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Articles 1 - 18 of 18
Full-Text Articles in Life Sciences
Effects Of Rapamycin Treatment On Neurogenesis And Synaptic Reorganization In The Dentate Gyrus After Controlled Cortical Impact Injury In Mice, Corwin R. Butler, Jeffery A. Boychuk, Bret N. Smith
Effects Of Rapamycin Treatment On Neurogenesis And Synaptic Reorganization In The Dentate Gyrus After Controlled Cortical Impact Injury In Mice, Corwin R. Butler, Jeffery A. Boychuk, Bret N. Smith
Physiology Faculty Publications
Post-traumatic epilepsy (PTE) is one consequence of traumatic brain injury (TBI). A prominent cell signaling pathway activated in animal models of both TBI and epilepsy is the mammalian target of rapamycin (mTOR). Inhibition of mTOR with rapamycin has shown promise as a potential modulator of epileptogenesis in several animal models of epilepsy, but cellular mechanisms linking mTOR expression and epileptogenesis are unclear. In this study, the role of mTOR in modifying functional hippocampal circuit reorganization after focal TBI induced by controlled cortical impact (CCI) was investigated. Rapamycin (3 or 10 mg/kg), an inhibitor of mTOR signaling, was administered by intraperitoneal …
Rfx Transcription Factors Are Essential For Hearing In Mice, Ran Elkon, Beatrice Milon, Laura Morrison, Manan Shah, Sarath Vijayakumar, Manoj Racherla, Carmen C. Leitch, Lorna Silipino, Shadan Hadi, Michèle Weiss-Gayet, Emmanuèle Barras, Christoph D. Schmid, Aouatef Ait-Lounis, Ashley Barnes, Yang Song, David J. Eisenman, Efrat Eliyahu, Gregory I. Frolenkov, Scott E. Strome, Bénédicte Durand, Norann A. Zaghloul, Sherri M. Jones, Walter Reith, Ronna Hertzano
Rfx Transcription Factors Are Essential For Hearing In Mice, Ran Elkon, Beatrice Milon, Laura Morrison, Manan Shah, Sarath Vijayakumar, Manoj Racherla, Carmen C. Leitch, Lorna Silipino, Shadan Hadi, Michèle Weiss-Gayet, Emmanuèle Barras, Christoph D. Schmid, Aouatef Ait-Lounis, Ashley Barnes, Yang Song, David J. Eisenman, Efrat Eliyahu, Gregory I. Frolenkov, Scott E. Strome, Bénédicte Durand, Norann A. Zaghloul, Sherri M. Jones, Walter Reith, Ronna Hertzano
Physiology Faculty Publications
Sensorineural hearing loss is a common and currently irreversible disorder, because mammalian hair cells (HCs) do not regenerate and current stem cell and gene delivery protocols result only in immature HC-like cells. Importantly, although the transcriptional regulators of embryonic HC development have been described, little is known about the postnatal regulators of maturating HCs. Here we apply a cell type-specific functional genomic analysis to the transcriptomes of auditory and vestibular sensory epithelia from early postnatal mice. We identify RFX transcription factors as essential and evolutionarily conserved regulators of the HC-specific transcriptomes, and detect Rfx1,2,3,5 and 7 in the developing HCs. …
Topological Data Analysis For Discovery In Preclinical Spinal Cord Injury And Traumatic Brain Injury, Jessica L. Nielson, Jesse Paquette, Aiwen W. Liu, Cristian F. Guandique, C. Amy Tovar, Tomoo Inoue, Karen-Amanda Irvine, John C. Gensel, Jennifer Kloke, Tanya C. Petrossian, Pek Y. Lum, Gunnar E. Carlsson, Geoffrey T. Manley, Wise Young, Michael S. Beattie, Jacqueline C. Bresnahan, Adam R. Ferguson
Topological Data Analysis For Discovery In Preclinical Spinal Cord Injury And Traumatic Brain Injury, Jessica L. Nielson, Jesse Paquette, Aiwen W. Liu, Cristian F. Guandique, C. Amy Tovar, Tomoo Inoue, Karen-Amanda Irvine, John C. Gensel, Jennifer Kloke, Tanya C. Petrossian, Pek Y. Lum, Gunnar E. Carlsson, Geoffrey T. Manley, Wise Young, Michael S. Beattie, Jacqueline C. Bresnahan, Adam R. Ferguson
Physiology Faculty Publications
Data-driven discovery in complex neurological disorders has potential to extract meaningful syndromic knowledge from large, heterogeneous data sets to enhance potential for precision medicine. Here we describe the application of topological data analysis (TDA) for data-driven discovery in preclinical traumatic brain injury (TBI) and spinal cord injury (SCI) data sets mined from the Visualized Syndromic Information and Outcomes for Neurotrauma-SCI (VISION-SCI) repository. Through direct visualization of inter-related histopathological, functional and health outcomes, TDA detected novel patterns across the syndromic network, uncovering interactions between SCI and co-occurring TBI, as well as detrimental drug effects in unpublished multicentre preclinical drug trial data …
Genetics Ignite Focus On Microglial Inflammation In Alzheimer's Disease, Manasi Malik, Ishita Parikh, Jared B. Vasquez, Conor Smith, Leon Tai, Guojun Bu, Mary Jo Ladu, David W. Fardo, G. William Rebeck, Steven Estus
Genetics Ignite Focus On Microglial Inflammation In Alzheimer's Disease, Manasi Malik, Ishita Parikh, Jared B. Vasquez, Conor Smith, Leon Tai, Guojun Bu, Mary Jo Ladu, David W. Fardo, G. William Rebeck, Steven Estus
Physiology Faculty Publications
In the past five years, a series of large-scale genetic studies have revealed novel risk factors for Alzheimer's disease (AD). Analyses of these risk factors have focused attention upon the role of immune processes in AD, specifically microglial function. In this review, we discuss interpretation of genetic studies. We then focus upon six genes implicated by AD genetics that impact microglial function: TREM2, CD33, CR1, ABCA7, SHIP1, and APOE. We review the literature regarding the biological functions of these six proteins and their putative role in AD pathogenesis. We then present a model for how …
A Novel C-Terminal Cib2 (Calcium And Integrin Binding Protein 2) Mutation Associated With Non-Syndromic Hearing Loss In A Hispanic Family, Kunjan Patel, Arnaud P. Giese, J. M. Grossheim, Rashima S. Hegde, Maria Delio, Joy Samanich, Saima Riazuddin, Gregory I. Frolenkov, Jinlu Cai, Zubair M. Ahmed, Bernice E. Morrow
A Novel C-Terminal Cib2 (Calcium And Integrin Binding Protein 2) Mutation Associated With Non-Syndromic Hearing Loss In A Hispanic Family, Kunjan Patel, Arnaud P. Giese, J. M. Grossheim, Rashima S. Hegde, Maria Delio, Joy Samanich, Saima Riazuddin, Gregory I. Frolenkov, Jinlu Cai, Zubair M. Ahmed, Bernice E. Morrow
Physiology Faculty Publications
Hearing loss is a complex disorder caused by both genetic and environmental factors. Previously, mutations in CIB2 have been identified as a common cause of genetic hearing loss in Pakistani and Turkish populations. Here we report a novel (c.556C>T; p.(Arg186Trp)) transition mutation in the CIB2 gene identified through whole exome sequencing (WES) in a Caribbean Hispanic family with non-syndromic hearing loss. CIB2 belongs to the family of calcium-and integrin-binding (CIB) proteins. The carboxy-termini of CIB proteins are associated with calcium binding and intracellular signaling. The p.(Arg186Trp) mutation is localized within predicted type II PDZ binding ligand at the carboxy …
Workforce Fitness: Description, Contextual Issues, And Implications For Public Health, Nicolaas P. Pronk
Workforce Fitness: Description, Contextual Issues, And Implications For Public Health, Nicolaas P. Pronk
Frontiers in Public Health Services and Systems Research
Workforce fitness matters for the prevention of premature death, chronic diseases, productivity loss, excess medical care costs, loss of income or family earnings, and other social and economic concerns. Yet fitness levels appear to be relatively low and declining. Over the past half century obesity has doubled, physical activity levels are below par, and cardiorespiratory fitness often does not meet minimally acceptable job standards. During this time, daily occupational energy expenditure has decreased by more than 100 calories. It is recommended for employers to consider best practices and design workplace wellness programs accordingly. Regulations that protect and promote worker health, …
Endogenous Opioid-Masked Latent Pain Sensitization: Studies From Mouse To Human, Manuel P. Pereira, Renee R. Donahue, Jørgen B. Dahl, Marianne Werner, Bradley K. Taylor, Mads U. Werner
Endogenous Opioid-Masked Latent Pain Sensitization: Studies From Mouse To Human, Manuel P. Pereira, Renee R. Donahue, Jørgen B. Dahl, Marianne Werner, Bradley K. Taylor, Mads U. Werner
Physiology Faculty Publications
Following the resolution of a severe inflammatory injury in rodents, administration of mu-opioid receptor inverse agonists leads to reinstatement of pain hypersensitivity. The mechanisms underlying this form of latent pain sensitization (LS) likely contribute to the development of chronic pain, but LS has not yet been demonstrated in humans. Using a C57BL/6 mouse model of cutaneous mild heat injury (MHI) we demonstrated a dose-dependent reinstatement of pain sensitization, assessed as primary (P < 0.001) and secondary hyperalgesia (P < 0.001) by naloxone (0.3–10 mg/kg), 168 hrs after the induction of MHI. Forward-translating the dose data to a human MHI model (n = 12) we could show that LS does indeed occur after naloxone 2 mg/kg, 168 hrs after a MHI. Our previous unsuccessful efforts to demonstrate unmasking of LS in humans are thus likely explained by an insufficient naloxone dose (0.021 mg/kg). However, while LS was consistently demonstrated in 21/24 mice, LS was only seen in 4/12 subjects. This difference is likely due to selection bias since the C57BL/6 mouse strain exhibits markedly enhanced pain sensitivity in assays of acute thermal nociception. Future exploratory studies in humans should prioritize inclusion of “high-sensitizers” prone to develop LS and use post-surgical models to elucidate markers of vulnerability to chronic postsurgical pain.
The 133-Kda N-Terminal Domain Enables Myosin 15 To Maintain Mechanotransducing Stereocilia And Is Essential For Hearing, Qing Fang, Artur A. Indzhykulian, Mirna Mustapha, Gavin P. Riordan, David F. Dolan, Thomas B. Friedman, Inna A. Belyantseva, Gregory I. Frolenkov, Sally A. Camper, Jonathan E. Bird
The 133-Kda N-Terminal Domain Enables Myosin 15 To Maintain Mechanotransducing Stereocilia And Is Essential For Hearing, Qing Fang, Artur A. Indzhykulian, Mirna Mustapha, Gavin P. Riordan, David F. Dolan, Thomas B. Friedman, Inna A. Belyantseva, Gregory I. Frolenkov, Sally A. Camper, Jonathan E. Bird
Physiology Faculty Publications
The precise assembly of inner ear hair cell stereocilia into rows of increasing height is critical for mechanotransduction and the sense of hearing. Yet, how the lengths of actin-based stereocilia are regulated remains poorly understood. Mutations of the molecular motor myosin 15 stunt stereocilia growth and cause deafness. We found that hair cells express two isoforms of myosin 15 that differ by inclusion of an 133-kDa N-terminal domain, and that these isoforms can selectively traffic to different stereocilia rows. Using an isoform-specific knockout mouse, we show that hair cells expressing only the small isoform remarkably develop normal stereocilia bundles. However, …
Serum Amyloid A Facilitates Early Lesion Development In Ldlr-/- Mice, Paulette A. Krishack, Clarissa V. Bhanvadia, John Lukens, Timothy J. Sontag, Maria C. De Beer, Godfrey S. Getz, Catherine A. Reardon
Serum Amyloid A Facilitates Early Lesion Development In Ldlr-/- Mice, Paulette A. Krishack, Clarissa V. Bhanvadia, John Lukens, Timothy J. Sontag, Maria C. De Beer, Godfrey S. Getz, Catherine A. Reardon
Physiology Faculty Publications
BACKGROUND: Atherosclerosis is a chronic inflammatory disorder, and several studies have demonstrated a positive association between plasma serum amyloid A (SAA) levels and cardiovascular disease risk. The aim of the study was to examine whether SAA has a role in atherogenesis, the underlying basis of most cardiovascular disease.
METHODS AND RESULTS: Mice globally deficient in acute-phase isoforms Saa1 and Saa2 (Saa-/-) were crossed to Ldlr-/- mice (Saa-/-Ldlr-/-). Saa-/-Ldlr-/- mice demonstrated a 31% reduction in lesional area in the ascending aorta but not in the aortic root or innominate …
Myocyte Contractility Can Be Maintained By Storing Cells With The Myosin Atpase Inhibitor 2,3 Butanedione Monoxime, Charles S. Chung, Charles Mechas, Kenneth S. Campbell
Myocyte Contractility Can Be Maintained By Storing Cells With The Myosin Atpase Inhibitor 2,3 Butanedione Monoxime, Charles S. Chung, Charles Mechas, Kenneth S. Campbell
Physiology Faculty Publications
Isolated intact myocytes can be used to investigate contractile mechanisms and to screen new therapeutic compounds. These experiments typically require euthanizing an animal and isolating fresh cells each day or analyzing cultured myocytes, which quickly lose their rod-shaped morphology. Recent data suggest that the viability of canine myocytes can be prolonged using low temperature and N-benzyl-p-toluene sulfonamide (an inhibitor of skeletal myosin ATPase). We performed similar studies in rat myocytes in order to test whether the cardiac myosin ATPase inhibitors 2,3-Butanedione monoxime (BDM) and blebbistatin help to maintain cell-level function over multiple days. Myocytes were isolated from rats and separated …
Macrophage Migration Inhibitory Factor Mediates Par-Induced Bladder Pain., Dimitrios E. Kouzoukas, Katherine L. Meyer-Siegler, Fei Ma, Karin N. Westlund, David E. Hunt, Pedro L. Vera
Macrophage Migration Inhibitory Factor Mediates Par-Induced Bladder Pain., Dimitrios E. Kouzoukas, Katherine L. Meyer-Siegler, Fei Ma, Karin N. Westlund, David E. Hunt, Pedro L. Vera
Physiology Faculty Publications
INTRODUCTION: Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is constitutively expressed in urothelial cells that also express protease-activated receptors (PAR). Urothelial PAR1 receptors were shown to mediate bladder inflammation. We showed that PAR1 and PAR4 activator, thrombin, also mediates urothelial MIF release. We hypothesized that stimulation of urothelial PAR1 or PAR4 receptors elicits release of urothelial MIF that acts on MIF receptors in the urothelium to mediate bladder inflammation and pain. Thus, we examined the effect of activation of specific bladder PAR receptors on MIF release, bladder pain, micturition and histological changes.
METHODS: MIF release was measured …
Bacterial Symbionts, Buchnera, And Starvation On Wing Dimorphism In English Grain Aphid, Sitobion Avenae (F.) (Homoptera: Aphididae), Fangmei Zhang, Xiangrui Li, Yunhui Zhang, Brad Coates, Xuguo Joe Zhou, Dengfa Cheng
Bacterial Symbionts, Buchnera, And Starvation On Wing Dimorphism In English Grain Aphid, Sitobion Avenae (F.) (Homoptera: Aphididae), Fangmei Zhang, Xiangrui Li, Yunhui Zhang, Brad Coates, Xuguo Joe Zhou, Dengfa Cheng
Entomology Faculty Publications
Wing dimorphism in aphids can be affected by multiple cues, including both biotic (nutrition, crowding, interspecific interactions, the presence of natural enemies, maternal and transgenerational effects, and alarm pheromone) and abiotic factors (temperature, humidity, and photoperiod). The majority of the phloem-feeding aphids carry Buchnera, an obligate symbiotic proteobacteria. Buchnera has a highly reduced genome size, but encode key enzymes in the tryptophan biosynthetic pathway and is crucial for nutritional balance, development and reproduction in aphids. In this study, we investigated the impact of two nutritional-based biotic factors, symbionts and starvation, on the wing dimorphism in the English grain aphid, …
The Endogenous Molecular Clock Orchestrates The Temporal Separation Of Substrate Metabolism In Skeletal Muscle, Brian A. Hodge, Yuan Wen, Lance A. Riley, Xiping Zhang, Jonathan H. England, Brianna D. Harfmann, Elizabeth A. Schroder, Karyn A. Esser
The Endogenous Molecular Clock Orchestrates The Temporal Separation Of Substrate Metabolism In Skeletal Muscle, Brian A. Hodge, Yuan Wen, Lance A. Riley, Xiping Zhang, Jonathan H. England, Brianna D. Harfmann, Elizabeth A. Schroder, Karyn A. Esser
Physiology Faculty Publications
BACKGROUND: Skeletal muscle is a major contributor to whole-body metabolism as it serves as a depot for both glucose and amino acids, and is a highly metabolically active tissue. Within skeletal muscle exists an intrinsic molecular clock mechanism that regulates the timing of physiological processes. A key function of the clock is to regulate the timing of metabolic processes to anticipate time of day changes in environmental conditions. The purpose of this study was to identify metabolic genes that are expressed in a circadian manner and determine if these genes are regulated downstream of the intrinsic molecular clock by …
Proteomic Analysis Of Media From Lung Cancer Cells Reveals Role Of 14-3-3 Proteins In Cachexia, Julie B. Mclean, Jennifer S. Moylan, Erin M. Wolf Horrell, Francisco H. Andrade
Proteomic Analysis Of Media From Lung Cancer Cells Reveals Role Of 14-3-3 Proteins In Cachexia, Julie B. Mclean, Jennifer S. Moylan, Erin M. Wolf Horrell, Francisco H. Andrade
Physiology Faculty Publications
Aims: At the time of diagnosis, 60% of lung cancer patients present with cachexia, a severe wasting syndrome that increases morbidity and mortality. Tumors secrete multiple factors that contribute to cachectic muscle wasting, and not all of these factors have been identified. We used Orbitrap electrospray ionization mass spectrometry to identify novel cachexia-inducing candidates in media conditioned with Lewis lung carcinoma cells (LCM).
Results: One-hundred and 58 proteins were confirmed in three biological replicates. Thirty-three were identified as secreted proteins, including 14-3-3 proteins, which are highly conserved adaptor proteins known to have over 200 binding partners. We confirmed the …
Enhanced Nmda Receptor-Mediated Modulation Of Excitatory Neurotransmission In The Dorsal Vagal Complex Of Streptozotocin-Treated, Chronically Hyperglycemic Mice, Eva C. Bach, Katalin Cs. Halmos, Bret N. Smith
Enhanced Nmda Receptor-Mediated Modulation Of Excitatory Neurotransmission In The Dorsal Vagal Complex Of Streptozotocin-Treated, Chronically Hyperglycemic Mice, Eva C. Bach, Katalin Cs. Halmos, Bret N. Smith
Physiology Faculty Publications
A variety of metabolic disorders, including complications experienced by diabetic patients, have been linked to altered neural activity in the dorsal vagal complex. This study tested the hypothesis that augmentation of N-Methyl-D-Aspartate (NMDA) receptor-mediated responses in the vagal complex contributes to increased glutamate release in the dorsal motor nucleus of the vagus nerve (DMV) in mice with streptozotocin-induced chronic hyperglycemia (i.e., hyperglycemic mice), a model of type 1 diabetes. Antagonism of NMDA receptors with AP-5 (100 μM) suppressed sEPSC frequency in vagal motor neurons recorded in vitro, confirming that constitutively active NMDA receptors regulate glutamate release in the DMV. There …
Determining The Role Of Il-4 Induced Neuroinflammation In Microglial Activity And Amyloid-Ss Using Bv2 Microglial Cells And App/Ps1 Transgenic Mice, Clare H. Latta, Tiffany L. Sudduth, Erica M. Weekman, Holly M. Brothers, Erin L. Abner, Gabriel J. Popa, Michael D. Mendenhall, Floracita Gonzalez-Oregon, Kaitlyn Braun, Donna M. Wilcock
Determining The Role Of Il-4 Induced Neuroinflammation In Microglial Activity And Amyloid-Ss Using Bv2 Microglial Cells And App/Ps1 Transgenic Mice, Clare H. Latta, Tiffany L. Sudduth, Erica M. Weekman, Holly M. Brothers, Erin L. Abner, Gabriel J. Popa, Michael D. Mendenhall, Floracita Gonzalez-Oregon, Kaitlyn Braun, Donna M. Wilcock
Physiology Faculty Publications
Background
Microglia are considered the resident immune cells of the central nervous system (CNS). In response to harmful stimuli, an inflammatory reaction ensues in which microglia are activated in a sequenced spectrum of pro- and antiinflammatory phenotypes that are akin to the well-characterized polarization states of peripheral macrophages. A “classically” activated M1 phenotype is known to eradicate toxicity. The transition to an “alternatively” activated M2 phenotype encompasses neuroprotection and repair. In recent years, inflammation has been considered an accompanying pathology in response to the accumulation of extracellular amyloid-β (Aβ) in Alzheimer’s disease (AD). This study aimed to drive an M2a-biased …
Smooth-Muscle Bmal1 Participates In Blood Pressure Circadian Rhythm Regulation, Zhongwen Xie, Wen Su, Shu Liu, Guogang Zhao, Karyn Esser, Elizabeth A. Schroder, Mellani Lefta, Harald M. Stauss, Zhenheng Guo, Ming Cui Gong
Smooth-Muscle Bmal1 Participates In Blood Pressure Circadian Rhythm Regulation, Zhongwen Xie, Wen Su, Shu Liu, Guogang Zhao, Karyn Esser, Elizabeth A. Schroder, Mellani Lefta, Harald M. Stauss, Zhenheng Guo, Ming Cui Gong
Physiology Faculty Publications
As the central pacemaker, the suprachiasmatic nucleus (SCN) has long been considered the primary regulator of blood pressure circadian rhythm; however, this dogma has been challenged by the discovery that each of the clock genes present in the SCN is also expressed and functions in peripheral tissues. The involvement and contribution of these peripheral clock genes in the circadian rhythm of blood pressure remains uncertain. Here, we demonstrate that selective deletion of the circadian clock transcriptional activator aryl hydrocarbon receptor nuclear translocator-like (Bmal1) from smooth muscle, but not from cardiomyocytes, compromised blood pressure circadian rhythm and decreased blood …
The Effects Of Spinal Manipulative Therapy On Isokinetic Strength And Postactivation Potentiation, Grant D. Sanders
The Effects Of Spinal Manipulative Therapy On Isokinetic Strength And Postactivation Potentiation, Grant D. Sanders
Theses and Dissertations--Kinesiology and Health Promotion
Spinal manipulative therapy (SMT) is a therapeutic procedure employed by various healthcare practitioners for alleviating acute and chronic musculoskeletal complaints. This form of treatment is also delivered to enhance the performance and augment the rehabilitation of athletes. However, despite research findings alleging the strength-modulating effects of SMT alongside numerous professional athletes’ positive anecdotal claims concerning its results, the physiological processes to explain its effects remain largely unexplained. Therefore, the purpose of this work was to investigate the effects of SMT in a college-aged sample population with two experiments.
The first study examined the effect of SMT targeting the lumbosacral region …