Digital Commons Network^™

Transcranial Direct Current Stimulation (Tdcs) Improves Performance On Spelling And Word Detection Tasks, J. Kevin Wilson

Psychology ETDs

Deficits in written language involving spelling can have negative effects on a person’s education and occupation. Conventional spelling therapy is a time consuming and cost-prohibitive option, if even available, highlighting the need for improved methods for remediation. One possible way to address this need may be through the use of transcranial direct current stimulation (tDCS). This study sought to examine the effects of tDCS on performance during spelling, word detection, and facial recognition tasks. Active or sham tDCS was randomly assigned to typically functioning adults. The anode electrode was placed over Broca’s area (F7 in the 10/20 EEG system) and …

Credibility, Replicability, And Reproducibility In Simulation For Biomedicine And Clinical Applications In Neuroscience., Lealem Mulugeta, Andrew Drach, Ahmet Erdemir, C A Hunt, Marc Horner, Joy P. Ku, Jerry G Myers, Rajanikanth Vadigepalli, William W. Lytton

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Modeling and simulation in computational neuroscience is currently a research enterprise to better understand neural systems. It is not yet directly applicable to the problems of patients with brain disease. To be used for clinical applications, there must not only be considerable progress in the field but also a concerted effort to use best practices in order to demonstrate model credibility to regulatory bodies, to clinics and hospitals, to doctors, and to patients. In doing this for neuroscience, we can learn lessons from long-standing practices in other areas of simulation (aircraft, computer chips), from software engineering, and from other biomedical …

Development Of A Positron-Emitting Surrogate Microsphere For Image-Based Dosimetry In Yttrium-90 Radioembolization Therapy, Gregory D. Chambers

Nuclear Engineering ETDs

Radioembolization of liver tumors using yttrium-90 (Y-90) labeled microspheres is a proven method of treatment. The primary decay mode of Y-90 is beta-minus decay. The electrons produced during decay deliver a cytotoxic radiation dose in a localized volume. The radiation dose is sufficient to kill tumor cells yet spare the normal liver. The Y-90 microspheres are delivered via a catheter that has been placed in an artery that supplies blood to the tumor. Microspheres are injected and the blood distributes the microspheres. The current practice involves two separate procedures. The first procedure is an assessment of the vasculature of the …

Regulation Of Nociceptive Glutamatergic Signaling By Presynaptic Kv3.4 Channels In The Rat Spinal Dorsal Horn., Tanziyah Muqeem, Biswarup Ghosh, Vitor Pinto, Angelo C. Lepore, Manuel Covarrubias

Farber Institute for Neuroscience Faculty Papers

Presynaptic voltage-gated K⁺ (Kv) channels in dorsal root ganglion (DRG) neurons are thought to regulate nociceptive synaptic transmission in the spinal dorsal horn. However, the Kv channel subtypes responsible for this critical role have not been identified. The Kv3.4 channel is particularly important because it is robustly expressed in DRG nociceptors, where it regulates action potential (AP) duration. Furthermore, Kv3.4 dysfunction is implicated in the pathophysiology of neuropathic pain in multiple pain models. We hypothesized that, through their ability to modulate AP repolarization, Kv3.4 channels in DRG nociceptors help to regulate nociceptive synaptic transmission. To test this hypothesis, we …

Puma Amplifies Necroptosis Signaling By Activating Cytosolic Dna Sensors., Dongshi Chen, Jingshan Tong, Liheng Yang, Liang Wei, Donna B. Stolz, Jian Yu, Jianke Zhang, Lin Zhang

Department of Microbiology and Immunology Faculty Papers

Necroptosis, a form of regulated necrotic cell death, is governed by RIP1/RIP3-mediated activation of MLKL. However, the signaling process leading to necroptotic death remains to be elucidated. In this study, we found that PUMA, a proapoptotic BH3-only Bcl-2 family member, is transcriptionally activated in an RIP3/MLKL-dependent manner following induction of necroptosis. The induction of PUMA, which is mediated by autocrine TNF-α and enhanced NF-κB activity, contributes to necroptotic death in RIP3-expressing cells with caspases inhibited. On induction, PUMA promotes the cytosolic release of mitochondrial DNA and activation of the DNA sensors DAI/Zbp1 and STING, leading to enhanced RIP3 and MLKL …

Optimizing Vaccine Immunotherapy For Prostate Cancer, G. Hattier, E. K. Bongiorno, C. Portocarrero, Trevor R. Baybutt, Adam E. Snook, U. Rodeck

Sigma Xi Student Research Day

Introduction: Treatment options for metastatic prostate cancer are limited and cures are rare. In other cancers immunotherapy has shown remarkable efficacy in certain patient subsets particularly when combined with other treatment modalities. Our previous work showed that combining radiation and vaccine therapy slows the growth of syngeneic prostate cancer in mice more effectively than single modality treatment arms. Here we tested the hypothesis that addition of immune checkpoint inhibitors targeting the PD1/PD-L1 axis further improves efficacy of the dual radiation/vaccine treatment.

Methods: Mice were injected with tumor cells expressing human prostate specific antigen (TPSA-23). The mice were divided into six …

Multiple Sclerosis Identification Based On Fractional Fourier Entropy And A Modified Jaya Algorithm, Shui-Hua Wang, Hong Cheng, Preetha Phillips, Yu-Dong Zhang

Publications and Research

Aim: Currently, identifying multiple sclerosis (MS) by human experts may come across the problem of “normal-appearing white matter”, which causes a low sensitivity. Methods: In this study, we presented a computer vision based approached to identify MS in an automatic way. This proposed method first extracted the fractional Fourier entropy map from a specified brain image. Afterwards, it sent the features to a multilayer perceptron trained by a proposed improved parameter-free Jaya algorithm. We used cost-sensitivity learning to handle the imbalanced data problem. Results: The 10 × 10-fold cross validation showed our method yielded a sensitivity of 97.40 ± 0.60%, …

Inhibition Of Dna Methyltransferase Leads To Increased Genomic 5-Hydroxymethylcytosine Levels In Hematopoietic Cells., Borbála Vető, Pál Szabó, Caroline Bacquet, Anna Apró, Edit Hathy, Judit Kiss, János M. Réthelyi, Flóra Szeri, Dávid Szüts, Tamás Arányi

Department of Dermatology and Cutaneous Biology Faculty Papers

5-Hydroxymethylcytosine (5hmC) is produced from 5-methylcytosine (5mC) by Ten-eleven translocation (TET) dioxygenases. The epigenetic modification 5hmC has crucial roles in both cellular development and differentiation. The 5hmC level is particularly high in the brain. While 5mC is generally associated with gene silencing/reduced expression, 5hmC is a more permissive epigenetic mark. To understand its physiological function, an easy and accurate quantification method is required. Here, we have developed a novel LC-MS/MS-based approach to quantify both genomic 5mC and 5hmC contents. The method is based on the liberation of nucleobases by formic acid. Applying this method, we characterized the levels of DNA …

A Closer Look At The Global Management Of Spina Bifida: The Implementation Of Endoscopic Third Ventriculostomy In The Treatment Of Spina Bifida-Related Hydrocephalus In Africa, Caryssa Burckart

Senior Honors Theses

Spina bifida, specifically myelomeningocele, is a debilitating neural tube defect that affects patients and families throughout the world. Traditional management and treatment methods are described, followed by an explanation of why this is often inadequate in providing care for those in impoverished areas of the world, including many regions of Africa. Endoscopic third ventriculostomy is proposed as a promising alternative to traditional methods for treating hydrocephalus, an often associated condition, and the implementation of this treatment method in Africa is explored. In order to relieve Africa of the burden of spina bifida-related hydrocephalus and improve global management of spina bifida, …

Sling Complications, David L. Howard, Andrea Mcglynn, Joy A. Greer

Research Briefs

No abstract provided.

Chemiluminescent Agents For In Vivo Imaging, Jian Cao

Chemistry Theses and Dissertations

Chemiluminescence is the light production directly from a highly exothermic chemical reaction by generating electronically excited species, and the light will be generated upon relaxation to the ground state. We utilize this light as the readout to construct imaging agents for reactive species. Chemiluminescence as an imaging modality has many advantages compared with current widely used imaging modalities, such as fluorescence and bioluminescence. The main advantages are the elimination of extraneous light excitation or genetic modification, which are required for fluorescence and bioluminescence imaging. Therefore, chemiluminescence as a imaging modality holds great potential for in vivo imaging.

In this dissertation, …

Limited Immune Surveillance In Lymphoid Tissue By Cytolytic Cd4+ T Cells During Health And Hiv Disease., Marcus Buggert, Son Nguyen, Laura M. Mclane, Maria Steblyanko, Nadia Anikeeva, Dominic Paquin-Proulx, Perla M Del Rio Estrada, Yuria Ablanedo-Terrazas, Kajsa Noyan, Morgan A. Reuter, Korey Demers, Johan K. Sandberg, Michael A. Eller, Hendrik Streeck, Marianne Jansson, Piotr Nowak, Anders Sönnerborg, David H. Canaday, Ali Naji, E. John Wherry, Merlin L. Robb, Steven G Deeks, Gustavo Reyes-Teran, Yuri Sykulev, Annika C. Karlsson, Michael R. Betts

Department of Medical Oncology Faculty Papers

CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cells expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and …

Recurrent Vulvar Carcinoma: Complex Surgical Treatment Via Perineal Excision And Reconstruction With Musculocutaneous Flap, Dragoș Popa, Cosmin V. Obleagă, Ștefan Paitici, Stelian Ș. Mogoanta, Ionică D. Vîlcea, Pouya Pourgolafshan, Cristian Gheorghe, Manuela I. Vasile, Raluca Câmpeanu, Cecil S. Mirea

Journal of Mind and Medical Sciences

Vulvar cancer is a malignant disease having a low frequency and with well-established surgical and oncological treatments based on the stage of the disease. The most important therapeutic problem encountered is represented by cases of perineal local regional recurrence, which are common in patients with large primary tumors and can occur even if the margins of the resection had no tumoral invasion.

We present a case study of a 64-year-old patient diagnosed one year ago with squamous vulvar carcinoma (G3) for which a vulvectomy was performed after neoadjuvant radiotherapy. The patient later developed local recurrence with invasion of the anal …

Expression Of Carbonic Anhydrase Iii, A Nucleus Pulposus Phenotypic Marker, Is Hypoxia-Responsive And Confers Protection From Oxidative Stress-Induced Cell Death., Elizabeth S. Silagi, Philip Batista, Irving Shapiro, Makarand V. Risbud

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

The integrity of the avascular nucleus pulposus (NP) phenotype plays a crucial role in the maintenance of intervertebral disc health. While advances have been made to define the molecular phenotype of healthy NP cells, the functional relevance of several of these markers remains unknown. In this study, we test the hypothesis that expression of Carbonic Anhydrase III (CAIII), a marker of the notochordal NP, is hypoxia-responsive and functions as a potent antioxidant without a significant contribution to pH homeostasis. NP, but not annulus fibrosus or end-plate cells, robustly expressed CAIII protein in skeletally mature animals. Although CAIII expression was hypoxia-inducible, …

Spsnet: Subpopulation-Sensitive Network-Based Analysis Of Heterogeneous Gene Expression Data., Abha Belorkar, Rajanikanth Vadigepalli, Limsoon Wong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Transcriptomic datasets often contain undeclared heterogeneity arising from biological variation such as diversity of disease subtypes, treatment subgroups, time-series gene expression, nested experimental conditions, as well as technical variation due to batch effects, platform differences in integrated meta-analyses, etc. However, current analysis approaches are primarily designed to handle comparisons between experimental conditions represented by homogeneous samples, thus precluding the discovery of underlying subphenotypes. Unsupervised methods for subtype identification are typically based on individual gene level analysis, which often result in irreproducible gene signatures for potential subtypes. Emerging methods to study heterogeneity have been largely developed in the context of …

Cortical Thinning And Neuropsychiatric Outcomes In Children Exposed To Prenatal Adversity: A Role For Placental Crh?, Curt A. Sandman, Megan M. Curran, Elyssia Poggi Davis, Laura M. Glynn, Kevin Head, Tallie Z. Baram

Psychology Faculty Articles and Research

Exposure to early life adversity may disrupt the development and maturation of neurons and brain circuits, which, in turn, underlie neurodevelopment and mental illnesses. During fetal life, maternal adversity is conveyed to the developing brain via several molecular signals, including the stress hormone corticotropin releasing hormone (CRH). Employing a large well characterized prospective cohort, we find that fetal exposure to placental-origin CRH levels predicts structural and functional brain outcomes in children. Specifically, elevated placental CRH levels portend thinning of selective cortical regions of exposed individuals, with commensurate cognitive and emotional deficits. Notably, the relations of placental-origin CRH to cortical thinning …

Surgeon Volume, David L. Howard, Andrea Mcglynn, Joy A. Greer

Research Briefs

No abstract provided.

Vmpfc Activation During A Stressor Predicts Positive Emotions During Stress Recovery, Xi Yang, Katelyn M. Garcia, Youngkyoo Jung, Christopher T. Whitlow, Kateri Mcrae, Christian E. Waugh

Psychology: Faculty Scholarship

Despite accruing evidence showing that positive emotions facilitate stress recovery, the neural basis for this effect remains unclear. To identify the underlying mechanism, we compared stress recovery for people reflecting on a stressor while in a positive emotional context with that for people in a neutral context. While blood–oxygen-level dependent data were being collected, participants (N = 43) performed a stressful anagram task, which was followed by a recovery period during which they reflected on the stressor while watching a positive or neutral video. Participants also reported positive and negative emotions throughout the task as well as retrospective thoughts …

Endoscopic Full-Thickness Resection Of A Gastric Subepithelial Tumor, Bhavtosh Dedania, Tejal Mistry, Jamie Buryanek, Shashideep Singhal

Faculty, Staff and Student Publications

No abstract provided.

Representing Diversity In The Dish: Using Patient-Derived In Vitro Models To Recreate The Heterogeneity Of Neurological Disease, Layla T. Ghaffari, Alexander Starr, Andrew T. Nelson, Rita Sattler

Department of Neuroscience Faculty Papers

Neurological diseases, including dementias such as Alzheimer's disease (AD) and fronto-temporal dementia (FTD) and degenerative motor neuron diseases such as amyotrophic lateral sclerosis (ALS), are responsible for an increasing fraction of worldwide fatalities. Researching these heterogeneous diseases requires models that endogenously express the full array of genetic and epigenetic factors which may influence disease development in both familial and sporadic patients. Here, we discuss the two primary methods of developing patient-derived neurons and glia to model neurodegenerative disease: reprogramming somatic cells into induced pluripotent stem cells (iPSCs), which are differentiated into neurons or glial cells, or directly converting (DC) somatic …

Breaking Symmetry In Viral Icosahedral Capsids As Seen Through The Lenses Of X-Ray Crystallography And Cryo-Electron Microscopy., Kristin N. Parent, Jason R. Schrad, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

The majority of viruses on Earth form capsids built by multiple copies of one or more types of a coat protein arranged with 532 symmetry, generating an icosahedral shell. This highly repetitive structure is ideal to closely pack identical protein subunits and to enclose the nucleic acid genomes. However, the icosahedral capsid is not merely a passive cage but undergoes dynamic events to promote packaging, maturation and the transfer of the viral genome into the host. These essential processes are often mediated by proteinaceous complexes that interrupt the shell's icosahedral symmetry, providing a gateway through the capsid. In this review, …

Predicting Risk Factors Of Working Aged Hemorrhagic Stroke Patients In A Tertiary Teaching Hospital In Chiang Mai, Suphannee Triamvisit, Wilaiwan Chongruksut, Wanarak Watcharasaksilp, Rujee Rattanasathien

Asian/Pacific Island Nursing Journal

Stroke is the third leading cause of morbidity and mortality in Thailand accounting for a significant and increasing share of hospital costs. The purpose of this project is to study the epidemiology of the prevalence and its predicting factors of working aged hemorrhagic stroke (HS) patients admitted at a tertiary teaching hospital in Chiang Mai, Thailand.

We conducted a five-year retrospective descriptive study. The subjects in this study were patients diagnosed with HS, between 15-59 years of age, and admitted to a tertiary teaching hospital in Chiang Mai, Thailand from January 2009 to December 2013. A total of …

Genome-Wide Profiling Reveals Functional Diversification Of ∆Fosb Gene Targets In The Hippocampus Of An Alzheimer's Disease Mouse Model., Jason C. You, Gabriel S. Stephens, Chia-Hsuan Fu, Xiaohong Zhang, Yin Liu, Jeannie Chin

Department of Neuroscience Faculty Papers

The activity-induced transcription factor ∆FosB has been implicated in Alzheimer's disease (AD) as a critical regulator of hippocampal function and cognition downstream of seizures and network hyperexcitability. With its long half-life (> 1 week), ∆FosB is well-poised to modulate hippocampal gene expression over extended periods of time, enabling effects to persist even during seizure-free periods. However, the transcriptional mechanisms by which ∆FosB regulates hippocampal function are poorly understood due to lack of identified hippocampal gene targets. To identify putative ∆FosB gene targets, we employed high-throughput sequencing of genomic DNA bound to ∆FosB after chromatin immunoprecipitation (ChIP-sequencing). We compared ChIP-sequencing results …

Microrna 1207-3p In Prostate Cancer, Dibash Das

Dissertations, Theses, and Capstone Projects

Prostate cancer (PCa) is the most commonly diagnosed male cancer and the second leading cause of cancer-related death for men in the United States. Understanding the molecular mechanisms involved in progression from the asymptomatic androgen-dependent PCa to the lethal castration resistant prostate cancer (CRPC) is a major challenge. MicroRNAs (miRNAs), are known to be dysregulated in PCa. MicroRNA-1207-3p (miR-1207-3p) is encoded by the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of miR-1207-3p in PCa is unclear. We have discovered that miR-1207-3p is significantly underexpressed in PCa cell lines …

Disconnect Between Genes Associated With Ischemic Heart Disease And Targets Of Ischemic Heart Disease Treatments, C Mary Schooling, J. V. Huang, J. V. Zhao, M.K. Kwok, S. L. Au Yeung, S. L. Lin

Publications and Research

Background: Development of pharmacological treatments to mitigate ischemic heart disease (IHD) has encompassed disappointing results and expensive failures, which has discouraged investment in new approaches to prevention and control.Newtreatments aremost likely to be successful if they act on genetically validated targets. We assessed whether existing pharmacological treatments for IHD reduction are acting on genetically validated targets and whether all such targets for IHD are currently being exploited. Methods: Genes associatedwith IHDwere obtained fromthe loci of single nucleotide polymorphisms reported in either of two recent genome wide association studies supplemented by a gene-based analysis (accounting for linkage disequilibrium) of CARDIoGRAMplusC4D 1000 …

V-Atpase Roles In Prostate Cancer, Yamhilette Licon Munoz

Biomedical Sciences ETDs

Vacuolar ATPase (V-ATPase) is responsible for maintaining the acidic pH of the endomembrane system in eukaryotic cells. V-ATPase active transport of protons generates the differential luminal pH in lysosomes, endosomes, and the Golgi. In addition to intracellular V-ATPase, cancer cells have V-ATPase at the plasma membrane. Plasmalemmal V-ATPase acidifies the extracellular milieu and enhances cell motility and invasion, evidence that V-ATPase contributes to tumorigenic phenotypes. We studied V-ATPase cellular functions in prostate cancer (PCa), the most commonly diagnosed cancer for men in the United States. V-ATPase inhibitors decreased invasion and migration of PCa cells. In aggressive PCa cell lines, C4-2B …

The Challenged Brain Bps 205g, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Transspinal Direct Current Stimulation Produces Persistent Plasticity In Human Motor Pathways, Lynda M. Murray, Behdad Tahayori, Maria Knikou

Publications and Research

The spinal cord is an integration center for descending, ascending, and segmental neural signals. Noninvasive transspinal stimulation may thus constitute an effective method for concomitant modulation of local and distal neural circuits. In this study, we established changes in cortical excitability and input/output function of corticospinal and spinal neural circuits before, at 0–15 and at 30–45 minutes after cathodal, anodal, and sham transspinal direct current stimulation (tsDCS) to the thoracic region in healthy individuals. We found that intracortical inhibition was different among stimulation polarities, however remained unchanged over time. Intracortical facilitation increased after cathodal and anodal tsDCS delivered with subjects …

Anti-Correlated Cortical Networks Arise From Spontaneous Neuronal Dynamics At Slow Timescales, Nathan X. Kodama, Tianyi Feng, James J. Ullett, Hillel J. Chiel, Siddharth S. Sivakumar, Roberto F. Galán

Faculty Scholarship

In the highly interconnected architectures of the cerebral cortex, recurrent intracortical loops disproportionately outnumber thalamo-cortical inputs. These networks are also capable of generating neuronal activity without feedforward sensory drive. It is unknown, however, what spatiotemporal patterns may be solely attributed to intrinsic connections of the local cortical network. Using high-density microelectrode arrays, here we show that in the isolated, primary somatosensory cortex of mice, neuronal firing fluctuates on timescales from milliseconds to tens of seconds. Slower firing fluctuations reveal two spatially distinct neuronal ensembles, which correspond to superficial and deeper layers. These ensembles are anti-correlated: when one fires more, the …

Sooty Mangabey Genome Sequence Provides Insight Into Aids Resistance In A Natural Siv Host, David Palesch, Steven E. Bosinger, Gregory K. Tharp, Thomas H. Vanderford, Mirko Paiardini, Ann Chahroudi, Zachary P. Johnson, Frank Kirchhoff, Beatrice H. Hahn, Robert B. Norgren, Nirav B. Patel, Donald L. Sodora, Reem A. Dawoud, Caro-Beth Stewart, Sara M. Seepo, R. Alan Harris, Yue Liu, Muthuswamy Raveendran, Yi Han, Adam English, Gregg W.C. Thomas, Matthew W. Hahn, Lenore Pipes, Christopher E. Mason, Donna M. Muzny, Richard A. Gibbs, Daniel Sauter, Kim Worley, Jeffrey Rogers, Guido Silvestri

Journal Articles: Genetics, Cell Biology & Anatomy

In contrast to infections with human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques, SIV infection of a natural host, sooty mangabeys (Cercocebus atys), is non-pathogenic despite high viraemia. Here we sequenced and assembled the genome of a captive sooty mangabey. We conducted genome-wide comparative analyses of transcript assemblies from C. atys and AIDS-susceptible species, such as humans and macaques, to identify candidates for host genetic factors that influence susceptibility. We identified several immune-related genes in the genome of C. atys that show substantial sequence divergence from macaques or humans. One of these sequence divergences, a …