioural problems in order to treat the dogs. Twenty-two dogs were evaluated according to their behavioural problem by a veterinarian and a dog trainer. The dogs participated in a behavioural and physiological test, and the results were compared to characteristics gathered by a Canine Behavioural Assessment and Research Questionnaire (C-BARQ), filled in by the dogs’ owners. The result showed that the total amount of stress related behaviour correlated positively to the C-BARQ score for attachment and attention-seeking behaviour and had a tendency of positive correlation to energy level and owner-directed aggression. Both the veterinarian behavioural problem score and trainer behavioural problem score had a tendency of positive correlation to stranger-directed fear. Dogs that, according to the C-BARQ, were found to be very attached and attention-seeking, showed high energy level or owner-directed aggression were likely to show stress related behaviours during the test in my study. By addressing the stress, the behavioural problems may be eased.