268 research outputs found

    Florida: The Mediated State

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    The Mediated State addresses the perceived and the real experience linked to Florida and demonstrates the state acts as a bellwether for understanding postwar America in the late twentieth and early twenty-first centuries. Examining historical shifts linked to perceptions of the state, Chambliss and Cummings argue contemporary observers, like their historical antecedents, look to Florida to glean some greater understanding of the broader national experience

    Oral History Interview with President Emeritus Thaddeus Seymour, January 30, 2009.

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    Thaddeus Seymour came to Rollins in 1978 as the twelfth president of the College. During his twelve-year tenure, he not only transformed the school through fund-raising efforts, but also enhanced the academic excellence of its liberal arts education and strengthened the relationship with the local community. Seymour was born on June 29, 1928, in New York City. His father was Whitney North Seymour, a well-known attorney and president of the American Bar Association. Seymour attended Princeton and the University of California at Berkley as an undergraduate. From there, he went to the University of North Carolina, studied eighteenth-century English literature, and received his master’s degree and Ph.D. Seymour began his academic career as an English professor at Dartmouth, and five years later became Dean of the College. Before coming to Rollins, Seymour served as president of Wabash College in Indiana for nine years. While at Rollins, Seymour led the college’s centennial celebration, rededicated the Walk of Fame, raised funds for the construction of the Olin Library and the Cornell Social Science Building, reinstated Fox Day, and actively contributed to various community activities. He served as chairman, vice-chairman, and committee member of numerous academic and civic organizations. Throughout his life, Seymour has been widely known not only as dean and college president, but also an inspiring teacher, a caring counselor, a supportive friend, a charming magician and a leading citizen of the community. Upon his retirement in 1990, Seymour received an honorary degree from Rollins College. He has also been recognized with honorary doctorates from Wilkes College (PA), Butler University, and Indiana State University. In 1994, he received the Citizen\u27s Award from the Sullivan Committee. Three years later, in 1997, Seymour and his wife, Polly, became Winter Park’s Citizens of the Year, in recognition of their continued service to the community

    Oral History Interview with President Emeritus Thaddeus Seymour, February 20, 2009.

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    Thaddeus Seymour came to Rollins in 1978 as the twelfth president of the College. During his twelve-year tenure, he not only transformed the school through fund-raising efforts, but also enhanced the academic excellence of its liberal arts education and strengthened the relationship with the local community. Seymour was born on June 29, 1928, in New York City. His father was Whitney North Seymour, a well-known attorney and president of the American Bar Association. Seymour attended Princeton and the University of California at Berkley as an undergraduate. From there, he went to the University of North Carolina, studied eighteenth-century English literature, and received his master’s degree and Ph.D. Seymour began his academic career as an English professor at Dartmouth, and five years later became Dean of the College. Before coming to Rollins, Seymour served as president of Wabash College in Indiana for nine years. While at Rollins, Seymour led the college’s centennial celebration, rededicated the Walk of Fame, raised funds for the construction of the Olin Library and the Cornell Social Science Building, reinstated Fox Day, and actively contributed to various community activities. He served as chairman, vice-chairman, and committee member of numerous academic and civic organizations. Throughout his life, Seymour has been widely known not only as dean and college president, but also an inspiring teacher, a caring counselor, a supportive friend, a charming magician and a leading citizen of the community. Upon his retirement in 1990, Seymour received an honorary degree from Rollins College. He has also been recognized with honorary doctorates from Wilkes College (PA), Butler University, and Indiana State University. In 1994, he received the Citizen\u27s Award from the Sullivan Committee. Three years later, in 1997, Seymour and his wife, Polly, became Winter Park’s Citizens of the Year, in recognition of their continued service to the community

    A Salmonella Small Non-Coding RNA Facilitates Bacterial Invasion and Intracellular Replication by Modulating the Expression of Virulence Factors

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    Small non-coding RNAs (sRNAs) that act as regulators of gene expression have been identified in all kingdoms of life, including microRNA (miRNA) and small interfering RNA (siRNA) in eukaryotic cells. Numerous sRNAs identified in Salmonella are encoded by genes located at Salmonella pathogenicity islands (SPIs) that are commonly found in pathogenic strains. Whether these sRNAs are important for Salmonella pathogenesis and virulence in animals has not been reported. In this study, we provide the first direct evidence that a pathogenicity island-encoded sRNA, IsrM, is important for Salmonella invasion of epithelial cells, intracellular replication inside macrophages, and virulence and colonization in mice. IsrM RNA is expressed in vitro under conditions resembling those during infection in the gastrointestinal tract. Furthermore, IsrM is found to be differentially expressed in vivo, with higher expression in the ileum than in the spleen. IsrM targets the mRNAs coding for SopA, a SPI-1 effector, and HilE, a global regulator of the expression of SPI-1 proteins, which are major virulence factors essential for bacterial invasion. Mutations in IsrM result in disregulation of expression of HilE and SopA, as well as other SPI-1 genes whose expression is regulated by HilE. Salmonella with deletion of isrM is defective in bacteria invasion of epithelial cells and intracellular replication/survival in macrophages. Moreover, Salmonella with mutations in isrM is attenuated in killing animals and defective in growth in the ileum and spleen in mice. Our study has shown that IsrM sRNA functions as a pathogenicity island-encoded sRNA directly involved in Salmonella pathogenesis in animals. Our results also suggest that sRNAs may represent a distinct class of virulence factors that are important for bacterial infection in vivo

    Sedimentary Environment Influences the Effect of an Infaunal Suspension Feeding Bivalve on Estuarine Ecosystem Function

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    The suspension feeding bivalve Austrovenus stutchburyi is a key species on intertidal sandflats in New Zealand, affecting the appearance and functioning of these systems, but is susceptible to several environmental stressors including sedimentation. Previous studies into the effect of this species on ecosystem function have been restricted in space and time, limiting our ability to infer the effect of habitat change on functioning. We examined the effect of Austrovenus on benthic primary production and nutrient dynamics at two sites, one sandy, the other composed of muddy-sand to determine whether sedimentary environment alters this key species' role. At each site we established large (16 m2) plots of two types, Austrovenus addition and removal. In winter and summer we deployed light and dark benthic chambers to quantify oxygen and nutrient fluxes and measured sediment denitrification enzyme activity to assess denitrification potential. Rates of gross primary production (GPP) and ammonium uptake were significantly increased when Austrovenus was added, relative to removed, at the sandy site (GPP, 1.5 times greater in winter and summer; ammonium uptake, 8 times greater in summer; 3-factor analysis of variance (ANOVA), p<0.05). Denitrification potential was also elevated in Austrovenus addition plots at the sandy site in summer (by 1.6 times, p<0.1). In contrast, there was no effect of Austrovenus treatment on any of these variables at the muddy-sand site, and overall rates tended to be lower at the muddy-sand site, relative to the sandy site (e.g. GPP was 2.1 to 3.4 times lower in winter and summer, respectively, p<0.001). Our results suggest that the positive effects of Austrovenus on system productivity and denitrification potential is limited at a muddy-sand site compared to a sandy site, and reveal the importance of considering sedimentary environment when examining the effect of key species on ecosystem function

    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

    The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

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    Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

    New genetic loci link adipose and insulin biology to body fat distribution.

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    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
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