Digital Commons Network^™

Myosin V Regulates Spatial Localization Of Different Forms Of Neurotransmitter Release In Central Synapses, Dario Maschi, Michael W Gramlich, Vitaly A Klyachko

Open Access Publications

Synaptic active zone (AZ) contains multiple specialized release sites for vesicle fusion. The utilization of release sites is regulated to determine spatiotemporal organization of the two main forms of synchronous release, uni-vesicular (UVR) and multi-vesicular (MVR). We previously found that the vesicle-associated molecular motor myosin V regulates temporal utilization of release sites by controlling vesicle anchoring at release sites in an activity-dependent manner. Here we show that acute inhibition of myosin V shifts preferential location of vesicle docking away from AZ center toward periphery, and results in a corresponding spatial shift in utilization of release sites during UVR. Similarly, inhibition …

Comprehensive Mirnome-Wide Profiling In A Neuronal Cell Model Of Synucleinopathy Implies Involvement Of Cell Cycle Genes, Elisabeth Findeiss, Sigrid C Schwarz, Valentin Evsyukov, Thomas W Rösler, Matthias Höllerhage, Tasnim Chakroun, Niko-Petteri Nykänen, Yimin Shen, Wolfgang Wurst, Michael Kohl, Jörg Tost, Günter U Höglinger

Open Access Publications

Growing evidence suggests that epigenetic mechanisms like microRNA-mediated transcriptional regulation contribute to the pathogenesis of parkinsonism. In order to study the influence of microRNAs (miRNAs), we analyzed the miRNome 2 days prior to major cell death in α-synuclein-overexpressing Lund human mesencephalic neurons, a well-established cell model of Parkinson's disease (PD), by next-generation sequencing. The expression levels of 23 miRNAs were significantly altered in α-synuclein-overexpressing cells, 11 were down- and 12 upregulated (

Initial Clinical Experience Of Mr-Guided Radiotherapy For Non-Small Cell Lung Cancer, Cathryn B Crockett, Pamela Samson, Robert Chuter, Michael Dubec, Corinne Faivre-Finn, Olga L Green, Sara L Hackett, Fiona Mcdonald, Clifford Robinson, Anna-Maria Shiarli, Michael W Straza, Joost J C Verhoeff, Maria Werner-Wasik, Gregory Vlacich, David Cobben

Open Access Publications

Curative-intent radiotherapy plays an integral role in the treatment of lung cancer and therefore improving its therapeutic index is vital. MR guided radiotherapy (MRgRT) systems are the latest technological advance which may help with achieving this aim. The majority of MRgRT treatments delivered to date have been stereotactic body radiation therapy (SBRT) based and include the treatment of (ultra-) central tumors. However, there is a move to also implement MRgRT as curative-intent treatment for patients with inoperable locally advanced NSCLC. This paper presents the initial clinical experience of using the two commercially available systems to date: the ViewRay MRIdian and …

Whipworm-Associated Intestinal Microbiome Members Consistent Across Both Human And Mouse Hosts, Bruce A Rosa, Caroline Snowden, John Martin, Kerstin Fischer, Jonah Kupritz, Ethiopia Beshah, Taniawati Supali, Lincoln Gankpala, Peter U Fischer, Joseph F Urban, Makedonka Mitreva

Open Access Publications

The human whipworm

De Novo Synthesis Of Phosphatidylcholine Is Essential For The Promastigote But Not Amastigote Stage In Leishmania Major, Samrat Moitra, Somrita Basu, Mattie Pawlowic, Fong-Fu Hsu, Kai Zhang

Open Access Publications

Phosphatidylcholine (PC) is the most abundant type of phospholipids in eukaryotes constituting ~30% of total lipids in

Neuroscience Of Object Relations In Health And Disorder: A Proposal For An Integrative Model, Dragan M Svrakic, Charles F Zorumski

Open Access Publications

Recent advances in the neuroscience of episodic memory provide a framework to integrate object relations theory, a psychoanalytic model of mind development, with potential neural mechanisms. Object relations are primordial cognitive-affective units of the mind derived from survival- and safety-level experiences with caretakers during phase-sensitive periods of infancy and toddlerhood. Because these are learning experiences, their neural substrate likely involves memory, here affect-enhanced episodic memory. Inaugural object relations are encoded by the hippocampus-amygdala synaptic plasticity, and systems-consolidated by medial prefrontal cortex (mPFC). Self- and object-mental representations, extracted from these early experiences, are at first dichotomized by contradictory affects evoked by …

Therapeutic Ultrasound-Enhanced Immune Checkpoint Inhibitor Therapy, Jinyun Yuan, Dezhuang Ye, Si Chen, Hong Chen

Open Access Publications

No abstract provided.

Cerebrospinal Fluid Ncam-1 Concentration Is Associated With Neurodevelopmental Outcome In Post-Hemorrhagic Hydrocephalus Of Prematurity, David D. Limbrick, Diego M. Morales, Et Al.

Open Access Publications

OBJECTIVE: Efforts directed at mitigating neurological disability in preterm infants with intraventricular hemorrhage (IVH) and post hemorrhagic hydrocephalus (PHH) are limited by a dearth of quantifiable metrics capable of predicting long-term outcome. The objective of this study was to examine the relationships between candidate cerebrospinal fluid (CSF) biomarkers of PHH and neurodevelopmental outcomes in infants undergoing neurosurgical treatment for PHH.

STUDY DESIGN: Preterm infants with PHH were enrolled across the Hydrocephalus Clinical Research Network. CSF samples were collected at the time of temporizing neurosurgical procedure (n = 98). Amyloid precursor protein (APP), L1CAM, NCAM-1, and total protein (TP) were compared …

Clinical Prediction Rule For Sars-Cov-2 Infection From 116 U.S. Emergency Departments 2-22-2021, Jeffrey A. Kline, Stacey House, Et Al.

Open Access Publications

OBJECTIVES: Accurate and reliable criteria to rapidly estimate the probability of infection with the novel coronavirus-2 that causes the severe acute respiratory syndrome (SARS-CoV-2) and associated disease (COVID-19) remain an urgent unmet need, especially in emergency care. The objective was to derive and validate a clinical prediction score for SARS-CoV-2 infection that uses simple criteria widely available at the point of care.

METHODS: Data came from the registry data from the national REgistry of suspected COVID-19 in EmeRgency care (RECOVER network) comprising 116 hospitals from 25 states in the US. Clinical variables and 30-day outcomes were abstracted from medical records …

Genetic Association Analysis Of The Cardiovascular Biomarker: N-Terminal Fragment Of Pro-B-Type Natriuretic Peptide (Nt-Probnp), Yuan Yang, Joseph M. Zmuda, Mary K. Wojczynski, Bharat Thyagarajan, Kaare Christensen, Ryan K. Cvejkus, Allison L. Kuipers

Open Access Publications

BACKGROUND: NT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP. Therefore, we estimated the heritability of and examined genetic associations of SNPs in the BNP gene region with circulating NT-proBNP and prevalent CVD in 4,331 participants from the Long Life Family Study (LLFS).

METHODS AND RESULTS: Genotypes of 10 SNPs from the NPPB and NPPA regions that encode BNP and A-type natriuretic peptide, respectively, were tested for association with NT-proBNP and prevalent cardiovascular disease and risk factors. We performed analyses using the Sequential Oligogenic Linkage Analysis (SOLAR) program to …

Acute Symptoms Of Mild To Moderate Covid-19 Are Highly Heterogeneous Across Individuals And Over Time, Thomas L. Rodebaugh, Madelyn R. Frumkin, Angela M. Reiersen, Eric J. Lenze, Michael S. Avidan, J. Philip Miller, Jay F. Piccirillo, Charles F. Zorumski, Caline Mattar

Open Access Publications

Background: The symptoms of coronavirus disease 2019 (COVID-19) appear to be heterogenous, and the typical course of these symptoms is unknown. Our objectives were to characterize the common trajectories of COVID-19 symptoms and to assess how symptom course predicts other symptom changes as well as clinical deterioration.

Methods: One hundred sixty-two participants with acute COVID-19 responded to surveys up to 31 times for up to 17 days. Several statistical methods were used to characterize the temporal dynamics of these symptoms. Because 9 participants showed clinical deterioration, we explored whether these participants showed any differences in symptom profiles.

Results: Trajectories varied …

Genomic And Neoantigen Evolution From Primary Tumor To First Metastases In Head And Neck Squamous Cell Carcinoma, Charles R. Schutt, Hua Sun, Jaya Sarin Pradhan, Yvonne Saenger, Jessica Ley, Douglas Adkins, Matthew Ingham, Li Ding, Brian A. Van Tine

Open Access Publications

Head and neck cell squamous-cell carcinomas (HNSCC) are a group of common cancers typically associated with tobacco use and human papilloma virus infection. Up to half of all cases will suffer a recurrence after primary treatment. As such, new therapies are needed, including therapies which promote the anti-tumor immune response. Prior work has characterized changes in the mutation burden between primary and recurrent tumors; however, little work has characterized the changes in neoantigen evolution. We characterized genomic and neoantigen changes between 23 paired primary and recurrent HNSCC tumors. Twenty-three biopsies from patients originally diagnosed with locally advanced disease were identified …

Cognitive Gain Or Handicap: Magical Ideation And Self-Absorption In Clinical And Non-Clinical Participants, János Kállai, Gábor Vincze, Imre András Török, Rita Hargitai, Sándor Rózsa, István Hartung, István Tamás, András Láng, Róbert Herold

Open Access Publications

No abstract provided.

Correspondence Between Perceived Pubertal Development And Hormone Levels In 9-10 Year-Olds From The Adolescent Brain Cognitive Development Study, Megan M. Herting, Andrey P. Anokhin, Deanna M. Barch, Nico Dosenbach, Paul E.A. Glaser, Andrew C. Heath, Nicole R. Karcher, Et Al

Open Access Publications

No abstract provided.

Mr-Guided Adaptive Radiotherapy For Bladder Cancer, Adham Hijab, Boris Tocco, Ian Hanson, Hanneke Meijer, Christina Junker Nyborg, Anders Smedegaard Bertelsen, Robert Jan Smeenk, Gillian Smith, Jeff Michalski, Brian C Baumann, Shaista Hafeez

Open Access Publications

Radiotherapy has an important role in the curative and palliative treatment settings for bladder cancer. As a target for radiotherapy the bladder presents a number of technical challenges. These include poor tumor visualization and the variability in bladder size and position both between and during treatment delivery. Evidence favors the use of magnetic resonance imaging (MRI) as an important means of tumor visualization and local staging. The availability of hybrid systems incorporating both MRI scanning capabilities with the linear accelerator (MR-Linac) offers opportunity for in-room and real-time MRI scanning with ability of plan adaption at each fraction while the patient …

Transcriptome Analysis Of Dnmt3l Knock-Out Mice Derived Multipotent Mesenchymal Stem/Stromal Cells During Osteogenic Differentiation, Chih-Yi Yang, Rita Jui-Hsien Lu, Ming-Kang Lee, Felix Shih-Hsian Hsiao, Ya-Ping Yen, Chun-Chun Cheng, Pu-Sheng Hsu, Yi-Tzang Tsai, Shih-Kuo Chen, I-Hsuan Liu, Pao-Yang Chen, Shau-Ping Lin

Open Access Publications

Multipotent mesenchymal stem/stromal cells (MSCs) exhibit great potential for cell-based therapy. Proper epigenomic signatures in MSCs are important for the maintenance and the subsequent differentiation potential. The DNA methyltransferase 3-like (DNMT3L) that was mainly expressed in the embryonic stem (ES) cells and the developing germ cells plays an important role in shaping the epigenetic landscape. Here, we report the reduced colony forming ability and impaired

Gestational Age-Specific Complete Blood Count Signatures In Necrotizing Enterocolitis, Julia M Pantalone, Silvia Liu, Oluwabunmi O Olaloye, Erica C Prochaska, Toby Yanowitz, Melissa M Riley, Justin R Buland, Beverly S Brozanski, Misty Good, Liza Konnikova

Open Access Publications

No abstract provided.

Machine Learning Analytics Of Resting-State Functional Connectivity Predicts Survival Outcomes Of Glioblastoma Multiforme Patients, Bidhan Lamichhane, Andy G S Daniel, John J Lee, Daniel S Marcus, Joshua S Shimony, Eric C Leuthardt

Open Access Publications

Glioblastoma multiforme (GBM) is the most frequently occurring brain malignancy. Due to its poor prognosis with currently available treatments, there is a pressing need for easily accessible, non-invasive techniques to help inform pre-treatment planning, patient counseling, and improve outcomes. In this study we determined the feasibility of resting-state functional connectivity (rsFC) to classify GBM patients into short-term and long-term survival groups with respect to reported median survival (14.6 months). We used a support vector machine with rsFC between regions of interest as predictive features. We employed a novel hybrid feature selection method whereby features were first filtered using correlations between …

Ontogenetic Oxycodone Exposure Affects Early Life Communicative Behaviors, Sensorimotor Reflexes, And Weight Trajectory In Mice, Elena Minakova, Simona Sarafinovska, Marwa O Mikati, Kia M Barclay, Katherine B Mccullough, Joseph D Dougherty, Ream Al-Hasani, Susan E Maloney

Open Access Publications

Nationwide, opioid misuse among pregnant women has risen four-fold from 1999 to 2014, with commensurate increase in neonates hospitalized for neonatal abstinence syndrome (NAS). NAS occurs when a fetus exposed to opioids

Srf Is Required For Maintenance Of Astrocytes In Non-Reactive State In The Mammalian Brain, Monika Jain, Soumen Das, Paul P Y Lu, Garima Virmani, Sumitha Soman, Surya Chandra Rao Thumu, David H Gutmann, Narendrakumar Ramanan

Open Access Publications

Astrocytes play several critical roles in the normal functioning of the mammalian brain, including ion homeostasis, synapse formation, and synaptic plasticity. Following injury and infection or in the setting of neurodegeneration, astrocytes become hypertrophic and reactive, a process termed astrogliosis. Although acute reactive gliosis is beneficial in limiting further tissue damage, chronic gliosis becomes detrimental for neuronal recovery and regeneration. Several extracellular factors have been identified that generate reactive astrocytes; however, very little is known about the cell-autonomous transcriptional mechanisms that regulate the maintenance of astrocytes in the normal non-reactive state. Here, we show that conditional deletion of the stimulus-dependent …

Brain Volumetric Deficits In Mapt Mutation Carriers: A Multisite Study, Stephanie A. Chu, Nupur Ghoshal, Et Al

Open Access Publications

No abstract provided.

Defining Intermediates And Redundancies In Coenzyme Q Precursor Biosynthesis, Kyle P. Robinson, Adam Jochem, Sheila E. Johnson, Thiruchelvi R. Reddy, Jason D. Russell, Joshua J. Coon, David J. Pagliarini

Open Access Publications

No abstract provided.

The Position Of Single-Base Deletions In The Vntr Sequence Of The Carboxyl Ester Lipase (Cel) Gene Determines Proteotoxicity, Anny Gravdal, Xunjun Xiao, Miriam Cnop, Khadija El Jellas, Stefan Johansson, Pål R. Njølstad, Mark E. Lowe, Bente B. Johansson, Anders Molven, Karianne Fjeld

Open Access Publications

No abstract provided.

High-Fat Diet Activates Liver Ipla2Γ Generating Eicosanoids That Mediate Metabolic Stress, Sung Ho Moon, Beverly Gibson Dilthey, Xinping Liu, Shaoping Guan, Harold F. Sims, Richard W. Gross

Open Access Publications

No abstract provided.

4Β-Hydroxycholesterol Is A Prolipogenic Factor That Promotes Srebp1c Expression And Activity Through The Liver X Receptor, Ofer Moldavski, Peter-James H. Zushin, Charles A. Berdan, Robert J. Van Eijkeren, Xuntian Jiang, Mingxing Qian, Daniel S. Ory, Douglas F. Covey, Daniel K. Nomura, Andreas Stahl, Ethan J. Weiss, Roberto Zoncu

Open Access Publications

No abstract provided.

Generation Of A Gene-Corrected Human Isogenic Ipsc Line From An Alzheimer’S Disease Ipsc Line Carrying The London Mutation In App (V717i), Damian Hernandez, Stephanie Morgan Schlicht, Maciej Daniszewski, Celeste M. Karch, Dominantly Inherited Network (Dian), Alison M. Goate, Alice Pebay

Open Access Publications

No abstract provided.

Familial Lipomas Without Classic Neurofibromatosis-1 Caused By A Missense Germline Nf1 Mutation, Erika Ramirez, Stephanie M. Morris, Tychele N. Turner, David H. Gutmann

Open Access Publications

No abstract provided.

Cytokine Profiling In Plasma From Patients With Brain Tumors Versus Healthy Individuals Using 2 Different Multiplex Immunoassay Platforms, Diane Elizabeth Bender, Maximilian O. Schaettler, Kathleen C.F. Sheehan, Tanner M. Johanns, Gavin P. Dunn

Open Access Publications

No abstract provided.

Resting-State Functional Connectivity Disruption As A Pathological Biomarker In Autosomal Dominant Alzheimer Disease, Robert X. Smith, Jeremy F. Strain, Aaron Tanenbaum, Anne M. Fagan, Jason Hassenstab, Eric Mcdade, Suzanne E. Schindler, Brian A. Gordon, Chengjie Xiong, Celeste Karch, David M. Holtzman, Daniel S. Marcus, John C. Morris, Tammie L.S. Benzinger, Randall J. Bateman, Beau M. Ances, Et Al.

Open Access Publications

No abstract provided.

Cisplatin +/− Rucaparib After Preoperative Chemotherapy In Patients With Triple-Negative Or Brca Mutated Breast Cancer, Maitri Kalra, Yang Tong, David R. Jones, Tom Walsh, Michael A. Danso, Cynthia X. Ma, Paula Silverman, Mary-Claire King, Sunil S. Badve, Susan M. Perkins, Kathy D. Miller

Open Access Publications

No abstract provided.