Search results for "expression"

Inducible knockdown of procollagen I protects mice from liver fibrosis and leads to dysregulated matrix genes and attenuated inflammation.

2017

Organ fibrosis is characterized by a chronic wound-healing response, with excess deposition of extracellular matrix components. Here, collagen type I represents the most abundant scar component and a primary target for antifibrotic therapies. Liver fibrosis can progress to cirrhosis and primary liver cancer, which are the major causes of liver related morbidity and mortality. However, a (pro-)collagen type I specific therapy remains difficult and its therapeutic abrogation may incur unwanted side effects. We therefore designed tetracycline-regulated procollagen alpha1(I) short hairpin (sh)RNA expressing mice that permit a highly efficient inducible knockdown of the procollagen alpha1(I) gen…

Ectopic expression of CXCL13, BAFF, APRIL and LT-ß is associated with artery tertiary lymphoid organs in giant cell arteritis

2016

ObjectivesTo investigate whether artery tertiary lymphoid organs (ATLOs) are present in giant cell arteritis (GCA) and that their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines.MethodsReverse transcriptase PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic ATLOs in GCA and the expression of chemokines/chemokine receptors and cytokines involved in lymphoneogenesis in the temporal artery samples obtained from 50 patients with GCA and 30 controls. The presence of lymphatic conduits, of follicular dendritic cells (FDCs) precursors and lymphoid tissue inducer cells was also investigated. F…

New ΦBT1 site-specific integrative vectors with neutral phenotype in Streptomyces.

2016

Integrative plasmids are one of the best options to introduce genes in low copy and in a stable form into bacteria. The ΦC31-derived plasmids constitute the most common integrative vectors used in Streptomyces. They integrate at different positions (attB and pseudo-attB sites) generating different mutations. The less common ΦBT1-derived vectors integrate at the unique attB site localized in the SCO4848 gene (S. coelicolor genome) or their orthologues in other streptomycetes. This work demonstrates that disruption of SCO4848 generates a delay in spore germination. SCO4848 is co-transcribed with SCO4849, and the spore germination phenotype is complemented by SCO4849. Plasmids pNG1-4 were crea…

2018

Secondary sexual trait expression can be influenced by fixed individual factors (such as genetic quality) as well as by dynamic factors (such as age and environmentally induced gene expression) that may be associated with variation in condition or quality. In particular, melanin-based traits are known to relate to condition and there is a well-characterized genetic pathway underpinning their expression. However, the mechanisms linking variable trait expression to genetic quality remain unclear. One plausible mechanism is that genetic quality could influence trait expression via differential methylation and differential gene expression. We therefore conducted a pilot study examining DNA meth…

2017

AbstractWe asked if essentiality for either fertility or viability differentially affects sequence evolution of human testis proteins. Based on murine knockout data, we classified a set of 965 proteins expressed in human seminiferous tubules into three categories: proteins essential for prepubertal survival (“lethality proteins”), associated with male sub- or infertility (“male sub-/infertility proteins”), and nonessential proteins. In our testis protein dataset, lethality genes evolved significantly slower than nonessential and male sub-/infertility genes, which is in line with other authors’ findings. Using tissue specificity, connectivity in the protein-protein interaction (PPI) network,…

Discovering new proteins in plant mitochondria by RNA editing simulation

2016

In plant mitochondria an essential mechanism for gene expression is RNA editing, often influencing the synthesis of functional proteins. RNA editing alters the linearity of genetic information transfer. Indeed it causes differences between RNAs and their coding DNA sequences that hinder both experimental and computational research of genes. Therefore common software tools for gene search, successfully applied to find canonical genes, often fail in discovering genes encrypted in the genome of plants. Here we propose a novel strategy useful to identify candidate coding sequences resulting from possible editing substitutions. In particular, we consider c!u substitutions leading to the creation…

Model-based design of RNA hybridization networks implemented in living cells

2017

[EN] Synthetic gene circuits allow the behavior of living cells to be reprogrammed, and non-coding small RNAs (sRNAs) are increasingly being used as programmable regulators of gene expression. However, sRNAs (natural or synthetic) are generally used to regulate single target genes, while complex dynamic behaviors would require networks of sRNAs regulating each other. Here, we report a strategy for implementing such networks that exploits hybridization reactions carried out exclusively by multifaceted sRNAs that are both targets of and triggers for other sRNAs. These networks are ultimately coupled to the control of gene expression. We relied on a thermo-dynamic model of the different stable…

Chromatin Immunoprecipitation Assay to Identify Genomic Binding Sites of Regulatory Factors

2016

DNA-protein interactions are vital to fundamental cellular events including transcription, replication, DNA repair, and recombination. Thus, their study holds the key to our understanding of mechanisms underlying normal development and homeostasis as well as disease. Transcriptional regulation is a highly complex process that involves recruitment of numerous factors resulting in formation of multi-protein complexes at gene promoters to regulate gene expression. The studied proteins can be, for example, transcription factors, epigenetic regulators, co-activators, co-repressors, or ligand-activated nuclear receptors as estrogen receptor-α (ERα) bound either directly to the DNA or indirectly b…

2018

Aging is a multi-factorial process, where epigenetic factors play one of the major roles in declines of gene expression and organic function. DNA methylation at CpG islands of promoters can directly change the expression of the neighbouring gene mostly through inhibition. Furthermore, it is known that DNA methylation patterns change during aging In our study, we investigated gene regulation through DNA methylation of genes up- and downregulated in long-lived people compared to a younger cohort. Our data revealed that comparatively highly methylated genes were associated with high expression in long-lived people (e.g. over 85). Genes with lower levels of methylation were associated with low …

Temperature-responsive miRNAs in Drosophila orchestrate adaptation to different ambient temperatures

2017

The majority of Drosophila genes are expressed in a temperature-dependent manner, but the way in which small RNAs may contribute to this effect is completely unknown as we currently lack an idea of how small RNA transcriptomes change as a function of temperature. Applying high-throughput sequencing techniques complemented by quantitative real-time PCR experiments, we demonstrate that altered ambient temperature induces drastic but reversible changes in sequence composition and total abundance of both miRNA and piRNA populations. Further, mRNA sequencing reveals that the expression of miRNAs and their predicted target transcripts correlates inversely, suggesting that temperature-responsive m…