GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Folder 27, Correspondence, Sewell, 1931

Captain Robert Goldthwaite Carter (October 29, 1845 - January 4, 1936) served as an officer in the U.S Cavalry, both during the Civil War and the Indian Wars. He received the Medal of Honor for single-handedly holding off a Comanche raiding party in Blanco Canyon near the Brazos River (Texas) on October 10, 1871. The citation reads: "Held the left of the line with a few men during the charge of a large body of Indians, after the right of the line had retreated, and by delivering a rapid fire succeeded in checking the enemy until other troops came to the rescue." Carter authored several books, the most notable of which pertaining to this collection being On the Border with Mackenzie (1935). It documented his service under Colonel Ranald Mackenzie in northern Mexico in the late 1870s, and about his service more generally during the Indian Wars.The Robert G. Carter Papers consists of correspondence between Captain Carter and researchers, manuscript publishers, family members, and others. It bulks with correspondence about On the Border with Mackenzie (1935), but also documents discussions about his other manuscripts, concerning their contents as well as their sale and distribution. A small amount of correspondence with his family is present, as are correspondence relating to his finances. Lastly, two folders of material consist exclusively of letters exchanged with Clifford B. Jones of the Swenson Cattle Company (and the Spur Ranch) and Freeport Sulphur Company

Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies

Mature T cell cancers are typically aggressive, treatment resistant and associated with poor prognosis. Clinical application of immunotherapeutic approaches has been limited by a lack of target antigens that discriminate malignant from healthy (normal) T cells. Unlike B cell depletion, pan–T cell aplasia is prohibitively toxic. We report a new targeting strategy based on the mutually exclusive expression of T cell receptor β-chain constant domains 1 and 2 (TRBC1 and TRBC2). We identify an antibody with unique TRBC1 specificity and use it to demonstrate that normal and virus-specific T cell populations contain both TRBC1+ and TRBC2+ compartments, whereas malignancies are restricted to only one. As proof of concept for anti-TRBC immunotherapy, we developed anti-TRBC1 chimeric antigen receptor (CAR) T cells, which recognized and killed normal and malignant TRBC1+, but not TRBC2+, T cells in vitro and in a disseminated mouse model of leukemia. Unlike nonselective approaches targeting the entire T cell population, TRBC-targeted immunotherapy could eradicate a T cell malignancy while preserving sufficient normal T cells to maintain cellular immunity

Historical Ecology in Kiribati: Linking Past with Present.

v. ill. 23 cm.QuarterlyCompared with ‘‘high’’ islands, atolls and table reefs have received little attention from archaeologists focusing on historical ecology in Oceania. Limited archaeological investigations in the three archipelagoes composing the Republic of Kiribati (Gilbert, Phoenix, and Line Groups) reflect primarily culture historical reconstructions. Given the unique environmental challenges posed by coral islands, their potential for prehistoric ecological research should be recognized. By contrast, the last 50 years have witnessed a host of environmental studies, from agricultural improvements to sea-level rise and contemporary human impact on terrestrial and marine resources. In an attempt to better understand the influence of natural and human-induced processes in the more distant past, this paper explores several themes of relevance to coral islands in general. These include (1) natural and anthropogenic change on geomorphology and ecosystems, (2) anthropogenic impacts on faunal resources, (3) environmental evidence for human colonization, (4) interisland exchange networks and population mobility, and (5) social evolution