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Pathophysiology of Fluorosis and Calcium Dose Prediction for Its Reversal in Children: Mathematical Modeling, Analysis, and Simulation of Three Clinical Case Studies
Published in P. Mereena Luke, K. R. Dhanya, Didier Rouxel, Nandakumar Kalarikkal, Sabu Thomas, Advanced Studies in Experimental and Clinical Medicine, 2021
Suja George, A. B. Gupta, Mayank Mehta, Akshara Goyal
RRM mathematically represented the biological changes as observed in the various biochemical parameters within the human body due to the prolonged intake of high fluoride which caused fluorosis. Delta Calcium model predicted the daily calcium dose requirement in order to prevent the harmful effects due to high fluoride intake as well as to reverse the fluoride deposition in individuals suffering from fluorosis.
Introduction to Genomics
Published in Altuna Akalin, Computational Genomics with R, 2020
The majority of splicing repressors are heterogeneous nuclear ribonucleoproteins (hnRNPs). If splicing repressor protein bind silencer elements, they reduce the chance of a nearby site being used as a splice junction. On the contrary, splicing enhancers are sites to which splicing activator proteins bind and binding on that region increases the probability that a nearby site will be used as a splice junction (Wang and Burge, 2008). Most of the activator proteins that bind to splicing enhancers are members of the SR protein family. Such proteins can recognize specific RNA recognition motifs. By regulating splicing exons can be skipped or included, which creates protein diversity (Wang and Burge, 2008).
Antibacterial, pH Neutralizing, and Remineralizing Fillers in Polymeric Restorative Materials
Published in Mary Anne S. Melo, Designing Bioactive Polymeric Materials for Restorative Dentistry, 2020
Abdulrahman A. Balhaddad, Maria S. Ibrahim, Michael D. Weir, Hockin H.K. Xu
Several drawbacks were reported with the use of MTA, such as the delayed setting time and the poor handling properties (Asgary et al. 2008). The use of other strategies such as the incorporation of antibiotics was suggested, but the clinical benefits were less compared to MTA AlShwaimi et al. 2016). Therefore, more efforts have been directed to modify MTA to improve the setting time and the handling properties. As a result, materials such as Angelus MTA, BioAggregate, EndoSequence BC RRM, and Biodentine were designed (Komabayashi et al. 2016).
Improved antibody pharmacokinetics by disruption of contiguous positive surface potential and charge reduction using alternate human framework
Published in mAbs, 2023
Romain Ollier, Aline Fuchs, Florence Gauye, Katarzyna Piorkowska, Sébastien Menant, Monisha Ratnam, Paolo Montanari, Florence Guilhot, Didier Phillipe, Mickael Audrain, Anne-Laure Egesipe, Damien Névoltris, Tamara Seredenina, Andrea Pfeifer, Marie Kosco-Vilbois, Tariq Afroz
To treat neurodegenerative disorders which are chronic, slow evolving diseases, an optimal PK profile is essential to allow sustained mAb exposure in the central nervous system when using immunotherapies. ACI-5891 was identified as an effective mAb to target TDP-43 in amyotrophic lateral sclerosis and frontotemporal dementia, two disorders mediated by pathological species of TDP-43.25 TDP-43 functions intracellularly, mainly in the nucleus, to regulate gene transcription and RNA metabolism (e.g., splicing, processing, stability, translation and transport).26 In the healthy, physiological state, TDP-43 has a modular structure with the N-terminal domain taking part in inter-molecular interactions for TDP-43 oligomerization.27 The two RNA recognition motifs confer nucleic acid binding specificity whereas28 the C-terminal region of the protein is involved in protein-protein interactions required for its function in RNA processing.29 In disease, TDP-43 can acts as a ‘prion-like’ protein, misfolding into β-sheet structures that results in the aberrant accumulation with aggregate formation in the cytoplasm of affected neuron and glial cells.30 Subsequent cell-to-cell propagation of TDP-43 pathology is mediated by transmission of misfolded seeding species.31–33 Even though the structural features of extracellular seeding-competent TDP-43 remain to be deciphered, capture and clearance of these species by a mAb have been shown to significantly decrease pathological TDP-43 in animal models of these diseases.25
Advancing mechanistic understanding and biomarker development in amyotrophic lateral sclerosis
Published in Expert Review of Proteomics, 2021
Alexander G Thompson, Patrick Oeckl, Emily Feneberg, Robert Bowser, Markus Otto, Roman Fischer, Benedikt Kessler, Martin R Turner
Current leading hypotheses as to how hexanucleotide repeat expansion in an intronic region of C9orf72 leads to neuronal loss and TDP-43 accumulation center on three potentially synergistic mechanisms: loss of function of C9orf72 protein due to haploinsufficiency, toxicity due to sense and antisense repeat RNA transcription products of the GGGGCC repeat region, and toxicity due dipeptide repeat proteins formed through repeat-associated non-AUG translation [51]. Recent work has explored mechanisms of toxicity of C9orf72 hexanucleotide repeat expansion using proteomics, including the interactome of dipeptide repeat proteins, with notably consistent enrichment of ribosomal proteins across studies, as well as RNA splicing and mitochondrial proteins and proteins involved in autophagy and proteasomal systems detected in the interactomes of the toxic arginine-containing dipeptides [52–56]. Protein interactors of repeat RNA transcripts have also been identified using proteomics, with enrichment (perhaps unsurprisingly) of proteins involved in RNA metabolism and containing RNA recognition motifs [57].
Common mutations of interest in the diagnosis of amyotrophic lateral sclerosis: how common are common mutations in ALS genes?
Published in Expert Review of Molecular Diagnostics, 2020
Benedetta Perrone, Francesca Luisa Conforti
In 2009, the fused in sarcoma/translocated in liposarcoma (FUS/TLS) protein was linked to ALS, as a component of inclusions found in ALS patients. Successively, mutations in the FUS gene within a linkage region on chromosome 16, causing severe loss of motor neurons in the spinal cord, moderate loss of upper motor neurons, were discovered and associated with juvenile ALS [73]. Although rare cases of ALS-FTLD or pure FTLD have been reported, most patients with FUS mutations develop a classic ALS phenotype without cognitive defect [73,74]. FUS is an RNA-binding protein involved in DNA repair, neuronal development, maintenance and/or degeneration, and RNA metabolism [19]. This 526-amino-acid-long protein, expressed ubiquitously, contains an N-terminal domain (rich in Ser, Tyr, Gly, and Gln; SYGQ-rich), multiple nucleic-acid-binding domains including an RNA-recognition motif (RRM), three Arg-Gly-Gly repeat regions (RGG), a zinc-finger motif and a highly conserved C-terminal atypical nuclear localization of ProTyr (NLS) [75] (Figure 4).