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Search Results: 1 - 10 of 5482 matches for " Susan Barnett "
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Subcellular localization of Mayven following expression of wild type and mutant EGFP tagged cDNAs
Paul Montague, Peter GE Kennedy, Susan C Barnett
BMC Neuroscience , 2010, DOI: 10.1186/1471-2202-11-63
Abstract: The subcellular location of Mayven in OEC transfectants showed a characteristic distribution with intense foci of staining towards the process tips corresponding to regions of accumulated Mayven overlapping in part with lammelipodial actin and was absent from the filipodia and the outer membrane. This signature pattern was also observed in Schwann cells, Oli-Neu cells, astrocytes and the neuroblastoma cell line B104 transfectants and resembled the exogenous and endogenous Mayven distribution in oligodendrocytes. This contrasted with the localization pattern in non-neural cells. There was a re-localization of Mayven in OEC transfectants following drug treatment to challenge the integrity of the actin cytoskeleton while breakdown of the microtubular component had no discernible impact on the accumulation of Mayven in the process tips. Deletion of the first three amino acids of the SH3 motif of the putative Fyn Kinase binding domain at the amino terminus significantly compromised this signature pattern as did the removal of the last Kelch repeat unit of six unit Kelch domain comprising the carboxyl terminus. In addition, there was a reduction in process length in mutant transfectants. Co-expression studies with a haemagglutinin (HA) tagged wild type Mayven cDNA and EGFP tagged mutant cDNAs suggested a homomeric interaction mediated by the BTB/POZ domain.Exogenous Mayven is transported to the lamellipodia in neural transfectants associating with the actin cytoskeletal network. In addition to the importance of the internal BTB/POZ domain, this subcellular distribution pattern is dependent on the presence of an intact amino and carboxyl terminus.Actin polymerization driven membrane protrusion, initially results in the formation of fine filipodia projections comprising parallel actin bundles. The filipodia widen to form lamellipodia by creating a branched mesh network of orthogonal actin. Consequent recruitment of microtubules provides mechanical stability to the extending
Time-Lapse Imaging of the Dynamics of CNS Glial-Axonal Interactions In Vitro and Ex Vivo
Kalliopi Ioannidou, Kurt I. Anderson, David Strachan, Julia M. Edgar, Susan C. Barnett
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0030775
Abstract: Background Myelination is an exquisite and dynamic example of heterologous cell-cell interaction, which consists of the concentric wrapping of multiple layers of oligodendrocyte membrane around neuronal axons. Understanding the mechanism by which oligodendrocytes ensheath axons may bring us closer to designing strategies to promote remyelination in demyelinating diseases. The main aim of this study was to follow glial-axonal interactions over time both in vitro and ex vivo to visualize the various stages of myelination. Methodology/Principal Findings We took two approaches to follow myelination over time: i) time-lapse imaging of mixed CNS myelinating cultures generated from mouse spinal cord to which exogenous GFP-labelled murine cells were added, and ii) ex vivo imaging of the spinal cord of shiverer (Mbp mutant) mice, transplanted with GFP-labelled murine neurospheres. We demonstrate that oligodendrocyte-axonal interactions are dynamic events with continuous retraction and extension of oligodendroglial processes. Using cytoplasmic and membrane-GFP labelled cells to examine different components of the myelin-like sheath, we provide evidence from time-lapse fluorescence microscopy and confocal microscopy that the oligodendrocytes' cytoplasm-filled processes initially spiral around the axon in a corkscrew-like manner. This is followed subsequently by focal expansion of the corkscrew process to form short cuffs, which then extend longitudinally along the axons. We predict from this model that these spiral cuffs must extend over each other first before extending to form internodes of myelin. Conclusion These experiments show the feasibility of visualizing the dynamics of glial-axonal interaction during myelination over time. Moreover, these approaches complement each other with the in vitro approach allowing visualization of an entire internodal length of myelin and the ex vivo approach validating the in vitro data.
Calponin is expressed by subpopulations of connective tissue cells but not olfactory ensheathing cells in the neonatal olfactory mucosa
Mercedes Tomé, Edina Silad?ic, Alessandra Santos-Silva, Susan C Barnett
BMC Neuroscience , 2007, DOI: 10.1186/1471-2202-8-74
Abstract: In this study we show that: i) proteinase K pretreatment had no effect on calponin staining in both OECs and Schwann cells. ii) calponin immunoreactivity was not expressed by embryonic or neonatal OECs in vitro and in vivo although connective tissue from the olfactory mucosa was strongly positive in neonatal rats but not embryonic rats, iii) calponin expression in the olfactory mucosa was heterogeneous, defining subpopulations of connective tissue cells iv) using functional confrontation assays between OECs or Schwann cells with astrocytes, calponin was expressed heterogeneously by astrocytes.It is concluded that calponin is heterogeneously expressed by neonatal mucosal connective tissue but not expressed by neonatal OECs, embryonic OECs, and neonatal Schwann cells. Furthermore, we propose that calponin is not a specific marker for OECs generated from any developmental age.Olfactory ensheathing cells (OECs) are the glial cells of the primary olfactory system [1]. The olfactory system is comprised of both PNS and CNS tissue and known for its ability to support neurogenesis throughout life [2,3]. It is believed that the role of OECs in the olfactory system is to direct the newly generated axons to their correct position in the CNS environment of the olfactory bulb [2]. OECs have become cells of interest due to their potential as candidates for transplant-mediated repair of CNS pathologies, such as spinal cord injury and multiple sclerosis [4-7]. Several studies have demonstrated that transplanted OECs can in the right environment, myelinate experimentally created demyelinated axons [8-10]. However, it has been suggested that myelination seen after transplantation of OECs is due to contaminating Schwann cells [11] or by host Schwann cells invading the lesion site [12-14].It has been extremely difficult to confirm if OECs can indeed myelinate axons in vivo due to the inability to distinguish OECs from Schwann cells using cell markers. This is because they share many cha
Metabolic Regulation of Neuronal Plasticity by the Energy Sensor AMPK
Wyatt B. Potter,Kenneth J. O'Riordan,David Barnett,Susan M. K. Osting,Matthew Wagoner,Corinna Burger,Avtar Roopra
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0008996
Abstract: Long Term Potentiation (LTP) is a leading candidate mechanism for learning and memory and is also thought to play a role in the progression of seizures to intractable epilepsy. Maintenance of LTP requires RNA transcription, protein translation and signaling through the mammalian Target of Rapamycin (mTOR) pathway. In peripheral tissue, the energy sensor AMP-activated Protein Kinase (AMPK) negatively regulates the mTOR cascade upon glycolytic inhibition and cellular energy stress. We recently demonstrated that the glycolytic inhibitor 2-deoxy-D-glucose (2DG) alters plasticity to retard epileptogenesis in the kindling model of epilepsy. Reduced kindling progression was associated with increased recruitment of the nuclear metabolic sensor CtBP to NRSF at the BDNF promoter. Given that energy metabolism controls mTOR through AMPK in peripheral tissue and the role of mTOR in LTP in neurons, we asked whether energy metabolism and AMPK control LTP. Using a combination of biochemical approaches and field-recordings in mouse hippocampal slices, we show that the master regulator of energy homeostasis, AMPK couples energy metabolism to LTP expression. Administration of the glycolytic inhibitor 2-deoxy-D-glucose (2DG) or the mitochondrial toxin and anti-Type II Diabetes drug, metformin, or AMP mimetic AICAR results in activation of AMPK, repression of the mTOR pathway and prevents maintenance of Late-Phase LTP (L-LTP). Inhibition of AMPK by either compound-C or the ATP mimetic ara-A rescues the suppression of L-LTP by energy stress. We also show that enhanced LTP via AMPK inhibition requires mTOR signaling. These results directly link energy metabolism to plasticity in the mammalian brain and demonstrate that AMPK is a modulator of LTP. Our work opens up the possibility of using modulators of energy metabolism to control neuronal plasticity in diseases and conditions of aberrant plasticity such as epilepsy.
John Muir and “Godful” Nature
Raymond Barnett
Religions , 2012, DOI: 10.3390/rel3020266
Abstract: John Muir, America’s most influential conservationist, held a special view of Nature, one that treated Nature as “Godful” and “unredeemed” because, unlike humankind, Nature has not “fallen”. It is a view that asks us to adopt a gaiacentric, not anthropocentric, perspective on our place in the universe. This article explores the meaning and development of that view and how it came to define Muir’s faith and serve his noble purpose of preserving the Wilderness.
Lixisenatide: evidence for its potential use in the treatment of type 2 diabetes
Barnett AH
Core Evidence , 2011, DOI: http://dx.doi.org/10.2147/CE.S15525
Abstract: enatide: evidence for its potential use in the treatment of type 2 diabetes Review (5037) Total Article Views Authors: Barnett AH Published Date September 2011 Volume 2011:6 Pages 67 - 79 DOI: http://dx.doi.org/10.2147/CE.S15525 Anthony H Barnett University of Birmingham and BioMedical Research Centre, Heart of England National Health Service Foundation Trust, Birmingham, UK Abstract: Lixisenatide is a once-daily glucagon-like peptide 1 (GLP-1) receptor agonist mimicking several favorable actions of endogenous GLP-1 that result in improved glycemic control with little or no hypoglycemia and weight loss. Phase II trials have shown that lixisenatide 20 μg once daily restores first-phase insulin release in patients with type 2 diabetes and improves the second-phase insulin response. Administered once or twice daily for 4 weeks, it significantly reduced postprandial and fasting blood glucose levels, and glycosylated hemoglobin (HbA1c). The efficacy and safety of lixisenatide once daily is being assessed in the GETGOAL Phase III clinical trial program. Results have shown beneficial effects on HbA1c compared with placebo in combination with commonly used antidiabetes agents, with no increased risk of hypoglycemia and with beneficial weight reduction. Adverse effects were similar to those observed for available GLP-1 receptor agonists, the most frequent being gastrointestinal. Both GLP-1 receptor agonists and long-acting insulin analogs have demonstrated protective effects on beta cells in preclinical studies. This, along with the pronounced effect of lixisenatide on postprandial plasma glucose, provides a rationale for combining it with long-acting basal insulin analogs, in the hope that the additive effects on glycemic control combined with a potential benefit on islet cells may lead to a new treatment approach to control blood glucose better and prevent long-term complications in patients with type 2 diabetes.
Getting Real About Teaching Effectiveness and Teacher Retention
Barnett Berry
Journal of Curriculum and Instruction , 2010,
Abstract: In this issue of the Journal of Curriculum and Instruction, a set of papers drawing on a range of data offers more substantiation that teaching is a complex activity that takes time to learn. Those who enter through more comprehensive teacher education programs, rather than short-cut alternative ones, learn more deeply about their profession and are more likely to remain in teaching. Let me briefly offer a few highlights from this new research, and then couch it in a larger set of empirical evidence, with implications for policy and practice.
Constructing New Theory for Identifying Students with Emotional Disturbance: A Constructivist Approach to Grounded Theory
Dori Barnett
Grounded Theory Review : an International Journal , 2012,
Abstract: A grounded theory study that examined how practitioners in a county alternative and correctional education setting identify youth with emotional and behavioral difficulties for special education services provides an exemplar for a constructivist approach to grounded theory methodology. Discussion focuses on how a constructivist orientation to grounded theory methodology informed research decisions, shaped the development of the emergent grounded theory, and prompted a way of thinking about data collection and analysis. Implications for future research directions and policy and practice in the field of special and alternative education are discussed.
Restrictions and Their Anomalies:The Third Forum and the Regulation of Religion in Tibet
Robert Barnett
Journal of Current Chinese Affairs , 2012,
Abstract: In 1994, at a meeting known as the Third Forum on Tibet Work, the Chinese authorities announced a series of restrictions on religious practice in the Tibetan Autonomous Region. Described by many outsiders in terms of abuses of rights, in fact those measures differed in important ways. By analysing the target, rationale and procedure of these restrictions, it becomes clear that some were relatively routine, while others were anomalous – their purpose was not explained by officials, the source of their authority was not clear, or the restrictions were simply not admitted to at all. These anomalous orders can be linked to major changes in underlying discourses of modernization and development among officials in Tibet at the time. They reflected undeclared shifts in attitudes to religion and cultural difference, and seeded the dramatic worsening in state–society relations that has taken place in Tibetan areas since that time.
Learning from History: Examining Yield Spreads as a Predictor of Real Economic Activity
Nicholas Barnett
Michigan Journal of Business , 2012,
Abstract: Economists often use complicated models in an attempt to predict economic activity; however, in recent years, attention has shifted toward more simplistic forecasting methods that have the potential to yield equally useful results. One such method involves examining the predictive power of interest rate yield spreads. The spread in interest rates offered for different debt securities with identical maturities reflects the required compensation investors demand for bearing extra risk. Within the market forces driving yield spreads lies tacit information of market expectations. The goal of this study is to examine yield spreads of various debt securities and compare changes in those spreads to changes in economic activity across the past 50 years. By using statistical methods to compare the relationships of various yield spreads to real economic activity, this paper will show the value of using interest rate yield spreads to forecast economic activity and determine which spreads are most valuable as predictors.
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