Search results for "CCT."
showing 10 items of 39 documents
Modeling of Myotonic Dystrophy Cardiac Phenotypes in Drosophila
2018
After respiratory distress, cardiac dysfunction is the second most common cause of fatality associated with the myotonic dystrophy (DM) disease. Despite the prevalance of heart failure in DM, physiopathological studies on heart symptoms have been relatively scarce because few murine models faithfully reproduce the cardiac disease. Consequently, only a small number of candidate compounds have been evaluated in this specific phenotype. To help cover this gap Drosophila combines the amenability of its invertebrate genetics with the possibility of quickly acquiring physiological parameters suitable for meaningful comparisons with vertebrate animal models and humans. Here we review available des…
Chaperoning the Mononegavirales: Current Knowledge and Future Directions
2018
This article belongs to the Special Issue Breakthroughs in Viral Replication.
Quantitative analysis of the impact of a human pathogenic mutation on the CCT5 chaperonin subunit using a proxy archaeal ortholog
2017
The human chaperonin complex is a ~ 1 MDa nanomachine composed of two octameric rings formed from eight similar but non-identical subunits called CCT. Here, we are elucidating the mechanism of a heritable CCT5 subunit mutation that causes profound neuropathy in humans. In previous work, we introduced an equivalent mutation in an archaeal chaperonin that assembles into two octameric rings like in humans but in which all subunits are identical. We reported that the hexadecamer formed by the mutant subunit is unstable with impaired chaperoning functions. This study quantifies the loss of structural stability in the hexadecamer due to the pathogenic mutation, using differential scanning calorim…
Customised next-generation sequencing multigene panel to screen a large cohort of individuals with chromatin-related disorder
2020
BackgroundThe regulation of the chromatin state by epigenetic mechanisms plays a central role in gene expression, cell function, and maintenance of cell identity. Hereditary disorders of chromatin regulation are a group of conditions caused by abnormalities of the various components of the epigenetic machinery, namely writers, erasers, readers, and chromatin remodelers. Although neurological dysfunction is almost ubiquitous in these disorders, the constellation of additional features characterizing many of these genes and the emerging clinical overlap among them indicate the existence of a community of syndromes. The introduction of high-throughput next generation sequencing (NGS) methods f…
CTCF and BORIS Regulate Rb2/p130 Gene Transcription: A Novel Mechanism and a New Paradigm for Understanding the Biology of Lung Cancer
2011
Abstract Although innumerable investigations regarding the biology of lung cancer have been carried out, many aspects thereof remain to be addressed, including the role played by the retinoblastoma-related protein Rb2/p130 during the evolution of this disease. Here we report novel findings on the mechanisms that control Rb2/p130 gene expression in lung fibroblasts and characterize the effects of Rb2/p130 deregulation on the proliferative features of lung cancer cells. We revealed for the first time that in lung fibroblasts the expression of Rb2/p130 gene is directly controlled by the chromatin insulator CCCTC-binding factor, CTCF, which by binding to the Rb2/p130 gene promoter induces, and/…
7C: Computational Chromosome Conformation Capture by Correlation of ChIP-seq at CTCF motifs.
2019
Abstract Background Knowledge of the three-dimensional structure of the genome is necessary to understand how gene expression is regulated. Recent experimental techniques such as Hi-C or ChIA-PET measure long-range chromatin interactions genome-wide but are experimentally elaborate, have limited resolution and such data is only available for a limited number of cell types and tissues. Results While ChIP-seq was not designed to detect chromatin interactions, the formaldehyde treatment in the ChIP-seq protocol cross-links proteins with each other and with DNA. Consequently, also regions that are not directly bound by the targeted TF but interact with the binding site via chromatin looping are…
GENETIC CHAPERONOPATHIES ASSOCIATED WITH GROUP II CHAPERONIN VARIANTS
2020
Genetic chaperonopathies manifest themselves from very early in life. Chaperonopathies related to neurodegenerative disorders discussed in “Introduction” section are a heterogeneous group of disorders which affect one or more of the various physiological systems, for example, the nervous system. This heterogeneity is due, in particular, to the not fully known molecular activity, which every single molecular chaperone has within a specific tissue. My general questions about them were 1) why a mutation on a molecular chaperone that is expressed by most, if not all cytotypes, seems to affect the functioning of a single physiological system? 2) why do different mutations on the same molecular c…
Myelin pathology: Involvement of molecular chaperones and the promise of chaperonotherapy
2019
The process of axon myelination involves various proteins including molecular chaperones. Myelin alteration is a common feature in neurological diseases due to structural and functional abnormalities of one or more myelin proteins. Genetic proteinopathies may occur either in the presence of a normal chaperoning system, which is unable to assist the defective myelin protein in its folding and migration, or due to mutations in chaperone genes, leading to functional defects in assisting myelin maturation/migration. The latter are a subgroup of genetic chaperonopathies causing demyelination. In this brief review, we describe some paradigmatic examples pertaining to the chaperonins Hsp60 (HSPD1,…
Viable Systems Approach and Consumer Culture Theory: A Conceptual Framework
2013
The aim of this study is to depict the relational dynamics between the firm/ brand and the individual/consumer or communities of consumers. To this aim we propose a conceptual framework, integrating the viable systems approach (VSA) with consumer culture theory (CCT), which considers the individual as an active co-maker of the product/brand (‘prosumer’). The VSA view of the firm overcomes the limitations of CCT research, which is mainly focused on the individual, giving little consideration to the other actors in the context. Among the different approaches under the umbrella of viable systems we chose the VSA because of its emphasis on the analysis of the systemic external relations with th…
Predicting breakthrough of vanadium in fixed-bed absorbent columns with complex groundwater chemistries: A multi-component granular ferric hydroxide−…
2020
Granular ferric hydroxide (GFH) is often used for fixed bed adsorbent (FBA) columns in groundwater purification units around the world to remove arsenate contaminations. Groundwater can contain also other toxic (e.g., antimonite and vanadate) and non-toxic oxo-anions (phosphate and silicic acid) that are known to affect FBA lifetimes. Therefore, understanding the breakthrough of toxic compounds intended for removal by FBA is essential to their design, and is important to predict accurately breakthrough curves (BTCs) for FBAs in waterworks to plan future operating costs. Rapid small-scale column tests (RSCCT) and pilot-scale FBA were used to simulate vanadate BTCs for complex groundwater che…