Search results for "Regulatory"
showing 10 items of 740 documents
Prediction of Chromatin Accessibility in Gene-Regulatory Regions from Transcriptomics Data
2017
AbstractThe epigenetics landscape of cells plays a key role in the establishment of cell-type specific gene expression programs characteristic of different cellular phenotypes. Different experimental procedures have been developed to obtain insights into the accessible chromatin landscape including DNase-seq, FAIRE-seq and ATAC-seq. However, current downstream computational tools fail to reliably determine regulatory region accessibility from the analysis of these experimental data. In particular, currently available peak calling algorithms are very sensitive to their parameter settings and show highly heterogeneous results, which hampers a trustworthy identification of accessible chromatin…
On the origin of BAG(3) and its consequences for an expansion of BAG3's role in protein homeostasis
2021
The B-cell CLL 2-associated athanogene (BAG) protein family in general and BAG3, in particular, are pivotal elements of cellular protein homeostasis, with BAG3 playing a major role in macroautophagy. In particular, in the contexts of senescence and degeneration, BAG3 has exhibited an essential role often related to its capabilities to organize and remove aggregated proteins. Exciting studies in different species ranging from human, murine, zebrafish, and plant samples have delivered vital insights into BAG3s' (and other BAG proteins') functions and their regulations. However, so far no studies have addressed neither BAG3's evolution nor its phylogenetic position in the BAG family.
Combined immunotherapy: CTLA-4 blockade potentiates anti-tumor response induced by transcutaneous immunization.
2017
Abstract Background The epidermal application of the Toll Like Receptor 7 agonist imiquimod and a T-cell peptide epitope (transcutaneous immunization, TCI) mediates systemic peptide-specific cytotoxic T-cell (CTL) responses and leads to tumor protection in a prophylactic tumor setting. However, it does not accomplish memory formation or permanent defiance of tumors in a therapeutic set-up. As a distinct immunologic approach, CTLA-4 blockade augments systemic immune responses and has shown long-lasting effects in preclinical experiments as well as in clinical trials. Objective The study investigates the vaccination capacity of TCI in combination with the checkpoint inhibitor CTLA-4 in matter…
Identification of microRNAS differentially regulated by water deficit in relation to mycorrhizal treatment in wheat.
2019
Arbuscular mycorrhizal fungi (AMF) are soil microrganisms that establish symbiosis with plants positively influencing their resistance to abiotic stresses. The aim of this work was to identify wheat miRNAs differentially regulated by water deficit conditions in presence or absence of AMF treatment. Small RNA libraries were constructed for both leaf and root tissues considering four conditions: control (irrigated) or water deficit in presence/absence of mycorrhizal (AMF) treatment. A total of 12 miRNAs were significantly regulated by water deficit in leaves: five in absence and seven in presence of AMF treatment. In roots, three miRNAs were water deficit-modulated in absence of mycorrhizal t…
Regulating T-cell differentiation through the polyamine spermidine
2021
Background The cross-talk between the host and its microbiota plays a key role in the promotion of health. The production of metabolites such as polyamines by intestinal-resident bacteria is part of this symbiosis shaping host immunity. The polyamines putrescine, spermine, and spermidine are abundant within the gastrointestinal tract and might substantially contribute to gut immunity. Objective We aimed to characterize the polyamine spermidine as a modulator of T-cell differentiation and function. Methods Naive T cells were isolated from wild-type mice or cord blood from healthy donors and submitted to polarizing cytokines, with and without spermidine treatment, to evaluate CD4+ T-cell diff…
L1-Penalized Censored Gaussian Graphical Model
2018
Graphical lasso is one of the most used estimators for inferring genetic networks. Despite its diffusion, there are several fields in applied research where the limits of detection of modern measurement technologies make the use of this estimator theoretically unfounded, even when the assumption of a multivariate Gaussian distribution is satisfied. Typical examples are data generated by polymerase chain reactions and flow cytometer. The combination of censoring and high-dimensionality make inference of the underlying genetic networks from these data very challenging. In this article, we propose an $\ell_1$-penalized Gaussian graphical model for censored data and derive two EM-like algorithm…
Model selection for factorial Gaussian graphical models with an application to dynamic regulatory networks.
2016
Abstract Factorial Gaussian graphical Models (fGGMs) have recently been proposed for inferring dynamic gene regulatory networks from genomic high-throughput data. In the search for true regulatory relationships amongst the vast space of possible networks, these models allow the imposition of certain restrictions on the dynamic nature of these relationships, such as Markov dependencies of low order – some entries of the precision matrix are a priori zeros – or equal dependency strengths across time lags – some entries of the precision matrix are assumed to be equal. The precision matrix is then estimated by l 1-penalized maximum likelihood, imposing a further constraint on the absolute value…
A Systematic Study of Dysregulated MicroRNA in Type 2 Diabetes Mellitus
2017
MicroRNAs (miRNAs) are small noncoding RNAs that modulate the cellular transcriptome at the post-transcriptional level. miRNA plays important roles in different disease manifestation, including type 2 diabetes mellitus (T2DM). Many studies have characterized the changes of miRNAs in T2DM, a complex systematic disease; however, few studies have integrated these findings and explored the functional effects of the dysregulated miRNAs identified. To investigate the involvement of miRNAs in T2DM, we obtained and analyzed all relevant studies published prior to 18 October 2016 from various literature databases. From 59 independent studies that met the inclusion criteria, we identified 158 dysregu…
IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively
2016
International audience; Interferon regulatory factor-8 (IRF8) has been proposed to be essential for development of monocytes, plasmacytoid dendritic cells (pDCs) and type 1 conventional dendritic cells (cDC1s) and remains highly expressed in differentiated DCs. Transcription factors that are required to maintain the identity of terminally differentiated cells are designated `' terminal selectors.'' Using BM chimeras, conditional Irf8(fl/fl) mice and various promotors to target Cre recombinase to different stages of monocyte and DC development, we have identified IRF8 as a terminal selector of the cDC1 lineage controlling survival. In monocytes, IRF8 was necessary during early but not late d…
Alternative Splice Forms of CYLD Mediate Ubiquitination of SMAD7 to Prevent TGFB Signaling and Promote Colitis
2018
Background & Aims The CYLD lysine 63 deubiquitinase gene (CYLD) encodes tumor suppressor protein that is mutated in familial cylindromatosus, and variants have been associated with Crohn disease (CD). Splice forms of CYLD that lack exons 7 and 8 regulate transcription factors and functions of immune cells. We examined the expression of splice forms of CYLD in colon tissues from patients with CD and their effects in mice. Methods We performed immunohistochemical analyses of colon tissues from patients with untreated CD and patients without inflammatory bowel diseases (controls). We obtained mice that expressed splice forms of CYLD (sCYLD mice) without or with SMAD7 (sCYLD/SMAD7 mice) from tr…