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Author  |
Li, M.; Zhao, H.; Ananiev, G.E.; Musser, M.T.; Ness, K.H.; Maglaque, D.L.; Saha, K.; Bhattacharyya, A.; Zhao, X. |
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Title |
Establishment of Reporter Lines for Detecting Fragile X Mental Retardation (FMR1) Gene Reactivation in Human Neural Cells |
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Journal Article |
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Year |
2017 |
Publication |
Stem Cells (Dayton, Ohio) |
Abbreviated Journal |
Stem Cells |
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Volume |
35 |
Issue |
1 |
Pages |
158-169 |
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Keywords |
Drug discovery; Fmr1; Fmrp; Fragile X syndrome; High throughput; Induced pluripotent stem cells; Luciferase |
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Abstract |
Human patient-derived induced pluripotent stem cells (hiPSCs) provide unique opportunities for disease modeling and drug development. However, adapting hiPSCs or their differentiated progenies to high throughput assays for phenotyping or drug screening has been challenging. Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and a major genetic cause of autism. FXS is caused by mutational trinucleotide expansion in the FMR1 gene leading to hypermethylation and gene silencing. One potential therapeutic strategy is to reactivate the silenced FMR1 gene, which has been attempted using both candidate chemicals and cell-based screening. However, molecules that effectively reactivate the silenced FMR1 gene are yet to be identified; therefore, a high throughput unbiased screen is needed. Here we demonstrate the creation of a robust FMR1-Nluc reporter hiPSC line by knocking in a Nano luciferase (Nluc) gene into the endogenous human FMR1 gene using the CRISPR/Cas9 genome editing method. We confirmed that luciferase activities faithfully report FMR1 gene expression levels and showed that neural progenitor cells derived from this line could be optimized for high throughput screening. The FMR1-Nluc reporter line is a good resource for drug screening as well as for testing potential genetic reactivation strategies. In addition, our data provide valuable information for the generation of knockin human iPSC reporter lines for disease modeling, drug screening, and mechanistic studies. Stem Cells 2017;35:158-169. |
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Department of Neuroscience, University of Wisconsin-Madison, Madison, Wisconsin, USA |
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1066-5099 |
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PMID:27422057 |
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Call Number |
ref @ user @ |
Serial |
95937 |
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Author |
Liu, Y.; Shen, Y.; Sun, T.; Yang, W. |
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Title |
Mechanisms regulating radiosensitivity of glioma stem cells |
Type |
Journal Article |
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Year |
2017 |
Publication |
Neoplasma |
Abbreviated Journal |
Neoplasma |
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Volume |
64 |
Issue |
5 |
Pages |
655-665 |
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Keywords |
glioma stem cells; radiosensitivity signaling pathways. |
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Abstract |
Malignant glioblastoma (GBM) has become a very common and difficult brain tumor given its low cure rate and high recurrence rate. GBMs are resistant to treatments because glioma stem cells (GSCs)/glioma-initiating cells (GICs), a specific subpopulation of GBM, possess properties of tumor stem cells, such as unlimited proficiency, self-renewal, differentiation and resistance to chemotherapy and radiotherapy, and exhibit a very strong DNA repair capability. Radiotherapy has become a preponderant treatment, and researchers have found many significant tumor microenvironmental factors and valuable signaling pathways regulating the GSC radioresistance, including NOTCH, Wnt/beta-catenin, Hedgehog, STAT3, and PI3K/AKT/mTOR. Therefore, we seek to boost GSC radiosensitivity through activating or inactivating pathways alone or together to eliminate the likely source of glioma and prolong survival of patients. |
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0028-2685 |
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PMID:28592117 |
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Call Number |
ref @ user @ |
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96582 |
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Loza-Correa, M.; Kou, Y.; Taha, M.; Kalab, M.; Ronholm, J.; Schlievert, P.M.; Cahill, M.P.; Skeate, R.; Cserti-Gazdewich, C.; Ramirez-Arcos, S. |
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Title |
Septic transfusion case caused by a platelet pool with visible clotting due to contamination with Staphylococcus aureus |
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Journal Article |
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Year |
2017 |
Publication |
Transfusion |
Abbreviated Journal |
Transfusion |
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Volume |
57 |
Issue |
5 |
Pages |
1299-1303 |
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Keywords |
Aged; Anti-Bacterial Agents/therapeutic use; Central Venous Catheters/microbiology; Erythrocyte Transfusion/adverse effects; Female; Humans; Leukemia, Myeloid, Acute/therapy; Platelet Transfusion/*adverse effects; Sepsis/*etiology; Staphylococcal Infections/*transmission; *Staphylococcus aureus; Transfusion Reaction/*microbiology |
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BACKGROUND: Contamination of platelet concentrates (PCs) with Staphylococcus aureus is one of the most significant ongoing transfusion safety risks in developed countries. CASE REPORT: This report describes a transfusion reaction in an elderly patient diagnosed with acute myeloid leukemia, transfused with a 4-day-old buffy coat PC through a central venous catheter. The transfusion was interrupted when a large fibrous clot in the PC obstructed infusion pump flow. Shortly afterward, a red blood cell (RBC) unit transfusion started. After septic symptoms were developed, the RBC transfusion was also interrupted. While the RBC unit tested negative for bacterial contamination, the PC and the patient samples were found to be contaminated with a S. aureus strain that exhibited the same phenotypic and genome sequencing profiles. The isolated S. aureus forms biofilms and produces the superantigen enterotoxin-like U, which was detected in a sample of the transfused PCs. The patient received posttransfusion antibiotic treatment and had her original central line removed and replaced. DISCUSSION: As the implicated PC had been tested for bacterial contamination during routine screening yielding negative results, this is a false-negative transfusion sepsis case. Using a point-of-care test could have prevented the transfusion reaction. This report highlights the increasing incidence of S. aureus as a major PC contaminant with grave clinical implications. Importantly, S. aureus is able to interact with platelet components resulting in visible changes in PCs. CONCLUSION: Visual inspection of blood components before transfusion is an essential safety practice to interdict the transfusion of bacterially contaminated units. |
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Canadian Blood Services |
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0041-1132 |
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PMID:28205241 |
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Call Number |
ref @ user @ |
Serial |
99087 |
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Author |
Loza-Correa, M.; Kou, Y.; Taha, M.; Kalab, M.; Ronholm, J.; Schlievert, P.M.; Cahill, M.P.; Skeate, R.; Cserti-Gazdewich, C.; Ramirez-Arcos, S. |
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Title |
Septic transfusion case caused by a platelet pool with visible clotting due to contamination with Staphylococcus aureus |
Type |
Journal Article |
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Year |
2017 |
Publication |
Transfusion |
Abbreviated Journal |
Transfusion |
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Volume |
57 |
Issue |
5 |
Pages |
1299-1303 |
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Keywords |
Aged; Anti-Bacterial Agents/therapeutic use; Central Venous Catheters/microbiology; Erythrocyte Transfusion/adverse effects; Female; Humans; Leukemia, Myeloid, Acute/therapy; Platelet Transfusion/*adverse effects; Sepsis/*etiology; Staphylococcal Infections/*transmission; *Staphylococcus aureus; Transfusion Reaction/*microbiology |
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Abstract |
BACKGROUND: Contamination of platelet concentrates (PCs) with Staphylococcus aureus is one of the most significant ongoing transfusion safety risks in developed countries. CASE REPORT: This report describes a transfusion reaction in an elderly patient diagnosed with acute myeloid leukemia, transfused with a 4-day-old buffy coat PC through a central venous catheter. The transfusion was interrupted when a large fibrous clot in the PC obstructed infusion pump flow. Shortly afterward, a red blood cell (RBC) unit transfusion started. After septic symptoms were developed, the RBC transfusion was also interrupted. While the RBC unit tested negative for bacterial contamination, the PC and the patient samples were found to be contaminated with a S. aureus strain that exhibited the same phenotypic and genome sequencing profiles. The isolated S. aureus forms biofilms and produces the superantigen enterotoxin-like U, which was detected in a sample of the transfused PCs. The patient received posttransfusion antibiotic treatment and had her original central line removed and replaced. DISCUSSION: As the implicated PC had been tested for bacterial contamination during routine screening yielding negative results, this is a false-negative transfusion sepsis case. Using a point-of-care test could have prevented the transfusion reaction. This report highlights the increasing incidence of S. aureus as a major PC contaminant with grave clinical implications. Importantly, S. aureus is able to interact with platelet components resulting in visible changes in PCs. CONCLUSION: Visual inspection of blood components before transfusion is an essential safety practice to interdict the transfusion of bacterially contaminated units. |
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Canadian Blood Services |
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0041-1132 |
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Notes |
PMID:28205241 |
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Call Number |
ref @ user @ |
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100117 |
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Author |
Ludwig, K.; Kornblum, H.I. |
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Title |
Molecular markers in glioma |
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Journal Article |
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Year |
2017 |
Publication |
Journal of Neuro-Oncology |
Abbreviated Journal |
J Neurooncol |
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Pages |
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Keywords |
Glioblastoma; Glioma stem cell; Molecular markers; Mutations; Pathways |
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Abstract |
Gliomas are the most malignant and aggressive form of brain tumors, and account for the majority of brain cancer related deaths. Malignant gliomas, including glioblastoma are treated with radiation and temozolomide, with only a minor benefit in survival time. A number of advances have been made in understanding glioma biology, including the discovery of cancer stem cells, termed glioma stem cells (GSC). Some of these advances include the delineation of molecular heterogeneity both between tumors from different patients as well as within tumors from the same patient. Such research highlights the importance of identifying and validating molecular markers in glioma. This review, intended as a practical resource for both clinical and basic investigators, summarizes some of the more well-known molecular markers (MGMT, 1p/19q, IDH, EGFR, p53, PI3K, Rb, and RAF), discusses how they are identified, and what, if any, clinical relevance they may have, in addition to discussing some of the specific biology for these markers. Additionally, we discuss identification methods for studying putative GSC's (CD133, CD15, A2B5, nestin, ALDH1, proteasome activity, ABC transporters, and label-retention). While much research has been done on these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature. Furthermore, it is unlikely that the investigator will be able to utilize one single marker to prospectively identify and isolate GSC from all, or possibly, any gliomas. |
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Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. Hkornblum@mednet.ucla.edu |
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English |
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ISSN |
0167-594X |
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Notes |
PMID:28233083 |
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Call Number |
ref @ user @ |
Serial |
96605 |
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