In the present in vitro study, interactions between P. aeruginosa (sessile biofilms as well as planktonic cells) and PMNs were analyzed by means of DNA microarray based transcriptomics. We found that the P. aeruginosa wild type biofilms, in contrast to planktonic cultures and quorum sensing (QS) deficient strains, respond to PMN exposure in a rather aggressive manner. The response does not involve protective mechanisms such as those involved in oxidative stress. Rather it is dominated by QS controlled virulence determinants such as those encoded by pqs, phz, rhlAB, all of which are designed to cripple Eukaryotic cells including PMNs and macrophages. Our comparative analysis supports the view that QS plays a major role in mechanisms by which P. aeruginosa evades host defense systems.
Pseudomonas aeruginosa recognizes and responds aggressively to the presence of polymorphonuclear leukocytes.
No sample metadata fields
View SamplesCase story. A patient with massive infiltration of the visceral adipose tissue depot by BAT in a patient with a catecholamine secreting paraganglioma. BAT tissue was identified by protein expression of UCP1 (western blotting and immunostaining)
Chronic adrenergic stimulation induces brown adipose tissue differentiation in visceral adipose tissue.
Specimen part
View SamplesHematopoietic stem cells (HSCs) primarily reside in the bone marrow where signals generated by stromal cells regulate their self-renewal, proliferation, and trafficking. Endosteal osteoblasts and perivascular stromal cells including endothelial cells3, CXCL12-abundant reticular (CAR) cells, leptin-receptor positive stromal cells, and nestin-GFP positive mesenchymal progenitors have all been implicated in HSC maintenance. However, it is unclear if specific hematopoietic progenitor cell (HPC) subsets reside in distinct niches defined by the surrounding stromal cells and the regulatory molecules they produce. CXCL12 (stromal-derived factor-1, SDF-1) regulates both HSCs and lymphoid progenitors and is expressed by all of these stromal cell populations.
CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
G-CSF regulates hematopoietic stem cell activity, in part, through activation of Toll-like receptor signaling.
Specimen part, Treatment
View SamplesRecent studies demonstrate that inflammatory signals regulate hematopoietic stem cells (HSCs). Granulocyte-colony stimulating factor (G-CSF) is often induced with infection and plays a key role in the stress granulopoiesis response. However, its effects on HSCs are less clear. Herein, we show that treatment with G-CSF induces expansion and increased quiescence of phenotypic HSCs, but causes a marked, cell-autonomous HSC repopulating defect associated with induction of toll-like receptor (TLR) expression and signaling. The G-CSF-mediated expansion of HSCs is reduced in mice lacking TLR2, TLR4 or the TLR signaling adaptor MyD88. Induction of HSC quiescence is abrogated in mice lacking MyD88 or in mice treated with antibiotics to suppress intestinal flora. Finally, loss of TLR4 or germ free conditions mitigates the G-CSF-mediated HSC repopulating defect. These data suggest that low level TLR agonist production by commensal flora contributes to the regulation of HSC function and that G-CSF negatively regulates HSCs, in part, by enhancing TLR signaling.
G-CSF regulates hematopoietic stem cell activity, in part, through activation of Toll-like receptor signaling.
Specimen part, Treatment
View SamplesRecent studies demonstratethat inflammatory signals regulate hematopoietic stem cells (HSCs). Granulocyte-colony stimulating factor (G-CSF) is often induced with infection and plays a key role in the stress granulopoiesis response. However, its effects on HSCs are less clear. Herein, we show that treatment with G-CSF induces expansion and increased quiescence of phenotypic HSCs, but causes a marked, cell-autonomous HSC repopulating defect associated with induction of toll-like receptor (TLR) expression and signaling. The G-CSF-mediated expansion of HSCs is reduced in mice lacking TLR2, TLR4 or the TLR signaling adaptor MyD88. Induction of HSC quiescence is abrogated in mice lacking MyD88 or in mice treated with antibiotics to suppress intestinal flora. Finally, loss of TLR4 or germ free conditions mitigates the G-CSF-mediated HSC repopulating defect. These data suggest that low level TLR agonist production by commensal flora contributes to the regulation of HSC function and that G-CSF negatively regulates HSCs, in part, by enhancing TLR signaling.
G-CSF regulates hematopoietic stem cell activity, in part, through activation of Toll-like receptor signaling.
Specimen part, Treatment
View SamplesA Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and Function
A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function.
No sample metadata fields
View SamplesThe concept of tumor stem cells (TSCs) provides a new paradigm for understanding tumor biology, although it remains unclear whether TSCs will prove to be a more robust model than traditional cancer cell lines. We demonstrate marked phenotypic and genotypic differences between primary human tumor-derived TSCs and their matched glioma cell lines. TSCs derived directly from primary glioblastomas harbor extensive similarities to normal NSC and recapitulate the genotype, gene expression patterns and in vivo biology of human glioblastomas. By contrast, the matched, traditionally grown tumor cell lines do not secondary to in vitro genomic alterations. These findings suggest that TSCs may be a more reliable model than many commonly utilized cancer cell lines for understanding the biology of primary human tumors. Analysis of gene expression data is described in Lee et al., Cancer Cell, 2006.
Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines.
No sample metadata fields
View SamplesThe endocytic receptor megalin constitutes the main pathway for clearance of plasma proteins from the glomerular filtrate in the proximal tubules. However, little is know about the mechanisms that control receptor activity. A widely discussed hypothesis states that the intracellular domain (ICD) of megalin, released upon ligand binding, acts as a transcription regulator to suppress receptor expression - a mechanism proposed to safeguard the proximal tubules from protein overload. Here, we have put this hypothesis to the test by generating a mouse model co-expressing the soluble ICD and the full-length receptor. Despite pronounced expression in the proximal tubules, the ICD failed to exert any effects on renal proximal tubular function such as megalin expression, protein retrieval, or renal gene transcription. Thus, our data argue that the ICD does not play a role in regulation of megalin activity in vivo in the proximal tubules.
The soluble intracellular domain of megalin does not affect renal proximal tubular function in vivo.
Sex, Age, Specimen part
View SamplesThe ts-p53 E285K protein is a rare p53 mutant with temperature-sensitive (ts) loss of function characteristics. In cancer cells, which express ts-p53 E285K intriniscally, endogenous wild type p53 activity is reconstituted by appropriate cultivation temperature (permissive condition). At non-appropriate cultivation temperature (restrictive condition) this p53 mutant is inactive. The present study took advantage of this mechanism and employed IPH-926 lobular breast cancer cells and BT-474 ductal breast cancer cells, which both harbor endogenous ts-p53 E285K, for the transcriptional profiling of p53-responsive genes. This new approach eliminated the need for genetic modification or cytotoxic stimulation to achive a p53 response in the cells being investigated .
IPH-926 lobular breast cancer cells harbor a p53 mutant with temperature-sensitive functional activity and allow for profiling of p53-responsive genes.
Specimen part, Cell line, Treatment
View Samples