Cellular and humoral immune responses and protection against schistosomes induced by a radiation-attenuated vaccine in chimpanzees

The radiation-attenuated Schistosoma mansoni vaccine is highly effective in rodents and primates but has never been tested in humans, primarily for safety reasons. To strengthen its status as a paradigm for a human recombinant antigen vaccine, we have undertaken a small-scale vaccination and challenge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, and parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic stages of challenge infection up to chemotherapeutic cure. Vaccination induced a strong in vitro proliferative response and early gamma interferon production, but type 2 cytokines were dominant by the time of challenge. The controls showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reached high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccination were manifested as an amelioration of acute disease and overall morbidity, revealed by differences in gamma-glutamyl transferase level, leukocytosis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 46% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection

Exposure to Nonhuman Primates in Rural Cameroon

A high percentage of rural villagers are exposed to blood of nonhuman primates and risk acquiring infectious diseases

Melanocortin Receptor 4 Deficiency Affects Body Weight Regulation, Grooming Behavior, and Substrate Preference in the Rat

Obesity is caused by an imbalance between energy intake and expenditure and has become a major health-care problem in western society. The central melanocortin system plays a crucial role in the regulation of feeding and energy expenditure, and functional loss of melanocortin receptor 4 (MC4R) is the most common genetic cause of human obesity. In this study, we present the first functional Mc4r knockout model in the rat, resulting from an N-ethyl-N-nitrosourea mutagenesis–induced point mutation. In vitro observations revealed impaired membrane-binding and subsequent nonfunctionality of the receptor, whereas in vivo observations showed that functional loss of MC4R increased body weight, food intake, white adipose mass, and changed substrate preference. In addition, intracerebroventricular (ICV) administration of Agouti-Related Protein79–129 (AgRP79–129), an MC4R inverse agonist, or Melanotan-II (MTII), an MC4R agonist, did affect feeding behavior in wild-type rats but not in homozygous mutant rats, confirming complete loss of MC4R function in vivo. Finally, ICV administration of MTII induced excessive grooming behavior in wild-type rats, whereas this effect was absent in homozygous mutant rats, indicating that MTII-induced grooming behavior is exclusively regulated via MC4R pathways. Taken together, we expect that the MC4R rat model described here will be a valuable tool for studying monogenic obesity in humans. More specifically, the relative big size and increased cognitive capacity of rats as compared to mice will facilitate complex behavioral studies and detailed mechanistic studies regarding central function of MC4R, both of which ultimately may help to further understand the specific mechanisms that induce obesity during loss of MC4R function

Contextualizing consolidation : British Columbia school consolidation from the perspective of the Prince George region

Throughout the first half of this century controversy surrounded the division of governance between provincial and local authorities. In a general sense this thesis examines the centralizing forces of equality of opportunity promoted by the provincial government versus the forces of decentralization found in the principle of local autonomy. Specifically this thesis examines the reasons why the school districts in die central interior o f British Columbia, around Prince George, were consolidated with little or no opposition in 1946 following the recommendations of the Cameron Report. This thesis is a case study of the region approximately in the center of the province that was to become School District No. 57. A variety of sources were used and include printed and manuscript documents from the Premiers Papers and Department of Education, including extensive use of the school inspectors' reports for schools in the region between 1940 and 1946 found in the British Columbia Archives in Victoria. Local histories and oral interviews of participants of the consolidation process were used to contextualize the consolidation process in the Prince George region. Chapters I and II discuss the founding of two types o f societies in the region and the schools they inaugurated. The urban society of Prince George was founded by land promoters bolstered with the spirit of boosterism that originated on the Canadian Prairies before the turn of the century. Boosters actively promoted the development of the civic infrastructure including schools to reinforce the city's central place to secure future growth. Rural communities, founded to tap the wealth of the forests, were inextricably tied to the economic problems of the sawmills they depended upon. Spatially dispersed by geographic factors and tied to the economic fluctuations of the prairie market, these communities lived on the edge o f extinction. Bodi the city and rural schools were plagued with the problems of rural education in B C during their early years. Teacher transiency and teachers low on qualifications and experience affected the quality of education. The founding differences between the two societies were reflected in the inspectoral reports. The inspectors generally praised the Prince George City trustees and their schools. They were dynamic and well-organized with the best educational intentions. The rural schools to the inspectors were "inefficient" exemplified by pupil retardation and the barest of elementary programs in buildings that had in style changed little since British Columbia's first superintendent of Education, John Jessop. The Department of Education personnel began to blame this inefficiency on the local trustees believing that local autonomy had broken down, exemplified by the number of Official Trusteeships in the province. The evidence from the Prince George region suggests some trustees did "give up". Narrow social hierarchies in the rural communities forced many trustees to serve for years. Official Trusteeships were a growing trend through the 1920s and 1930s to raise school efficiency just when school expansion was at its greatest in the central interior. Chapters III and IV discuss the Cameron Report and its implementation at the regional level. Cameron was concerned with the effects of decentralization on equality of opportunity for students and equality of burden between school districts and the provincial government. His recommendations formed a new relationship between the provincial government and local authorities. The essential local ingredient of educational financing; property taxation, was standardized and partly centralized. Local autonomy was reshaped through consolidation with more powerful school boards to attack local educational problems. Consolidation was successful with little opposition in the Prince George region because of the new trustees. Knowledgable in the methodis of boosterism, innovative and dynamic, they offered material progress to the region immediately. Consolidation also afforded the rural population equality of opportunity through the Prince George high school built as a regional educational centre. This thesis raises the question o f how the educational departments' personnel interpreted the facts they used to consolidate the school districts in 1946. The problems of education in the central interior were an extension of the economic problems of the region. This thesis contextualizes the urban based recommendations highlighting the role of the local community in extracting those points that were really important to the local people.Education, Faculty ofGraduat