The molecular basis of calcineurin inhibitor toxicity (CNIT) in kidney transplantation (KT) and its contribution to chronic allograft dysfunction (CAD) with interstitial fibrosis (IF) and tubular atrophy (TA) were evaluated.
Evaluation of molecular profiles in calcineurin inhibitor toxicity post-kidney transplant: input to chronic allograft dysfunction.
Specimen part
View SamplesNFX1-91, a novel E6 cellular downstream target, functions as a transcriptional regulator and is involved in repressing hTERT expression. Other functions and downstream targets regulated by NFX1-91 were not well understood. We used microarrays to determine gene expression deregulated when NFX1-91 was knocked down.
NFX1 plays a role in human papillomavirus type 16 E6 activation of NFkappaB activity.
Cell line
View SamplesThe CMVpp65 protein contains 2 bipartite nuclear localization signals (NLS) at 415-438aa and 537-561aa near the carboxy terminus of CMVpp65 and a phosphate binding site related to kinase activity at lysine-436. A mutation of pp65 having K436N (CMVpp65mII) and further deletion of aa537-561 resulted in a novel protein (pp65mIINLSKO) that is kinase-less and has markedly reduced nuclear localization. The purpose of this report was to study the biologic characterization of this protein and its immunogenicity compared to native pp65.Using RNA microarray analysis, expression of the CMVpp65mIINLSKO had less effect on cell cycle pathways than did the native CMVpp65 and a greater effect on cell surface signalling pathways involving immune activity. It is concluded that the removal of the primary NLS motif from pp65 does not impair its immunogenicity and may actually be advantageous in the design of a vaccine.
Biologic and immunologic effects of knockout of human cytomegalovirus pp65 nuclear localization signal.
No sample metadata fields
View SamplesThe use of low quality RNA samples in whole-genome gene expression profiling remains controversial. It is unclear if transcript degradation in low quality RNA samples occurs uniformly, in which case the effects of degradation can be normalized, or whether different transcripts are degraded at different rates, potentially biasing measurements of expression levels. This concern has rendered the use of low quality RNA samples in whole-genome expression profiling problematic. Yet, low quality samples are at times the sole means of addressing specific questions – e.g., samples collected in the course of fieldwork.
RNA-seq: impact of RNA degradation on transcript quantification.
No sample metadata fields
View SamplesFunctional discrimination between normal centroblast and centrocyte obtained from human inflamed tonsils after cell sorting.
CXCR4 expression functionally discriminates centroblasts versus centrocytes within human germinal center B cells.
Specimen part
View SamplesTotal RNA from three replicate cultures of wild-type and mutant strains was isolated and the expression profiles were determined using Affymetrix arrays. Comparisons between the sample groups allow the identification of genes regulated by histone H2B K111A mutant.
Novel functional residues in the core domain of histone H2B regulate yeast gene expression and silencing and affect the response to DNA damage.
No sample metadata fields
View SamplesTotal RNA from three replicate cultures of wild-type and mutant strains was isolated and the expression profiles were determined using Affymetrix arrays. Comparisons between the sample groups allow the identification of genes regulated by histone H2B R102A mutant.
Novel functional residues in the core domain of histone H2B regulate yeast gene expression and silencing and affect the response to DNA damage.
No sample metadata fields
View SamplesThe goal of the study was to determine the effect of lentiviral- mediated overexpression of miR-495 (LV-miR-495) on the levels of gene expression in the nuclues accumbens of rats relative to control rats injected with the empty vector (LV-GFP).
In silico identification and in vivo validation of miR-495 as a novel regulator of motivation for cocaine that targets multiple addiction-related networks in the nucleus accumbens.
No sample metadata fields
View SamplesImmunosuppression is needed in HLA identical sibling renal transplantation. We conducted a tolerance trial in this patient cohort using Alemtuzumab induction, donor hematopoietic stem cells, tacrolimus/mycophenolate immunosuppression converted to sirolimus, planning complete drug withdrawal by 24 months post-transplantation. After an additional 12 months with no immunosuppression, normal biopsies and renal function, recipients were considered tolerant. Twenty recipients were enrolled. Of the first 10 (>36 months post-transplantation), 5 had immunosuppression successfully withdrawn for 16-36 months (tolerant), 2 had disease recurrence and 3 had subclinical rejection in protocol biopsies (non-tolerant). Microchimerism disappeared after 1 year, and CD4+CD25highCD127-FOXP3+ T cells and CD19+IgD/M+CD27- B cells increased to 5 years post-transplantation in both groups, whereas immune/inflammatory gene expression pathways in the peripheral blood and urine were differentially downregulated in tolerant compared to non-tolerant recipients. Therefore, in this HLA identical renal transplant tolerance trial, absent chimerism, Treg and Breg immunophenotypes were indistinguishable between tolerant and non-tolerant recipients, but global genomic changes indicating immunomodulation were observed only in tolerant recipients.
Genomic biomarkers correlate with HLA-identical renal transplant tolerance.
Specimen part, Time
View SamplesTacrolimus and Sirolimus are commonly used to maintain immunosuppression in kidney transplantation. However, their effects on immune cells and allograft molecular profiles have not been elucidated.
Cellular and molecular immune profiles in renal transplant recipients after conversion from tacrolimus to sirolimus.
Specimen part, Treatment
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