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1

LEE, Kuan-Der, Seung Joon BAEK, and Rong-Fong SHEN. "Multiple factors regulating the expression of human thromboxane synthase gene." Biochemical Journal 319, no. 3 (1996): 783–91. http://dx.doi.org/10.1042/bj3190783.

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Characterization of the 5.5 kb promoter of human thromboxane synthase (TS) gene revealed a proximal positive regulatory sequence (PPRS, -90 to -25 bp) and several distal repressive elements. The maximal promoter activity was found to reside within the first 285 bp, ∼75% of which was contributed by the PPRS. The sequence between -365 and -665 bp exerted a strong repressive effect (∼55%) on reporter gene expression independent of orientation and position, consistent with properties expected for a silencer. The sequence upstream of -665 bp to -5.5 kb contains mainly repressive elements which furt
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2

Siddiqui, Mohammad Aarif, Paradesi Naidu Gollavilli, Vignesh Ramesh, et al. "Thymidylate synthase drives the phenotypes of epithelial-to-mesenchymal transition in non-small cell lung cancer." British Journal of Cancer 124, no. 1 (2020): 281–89. http://dx.doi.org/10.1038/s41416-020-01095-x.

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Abstract Background Epithelial-to-mesenchymal transition (EMT) enhances motility, stemness, chemoresistance and metastasis. Little is known about how various pathways coordinate to elicit EMT’s different functional aspects in non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) has been previously correlated with EMT transcription factor ZEB1 in NSCLC and imparts resistance against anti-folate chemotherapy. In this study, we establish a functional correlation between TS, EMT, chemotherapy and metastasis and propose a network for TS mediated EMT. Methods Published datasets were analyse
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3

Gribaudo, Giorgio, Ludovica Riera, Thomas L. Rudge, Patrizia Caposio, Lee F. Johnson, and Santo Landolfo. "Human cytomegalovirus infection induces cellular thymidylate synthase gene expression in quiescent fibroblasts." Journal of General Virology 83, no. 12 (2002): 2983–93. http://dx.doi.org/10.1099/0022-1317-83-12-2983.

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Productive infection of non-proliferating cells by cytomegalovirus (CMV) requires the coordinated stimulation of host biochemical pathways that prepare cells to synthesize DNA. Here we illustrate the ability of human CMV (HCMV) to stimulate cellular thymidylate synthase (TS) gene expression in quiescent human embryonic lung fibroblasts. TS mRNA and protein levels are nearly undetectable in quiescent cells, but are greatly increased following HCMV infection. Inhibition of TS activity was shown to impair HCMV DNA synthesis, demonstrating that TS upregulation is required for efficient HCMV replic
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4

Gribaudo, Giorgio, Ludovica Riera, David Lembo, et al. "Murine Cytomegalovirus Stimulates Cellular Thymidylate Synthase Gene Expression in Quiescent Cells and Requires the Enzyme for Replication." Journal of Virology 74, no. 11 (2000): 4979–87. http://dx.doi.org/10.1128/jvi.74.11.4979-4987.2000.

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ABSTRACT Herpesviruses accomplish DNA replication either by expressing their own deoxyribonucleotide biosynthetic genes or by stimulating the expression of the corresponding cellular genes. Cytomegalovirus (CMV) has adopted the latter strategy to allow efficient replication in quiescent cells. In the present report, we show that murine CMV (MCMV) infection of quiescent fibroblasts induces both mRNA and protein corresponding to the cellular thymidylate synthase (TS) gene, which encodes the enzyme that catalyzes the de novo synthesis of thymidylic acid. The increase in TS gene expression was due
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5

Kaytor, M. D., and D. M. Livingston. "Saccharomyces cerevisiae RAD52 alleles temperature-sensitive for the repair of DNA double-strand breaks." Genetics 137, no. 4 (1994): 933–44. http://dx.doi.org/10.1093/genetics/137.4.933.

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Abstract We have screened for mutations of the Saccharomyces cerevisiae RAD52 gene which confer a temperature-sensitive (ts) phenotype with respect to either the repair of DNA lesions caused by methyl methanesulfonate (MMS) or the recombination of an intrachromosomal recombination reporter. We were readily able to isolate alleles ts for the repair of lesions caused by MMS but were unable to find alleles with a severe ts deficiency in intrachromosomal recombination. We extensively characterized four strains conferring ts growth on MMS agar. These strains also exhibit ts survival when exposed to
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6

Fenn, Kathleen, Veena M. Singh, Shing Mirn Lee, et al. "Diagnosis of leptomeningeal metastasis (LM) through identification of circulating tumor cells (CTCs) in cerebrospinal fluid (CSF)." Journal of Clinical Oncology 38, no. 15_suppl (2020): 3567. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.3567.

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3567 Background: Diagnosis of LM from solid tumors can be challenging. The TargetSelector (TS) CTC detection assay has demonstrated highly specific and sensitive CTC capture both for epithelial (CK+) and non-epithelial (CK-) subsets. The assay utilizes a ten-antibody (ab) capture cocktail followed by biotinylated secondary abs that bind to CTCs, enriched in a microfluidic device. TS targeted next-generation sequencing (NGS) assay detects somatic mutations in 12 breast cancer-related genes. The aim was to determine whether TS can improve sensitivity in the diagnosis of LM compared to CSF cytolo
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7

Kim, Eui Hyun, and Seok-Gu Kang. "CSIG-25. DIFFERENTIAL YAP ACTIVITY IN HUMAN GLIOBLASTOMA TUMORSPHERES AS A POTENTIAL BIOMARKER." Neuro-Oncology 24, Supplement_7 (2022): vii44. http://dx.doi.org/10.1093/neuonc/noac209.174.

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Abstract BACKGROUND Hippo/YAP signaling pathway has emerged as an important driver of GBM. However, the clinical significance and expression correlation of YAP in GBM is still unknown. The purpose of this study is to elucidate the regulatory functions of YAP in response to tumorspheres (TS) in GBM. Material and METHODS In GBM-tumorspheres (TS), mRNA levels of Yap1 and TAZ were determined by RNA-Seq, and nuclear YAP1 expression level and its correlation with tumor aggressiveness were assessed through nucleus cytosolic fractionation, quantitative confocal microscopy, western blot, and TEAD4 repo
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8

Ratinier, Maxime, Steeve Boulant, Christophe Combet, Paul Targett-Adams, John McLauchlan, and Jean-Pierre Lavergne. "Transcriptional slippage prompts recoding in alternate reading frames in the hepatitis C virus (HCV) core sequence from strain HCV-1." Journal of General Virology 89, no. 7 (2008): 1569–78. http://dx.doi.org/10.1099/vir.0.83614-0.

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Since the first report of frameshifting in HCV-1, its sequence has been the paradigm for examining the mechanism that directs alternative translation of the hepatitis C virus (HCV) genome. The region encoding the core protein from this strain contains a cluster of 10 adenines at codons 8–11, which is thought to direct programmed ribosomal frameshifting (PRF), but formal evidence for this process has not been established unequivocally. To identify the mechanisms of frameshifting, this study used a bicistronic dual luciferase reporter system in a coupled transcription/translation in vitro assay.
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9

Tomikawa, Junko, Shuji Takada, Kohji Okamura, et al. "Exploring trophoblast-specific Tead4 enhancers through chromatin conformation capture assays followed by functional screening." Nucleic Acids Research 48, no. 1 (2019): 278–89. http://dx.doi.org/10.1093/nar/gkz1034.

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Abstract Tead4 is critical for blastocyst development and trophoblast differentiation. We assayed long-range chromosomal interactions on the Tead4 promoter in mouse embryonic stem (ES) cells and trophoblast stem (TS) cells. Using luciferase reporter assays with ES and TS cells for 34 candidate enhancer regions, we identified five genomic fragments that increased Tead4 promoter activity in a TS-specific manner. The five loci consisted of three intra- and two inter-chromosomal loci relative to Tead4 on chromosome 6. We established five mouse lines with one of the five enhancer elements deleted a
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10

Otsuka, Kai, Hong Yang, Shin Matsubara, et al. "Evidence for a functional role of Start, a long noncoding RNA, in mouse spermatocytes." PLOS ONE 17, no. 8 (2022): e0273279. http://dx.doi.org/10.1371/journal.pone.0273279.

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A mouse testis-specific long noncoding RNA (lncRNA), Start, is localized in the cytosol of Leydig cells and in the nucleus of pachytene spermatocytes. We previously showed that Start regulates steroidogenesis through controlling the expression of Star and Hsd3b1 genes in Leydig cells, but its function in germ cells was not known. Here we verified that a spermatocyte-specific protease gene, Prss43/Tessp-3, was downregulated in Start-knockout testes. To investigate the transcriptional regulatory activity of Start in spermatocytes, we first performed a series of reporter gene assays using a thymi
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11

Lloyd, Megan G., Michael B. Yee, Joseph S. Flot, et al. "Development of Robust Varicella Zoster Virus Luciferase Reporter Viruses for In Vivo Monitoring of Virus Growth and Its Antiviral Inhibition in Culture, Skin, and Humanized Mice." Viruses 14, no. 4 (2022): 826. http://dx.doi.org/10.3390/v14040826.

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There is a continued need to understand varicella-zoster virus (VZV) pathogenesis and to develop more effective antivirals, as it causes chickenpox and zoster. As a human-restricted alphaherpesvirus, the use of human skin in culture and mice is critical in order to reveal the important VZV genes that are required for pathogenesis but that are not necessarily observed in the cell culture. We previously used VZV-expressing firefly luciferase (fLuc), under the control of the constitutively active SV40 promoter (VZV-BAC-Luc), to measure the VZV spread in the same sample. However, the fLuc expressi
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12

Gerdemann, Ulrike, James Kaminski, Alexandre Albanese, et al. "Using single-cell transcriptomics to reveal CD226 upregulation and enhancement of CD19-CAR-T function in the inhibitory CNS microenvironment of refractory CNS lymphoma." Journal of Clinical Oncology 43, no. 16_suppl (2025): 2020. https://doi.org/10.1200/jco.2025.43.16_suppl.2020.

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2020 Background: Refractory CNS lymphoma (CNSL) has a poor prognosis, with 5-year survival of ~30%. We conducted a trial of axi-cel for CNSL, where we achieved a CR of 67%. To deeply interrogate the immune mediators of response, we collected daily paired CSF and peripheral blood (PB) samples post-CAR T infusion. This enabled single-cell transcriptional profiling at an unprecedented depth, identifying key drivers of CD19 CAR T responses and compartment-specific mechanisms of CAR T function. Methods: CNSL patients were enrolled in the ‘Axi-cel in CNS Lymphoma’ Trial, NCT04608487. PB and CSF samp
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13

Kim, Chulyong, Ali Zamat, Zizhen Zha, Shwetha Sridhar, Gabe Kwong, and Costas Arvanitis. "EXTH-63. FOCUSED ULTRASOUND HYPERTHERMIA MEDIATED CONTROL OF THERMAL RESPONSIVE CAR T CELL ACTIVITY IN BREAST CANCER BRAIN METASTASIS." Neuro-Oncology 26, Supplement_8 (2024): viii251. http://dx.doi.org/10.1093/neuonc/noae165.0993.

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Abstract HER2-targeted therapies are promising treatment options for metastatic breast cancer and have improved the median overall survival. However, breast cancer brain metastasis (BCBM), observed in up to 50% of HER2-positive breast cancer patients, remains a clinical challenge. While Chimeric Antigen Receptor (CAR) T cell therapy is promising therapeutic strategy to address the unmet need in treating BCBM, improving its effectiveness and safety is critical for clinical translation. We hypothesized that spatially and temporally controlled activity of CAR-T cells with a thermal gene switch (T
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14

Sablina, A. A., G. V. Ilyinskaya, S. N. Rubtsova, L. S. Agapova, P. M. Chumakov, and B. P. Kopnin. "Activation of p53-mediated cell cycle checkpoint in response to micronuclei formation." Journal of Cell Science 111, no. 7 (1998): 977–84. http://dx.doi.org/10.1242/jcs.111.7.977.

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Inactivation of p53 tumor-suppressor leads to genetic instability and, in particular, to accumulation of cells with abnormal numbers of chromosomes. In order to better define the role of p53 function in maintaining genome integrity we investigated the involvement of p53 in the control of proliferation of micronucleated cells resulting from abnormal chromosome segregation. Using cell lines expressing temperature-sensitive (ts) p53 or containing p53 genetic suppressor element (p53-GSE) we showed that inhibition of p53 function increases the frequency of cells with micronuclei. Immunofluorescence
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15

Prima, Victor, Lia Gore, Aimee Caires, et al. "Chimeric MEF2D and Dazap1 Fusion Proteins Are Created by a Variant t(1;19)(q23;p13.3) in Acute Lymphoblastic Leukemia (ALL)." Blood 104, no. 11 (2004): 548. http://dx.doi.org/10.1182/blood.v104.11.548.548.

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Abstract The t(1;19)(q23;p13) is one of the most common chromosome translocations in ALL. In 90–95% of ALL cases with a t(1;19), the 19p13.3 gene E2A is fused to PBX1 located at 1q23, producing E2A-PBX1 chimeric proteins that possess transforming properties. The molecular abnormalities present in the 5–10% of ALL cases with a t(1;19) but no E2A-PBX1 fusion are unknown. TS-2 is an ALL cell line with a t(1;19)(q23;p13.3) but no E2A-PBX1 fusion. We used fluoresence in situ hybridization to localize the chromosome 19 breakpoint in TS-2 to a region approximately 400 kilobases telomeric to E2A and f
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16

Zhou, Z., and S. J. Elledge. "Isolation of crt mutants constitutive for transcription of the DNA damage inducible gene RNR3 in Saccharomyces cerevisiae." Genetics 131, no. 4 (1992): 851–66. http://dx.doi.org/10.1093/genetics/131.4.851.

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Abstract Ribonucleotide reductase is an essential enzyme that catalyzes the rate limiting step for production of the deoxyribonucleotides required for DNA synthesis. It is encoded by three genes, RNR1, RNR2 and RNR3, each of which is inducible by agents that damage DNA or block DNA replication. To probe the signaling pathway mediating this DNA damage response, we have designed a general selection system for isolating spontaneous trans-acting mutations that alter RNR3 expression using a chromosomal RNR3-URA3 transcriptional fusion and an RNR3-lacZ reporter plasmid. Using this system, we have is
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17

Chang, Hye Jung, Moon Young Choi, Min-Hee Cho, Kyoung Eun Lee, and Soon-Nam Lee. "Molecular mechanism of chemoresistance and restoration in human gastric cancer cells." Journal of Clinical Oncology 37, no. 15_suppl (2019): e15544-e15544. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e15544.

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e15544 Background: Gastric cancer is characterized by a high rate of relapse and failure of chemotherapy because of the emergence of drug resistant cells. Hence, resistance to chemotherapy is a major obstacle for the management of gastric cancer. It might be related with the development of cancer stem cells (CSCs). The aim of this study is to investigate the characteristics of the 5-fluorouracil (FU) resistant gastric cancer and to study how to restore the chemosensitivity. Methods: We used the AGS gastric cancer cell line (AGS) and transformed it into a 5-FU resistant cell line (AGS-R). AGS-R
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18

Akada, Rinji, Lorena Kallal, Douglas I. Johnson та Janet Kurjan. "Genetic Relationships Between the G Protein βγ Complex, Ste5p, Ste20p and Cdc42p: Investigation of Effector Roles in the Yeast Pheromone Response Pathway". Genetics 143, № 1 (1996): 103–17. http://dx.doi.org/10.1093/genetics/143.1.103.

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Abstract The Saccharomyces cerevisiae G protein βγ dimer, Ste4p/Ste18p, acts downstream of the a subunit, Gpalp, to activate the pheromone response pathway and therefore must interact with a downstream effector. Synthetic sterile mutants that exacerbate the phenotype of ste4-ts mutations were isolated to identify proteins that functionally interact with Ste4p. The identification of a stel8 mutant indicated that this screen could identify proteins that interact directly with Ste4p. The other mutations were in STE5 and the STE20 kinase gene, which act near Ste4p in the pathway, and a new gene ca
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19

Cui, Xiaogang, Tianqi Yuan, Zhengyu Fang, Jiao Feng, and Changxin Wu. "Bta-miR-125a Regulates Milk-Fat Synthesis by Targeting SAA1 mRNA in Bovine Mammary Epithelial Cells." Agriculture 12, no. 3 (2022): 344. http://dx.doi.org/10.3390/agriculture12030344.

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The nutritional value of cow milk mainly depends on its fatty acid content and protein composition. The identification of genes controlling milk production traits and their regulatory mechanisms is particularly important for accelerating genetic progress in the breeding of dairy cows. On the basis of mammary gland transcriptome analyses, in this study we identified an miRNA, bta-miR-125a, that could control bovine milk-fat production by targeting the 3′ untranslated region (UTR) of the serum amyloid A-1 (SAA1) mRNA. The presence of synthetic bta-miR-125a (i.e., an miR-125a mimic) significantly
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20

Liu, Zhimei, Yue Zhao, Sujun Wu, Shiyu Qi, Yefeng Qiu, and Zhengxing Lian. "Site-Specific Integration by Circular Donor Improves CRISPR/Cas9-Mediated Homologous Recombination in Human Cell Lines." International Journal of Molecular Sciences 25, no. 20 (2024): 11320. http://dx.doi.org/10.3390/ijms252011320.

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The technology for obtaining the high-efficiency expression of target proteins through site-specific recombination has made progress. However, using the CRISPR/Cas9 system for site-specific integration of long fragments and the expression of active proteins remains a challenge. This study optimized the linear DNA circularization system, eliminated the prokaryotic plasmid backbone on the traditional foreign gene vector, and generated a homologous arm-free circular donor template with a single guide RNA target site (sgRNA TS). This strategy significantly increased the co-transfection efficiency
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21

Gadal, Olivier, Daniela Strauss, Elisabeth Petfalski, et al. "Rlp7p is associated with 60S preribosomes, restricted to the granular component of the nucleolus, and required for pre-rRNA processing." Journal of Cell Biology 157, no. 6 (2002): 941–52. http://dx.doi.org/10.1083/jcb.200111039.

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Many analyses have examined subnucleolar structures in eukaryotic cells, but the relationship between morphological structures, pre-rRNA processing, and ribosomal particle assembly has remained unclear. Using a visual assay for export of the 60S ribosomal subunit, we isolated a ts-lethal mutation, rix9-1, which causes nucleolar accumulation of an Rpl25p-eGFP reporter construct. The mutation results in a single amino acid substitution (F176S) in Rlp7p, an essential nucleolar protein related to ribosomal protein Rpl7p. The rix9-1 (rlp7-1) mutation blocks the late pre-RNA cleavage at site C2 in I
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22

Falcone, G., S. Alemà, and F. Tatò. "Transcription of muscle-specific genes is repressed by reactivation of pp60v-src in postmitotic quail myotubes." Molecular and Cellular Biology 11, no. 6 (1991): 3331–38. http://dx.doi.org/10.1128/mcb.11.6.3331-3338.1991.

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Quail myogenic cells infected with temperature sensitive (ts) mutants of Rous sarcoma virus (RSV) exhibit a temperature-dependent transformation and block of differentiation. When the cells are allowed to differentiate at the restrictive temperature (41 degrees C) and then shifted back to the permissive temperature (35 degrees C), a sharp reduction in the accumulation of muscle-specific mRNAs is observed, following reactivation of the transforming protein pp60v-src. A kinetic analysis of this down-regulation reveals that the reduction in the accumulation of muscle-specific transcripts occurs f
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23

Gil-Varea, Elia, Maria Fedetz, Herena Eixarch, et al. "A New Risk Variant for Multiple Sclerosis at 11q23.3 Locus Is Associated with Expansion of CXCR5+ Circulating Regulatory T Cells." Journal of Clinical Medicine 9, no. 3 (2020): 625. http://dx.doi.org/10.3390/jcm9030625.

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Genome-wide association studies and meta-analysis have contributed to the identification of more than 200 loci associated with multiple sclerosis (MS). However, a proportion of MS heritability remains unknown. We aimed to uncover new genetic variants associated with MS and determine their functional effects. For this, we resequenced the exons and regulatory sequences of 14 MS risk genes in a cohort of MS patients and healthy individuals (n = 1070) and attempted to validate a selection of signals through genotyping in an independent cohort (n = 5138). We identified three new MS-associated varia
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24

Falcone, G., S. Alemà, and F. Tatò. "Transcription of muscle-specific genes is repressed by reactivation of pp60v-src in postmitotic quail myotubes." Molecular and Cellular Biology 11, no. 6 (1991): 3331–38. http://dx.doi.org/10.1128/mcb.11.6.3331.

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Quail myogenic cells infected with temperature sensitive (ts) mutants of Rous sarcoma virus (RSV) exhibit a temperature-dependent transformation and block of differentiation. When the cells are allowed to differentiate at the restrictive temperature (41 degrees C) and then shifted back to the permissive temperature (35 degrees C), a sharp reduction in the accumulation of muscle-specific mRNAs is observed, following reactivation of the transforming protein pp60v-src. A kinetic analysis of this down-regulation reveals that the reduction in the accumulation of muscle-specific transcripts occurs f
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25

Ao, Wanyuan, and Dave Pilgrim. "Caenorhabditis elegans Unc-45 Is a Component of Muscle Thick Filaments and Colocalizes with Myosin Heavy Chain B, but Not Myosin Heavy Chain a." Journal of Cell Biology 148, no. 2 (2000): 375–84. http://dx.doi.org/10.1083/jcb.148.2.375.

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In the nematode Caenorhabditis elegans, animals mutant in the gene encoding the protein product of the unc-45 gene (UNC-45) have disorganized muscle thick filaments in body wall muscles. Although UNC-45 contains tetratricopeptide repeats (TPR) as well as limited similarity to fungal proteins, no biochemical role has yet been found. UNC-45 reporters are expressed exclusively in muscle cells, and a functional reporter fusion is localized in the body wall muscles in a pattern identical to thick filament A-bands. UNC-45 colocalizes with myosin heavy chain (MHC) B in wild-type worms as well as in t
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26

Pardee, Timothy S., Charles Okechukwu, Kristin Pladna, and William Gmeiner. "Capped F10, a novel DNA directed fluoropyrimidine, in TP53 mutated acute myeloid leukemia (AML)." Journal of Clinical Oncology 41, no. 16_suppl (2023): 7046. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.7046.

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7046 Background: Acute myeloid leukemia (AML) is an aggressive malignancy characterized by resistance to treatment and poor outcomes. One of the most devastating mutations in AML involves loss of the tumor suppressor TP53. AML harboring this loss carries a dismal prognosis and there is a clear need for new approaches. Methods: To identify new therapeutics, a TP53 null and WT isogenic cell line pair was generated using CRISPR/CAS9 using a murine AML cell line. Clonal isolates were obtained and loss of detectable TP53 was confirmed by Western Blotting. A high throughput screen of currently FDA a
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27

Da Costa, Bruno, Alix Sausset, Sandie Munier, et al. "Temperature-Sensitive Mutants in the Influenza A Virus RNA Polymerase: Alterations in the PA Linker Reduce Nuclear Targeting of the PB1-PA Dimer and Result in Viral Attenuation." Journal of Virology 89, no. 12 (2015): 6376–90. http://dx.doi.org/10.1128/jvi.00589-15.

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ABSTRACTThe influenza virus RNA-dependent RNA polymerase catalyzes genome replication and transcription within the cell nucleus. Efficient nuclear import and assembly of the polymerase subunits PB1, PB2, and PA are critical steps in the virus life cycle. We investigated the structure and function of the PA linker (residues 197 to 256), located between its N-terminal endonuclease domain and its C-terminal structured domain that binds PB1, the polymerase core. Circular dichroism experiments revealed that the PA linker by itself is structurally disordered. A large series of PA linker mutants exhi
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28

Zee, Rebecca S., Evaristus C. Mbanefo, Loc H. Le, et al. "IPSE, a parasite-derived host immunomodulatory protein, is a potential therapeutic for hemorrhagic cystitis." American Journal of Physiology-Renal Physiology 316, no. 6 (2019): F1133—F1140. http://dx.doi.org/10.1152/ajprenal.00468.2018.

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Chemotherapy-induced hemorrhagic cystitis is characterized by bladder pain and voiding dysfunction caused by hemorrhage and inflammation. Novel therapeutic options to treat hemorrhagic cystitis are needed. We previously reported that systemic administration of the Schistosomiasis hematobium-derived protein H-IPSEH06 (IL-4-inducing principle from Schistosoma mansoni eggs) is superior to three doses of MESNA in alleviating hemorrhagic cystitis (Mbanefo EC, Le L, Pennington LF, Odegaard JI, Jardetzky TS, Alouffi A, Falcone FH, Hsieh MH. FASEB J 32: 4408–4419, 2018). Based on prior reports by othe
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29

Okechukwu, Charles, Kristin Pladna, William Gmeiner, and Timothy Pardee. "Thymidylate Synthase Inhibition with Capped F10 Is Effective in TP53 Null Acute Myeloid Leukemia (AML)." Blood 142, Supplement 1 (2023): 1430. http://dx.doi.org/10.1182/blood-2023-180057.

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Acute myeloid leukemia (AML) is an aggressive cancer of the myeloid linage characterized by progressive marrow failure and death. Responses to therapy are between 50 and 80% but relapse is common and salvage rates once relapsed are low. The risk of relapse is greatly influenced by specific somatic mutations. One of the highest risk mutations in AML involves loss of the tumor suppressor TP53. Patients with AML harboring loss of TP53 function have a dismal prognosis and there is a clear need for new approaches. To identify novel agents with activity against TP53 null AML, a TP53 null and WT isog
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30

Porcu, P., A. Ferber, Z. Pietrzkowski, et al. "The growth-stimulatory effect of simian virus 40 T antigen requires the interaction of insulinlike growth factor 1 with its receptor." Molecular and Cellular Biology 12, no. 11 (1992): 5069–77. http://dx.doi.org/10.1128/mcb.12.11.5069-5077.1992.

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We have used a plasmid expressing a temperature-sensitive (ts) mutant of simian virus 40 (SV40) T antigen, stably transfected into 3T3 cells, to study the role of insulinlike growth factor 1 (IGF-1) and its receptor in T-antigen-mediated growth. While 3T3 cells do not grow in serum-free medium, in 1% serum, or with the sole addition of either platelet-derived growth factor (PDGF) or IGF-1, cells expressing the tsA T antigen (BALB 58 cells) grow at 34 degrees C in either PDGF or 1% serum but not in IGF-1. At the restrictive temperature (39.6 degrees C), these cells can only grow in 10% serum. W
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31

Porcu, P., A. Ferber, Z. Pietrzkowski, et al. "The growth-stimulatory effect of simian virus 40 T antigen requires the interaction of insulinlike growth factor 1 with its receptor." Molecular and Cellular Biology 12, no. 11 (1992): 5069–77. http://dx.doi.org/10.1128/mcb.12.11.5069.

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We have used a plasmid expressing a temperature-sensitive (ts) mutant of simian virus 40 (SV40) T antigen, stably transfected into 3T3 cells, to study the role of insulinlike growth factor 1 (IGF-1) and its receptor in T-antigen-mediated growth. While 3T3 cells do not grow in serum-free medium, in 1% serum, or with the sole addition of either platelet-derived growth factor (PDGF) or IGF-1, cells expressing the tsA T antigen (BALB 58 cells) grow at 34 degrees C in either PDGF or 1% serum but not in IGF-1. At the restrictive temperature (39.6 degrees C), these cells can only grow in 10% serum. W
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32

Zhong, Hua, Chun Wang, Chen Fangyuan, Lan Xu, Jihua Zhong, and HU Jiong. "MiR-146a Expression Level As a Molecular Marker in Acute Promyleocytic Leukemia." Blood 120, no. 21 (2012): 4821. http://dx.doi.org/10.1182/blood.v120.21.4821.4821.

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Abstract Abstract 4821 MiR-146a which is located on chromosomes 5 may be involved in normal hemtopoisis and the pathogenesis of several hematopoietic diseases through inhibiting the expression of its targets. Acute promyelocytic leukemia (APL) cell line NB4 was taken as research model to find out whether miR-146a expression was associated to cell differentiation and proliferation. The miR-146a expression level of NB4 cells decreased after ATRA treatment, meanwhile the expression level of its predicted target gene Smad4 increased simultaneously. MiR-146a expression plasmid, no related negative
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33

Meyer, Léa, Alix Sausset, Laura Sedano, Bruno Da Costa, Ronan Le Goffic, and Bernard Delmas. "Codon Deletions in the Influenza A Virus PA Gene Generate Temperature-Sensitive Viruses." Journal of Virology 90, no. 7 (2016): 3684–93. http://dx.doi.org/10.1128/jvi.03101-15.

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ABSTRACTThe influenza virus RNA-dependent RNA polymerase, which is composed of three subunits, PB1, PB2, and PA, catalyzes genome replication and transcription within the cell nucleus. The PA linker (residues 197 to 256) can be altered by nucleotide substitutions to engineer temperature-sensitive (ts), attenuated mutants that display a defect in the transport of the PA–PB1 complex to the nucleus at a restrictive temperature. In this study, we investigated the ability of the PA linker to tolerate deletion mutations for furtherin vitroandin vivocharacterization. Four viable mutants with single-c
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34

Asare, Emmanuel, JoAnn Mugavero, Ping Jiang, Eckard Wimmer, and Aniko V. Paul. "A Single Amino Acid Substitution in Poliovirus Nonstructural Protein 2CATPaseCauses Conditional Defects in Encapsidation and Uncoating." Journal of Virology 90, no. 14 (2016): 6174–86. http://dx.doi.org/10.1128/jvi.02877-15.

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ABSTRACTThe specificity of encapsidation of C-cluster enteroviruses depends on an interaction between capsid proteins and nonstructural protein 2CATPase. In particular, residue N252of poliovirus 2CATPaseinteracts with VP3 of coxsackievirus A20, in the context of a chimeric virus. Poliovirus 2CATPasehas important roles both in RNA replication and encapsidation. In this study, we searched for additional sites in 2CATPase, near N252, that are required for encapsidation. Accordingly, segments adjacent to N252were analyzed by combining triple and single alanine mutations to identify residues requir
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35

Carr, Allison, and Adrian Ting. "Abstract 1380: Role of cytokine-induced cell death on efficacy of teclistamab-mediated T cell killing of multiple myeloma cells." Cancer Research 85, no. 8_Supplement_1 (2025): 1380. https://doi.org/10.1158/1538-7445.am2025-1380.

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Abstract Multiple myeloma (MM) is the second most common hematologic malignancy among US adults, characterized by high rates of relapse and refractory disease. Anti-Myeloma T cell immunotherapies, such as chimeric antigen receptors (CAR-Ts) and bispecific T cell engagers (BiTEs), have been able to induce deep responses in the clinic and extending survival for many. However, even these responses are not durable and majority of patients still relapse. MM cell signaling in response to cytokines released by these T cells, such as Tumor Necrosis Factor (TNF) Alpha, and Interferon gamma (IFNγ), may
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36

Pardee, Timothy, Evan Gomes, Jamie Jennings-Gee, David L. Caudell, and William Gmeiner. "The Novel Fluoropyrimidine FdUMP[10] Is Highly Active Against Acute Myeloid Leukemia." Blood 116, no. 21 (2010): 3302. http://dx.doi.org/10.1182/blood.v116.21.3302.3302.

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Abstract Abstract 3302 Acute Myeloid Leukemia (AML) is an aggressive myeloid malignancy that leads to marrow failure and death. This disease affects approximately 12,000 people per year in the United States, causing 9,000 deaths. Despite decades of research, therapy remains essentially unchanged and outcomes are poor. In patients over the age of 60 less then 10% of patients survive 5 years from diagnosis. There is a desperate need for the identification of new active agents with favorable toxicity profiles. The novel polymeric fluoropyrimidine (FP) FdUMP[10] is an oligodeoxynucleotide pro-drug
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37

Krabbendam, Hans. "Elke van Cassel, A Cold War Magazine of Causes: A critical history of the Reporter, 1949-1968." Tijdschrift voor Tijdschriftstudies, no. 23 (June 1, 2008): 47. http://dx.doi.org/10.18352/ts.232.

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38

Fields, Hannah, Juliana Velez Lujan, Kan Xing Wu, et al. "Abstract 8: Deep Immunomics pipeline for discovery and validation of novel cancer-specific T cell receptors." Cancer Research 84, no. 6_Supplement (2024): 8. http://dx.doi.org/10.1158/1538-7445.am2024-8.

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Abstract Background: T cell receptor-engineered T cell (TCR-T) therapy has been studied as a high potential approach for cancer treatment. Beyond cell-surface tumor antigens, TCR-Ts can recognize HLA-presented intracellular epitopes which allows them to address a wide range of cancer-specific targets. Existing TCR-T therapies focus on a limited number of epitopes, many of which are restricted to HLA allele HLA-A*02:01. Identification of novel anti-tumor TCRs covering a broad range of HLA alleles is necessary to address unmet clinical needs. Natural T cells undergo thymic selection and present
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39

Ocias, Lukas Frans, Dennis Lund Hansen, Thomas Kielsgaard Kristensen, et al. "No Development of Neutralizing Antibodies Against Recombinant Interferon-Alpha in Ph-Negative Myeloproliferative Neoplasms - a Prospective Study." Blood 126, no. 23 (2015): 5177. http://dx.doi.org/10.1182/blood.v126.23.5177.5177.

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Abstract Background Treatment of Philadelphia chromosome negative chronic myeloproliferative neoplasms (MPNs) with recombinant pegylated interferon alpha2a/b (rIFN-alpha) has proven effective. It is well known that prolonged therapy with recombinant type 1 interferons (IFN-alpha and IFN-beta) may induce neutralizing antibodies (nAbs) against the drug leading to treatment failure. Most data on type 1 IFN immunogenicity are available from studies of patients with multiple sclerosis treated with rIFN-beta, and patients with hepatitis C treated with rIFN-alpha. A few reports have demonstrated nAbs
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40

Hakata, Takuro, Ichiro Yamauchi, Daisuke Kosugi, et al. "High-throughput Screening for Cushing Disease: Therapeutic Potential of Thiostrepton via Cell Cycle Regulation." Endocrinology 165, no. 9 (2024). http://dx.doi.org/10.1210/endocr/bqae089.

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Abstract Cushing disease is a life-threatening disorder caused by autonomous secretion of ACTH from pituitary neuroendocrine tumors (PitNETs). Few drugs are indicated for inoperative Cushing disease, in particular that due to aggressive PitNETs. To explore agents that regulate ACTH-secreting PitNETs, we conducted high-throughput screening (HTS) using AtT-20, a murine pituitary tumor cell line characterized by ACTH secretion. For the HTS, we constructed a live cell–based ACTH reporter assay for high-throughput evaluation of ACTH changes. This assay was based on HEK293T cells overexpressing comp
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41

Yu, Wei, V. Praveen Chakravarthi, Shaon Borosha, et al. "Transcriptional regulation of Satb1 in mouse trophoblast stem cells." Frontiers in Cell and Developmental Biology 10 (December 14, 2022). http://dx.doi.org/10.3389/fcell.2022.918235.

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SATB homeobox proteins are important regulators of developmental gene expression. Among the stem cell lineages that emerge during early embryonic development, trophoblast stem (TS) cells exhibit robust SATB expression. Both SATB1 and SATB2 act to maintain the trophoblast stem-state. However, the molecular mechanisms that regulate TS-specific Satb expression are not yet known. We identified Satb1 variant 2 as the predominant transcript in trophoblasts. Histone marks, and RNA polymerase II occupancy in TS cells indicated an active state of the promoter. A novel cis-regulatory region with active
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42

DeMaso, Christina R., Lovkesh Karwal, Melissa Zahralban-Steele, et al. "Specificity and Breadth of the Neutralizing Antibody Response to a Live Attenuated Tetravalent Dengue Vaccine." Journal of Infectious Diseases, June 30, 2022. http://dx.doi.org/10.1093/infdis/jiac272.

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Abstract An effective dengue vaccine should ideally induce broadly neutralizing antibody (nAb) responses against all four dengue virus (DENV) serotypes. We characterized the specificity and breadth of the nAb response to TAK-003, a live attenuated tetravalent dengue vaccine, in serum samples from phase 2 and 3 clinical trials. Microneutralization tests using post-vaccination serum showed comparable neutralization against diverse DENV-1−4 genotypes. Reporter virus particle neutralization assays post- depletion of anti-DENV-2 nAbs demonstrated that the nAb response to DENV-1, -3 and -4 comprises
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43

Dragon, Anna Christina, Luca Marie Beermann, Melina Umland, et al. "CAR-Ts redirected against the Thomsen-Friedenreich antigen CD176 mediate specific elimination of malignant cells from leukemia and solid tumors." Frontiers in Immunology 14 (October 17, 2023). http://dx.doi.org/10.3389/fimmu.2023.1219165.

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IntroductionChimeric antigen receptor-engineered T cells (CAR-Ts) are investigated in various clinical trials for the treatment of cancer entities beyond hematologic malignancies. A major hurdle is the identification of a target antigen with high expression on the tumor but no expression on healthy cells, since “on-target/off-tumor” cytotoxicity is usually intolerable. Approximately 90% of carcinomas and leukemias are positive for the Thomsen-Friedenreich carbohydrate antigen CD176, which is associated with tumor progression, metastasis and therapy resistance. In contrast, CD176 is not accessi
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44

Brodsky, Jennifer, Zeinab Tashi, Sharon K. Christopher, et al. "Microglia Express Tie2 in a Longitudinal Imaging Study of Acute Neural Injury in Mice." Molecular Biology of the Cell, July 16, 2025. https://doi.org/10.1091/mbc.e25-05-0257.

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The Tie2 receptor tyrosine kinase is expressed both in stroke recovery and cancer progression by vascular endothelial and myeloid lineage cells. Tie2 mechanisms have been described in vascular maturation, but the receptor's immune role remains poorly understood. Here we describe the expression of Tie2 in microglia in response to an acute neural injury, uncovering a potential new role for these cells. Using MRI and the Ts-Biotag multimodal reporter mouse, we noninvasively imaged Tie2 expression dynamics in a longitudinal study of neural injury to identify key timepoints in wound signaling and h
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45

Di Gregorio, Enza, Chiara Papi, Laura Conti, et al. "A Magnetic Resonance Imaging ‐ Chemical Exchange Saturarion Transfer (MRI‐CEST) method for the detection of water cycling across cellular membranes." Angewandte Chemie, October 31, 2023. http://dx.doi.org/10.1002/ange.202313485.

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Water cycling across the membrane transporters is considered a hallmark of cellular metabolism and it could be of high diagnostic relevance in the characterization of tumors and other diseases. The method relies on the response of intracellular proton exchanging molecules to the presence of extracellular Gd‐based contrast agents (GBCAs). Paramagnetic GBCAs enhances the relaxation rate of water molecules in the extracellular compartment and, through membrane exchange, the relaxation enhancement is transferred to intracellular molecules. The effect is detected at the MRI‐CEST (Magnetic Resonance
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46

Di Gregorio, Enza, Chiara Papi, Laura Conti, et al. "A Magnetic Resonance Imaging ‐ Chemical Exchange Saturarion Transfer (MRI‐CEST) method for the detection of water cycling across cellular membranes." Angewandte Chemie International Edition, October 31, 2023. http://dx.doi.org/10.1002/anie.202313485.

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Water cycling across the membrane transporters is considered a hallmark of cellular metabolism and it could be of high diagnostic relevance in the characterization of tumors and other diseases. The method relies on the response of intracellular proton exchanging molecules to the presence of extracellular Gd‐based contrast agents (GBCAs). Paramagnetic GBCAs enhances the relaxation rate of water molecules in the extracellular compartment and, through membrane exchange, the relaxation enhancement is transferred to intracellular molecules. The effect is detected at the MRI‐CEST (Magnetic Resonance
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47

Hyde-Lay, Barbara, Mackenzie Charter, and Coral Murrant. "The morphology and network architecture of pericytes in skeletal muscle and their potential involvement in blood flow control." Physiology 40, S1 (2025). https://doi.org/10.1152/physiol.2025.40.s1.1622.

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Capillaries are critical coordinators of the microvasculature important in directing blood flow to metabolically active tissue. The architecture of capillary units (CUs) are integral in delivering blood flow to active skeletal muscle fibers. Throughout many tissues capillaries are associated and share a basement membrane with pericytes. In the brain, three types of pericytes have been documented, 1) ensheathing, 2) mesh-type, and 3) thin strand (TS) pericytes; and have been shown to be involved in blood flow control. However, in skeletal muscle the types of pericytes present, their association
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48

Li, Chuanling, Jian-Xiu Shang, Chenlei Qiu, et al. "Plastid-Localized EMB2726 Is Involved in Chloroplast Biogenesis and Early Embryo Development in Arabidopsis." Frontiers in Plant Science 12 (July 23, 2021). http://dx.doi.org/10.3389/fpls.2021.675838.

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Embryogenesis is a critical developmental process that establishes the body organization of higher plants. During this process, the biogenesis of chloroplasts from proplastids is essential. A failure in chloroplast development during embryogenesis can cause morphologically abnormal embryos or embryonic lethality. In this study, we isolated a T-DNA insertion mutant of the Arabidopsis gene EMBRYO DEFECTIVE 2726 (EMB2726). Heterozygous emb2726 seedlings produced about 25% albino seeds with embryos that displayed defects at the 32-cell stage and that arrested development at the late globular stage
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49

Tan, Bibo, Yong Li, Qun Zhao, Liqiao Fan, and Dong Wang. "ZNF139 increases multidrug resistance in gastric cancer cells by inhibiting miR-185." Bioscience Reports 38, no. 5 (2018). http://dx.doi.org/10.1042/bsr20181023.

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It has been reported that the expression of zinc finger protein 139 (ZNF139) and microRNA-185 (miR-185) were associated with proliferation, drug resistance of gastric cancer (GC) cells. However, the detailed mechanisms have not been fully investigated. The expression of ZNF139 in both GC tissues and cell lines was tested, then SGC7901/ADR or SGC7901 cells were transfected with ZNF139-siRNA, miR-185 analog, or pcDNA-ZNF139. Cell activity was determined by MTT assay. Real-time PCR and Western blot were utilized to detect ZNF139, miR-185, and multidrug resistance (MDR) related genes including MDR
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50

Cao, Xiaoying, Lingxia Xu, Ludan Li, Wen Wan, and Jihong Jiang. "TcMYB29a, an ABA-Responsive R2R3-MYB Transcriptional Factor, Upregulates Taxol Biosynthesis in Taxus chinensis." Frontiers in Plant Science 13 (March 4, 2022). http://dx.doi.org/10.3389/fpls.2022.804593.

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Paclitaxel (Taxol), a highly modified diterpene agent mainly obtained from Taxus species, is the most widely used anticancer drug. Abscisic acid (ABA) is a well-known stress hormone that plays important roles in the secondary metabolism of plants, and it can also induce the accumulation of taxol in Taxus cell suspension cultures. However, the mechanism behind the regulation of taxol biosynthesis by ABA remains largely unknown. In previous research, a R2R3 MYB transcription factor (TF) TcMYB29a was observed to show a significant correlation with taxol biosynthesis, indicative of its potential r
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