Chiropteran types I and II interferon genes inferred from genome sequencing traces by a statistical gene-family assembler.

BACKGROUND: The rate of emergence of human pathogens is steadily increasing; most of these novel agents originate in wildlife. Bats, remarkably, are the natural reservoirs of many of the most pathogenic viruses in humans. There are two bat genome projects currently underway, a circumstance that promises to speed the discovery host factors important in the coevolution of bats with their viruses. These genomes, however, are not yet assembled and one of them will provide only low coverage, making the inference of most genes of immunological interest error-prone. Many more wildlife genome projects are underway and intend to provide only shallow coverage. RESULTS: We have developed a statistical method for the assembly of gene families from partial genomes. The method takes full advantage of the quality scores generated by base-calling software, incorporating them into a complete probabilistic error model, to overcome the limitation inherent in the inference of gene family members from partial sequence information. We validated the method by inferring the human IFNA genes from the genome trace archives, and used it to infer 61 type-I interferon genes, and single type-II interferon genes in the bats Pteropus vampyrus and Myotis lucifugus. We confirmed our inferences by direct cloning and sequencing of IFNA, IFNB, IFND, and IFNK in P. vampyrus, and by demonstrating transcription of some of the inferred genes by known interferon-inducing stimuli. CONCLUSION: The statistical trace assembler described here provides a reliable method for extracting information from the many available and forthcoming partial or shallow genome sequencing projects, thereby facilitating the study of a wider variety of organisms with ecological and biomedical significance to humans than would otherwise be possible.

Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites.

PURPOSE: Evaluating genetic susceptibility may clarify effects of known environmental factors and also identify individuals at high risk. We evaluated the association of four insulin-related pathway gene polymorphisms in insulin-like growth factor-1 (IGF-I) (CA)( n ) repeat, insulin-like growth factor-2 (IGF-II) (rs680), insulin-like growth factor-binding protein-3 (IGFBP-3) (rs2854744), and adiponectin (APM1 rs1501299) with colon cancer risk, as well as relationships with circulating IGF-I, IGF-II, IGFBP-3, and C-peptide in a population-based study. METHODS: Participants were African Americans (231 cases and 306 controls) and Whites (297 cases, 530 controls). Consenting subjects provided blood specimens and lifestyle/diet information. Genotyping for all genes except IGF-I was performed by the 5'-exonuclease (Taqman) assay. The IGF-I (CA)(n) repeat was assayed by PCR and fragment analysis. Circulating proteins were measured by enzyme immunoassays. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by logistic regression. RESULTS: The IGF-I (CA)( 19 ) repeat was higher in White controls (50 %) than African American controls (31 %). Whites homozygous for the IGF-I (CA)(19) repeat had a nearly twofold increase in risk of colon cancer (OR = 1.77; 95 % CI = 1.15-2.73), but not African Americans (OR = 0.73, 95 % CI 0.50-1.51). We observed an inverse association between the IGF-II Apa1 A-variant and colon cancer risk (OR = 0.49, 95 % CI 0.28-0.88) in Whites only. Carrying the IGFBP-3 variant alleles was associated with lower IGFBP-3 protein levels, a difference most pronounced in Whites (p-trend <0.05). CONCLUSIONS: These results support an association between insulin pathway-related genes and elevated colon cancer risk in Whites but not in African Americans.

Shifting Loyalties: World War I and the Conflicted Politics of Patriotism in the British Caribbean

This dissertation examines how the crisis of World War I impacted imperial policy and popular claims-making in the British Caribbean. Between 1915 and 1918, tens of thousands of men from the British Caribbean volunteered to fight in World War I and nearly 16,000 men, hailing from every British colony in the region, served in the newly formed British West Indies Regiment (BWIR). Rousing appeals to imperial patriotism and manly duty during the wartime recruitment campaigns and postwar commemoration movement linked the British Empire, civilization, and Christianity while simultaneously promoting new roles for women vis-à-vis the colonial state. In Jamaica and Trinidad and Tobago, the two colonies that contributed over seventy-five percent of the British Caribbean troops, discussions about the meaning of the war for black, coloured, white, East Indian, and Chinese residents sparked heated debates about the relationship among race, gender, and imperial loyalty.

To explore these debates, this dissertation foregrounds the social, cultural, and political practices of BWIR soldiers, tracing their engagements with colonial authorities, military officials, and West Indian civilians throughout the war years. It begins by reassessing the origins of the BWIR, and then analyzes the regional campaign to recruit West Indian men for military service. Travelling with newly enlisted volunteers across the Atlantic, this study then chronicles soldiers' multi-sited campaign for equal status, pay, and standing in the British imperial armed forces. It closes by offering new perspectives on the dramatic postwar protests by BWIR soldiers in Italy in 1918 and British Honduras and Trinidad in 1919, and reflects on the trajectory of veterans' activism in the postwar era.

This study argues that the racism and discrimination soldiers experienced overseas fueled heightened claims-making in the postwar era. In the aftermath of the war, veterans mobilized collectively to garner financial support and social recognition from colonial officials. Rather than withdrawing their allegiance from the empire, ex-servicemen and civilians invoked notions of mutual obligation to argue that British officials owed a debt to West Indians for their wartime sacrifices. This study reveals the continued salience of imperial patriotism, even as veterans and their civilian allies invoked nested local, regional, and diasporic loyalties as well. In doing so, it contributes to the literature on the origins of patriotism in the colonial Caribbean, while providing a historical case study for contemporary debates about "hegemonic dissolution" and popular mobilization in the region.

This dissertation draws upon a wide range of written and visual sources, including archival materials, war recruitment posters, newspapers, oral histories, photographs, and memoirs. In addition to Colonial Office records and military files, it incorporates previously untapped letters and petitions from the Jamaica Archives, National Archives of Trinidad and Tobago, Barbados Department of Archives, and US National Archives.

Primary care physician decision making regarding severe obesity treatment and bariatric surgery: a qualitative study.

BACKGROUND: Less than 1% of severely obese US adults undergo bariatric surgery annually. It is critical to understand the factors that contribute to its utilization. OBJECTIVES: To understand how primary care physicians (PCPs) make decisions regarding severe obesity treatment and bariatric surgery referral. SETTING: Focus groups with PCPs practicing in small, medium, and large cities in Wisconsin. METHODS: PCPs were asked to discuss prioritization of treatment for a severely obese patient with multiple co-morbidities and considerations regarding bariatric surgery referral. Focus group sessions were analyzed by using a directed approach to content analysis. A taxonomy of consensus codes was developed. Code summaries were created and representative quotes identified. RESULTS: Sixteen PCPs participated in 3 focus groups. Four treatment prioritization approaches were identified: (1) treat the disease that is easiest to address; (2) treat the disease that is perceived as the most dangerous; (3) let the patient set the agenda; and (4) address obesity first because it is the common denominator underlying other co-morbid conditions. Only the latter approach placed emphasis on obesity treatment. Five factors made PCPs hesitate to refer patients for bariatric surgery: (1) wanting to "do no harm"; (2) questioning the long-term effectiveness of bariatric surgery; (3) limited knowledge about bariatric surgery; (4) not wanting to recommend bariatric surgery too early; and (5) not knowing if insurance would cover bariatric surgery. CONCLUSION: Decision making by PCPs for severely obese patients seems to underprioritize obesity treatment and overestimate bariatric surgery risks. This could be addressed with PCP education and improvements in communication between PCPs and bariatric surgeons.