Natural Resources Policy and Law: Trends and Directions

This digital resource contains only an abstract, cover image and table of contents information from the published book. Print copy of book is available in the University of Colorado’s Wise Law Library: http://lawpac.colorado.edu/record=b143382~S0 Contents: Rethinking resources : reflections on a new generation of natural resources law and policy / Lawrence J. MacDonnell, Sarah F. Bates -- Natural resources law : an historical perspective / Clyde O. Martz -- Trends in public land law : (a title the inaccuracy of which should become manifest) / George Cameron Coggins -- Mineral law in the United States : a study in legal change / Lawrence J. MacDonnell -- Oil and gas law at the end of its great era / Richard C. Maxwell -- Water resources : a wider world / David H. Getches -- Bringing an ecological perspective to natural resources law : fulfilling the promise of the public trust / Joseph L. Sax -- Environmental law, but not environmental protection / A. Dan Tarlock -- Shifting paradigms of tort and property in the transformation of natural resources law / Richard J. Lazarus -- A view toward the future : lessons from Tahoe and the Truckee / Charles F. Wilkinsonhttps://scholar.law.colorado.edu/books_reports_studies/1140/thumbnail.jp

Mechanisms of Oct4 in the entry to, maintenance of, and exit from pluripotency

Pluripotency is defined as the capacity to give rise to all cell types of the embryo proper. It arises in the early mammalian embryo but is lost after a short period of time as cells differentiate and become committed to different lineages. Prior to implantation, mouse epiblast cells enter the pluripotent naïve state, which can be captured in vitro in the form of embryonic stem cells. These cells are characterized by a capacity for indefinite self-renewal, and the ability to re-enter normal development upon being returned to the naïve epiblast. A complex transcription factor network promotes this state. Overexpression of one of many of these factors leads to stabilisation of the naïve state, with enhanced self-renewal and reduced spontaneous differentiation. However, the transcription factor Oct4 must be maintained within a tight window of expression; depletion results in extraembryonic differentiation, while overexpression also results in exit from pluripotency. Oct4 was identified as a protein expressed in the early embryo and in germ cells, and was subsequently discovered to be essential for the establishment of the naïve epiblast. In vitro studies determined that loss of Oct4 in ESCs induced trophoblast differentiation. Meanwhile, overexpression of Oct4 led to differentiation of ESCs, and constitutive expression of Oct4 was not sufficient to replace any of the extrinsic factors required for ESC self-renewal. Despite these dramatic phenotypes, the essential role of Oct4 remains unclear, further complicated by the finding that a reduced level of Oct4 promotes self-renewal at the expense of differentiation capacity. In this work, I generated a novel Oct4 fusion protein capable of rapid inducible degradation in order to study the immediate responses to removal of Oct4. This system utilizes the auxin responsive degradation domain of the Arabidopsis thaliana IAA17 protein to recruit a transgenic F-box protein Tir1 on addition of the small molecule auxin to the culture medium. Subsequent ubiquitination by the endogenous SCF complex leads to rapid proteolytic degradation of the Oct4 fusion protein, resulting in loss of detectable protein in as little as two hours. This system allows the study of immediate responses to loss of Oct4 in contrast to conventional depletion systems in which Oct4 levels decay over a protracted period making it difficult to disentangle direct and indirect effects. I established that several pluripotency-associated genes require Oct4 for their transcription. RNA levels of these factors decrease rapidly on depletion of Oct4, prior to significant changes in the expression of other key pluripotency factors such as Nanog and before protein levels of other factors can change dramatically. Furthermore, I established that the presence of Oct4 antagonises chromatin binding by a naïve transcription factor, revealing a possible mechanism by which increased Oct4 levels are detrimental to the naïve state. Together, these findings may be sufficient to explain the simultaneous requirement for, and antagonistic activity of, Oct4 in naïve pluripotent cells. I also found that an ESC level of Oct4 facilitates cell identity transitions. Cells constitutively expressing Oct4 and differentiated in vivo could be reverted to naïve pluripotency in vitro through the application of defined naïve pluripotency growth conditions. Additionally, in the course of these experiments I examined the phenotypic abnormalities that occur in mouse embryonic development under continuous expression of Oct4. In keeping with previous work, we observed abnormalities in limb development and in the skin. We also observed exencephaly in a number of embryos. In conventional exit from pluripotency, female cells must inactive an X chromosome in order to balance X-linked gene expression between males and females. This is achieved via expression of Xist from a single X chromosome, where it orchestrates chromosome-wide silencing. I show that Oct4 plays an important role in the regulation of Xist during the exit from pluripotency. Normally, Oct4 expression persists after the downregulation of most naïve transcription factors during early differentiation. I propose that this allows Oct4 to antagonise expression of the Xist, and thus ensure proper control over X chromosome inactivation. Together this work focuses on the dual roles of Oct4 in regulating both pluripotency and differentiation. I address the contradictory phenotypes relating to altered expression of Oct4, and establish a unifying theory to explain them. I put forward evidence that Oct4 promotes cell fate transitions by regulating naïve transcription factors. I propose that the environment plays a key role in determining cell identity, while Oct4 acts to maintain plasticity by preventing cells from being trapped within otherwise stable states.This work was funded by an MRC DTA PhD studentship in Stem Cell Biology & Medicine

Auxin-degron system identifies immediate mechanisms of OCT4.

The pluripotency factor OCT4 is essential for the maintenance of naive pluripotent stem cells in vitro and in vivo. However, the specific role of OCT4 in this process remains unknown. Here, we developed a rapid protein-level OCT4 depletion system that demonstrates that the immediate downstream response to loss of OCT4 is reduced expression of key pluripotency factors. Our data show a requirement for OCT4 for the efficient transcription of several key pluripotency factors and suggest that expression of trophectoderm markers is a subsequent event. In addition, we find that NANOG is able to bind to the genome in the absence of OCT4, and this binding is in fact enhanced. Globally, however, the active enhancer-associated histone mark H3K27ac is depleted. Our work establishes that, while OCT4 is required for the maintenance of the naive transcription factor network, at a normal embryonic stem cell levels it antagonizes this network through inhibition of NANOG binding

Institute of Archaeology & Horn Archaeological Museum Newsletter Volume 20.4

ASOR Meets in Boston, Paul J. Ray, Jr. New Staff, Paul J. Ray, Jr. Jim Sauer Dies, Lawrence T. Geraty, modified by Robert Bates Madaba Plains project Tall Al - \u27Umayri, Jordan Random Surveyhttps://digitalcommons.andrews.edu/iaham-news/1000/thumbnail.jp

Clinical outcome data for symptomatic breast cancer: the breast cancer clinical outcome measures (BCCOM) project

Background: Data collection for screen-detected breast cancer in the UK is fully funded which has led to improvements in clinical practice. However data on symptomatic breast cancer are deficient, and the aim of this project was to monitor the current practice. Methods: A data set was designed together with surrogate outcome measures to reflect best practice. Data from cancer registries initially required the consent of clinicians, but in the third year anonymised data were available. Results: The quality of data improved but this varied by region and only a third of cases were validated by clinicians. Regional variations in mastectomy rates were identified and one third of patients who underwent conservative surgery for invasive breast cancer were not recorded as receiving radiotherapy. Conclusions: National data are essential to ensure that all patients receive appropriate treatment for breast cancer, but variations still exist in the UK and further improvement in data capture is required

Searching Out the Headwaters: Change and Rediscovery in Western Water Policy

This digital resource contains only an abstract, cover image and table of contents information from the published book. Print copy of book is available in the University of Colorado’s Wise Law Library: http://lawpac.colorado.edu/record=b139018~S0 Contents: The West\u27s Gordian Knot -- Water in a changing West -- Voices -- The West today -- River basin stories -- Losing sight of the headwaters -- The journey to rediscovery -- Change and rediscovery in western water -- History need not repeat itself -- Appendix : The language of waterhttps://scholar.law.colorado.edu/books_reports_studies/1139/thumbnail.jp

Searching Out the Headwaters: Change and Rediscovery in Western Water Policy

This digital resource contains only an abstract, cover image and table of contents information from the published book. Print copy of book is available in the University of Colorado’s Wise Law Library: http://lawpac.colorado.edu/record=b139018~S0 Contents: The West\u27s Gordian Knot -- Water in a changing West -- Voices -- The West today -- River basin stories -- Losing sight of the headwaters -- The journey to rediscovery -- Change and rediscovery in western water -- History need not repeat itself -- Appendix : The language of waterhttps://scholar.law.colorado.edu/books_reports_studies/1139/thumbnail.jp

The Maine Annex, vol. 1, no. 2

The Maine Annex, published by the students of the University of Maine at the Brunswick Campus, was launched January 10, 1947. Editors introduced the publication as the product of a group of progressive students attending the Brunswick Campus. The goal of the publication, according to editors, was to tell the story of our life on this campus. The four-page, tabloid-sized paper included display advertising from area businesses. Stories in this issue of The Maine Annex are news items of interest to World War II Veterans, including international news from Europe and tips regarding the filing of federal paperwork to secure veterans benefits