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- Type:
- Dataset
- Description/Abstract:
- Retrospective chart review project of subjects receiving lumbar epidural steroid injections for low back pain associated with degenerative disc disease. The primary objective was to compare the efficacy of two different steroids used during the time period studied, methylprednisolone and triamcinolone.
- Creator/Author:
- Strong, Judith
- Submitter:
- Judith Strong
- Date Uploaded:
- 08/24/2023
- Date Modified:
- 08/15/2024
- Date Created:
- 2023-08
- License:
- Open Data Commons Public Domain Dedication and License (PDDL)
- Type:
- Dataset
- Description/Abstract:
- ABSTRACT Purpose: Tongue manometry (i.e. tongue pressure measurement) is a commonly used assessment for patients with suspected oral-motor involvement in swallowing disorders. Availability of lingual manometry has changed in recent years, with the introduction of the TongueometerTM device being a more affordable tongue manometry system. The purpose of this study was to test concurrent (criterion) validity of the TongueometerTM compared to the current standard reference device, the Iowa Oral Performance Instrument, IOPI®. Method: Adults without dysphagia were recruited for participation in this study. Standard lingual measurements (swallowing-related pressures, maximum isometric pressure (MIP), and maximum isometric endurance) were recorded, with the bulb anteriorly placed, with both devices, in a randomized order. The Bland-Altman method was used to determine concurrent (criterion) validity of these measurements compared to the clinical standard IOPI® device. A recently available suggested corrective value by Curtis and colleagues (2023) was also applied, with comparisons made between devices both with and without the Curtis correction. Results: The final sample included 70 adult participants aged 20-89 years (average age 52.3 years). Measures with the TongueometerTM device were significantly lower when compared with the same measures taken using the IOPI® (p<0.01) for all measures including MIP, endurance, and swallow pressures. The correction suggested by Curtis and colleagues did not ameliorate these differences. Conclusions: The TongueometerTM lingual measurements were consistently lower compared to the IOPI®. Clinical use of values taken with the TongueometerTM device should be compared to normative data published for each specific device. Available features of each device (e.g. display, bulb texture, technology/application) should be considered when selecting which device to use with an individual patient.
- Creator/Author:
- Krekeler, Brittany
- Submitter:
- Brittany Krekeler
- Date Uploaded:
- 01/26/2024
- Date Modified:
- 01/26/2024
- Date Created:
- 2020-01-01
- License:
- Open Data Commons Public Domain Dedication and License (PDDL)
- Type:
- Dataset
- Description/Abstract:
- Data from qualitative study "Employing Strategies to Address Implicit Racial Bias in the Home Visit Setting" Includes: written reflections by FM residents, resident focus group data, commitments-to-change, and 3-month follow up survey data
- Creator/Author:
- Goroncy, Anna
- Submitter:
- Anna Goroncy
- Date Uploaded:
- 03/03/2023
- Date Modified:
- 03/03/2023
- Date Created:
- 2020-01
- License:
- Open Data Commons Attribution License (ODC-By)
- Type:
- Document
- Description/Abstract:
- This is a preprint of a to be submitted paper that demonstrates that: (1) many important food allergens (eggs, milk, peanuts, tree nuts) induce the unfolded protein response (UPR) in intestinal epithelial cells; (2) induction of the UPR, in turn, stimulates the expression of pro-Th2 cytokines (IL-25, IL-33, TSLP) that are required for the induction of food allergy by these cytokines; (3) egg allergy is suppressed in mouse models by the UPR inhibitor, metformin (a drug widely used to treat diabetes mellitus); and (4) metformin appears to have a protective effects in humans who have alpha-gal syndrome, which is a form of food allergy.
- Creator/Author:
- Finkelman, Fred
- Submitter:
- Fred Finkelman
- Date Uploaded:
- 06/02/2020
- Date Modified:
- 06/02/2020
- Date Created:
- 2020-06-02
- License:
- Open Data Commons Attribution License (ODC-By)
- Type:
- Dataset
- Description/Abstract:
- This data set and accompanying files represents air monitoring data collected by the Environmental Protection Agency from 2009-08-17 to 2012-02-25 at the Warren Elementary School in Marietta, Ohio (39.393536, -81.554015). The variables of interest were the amount of manganese and lead in the air measured as PM10 particle size. The visualizations were created from monthly averages for the concentration of airborne manganese. The data was collected using the TO-15 collection systems for air monitoring device. (reference - https://www3.epa.gov/air/sat/pdfs/VocTechdocwithappendix1209.pdf) The files included are: The raw data - Marietta_WarrenElementraySchool_Raw.csv . Aggregated monthly averages of the raw data - Marietta_WarrenElementraySchool_Processed.csv. How the raw data are processed into monthly averages - Marietta_WarrenElementraySchool_WorkingFile.xlsx. How the video is generated- Marietta_WarrenElementraySchool.ppt. Video - Marietta_WarrenElementraySchool.mp4 - generated from Marietta_WarrenElementraySchool.ppt.
- Creator/Author:
- Erin Hayes; Zhiyuan Yao, and Tim Hilbert
- Submitter:
- Amy Koshoffer
- Date Uploaded:
- 10/26/2018
- Date Modified:
- 07/11/2019
- Date Created:
- 2009-08-17 to 2012-02-25
- License:
- CC0 1.0 Universal
- Type:
- Dataset
- Description/Abstract:
- This data set and accompanying files represents air monitoring data collected by the Environmental Protection Agency from 2009-08-17 to 2012-02-25 at the Ohio Valley Educational Service Center in Marietta, Ohio (39.443477 , -81.452199). The variables of interest were the amount of manganese and lead in the air measured as PM10 particle size. The visualizations were created from monthly averages for the concentration of airborne manganese The data was collected using the TO-15 collection systems for air monitoring device. (reference - https://www3.epa.gov/air/sat/pdfs/VocTechdocwithappendix1209.pdf) The files included are: The raw data - Marietta_OhioValleyEducationalServiceCenter_Raw.csv . Aggregated monthly averages of the raw data - Marietta_OhioValleyEducationalServiceCenter_Processed.csv. How the raw data are processed into monthly averages - Marietta_OhioValleyEducationalServiceCenter_WorkingFile.xlsx. How the video is generated- Marietta_OhioValleyEducationalServiceCenter.ppt. Video - Marietta_OhioValleyEducationalServiceCenter - generated from Marietta_OhioValleyEducationalServiceCenter.ppt.
- Creator/Author:
- Yao, Zhiyuan; Hilbert, Tim, and Haynes, Erin
- Submitter:
- Amy Koshoffer
- Date Uploaded:
- 10/27/2018
- Date Modified:
- 07/11/2019
- Date Created:
- 2009-08-17 to 2012-02-25
- License:
- CC0 1.0 Universal
- Type:
- Dataset
- Description/Abstract:
- This data set and accompanying files represents air monitoring data collected by the Environmental Protection Agency from 2009-08-12 to 2012-01-28 at the East Liverpool East Elementary School, in East Liverpool, Ohio (40.635093 , -80.545558). The variables of interest were the amount of manganese and lead in the air measured as PM10 particle size. The visualizations were created from monthly averages for the concentration of airborne manganese. The data was collected using the TO-15 collection systems for air monitoring device. (reference - https://www3.epa.gov/air/sat/pdfs/VocTechdocwithappendix1209.pdf) The files included are: The raw data - EastLiverpoolEastElementarySchool_Raw.csv . Aggregated monthly averages of the raw data - EastLiverpoolEastElementarySchool_Processed.csv. How the raw data are processed into monthly averages - Marietta_EastLiverpoolEastElementarySchool_WorkingFile.xlsx. How the video is generated- EastLiverpoolEastElementarySchool.ppt. Video - EastLiverpoolEastElementarySchool- generated from EastLiverpoolEastElementarySchool.ppt.
- Creator/Author:
- Yao, Zhiyuan; Hilbert, Tim, and Haynes, Erin
- Submitter:
- Amy Koshoffer
- Date Uploaded:
- 10/27/2018
- Date Modified:
- 07/11/2019
- Date Created:
- 2009-08-12 to 2012-01-28
- License:
- CC0 1.0 Universal
- Type:
- Dataset
- Description/Abstract:
- This data set and accompanying files represents air monitoring data collected by the Environmental Protection Agency from 2009-08-12 to 2012-01-28 at the East Liverpool Water Treatment Plant, in East Liverpool, Ohio (40.639501 , -80.523561). The variables of interest were the amount of manganese and lead in the air measured as PM10 particle size. The visualizations were created from monthly averages for the concentration of airborne manganese The data was collected using the TO-15 collection systems for air monitoring device. (reference - https://www3.epa.gov/air/sat/pdfs/VocTechdocwithappendix1209.pdf) The files included are: The raw data - EastLiverpool_WaterTreatmentPlant_Raw.csv . Aggregated monthly averages of the raw data - EastLiverpool_WaterTreatmentPlant_Processed.csv. How the raw data are processed into monthly averages - Marietta_EastLiverpool_WaterTreatmentPlant_WorkingFile.xlsx. How the video is generated- EastLiverpool_WaterTreatmentPlant.ppt. Video - EastLiverpool_WaterTreatmentPlant- generated from EastLiverpool_WaterTreatmentPlant.ppt.
- Creator/Author:
- Yao, Zhiyuan; Hilbert, Tim, and Haynes, Erin
- Submitter:
- Amy Koshoffer
- Date Uploaded:
- 10/27/2018
- Date Modified:
- 07/11/2019
- Date Created:
- 2009-01 to 2018-04
- License:
- CC0 1.0 Universal
- Type:
- Student Work
- Description/Abstract:
- Summary: The diagnosis of sarcoidosis is made by the combination of clinical features and biopsy results. The clinical features of sarcoidosis can be quite variable. We developed a Sarcoidosis Diagnostic Score (SDS) to summarize the clinical features of possible sarcoidosis patients. Biopsy confirmed sarcoidosis patients seen during a seven-month time period at the University of Cincinnati Sarcoidosis clinic were prospectively identified. Non-sarcoidosis patients seen at the same clinic were used as controls. Using a modified WASOG organ assessment instrument, we scored all patients for presence of biopsy, one or more highly probable symptom, and one or more at least probable symptom for each area. Two sarcoidosis scores were generated: SDS biopsy (with biopsy) and SDS clinical (without biopsy).The 980 evaluable patients were divided into two cohorts: an initial 600 patients (450 biopsy confirmed sarcoidosis, 150 controls) to establish cut-off values for SDS biopsy and SDS clinical and a validation cohort of 380 patients (103 biopsy confirmed sarcoidosis patients and 277 controls). The best cutoff value for SDS biopsy was > 6 (sensitivity =99.3%; specificity=100%). For the total the 980 patients, an SDS clinical > 3 had a sensitivity of 94.2%, specificity of 88.8%, and a likelihood ratio of 7.9. An SDS clinical score > 4 had a lower sensitivity of (76.9%) but higher specificity (98.6%). For sarcoidosis, the presence of specific clinical features, especially multi-organ involvement, can enhance the diagnostic certainty. The SDS scoring system quantitated the clinical features consistent with sarcoidosis. Awards/Publications: Published in CHEST Journal 2018 Oral presentation at the 2018 American Thoracic Society Conference
- Creator/Author:
- Lower, Elyse E., M.D.; Baughman, Robert P., M.D., and Bickett, Alexandra
- Submitter:
- Alexandra Bickett
- Date Uploaded:
- 05/24/2018
- Date Modified:
- 05/24/2018
- Date Created:
- 2018-04-15
- License:
- Attribution-ShareAlike 4.0 International
10. ELISA_QC
- Type:
- Student Work
- Description/Abstract:
- This program is meant to batch process ELISA standard curve data to generate Levey-Jennings control charts and report values that fall outisde of 2 and 3 standard deviations of the mean. The Instruction Manual contains a detailed guide on usage.
- Creator/Author:
- Wetzel, Hanna
- Submitter:
- Hanna Wetzel
- Date Uploaded:
- 04/21/2017
- Date Modified:
- 04/21/2017
- License:
- All rights reserved
- Type:
- Dataset
- Description/Abstract:
- ABSTRACT Helicobacter pylori (H. pylori) is the major risk factor for the development of gastric cancer. Our laboratory has reported that the Sonic Hedgehog (Shh) signaling pathway is an early response to infection that is fundamental to the initiation of H. pylori-induced gastritis. H. pylori also induces programmed death ligand 1 (PD-L1) expression on gastric epithelial cells, yet the mechanism is unknown. We hypothesize that H. pylori-induced PD-L1 expression within the gastric epithelium is mediated by the Shh signaling pathway during infection. To identify the role of Shh signaling as a mediator of H. pylori-induced PD-L1 expression, human gastric organoids generated from either induced pluripotent stem cells (HGOs) or tissue (huFGOs) were microinjected with bacteria and treated with Hedgehog/Gli inhibitor GANT61. Gastric epithelial monolayers generated from the huFGOs were also infected with H. pylori and treated with GANT61 to study the role of Hedgehog signaling as a mediator of induced PD-1 expression. A patient-derived organoid/autologous immune cell co-culture system infected with H. pylori and treated with PD-1 inhibitor (PD-1Inh) was developed to study the protective mechanism of PD-L1 in response to bacterial infection. H. pylori significantly increased PD-L1 expression in organoid cultures 48 hours post-infection when compared to uninfected controls. The mechanism was cytotoxic associated gene A (CagA) dependent. This response was blocked by pretreatment with GANT61. Anti-PD-L1 treatment of H. pylori infected huFGOs, co-cultured with autologous patient cytotoxic T lymphocytes and dendritic cells, induced organoid death. H. pylori-induced PD-L1 expression is mediated by the Shh signaling pathway within the gastric epithelium. Cells infected with H. pylori that express PD-L1 may be protected from the immune response, creating premalignant lesions progressing to gastric cancer.
- Creator/Author:
- Zavros, Yana
- Submitter:
- Yana Zavros
- Date Uploaded:
- 12/21/2018
- Date Modified:
- 12/21/2018
- Date Created:
- License:
- All rights reserved
- Type:
- Document
- Description/Abstract:
- This talk was the second panelist in the Health Equities and Disparities Session for the 4th Annual UC Data Day Conference hosted by UC Libraries. Tammy Mentzel, MPH, Assistant Director for Programs and Projects, University of Cincinnati, Academic Health Center, Cincinnati Cancer Center Talk Title(s): Understanding Health Disparities and Perceptions of Discrimination in Greater Cincinnati Tammy served as the Program Director for the Transformation of Mission-based Health Care through Diversity, Equity, and Inclusion project aimed at bolstering diversity in the health care workforce and eliminating health disparities in urban communities by identifying, testing and adopting evidence-based strategies and tools. Tammy was formerly in the College of Nursing at UC where she was a Research Associate and Program Director providing leadership and support on six funded research projects totaling over $4.6 million.
- Creator/Author:
- Mentzel, Tammy
- Submitter:
- Amy Koshoffer
- Date Uploaded:
- 04/12/2019
- Date Modified:
- 04/12/2019
- Date Created:
- 2019-04-01
- License:
- Attribution-NonCommercial 4.0 International
- Type:
- Document
- Description/Abstract:
- This presentation represents Panelists 3 and 4 as a joint presentation and This talk was the third panelist in the Health Equities and Disparities Session for the 4th Annual UC Data Day Conference hosted by UC Libraries. Joint Talk with Dr. Pickle and Stef Murwsky – Title: Developing Best Practices to Address LGBTQ and Health Disparities Sarah Pickle, MD (she/her/hers), Associate Professor, University of Cincinnati Department of Family and Community Medicine. Dr. Pickle and her colleagues are studying best practices for training future generations of health care professionals in transgender medicine. University of Cincinnati College of Medicine is one of the only US Medical Schools to have a nationally published, dedicated transgender medicine curriculum. Stef Murawsky, MA, WGSS, Ph.D. Candidate, Sociology Pronouns: they/them/theirs University of Cincinnati Department of Sociology I am currently completing a qualitative dissertation that explores transgender patient experiences of navigating and managing a stigmatized gender identity in biomedical contexts. I plan to generate a critical analysis of stigma in healthcare that demonstrates how structural, interpersonal and individual level transgender healthcare experiences are gendered and racialized.
- Creator/Author:
- Murawsky, Stef and Pickel, Sara
- Submitter:
- Amy Koshoffer
- Date Uploaded:
- 04/12/2019
- Date Modified:
- 04/12/2019
- Date Created:
- 2019-04-01
- License:
- Attribution-NonCommercial 4.0 International
- Type:
- Article
- Description/Abstract:
- Candida albicans is a leading pathogen in infections of central venous catheters, which are frequently infused with heparin. Binding of C. albicans to medically relevant concentrations of soluble and plate-bound heparin was demonstrable by confocal microscopy and enzyme-linked immunosorbent assay (ELISA). A sequencebased search identified 34 C. albicans surface proteins containing ≥1 match to linear heparin-binding motifs. The virulence factor Int1 contained the most putative heparin-binding motifs (n = 5); peptides encompassing 2 of 5 motifs bound to heparin-Sepharose. Alanine substitution of lysine residues K805/K806 in 804QKKHQIHK811 (motif 1 of Int1) markedly attenuated biofilm formation in central venous catheters in rats, whereas alanine substitution of K1595/R1596 in 1593FKKRFFKL1600 (motif 4 of Int1) did not impair biofilm formation. Affinity-purified immunoglobulin G (IgG) recognizing motif 1 abolished biofilm formation in central venous catheters; preimmune IgG had no effect. After heparin treatment of C. albicans, soluble peptides from multiple C. albicans surface proteins were detected, such as Eno1, Pgk1, Tdh3, and Ssa1/2 but not Int1, suggesting that heparin changes candidal surface structures and may modify some antigens critical for immune recognition. These studies define a new mechanism of biofilm formation for C. albicans and a novel strategy for inhibiting catheter-associated biofilms.
- Creator/Author:
- Andes, David R.; Lu, Jason Long; Tan, Queenie K., G.; Hostetter, Margaret K.; Greis, Kenneth D.; Zhang, Minlu; Orsborn, Kris I.; Porollo, Alexey, and Green, Julianne V.
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2013-07
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- OBJECTIVE: Damage to hair from UV exposure has been well reported in the literature and is known to be a highly complex process involving initiation via absorption of UV light followed by formation and propagation of reactive oxygen species (ROS). The objective of this work was to understand these mechanisms, explain the role of copper in accelerating the formation of ROS and identify strategies to reduce the hair damage caused by these reactive species. METHODS: The location of copper in hair was measured by Transmission electron microscopy–(TEM) X-ray energy dispersive spectroscopy (XEDS) and levels measured by ICP-OES. Protein changes were measured as total protein loss via the Lowry assay, and MALDI ToF was used to identify the biomarker protein fragments. TBARS assay was used to measure lipid peroxide formation. Sensory methods and dry combing friction were used to measure hair damage due to copper and UV exposure and to demonstrate the efficacy of N,N’ ethylenediamine disuccinic acid (EDDS) and histidine chelants to reduce this damage. RESULTS: In this work, a biomarker protein fragment formed during UV exposure is identified using mass spectrometry. This fragment originates from the calcium-binding protein S100A3. Also shown is the accelerated formation of this peptide fragment in hair containing low levels of copper absorbed from hair during washing with tap water containing copper ions. Transmission electron microscopy (TEM) X-ray energy dispersive spectroscopy (XEDS) studies indicate copper is located in the sulphur-poor endo-cuticle region, a region where the S100A3 protein is concentrated. A mechanism for formation of this peptide fragment is proposed in addition to the possible role of lipids in UV oxidation. A shampoo and conditioner containing chelants (EDDS in shampoo and histidine in conditioner) is shown to reduce copper uptake from tap water and reduce protein loss and formation of S100A3 protein fragment. In addition, the long-term consequences of UV oxidation and additional damage induced by copper are illustrated in a fourmonth wear study where hair was treated with a consumer relevant protocol of hair colouring treatments, UV exposure and regular shampoo and conditioning. CONCLUSIONS: The role of copper in accelerating UV damage to hair has been demonstrated as well as the ability of chelants such as EDDS and histidine in shampoo and conditioner products to reduce this damage.
- Creator/Author:
- McComb, D. W.; Marsh, J. M.; Sun, Y.; Chaudhary, T.; Flagler, M. J.; Coderch, L.; Mamak, M.; Greis, Kenneth D.; Rubio, L.; Williams, R. E. A., and Davis, M. G.
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2015-04
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Commonly used methods for isolated enzyme inhibitor screening typically rely on fluorescent or chemiluminescent detection techniques that are often indirect and/or coupled assays. Mass spectrometry (MS) has been widely reported for measuring the conversion of substrates to products for enzyme assays and has more recently been demonstrated as an alternative readout system for inhibitor screening. In this report, a high-throughput mass spectrometry (HTMS) readout platform, based on the direct measurement of substrate conversion to product, is presented. The rapid ionization and desorption features of a new generation matrix-assisted laser desorption ionization-triple quadrupole (MALDI-QqQ) mass spectrometer are shown to improve the speed of analysis to greater than 1 sample per second while maintaining excellent Z′ values. Furthermore, the readout was validated by demonstrating the ability to measure IC50 values for several known kinase inhibitors against cyclic AMP–dependent protein kinase (PKA). Finally, when the assay performance was compared with a common ADPaccumulation readout system, this HTMS approach produced better signal-to-background ratios, higher Z′ values, and a reagent cost of about $0.03 per well compared with about $0.60 per well for the fluorescence assay. Collectively, these data demonstrate that a MALDI-QqQ-MS–based readout platform offers significant advantages over the commonly used assays in terms of speed, sensitivity, reproducibility, and reagent cost. (Journal of Biomolecular Screening 2008:1007-1013)
- Creator/Author:
- Rathore, Rakesh; Corr, Jay; Scott, George; Greis, Kenneth D., and Vollmerhaus, Pauline
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2008-12
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- The primary structure of the major surface glycoconjugate of Leishmania donovani parasites, a lipophosphoglycan, has been further characterized. The repeating PO4-6Galp beta 1-4Man disaccharide units, which are a salient feature of the molecule, are shown to terminate with one of several neutral structures, the most abundant of which is the branched trisaccharide Galp beta 1-4(Manp alpha 1-2)Man. The phosphosaccharide core of lipophosphoglycan, which links the disaccharide repeats to a lipid anchor, contains 2 phosphate residues. One of the core phosphates has previously been localized on O-6 of the galactosyl residue distal to the lipid anchor; the second phosphate is now shown to be on O-6 of the mannosyl residue distal to the anchor and to bear an alpha-linked glucopyranosyl residue. Also, the anomeric configuration of the unusual 3-substituted Galf residue in the phosphosaccharide core is established as beta. The complete structure of the core is thus PO4-6Galp alpha 1-6Galp alpha 1-3Galf beta 1-3[Glcp alpha 1-PO4-6]Manp alpha 1-3Manp alpha 1-4GlcN alpha 1-. This further clarification of the structure of lipophosphoglycan may prove beneficial in determining the structure-function relationships of this highly unusual glycoconjugate.
- Creator/Author:
- Ferguson, Michael A. J.; Turco, Salvatore J.; Thomas, Jerry R.; Gorin, Philip A. J.; Homans, Steven W.; McConville, Malcom J.; Greis, Kenneth D., and Thomas-Oates, Jane E.
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/01/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 1992-05
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F0F1-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Tazdeficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacylCoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS.
- Creator/Author:
- Haffey, Wendy D.; Mandala, Satish K.; Purevjav, Enkhsalkhan; Huang, Yan; Javadov, Sabzali; Greis, Kenneth D.; Powers, Corey; Strauss, Arnold W.; Towbin, Jeffrey A., and Khuchua, Zaza
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2015-06
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Background: Role of apolipoprotein (apo) A-II on metabolism of high density lipoproteins (HDLs) is unknown. Results: Conformational changes of apoA-I, the major apolipoprotein of HDL, caused by apoA-II in discoidal HDL are confined to two regions of apoA-I. Conclusion: Interactions between the two major apolipoproteins in discoidal HDL are site specific. Significance: Functional implications of HDL complexes will significantly benefit from such structural information.
- Creator/Author:
- Gauthamadasa, Kekulawalage; Vaitinadin, Nataraja Sarma; Homan, Reyn; Macha, Stephen; Dresman, James L.; D. Silva, R. A. Gangani, and Greis, Kenneth D.
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/01/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2012-03
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Cardiac myosin binding protein-C (cMyBP-C) is a thick filament assembly protein that stabilizes sarcomeric structure and regulates cardiac function; however, the profile of cMyBP-C degradation after myocardial infarction (MI) is unknown. We hypothesized that cMyBP-C is sensitive to proteolysis and is specifically increased in the bloodstream post-MI in rats and humans. Under these circumstances, elevated levels of degraded cMyBP-C could be used as a diagnostic tool to confirm MI. To test this hypothesis, we first established that cMyBP-C dephosphorylation is directly associated with increased degradation of this myofilament protein, leading to its release in vitro. Using neonatal rat ventricular cardiomyocytes in vitro, we were able to correlate the induction of hypoxic stress with increased cMyBP-C dephosphorylation, degradation, and the specific release of N′-fragments. Next, to define the proteolytic pattern of cMyBP-C post-MI, the left anterior descending coronary artery was ligated in adult male rats. Degradation of cMyBP-C was confirmed by a reduction in total cMyBP-C and the presence of degradation products in the infarct tissue. Phosphorylation levels of cMyBP-C were greatly reduced in ischemic areas of the MI heart compared to non-ischemic regions and sham control hearts. Post-MI plasma samples from these rats, as well as humans, were assayed for cMyBP-C and its fragments by sandwich ELISA and immunoprecipitation analyses. Results showed significantly elevated levels of cMyBP-C in the plasma of all post-MI samples. Overall, this study suggests that cMyBP-C is an easily releasable myofilament protein that is dephosphorylated, degraded and released into the circulation post-MI. The presence of elevated levels of cMyBP-C in the blood provides a promising novel biomarker able to accurately rule in MI, thus aiding in the further assessment of ischemic heart disease.
- Creator/Author:
- Muthusamy, Saminathan; Nair, Nandini; McElligott, Andrew; Martin, Jody L.; Govindan, Suresh; Gongora, Enrique; henderson, Kyle K.; Greis, Kenneth D.; Barefield, David; Luther, Pradeep K.; Sadayappan, Sakthivel, and Winegrad, Saul
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2012-01
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- An extracellular phosphoglycan (exPG), present in the culturem edium of the promastigote form L oefi shmania donovani, was purified and structurally characterized. The purification scheme included ethanol precipitation of the culture medium, anion exchange chromatography, hydrophobic chromatography on phenyl-Sepharose, and preparative polyacrylamgeild e electrophoresis. Structural analysis by ‘H-’H NMR, methylation linkage analysis, and glycosidase digestion revealed that the exPG consisted of thfoel lowing structure: (CAP)+[P04-6Galp@1-4Manpal]lo-11-POr6GalpB1-4Man. The capw as found to be ones eovf eral small, neutral oligosaccharides, the most abundant of which was the trisaccharide Galp@l-4(Manpal-2)Man. The results indicated structural analogy to the cellular-derived lipophosphoglycan (LPG) from L. donovani. The important exceptions are a lacko f the lipid anchor, the entire phosphosaccharide core, and several of the repeating disaccharide units. Although the function of exPGis presently unknowni,t may play a protective role for the promastigote in the insect vector or during infection of a mammalian host
- Creator/Author:
- Turco, Salvatore J.; Thomas, Jerry R.; Homans, Steven W.; Ferguson, Michael A.; McConville, Malcolm J., and Greis, Kenneth D.
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/01/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 1992-04
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Lupus nephritis (LN) is among the main determinants of poor prognosis in systemic lupus erythematosus (SLE). The objective of this study was to 1) isolate and identify proteins contained in the LN urinary protein signature (PS) of children with SLE; 2) assess the usefulness of the PS-proteins for detecting activity of LN over time. Using surface-enhanced or matrix assisted laser desorption/ ionization time of flight mass spectrometry, the proteins contained in the LN urinary PS were identified. They were transferrin (Tf), ceruloplasmin (Cp), α1-acid-glycoprotein (AGP), lipocalintype prostaglandin-D synthetase (L-PGDS), albumin and albumin-related fragments. Serial plasma and urine samples were analyzed using immunonephelometry or ELISA in 98 children with SLE (78% African-American) and 30 controls with juvenile idiopathic arthritis. All urinary PS-proteins were significantly higher with active versus inactive LN or in patients without LN (all p<0.005), and their combined area under the receiver operating characteristic curve was 0.85. As early as 3 months before a clinical diagnosis of worsening LN, significant increases of urinary Tf, AGP (both p < 0.0001) and L-PGDS (p < 0.01) occurred, indicating that these PS-proteins are biomarkers of LN activity and may help anticipate the future course of LN. Systemic Lupus Erythematosus (SLE) is an inflammatory autoimmune disease and lupus nephritis (LN) is one of the main determinants of poor prognosis (1). Currently, LN is gauged by measuring circulating and excreted indicators of renal dysfunction, with supporting information from kidney biopsies. The latter constitute the current standard for diagnosing LN, providing a direct assessment of the presence, severity and activity of LN, and the degree of renal damage (2). Due to the invasive nature of kidney biopsies, clinicians base LN activity and its therapy on the results of urinary protein excretion, urinary sediment, creatinine clearance and serum albumin. These traditional markers are not accurate in assessing whether active LN is present or not, and none of them is predictive, i.e. can anticipate the course of LN. Using Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF MS) technology, we previously identified a LN urinary protein signature (PS), consisting of eight candidate biomarkers at the mass-to-charge ratios (m/z) of 2.763, 22, 23, 44, 56, 79, 100, and 133 kDa (3). In this study, we present the identification of the specific proteins contained in this PS of children with LN. We further assayed plasma and urine samples of SLE patients and controls with juvenile idiopathic arthritis (JIA) to investigate the concurrent and predictive validity of the PS-proteins to serve as biomarkers of LN activity.
- Creator/Author:
- Tucker, Lori; Brunner, Hermine I.; Wiers, Kristina; Olson, Judyann; Suzuki, Michiko; Onel, Karen; Ying, Jun; Greis, Kenneth D.; Devarajan, Prasad; Haines, Kathleen; O'Neil, Kathleen M.; Silverman, Earl D.; Klein-Gitelman, Marisa S., and Brooks, Elizabeth B.
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2009-02
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Background: Acid -glucosidase is trafficked to the lysosome by LIMP-2. Results: A unique 11-amino acid sequence on acid -glucosidase was critical for its LIMP-2-dependent targeting to the lysosome. Conclusion: This sequence is essential for oligosaccharide-independent targeting of synthesized acid -glucosidase to the lysosome. Significance: Modification of this sequence has basic/therapeutic implications for Gaucher disease and its comorbidities (e.g. Parkinson disease).
- Creator/Author:
- Grabowski, Gregory A.; Haffey, Wendy D.; Greis, Kenneth D., and Llou, Benjamin
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2014-09
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- In the pharmaceutical industry, there is a tremendous need for qualitative and quantitative analysis of target analytes such as peptides, proteins, drugs, metabolites, biomarkers, impurities, and degradation products in various mixtures including synthetic reactions, in vitro cultures, biological fluids, drug substances, finished products, and many others. To provide adequate specificity for analysis in these complex mixtures, multidimensional analytical techniques are required. Mass spectrometry plays a central role in many of these multidimensional approaches to mixture analysis because it provides an unparalleled combination of sensitivity and specificity that is useful for both molecular identification and quantitative applications. Recent innovations in mass spectrometry and industrial implementation of these advances have transformed many aspects of pharmaceutical research and development. Data that were previously unattainable, or were not collected due to exorbitant cost or time constraints, can now be obtained using mass spectrometry-based technologies. The impact of these innovations has been most dramatically felt in early stages of discovery, as more data are available to make critical decisions, such as selecting compounds for advancement to costly preclinical and clinical trials. New MS technologies have also accelerated the progression of drug candidates through development and toward regulatory approval. Here, five major categories of pharmaceutical applications of mass spectrometry are reviewed. They are new chemical entity characterization, biomacromolecule characterization, bioanalytical quantitation, metabolite identification, and impurity and degradation product identification. A brief historical perspective and evolution of technologies for each application area are presented. Those discussions are followed with a description of the current strategies for implementation of the tremendous capabilities of the state-of-the-art approaches, along with representative applications. In addition, emerging technologies for each application area are presented to indicate the future directions of instrumentation for mixture analysis in the pharmaceutical industry. (Int J Mass Spectrom 212 (2001) 135–196) © 2001 Elsevier Science B.V.
- Creator/Author:
- Harbol, Kevin L.; Greis, Kenneth D.; Hoke, Steven H.; Morand, Kenneth L.; Baker, Timothy R., and Dobson, Roy L. M.
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2001-11
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Organovanadium compounds have been shown to be insulin sensitizers in vitro and in vivo. One potential biochemical mechanism for insulin sensitization by these compounds is that they inhibit protein tyrosine phosphatases (PTPs) that negatively regulate insulin receptor activation and signaling. In this study, bismaltolato oxovanadium (BMOV), a potent insulin sensitizer, was shown to be a reversible, competitive phosphatase inhibitor that inhibited phosphatase activity in cultured cells and enhanced insulin receptor activation in vivo. NMR and X-ray crystallographic studies of the interaction of BMOV with two different phosphatases, HCPTPA (human low molecular weight cytoplasmic protein tyrosine phosphatase) and PTP1B (protein tyrosine phosphatase 1B), demonstrated uncomplexed vanadium (VO ) in the active site. Taken together, these findings support phosphatase inhibition as a mechanism for insulin sensitization by BMOV 4 and other organovanadium compounds and strongly suggest that uncomplexed vanadium is the active component of these compounds.
- Creator/Author:
- Diven, Conrad; Peters, Kevin G.; Evdokimov, Artem; Howard, Brian W.; Soper, Shari; Genbauffe, Frank; Greis, Kenneth D.; Rastogi, Vinit; Eby-Wilkens, Elaine; Pokross, Matthew, and Maier, Matthew
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/01/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2003-09
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Bacterial methionine aminopeptidase (MAP) is a protease that removes methionine from the N termini of newly synthesized bacterial proteins after the peptide deformylase enzyme cleaves the formyl group from the initiator formylmethionine. MAP is an essential bacterial gene product and thus represents a potential target for therapeutic intervention. A fundamental challenge in the antibacterial drug discovery field is demonstrating conclusively that compounds with in vitro enzyme inhibition activity produce the desired antibacterial effect by interfering with the same target in whole bacterial cells. One way to address the activity of inhibitor compounds is by profiling cellular biomarkers in whole bacterial cells using compounds that are known inhibitors of a particular target. However, in the case of MAP, no specific inhibitors were available for such studies. Instead, a genetically attenuated MAP strain was generated in which MAP expression was placed under the control of an inducible arabinose promoter. Thus, MAP inhibition in whole cells could be mimicked by growth in the absence of arabinose. This genetically attenuated strain was used as a benchmark for MAP inhibition by profiling whole-cell lysates for unprocessed proteins using surface-enhanced laser desorption ionization–time of flight mass spectrometry (MS). Eight proteins between 4 and 14 kDa were confirmed as being unprocessed and containing the initiator methionine by adding back purified MAP to the preparations prior to MS analysis. Upon establishing these unprocessed proteins as biomarkers for MAP inhibition, the assay was used to screen small-molecule chemical inhibitors of purified MAP for whole-cell activity. Fifteen compound classes yielded three classes of compound with whole-cell activity for further optimization by chemical expansion. This report presents the development, validation, and implementation of a whole-cell inhibition assay for MAP.
- Creator/Author:
- Siehnel, Richard; Howard, Jeremy; Zhou, Songtao; Layh-Schmitt, Gerlinde; Greis, Kenneth D.; Curnow, Alan, and Klanke, Chuck
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2005-09
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Proteomic analysis of biological samples in disease models or therapeutic intervention studies requires the ability to detect and identify biologically relevant proteins present in relatively low concentrations. The detection and analysis of these low-level proteins is hindered by the presence of a few proteins that are expressed in relatively high concentrations. In the case of muscle tissue, highly abundant structural proteins, such as actin, myosin, and tropomyosin, compromise the detection and analysis of more biologically relevant proteins. We have developed a practical protocol which exploits high-pH extraction to reduce or remove abundant structural proteins from skeletal muscle crude membrane preparations in a manner suitable for two dimensional gel electrophoresis. An initial whole-cell muscle lysate is generated by homogenization of powdered tissue in Tris-base. This lysate is subsequently partitioned into a supernatant and pellet containing the majority of structural proteins. Treatment of the pellet with high-pH conditions effectively releases structural proteins from membrane compartments which are then removed through ultracentrifugation. Mass spectrometric identification shows that the majority of protein spots reduced or removed by high-pH treatment were contractile proteins or contractile-related proteins. Removal of these proteins enabled successful detection and identification of minor proteins. Structural protein removal also results in significant improvement of gel quality and the ability to load higher amounts of total protein for the detection of lower abundant protein classes.
- Creator/Author:
- Wang, Feng; Jarrold, Bradley; Burt, Thomas; DeMuth, Jeffrey, and Greis, Kenneth D.
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/01/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2005-06
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Data-independent acquisition (DIA)-based proteomics has become increasingly complicated in recent years because of the vast number of workflows described, coupled with a lack of studies indicating a rational framework for selecting effective settings to use. To address this issue and provide a resource for the proteomics community, we compared 12 DIA methods that assay tryptic peptides using various mass-isolation windows. Our findings indicate that the most sensitive single injection LC-DIA method uses 6 m/z isolation windows to analyze the densely populated tryptic peptide range from 450 to 730 m/z, which allowed quantification of 4465 Escherichia coli peptides. In contrast, using the sequential windowed acquisition of all theoretical fragmentions (SWATH) approach with 26 m/z isolation windows across the entire 400–1200 m/z range, allowed quantification of only 3309 peptides. This reduced sensitivity with 26 m/z windows is caused by an increase in co-eluting compounds with similar precursor values detected in the same tandemMS spectra, which lowers the signal-to-noise of peptide fragment-ion chromatograms and reduces the amount of low abundance peptides that can be quantified from 410 to 920 m/z. Above 920 m/z, more peptides were quantified with 26 m/z windows because of substantial peptide 13C isotope distributions that parse peptide ions into separate isolation windows. Because reproducible quantification has been a long-standing aimof quantitative proteomics, and is a socalled trait of DIA, we sought to determine whether precursor-level chromatograms used in some methods rather than their fragment-level counterparts have similar precision. Our data show that extracted fragment-ion chromatograms are the reason DIA provides superior reproducibility. Copyright © 2015 John Wiley & Sons, Ltd.
- Creator/Author:
- Haffey, Wendy D.; Norris, Jeremy L.; McCullumsmith, Robert E.; Heaven, Michael R.; Cobbs, Archie L.; Funk, Adam J., and Greis, Kenneth D.
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2016-01
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- We have designed ROS-activated cytotoxic agents that are active against AML cancer cells. In this study the mechanism and synergistic effects against cells co-expressing the AML oncogenes MLL-AF9 fusion and FLT3-ITD was investigated. The agent had an IC50 value of 1.8±0.3 μM with a selectivity of 9-fold compared to untransformed cells. Treatment induced DNA strand breaks, apoptosis, and cell cycle arrest. Proteomics and transcriptomics revealed enhanced expression of the pentose phosphate pathway, DNA repair, and pathways common to cell stress. Western blotting confirmed repair by homologous recombination. Importantly, RAC1 treatment was synergistic in combination with multiple pathway targeting therapies in AML cells but less so in untransformed cells. Taken together, these results demonstrate that RAC1 can selectively target poor prognosis AML and do so by creating DNA double strand breaks that require homologous recombination.
- Creator/Author:
- Wunderlich, Mark; Mulloy, James C.; Greis, Kenneth D.; Merino, Edward J.; Thowfeik, Fathima Shazna; Wyder, Michael; AbdulSalam, Safnas F., and Kadekaro, Ana L.
- Submitter:
- Kenneth Greis
- Date Uploaded:
- 03/03/2017
- Date Modified:
- 04/07/2017
- Date Created:
- 2015-09
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Not Available
- Creator/Author:
- Maes, L. A.; Rugg. N; Dumont, L. J.; Cancelas, Jose A.; Zia, M.; Hess, J. R.; Whitley, P. H.; Siegel, A. H.; Szczepiokowski, Z. M., and Herschel, L.
- Submitter:
- Jose Cancelas
- Date Uploaded:
- 02/08/2017
- Date Modified:
- 04/10/2017
- Date Created:
- 2014-10
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Chromosome 5q deletions (del[5q]) are common in high-risk (HR) myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML); however, the gene regulatory networks that sustain these aggressive diseases are unknown. Reduced miR-146a expression in del(5q) HR MDS/AML and miR-146a/ hematopoietic stem/progenitor cells (HSPCs) results in TRAF6/NF-kB activation. Increased survival and proliferation of HSPCs from miR-146alow HR MDS/AML is sustained by a neighboring haploid gene, SQSTM1 (p62), expressed from the intact 5q allele. Overexpression of p62 from the intact allele occurs through NF-kB-dependent feedforward signaling mediated by miR-146a deficiency. p62 is necessary for TRAF6-mediated NF-kB signaling, as disrupting the p62-TRAF6 signaling complex results in cell-cycle arrest and apoptosis of MDS/AML cells. Thus, del(5q) HR MDS/AML employs an intrachromosomal gene network involving loss of miR-146a and haploid overexpression of p62 via NF-kB to sustain TRAF6/NF-kB signaling for cell survival and proliferation. Interfering with the p62-TRAF6 signaling complex represents a therapeutic option in miR-146a-deficient and aggressive del(5q) MDS/AML.
- Creator/Author:
- Komurov, K.; Maciejewski, J. P.; Bolanos, L.; Grimes, H. L.; Cancelas, Jose A.; Chen, X.; Barker, B.; Weirauch, M. T.; Jerez, A.; Liu, X.; Makishima, H.; Christie, S.; Starczynowski, D. T.; Rao, D. S., and Fang, J.
- Submitter:
- Jose Cancelas
- Date Uploaded:
- 02/08/2017
- Date Modified:
- 04/10/2017
- Date Created:
- 2014-09
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Patients in organ failure of vascular origin have increased circulating hematopoietic stem cells and progenitors (HSC/P). Plasma levels of angiotensin II (Ang-II), are commonly increased in vasculopathies. Hyperangiotensinemia results in activation of a very distinct Ang-II receptor set, Rho-family GTPase members, and actin in bone marrow endothelial cells (BMEC) and HSC/P, which results in decreased membrane integrin activation in both BMEC and HSC/P, and in HSC/P de-adhesion and mobilization. The Ang-II effect can be reversed pharmacologically and genetically by inhibiting Ang-II production or signaling through BMEC AT2R, HSCP AT1R/ AT2R or HSC/P RhoA, but not by interfering with other vascular tone mediators. Hyperangiotensinemia and high counts of circulating HSC/P seen in sickle cell disease (SCD) as a result of vascular damage, is significantly decreased by Ang-II inhibitors. Our data define for the first time the role of Ang-II HSC/P traffic regulation and redefine the hematopoietic consequences of anti-angiotensin therapy in SCD.
- Creator/Author:
- Inagami, T.; Hill, S. E.; Wellendorf, A. M.; Perumbeti, A.; Nayak, R. C.; Bezold, K. Y.; Zheng, Y.; Chang, K. H.; Pirman, M.; Loberg, A.; Cancelas, Jose A.; Roy, S.; Malik, P.; Starnes, J., and Zhou, X.
- Submitter:
- Jose Cancelas
- Date Uploaded:
- 02/08/2017
- Date Modified:
- 04/10/2017
- Date Created:
- 2015-01
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Severe congenital neutropenia (SCN) is often associated with inherited heterozygous point mutations in ELANE, which encodes neutrophil elastase (NE). However, a lack of appropriate models to recapitulate SCN has substantially hampered the understanding of the genetic etiology and pathobiology of this disease. To this end, we generated both normal and SCN patient–derived induced pluripotent stem cells (iPSCs), and performed genome editing and differentiation protocols that recapitulate the major features of granulopoiesis. Pathogenesis of ELANE point mutations was the result of promyelocyte death and differentiation arrest, and was associated with NE mislocalization and activation of the unfolded protein response/ER stress (UPR/ER stress). Similarly, high-dose G-CSF (or downstream signaling through AKT/BCL2) rescues the dysgranulopoietic defect in SCN patient–derived iPSCs through C/EBPβ-dependent emergency granulopoiesis. In contrast, sivelestat, an NE-specific small-molecule inhibitor, corrected dysgranulopoiesis by restoring normal intracellular NE localization in primary granules; ameliorating UPR/ER stress; increasing expression of CEBPA, but not CEBPB; and promoting promyelocyte survival and differentiation. Together, these data suggest that SCN disease pathogenesis includes NE mislocalization, which in turn triggers dysfunctional survival signaling and UPR/ER stress. This paradigm has the potential to be clinically exploited to achieve therapeutic responses using lower doses of G-CSF combined with targeting to correct NE mislocalization.
- Creator/Author:
- Lutzko, C.; Mehta, P.; Kalfa, T.; Aronow, B. J.; Myers, K.; Grimes, H. L.; Horwitz, M.; Cancelas, Jose A.; Valencia, C. A.; Trump, L., and Nayak, R. C.
- Submitter:
- Jose Cancelas
- Date Uploaded:
- 02/08/2017
- Date Modified:
- 04/10/2017
- Date Created:
- 2015-07
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Not Available
- Creator/Author:
- Moscat, J.; Nayak, R. C.; Aronow, B.; Duran, A., and Cancelas, Jose A.
- Submitter:
- Jose Cancelas
- Date Uploaded:
- 02/08/2017
- Date Modified:
- 04/10/2017
- Date Created:
- 2014-12
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Not Available.
- Creator/Author:
- Cancelas, Jose A. and Taniguchi, E.
- Submitter:
- Jose Cancelas
- Date Uploaded:
- 02/08/2017
- Date Modified:
- 04/10/2017
- Date Created:
- 2012-09-01
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Not Available
- Creator/Author:
- Rugg, N. and Cancelas, Jose A.
- Submitter:
- Jose Cancelas
- Date Uploaded:
- 02/08/2017
- Date Modified:
- 04/10/2017
- Date Created:
- 2016-10-04
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- PM-18. EGFR-STAT3 ACTIVATES b-CATENIN SIGNALING TO DRIVE NEUROFIBROMA INITIATION IN NF1, AND PLAYS A ROLE IN TUMOR MAINTENANCE Nancy Ratner1, Vincent Keng2, Deanna M. Patmore1, Jed K. Kendall1, Edwin Jousma1, Kwangmin Choi1, Danhua Fan2, Eric B. Schwartz2, James R. Fuchs2, Yuanshu Zou2, Mi-Ok Kim1, Eva Dombi5, David E. Levy6, Jose A. Cancelas1, Anat Stemmer-Rachamimov4, Robert J. Spinner3, and David A. Largaespada2; 1 Cincinnati Children’s, Cincinnati, OH, USA; 2 University of Minnesota, Minneapolis, MN, USA; 3 Mayo Clinic, Rochester, MN, USA; 4 Massachusetts General Hospital, Boston, MA, USA; 5 National Cancer Institute Pediatric Branch, Bethesda, MD, USA; 6 New York University School of Medicine, New York, NY, USA To identify genes and signaling pathways that drive peripheral nerve tumor initiationand growth beyond the Ras-MAPK pathwaywe used unbiased insertional mutagenesis screening. We identified Stat3 as a potential driver of Neurofibromatosis type 1 neurofibroma. Targeted genetic deletion of Stat3 in Schwann cell precursors (SCPs) and Schwann cells (SCs) largely prevented neurofibroma formation, and self-renewal of tumor initiating cells. Genetic gain- and loss-of-function identified EGFR as the major upstream regulator of P-Stat3 in mouse and human neurofibroma SCP and in neurofibroma initiation; IL-6 reinforced EGFR/Jak/Stat signaling. Preclinical tests of a Jak2/ Stat3 inhibitor reduced established neurofibroma growth, supporting an additional role for Stat3 in benign nerve tumor maintenance. Unexpectedly, downstream of Stat3, we identified b-catenin, and b-catenin expression rescued phenotypic effects of Stat3 loss in SCPs. Phosphorylated STAT3 (Y705) and b-catenin were strongly correlated in NF1 human plexiform neurofibromas. The data support testing of JAK/STAT inhibition and Wnt/ b-catenin pathway inhibition in neurofibroma therapeutic trials. Supported by: NIH R01 NS28840 to N.R. and NIH P50 NS057531 to N.R. and D.L.), a DAMD New Investigator Award (W81XWH-11-1-0259) and an Ohio State University Comprehensive Cancer Center Pelotonia Idea Grant (to J.W.). The American Cancer Society (IRG-67-003-44) supported J.R.F.
- Creator/Author:
- Schwartz, E. B.; Ratner, N.; Largaespada, D. A.; Cancelas, Jose A., and Stemmer-Rachamimov, A. O.
- Submitter:
- Jose Cancelas
- Date Uploaded:
- 02/08/2017
- Date Modified:
- 04/10/2017
- Date Created:
- 2014-11
- License:
- All rights reserved
- Type:
- Article
- Description/Abstract:
- Overnight, room temperature hold (ONH) of whole blood before component processing offers several benefits. This study evaluated the storage and in vivo recovery characteristics of ONH red blood cells (RBCs) stored in additive solution-7 (AS-7).
- Creator/Author:
- Szczerpiorkowski, Z. M.; Whitley, P.; Maes, L. A.; Dumont, L. J.; Cancelas, Jose A.; Zia, M.; Hess, J. R.; Rugg, N., and Herschel, L.
- Submitter:
- Jose Cancelas
- Date Uploaded:
- 02/08/2017
- Date Modified:
- 04/10/2017
- Date Created:
- 2014-10
- License:
- All rights reserved
39. Insertional Mutagenesis Identifies a STAT3/Arid1b/ b-catenin Pathway Driving Neurofibroma Initiation
- Type:
- Article
- Description/Abstract:
- Wu et al. map an Nf1-Stat3-Arid1b/ b-catenin pathway that initiates Neurofibromatosis type 1 (Nf1) neurofibromas, using unbiased insertional mutagenesis screening. Stat3 transcriptionally represses Gsk3b and Arid1b, thereby activating b-catenin in Schwann cell precursors and resulting in neurofibroma initiation and maintenance. Stat3-mediated modification plays a role in early tumorigenesis.
- Creator/Author:
- Spinner, R. J.; Ratner, N.; Largaespada, D. A.; Keng, V.; Patmore, D. M.; Wu, J., and Cancelas, Jose A.
- Submitter:
- Jose Cancelas
- Date Uploaded:
- 02/08/2017
- Date Modified:
- 04/10/2017
- Date Created:
- 2016-02
- License:
- All rights reserved
- Type:
- Image
- Description/Abstract:
- The Retrosplenial Cortex (RSC) has a persistent role in the establishment of spatial and contextual memory, with also the connections between visuo-spatial association cortices. The RSC’s ability to form afferent and efferent connections with the Parahippocampal areas of the brain allow it to be another prime location in the brains of both rodents and humans where multiple cues are linked together in memory formation, storage and retrieval of Long Term Memories. Due to the high nature of memory formation and retrieval, the RSC has become a section of the brain that in recent years has been more heavily focused on for the research of Alzheimer’s and Dementia. The RSC has not been examined fully in previous studies with examination of the expression of the apolipoprotein E (APOE) gene along with other genetic and regulatory factors. There are 3 major alleles of the APOE gene (APOE2, APOE3, and APOE4), with APOE4 having the greatest risk for AD. In this research, I identify the relative connection between DEK the proto-oncogene and APOE3 and APOE4 in a rodent model, looking specifically at the RSC and how it affects spatial memory with an induced model of chronic stress.
- Creator/Author:
- Solomon, Matia B.; Balmer, Nikolaus J.; Selmanovic, Din; Nguyen, Elizabeth T., and Ghisays, Valentina
- Submitter:
- Din Selmanovic
- Date Uploaded:
- 06/27/2018
- Date Modified:
- 06/27/2018
- Date Created:
- 2018-04-13
- License:
- Public Domain Mark 1.0
- Type:
- Dataset
- Description/Abstract:
- A raw dataset produced using the clot on a suture experimental set up in the Holland lab (previously published in Bader 2015 & other articles). Data gathered and further analyzed using MATLAB 2012b.
- Creator/Author:
- Huang, Shenwen; Holland, Christy, and Shekhar, Himanshu
- Submitter:
- Shenwen Huang
- Date Uploaded:
- 05/05/2017
- Date Modified:
- 05/08/2017
- License:
- Public Domain Mark 1.0
- Type:
- Dataset
- Description/Abstract:
- Scanning electron microscopy (SEM) images of the surfaces of porcine and human clots, at 800x, 3500x, and 7000x magnification.
- Creator/Author:
- Huang, Shenwen; Holland, Christy, and Shekhar, Himanshu
- Submitter:
- Shenwen Huang
- Date Uploaded:
- 04/11/2017
- Date Modified:
- 05/08/2017
- License:
- Public Domain Mark 1.0
- Type:
- Dataset
- Description/Abstract:
- A raw dataset produced using the clot on a suture experimental set up in the Holland lab (previously published in Bader 2015 & other articles). Data gathered and further analyzed using MATLAB 2012b.
- Creator/Author:
- Huang, Shenwen; Holland, Christy, and Shekhar, Himanshu
- Submitter:
- Shenwen Huang
- Date Uploaded:
- 01/05/2017
- Date Modified:
- 05/08/2017
- License:
- Public Domain Mark 1.0
- Type:
- Dataset
- Description/Abstract:
- A raw dataset produced using the clot on a suture experimental set up in the Holland lab (previously published in Bader 2015 & other articles). Data gathered and further analyzed using MATLAB 2012b.
- Creator/Author:
- Huang, Shenwen; Holland, Christy, and Shekhar, Himanshu
- Submitter:
- Shenwen Huang
- Date Uploaded:
- 01/05/2017
- Date Modified:
- 05/08/2017
- License:
- Public Domain Mark 1.0
- Type:
- Dataset
- Description/Abstract:
- A raw dataset produced using the clot on a suture experimental set up in the Holland lab (previously published in Bader 2015 & other articles). Data gathered and further analyzed using MATLAB 2012b.
- Creator/Author:
- Huang, Shenwen; Holland, Christy, and Shekhar, Himanshu
- Submitter:
- Shenwen Huang
- Date Uploaded:
- 01/05/2017
- Date Modified:
- 05/08/2017
- License:
- Public Domain Mark 1.0
- Type:
- Dataset
- Description/Abstract:
- A raw dataset produced using the clot on a suture experimental set up in the Holland lab (previously published in Bader 2015 & other articles). Data gathered and further analyzed using MATLAB 2012b.
- Creator/Author:
- Huang, Shenwen; Holland, Christy, and Shekhar, Himanshu
- Submitter:
- Shenwen Huang
- Date Uploaded:
- 01/05/2017
- Date Modified:
- 05/08/2017
- License:
- Public Domain Mark 1.0
- Type:
- Dataset
- Description/Abstract:
- A raw dataset produced using the clot on a suture experimental set up in the Holland lab (previously published in Bader 2015 & other articles). Data gathered and further analyzed using MATLAB 2012b.
- Creator/Author:
- Huang, Shenwen; Holland, Christy, and Shekhar, Himanshu
- Submitter:
- Shenwen Huang
- Date Uploaded:
- 12/22/2016
- Date Modified:
- 05/08/2017
- License:
- Public Domain Mark 1.0
- Type:
- Dataset
- Description/Abstract:
- A raw dataset produced using the clot on a suture experimental set up in the Holland lab (previously published in Bader 2015 & other articles). Data gathered and further analyzed using MATLAB 2012b.
- Creator/Author:
- Huang, Shenwen; Holland, Christy, and Shekhar, Himanshu
- Submitter:
- Shenwen Huang
- Date Uploaded:
- 12/22/2016
- Date Modified:
- 05/08/2017
- License:
- Public Domain Mark 1.0
- Type:
- Dataset
- Description/Abstract:
- A raw dataset produced using the clot on a suture experimental set up in the Holland lab (previously published in Bader 2015 & other articles). Data gathered and further analyzed using MATLAB 2012b.
- Creator/Author:
- Huang, Shenwen; Holland, Christy, and Shekhar, Himanshu
- Submitter:
- Shenwen Huang
- Date Uploaded:
- 12/22/2016
- Date Modified:
- 05/08/2017
- License:
- Public Domain Mark 1.0
- Type:
- Dataset
- Description/Abstract:
- A raw dataset produced using the clot on a suture experimental set up in the Holland lab (previously published in Bader 2015 & other articles). Data gathered and further analyzed using MATLAB 2012b.
- Creator/Author:
- Huang, Shenwen; Holland, Christy, and Shekhar, Himanshu
- Submitter:
- Shenwen Huang
- Date Uploaded:
- 12/22/2016
- Date Modified:
- 05/08/2017
- License:
- Public Domain Mark 1.0
- Type:
- Dataset
- Description/Abstract:
- Metadata about common standardized ontologies used in medicine
- Creator/Author:
- Meinken, John
- Submitter:
- John Meinken
- Date Uploaded:
- 04/05/2016
- Date Modified:
- 04/05/2016
- License:
- Attribution 4.0 International
- Type:
- Student Work
- Description/Abstract:
- How wnt affects gut tube patterning
- Creator/Author:
- Macdonald, Melissa
- Submitter:
- Melissa Macdonald
- Date Uploaded:
- 10/04/2016
- Date Modified:
- 10/04/2016
- License:
- All rights reserved
- Type:
- Student Work
- Description/Abstract:
- How bmp regulates formation of gut tube
- Creator/Author:
- Macdonald, Melissa
- Submitter:
- Melissa Macdonald
- Date Uploaded:
- 10/04/2016
- Date Modified:
- 10/04/2016
- License:
- All rights reserved
- Type:
- Student Work
- Description/Abstract:
- Creating a database for medical research
- Creator/Author:
- Macdonald, Melissa
- Submitter:
- Melissa Macdonald
- Date Uploaded:
- 10/04/2016
- Date Modified:
- 10/04/2016
- License:
- All rights reserved