Finding the cost of freedom : academic freedom discourse as it pertains to the part-time instructor in higher education

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.Title from title screen of research.pdf file (viewed on June 9, 2009)Vita.Thesis (Ph. D.) University of Missouri-Columbia 2008.Academic freedom has been an important facet of college teaching. However, the meaning of academic freedom is often nebulous and varied for many members of the college faculty. An estimated 48 percent of teaching faculty in higher education are hired on a part-time basis. With so many college courses being taught by faculty who do not have tenure or full time appointments I raise the question: what meanings are attached to the concept of academic freedom by the part-time instructor? To answer this question the study incorporated a research strategy of discourse analysis and autoethnography. The study revealed the meanings attached to the concept of academic freedom by the part-time instructor are: having continuous or permanent employment so he or she can express himself or herself freely in the classroom without fear of not being re-hired; being able to negotiate the basic conditions of employment, providing a freedom of choice; being free to develop course materials and to have intellectual property rights in relation to those materials; receiving an honest evaluation with access to a grievance process and thereby providing for the free flow of information; and, for women part-time instructors, no repercussion when taking maternity leave. These are not the traditional meanings of academic freedom associated with higher education. What the study revealed is a new definition of academic freedom that encompasses structural components.Includes bibliographical reference

Developmental regulation of Hand1 via nucleolar sequestration.

The bHLH transcription factor Hand1 is essential for placentation and cardiac morphogenesis in the developing embryo. However, how the activity of Hand1 is regulated in either lineage remains largely unknown. Here we demonstrate that Hand1 is anchored in the nucleolus and negatively-regulated by the murine orthologue of the human I-mfa domain-containing protein (HIC). Nucleolar sequestration controls Hand1 activity during the differentiation of rat choriocarcinoma-1 (Rcho-1) trophoblast cells. Hand1 is sequestered in the nucleoli of Rcho-1 stem cells but is released into the nucleoplasm at the onset of their differentiation into trophoblast giant cells. Site-specific phosphorylation of Hand1 was previously shown to modulate the affinity of Hand1 for its nucleoplasm E-factor binding partners. We demonstrate that Hand1 phosphorylation is required for its nucleolar release, as a pre-requisite for dimerisation and biological function. Moreover, the polo-like kinase Plk4 (Sak) is responsible for this phosphorylation event. Plk4 localises to the nucleolus of Rcho-1 stem cells at phase G2 and interacts with Hand1 in vitro and in vivo to promote mitotic cell cycle exit and entry into the endocycle. We also demonstrate that the B568 subunit of the PP2A phosphatase, shown previously to target Hand1 for dephosphorylation, is exported from the nucleus during Rcho-1 differentiation. In this thesis we present findings that describe a novel mode of Hand1 regulation that is a crucial step in trophoblast stem cell differentiation and placentation and support previous studies that implicate the nucleolus as a molecular 'sink'. We suggest that nucleolar sequestration is an important mode of protein regulation and this may impact on a broad range of transcription factors

Prevention and extinguishment of fires involving hypergolic propellants Final report

Halon 1301 system effectiveness in prevention and extinguishment of hypergolic propellant fire

In search of nonribosomal nucleolar protein function and regulation

The life of the nucleolus has proven to be more colorful and multifaceted than had been envisioned a decade ago. A large number of proteins found in this subnuclear compartment have no identifiable tie either to the ribosome biosynthetic pathway or to the other newly established activities occurring within the nucleolus. The questions of how and why these proteins end up in this subnuclear compartment remain unanswered and are the focus of intense current interest. This review discusses our thoughts on the discovery of nonribosomal proteins in the nucleolus

C. elegans Nucleostemin Is Required for Larval Growth and Germline Stem Cell Division

The nucleolus has shown to be integral for many processes related to cell growth and proliferation. Stem cells in particular are likely to depend upon nucleolus-based processes to remain in a proliferative state. A highly conserved nucleolar factor named nucleostemin is proposed to be a critical link between nucleolar function and stem-cell–specific processes. Currently, it is unclear whether nucleostemin modulates proliferation by affecting ribosome biogenesis or by another nucleolus-based activity that is specific to stem cells and/or highly proliferating cells. Here, we investigate nucleostemin (nst-1) in the nematode C. elegans, which enables us to examine nst-1 function during both proliferation and differentiation in vivo. Like mammalian nucleostemin, the NST-1 protein is localized to the nucleolus and the nucleoplasm; however, its expression is found in both differentiated and proliferating cells. Global loss of C. elegans nucleostemin (nst-1) leads to a larval arrest phenotype due to a growth defect in the soma, while loss of nst-1 specifically in the germ line causes germline stem cells to undergo a cell cycle arrest. nst-1 mutants exhibit reduced levels of rRNAs, suggesting defects in ribosome biogenesis. However, NST-1 is generally not present in regions of the nucleolus where rRNA transcription and processing occurs, so this reduction is likely secondary to a different defect in ribosome biogenesis. Transgenic studies indicate that NST-1 requires its N-terminal domain for stable expression and both its G1 GTPase and intermediate domains for proper germ line function. Our data support a role for C. elegans nucleostemin in cell growth and proliferation by promoting ribosome biogenesis

Evolutionarily Conserved Transcriptional Co-Expression Guiding Embryonic Stem Cell Differentiation

Understanding the molecular mechanisms controlling pluripotency in embryonic stem cells (ESCs) is of central importance towards realizing their potentials in medicine and science. Cross-species examination of transcriptional co-expression allows elucidation of fundamental and species-specific mechanisms regulating ESC self-renewal or differentiation.We examined transcriptional co-expression of ESCs from pathways to global networks under the framework of human-mouse comparisons. Using generalized singular value decomposition and comparative partition around medoids algorithms, evolutionarily conserved and divergent transcriptional co-expression regulating pluripotency were identified from ESC-critical pathways including ACTIVIN/NODAL, ATK/PTEN, BMP, CELL CYCLE, JAK/STAT, PI3K, TGFbeta and WNT. A set of transcription factors, including FOX, GATA, MYB, NANOG, OCT, PAX, SOX and STAT, and the FGF response element were identified that represent key regulators underlying the transcriptional co-expression. By transcriptional intervention conducted in silico, dynamic behavior of pathways was examined, which demonstrate how much and in which specific ways each gene or gene combination effects the behavior transition of a pathway in response to ESC differentiation or pluripotency induction. The global co-expression networks of ESCs were dominated by highly connected hub genes such as IGF2, JARID2, LCK, MYCN, NASP, OCT4, ORC1L, PHC1 and RUVBL1, which are possibly critical in determining the fate of ESCs.Through these studies, evolutionary conservation at genomic, transcriptomic, and network levels is shown to be an effective predictor of molecular factors and mechanisms controlling ESC development. Various hypotheses regarding mechanisms controlling ESC development were generated, which could be further validated by in vitro experiments. Our findings shed light on the systems-level understanding of how ESC differentiation or pluripotency arises from the connectivity or networks of genes, and provide a "road-map" for further experimental investigation

Nucleolus: the fascinating nuclear body

Nucleoli are the prominent contrasted structures of the cell nucleus. In the nucleolus, ribosomal RNAs are synthesized, processed and assembled with ribosomal proteins. RNA polymerase I synthesizes the ribosomal RNAs and this activity is cell cycle regulated. The nucleolus reveals the functional organization of the nucleus in which the compartmentation of the different steps of ribosome biogenesis is observed whereas the nucleolar machineries are in permanent exchange with the nucleoplasm and other nuclear bodies. After mitosis, nucleolar assembly is a time and space regulated process controlled by the cell cycle. In addition, by generating a large volume in the nucleus with apparently no RNA polymerase II activity, the nucleolus creates a domain of retention/sequestration of molecules normally active outside the nucleolus. Viruses interact with the nucleolus and recruit nucleolar proteins to facilitate virus replication. The nucleolus is also a sensor of stress due to the redistribution of the ribosomal proteins in the nucleoplasm by nucleolus disruption. The nucleolus plays several crucial functions in the nucleus: in addition to its function as ribosome factory of the cells it is a multifunctional nuclear domain, and nucleolar activity is linked with several pathologies. Perspectives on the evolution of this research area are proposed

Cell cycle switch to endocycle: the nucleolus lends a hand.

The bHLH transcription factor Hand1 is essential for placentation and cardiac morphogenesis but how its developmental activity is regulated is largely unknown. We recently showed that Hand1 is sequestered in the nucleoli of rodent trophoblast stem (TS) cells by the I-mfa domain-containing protein HICp40 and that this is associated with their proliferation and continuing self-renewal. However when these cells commit to differentiate into trophoblast giant (TG) cells, Hand1 is phosphorylated by the polo-like kinase Plk4 (Sak) and released into the nucleus to activate downstream target genes. This event underlies the release of Hand1 from the nucleolus and represents the 'molecular switch' that promotes mitotic cell cycle exit and the onset of endoreduplication. In this brief discussion we examine the wider implications of these findings and address some of the unanswered questions that remain

Developmental regulation of Hand1 via nucleolar sequestration

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The significance of pollution and infectious agents in the aetiology of proliferative disorders of marine and freshwater fishes

Liver neoplasia in wild fishes has been proposed previously as a biomarker of carcinogen exposure and effect but the significance of pollution and infectious agents in the aetiology of this condition has not been fully assessed. The aim of the present study was to address this problem. Two field studies were conducted. Firstly, dab livers (n=439) were examined from 6 stations along a pollution gradient in the southern North Sea. Two hepatocellular adenomas and one rare 'hepatocellular carcinoma (HC) were detected in dab livers from the most polluted Stations 3 & 5. One distinctive feature of the HC was the presence of numerous enlarged hepatocytes with a fibrillar-like cytoplasm. Prevalences of preneoplastic foci of cellular alteration (FCA) were significantly higher (p < 0.05) in the livers of dab from Station 3, compared to control Station 7, where prevalences were zero. Other histopathological features such as hepatocellular vacuolation, probably resulting from excess lipid accumulation, and melanomacrophage centre (MMe) proliferation, were also significantly more prevalent (p<0.05) at Station 3 than at Station 7. The second field study examined 400 fishes, primarily freshwater channel catfish, from the Grand River, a polluted tributary of Lake Michigan. One channel catfish bore a fibrosarcoma, but no neoplastic foci were detected in livers. Prevalences of hepatic FCA were also low (0.75%) and this probably resulted from the refractive properties of the sampled species. The present study also examined the effects of known carcinogens in the development of liver neoplasia in European sea bass under laboratory conditions. This represented the first long-term investigation of sea bass as a marine model for experimental hepatocarcinogenesis. Methods for culturing sea bass fry in a recirculating artificial seawater system were established. Fry were then exposed to a single dose of either aflatoxin B[sub]1 (AFB[sub]1) or N-Methyl-N'-Nitro-Nitrosoguanidine (MNNG) by immersion in static solutions for 30 minutes. They were then grown-on for up to 8 months in a system free from infectious agents. The effects of exposure on the specific cytochrome P-450 content of sea bass gill and liver micro somes was assessed spectrally, and the toxicity of the compounds was confirmed in vitro by the neutral red assay. In exposed fry a chronic toxic effect, characterised by marked enlargement of both cellular and nuclear diameters (megalocytosis), was induced in the hepatocytes following exposure to 0.5, 1.0, and 2.0 ppm AFB[sub]1. A dose response was observed up to 1. O ppm AFB[sub]1 Liver lesions worsened up until 6 months post-exposure, when they were visible grossly as pale multicentric nodules. They persisted to the final sampling point of 8 months, when there was also evidence of MMG proliferation and liver regeneration. Although parasites were associated with wild caught fishes, no infectious agents were demonstrated within any preneoplastic, neoplastic, or megalocytic liver lesions examined in the present study by light and electron microscopy. It is concluded from field and laboratory results that liver neoplasia is a chronic, 1?robably non-infectious disease which justifiably should be considered a reliable biomarker of carcinogen exposure and effect in wild fish