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Magneto-Electric Nano-Particles For Non-Invasive Brain Stimulation, Kun Yue, Rakesh Guduru, Jeongmin Hong, Ping Liang, Madhavan Nair, Sakhrat Khizroev 2012 Center for Nanomedicine, College of Engineering and Computing, Florida International University, Miami, Florida

Magneto-Electric Nano-Particles For Non-Invasive Brain Stimulation, Kun Yue, Rakesh Guduru, Jeongmin Hong, Ping Liang, Madhavan Nair, Sakhrat Khizroev

HWCOM Faculty Publications

This paper for the first time discusses a computational study of using magneto-electric (ME) nanoparticles to artificially stimulate the neural activity deep in the brain. The new technology provides a unique way to couple electric signals in the neural network to the magnetic dipoles in the nanoparticles with the purpose to enable a non-invasive approach. Simulations of the effect of ME nanoparticles for non-invasively stimulating the brain of a patient with Parkinson’s Disease to bring the pulsed sequences of the electric field to the levels comparable to those of healthy people show that the optimized values for the concentration ...


Exogenous Alpha-Synuclein Induces Cell Death Related Proteins In C6 Oligodendrocyte-Like Cells Corresponding To Protein Expression Observed In Multiple System Atrophy, Derrick Samuel Hilton 2012 Western Michigan University

Exogenous Alpha-Synuclein Induces Cell Death Related Proteins In C6 Oligodendrocyte-Like Cells Corresponding To Protein Expression Observed In Multiple System Atrophy, Derrick Samuel Hilton

Dissertations

Multiple System Atrophy (MSA) consists of three disorders; Autonomic Dysfunction, Cerebellar Ataxia, and Parkinsonism. In MSA, the protein Alpha-Synuclein (SNCA) appears in the central nervous system as misfolded protein aggregates primarily in oligodendrocytes. This dissertation reports the results from studies examining the effect of exogenous SNCA has on a cell model: C6 oligodendrocyte-like cells. Treated cells were evaluated using western blot and DNA microarray. In addition the expression of proteins was evaluated using immunocytochemistry in MSA patient tissue.

C6 cells were shown to take up SNCA when added to the media. SNCA also underwent a truncation when taken up by ...


Long-Term Cardiac Rhythm And Repolarization Abnormalities In Refractory Focal And Generalized Epilepsy, maromi nei 2012 Jefferson Medical College

Long-Term Cardiac Rhythm And Repolarization Abnormalities In Refractory Focal And Generalized Epilepsy, Maromi Nei

maromi nei

This prospective study evaluated 19 individuals with refractory focal or generalized epilepsy utilizing an implantable cardiac loop recorder. Recording averaged 15 months (range 12–19 months) in 18 patients and 1.5 months in one patient. A median of 37 seizures per patient (range 3–657) occurred, with 1,477 seizures total. Cardiac arrhythmias and repolarization abnormalities occurred frequently (in 42% of patients) in refractory epilepsy, particularly during generalized tonic–clonic and tonic seizures. Patients with Lennox-Gastaut syndrome may be at high risk for cardiac abnormalities.


Therapeutic Silencing Of Mutant Huntingtin By Targeting Single Nucleotide Polymorphisms: A Dissertation, Edith L. Pfister 2012 University of Massachusetts Medical School

Therapeutic Silencing Of Mutant Huntingtin By Targeting Single Nucleotide Polymorphisms: A Dissertation, Edith L. Pfister

GSBS Dissertations and Theses

Huntington’s disease (HD) is an autosomal dominant, progressive neurodegenerative disorder. Invariably fatal, HD is caused by expansion of the CAG repeat region in exon 1 of the Huntingtin gene which creates a toxic protein with an extended polyglutamine tract 1. Silencing mutant Huntingtin messenger RNA (mRNA) is a promising therapeutic approach 2-6. The ideal silencing strategy would reduce mutant Huntingtin while leaving the wild-type mRNA intact. Unfortunately, targeting the disease causing CAG repeat expansion is difficult and risks targeting other CAG repeat containing genes.

We examined an alternative strategy, targeting single nucleotide polymorphisms (SNPs) in the Huntingtin mRNA. The ...


Genetic Determinants Of Cerebral Edema In Severe Traumatic Brain Injury: A Pilot Study Of The Role Of Cacna1 And Aqp4 Gene Mutations, Raphael A. Carandang, Susanne Muehlschlegel, Wiley R. Hall, Cynthia Ouillette, Robert H. Brown Jr. 2012 University of Massachusetts Medical School

Genetic Determinants Of Cerebral Edema In Severe Traumatic Brain Injury: A Pilot Study Of The Role Of Cacna1 And Aqp4 Gene Mutations, Raphael A. Carandang, Susanne Muehlschlegel, Wiley R. Hall, Cynthia Ouillette, Robert H. Brown Jr.

UMass Center for Clinical and Translational Science Research Retreat

Cerebral edema is the one of the most significant predictors of poor outcome after traumatic brain injury. It is still unclear what the pathophysiological and cellular mechanisms and predictors of post-traumatic edema are. The exponential growth in genetic information has opened an avenue for investigation in traumatic brain injury and implicated specific genes in the pathophysiology of post-traumatic injury edema. Two examples are the Aquaporin-4 and CACNA1 genes, which respectively encode water and calcium channels. The Aquaporin-4 gene on chromosome 18q11.2-12.1 encodes the Aquaporin-4 protein (AQP4) water channel. AQP4 is one of the bidirectional high capacity water channels ...


Occult Cervical Spinal Dural Arteriovenous Fistula Masquerading As Acute Spinal Cord Ischemia, Saef Izzy, Bilal Hameed, Chutima Saipetch, Eugene Lin, David Paydarfar 2012 University of Massachusetts Medical School

Occult Cervical Spinal Dural Arteriovenous Fistula Masquerading As Acute Spinal Cord Ischemia, Saef Izzy, Bilal Hameed, Chutima Saipetch, Eugene Lin, David Paydarfar

UMass Center for Clinical and Translational Science Research Retreat

Acute presentation of upper and lower extremity motor weakness is commonly attributed to intracerebral ischemic infarct upon initial examination. For those that exhibit acute onset of bilateral weakness, it is important to expand the differential diagnosis to include spinal cord ischemic involvement. One cause of ischemic lesions is spinal dural arteriovenous (AV) fistulas which are generally found in the thoraco-lumbar region. They present with progressive paraplegia or quadriplegia due to changes in the spinal venous pressure and eventual myelopathy. We present a 60 year old gentleman with bilateral upper extremity weakness and right lower extremity weakness preceded by upper back ...


Incidence Rates Of Icu Complications In Moderate-Severe Traumatic Brain Injury (Tbi), Susanne Muehlschlegel, Raphael A. Carandang, Cynthia Ouillette, Wiley R. Hall, Frederick A. Anderson Jr., Robert J. Goldberg 2012 University of Massachusetts Medical School

Incidence Rates Of Icu Complications In Moderate-Severe Traumatic Brain Injury (Tbi), Susanne Muehlschlegel, Raphael A. Carandang, Cynthia Ouillette, Wiley R. Hall, Frederick A. Anderson Jr., Robert J. Goldberg

UMass Center for Clinical and Translational Science Research Retreat

Retrospective studies suggest that non-neurologic organ failure may contribute to 2/3 of all deaths after TBI, but the actual incidence rates of specific intensive care unit (ICU) complications in moderate-severe TBI are not known. In a prospective observational cohort study of consecutive TBI patients from a single Level I trauma center (UMASS) over the period 11/2009 – 2/2012, we identified the ten most common medical complications after ICU admission according to strict pre-specified criteria in 170 moderate-severe TBI patients. The mean age of the study sample was 51 years, 72% were men, and the median GCS and injury ...


Impact Of Medical And Neurological Icu Complications On Moderate-Severe Traumatic Brain Injury (Tbi), Susanne Muehlschlegel, Raphael A. Carandang, Cynthia Ouillette, Wiley R. Hall, Frederick A. Anderson Jr., Robert J. Goldberg 2012 University of Massachusetts Medical School

Impact Of Medical And Neurological Icu Complications On Moderate-Severe Traumatic Brain Injury (Tbi), Susanne Muehlschlegel, Raphael A. Carandang, Cynthia Ouillette, Wiley R. Hall, Frederick A. Anderson Jr., Robert J. Goldberg

UMass Center for Clinical and Translational Science Research Retreat

Certain admission characteristics are known predictors of adverse outcomes in patients with moderate-severe TBI, but explain only 1/3 of outcome variability. Intensive care unit (ICU) complications occur frequently in this population, but their impact on patient outcomes remains poorly defined. In a prospective observational cohort study of 170 consecutive moderate-severe TBI patients admitted to Level I trauma center (UMASS) over the period 11/2009–2/2012, we examined the association of ICU complications and 3-month outcome (Glasgow Outcome Scale [GOS]). The mean age was 51 years, 72% were men, and the median GCS and injury severity scores were 4 ...


C. Elegans Pat-9 Is A Nuclear Zinc Finger Protein Critical For The Assembly Of Muscle Attachments, Qian Liu, Takako I. Jones, Rebecca A. Bachmann, Mitchell Meghpara, Lauren Rogowski, Benjamin D. Williams, Peter L. Jones 2012 University of Illinois at Urbana-Champaign

C. Elegans Pat-9 Is A Nuclear Zinc Finger Protein Critical For The Assembly Of Muscle Attachments, Qian Liu, Takako I. Jones, Rebecca A. Bachmann, Mitchell Meghpara, Lauren Rogowski, Benjamin D. Williams, Peter L. Jones

Peter Jones Lab Publications

BACKGROUND: Caenorhabditis elegans sarcomeres have been studied extensively utilizing both forward and reverse genetic techniques to provide insight into muscle development and the mechanisms behind muscle contraction. A previous genetic screen investigating early muscle development produced 13 independent mutant genes exhibiting a Pat (paralyzed and arrested elongation at the two-fold length of embryonic development) muscle phenotype. This study reports the identification and characterization of one of those genes, pat-9.

RESULTS: Positional cloning, reverse genetics, and plasmid rescue experiments were used to identify the predicted C. elegans gene T27B1.2 (recently named ztf-19) as the pat-9 gene. Analysis of pat-9 showed ...


Improved Techniques For Acquisition And Analysis Of Dynamic Contrast-Enhanced Magnetic Resonance Imaging For Detecting Vascular Permeability In The Central Nervous System, Cheukkai Hui 2012 The University of Texas Graduate School of Biomedical Sciences at Houston

Improved Techniques For Acquisition And Analysis Of Dynamic Contrast-Enhanced Magnetic Resonance Imaging For Detecting Vascular Permeability In The Central Nervous System, Cheukkai Hui

UT GSBS Dissertations and Theses (Open Access)

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive technique for quantitative assessment of the integrity of blood-brain barrier and blood-spinal cord barrier (BSCB) in the presence of central nervous system pathologies. However, the results of DCE-MRI show substantial variability. The high variability can be caused by a number of factors including inaccurate T1 estimation, insufficient temporal resolution and poor contrast-to-noise ratio. My thesis work is to develop improved methods to reduce the variability of DCE-MRI results. To obtain fast and accurate T1 map, the Look-Locker acquisition technique was implemented with a novel and truly centric k-space segmentation scheme. In ...


Novel Use Of Dual Anti-Inflammatory Therapy To Overcome Drug Resistance And Improve Functional Recovery Following Spinal Cord Injury, Jennifer Dulin 2012 The University of Texas Graduate School of Biomedical Sciences at Houston

Novel Use Of Dual Anti-Inflammatory Therapy To Overcome Drug Resistance And Improve Functional Recovery Following Spinal Cord Injury, Jennifer Dulin

UT GSBS Dissertations and Theses (Open Access)

Over 1.2 million Americans are currently living with a traumatic spinal cord injury (SCI). Despite the need for effective therapies, there are currently no proven effective treatments that can improve recovery of function in SCI patients. Many therapeutic compounds have shown promise in preclinical models of SCI, but all of these have fallen short in clinical trials.

P-glycoprotein (Pgp) is an active transporter expressed on capillary endothelial cell membranes at the blood-spinal cord barrier (BSCB). Pgp limits passive diffusion of blood-borne drugs into the CNS, by actively extruding drugs from the endothelial cell membrane. Pgp can become pathologically up-regulated ...


Development Of A Microfluidic Device Coupled To Microdialysis Sampling For The Pre-Concentration Of Cytokines, Randy Francisco Espinal Cabrera 2012 University of Arkansas, Fayetteville

Development Of A Microfluidic Device Coupled To Microdialysis Sampling For The Pre-Concentration Of Cytokines, Randy Francisco Espinal Cabrera

Theses and Dissertations

A proof-of-concept microfluidic device combined with heparin-immobilized magnetic beads was created to concentrate cytokine proteins collected from microdialysis samples. Cytokines are known to be related to several diseases such as cancer, and Parkinson's diseases, so to be able to develop more effective diseases treatments their interactions have to be well understood. Amine-functionalized polystyrene and carboxyl-functionalized magnetic microspheres of ~6.0 ìm in diameter were used to immobilize heparin. The amount of heparin immobilized on polystyrene beads was 5.82 x 10-8 ± 0.36 x 10-8 M per 1.0 x 106 beads and for magnetic beads was 0.64 ...


Er-Localized Lull1 Function Is Required For The Abnormal Inm Concentration Of Disease-Related Delta-E Torsina, Kristen Nicole Holbrook 2012 University of Tennessee, Knoxville

Er-Localized Lull1 Function Is Required For The Abnormal Inm Concentration Of Disease-Related Delta-E Torsina, Kristen Nicole Holbrook

Masters Theses

DYT1 dystonia is an autosomal dominant neurological disease caused by a single amino acid deletion in the protein torsinA, resulting in expression of a mutant ΔE [delta E] torsinA isoform in DYT1 patients. Research has consistently found ΔE [delta E] torsinA abnormally concentrated in the nuclear envelope (NE) lumen of the endoplasmic reticulum (ER), and this has led to the hypothesis NE accumulation of ΔE [delta E] torsinA may underlie disease pathogenesis.

We first investigated where and how ΔE [delta E] NE accumulation occurs. We found that ΔE [delta E] torsinA accumulates at the inner nuclear membrane (INM) NE subdomain ...


Parkinson’S Disease: Molecular Mechanisms And Treatments, Delia Vahey 2012 Liberty University

Parkinson’S Disease: Molecular Mechanisms And Treatments, Delia Vahey

Senior Honors Theses

Parkinson’s disease is a motor system disorder that is caused primarily by the loss of dopamine-producing brain cells. The most affected brain structure is the pars compacta of the substantia nigra. This area of the brain is essential to the control of voluntary movement, and so its impairment leads to symptoms such as tremors, rigidity, and impaired balance. The neuronal protein alpha-synuclein has been shown to be heavily involved in the pathogenesis of the disease at the cellular level. The currently available treatments for PD mainly target dopamine regulation, and there been no cure developed for the disease at ...


Biotinidase Deficiency In Pakistani Children; What Needs To Be Known And Done, Bushra Afroze, Mohammad Wasay 2012 Aga Khan University

Biotinidase Deficiency In Pakistani Children; What Needs To Be Known And Done, Bushra Afroze, Mohammad Wasay

Department of Medicine

No abstract provided.


Microrna-Regulated, Systemically Delivered Raav9: A Step Closer To Cns-Restricted Transgene Expression, Jun Xie, Qing Xie, Hongwei Zhang, Stefan L. Ameres, Jui-Hung Hung, Qin Su, Ran He, Xin Mu, Seemin Seher Ahmed, Soyeon Park, Hiroki Kato, Chengjian Li, Christian Mueller, Craig C. Mello, Zhiping Weng, Terence R. Flotte, Phillip D. Zamore, Guangping Gao 2012 University of Massachusetts Medical School

Microrna-Regulated, Systemically Delivered Raav9: A Step Closer To Cns-Restricted Transgene Expression, Jun Xie, Qing Xie, Hongwei Zhang, Stefan L. Ameres, Jui-Hung Hung, Qin Su, Ran He, Xin Mu, Seemin Seher Ahmed, Soyeon Park, Hiroki Kato, Chengjian Li, Christian Mueller, Craig C. Mello, Zhiping Weng, Terence R. Flotte, Phillip D. Zamore, Guangping Gao

Christian Mueller

Recombinant adeno-associated viruses (rAAVs) that can cross the blood-brain-barrier and achieve efficient and stable transvascular gene transfer to the central nervous system (CNS) hold significant promise for treating CNS disorders. However, following intravascular delivery, these vectors also target liver, heart, skeletal muscle, and other tissues, which may cause untoward effects. To circumvent this, we used tissue-specific, endogenous microRNAs (miRNAs) to repress rAAV expression outside the CNS, by engineering perfectly complementary miRNA-binding sites into the rAAV9 genome. This approach allowed simultaneous multi-tissue regulation and CNS-directed stable transgene expression without detectably perturbing the endogenous miRNA pathway. Regulation of rAAV expression by miRNA ...


Autophagy And Apoptotic Genes Implicated In Alzheimer’S Disease Are Modulated Following Infection Of Neuronal Cells With Chlamydia Pneumoniae, Denah M. Appelt, Ian Kohler, Annette K. Slutter, Juliana Zoga, Susan T. Hingley, Brian J. Balin 2012 Philadelphia College of Osteopathic Medicine

Autophagy And Apoptotic Genes Implicated In Alzheimer’S Disease Are Modulated Following Infection Of Neuronal Cells With Chlamydia Pneumoniae, Denah M. Appelt, Ian Kohler, Annette K. Slutter, Juliana Zoga, Susan T. Hingley, Brian J. Balin

Scholarly Posters

Background: The focus of the current studies was to determine the relationship between the molecular mechanisms interconnecting autophagy and apoptosis following Chlamydia pneumoniae infection in neuronal cells. Dysfunctions in apoptosis and autophagy have been implicated in the neurodegeneration associated with Alzheimer’s disease (AD). Autophagy in AD pathogenesis has been shown to play a role in amyloid processing through the endosomal-lysosomal system. Apoptosis may contribute to the neuronal cell loss observed in AD; however, there is limited evidence of the apoptotic process proceeding to terminal completion. Although Aβ1-42 has been shown to induce apoptosis in neurons and may be an ...


The Cellular Nucleic Acid Binding Protein Regulates The Alzheimer’S Disease Β-Secretase Protein Bace1, Christopher J. Holler 2012 University of Kentucky

The Cellular Nucleic Acid Binding Protein Regulates The Alzheimer’S Disease Β-Secretase Protein Bace1, Christopher J. Holler

Theses and Dissertations--Molecular and Cellular Biochemistry

Alzheimer’s disease (AD) is the most common neurodegenerative disease affecting the elderly population and is believed to be caused by the overproduction and accumulation of the toxic amyloid beta (Aβ) peptide in the brain. Aβ is produced by two separate enzymatic cleavage events of the larger membrane bound amyloid precursor protein, APP. The first, and rate-limiting, cleavage event is made by beta-secretase, or BACE1, and is thus an attractive therapeutic target. Our lab, as well as many others, has shown that BACE1 protein and activity are increased in late-stage sporadic AD. We have extended these findings to show that ...


Blast-Induced Brain Injury: Influence Of Shockwave Components, Dexter V. Reneer 2012 University of Kentucky

Blast-Induced Brain Injury: Influence Of Shockwave Components, Dexter V. Reneer

Theses and Dissertations--Neuroscience

Blast-induced traumatic brain injury (bTBI) has been described as the defining injury of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF). Previously, most blast injury research has focused on the effects of blast on internal, gas filled organs due to their increased susceptibility. However, due to a change in enemy tactics combined with better armor and front-line medical care, bTBI has become one of the most common injuries due to blast. Though there has been a significant amount of research characterizing the brain injury produced by blast, a sound understanding of the contribution of each component of the shockwave to ...


The Effect Of Load On Movement Coordination During Sled Towing, Michael Lawrence, Daniel Leib, Cara Masterson, Erin Hartigan 2012 University of New England

The Effect Of Load On Movement Coordination During Sled Towing, Michael Lawrence, Daniel Leib, Cara Masterson, Erin Hartigan

Daniel Leib

INTRODUCTION Towing sleds while walking is a popular resistance exercise for the healthy athlete. One reason for the popularity of sled towing is that it is widely believed to be a ‘functional’ exercise. Preliminary research suggests towing while walking can increases lower extremity moment impulses; however whether towing a sled utilizes the same coordination patterns as un-resisted walking is unknown. While altered patterns may not be as relevant to a healthy athlete, sled towing is also sometimes used in the rehabilitation of athletes who sustained a lower extremity injury (anterior cruciate ligament rupture) with the goal of regaining movement symmetry ...


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