Project description:Emerging data suggest that some high-risk subjects benefit more than others from preventive intervention. The goal of this study was to determine the efficacy of sulindac (Sul) and/or atorvastatin (Atorva) against spontaneous colorectal adenomas in Apc+/Min-FCCC mice in which the tumor-bearing status was known at the time of treatment initiation. Administration of Sul/Atorva to tumor-bearing mice led to a 43% reduction in the multiplicity of colorectal adenomas as compared to that of untreated tumor-bearing mice. Atorvastatin completely inhibited the formation of microadenomas in mice that were tumor-free at baseline, with associated decreases in the expression of inflammatory mediators observed. Expression of Hoxb13 and Rprm was enhanced significantly following Sul/Atorva treatment, suggesting the importance of cell cycle regulation in colon tumor inhibition. The tumor status of animals at treatment initiation dictates response to atorvastatin, sulindac and Sul/Atorva. The tumor inhibition observed with Sul/Atorva in tumor-bearing mice was greater than that achieved with either agent alone.
Project description:Transposon insertion site sequencing (TIS) is a powerful method for associating genotype to phenotype. However, all TIS methods described to date use short nucleotide sequence reads which cannot uniquely determine the locations of transposon insertions within repeating genomic sequences where the repeat units are longer than the sequence read length. To overcome this limitation, we have developed a TIS method using Oxford Nanopore sequencing technology that generates and uses long nucleotide sequence reads; we have called this method LoRTIS (Long Read Transposon Insertion-site Sequencing). This experiment data contains sequence files generated using Nanopore and Illumina platforms. Biotin1308.fastq.gz and Biotin2508.fastq.gz are fastq files generated from nanopore technology. Rep1-Tn.fastq.gz and Rep1-Tn.fastq.gz are fastq files generated using Illumina platform. In this study, we have compared the efficiency of two methods in identification of transposon insertion sites.
Project description:Chromatin State Profilining using multiple histone modifications in human craniofacial tissue spanning 4.5 post conception weeks to 10 pcw The raw FASTQ sequence files are being deposited in dbGAP
Project description:Results: Prenatal SUL altered baseline lung genes involved in organ/cell development and grow (e.g., Ibsp, Ctsk, Igfbp5) and ARE responses (e.g., Aldh3a1, Maff, Mafg) in Nrf2+/+ neonates and in cell morphogenesis and cell death and organismal injury/abnormality inhibition (e.g., Neat1, Nox4, Vegfa, Igfbp2, Trp53) in Nrf2-/- neonates. In hyperoxia-exposed lung, prenatal SULincreased organogenesis/development genes (e.g., Prss35, Cep128) and decreased inflammatory genes (H2-D1, Cd40, Lcn2, Cdh22) in Nrf2+/+ pups. In Nrf2-/- mice exposed to hyperoxia, prenatal SFN decreased hyperoxia-upregulated many immune and inflammatory response genes (e.g., Ccl9, Btla, Ncf4, Ltb, Selplg, Csf2rb) and upregulated many DNA repair/damage checkpoint genes (e.g., Uimc1, Neil3, Nbn, Smc4, Smc6). Conclusion: Overall, prenatal maternal SUL altered genes differentially in Nrf2+/+ and Nrf2-/- lungs. However, SUL-mediated transcriptome changes affected similar biological functions benificial to host defense and organ development in both strain. Compensatory differential lung transcriptome changes in Nrf2-/- neonates may resulted in the manifest protection of their severe hyperoxic lung injury.
Project description:Temporal analysis of Irf4 and PU.1 genome binding during B cell activation and differentiation in vitro using antigen (NP-Ficoll) CD40L and IL-2/4/5 cytokines (see Molecular Systems Biology 7:495 for details of cellular system). The results provide insight in the target genes and binding specificity of IRF4 and PU.1 during coordination of different programs of B cell differentiation. Regrettably three of the FASTQ raw sequence files in our study were corrupted during storage. FASTQ data from our experimental and control groups are available for download via GEO SRA; however, two groups are missing select raw sequence files. These include one PU.1 Day 3 group file (Sample GSM1133499) and two of four input files used to generate a concatenated “super” input file (Sample GSM1133490); the raw data provided for input consists of the two input files recovered. Importantly, FASTA sequences for both of these datasets are available as supplementary data through GEO, and we can make available upon request (rsciamma@uchicago.edu) all files in our study in the ELAND-extended alignment format. Please note that GEO no longer supports this format.