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Fluorescent Peptide For Detecting Factor Xiiia Activity And Fibrin In Whole Blood Clots Forming Under Flow, Yue Liu, Jennifer Crossen, Timothy J. Stalker, Scott L. Diamond

Cardeza Foundation for Hematologic Research

Background

During clotting, thrombin generates fibrin monomers and activates plasma-derived transglutaminase factor (F) XIIIa; collagen and thrombin-activated platelets offer thrombin-independent cellular FXIIIa (cFXIIIa) for clotting. Detecting fibrin on collagen and tissue factor surfaces in whole blood clotting typically uses complex reagents like fluorescent fibrinogen or antifibrin antibody.

Objectives

We want to test whether the peptide using the α2- antiplasmin crosslinking mechanism by FXIIIa is a useful tool in both monitoring FXIIIa activity, and visualize and monitor fibrin formation, deposition, and extent of crosslinking within fibrin structures in whole blood clots formed under flow.

Methods

We tested a fluorescent peptide derived …

C9orf72 Poly(Pr) Mediated Neurodegeneration Is Associated With Nucleolar Stress, M. E. Cicardi, J. H. Hallgren, D. Mawrie, K. Krishnamurthy, S. S. Markandaiah, A. T. Nelson, V. Kankate, E. N. Anderson, P. Pasinelli, U. B. Pandey, C. M. Eischen, D. Trotti

Farber Institute for Neuroscience Faculty Papers

The ALS/FTD-linked intronic hexanucleotide repeat expansion in the C9orf72 gene is aberrantly translated in the sense and antisense directions into dipeptide repeat proteins, among which poly proline-arginine (PR) displays the most aggressive neurotoxicity in-vitro and in-vivo. PR partitions to the nucleus when heterologously expressed in neurons and other cell types. We show that by lessening the nuclear accumulation of PR, we can drastically reduce its neurotoxicity. PR strongly accumulates in the nucleolus, a nuclear structure critical in regulating the cell stress response. We determined that, in neurons, PR caused nucleolar stress and increased levels of the transcription factor p53. …

Gene Signature Reveals Decreased Sox10-Dependent Transcripts In Malignant Cells From Immune Checkpoint Inhibitor-Resistant Cutaneous Melanomas, Timothy J. Purwin, Signe Caksa, Ahmet Sacan, Claudia Capparelli, Andrew E. Aplin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Evidence is mounting for cross-resistance between immune checkpoint and targeted kinase inhibitor therapies in cutaneous melanoma patients. Since the loss of the transcription factor, SOX10, causes tolerance to MAPK pathway inhibitors, we used bioinformatic techniques to determine if reduced SOX10 expression/activity is associated with immune checkpoint inhibitor resistance. We integrated SOX10 ChIP-seq, knockout RNA-seq, and knockdown ATAC-seq data from melanoma cell models to develop a robust SOX10 gene signature. We used computational methods to validate this signature as a measure of SOX10-dependent activity in independent single-cell and bulk RNA-seq SOX10 knockdown, cell line panel, and MAPK inhibitor drug-resistant datasets. Evaluation …

Increased Sirt3 Combined With Parp Inhibition Rescues Motor Function Of Sbma Mice, David R. Garcia Castro, Joseph R. Mazuk, Erin M. Heine, Daniel Simpson, R. Seth Pinches, Caroline Lozzi, Kathryn Hoffman, Phillip Morrin, Dylan Mathis, Maria V. Lebedev, Elyse Nissley, Kang Hoo Han, Tyler Farmer, Diane E. Merry, Qiang Tong, Maria Pennuto, Heather L. Montie

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease with substantial mitochondrial and metabolic dysfunctions. SBMA is caused by polyglutamine (polyQ) expansion in the androgen receptor (AR). Activating or increasing the NAD+-dependent deacetylase, SIRT3, reduced oxidative stress and death of cells modeling SBMA. However, increasing diminished SIRT3 in AR100Q mice failed to reduce acetylation of the SIRT3 target/antioxidant, SOD2, and had no effect on increased total acetylated peptides in quadriceps. Yet, overexpressing SIRT3 resulted in a trend of motor recovery, and corrected TCA cycle activity by decreasing acetylation of SIRT3 target proteins. We sought to boost blunted SIRT3 activity …

Differential Response Of C9orf72 Transcripts Following Neuronal Depolarization, Layla T. Ghaffari, Davide Trotti, Aaron R. Haeusler

Farber Institute for Neuroscience Faculty Papers

The (G4C2)n nucleotide repeat expansion (NRE) mutation in C9orf72 is the most common genetic cause of ALS and FTD. The biological functions of C9orf72 are becoming understood, but it is unclear if this gene is regulated in a neural-specific manner. Neuronal activity is a crucial modifier of biological processes in health and neurodegenerative disease contexts. Here, we show that prolonged membrane depolarization in healthy human iPSC-cortical neurons leads to a significant downregulation of a transcript variant 3 (V3) of C9orf72, with a concomitant increase in variant 2 (V2), which leads to total C9orf72 RNA transcript levels remaining unchanged. However, the …

1485-Pub: Assessing Correlates Of Microvascular Complications Among Patients With Diabetes Mellitus, Kenneth Izuora, Amalie Alver, Arpita Basu, Kavita Batra, Shelley J. Williams, Jeffrey L. Ebersole

Internal Medicine Faculty Publications

Background: Microvascular complications associated with diabetes (DM) are important predictors of morbidity and mortality. Understanding the factors associated with these complications is important in reducing their burden. Method: Using a cross-sectional study design, seventy-one ambulatory patients with Type 2 DM (female 60.6%, white 36.6%, mean age 64.1± 10.3 years, and mean duration of DM 15.8±9.1 years) were recruited using an investigator-administered questionnaire and chart review. Variables of demographics, smoking, HbA1c, DM duration, and complications were collected. CRP was measured and oral health status was assessed by a clinical exam. Data were analyzed using Chi-square/Fisher exact tests and binomial logistic regression …

Disinfectants In Interventional Practices, Mayank Aranke, Roya Moheimani, Melissa Phuphanich, Alan D. Kaye, Anh L. Ngo, Omar Viswanath, Jared Herman

School of Medicine Faculty Publications

Purpose of Review: This review aims to provide relevant, aggregate information about a variety of disinfectants and antiseptics, along with potential utility and limitations. While not exhaustive, this review’s goal is to add to the body of literature available on this topic and give interventional providers and practitioners an additional resource to consider when performing procedures. Recent Findings: In the current SARS-CoV2 epidemiological environment, infection control and costs associated with healthcare-associated infections (HAIs) are of paramount importance. Even before the onset of SARS-CoV2, HAIs affected nearly 2million patients a year in the USA and resulted in nearly 90,000 deaths, all …

Improved De Novo Alignment Of A Girardia Dorotocephala Ma-C2 (2n = 24) Transcriptome, Labib Rouhana, J F. Ryan, Eugene M. P. Almazan

Biological Sciences Faculty Publications

Improved De novo alignment of a Girardia dorotocephala MA-C2 (2n = 24) transcriptome.

Data From: Docosahexaenoic Acid Consumption Impedes Early Interferon- And Chemokine-Related Gene Expression While Suppressing Silica-Triggered Flaring Of Murine Lupus, Abby D. Benninghoff, James Pestka

Browse all Datasets

The dataset contains five files of tabular data with an accompanying README file.

Supplementary file 1: Customized probe annotation file for the Nanostring nCounter Mouse PanCancer Immune Profiling Panel (catalog # 115000142). This file is provided as supporting material for a journal article.

Supplementary file 2: Microsoft Excel document with output from nSolver for differential expression analyses for pairwise comparisons noted by each named sheet. This data set is supporting material for a journal article.

Supplementary file 3: Microsoft Excel document with output from nSolver for global and directed significance scores for immune pathways. This data set is supporting material …

Role Of Eif4g1 In Non-Small Cell Lung Cancer Pathogenesis And Targeted Therapy, Zhiqiang Qin, Lu Dai, Luis Del Valle

School of Medicine Faculty Publications

American Association for Cancer Research Annual Meeting 2019, March 29 - April 3, 2019, Atlanta, GA

Data From: Mapping Of Dynamic Transcriptome Changes Associated With Silica-Triggered Autoimmune Pathogenesis In The Lupus-Prone Nzbwf1 Mouse, James Pestka, Abby D. Benninghoff

Browse all Datasets

The dataset contains six files of tabular data with an accompanying README file.

Supplementary file 1: Customized probe annotation file for the Nanostring nCounter Mouse PanCancer Immune Profiling Panel (catalog # 115000142). This file is provided as supporting material for a journal article. Codes for columns are in file.

Supplementary file 2: Microsoft Excel document with output from nSolver for differential expression analyses for pairwise comparisons noted by each named sheet. This data set is supporting material for a journal article. Codes for columns are listed in README.

Supplementary File 3: Microsoft Excel document with output from nSolver for global …

Assessment Of Interprofessional Team Collaboration Scale (Aitcs): Further Testing And Instrument Revision., Carole Orchard, Linda L Pederson, Emily Read, Cornelia Mahler, Heather Laschinger

Nursing Publications

INTRODUCTION: The need to be able to assess collaborative practice in health care teams has been recognized in response to the direction for team-based care in a number of policy documents. The purpose of this study is to report on further refinement of such a measurement instrument, the Assessment of Interprofessional Team Collaboration Scale (AITCS) first published in 2012. To support this refinement, two objectives were set: Objective 1: to determine whether the items from the data collected in 2016 load on the same factors as found for the 2012 version of the 37-item AITCS. Objective 2: to determine whether …

The Large-Scale Organization Of Shape Processing In The Ventral And Dorsal Pathways, Erez Freud, Jody C. Culham, David C. Plaut, Marlene Behrmann

Brain and Mind Institute Researchers' Publications

Although shape perception is considered a function of the ventral visual pathway, evidence suggests that the dorsal pathway also derives shape-based representations. In two psychophysics and neuroimaging experiments, we characterized the response properties, topographical organization and perceptual relevance of these representations. In both pathways, shape sensitivity increased from early visual cortex to extrastriate cortex but then decreased in anterior regions. Moreover, the lateral aspect of the ventral pathway and posterior regions of the dorsal pathway were sensitive to the availability of fundamental shape properties, even for unrecognizable images. This apparent representational similarity between the posterior-dorsal and lateral-ventral regions was corroborated …

Attenuation Of Postoperative Adhesions Using A Modeled Manual Therapy (Data Files), Geoffrey M. Bove, Susan L. Chapelle, Katherine E. Hanlon, Michael P. Diamond, David J. Mokler

Biomedical Sciences Faculty Publications

These files include data and figures utilized to research and communicate the following:

Postoperative adhesions are pathological attachments that develop between abdominopelvic structures following surgery. Considered unavoidable and ubiquitous, postoperative adhesions lead to bowel obstructions, infertility, pain, and reoperations, and represent a substantial health care challenge. Despite over a century of research, no preventive treatment exists. Based on the hypothesis that postoperative adhesions develop from a lack of movement of the abdominopelvic organs, we proposed a relatively simple treatment approach using a modified manual therapy technique that mobilizes abdominopelvic structures in the immediate postoperative period while they are otherwise rendered …

Dynamical System Modeling To Simulate Donor T Cell Response To Whole Exome Sequencing-Derived Recipient Peptides: Understanding Randomness In Alloreactivity Incidence Following Stem Cell Transplantation, Vishal Koparde, Badar Abdul Razzaq, Tara Suntum, Roy Sabo, Allison Scalora, Myrna Serrano, Max Jameson-Lee, Charles Hall, David Kobulnicky, Nihar Sheth, Juliana Feltz, Daniel Contaifer, Dayanjan Wijesinghe, Jason Reed, Catherine Roberts, Rehan Qayyum, Gregory Buck, Michael Neale, Amir Toor

Massey Comprehensive Cancer Center Data

Quantitative relationship between the magnitude of variation in minor histocompatibility antigens (mHA) and graft versus host disease (GVHD) pathophysiology in stem cell transplant (SCT) donor-recipient pairs (DRP) is not established. In order to elucidate this relationship, whole exome sequencing (WES) was performed on 27 HLA matched related (MRD), & 50 unrelated donors (URD), to identify nonsynonymous single nucleotide polymorphisms (SNPs). An average 2,463 SNPs were identified in MRD, and 4,287 in URD DRP (p

Perspectives On: Sgp Symposium On Mitochondrial Physiology And Medicine: Molecular Identities Of Mitochondrial Ca2+ Influx Mechanism: Updated Passwords For Accessing Mitochondrial Ca2+-Linked Health And Disease., Jin O-Uchi, Shi Pan, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

No abstract provided.

Susceptibility Of Chlamydia Trachomatis To The Excipient Hydroxy-Ethylcellulose: Ph And Concentration Dependence Of Antimicrobial Activity, Ali A. Abdul-Sater, David M. Ojcius, M. P. Meyer

All Dugoni School of Dentistry Faculty Articles

Hydroxyethyl cellulose (HEC) is used as a neutral excipient in microbicides used against sexually transmitted pathogens. However, HEC inhibits the infection of cervical epithelial cells by Chlamydia trachomatis at pH 5 in a concentration-dependent manner. At pH 7, infection is inversely dependent on the concentration of HEC, possibly due to pH-dependent calcium sequestration.

H-Ras Inhibits Rhoa/Rock Leading To Decrease In The Basal Tone In The Internal Anal Sphincter, Marcio A.F. De Godoy, Chirag A. Patel, Scott A. Waldman, Motoya Katsuki, Raymond F. Regan, Satish Rattan

Department of Medicine Faculty Papers

Background & Aims: Present studies evaluated the role of H-ras and its implications in the RhoA/Rho kinase (ROCK) pathway in regulating basal tone in the murine internal anal sphincter (IAS).

Methods: Studies were performed in the IAS from the wild type (H-ras^+/+) and knock-out (H-ras^-/-) mice. The basal tone of smooth muscle strips were measured by isometric force transducers. Length of smooth muscle cells (SMC) isolated from the IAS in the basal state was determined by phase contrast microscopy. Experiments were repeated in the presence of Y 27632 a ROCK inhibitor. Involvement of the RhoA/ROCK machinery …

Chemotherapeutic Cns Prophylaxis And Neuropsychologic Change In Children With Acute Lymphoblastic Leukemia: A Prospective Study, K. A. Espy, I. M. Moore, P. M. Kaufmann, J. H. Kramer, K. Matthay, J. J. Hutter

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

OBJECTIVE: To determine whether prophylactic CNS chemotherapy for childhood acute lymphoblastic leukemia is associated with declines in neuropsychological abilities. METHODS: Growth curve analysis was used to examine neuropsychological outcome and treatment-related change in children (N = 30) who were treated at two childhood cancer centers. A comprehensive test battery was administered at baseline (8 months), 2, 3, and 4 years postdiagnosis (age at diagnosis M = 5.90 years, SD = 4.2C). RESULTS: Results indicated modest declines in arithmetic, visual motor integration, and verbal fluency. Intrathecal and systemic treatment was related to poorer visual motor integration at 4 years postdiagnosis and …