Seasonal Movements, Migratory Behavior, and Site Fidelity of West Indian Manatees along the Atlantic Coast of the United States as Determined by Radio-telemetry

The study area encompassed the eastern coasts of Florida, Georgia, and South Carolina, including inland waterways such as the St. Johns River (Fig. 1). Manatees inhabited the relatively narrow band of water that lies between the barrier beaches and the mainland, occasionally venturing into the ocean close to shore. Between Miami and Fernandina Beach, Florida, 19 inlets provided manatees with corridors between the intracoastal waters and the Atlantic Ocean; the distance between adjacent inlets averaged 32 km(SD = 24 km) and varied from 3 to 88 km. Habitats used by manatees along this 900-km stretch ofcoastline varied widely and included estuaries, lagoons, rivers and creeks, shallow bays and sounds, and ocean inlets. Salinities in most areas were brackish, but ranged from completely fresh to completely marine. The predominant communities of aquatic vegetation also varied geographically and with salinity: seagrass meadows and mangrove swamps in brackish and marine waters along the southern half of peninsular Florida; salt marshes in northeastern Florida and Georgia; benthic macroalgae in estuarine and marine habitats; and a variety of submerged, floating, and emergent vegetation in freshwater rivers, canals, and streams throughout the region. Radio-telemetry has been used successfully to track manatees in other regions ofFlorida (Bengtson 1981, Powell and Rathbun 1984, Lefebvre and Frohlich 1986, Rathbun et al. 1990) and Georgia (Zoodsma 1991), but these early studies relied primarily on conventional VHF (very high frequency) transmitters and were limited in their spatial and temporal scope (see O'Shea and Kochman 1990 for overview). Typically, manatees were tagged at a thermal refuge in the winter and then tracked until the tag detached, usually sometime between the spring and fall of the same year. Our study differs from previous research on manatee movements in several important respects. First, we relied heavily on data from satellite-monitored transmitters using the Argos system, which yielded a substantially greater number of locations and more systematic collection of data compared to previous VHF tracking studies (Deutsch et al. 1998). Second, our tagging and tracking efforts encompassed the entire range of manatees along the Atlantic coast, from the Florida Keys to South Carolina, so inferences were not limited to a small geographic area. Third, we often used freshwater to lure manatees to capture sites, which allowed tagging in all months of the year; this provided more information about summer movement patterns than had previous studies which emphasized capture and tracking at winter aggregations. Finally, the study spanned a decade, and success in retagging animals and in replacing transmitters allowed long-term tracking ofmany individuals. This provided the opportunity to investigate variation in seasonal movements, migratory behavior, and site fidelity across years for individual manatees. (254 page document.

Screening and association testing of common coding variation in steroid hormone receptor co-activator and co-repressor genes in relation to breast cancer risk: the Multiethnic Cohort

<p>Abstract</p> <p>Background</p> <p>Only a limited number of studies have performed comprehensive investigations of coding variation in relation to breast cancer risk. Given the established role of estrogens in breast cancer, we hypothesized that coding variation in steroid receptor coactivator and corepressor genes may alter inter-individual response to estrogen and serve as markers of breast cancer risk.</p> <p>Methods</p> <p>We sequenced the coding exons of 17 genes (<it>EP300, CCND1, NME1, NCOA1, NCOA2, NCOA3, SMARCA4, SMARCA2, CARM1, FOXA1, MPG, NCOR1, NCOR2, CALCOCO1, PRMT1, PPARBP </it>and <it>CREBBP</it>) suggested to influence transcriptional activation by steroid hormone receptors in a multiethnic panel of women with advanced breast cancer (n = 95): African Americans, Latinos, Japanese, Native Hawaiians and European Americans. Association testing of validated coding variants was conducted in a breast cancer case-control study (1,612 invasive cases and 1,961 controls) nested in the Multiethnic Cohort. We used logistic regression to estimate odds ratios for allelic effects in ethnic-pooled analyses as well as in subgroups defined by disease stage and steroid hormone receptor status. We also investigated effect modification by established breast cancer risk factors that are associated with steroid hormone exposure.</p> <p>Results</p> <p>We identified 45 coding variants with frequencies ≥ 1% in any one ethnic group (43 non-synonymous variants). We observed nominally significant positive associations with two coding variants in ethnic-pooled analyses (<it>NCOR2</it>: His52Arg, OR = 1.79; 95% CI, 1.05–3.05; <it>CALCOCO1</it>: Arg12His, OR = 2.29; 95% CI, 1.00–5.26). A small number of variants were associated with risk in disease subgroup analyses and we observed no strong evidence of effect modification by breast cancer risk factors. Based on the large number of statistical tests conducted in this study, the nominally significant associations that we observed may be due to chance, and will need to be confirmed in other studies.</p> <p>Conclusion</p> <p>Our findings suggest that common coding variation in these candidate genes do not make a substantial contribution to breast cancer risk in the general population. Cataloging and testing of coding variants in coactivator and corepressor genes should continue and may serve as a valuable resource for investigations of other hormone-related phenotypes, such as inter-individual response to hormonal therapies used for cancer treatment and prevention.</p

Spatiotemporally separated antigen uptake by alveolar dendritic cells and airway presentation to T cells in the lung

Asthma pathogenesis is focused around conducting airways. The reasons for this focus have been unclear because it has not been possible to track the sites and timing of antigen uptake or subsequent antigen presentation to effector T cells. In this study, we use two-photon microscopy of the lung parenchyma and note accumulation of CD11b(+) dendritic cells (DCs) around the airway after allergen challenge but very limited access of these airway-adjacent DCs to the contents of the airspace. In contrast, we observed prevalent transepithelial uptake of particulate antigens by alveolar DCs. These distinct sites are temporally linked, as early antigen uptake in alveoli gives rise to DC and antigen retention in the airway-adjacent region. Antigen-specific T cells also accumulate in the airway-adjacent region after allergen challenge and are activated by the accumulated DCs. Thus, we propose that later airway hyperreactivity results from selective retention of allergen-presenting DCs and antigen-specific T cells in airway-adjacent interaction zones, not from variation in the abilities of individual DCs to survey the lung

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

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

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

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

Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer

Peer reviewe

Undutiful Spirit: Meeting Point

Undutiful Spirit is a practice-led forum founded by artists Rosie Morris and Harriet Sutcliffe and curator Gayle Meikle. The forum considers site-specific working methods generated through woman-identifying experiences. The presentation on Level 1 is the culmination of six-month residency at BALTIC during which they have been invited to research and develop their practice through close engagement with BALTIC Archive. The Archive chronicles BALTIC’s history, exhibitions and events through physical items and digital documentation.Responding to this material, Undutiful Spirit have designed a ‘meeting point’ to explore the history, present and future of the Archive. Throughout their residency, they have been burrowing, sifting and recycling the archive and its contents. For BALTIC’s birthday, they have created an intergenerational space for people to encounter, uncover, play with and discuss aspects from the history of the organisation.The material on display includes original correspondence, documentation, reproductions and newly recorded interviews. All the elements make visible different stages of artistic production from a woman’s perspective. Each day the display will change and you are invited to worm your way through and interact with the material. Memory Workers will be on hand to capture your interactions to deposit into the archive for the future.This presentation has been formed through contributions from Charlie Ambery, Sarah Bouttell, Eliza Brown, Briony Carlin, Emma Dean, Theresa Easton, Seren Hamer, Jesse Howarth, Laleh Khorramian, Gayle Meikle, Adrianne Murray-Neil, Lisa Murphy, Jessica Petley, Harriet Sutcliffe, Meg Tanner and conversations around the building.The project is generously supported by Newcastle Institute for Creative Practice, Newcastle Universit