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Analysis Of Clock-Regulated Genes In Neurospora Reveals Widespread Posttranscriptional Control Of Metabolic Potential, Jennifer M. M. Hurley, Arko Dasgupta, Jillian M. Emerson, Xiaoying Zhou, Carol S. Ringelberg, Nicole Knabe 2014 Dartmouth College

Analysis Of Clock-Regulated Genes In Neurospora Reveals Widespread Posttranscriptional Control Of Metabolic Potential, Jennifer M. M. Hurley, Arko Dasgupta, Jillian M. Emerson, Xiaoying Zhou, Carol S. Ringelberg, Nicole Knabe

Open Dartmouth: Faculty Open Access Articles

Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation-based feedback loops that control rhythmic transcription of a substantial fraction of these transcriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset ...


Syndecan 4 Is Required For Endothelial Alignment In Flow And Atheroprotective Signaling, Nicolas Baeyens, Mary Jo Mulligan-Kehoe, Federico Corti, David D. Simon, Tyler D. Ross, John M. Rhodes, Thomas Z. Wang 2014 Yale University

Syndecan 4 Is Required For Endothelial Alignment In Flow And Atheroprotective Signaling, Nicolas Baeyens, Mary Jo Mulligan-Kehoe, Federico Corti, David D. Simon, Tyler D. Ross, John M. Rhodes, Thomas Z. Wang

Open Dartmouth: Faculty Open Access Articles

Atherosclerotic plaque localization correlates with regions of disturbed flow in which endothelial cells (ECs) align poorly, whereas sustained laminar flow correlates with cell alignment in the direction of flow and resistance to atherosclerosis. We now report that in hypercholesterolemic mice, deletion of syndecan 4 (S4−/−) drastically increased atherosclerotic plaque burden with the appearance of plaque in normally resistant locations. Strikingly, ECs from the thoracic aortas of S4−/− mice were poorly aligned in the direction of the flow. Depletion of S4 in human umbilical vein endothelial cells (HUVECs) using shRNA also inhibited flow-induced alignment in vitro, which was rescued by re-expression ...


Swimming Against The Tide: Investigations Of The C-Bouton Synapse, Adam S. Deardorff, Shannon H. Romer, Patrick M. Sonner, Robert E. W. Fyffe 2014 Wright State University

Swimming Against The Tide: Investigations Of The C-Bouton Synapse, Adam S. Deardorff, Shannon H. Romer, Patrick M. Sonner, Robert E. W. Fyffe

Neuroscience, Cell Biology & Physiology Faculty Publications

C-boutons are important cholinergic modulatory loci for state-dependent alterations in motoneuron firing rate. m2 receptors are concentrated postsynaptic to C-boutons, and m2 receptor activation increases motoneuron excitability by reducing the action potential afterhyperpolarization. Here, using an intensive review of the current literature as well as data from our laboratory, we illustrate that C-bouton postsynaptic sites comprise a unique structural/functional domain containing appropriate cellular machinery (a “signaling ensemble”) for cholinergic regulation of outward K+ currents. Moreover, synaptic reorganization at these critical sites has been observed in a variety of pathologic states. Yet despite recent advances, there are still great challenges ...


Intravenous Pyruvate To Protect Heart And Brain During Closed-Chest Resuscitation And Recovery From Cardiac Arrest, Brandon H. Cherry 2014 University of North Texas Health Science Center of Fort Worth

Intravenous Pyruvate To Protect Heart And Brain During Closed-Chest Resuscitation And Recovery From Cardiac Arrest, Brandon H. Cherry

Theses and Dissertations

Cardiac arrest is a leading cause of death in the United States and Western Europe. Cardiopulmonary resuscitation (CPR) is the only means of sustaining the victim until application of defibrillatory countershocks. Although it has been over 50 years since its advent, CPR remains a work in progress. Many initially resuscitated victims later die from the damage sustained from ischemia-reperfusion, and treatments to combat the extensive ischemia-reperfusion injury sustained during cardiac arrest-resuscitation remain elusive. The major mechanism of injury underlying ischemia-reperfusion is the intense overproduction of reactive oxygen and nitrogen species (RONS) that accumulate during reperfusion and compromise normal cell function ...


Effects Of Various Partial Body Cooling Techniques On Core Temperature During Recovery From Prolonged Cycling-Induced Heat Stress, Afton Danielle Seeley 2014 Western Michigan University

Effects Of Various Partial Body Cooling Techniques On Core Temperature During Recovery From Prolonged Cycling-Induced Heat Stress, Afton Danielle Seeley

Master's Theses

The purpose of this study was to investigate the effects of using an ice-vest and a palm cooling device on core and skin temperatures, heart rate, and perceived thermal comfort during a one hour recovery period following exercise in the heat. Ten recreationally active adults cycled for one hour at 50% V02 peak on a cycle ergometer while exposed to 36°C 45%relative humidity environmental conditions. Following exercise, each subjectwas exposed to an ice vest, a palm cooling device, or a non cooling control while seated in the environmental chamber for 60 more minutes. No significant differencewas found ...


Comparison Of Dual- And Tri-Axial Accelerometer Accuracy, Lindsay Powell Toth 2014 Western Michigan University

Comparison Of Dual- And Tri-Axial Accelerometer Accuracy, Lindsay Powell Toth

Master's Theses

The purpose of this study was to investigate the accuracy of the Omron HJ-720ITC and the Fitbit Zip activity monitors with regard to step count, energy expenditure, and distance traveled measurements. The importance of this research rests in the success rates of pedometer-based physical activity interventions which have been shown to increase physical activity while also enabling weight loss and lowering blood pressure in the adult population. Activity monitors available for retail sale must be found accurate for proper participation in exercise interventions especially low-cost devices as used in this study.

In order to test the accuracy of the Omron ...


Nerve Blood Flow Control In Health & Disease:The Effects Of Type 1 Diabetes And Exercise Training, Terry D. Olver 2014 The University of Western Ontario

Nerve Blood Flow Control In Health & Disease:The Effects Of Type 1 Diabetes And Exercise Training, Terry D. Olver

Electronic Thesis and Dissertation Repository

Peripheral nerve blood flow (NBF) is critical to nerve health. Impaired NBF control may contribute to the progression of diabetes peripheral neuropathy. The purposes of this dissertation were: i) to investigate the acute and chronic effects of hyperglycemia on basal sciatic NBF (measured via Doppler ultrasound), ii) to examine the potential vasodilatory effects of insulin (euglycemic hyperinsulinemic clamp; 10 mµ•kg-1•min-1) on NBF control in healthy rats and rats with insulin-treated type 1 diabetes (DS) and iii) to determine if exercise training (~75% VO2max, 60 min/day, 5 days/wk for 10 wk) improves vasa ...


Motor Axon Synapses On Renshaw Cells Contain Higher Levels Of Aspartate Than Glutamate, Dannette Shanon Richards, Ronald W. Griffith, Shannon H. Romer, Francisco J. Alvarez 2014 Wright State University

Motor Axon Synapses On Renshaw Cells Contain Higher Levels Of Aspartate Than Glutamate, Dannette Shanon Richards, Ronald W. Griffith, Shannon H. Romer, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Motoneuron synapses on spinal cord interneurons known as Renshaw cells activate nicotinic, AMPA and NMDA receptors consistent with co-release of acetylcholine and excitatory amino acids (EAA). However, whether these synapses express vesicular glutamate transporters (VGLUTs) capable of accumulating glutamate into synaptic vesicles is controversial. An alternative possibility is that these synapses release other EAAs, like aspartate, not dependent on VGLUTs. To clarify the exact EAA concentrated at motor axon synapses we performed a quantitative postembedding colloidal gold immunoelectron analysis for aspartate and glutamate on motor axon synapses (identified by immunoreactivity to the vesicular acetylcholine transporter; VAChT) contacting calbindin-immunoreactive (-IR) Renshaw ...


Control Of Inflammation In Pancreatic Β-Cells: Role Of Arylpyrazole Compounds, Whitney Lyn Powell 2014 University of Tennessee - Knoxville

Control Of Inflammation In Pancreatic Β-Cells: Role Of Arylpyrazole Compounds, Whitney Lyn Powell

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

No abstract provided.


Adult Spinal Motoneurones Are Not Hyperexcitable In A Mouse Model Of Inherited Amyotrophic Lateral Sclerosis, Nicolas Delestrée, Marin Manuel, Caroline Iglesias, Sherif M. Elbasiouny, C. J. Heckman, Daniel Zytnicki 2014 Wright State University - Main Campus

Adult Spinal Motoneurones Are Not Hyperexcitable In A Mouse Model Of Inherited Amyotrophic Lateral Sclerosis, Nicolas Delestrée, Marin Manuel, Caroline Iglesias, Sherif M. Elbasiouny, C. J. Heckman, Daniel Zytnicki

Neuroscience, Cell Biology & Physiology Faculty Publications

In amyotrophic lateral sclerosis (ALS), an adult onset disease in which there is progressive degeneration of motoneurones, it has been suggested that an intrinsic hyperexcitability of motoneurones (i.e. an increase in their firing rates), contributes to excitotoxicity and to disease onset. Here we show that there is no such intrinsic hyperexcitability in spinal motoneurones. Our studies were carried out in an adult mouse model of ALS with a mutated form of superoxide dismutase 1 around the time of the first muscle fibre denervations. We showed that the recruitment current, the voltage threshold for spiking and the frequency–intensity gain ...


Effects Of Transcranial Direct Current Stimulation In Combination With Motor Practice On Dexterous Grasping And Manipulation In Healthy Older Adults, Pranav J Parikh, Kelly J Cole 2014 University of Iowa

Effects Of Transcranial Direct Current Stimulation In Combination With Motor Practice On Dexterous Grasping And Manipulation In Healthy Older Adults, Pranav J Parikh, Kelly J Cole

Department of Health and Human Physiology Publications

Transcranial anodal stimulation (tDCS) over primary motor cortex (M1) improves dexterous manipulation in healthy older adults. However, the beneficial effects of anodal tDCS in combination with motor practice on natural and clinically relevant functional manual tasks, and the associated changes in the digit contact forces are not known. To this end, we studied the effects of 20 min of tDCS applied over M1 for the dominant hand combined with motor practice (MP) in a sham‐controlled crossover study. We monitored the forces applied to an object that healthy elderly individuals grasped and manipulated, and their performances on the Grooved Pegboard ...


Substance P Differentially Modulates Firing Rate Of Solitary Complex (Sc) Neurons From Control And Chronic Hypoxia-Adapted Adult Rats, Nicole L. Nichols, Frank L. Powell, Jay B. Dean, Robert W. Putnam 2014 Wright State University

Substance P Differentially Modulates Firing Rate Of Solitary Complex (Sc) Neurons From Control And Chronic Hypoxia-Adapted Adult Rats, Nicole L. Nichols, Frank L. Powell, Jay B. Dean, Robert W. Putnam

Neuroscience, Cell Biology & Physiology Faculty Publications

NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS). Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus) neurons from control and chronic hypoxia-adapted (CHx) adult rats. We simultaneously measured intracellular pH and ...


Complexity Of Interferon-Γ Interactions With Hsv-1, Nancy J. Bigley 2014 Wright State University - Main Campus

Complexity Of Interferon-Γ Interactions With Hsv-1, Nancy J. Bigley

Neuroscience, Cell Biology & Physiology Faculty Publications

The intricacies involving the role of interferon-gamma (IFN-γ) in herpesvirus infection and persistence are complex. Herpes simplex virus type 1 (HSV-1) uses a variety of receptors to enter cells and is transported to and from the host cell nucleus over the microtubule railroad via retrograde and anterograde transport. IFN-γ exerts dual but conflicting effects on microtubule organization. IFN-γ stimulates production of suppressors of cytokine signaling 1 and 3 (SOCS1 and SOCS3), which are involved in microtubule stability and are negative regulators of IFN-γ signaling when overexpressed. IFN-γ also interferes with the correct assembly of microtubules causing them to undergo severe ...


Comparison Of Two Different Sprint Interval Training Work-To-Rest Ratios On Acute Metabolic And Inflammatory Responses, CHRISTOPHER R. HARNISH 2014 Virginia Commonwealth University

Comparison Of Two Different Sprint Interval Training Work-To-Rest Ratios On Acute Metabolic And Inflammatory Responses, Christopher R. Harnish

Theses and Dissertations

High intensity exercise is believed to yield greater results on health and human performance than moderate intensity exercise. Extensive research indicates that not only do high-intensity interval training (HIT) and sprint interval training (SIT) produce significant improvements in cardiovascular fitness and disease, they may be more effective at improving long-term metabolic function, including insulin sensitivity (Si), by producing more mitochondria. Moreover, compliance rates for HIT and SIT participation are reported to be the same or better than traditional moderate intensity exercise. Because lack of time is often cited as major hindrance to exercise participation, SIT is also seen as a ...


Antioxidant Rescue Of Nf1/Ras-Induced Myelin And Vasculature Dysfunction, Debra A. Mayes, Tilat A. Rizvi, Shyra J. Miller, Rachel Oberst, Anat Stemmer-Rachamimov, Nancy Ratner 2013 Wright State University - Main Campus

Antioxidant Rescue Of Nf1/Ras-Induced Myelin And Vasculature Dysfunction, Debra A. Mayes, Tilat A. Rizvi, Shyra J. Miller, Rachel Oberst, Anat Stemmer-Rachamimov, Nancy Ratner

Debra A. Mayes

No abstract provided.


Nf1 Loss And Ras Hyperactivation In Oligodendrocytes Induce Nos-Driven Defects In Myelin And Vasculature, Debra A. Mayes, Tilat A. Rizvi, Haley E. Titus-Mitchell, Rachel Oberst, Georgianne M. Ciraolo, Charles V. Vorhees, Andrew P. Robinson, Stephen D. Miller, Jose A. Cancelas, Anat O. Stemmer-Rachamimov, Nancy Ratner 2013 Wright State University - Main Campus

Nf1 Loss And Ras Hyperactivation In Oligodendrocytes Induce Nos-Driven Defects In Myelin And Vasculature, Debra A. Mayes, Tilat A. Rizvi, Haley E. Titus-Mitchell, Rachel Oberst, Georgianne M. Ciraolo, Charles V. Vorhees, Andrew P. Robinson, Stephen D. Miller, Jose A. Cancelas, Anat O. Stemmer-Rachamimov, Nancy Ratner

Debra A. Mayes

Patients with neurofibromatosis type 1 (NF1) and Costello syndrome Rasopathy have behavioral deficits. In NF1 patients, these may correlate with white matter enlargement and aberrant myelin. To model these features, we induced Nf1 loss or HRas hyperactivation in mouse oligodendrocytes. Enlarged brain white matter tracts correlated with myelin decompaction, downregulation of claudin-11, and mislocalization of connexin-32. Surprisingly, non-cell-autonomous defects in perivascular astrocytes and the blood-brain barrier (BBB) developed, implicating a soluble mediator. Nitric oxide (NO) can disrupt tight junctions and gap junctions, and NO and NO synthases (NOS1-NOS3) were upregulated in mutant white matter. Treating mice with the NOS inhibitor ...


Combining An Autologous Peripheral Nervous System “Bridge” And Matrix Modification By Chondroitinase Allows Robust, Functional Regeneration Beyond A Hemisection Lesion Of The Adult Rat Spinal Cord, John D. Houle, Veronica J. Tom, Debra A. Mayes, Gail Wagoner, Napoleon Phillips, Jerry Silver 2013 Wright State University - Main Campus

Combining An Autologous Peripheral Nervous System “Bridge” And Matrix Modification By Chondroitinase Allows Robust, Functional Regeneration Beyond A Hemisection Lesion Of The Adult Rat Spinal Cord, John D. Houle, Veronica J. Tom, Debra A. Mayes, Gail Wagoner, Napoleon Phillips, Jerry Silver

Debra A. Mayes

Chondroitinase-ABC (ChABC) was applied to a cervical level 5 (C5) dorsal quadrant aspiration cavity of the adult rat spinal cord to degrade the local accumulation of inhibitory chondroitin sulfate proteoglycans. The intent was to enhance the extension of regenerated axons from the distal end of a peripheral nerve (PN) graft back into the C5 spinal cord, having bypassed a hemisection lesion at C3. ChABC-treated rats showed (1) gradual improvement in the range of forelimb swing during locomotion, with some animals progressing to the point of raising their forelimb above the nose, (2) an enhanced ability to use the forelimb in ...


Anti-Tumor Effect Of Doxycycline On Glioblastoma Cells, Andrea Wang-Gillam, Eric Siegel, Debra A. Mayes, Laura F. Hutchins, Yi-Hong Zhou 2013 Wright State University - Main Campus

Anti-Tumor Effect Of Doxycycline On Glioblastoma Cells, Andrea Wang-Gillam, Eric Siegel, Debra A. Mayes, Laura F. Hutchins, Yi-Hong Zhou

Debra A. Mayes

AIM: Glioblastoma multiforme (GBM) is the most common primary brain tumor in humans, and it is highly invasive. Doxycycline, first identified as an antimicrobial agent, is a nonspecific inhibitor of matrix metalloproteinases (MMPs). Our objective was to investigate the anti-MMP effect of doxycycline at therapeutically acceptable levels on glioma cells in vitro. METHODS: The MTT assay was used to determine the anti-proliferative effects of doxycycline. MMP2 activity and expression were determined by gelatinase zymography and real-time quantitative RT-PCR, respectively. Cell invasion was assessed by Matrigel invasion assay. RESULTS: Doxycycline exerted mild anti-proliferative effects on all three glioma cell lines (U251HF ...


Perinatal Or Adult Nf1 Inactivation Using Tamoxifen-Inducible Plpcre Each Cause Neurofibroma Formation, Debra A. Mayes, Tilat A. Rizvi, Jose A. Cancelas, Nathan T. Kolasinski, Georgianne M. Ciraolo, Anat O. Stemmer-Rachamimov, Nancy Ratner 2013 Wright State University - Main Campus

Perinatal Or Adult Nf1 Inactivation Using Tamoxifen-Inducible Plpcre Each Cause Neurofibroma Formation, Debra A. Mayes, Tilat A. Rizvi, Jose A. Cancelas, Nathan T. Kolasinski, Georgianne M. Ciraolo, Anat O. Stemmer-Rachamimov, Nancy Ratner

Debra A. Mayes

OBJECTIVES Neurofibromas are tumors initiated by biallelic mutation of the NF1 tumor suppressor gene in the Schwann cell lineage. One idea within the field suggests that Nf1loss must occur within progenitor cells present within a critical window during Schwann cell development in order for neurofibromas to form. To test this hypothesis and to examine whethermyelinating Schwann cells can serve as aneurofibroma cell of origin, Nf1 loss was induced at perinatal or adult timepoints using a tamoxifen-inducible Plp-CreERT driver. RESULTS Perinatal loss of Nf1 resulted in small neurofibromas late in life, while adult loss caused large neurofibromas and morbidity beginning 4 ...


How Loss Of Neurofibromin In Oligodendrocytes Affects The Brain, Debra A. Mayes, Tilat A. Rizvi, Nathan T. Kolasinski, S. Miller, Nancy Ratner 2013 Wright State University - Main Campus

How Loss Of Neurofibromin In Oligodendrocytes Affects The Brain, Debra A. Mayes, Tilat A. Rizvi, Nathan T. Kolasinski, S. Miller, Nancy Ratner

Debra A. Mayes

Neurofibromatosis type 1 patients are predisposed to central nervous system (CNS) phenotypes including enlarged brains, delayed acquisition of motor skills, brain tumors, and cognitive deficits. Imaging and pathologic analysis suggest that changes in white matter myelination may underlie both the enlargement of white matter tracts that contributes to megancephaly, and/or hyper-intense signals visualized on MRI. To study the role(s) of Nf1 and HRasin oligodendrocytes, we examined the optic nerve and corpus callosum,myelinated fiber tracts.We studiedNf1heterozygous mice,tamoxifen-induced Nf1 loss in mature oligodendrocytes (Plp-CreERT), and a new transgenic model in which the CNPase promoter drives expression of ...


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