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"Rowland, Susan"
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Emerging Roles of Primary Cilia in Glioma
Primary cilia are microtubule-based organelles that are typically present on cells during the G0 or G1-S/G2 phases of the cell cycle. Recent studies of glioblastoma (GBM) biopsies, a brain tumor that is notorious for its aggressive growth and resistance to treatment, show that many cells in the tumor lack cilia. At this point, it remains unclear whether primary cilia promote or suppress glioma tumorigenesis. In this review, we will discuss the different roles that have been proposed for primary cilia in glioma and how cilia may contribute to the resistance of these tumors to current therapies.
Journal Article
Increasing Hippocampal Estrogen Receptor Alpha Levels via Viral Vectors Increases MAP Kinase Activation and Enhances Memory in Aging Rats in the Absence of Ovarian Estrogens
We previously demonstrated that aged ovariectomized rats that had received prior estradiol treatment in middle-age exhibited increased levels of estrogen receptor alpha (ERα) in the hippocampus as well as enhanced hippocampal dependent memory as compared to aged rats that had not received mid-life estradiol treatment. These effects persisted long after the estradiol treatment had been terminated. The goal of the current experiment was to determine if increased expression of ERα in the hippocampus, in the absence of exogenously administered estrogens, can impact the hippocampus and cognitive function in aging ovariectomized rats. Middle-aged rats were trained for 24 days on an eight-arm radial maze spatial memory task. All rats were then ovariectomized. Forty days later, rats received either lentiviral delivery to the hippocampus of the gene encoding ERα (lenti-ERα) or a control virus. Rats were tested on delay trials in the radial-maze in which delays of varying lengths were imposed between the fourth and fifth arm choices. Following behavior testing, hippocampi were immunostained using western blotting for ERα, the ERα-regulated protein choline acetyltransferase, and phosphorylation of the ERα-regulated kinases, ERK/MAPK and Akt. Results revealed that aging ovariectomized rats that received delivery of lenti-ERα to the hippocampus exhibited enhanced spatial memory as indicated by increased arm-choice accuracy across delays as compared to ovariectomized rats that received control virus. Western blot data revealed that lenti-ERα delivery significantly increased levels of ERα and phosphorylated ERK/MAPK and had no impact on levels of ChAT or phosphorylation of Akt. Results indicate that increasing hippocampal levels of ERα in aging females in the absence of ovarian or exogenously administered estrogens leads to increases in phosphorylation of ERK/MAPK as well as in enhanced memory.
Journal Article
The Ecocritical Psyche
The Ecocritical Psyche unites literary studies, ecocriticism, Jungian ideas, mythology and complexity evolution theory for the first time, developing the aesthetic aspect of psychology and science as deeply as it explores evolution in Shakespeare and Jane Austen.
In this book, Susan Rowland scrutinizes literature to understand how we came to treat 'nature' as separate from ourselves and encourages us to re-think what we call 'human.' By digging into symbolic, mythological and evolutionary fertility in texts such as The Secret Garden, The Tempest, Wuthering Heights and The Lion, the Witch and the Wardrobe , the book argues that literature is where the imagination, estranged from nature in modernity, is rooted in the non-human other.
The Ecocritical Psyche is unique in its interdisciplinary expansion of literature, psyche, science and myth. It develops Jungian aesthetics to show how Jung's symbols correlate with natural signifying, providing analytical psychology with a natural home in ecocritical literary theory. The book is therefore essential reading for seasoned analysts and those in training as well as academics involved in literary studies and Jungian psychology.
Introduction: The Problem of Writing and Nature for Jung and Evolution. The Problem of the Body In/Out of Nature for Jane Austen and Seamus Heaney. The Problem of Heaven and Hell for Emily Bronte. Re-figuring Evolution for Children's Literature. Hunting Signs with the Trickster Detectives. Shakespeare's Magical Power. The Writer and the Underworld.
Susan Rowland was Professor of English and Jungian Studies at the University of Greenwich, London, and now is Core Faculty at Pacifica Graduate Institute, California, USA. She was First Chair of the International Association for Jungian Studies from 2004-2006. Susan's work takes Jung into literary theory and literature into myth; her publications include Jung as a Writer (Routledge, 2005) and Psyche and the Arts (Routledge, 2008).
eBook
“RIPSSL”: A New Reflective Inquiry Protocol to Lift the Lid on Students’ Significant Extra-Curricular Learning Outcomes from Study Abroad
Education abroad generally has no overarching curriculum outside the formal study component. This paper presents the Reflective Inquiry Protocol for Surfacing Significant Learning (RIPSSL), a new approach for understanding and articulating significant learning from education abroad. Tests of RIPSSL show education abroad students use it to move beyond “it was great” when considering learning from their experiences. Our findings are important for educators and students as they work to recognize and articulate the value of education abroad. RIPSSL provides a reflective educational approach to evidence learning from life experiences by surfacing students’ significant learning in their own words.
Journal Article
Bicistronic Lentiviruses Containing a Viral 2A Cleavage Sequence Reliably Co-Express Two Proteins and Restore Vision to an Animal Model of LCA1
The disease processes underlying inherited retinal disease are complex and are not completely understood. Many of the corrective gene therapies designed to treat diseases linked to mutations in genes specifically expressed in photoreceptor cells restore function to these cells but fail to stop progression of the disease. There is growing consensus that effective treatments for these diseases will require delivery of multiple therapeutic proteins that will be selected to treat specific aspects of the disease process. The purpose of this study was to design a lentiviral transgene that reliably expresses all of the proteins it encodes and does so in a consistent manner among infected cells. We show, using both in vitro and in vivo analyses, that bicistronic lentiviral transgenes encoding two fluorescent proteins fused to a viral 2A-like cleavage peptide meet these expression criteria. To determine if this transgene design is suitable for therapeutic applications, we replaced one of the fluorescent protein genes with the gene encoding guanylate cyclase-1 (GC1) and delivered lentivirus carrying this transgene to the retinas of the GUCY1*B avian model of Leber congenital amaurosis-1 (LCA1). GUCY1*B chickens carry a null mutation in the GC1 gene that disrupts photoreceptor function and causes blindness at hatching, a phenotype that closely matches that observed in humans with LCA1. We found that treatment of these animals with the 2A lentivector encoding GC1 restored vision to these animals as evidenced by the presence of optokinetic reflexes. We conclude that 2A-like peptides, with proper optimization, can be successfully incorporated into therapeutic vectors designed to deliver multiple proteins to neural retinal. These results highlight the potential of this vector design to serve as a platform for the development of combination therapies designed to enhance or prolong the benefits of corrective gene therapies.
Journal Article
Membrane Localization of MinD Is Mediated by a C-Terminal Motif That Is Conserved across Eubacteria, Archaea, and Chloroplasts
MinD is a widely conserved ATPase that has been demonstrated to play a pivotal role in selection of the division site in eubacteria and chloroplasts. It is a member of the large ParA superfamily of ATPases that are characterized by a deviant Walker-type ATP-binding motif. MinD localizes to the cytoplasmic face of the inner membrane in Escherichia coli, and its association with the inner membrane is a prerequisite for membrane recruitment of the septation inhibitor MinC. However, the mechanism by which MinD associates with the membrane has proved enigmatic; it seems to lack a transmembrane domain and the amino acid sequence is devoid of hydrophobic tracts that might predispose the protein to interaction with lipids. In this study, we show that the extreme C-terminal region of MinD contains a highly conserved 8- to 12-residue sequence motif that is essential for membrane localization of the protein. We provide evidence that this motif forms an amphipathic helix that most likely mediates a direct interaction between MinD and membrane phospholipids. A model is proposed whereby the membrane-targeting motif mediates the rapid cycles of membrane attachment-release-reattachment that are presumed to occur during pole-to-pole oscillation of MinD in E. coli.
Journal Article
A Preclinical Assessment of Neural Stem Cells as Delivery Vehicles for Anti-Amyloid Therapeutics
Transplantation of neural stems cells (NSCs) could be a useful means to deliver biologic therapeutics for late-stage Alzheimer's disease (AD). In this study, we conducted a small preclinical investigation of whether NSCs could be modified to express metalloproteinase 9 (MMP9), a secreted protease reported to degrade aggregated Aβ peptides that are the major constituents of the senile plaques. Our findings illuminated three issues with using NSCs as delivery vehicles for this particular application. First, transplanted NSCs generally failed to migrate to amyloid plaques, instead tending to colonize white matter tracts. Second, the final destination of these cells was highly influenced by how they were delivered. We found that our injection methods led to cells largely distributing to white matter tracts, which are anisotropic conduits for fluids that facilitate rapid distribution within the CNS. Third, with regard to MMP9 as a therapeutic to remove senile plaques, we observed high concentrations of endogenous metalloproteinases around amyloid plaques in the mouse models used for these preclinical tests with no evidence that the NSC-delivered enzymes elevated these activities or had any impact. Interestingly, MMP9-expressing NSCs formed substantially larger grafts. Overall, we observed long-term survival of NSCs in the brains of mice with high amyloid burden. Therefore, we conclude that such cells may have potential in therapeutic applications in AD but improved targeting of these cells to disease-specific lesions may be required to enhance efficacy.
Journal Article
Viral Vector–mediated Delivery of Estrogen Receptor-α to the Hippocampus Improves Spatial Learning in Estrogen Receptor-α Knockout Mice
Estrogen, which influences both classical genomic and rapid membrane-associated signaling cascades, has been implicated in the regulation of hippocampal function, including spatial learning. Gene mutation studies suggest that estrogen effects are mediated by estrogen receptor-α (ER-α); however, because gonadal steroids influence the organization of the hippocampus during development, it has been difficult to distinguish developmental effects from those specific to adults. In this study we show that lentiviral delivery of the gene encoding ER-α to the hippocampus of adult ER-α-knockout (ER-αKO) mice restores hippocampal responsiveness to estrogen and rescues spatial learning. We propose that constitutive estrogen receptor activity is important for maintaining hippocampus-dependent memory function in adults.
Journal Article