66 research outputs found

    Chemoselective Chemistry: Engineering Materials and Cell Surfaces to Control Biological Interactions

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    The development of strategies to control the interface between biomolecules and a solid support is critical to a number of research areas, including drug discovery, tissue engineering, and gene microarray technology. In particular, tremendous effort has been extended toward interfacing material science with cell biology to conduct mechanistic cell adhesion, polarization, and migration studies. These investigations require the combined use of a model substrate that mimics the complex nature of the extracellular matrix and a synthetic chemical immobilization methodology to pattern biospecific, biomolecular cues for cellular recognition. Currently, self-assembled monolayers (SAMs) of alkanethiolates on gold represent the most well-studied and developed surface systems in biointerfacial science, enabling the design and implementation of complex, dynamic substrates for controlling biological interactions at the molecular level. This research is focused on employing chemoselective chemistry to engineer materials and cell surfaces for the control of biological interactions. Thus, smart biosurfaces and materials were manipulated to investigate peptide-cell, protein-carbohydrate, and lipid-cell interactions. A library of biomolecules was designed and synthesized to include chemoselective and bio-orthogonal functional groups, ketone and oxyamine. With this coupling methodology, biomaterials and cell surfaces were successfully engineered to examine a variety of cell behaviors, such as cell-biospecific ligand interactions, adhesion, polarization, migration, and cellular response to other cells. Chapter 1 provides an introduction to SAMs and a general discussion regarding the design and utility of dynamic SAM surfaces and for biological analyses. The use of SAMs on gold and indium tin oxide for cell adhesion studies is presented in Chapters 2 and 3, respectively. Chapter 4 demonstrates the development and application of a renewable carbohydrate microarray based on hydroquinone-terminated SAMs on gold. Hydroquinone was then incorporated with cell adhesive peptide, RGD, to survey selected carbohydrates and peptides for their combined effect on fibroblast adhesion, morphology, and migration; this data is discussed in Chapter 5. A cell-surface engineering strategy based on liposome delivery and membrane fusion to direct cell-cell contacts and generate 3D tissue-like structures is reported in Chapters 6 and 7. Finally, Chapter 8 describes my general conclusions and future research directions

    William Brooks

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    William Brooks was the sixth Postmaster of St. George from 1934 to 1951. He married Juanita Pulsipher, the author Juanita Brooks

    Chemokine CCL19 and Its Receptors CCR7 and CCRL1 in Chronic Rhinosinusitis

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    Chengetai R Mahomva,1,&ast; Kristine A Smith,1,&ast; Prince AB Minkah,2 Benjamin L Witt,3 Gretchen M Oakley,1 Richard R Orlandi,1 Jeremiah A Alt,1,2,4 Abigail Pulsipher1,2,4 1Department of Otolaryngology-Head and Neck Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA; 2Department of Molecular Pharmaceutics, University of Utah College of Pharmacy, Salt Lake City, UT, USA; 3Cytopathology Section, University of Utah School of Medicine, Salt Lake City, UT, USA; 4Utah Center for Nanomedicine, University of Utah College of Pharmacy, Salt Lake City, UT, USA&ast;These authors contributed equally to this workCorrespondence: Abigail Pulsipher, University of Utah School of Medicine, Department of Otolaryngology-Head and Neck Surgery, 36 South Wasatch Drive, Salt Lake City, UT, 84112, USA, Tel +1 4342493268, Fax +1 8015855744, Email [email protected]: CCL19 has been shown to predict disease severity in COVID-19 and treatment response in rheumatoid arthritis. CCL19 can exert both pro- and anti-inflammatory effects and is elevated in chronic rhinosinusitis (CRS). However, its role in CRS remains unknown. This study sought to determine the transcriptional changes in CCL19, its receptors, and associated cytokines and their association with disease severity in CRS.Methods: A clinical database of control subjects and patients with CRS was examined. Lund-Kennedy, Lund-Mackay, Sinonasal Outcomes Test 22 (SNOT-22), and rhinosinusitis disability index (RSDI) scores were collected at enrollment. mRNA was extracted from sinonasal tissues and subjected to multiplex gene expression analysis. Gene transcript differences between patients with CRS and controls were compared and correlated with disease severity metrics. Immunohistochemical analyses of CCL19, CCR7, and CCRL1 were conducted to compare differences in protein expression between cohorts. A subgroup analysis was performed to compare transcriptional and protein expression difference between patients with (CRSwNP) and without (CRSsNP) nasal polyps and controls.Results: Thirty-eight subjects (control group, n=7; CRS group, n=31) were included in this study. CCRL1 (p=0.0093) and CCR7 (p=0.017) levels were significantly elevated in CRS compared to those in controls. CCL19 (p=0.038) and CCR7 (p=0.0097) levels were elevated in CRSwNP and CCRL1 was elevated in CRSsNP (p=0.0004). CCR7 expression was significantly elevated in sinonasal epithelial cells in CRSwNP (p=0.04). CCL19 expression was positively correlated with TNFA expression (p< 0.0002). CCL19 and CCR7 expression was positively correlated with SNOT-22 and RSDI scores (p< 0.05).Conclusion: CCL19 and CCR7 may modulate TNF-α-driven pro-inflammatory signaling and contribute to increased disease severity in CRS. Mechanistic studies are required to further elucidate the role of CCRL1 in CRS.Keywords: chronic rhinosinusitis with nasal polyps, chemokines, cytokines, gene expression, protein expressio

    The Digital Archive of John Wompas

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    Data Description: The Digital Archive of John Wompas, by Jenny Hale Pulsipher In the course of writing my book on John Wompas, Swindler Sachem: The American Indian Who Sold His Birthright, Dropped out of Harvard, and Conned the King of England (Yale University Press, 2018), I gathered a great deal of information on such subjects as Indian slavery, Native land sales, the Atlantic maritime trade, and Native education in Massachusetts. This information contributed to the book by providing historical context for Wompas’s life, but most nitty-gritty details were tangential to the book’s purpose so do not appear in it. Because those details could help other scholars working on more narrowly focused books or articles, I have placed them here where they can be accessible to anyone who has the URL.** I also built this archive as a teaching resource. For many students starting out in the field of history, historical research is a mystery. Students read books that make arguments, but they don’t always understand how the author moved from the evidence to the claim. For a book like Swindler Sachem, which pulls bits of evidence from a multitude of archival, printed, and nontraditional sources, arriving at a conclusion may appear even more mysterious. By placing some photos and many transcriptions of my sources on a digital archive, paired with a timeline, I provide students with a chance to examine the evidence and come to their own conclusions, which they can compare to mine. They can also examine the tables of information I have gathered, organized below under Data on Indian Slavery and Servitude, Data on Sales of Indian Land in the New England Colonies, Data on Maritime New England, Data on Indian Literacy and Education, and Data on Native Female Property Ownership. I. Timeline John Wompas and Ann Prask Wompas Timeline, with Notes, Transcriptions, Scans, and Links to Primary Documents II. Data on Indian Slavery and Servitude A. Indian Captives in the Pequot War, 1637 B. Fates of Individual Captives in the Pequot War C. Indian Captives, Servants, and Slaves in the Era of King Philip\u27s War, 1673-1755 D. Instances of Slavery or Servitude in New England, Excluding Pequot and King Philip\u27s Wars, 1630-1675 E. Laws, Orders, and Advice Concerning Captives, Servants, and Slaves in the Era of King Philip\u27s War, 1672-1727 III. Data on Sales of Indian Land in the New England Colonies In order to find all of John Wompas’s land transactions, I searched land deed collections throughout New England. I also wanted to test my belief, based on scattered and anecdotal evidence, that the price English people paid Indians for unimproved land was significantly lower than the price unimproved land sold for between English buyers. To do this, I began filling in tables of land sale prices, particularly in Nipmuc Country in the last quarter of the seventeenth and the start of the eighteenth century. I gathered enough data to confirm my initial judgment. While I stopped far short of compiling all Indian land sales, I believe such a compilation could yield very interesting information. For instance, it could reveal whether particular Native groups or individuals were able to command better prices for their land than other Native groups or individuals. It could reveal which English individuals or communities paid higher or lower prices for Indian land and what the consequences of those patterns were. It could also allow scholars to examine patterns of Native land use across time, by tabulating instances where Indians reserved traditional land uses, where women signed deeds as owners of land, where sachems signed deeds signifying their traditional right to distribute land, where the consent of elders and/or community members was included in the deed, etc. With a complete compilation of land sale data, scholars could move beyond anecdotal evidence to draw well supported conclusions about patterns of land use and to identify and explain divergences from those patterns. A. Land Transactions of John Wompas and Ann Prask Wompas, 1662-1679 B. Land Sales in Nipmuc Country, 1643-1724 C. Indian Land Sales in Fairfield, Connecticut Colony, Late 17th Century D. Indian Land Sales in Plymouth Colony, 1641-1657 E. Indian Land Sales in Hampden County, Massachusetts Bay Colony, 1636-1763 F. English Transfers of Unimproved Land Near Worcester, Massachusetts Bay Colony, 1732-1733 IV. Data on Maritime New England A. Mariners\u27 Wages in 17th-century Massachusetts B. Native Sailors in the English Fishing and Merchant Fleet, New England, 1636-1700 C. Ships Docking in Boston, Massachusetts, 17th Century V. Data on Indian Literacy and Education A. Marks and Signatures of Native People of the Northeast, 17th Century B. Indian Scholars in Massachusetts Bay Colony, 1655-1672 C. Probable Indian Scholars, Late 17th-Century Massachusetts VI. Data on Native Female Property Ownership A. Inventory of the Estate of Ann Wompas B. Ann Wompas Inventory Compared to Those of Contemporary White Women in Cambridge, Massachusetts, Late 17th Century VII. Bibliography for Jenny Hale Pulsipher, Swindler Sachem: The American Indian Who Sold His Birthright, Dropped Out of Harvard, and Conned the King of England (Yale University Press, 2018). **Please scroll to the bottom of the page to download the data files
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