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Sara J White

Publications and source records attributed to Sara J White.

6 recordsLinked to original sources

Formation of the digestive system in zebrafish: III. Intestinal epithelium morphogenesis.

Recent analysis of a novel strain of transgenic zebrafish (gutGFP) has provided a detailed description of the early morphological events that occur during the development of the liver and pancreas. In this paper, we aim to complement these studies by providing an analysis of the morphological events that shape the zebrafish intestinal epithelium. One of our goals is to provide a framework for the future characterization of zebrafish mutant phenotypes in which intestinal epithelial morphogenesis has been disrupted. Our analysis encompasses the period between 26 and 126 h post-fertilization (hpf) and follows the growth, lumen formation and differentiation of a continuous layer of endoderm into a functional intestinal epithelium with three morphologically distinct segments: the intestinal bulb, mid-intestine and posterior intestine. Between 26 hpf and 76 hpf, the entire intestinal endoderm is a highly proliferative organ. To make a lumen, the zebrafish endoderm cells undergo apical membrane biogenesis, adopt a bilayer configuration and form small cavities that coalesce without cell death. Thereafter, the endoderm cells polarize and differentiate into distinct cell lineages. Enteroendocrine cells are distinguished first at 52 hpf in the caudal region of the intestine in a new stable transgenic line, Tg[nkx2.2a:mEGFP]. The differentiation of mucin-containing goblet cells is first evident at 100 hpf and is tightly restricted to a middle segment of the intestine, designated the mid-intestine, that is also demarcated by the presence of enterocytes with large supranuclear vacuoles. Meanwhile, striking expansion of the lumen in the rostral intestine forms the intestinal bulb. Here the epithelium elaborates folds and proliferating cells become progressively restricted to a basal compartment analogous to the crypts of Lieberkühn in mammals. At 126 hpf, the posterior intestine remains an unfolded monolayer of simple columnar epithelium.

Animals↗

Will there be a pharmacy leadership crises? An ASHP Foundation Scholar-in-residence report.

PURPOSE: Health-system pharmacy directors, managers, practitioners, students, and employers were surveyed to assess the situation of current and future leaders in pharmacy and generate recommendations for preventing shortages. METHODS: Online surveys were sent to pharmacy directors, pharmacy middle managers, current pharmacy practitioners pharmacy students, and employers recruiting for management positions using ASHP's membership and CareerPharm databases. Directors, managers, and practitioners were asked about their job satisfaction and future plans. The trends in demographics and attitudes toward the balance between family and work were assessed among directors, managers, practitioners, and students. Employers were asked about their perceived ease of filling managerial positions. RESULTS: While most pharmacy directors and middle managers were satisfied with their current positions, 80% of directors and 77% of middle managers anticipated leaving their jobs in the next decade. Men comprised 72% of directors, 50% of middle managers, 62% of practitioners, and 21% of pharmacy students. The majority of pharmacy students and practitioners reported being married to a working spouse and having children and expressed a desire to balance their personal life with their career. The top reasons cited by students and practitioners for not seeking leadership positions were having to give up clinical practice and competing responsibilities. More than half of employers felt it was more difficult to recruit managers now than it was three years ago. CONCLUSION: A significant gap in pharmacy leadership in the next 5-10 years is expected, as well as a shift in work force composition and attitude. Mentoring and residencies are important methods of fostering new leaders in the profession.

Humans↗

Analysis of the regulation of the A33 antigen gene reveals intestine-specific mechanisms of gene expression.

The A33 antigen is a transmembrane protein expressed almost exclusively by intestinal epithelial cells. The level of its expression is robust and uniform throughout the rostrocaudal axis of the human and mouse intestines. In the colon, strong expression is found in the basolateral membranes of both the proliferating cells in the lower regions of the crypts and the differentiating cells in the upper regions of crypts. Similarly, in the small intestine, the protein is highly expressed by all the epithelial cells in the crypts and by the differentiated cells migrating over the villi. Thus, the A33 antigen has emerged as a definitive marker for all intestinal epithelial cells, irrespective of cell lineage and differentiation status. To understand the molecular mechanisms mediating this rare tissue-specific expression pattern, we undertook a comprehensive analysis of the 5'-regulatory region of the human A33 antigen gene. This allowed us to point to positive cis-regulatory elements incorporating consensus Krüppel-like factor and caudal-related homeobox (CDX)-binding sites, located just upstream from the human A33 antigen transcription start site, as being important for the intestine-specific expression pattern of this gene. Further analysis provided evidence that the A33 antigen gene may be one of only a few target genes to be described thus far for the intestine-specific homeobox transcription factor, CDX1. Taken together, our data lead us to propose that the activity of CDX1 is pivotal in mediating the exquisite, intestine-specific expression pattern of the A33 antigen gene.

5' Flanking Region↗