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showing 10 items of 3636 documents
Targeting Nonsense: Optimization of 1,2,4-Oxadiazole TRIDs to Rescue CFTR Expression and Functionality in Cystic Fibrosis Cell Model Systems
2020
Cystic fibrosis (CF) patients develop a severe form of the disease when the cystic fibrosis transmembrane conductance regulator (CFTR) gene is affected by nonsense mutations. Nonsense mutations are responsible for the presence of a premature termination codon (PTC) in the mRNA, creating a lack of functional protein. In this context, translational readthrough-inducing drugs (TRIDs) represent a promising approach to correct the basic defect caused by PTCs. By using computational optimization and biological screening, we identified three new small molecules showing high readthrough activity. The activity of these compounds has been verified by evaluating CFTR expression and functionality after…
Quadruplex detection in human cells
2020
Abstract The precise detection of both DNA and RNA quadruplexes in human cells remains challenging. Efforts are being invested to design, synthesize and operate molecular tools to track and detect quadruplexes in cells. Such probes now have sufficient molecular specificity and suitable spectroscopic properties to shed light on quadruplexes in their cellular context, thus providing reliable details about their existence in cells. Herein, the most important steps in this line of development are summarized, from the very first attempts with organometallic complexes to the development of immunodetection technologies; and from in vitro to live-cell investigations performed with cell-permeable qu…
Neuronal Cytoskeleton in Intellectual Disability: From Systems Biology and Modeling to Therapeutic Opportunities
2021
Intellectual disability (ID) is a pathological condition characterized by limited intellectual functioning and adaptive behaviors. It affects 1–3% of the worldwide population, and no pharmacological therapies are currently available. More than 1000 genes have been found mutated in ID patients pointing out that, despite the common phenotype, the genetic bases are highly heterogeneous and apparently unrelated. Bibliomic analysis reveals that ID genes converge onto a few biological modules, including cytoskeleton dynamics, whose regulation depends on Rho GTPases transduction. Genetic variants exert their effects at different levels in a hierarchical arrangement, starting from the molecular lev…
Selective α-synuclein knockdown in monoamine neurons by intranasal oligonucleotide delivery: potential therapy for parkinson’s disease
2018
Progressive neuronal death in brainstem nuclei and widespread accumulation of α-synuclein are neuropathological hallmarks of Parkinson’s disease (PD). Reduction of α-synuclein levels is therefore a potential therapy for PD. However, because α-synuclein is essential for neuronal development and function, α-synuclein elimination would dramatically impact brain function. We previously developed conjugated small interfering RNA (siRNA) sequences that selectively target serotonin (5-HT) or norepinephrine (NE) neurons after intranasal administration. Here, we used this strategy to conjugate inhibitory oligonucleotides, siRNA and antisense oligonucleotide (ASO), with the triple monoamine reuptake …
Holistic Optimization of Bioinformatic Analysis Pipeline for Detection and Quantification of 2′-O-Methylations in RNA by RiboMethSeq
2020
International audience; A major trend in the epitranscriptomics field over the last 5 years has been the high-throughput analysis of RNA modifications by a combination of specific chemical treatment(s), followed by library preparation and deep sequencing. Multiple protocols have been described for several important RNA modifications, such as 5-methylcytosine (m5C), pseudouridine (ψ), 1-methyladenosine (m1A), and 2'-O-methylation (Nm). One commonly used method is the alkaline cleavage-based RiboMethSeq protocol, where positions of reads' 5'-ends are used to distinguish nucleotides protected by ribose methylation. This method was successfully applied to detect and quantify Nm residues in vari…
Promoter methylation status of ASC/TMS1/PYCARD is associated with decreased overall survival and TNM status in patients with early stage non-small ce…
2019
Background: Lung cancer is the leading cause of cancer-related death worldwide, with 5-year overall survival less than 15%. Therefore, it is essential to find biomarkers for early detection and prognosis. Aberrant DNA methylation is a common feature of human cancers and its utility is already recognized in cancer management. The aim of this study was to explore the diagnostic and prognostic value of the promoter methylation status of the ASC/TMS1/PYCARD and MyD88 genes, key adaptor molecules in the activation of the innate immune response and apoptosis pathways. Methods: A total of 50 non-small cell lung cancer (NSCLC) patients were enrolled in the study. Methylation of bisulphite converted…
Structural and mechanistic insights into the interaction of the circadian transcription factor BMAL1 with the KIX domain of the CREB-binding protein
2019
JBC papers in press xx, 16604-16619 (2019). doi:10.1074/jbc.RA119.009845
miRNAs Regulation and Its Role as Biomarkers in Endometriosis.
2016
MicroRNAs (miRNAs) are small non-coding RNAs (18-22 nt) that function as modulators of gene expression. Since their discovery in 1993 in C. elegans, our knowledge about their biogenesis, function, and mechanism of action has increased enormously, especially in recent years, with the development of deep-sequencing technologies. New biogenesis pathways and sources of miRNAs are changing our concept about these molecules. The study of the miRNA contribution to pathological states is a field of great interest in research. Different groups have reported the implication of miRNAs in pathologies such as cancer, diabetes, cardiovascular, and gynecological diseases. It is also well-known that miRNAs…
Biodegradable nano-polymers as delivery vehicles for therapeutic small non-coding ribonucleic acids.
2016
Nowadays, small non-coding Ribo Nucleic Acids (sncRNAs) such as siRNA, miRNA and shRNA are extremely serving to gene regulation. They are involved in many biological processes and in an increasing number of studies regarding a variety of application of sncRNAs toward human health and relieving diseases ranging from metabolic disorders to those involving various organ systems as well as different types of cancer. One of the most severe limitations for applying RNA interference technology is the absence of safe and effective carriers for in vivo delivery, including localizing the molecules to a specific site of interest and sustaining the presentation of the payloads for a controlled period o…
The role of extracellular calcium in bone metastasis
2016
AbstractThis review summarizes the role of extracellular calcium, as found present in the bone tissue, in the process of bone metastasis.