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Articles 10351 - 10380 of 14908

Full-Text Articles in Medical Specialties

Regenerative Medicine Therapy: Adipose Derived Extracellular Vesicles In Viral Myocarditis, David Gorelov, Damian N. Di Florio, Gary R. Salomon, Angita Jain, Nick E. Saikaili, Danielle J. Beetler, Swikriti Shrestha, Ming Tian, Joy Wolfram Phd, Delisa Fairweather Phd, Katelyn Bruno Phd, Judith D. Ochrietor Phd Apr 2020

Regenerative Medicine Therapy: Adipose Derived Extracellular Vesicles In Viral Myocarditis, David Gorelov, Damian N. Di Florio, Gary R. Salomon, Angita Jain, Nick E. Saikaili, Danielle J. Beetler, Swikriti Shrestha, Ming Tian, Joy Wolfram Phd, Delisa Fairweather Phd, Katelyn Bruno Phd, Judith D. Ochrietor Phd

Showcase of Osprey Advancements in Research and Scholarship (SOARS)

Objective: Myocarditis, inflammation of the heart muscle, is an autoimmune heart disease that can be caused by viruses, bacteria and toxins. Myocarditis can lead to dilated cardiomyopathy (DCM) and heart failure. Currently there are no disease-specific therapies for treating myocarditis or preventing progression to DCM. Adipose Extracellular Vesicles (AEVs) are lipid bilayer nanoparticles that are released into the outside environment of adipocytes and provide promising regenerative potential for inflammatory diseases like myocarditis.

Methods: Lipoaspirate was obtained from women and men and AEVs isolated from the lipoaspirate using tangential flow filtration. We injected wild type male BALB/c mice with 250uL AEVs …


Acetylation Of Histone H3k27 Signals The Transcriptional Elongation For Estrogen Receptor Alpha, Yujing Gao, Lijia Chen, Yali Han, Fangrui Wu, Wen-Si Yang, Zheng Zhang, Tong Huo, Yingmin Zhu, Chengtai Yu, Hong Kim, Mark Lee, Zhen Tang, Kevin Phillips, Bin He, Sung Yun Jung, Yongcheng Song, Bokai Zhu, Rui-Ming Xu, Qin Feng Apr 2020

Acetylation Of Histone H3k27 Signals The Transcriptional Elongation For Estrogen Receptor Alpha, Yujing Gao, Lijia Chen, Yali Han, Fangrui Wu, Wen-Si Yang, Zheng Zhang, Tong Huo, Yingmin Zhu, Chengtai Yu, Hong Kim, Mark Lee, Zhen Tang, Kevin Phillips, Bin He, Sung Yun Jung, Yongcheng Song, Bokai Zhu, Rui-Ming Xu, Qin Feng

Faculty, Staff and Students Publications

As approximately 70% of human breast tumors are estrogen receptor α (ERα)-positive, estrogen and ERα play essential roles in breast cancer development. By interrupting the ERα signaling pathway, endocrine therapy has been proven to be an effective therapeutic strategy. In this study, we identified a mechanism by which Transcription Start Site (TSS)-associated histone H3K27 acetylation signals the Super Elongation Complex (SEC) to regulate transcriptional elongation of the ESR1 (ERα) gene. SEC interacts with H3K27ac on ESR1 TSS through its scaffold protein AFF4. Depletion of AFF4 by siRNA or CRISPR/Cas9 dramatically reduces expression of ESR1 and its target genes, consequently inhibiting …


Integrating Mouse And Human Genetic Data To Move Beyond Gwas And Identify Causal Genes In Cholesterol Metabolism, Zhonggang Li, James A Votava, Gregory J M Zajac, Jenny N Nguyen, Fernanda B Leyva Jaimes, Sophia M Ly, Jacqueline A Brinkman, Marco De Giorgi, Sushma Kaul, Cara L Green, Samantha L St Clair, Sabrina L Belisle, Julia M Rios, David W Nelson, Mary G Sorci-Thomas, William R Lagor, Dudley W Lamming, Chi-Liang Eric Yen, Brian W Parks Apr 2020

Integrating Mouse And Human Genetic Data To Move Beyond Gwas And Identify Causal Genes In Cholesterol Metabolism, Zhonggang Li, James A Votava, Gregory J M Zajac, Jenny N Nguyen, Fernanda B Leyva Jaimes, Sophia M Ly, Jacqueline A Brinkman, Marco De Giorgi, Sushma Kaul, Cara L Green, Samantha L St Clair, Sabrina L Belisle, Julia M Rios, David W Nelson, Mary G Sorci-Thomas, William R Lagor, Dudley W Lamming, Chi-Liang Eric Yen, Brian W Parks

Faculty, Staff and Students Publications

Identifying the causal gene(s) that connects genetic variation to a phenotype is a challenging problem in genome-wide association studies (GWASs). Here, we develop a systematic approach that integrates mouse liver co-expression networks with human lipid GWAS data to identify regulators of cholesterol and lipid metabolism. Through our approach, we identified 48 genes showing replication in mice and associated with plasma lipid traits in humans and six genes on the X chromosome. Among these 54 genes, 25 have no previously identified role in lipid metabolism. Based on functional studies and integration with additional human lipid GWAS datasets, we pinpoint Sestrin1 as …


Principles Of Rna Processing From Analysis Of Enhanced Clip Maps For 150 Rna Binding Proteins, Eric L Van Nostrand, Gabriel A Pratt, Brian A Yee, Emily C Wheeler, Steven M Blue, Jasmine Mueller, Samuel S Park, Keri E Garcia, Chelsea Gelboin-Burkhart, Thai B Nguyen, Ines Rabano, Rebecca Stanton, Balaji Sundararaman, Ruth Wang, Xiang-Dong Fu, Brenton R Graveley, Gene W Yeo Apr 2020

Principles Of Rna Processing From Analysis Of Enhanced Clip Maps For 150 Rna Binding Proteins, Eric L Van Nostrand, Gabriel A Pratt, Brian A Yee, Emily C Wheeler, Steven M Blue, Jasmine Mueller, Samuel S Park, Keri E Garcia, Chelsea Gelboin-Burkhart, Thai B Nguyen, Ines Rabano, Rebecca Stanton, Balaji Sundararaman, Ruth Wang, Xiang-Dong Fu, Brenton R Graveley, Gene W Yeo

Faculty, Staff and Students Publications

BACKGROUND: A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale analysis across datasets. The development of enhanced CLIP (eCLIP) enabled the mapping of targets for 150 RBPs in K562 and HepG2, creating a unique resource of RBP interactomes profiled with a standardized methodology in the same cell types.

RESULTS: Our analysis of 223 eCLIP datasets reveals a range of binding modalities, including highly resolved positioning around splicing signals and mRNA …


De Novo Frameshift Variants In The Neuronal Splicing Factor Nova2 Result In A Common C-Terminal Extension And Cause A Severe Form Of Neurodevelopmental Disorder, Francesca Mattioli, Gaelle Hayot, Nathalie Drouot, Bertrand Isidor, Jérémie Courraud, Maria-Victoria Hinckelmann, Frederic Tran Mau-Them, Chantal Sellier, Alica Goldman, Aida Telegrafi, Alicia Boughton, Candace Gamble, Sebastien Moutton, Angélique Quartier, Nolwenn Jean, Paul Van Ness, Sarah Grotto, Sophie Nambot, Ganka Douglas, Yue Cindy Si, Jamel Chelly, Zohra Shad, Elisabeth Kaplan, Richard Dineen, Christelle Golzio, Nicolas Charlet-Berguerand, Jean-Louis Mandel, Amélie Piton Apr 2020

De Novo Frameshift Variants In The Neuronal Splicing Factor Nova2 Result In A Common C-Terminal Extension And Cause A Severe Form Of Neurodevelopmental Disorder, Francesca Mattioli, Gaelle Hayot, Nathalie Drouot, Bertrand Isidor, Jérémie Courraud, Maria-Victoria Hinckelmann, Frederic Tran Mau-Them, Chantal Sellier, Alica Goldman, Aida Telegrafi, Alicia Boughton, Candace Gamble, Sebastien Moutton, Angélique Quartier, Nolwenn Jean, Paul Van Ness, Sarah Grotto, Sophie Nambot, Ganka Douglas, Yue Cindy Si, Jamel Chelly, Zohra Shad, Elisabeth Kaplan, Richard Dineen, Christelle Golzio, Nicolas Charlet-Berguerand, Jean-Louis Mandel, Amélie Piton

Faculty, Staff and Students Publications

The neuro-oncological ventral antigen 2 (NOVA2) protein is a major factor regulating neuron-specific alternative splicing (AS), previously associated with an acquired neurologic condition, the paraneoplastic opsoclonus-myoclonus ataxia (POMA). We report here six individuals with de novo frameshift variants in NOVA2 affected with a severe neurodevelopmental disorder characterized by intellectual disability (ID), motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait, and abnormal brain MRI. The six variants lead to the same reading frame, adding a common proline rich C-terminal part instead of the last KH RNA binding domain. We detected 41 genes differentially spliced after NOVA2 …


Phosphoinositides In Retinal Function And Disease, Theodore G Wensel Apr 2020

Phosphoinositides In Retinal Function And Disease, Theodore G Wensel

Faculty, Staff and Students Publications

Phosphatidylinositol and its phosphorylated derivatives, the phosphoinositides, play many important roles in all eukaryotic cells. These include modulation of physical properties of membranes, activation or inhibition of membrane-associated proteins, recruitment of peripheral membrane proteins that act as effectors, and control of membrane trafficking. They also serve as precursors for important second messengers, inositol (1,4,5) trisphosphate and diacylglycerol. Animal models and human diseases involving defects in phosphoinositide regulatory pathways have revealed their importance for function in the mammalian retina and retinal pigmented epithelium. New technologies for localizing, measuring and genetically manipulating them are revealing new information about their importance for the …


Coronavirus Disease 2019 (Covid-19), Matthew Dunbar Apr 2020

Coronavirus Disease 2019 (Covid-19), Matthew Dunbar

Pharmacy Student Scholarship

No abstract provided.


Reaching The Peak, Mary I. Fisher Apr 2020

Reaching The Peak, Mary I. Fisher

Physical Therapy Faculty Publications

No abstract provided.


Reliability And Validity Of An Assessment Of Engagement In Nursing Home Residents During Bingocize®, Elizabeth Batson Apelt Apr 2020

Reliability And Validity Of An Assessment Of Engagement In Nursing Home Residents During Bingocize®, Elizabeth Batson Apelt

Masters Theses & Specialist Projects

Research suggests nursing home residents are often socially isolated and physically inactive despite overwhelming evidence that both social engagement and physical activity are crucial for healthy aging (Jones, Sung, & Moyle, 2018; Yen & Lin, 2018; Ice, 2002; Jansson et al., 2017). Bingocize® is a program that combines exercise and the game of Bingo to improve the quality of life, physical health, and social engagement of certified nursing facility (CNF) residents. The purpose of this study is to determine the level of social engagement displayed by CNF residents during Bingocize® using the Fun and Social Engagement Evaluation (FUSE). Reliability and …


Follicular Sensitivity Index: A Tool To Predict Successful Conception After Intra-Cytoplasmic Sperm Injection, Rehana Rehman, Amara Zafar, Nida Zahid, Nuruddin Badruddin Mohammed Apr 2020

Follicular Sensitivity Index: A Tool To Predict Successful Conception After Intra-Cytoplasmic Sperm Injection, Rehana Rehman, Amara Zafar, Nida Zahid, Nuruddin Badruddin Mohammed

Department of Biological & Biomedical Sciences

Follicular sensitivity index (FSI) is used for estimation of follicular responsiveness to controlled ovarian hyperstimulation (COH) during intra-cytoplasmic sperm injection (ICSI). In a retrospective study, FSI of 1,385 females was calculated as [pre-ovulatory follicle count (PFC) × 100,000]/ [antral follicle count (AFC) × total received stimulation doses]. Females were then categorised into low, middle and high FSI groups according to FSI tertile values. FSI was 8.65 ±2.82 in non-pregnant as compared to 12.02 ±2.04 (p <0.01) in pregnant cohort. FSI turned out to be a strong predictor of successful conception on the receiver operating curve with cutoff value 10.36 at 76% specificity, sensitivity of 86% and area under the curve (AUC; 0.83). Calculation of FSI can thus predict the chances of successful conception in females with different causes of infertility.


Compliance Of Hand Written Transfusion Requisition Form And Improvement After Online Request - A Clinical Audit, Nadia Nasir, Mohammad Usman Shaikh, Natasha Ali, Shabneez Hussain Apr 2020

Compliance Of Hand Written Transfusion Requisition Form And Improvement After Online Request - A Clinical Audit, Nadia Nasir, Mohammad Usman Shaikh, Natasha Ali, Shabneez Hussain

Department of Pathology and Laboratory Medicine

Objective: To assess the compliance of healthcare personnel with regard to sending completely filled transfusion requisition forms.
Methods: The audit was conducted at Aga Khan University Hospital, Karachi, and comprised requisition slips received at the hospital blood bank from September 2014 to February 2015. The British Committee for Standards in Haematology guidelines was used as the standard. Percentage of each variable on the proforma was analsyed. Rating Results: The audit and the re-audit both comprised 1000 transfusion requisition forms each. In the audit, The sum of total scores of all the transfusion requisition forms was 4911, indicating a compliance rate …


Exosomes In Transmission And Blocking Of Arthropod-Borne Flaviviral Infection And Pathogenesis, Wenshuo Zhou Apr 2020

Exosomes In Transmission And Blocking Of Arthropod-Borne Flaviviral Infection And Pathogenesis, Wenshuo Zhou

Biomedical Sciences Theses & Dissertations

Vector-borne diseases (VBDs) are human illnesses that are transmitted by vectors such as ticks, mosquitoes, and fleas. These arthropods transmit infectious pathogens such as viruses, protozoa, and bacteria, to humans during their blood-feeding. According to the estimation of the WHO, billions of people are affected by VBDs worldwide, and about 700,000 deaths are reported annually. Currently, very few reliable VBDs control approaches and vaccines available to treat various VBDs. Additionally, approaches to control arthropod’ proliferation and migration are difficult to develop. Furthermore, molecular determinants and mechanisms for the transmission are poorly understood. This work describes two studies identifying the novel …


Impedance Analysis Of Tissues In Nspef Treatment For Cancer Therapy, Edwin Ayobami Oshin Apr 2020

Impedance Analysis Of Tissues In Nspef Treatment For Cancer Therapy, Edwin Ayobami Oshin

Biomedical Engineering Theses & Dissertations

Nanosecond pulsed electric field (nsPEF) for cancer therapy is characterized by applications of high voltage pulses with low pulsed energy to induce non-thermal effects on tissues such as tumor ablation. It nonthermally treats tissues via electroporation. Electroporation is the increase in permeabilization of a cell membrane due to the application of high pulsed electric field. The objective of this study was to investigate the effect of nsPEF on tissue by monitoring the tissue’s impedance in real-time. Potato slices (both untreated and electroporated), and tumors extracted from female BALBc mice were studied. 100ns, 1-10kV pulses were applied to the tissues using …


Elucidating The Regulon Of A Fur-Like Protein In Mycobacterium Avium Subsp. Paratuberculosis (Map), Fernanda Miyagaki Shoyama, Taveesak Janetanakit, John P. Bannantine, Raul G. Barletta, Srinand Sreevatsan Apr 2020

Elucidating The Regulon Of A Fur-Like Protein In Mycobacterium Avium Subsp. Paratuberculosis (Map), Fernanda Miyagaki Shoyama, Taveesak Janetanakit, John P. Bannantine, Raul G. Barletta, Srinand Sreevatsan

Nebraska Center for Virology: Faculty Publications

Intracellular iron concentration is tightly regulated to maintain cell viability. Iron plays important roles in electron transport, nucleic acid synthesis, and oxidative stress. A Mycobacterium avium subsp. paratuberculosis (MAP)-specific genomic island carries a putative metal transport operon that includes MAP3773c, which encodes a Fur-like protein. Although well characterized as a global regulator of iron homeostasis in multiple bacteria, the function of Fur (ferric uptake regulator) in MAP is unknown as this organism also carries IdeR (iron dependent regulator), a native iron regulatory protein specific to mycobacteria. Computational analysis using PRODORIC identified 23 different pathways involved in respiration, metabolism, and virulence …


Provider Attitudes And Practice Patterns For Direct-Acting Antiviral Therapy For Patients With Hepatocellular Carcinoma, Nicole E Rich, Ju Dong Yang, Ponni V Perumalswami, Naim Alkhouri, Whitney Jackson, Neehar D Parikh, Neil Mehta, Reena Salgia, Andres Duarte-Rojo, Laura Kulik, Mina Rakoski, Adnan Said, Omobonike Oloruntoba, George N Ioannou, Maarouf A Hoteit, Andrew M Moon, Amol S Rangnekar, Sheila L Eswaran, Elizabeth Zheng, Janice H Jou, James Hanje, Anjana Pillai, Ruben Hernaez, Robert Wong, Steven Scaglione, Hrishikesh Samant, Devika Kapuria, Shaun Chandna, Russell Rosenblatt, Veeral Ajmera, Catherine T Frenette, Sanjaya K Satapathy, Parvez Mantry, Prasun Jalal, Binu V John, Oren K Fix, Michael Leise, Christina C Lindenmeyer, Avegail Flores, Nayan Patel, Z Gordon Jiang, Nyan Latt, Renumathy Dhanasekaran, Mobolaji Odewole, Sofia Kagan, Jorge A Marrero, Amit G Singal Apr 2020

Provider Attitudes And Practice Patterns For Direct-Acting Antiviral Therapy For Patients With Hepatocellular Carcinoma, Nicole E Rich, Ju Dong Yang, Ponni V Perumalswami, Naim Alkhouri, Whitney Jackson, Neehar D Parikh, Neil Mehta, Reena Salgia, Andres Duarte-Rojo, Laura Kulik, Mina Rakoski, Adnan Said, Omobonike Oloruntoba, George N Ioannou, Maarouf A Hoteit, Andrew M Moon, Amol S Rangnekar, Sheila L Eswaran, Elizabeth Zheng, Janice H Jou, James Hanje, Anjana Pillai, Ruben Hernaez, Robert Wong, Steven Scaglione, Hrishikesh Samant, Devika Kapuria, Shaun Chandna, Russell Rosenblatt, Veeral Ajmera, Catherine T Frenette, Sanjaya K Satapathy, Parvez Mantry, Prasun Jalal, Binu V John, Oren K Fix, Michael Leise, Christina C Lindenmeyer, Avegail Flores, Nayan Patel, Z Gordon Jiang, Nyan Latt, Renumathy Dhanasekaran, Mobolaji Odewole, Sofia Kagan, Jorge A Marrero, Amit G Singal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC.

METHODS: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses …


27 Å Cryo-Em Structure Of Rotavirus Core Protein Vp3, A Unique Capping Machine With A Helicase Activity, Dilip Kumar, Xinzhe Yu, Sue E Crawford, Rodolfo Moreno, Joanita Jakana, Banumathi Sankaran, Ramakrishnan Anish, Soni Kaundal, Liya Hu, Mary K Estes, Zhao Wang, B V Venkataram Prasad Apr 2020

27 Å Cryo-Em Structure Of Rotavirus Core Protein Vp3, A Unique Capping Machine With A Helicase Activity, Dilip Kumar, Xinzhe Yu, Sue E Crawford, Rodolfo Moreno, Joanita Jakana, Banumathi Sankaran, Ramakrishnan Anish, Soni Kaundal, Liya Hu, Mary K Estes, Zhao Wang, B V Venkataram Prasad

Faculty, Staff and Students Publications

In many viruses, including rotavirus (RV), the major pathogen of infantile gastroenteritis, capping of viral messenger RNAs is a pivotal step for efficient translation of the viral genome. In RV, VP3 caps the nascent transcripts synthesized from the genomic dsRNA segments by the RV polymerase VP1 within the particle core. Here, from cryo-electron microscopy, x-ray crystallography, and biochemical analyses, we show that VP3 forms a stable tetrameric assembly with each subunit having a modular domain organization, which uniquely integrates five distinct enzymatic steps required for capping the transcripts. In addition to the previously known guanylyl- and methyltransferase activities, we show …


Defining A Taxonomy Of Intracranial Hypertension: Is Icp More Than Just A Number?, W Andrew Kofke, Swarna Rajagopalan, Diana Ayubcha, Ramani Balu, Jovany Cruz-Navarro, Panumart Manatpon, Elizabeth Mahanna-Gabrielli Apr 2020

Defining A Taxonomy Of Intracranial Hypertension: Is Icp More Than Just A Number?, W Andrew Kofke, Swarna Rajagopalan, Diana Ayubcha, Ramani Balu, Jovany Cruz-Navarro, Panumart Manatpon, Elizabeth Mahanna-Gabrielli

Faculty, Staff and Students Publications

Intracranial pressure (ICP) monitoring and control is a cornerstone of neuroanesthesia and neurocritical care. However, because elevated ICP can be due to multiple pathophysiological processes, its interpretation is not straightforward. We propose a formal taxonomy of intracranial hypertension, which defines ICP elevations into 3 major pathophysiological subsets: increased cerebral blood volume, masses and edema, and hydrocephalus. (1) Increased cerebral blood volume increases ICP and arises secondary to arterial or venous hypervolemia. Arterial hypervolemia is produced by autoregulated or dysregulated vasodilation, both of which are importantly and disparately affected by systemic blood pressure. Dysregulated vasodilation tends to be worsened by arterial …


An In Vivo Genome-Wide Crispr Screen Identifies The Rna-Binding Protein Staufen2 As A Key Regulator Of Myeloid Leukemia, Jeevisha Bajaj, Michael Hamilton, Yutaka Shima, Kendall Chambers, Kyle Spinler, Eric L Van Nostrand, Brian A Yee, Steven M Blue, Michael Chen, David Rizzeri, Charles Chuah, Vivian G Oehler, H Elizabeth Broome, Roman Sasik, James Scott-Browne, Anjana Rao, Gene W Yeo, Tannishtha Reya Apr 2020

An In Vivo Genome-Wide Crispr Screen Identifies The Rna-Binding Protein Staufen2 As A Key Regulator Of Myeloid Leukemia, Jeevisha Bajaj, Michael Hamilton, Yutaka Shima, Kendall Chambers, Kyle Spinler, Eric L Van Nostrand, Brian A Yee, Steven M Blue, Michael Chen, David Rizzeri, Charles Chuah, Vivian G Oehler, H Elizabeth Broome, Roman Sasik, James Scott-Browne, Anjana Rao, Gene W Yeo, Tannishtha Reya

Faculty, Staff and Students Publications

Aggressive myeloid leukemias such as blast crisis chronic myeloid leukemia and acute myeloid leukemia remain highly lethal. Here we report a genome-wide in vivo CRISPR screen to identify new dependencies in this disease. Among these, RNA-binding proteins (RBPs) in general, and the double-stranded RBP Staufen2 (Stau2) in particular, emerged as critical regulators of myeloid leukemia. In a newly developed knockout mouse, loss of Stau2 led to a profound decrease in leukemia growth and improved survival in mouse models of the disease. Further, Stau2 was required for growth of primary human blast crisis chronic myeloid leukemia and acute myeloid leukemia. Finally, …


Nr2f1 Heterozygous Knockout Mice Recapitulate Neurological Phenotypes Of Bosch-Boonstra-Schaaf Optic Atrophy Syndrome And Show Impaired Hippocampal Synaptic Plasticity, Chun-An Chen, Wei Wang, Steen E Pedersen, Ayush Raman, Michelle L Seymour, Fernanda R Ruiz, Anping Xia, Meike E Van Der Heijden, Li Wang, Jiani Yin, Joanna Lopez, Megan E Rech, Richard A Lewis, Samuel M Wu, Zhandong Liu, Fred A Pereira, Robia G Pautler, Huda Y Zoghbi, Christian P Schaaf Mar 2020

Nr2f1 Heterozygous Knockout Mice Recapitulate Neurological Phenotypes Of Bosch-Boonstra-Schaaf Optic Atrophy Syndrome And Show Impaired Hippocampal Synaptic Plasticity, Chun-An Chen, Wei Wang, Steen E Pedersen, Ayush Raman, Michelle L Seymour, Fernanda R Ruiz, Anping Xia, Meike E Van Der Heijden, Li Wang, Jiani Yin, Joanna Lopez, Megan E Rech, Richard A Lewis, Samuel M Wu, Zhandong Liu, Fred A Pereira, Robia G Pautler, Huda Y Zoghbi, Christian P Schaaf

Faculty, Staff and Students Publications

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) has been identified as an autosomal-dominant disorder characterized by a complex neurological phenotype, with high prevalence of intellectual disability and optic nerve atrophy/hypoplasia. The syndrome is caused by loss-of-function mutations in NR2F1, which encodes a highly conserved nuclear receptor that serves as a transcriptional regulator. Previous investigations to understand the protein's role in neurodevelopment have mostly used mouse models with constitutive and tissue-specific homozygous knockout of Nr2f1. In order to represent the human disease more accurately, which is caused by heterozygous NR2F1 mutations, we investigated a heterozygous knockout mouse model and found that this model …


Metabolic Reprogramming By C-Met Inhibition As A Targetable Vulnerability In Glioblastoma, Trang Thi Thu Nguyen, Enyuan Shang, Georg Karpel-Massler, Markus D. Siegelin Mar 2020

Metabolic Reprogramming By C-Met Inhibition As A Targetable Vulnerability In Glioblastoma, Trang Thi Thu Nguyen, Enyuan Shang, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

The elucidation of better treatments for solid tumors and especially malignant glial tumors is a priority. Better understanding of the molecular underpinnings of treatment response and resistance are critical determinants in the success for this endeavor. Recently, a battery of novel tools have surfaced that allow to interrogate tumor cell metabolism to more precise extent than this was possible in the earlier days. At the forefront of these developments are the extracellular flux and carbon tracing analyses. Through utilization of these techniques our group made the recent observation that acute and chronic c-MET inhibition drives fatty acid oxidation that in …


Transcutaneous Auricular Vagus Nerve Stimulation-Paired Rehabilitation For Oromotor Feeding Problems In Newborns: An Open-Label Pilot Study, Bashar W. Badran, Dorothea D. Jenkins, Daniel Cook, Sean Thompson, Morgan Darcy, William H. Devries, Georgia Mappin, Philipp Summers, Marom Bikson, Mark S. George Mar 2020

Transcutaneous Auricular Vagus Nerve Stimulation-Paired Rehabilitation For Oromotor Feeding Problems In Newborns: An Open-Label Pilot Study, Bashar W. Badran, Dorothea D. Jenkins, Daniel Cook, Sean Thompson, Morgan Darcy, William H. Devries, Georgia Mappin, Philipp Summers, Marom Bikson, Mark S. George

Publications and Research

Neonates born premature or who suffer brain injury at birth often have oral feeding dysfunction and do not meet oral intake requirements needed for discharge. Low oral intake volumes result in extended stays in the hospital (>2 months) and can lead to surgical implant and explant of a gastrostomy tube (G-tube). Prior work suggests pairing vagus nerve stimulation (VNS) with motor activity accelerates functional improvements after stroke, and transcutaneous auricular VNS (taVNS) has emerged as promising noninvasive form of VNS. Pairing taVNS with bottle-feeding rehabilitation may improve oromotor coordination and lead to improved oral intake volumes, ultimately avoiding the …


The Sineb1 Element In The Long Non-Coding Rna Malat1 Is Necessary For Tdp-43 Proteostasis, Tuan M Nguyen, Elena B Kabotyanski, Lucas C Reineke, Jiaofang Shao, Feng Xiong, Joo-Hyung Lee, Julien Dubrulle, Hannah Johnson, Fabio Stossi, Phoebe S Tsoi, Kyoung-Jae Choi, Alexander G Ellis, Na Zhao, Jin Cao, Oluwatoyosi Adewunmi, Josephine C Ferreon, Allan Chris M Ferreon, Joel R Neilson, Michael A Mancini, Xi Chen, Jongchan Kim, Li Ma, Wenbo Li, Jeffrey M Rosen Mar 2020

The Sineb1 Element In The Long Non-Coding Rna Malat1 Is Necessary For Tdp-43 Proteostasis, Tuan M Nguyen, Elena B Kabotyanski, Lucas C Reineke, Jiaofang Shao, Feng Xiong, Joo-Hyung Lee, Julien Dubrulle, Hannah Johnson, Fabio Stossi, Phoebe S Tsoi, Kyoung-Jae Choi, Alexander G Ellis, Na Zhao, Jin Cao, Oluwatoyosi Adewunmi, Josephine C Ferreon, Allan Chris M Ferreon, Joel R Neilson, Michael A Mancini, Xi Chen, Jongchan Kim, Li Ma, Wenbo Li, Jeffrey M Rosen

Faculty, Staff and Students Publications

Transposable elements (TEs) comprise a large proportion of long non-coding RNAs (lncRNAs). Here, we employed CRISPR to delete a short interspersed nuclear element (SINE) in Malat1, a cancer-associated lncRNA, to investigate its significance in cellular physiology. We show that Malat1 with a SINE deletion forms diffuse nuclear speckles and is frequently translocated to the cytoplasm. SINE-deleted cells exhibit an activated unfolded protein response and PKR and markedly increased DNA damage and apoptosis caused by dysregulation of TDP-43 localization and formation of cytotoxic inclusions. TDP-43 binds stronger to Malat1 without the SINE and is likely 'hijacked' by cytoplasmic Malat1 to the …


Discovery Of A Bacterial Peptide As A Modulator Of Glp-1 And Metabolic Disease, Catherine Tomaro-Duchesneau, Stephanie L Levalley, Daniel Roeth, Liang Sun, Frank T Horrigan, Markus Kalkum, Joseph M Hyser, Robert A Britton Mar 2020

Discovery Of A Bacterial Peptide As A Modulator Of Glp-1 And Metabolic Disease, Catherine Tomaro-Duchesneau, Stephanie L Levalley, Daniel Roeth, Liang Sun, Frank T Horrigan, Markus Kalkum, Joseph M Hyser, Robert A Britton

Faculty, Staff and Students Publications

Early work in rodents highlighted the gut microbiota's importance in metabolic disease, including Type II Diabetes Mellitus (T2DM) and obesity. Glucagon-like peptide-1 (GLP-1), an incretin secreted by L-cells lining the gastrointestinal epithelium, has important functions: promoting insulin secretion, insulin sensitivity, and β-cell mass, while inhibiting gastric emptying and appetite. We set out to identify microbial strains with GLP-1 stimulatory activity as potential metabolic disease therapeutics. Over 1500 human-derived strains were isolated from healthy individuals and screened for GLP-1 modulation by incubating bacterial cell-free supernatants with NCI H716 L-cells. Approximately 45 strains capable of increasing GLP-1 were discovered. All GLP-1 positive …


Evaluation Of The Impact Of Social Collaborations On Sexual And Reproductive Health Knowledge, Lucki Word, Jaila Campbell, Manar T. Edriss, Destiny Stroman, Jewel Evans, Melanie Hanna-Johnson, Md, Anil N. F. Aranha, Phd Mar 2020

Evaluation Of The Impact Of Social Collaborations On Sexual And Reproductive Health Knowledge, Lucki Word, Jaila Campbell, Manar T. Edriss, Destiny Stroman, Jewel Evans, Melanie Hanna-Johnson, Md, Anil N. F. Aranha, Phd

Medical Student Research Symposium

Introduction: Developments in technology, such as the popularity of mobile devices and social media outlets, have enhanced the ability of individuals to communicate. Currently, search engines allow for easy exploration of information related to every topic of interest. Our study purpose was to evaluate the impact of technological and social collaborations on sexual and reproductive health knowledge (SRHK).

Methods: A 50-item survey instrument, integrating factors of sociodemographics, number/type of social collaborations, technological communication use, and SRHK, was developed to assess familiarity with sexual and reproductive health perceptions. The survey was provided to consenting patients in an ambulatory, primary care setting. …


The Effects Of Strength And Conditioning On Functional Movement Screen™ Scores In Secondary School Basketball., Rollin Ross Dexter, Christopher P. Renggli, James May, Lindsay Larkins Mar 2020

The Effects Of Strength And Conditioning On Functional Movement Screen™ Scores In Secondary School Basketball., Rollin Ross Dexter, Christopher P. Renggli, James May, Lindsay Larkins

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Purpose: Injury prevention and mitigation are among the primary responsibilities of Athletic Trainers. Research has indicated that basketball players at the secondary-school level suffer up to 2.1 time loss injuries (TLI) per 1,000 athletic exposures (AE). It has been suggested that Functional Movement Screen (FMS™) composite and individual task scores may help determine injury risk. Researchers have suggested that a variety of strength and conditioning strategies may positively alter both composite and individual FMS™ task scores and reduce movement asymmetry. Methods: During a retrospective analysis of the records of all junior varsity and varsity basketball players at one secondary school …


Effective Treatment Of An Apparent Lateral Ankle Sprain Using A Regional Interdependent Approach With Positional Release Therapy And Mulligan Concept, Joshua K. Underwood Mar 2020

Effective Treatment Of An Apparent Lateral Ankle Sprain Using A Regional Interdependent Approach With Positional Release Therapy And Mulligan Concept, Joshua K. Underwood

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Objective: Present a pair of clinical cases demonstrating the utilization of regional interdependent (RI) evaluation and treatment in an apparent lateral ankle sprain. The utilization of both Positional Release Therapy (PRT) and Mulligan Concept (MC) on secondary school athletes with an apparent acute lateral ankle sprain are presented. Background: Lateral ankle sprains are a common injury in athletics. While the MC has been shown to be an effective manual therapy in ankle sprains, if the treatment is not pain-free it is considered not warranted. The concept of RI attempts to connect apparently unconnected dysfunctions within the body which collectively contribute …


Student Athlete Perceptions Of Athletic Trainers’ Competence Based On Appearance And Dress, Jennifer J. Rogers Mar 2020

Student Athlete Perceptions Of Athletic Trainers’ Competence Based On Appearance And Dress, Jennifer J. Rogers

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Context: Physical appearance and dress attire may be a major influence on a person’s perception of an individual’s professional competence. Objective: To examine influence of Athletic Trainer (AT) physical appearance and dress attire on student-athletes’ perception of an AT’s competence. Design: Cross-Sectional Study Setting: NATA District 5 Participants: Student athletes (n=156; female: n=71; male: n=78) from NCAA Division III and NAIA institutions participated in the study. Interventions: Participants viewed one of four Body Mass Index (BMI) specific AT images [underweight BMI=18, normal weight BMI=24, overweight BMI=30, or an obese BMI=36] while answering 36 Student Athlete Response (SAR) Form survey questions …


The Effectiveness Of An Infrapatellar Strap On Reducing Pain Associated With Patellar Tendinopathy, Jenny Toonstra, Andrea Cripps Mar 2020

The Effectiveness Of An Infrapatellar Strap On Reducing Pain Associated With Patellar Tendinopathy, Jenny Toonstra, Andrea Cripps

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Purpose: To determine the effectiveness of an infrapatellar strap on pain reduction in participants with patellar tendinopathy. Methods: Articles were identified from PubMed, CINAHL, Medline, and SportDiscus using the string “((((patellar tendinitis OR patellar tendinopathy))) AND ((cho-pat strap OR infrapatellar strap OR compression device OR brace))) AND pain” from January 2009-January 2019, resulting in nine studies. After a review of the title and abstracts, six studies were reviewed in-depth. Of these articles, four studies met the inclusion criteria. Two independent reviewers assessed the level of evidence of included studies using the Oxford Center for Evidence-Based Medicine (2009). Changes in pain …


The Reliability Of Histamine Pharmacodynamic Response Phenotype Classification In Children With Allergic Disease., Shaun S Kumar, Xiaoxi Liu, Catherine M Sherwin, Bridgette Jones Mar 2020

The Reliability Of Histamine Pharmacodynamic Response Phenotype Classification In Children With Allergic Disease., Shaun S Kumar, Xiaoxi Liu, Catherine M Sherwin, Bridgette Jones

Manuscripts, Articles, Book Chapters and Other Papers

We have identified distinct histamine pharmacodynamic response phenotypes in children with allergic disease utilizing histamine iontophoresis with laser Doppler (HILD). These response phenotypes may be relevant in guiding therapeutic decision making for agents targeting the allergic response pathways. However, the reliability of these response phenotypes has not been assessed. Therefore, we performed HILD in children with allergic rhinitis and/or asthma on two to three separate occasions. HILD response-time data were analyzed in NONMEM using a linked effect PKPD model. Examination of observed vs. classified response phenotypes predicted response plots and the sum of residuals. The intraclass correlation coefficient (ICC) was …


Cell Type Composition And Circuit Organization Of Clonally Related Excitatory Neurons In The Juvenile Mouse Neocortex, Cathryn R Cadwell, Federico Scala, Paul G Fahey, Dmitry Kobak, Shalaka Mulherkar, Fabian H Sinz, Stelios Papadopoulos, Zheng H Tan, Per Johnsson, Leonard Hartmanis, Shuang Li, Ronald J Cotton, Kimberley F Tolias, Rickard Sandberg, Philipp Berens, Xiaolong Jiang, Andreas Savas Tolias Mar 2020

Cell Type Composition And Circuit Organization Of Clonally Related Excitatory Neurons In The Juvenile Mouse Neocortex, Cathryn R Cadwell, Federico Scala, Paul G Fahey, Dmitry Kobak, Shalaka Mulherkar, Fabian H Sinz, Stelios Papadopoulos, Zheng H Tan, Per Johnsson, Leonard Hartmanis, Shuang Li, Ronald J Cotton, Kimberley F Tolias, Rickard Sandberg, Philipp Berens, Xiaolong Jiang, Andreas Savas Tolias

Faculty, Staff and Students Publications

Clones of excitatory neurons derived from a common progenitor have been proposed to serve as elementary information processing modules in the neocortex. To characterize the cell types and circuit diagram of clonally related excitatory neurons, we performed multi-cell patch clamp recordings and Patch-seq on neurons derived from Nestin-positive progenitors labeled by tamoxifen induction at embryonic day 10.5. The resulting clones are derived from two radial glia on average, span cortical layers 2–6, and are composed of a random sampling of transcriptomic cell types. We find an interaction between shared lineage and connection type: related neurons are more likely to …