Ms. Coll. 251: Literary Models, Religion, and Romantic Science in John Syng Dorsey’s Poems, 1805-1818

John Syng Dorsey (1783-1818) was a Philadelphia surgeon and the author of The Elements of Surgery (1813), the first American textbook of surgery. He was also the author of Poems, 1805-1818 (UPenn Ms. Coll. 251), a forty-page collection that reveals his interests in spirituality, the history of science and medicine, and classical and eighteenth-century British poetry. Decades after Dorsey’s death, his son Robert Ralston Dorsey (1808-1869) revised his father’s poems, identified classical sources with Latin and Italian quotations, and completed Dorsey’s final, unfinished poem. This project analyzes Dorsey’s literary, scientific, and biblical allusions and contextualizes his Poems within early nineteenth-century literary history and Romantic science and medicine. This article is an expanded version of the annotated transcription and critical introduction published as “Religion, Writing, and Romantic Science in John Syng Dorsey’s Poems, 1805-1818” in Volume 1 (Fall/Winter 2017/18) of Journal of the Penn Manuscript Collective. Corrections to the original transcription, as well as the discovery of four pages of riddles at the back of the volume, reveal additional literary and theological allusions, information about the involvement of Dorsey’s wife’s family and his medical colleagues in Philadelphia charitable organizations, and Dorsey’s connections to elite early nineteenth-century Philadelphia society. The expanded introduction and annotations analyze this new evidence and discuss the five poems from Ms. Coll. 251 and eleven poems not included in the manuscript that Dorsey published in the Port Folio, an influential Philadelphia literary journal.https://repository.upenn.edu/manuscript_collective_transcription/1005/thumbnail.jp

Physiological and pharmacological characterization of the N1303K mutant CFTR

Background: N1303K, one of the common, severe disease-causing mutations in the CFTR gene, causes both defective biogenesis and gating abnormalities of the CFTR protein. The goals of the present study are to quantitatively assess the gating defects associated with the N1303K mutation and its pharmacological response to CFTR modulators including potentiators VX-770 and GLPG1837 and correctors VX-809, and VX-661. Methods: Gating behavior and pharmacological responses to CFTR potentiators were assessed using the patch-clamp technique in the excised, inside-out mode. We also examined the effects of GLPG1837, VX-770, VX-809 and VX-661 on N1303K-CFTR surface expression using Western blot analysis. Results: Like wild-type (WT) CFTR, N1303K-CFTR channels were activated by protein kinase A-dependent phosphorylation, but the open probability (P[o]) of phosphorylated N1303K-CFTR was extremely low ([less than or equal to]0.03 vs [about]0.45 in WT channels). In addition, N1303K mutants showed abnormal responses to ATP analogs or mutations that disrupt ATP hydrolysis and/or dimerization of CFTR's two nucleotide-binding domains (NBDs). However, the Po of N1303K-CFTR was dramatically increased by GLPG1837 ([about]17-fold) and VX-770 ([about]8-fold). In addition, VX-809 or VX-661 enhanced N1303K-CFTR maturation by 2 -3 fold, and co-treatment with GLPG1837 or VX-770 did not show any negative drug-drug interaction. Conclusion: N1303K has a more severe gating defect than previously reported Po of [about]0.1. Our results suggest a defective function of the NBDs in N1303K-CFTR. An improvement of channel function by GLPG1837 or VX-770 and an increase of Band C protein by VX-809 or VX-661 support a therapeutic strategy of combining CFTR potentiator and corrector for patients carrying the N1303K mutation.Includes bibliographical reference

Growth factor release from a chemically modified elastomeric poly(1,8‐octanediol‐co‐citrate) thin film promotes angiogenesis in vivo

The ultimate success of in vivo organ formation utilizing ex vivo expanded “starter” tissues relies heavily upon the level of vascularization provided by either endogenous or artificial induction of angiogenic or vasculogenic events. To facilitate proangiogenic outcomes and promote tissue growth, an elastomeric scaffold previously shown to be instrumental in the urinary bladder regenerative process was modified to release proangiogenic growth factors. Carboxylic acid groups on poly(1,8‐octanediol‐co‐citrate) films (POCfs) were modified with heparan sulfate creating a heparan binding POCf (HBPOCf). Release of proangiogenic growth factors vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and insulin‐like growth factor 1 (IGF‐1) from HBPOCfs demonstrated an approximate threefold increase over controls during a 30‐day time course in vitro . Atomic force microscopy demonstrated significant topological differences between films. Subcutaneous implantation of POCf alone, HBPOCf, POCf‐VEGF, and HBPOCf‐VEGF within the dorsa of nude rats yielded increased vascular growth in HBPOCf‐VEGF constructs. Vessel quantification studies revealed that POCfs alone contained 41.1 ± 4.1 vessels/mm 2 , while HBPOCf, POCf‐VEGF, and HBPOCF‐VEGF contained 41.7 ± 2.6, 76.3 ± 9.4, and 167.72 ± 15.3 vessels/mm 2 , respectively. Presence of increased vessel growth was demonstrated by CD31 and vWF immunostaining in HBPOCf‐VEGF implanted areas. Data demonstrate that elastomeric POCfs can be chemically modified and possess the ability to promote angiogenesis in vivo . © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90248/1/33306_ftp.pd

Apcdd1 is a dual BMP/Wnt inhibitor in the developing nervous system and skin.

Animal development and homeostasis depend on precise temporal and spatial intercellular signaling. Components shared between signaling pathways, generally thought to decrease specificity, paradoxically can also provide a solution to pathway coordination. Here we show that the Bone Morphogenetic Protein (BMP) and Wnt signaling pathways share Apcdd1 as a common inhibitor and that Apcdd1 is a taxon-restricted gene with novel domains and signaling functions. Previously, we showed that Apcdd1 inhibits Wnt signaling (Shimomura et al., 2010), here we find that Apcdd1 potently inhibits BMP signaling in body axis formation and neural differentiation in chicken, frog, zebrafish. Furthermore, we find that Apcdd1 has an evolutionarily novel protein domain. Our results from experiments and modeling suggest that Apcdd1 may coordinate the outputs of two signaling pathways that are central to animal development and human disease

Apcdd1 is a dual BMP/Wnt inhibitor in the developing nervous system and skin.

Animal development and homeostasis depend on precise temporal and spatial intercellular signaling. Components shared between signaling pathways, generally thought to decrease specificity, paradoxically can also provide a solution to pathway coordination. Here we show that the Bone Morphogenetic Protein (BMP) and Wnt signaling pathways share Apcdd1 as a common inhibitor and that Apcdd1 is a taxon-restricted gene with novel domains and signaling functions. Previously, we showed that Apcdd1 inhibits Wnt signaling (Shimomura et al., 2010), here we find that Apcdd1 potently inhibits BMP signaling in body axis formation and neural differentiation in chicken, frog, zebrafish. Furthermore, we find that Apcdd1 has an evolutionarily novel protein domain. Our results from experiments and modeling suggest that Apcdd1 may coordinate the outputs of two signaling pathways that are central to animal development and human disease