The majority of NK cells (~90%) are phenotypically characterized as CD56dimCD16+, while the remaining are CD56brightCD16-. The cytotoxic CD56dimCD16+ NK subset expresses higher levels of chemokine receptors, and therefore is preferentially recruited to sites of inflammation. Encounters between CD56dimCD16+ NK cells with target cells and locally secreted inflammatory cytokines synergize to induce activation of this subset, leading to dramatically increased cytotoxic activity against target cells and abundant pro-inflammatory cytokine production often equivalent to that of the CD56brightCD16- population. The early recruitment of activation of CD56dimCD16+ NK cells to sites of inflammation raises many important questions regarding the potential immune functions of these cells that extend beyond their cytotoxic capabilities. This study has sought to elucidate the genetic profile of activated CD56dimCD16+ NK cells via a series of laboratory-based approaches coupled with a bioinformatics persective.
Gene expression profiling of the human natural killer cell response to Fc receptor activation: unique enhancement in the presence of interleukin-12.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Effects of Electronic Cigarette Constituents on the Human Lung: A Pilot Clinical Trial.
Age, Specimen part
View SamplesDespite known age-related DNA methylation (aDNAm) changes in breast tumors, little is known about aDNAm in normal breast tissues. Breast tissues from a cross-sectional study of 121 cancer-free women, were assayed for genome-wide DNA methylation. mRNA expression was assayed by microarray technology. Analysis of covariance was used to identify aDNAms. Altered methylation was correlated with expression of the corresponding gene and with DNA methyltransferase protein DNMT3A, assayed by immunohistochemistry. Publically-available TCGA data were used for replication. 1,214 aDNAms were identified; 97% with increased methylation, and all on autosomes. Sites with increased methylation were predominantly in CpG lslands and non-enhancers. aDNAms with decreased methylation were generally located in intergenic regions, non-CpG Islands, and enhancers. Of the aDNAms identified, 650 are known to be involved in cancer, including ESR1 and beta-estradiol responsive genes. Expression of DNMT3A was positively associated with age. Two aDNAms showed significant associations with DNMT3A expression; KRR1 (OR 6.57, 95% CI: 2.51-17.23) and DHRS12 (OR 6.08, 95% CI: 2.33-15.86). A subset of aDNAms co-localized within vulnerable regions for somatic mutations in breast cancer. Expression of C19orf48 was inversely and significantly correlated with its methylation level. In the TCGA dataset, 84% and 64% of the previously identified aDNAms were correlated with age in both normal-adjacent and tumor breast tissues, with differential associations by histological subtype. Given the similarity of findings in the breast tissues of healthy women and breast tumors, and the effects on gene expression, aDNAms may be one pathway for increased breast cancer risk with age.
Landscape of genome-wide age-related DNA methylation in breast tissue.
Age, Race
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Canonical and atypical E2Fs regulate the mammalian endocycle.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor.
Specimen part, Subject
View SamplesE-cig use is continuing to increase, particularly among youth never-smokers, and is used by some smokers to quit. The acute and chronic toxicity of e-cig use is unclear generally in the context of increasing reports of inflammatory-type pneumonia in some e-cig users. To assess lung effects of e-cigs without nicotine or flavors, we conducted a pilot study with serial bronchoscopies over 4 weeks in 30 never-smokers, randomized either to a four-week intervention with the use of e-cigs containing only 50% propylene glycol (PG) and 50% vegetable glycerine (VG) or to a no-use control group. Compliance to the e-cig intervention was assessed by participants sending daily puff counts and by urinary propylene glycol (PG). Inflammatory cell counts and cytokines were determined in bronchoalveolar lavage (BAL) fluids. Genome-wide expression, microRNA, and mRNA were determined from bronchial epithelial cells. There were no significant differences in changes of BAL inflammatory cell counts or cytokines between baseline and follow-up, comparing the control and e-cig groups. However, in the intervention but not the control group, change in urinary PG as a marker of e-cig use and inhalation, was significantly correlated with change in cell counts (cell concentrations, macrophages, and lymphocytes) and cytokines (IL-8, IL-13, and TNF-α), although the absolute magnitude of changes was small. There were no significant changes in mRNA or microRNA gene expression. Although limited by study size and duration, this is the first experimental demonstration of an impact of e-cig use on inflammation in the human lung among never-smokers.
Effects of Electronic Cigarette Constituents on the Human Lung: A Pilot Clinical Trial.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles.
Specimen part
View SamplesTo understand the underlying cause and mechanisms of embryonic lethality observed in combined loss of E2f7 and E2f8, we compared global gene expression profiles of wild type, germline deleted and sox2-Cre/Cyp19-Cre deleted embryos and placentas.
Atypical E2F repressors and activators coordinate placental development.
Specimen part
View SamplestRNAs are transcribed and partially processed in the nucleus before they are exported to the cytoplasm where they have an essential role in protein synthesis. Surprisingly, mature cytoplasmic tRNAs shuttle between nucleus and cytoplasm and its distribution is nutrient-dependent. At least three members of -importin family, Los1, Mtr10, and Msn5, function in tRNA nuclear-cytoplasmic intracellular movement. To test the hypothesis that the tRNA retrograde pathway regulates translation of particular transcripts
Genome-wide investigation of the role of the tRNA nuclear-cytoplasmic trafficking pathway in regulation of the yeast Saccharomyces cerevisiae transcriptome and proteome.
Treatment
View SamplesTo understand the underlying cause and mechanisms of changes in hepatocyte ploidy upon Albumin-Cre mediated deletion of E2f7&8 and Mx1-Cre mediated deletion of E2f1,2&3, we analysed global gene expression of 6 weeks and 2 months liver tissues.
Canonical and atypical E2Fs regulate the mammalian endocycle.
Age, Specimen part
View Samples