Introduction: Fibrous dysplasia is a benign disorder of unknown etiology. It represents a disturbance of normal bone development - a defect in osteoblastic differentiation and maturation that originates in the mesenchymal precursor of the bone. It is characterized by slow progressive replacement of bone by abnormal isomorphic fibrous tissue.
View Article and Find Full Text PDFA major near-term medical impact of the genomic technology revolution will be the elucidation of mechanisms of cancer pathogenesis, leading to improvements in the diagnosis of cancer and the selection of cancer treatment. Next-generation sequencing technologies have accelerated the characterization of a tumor, leading to the comprehensive discovery of all the major alterations in a given cancer genome, followed by the translation of this information using computational and immunoinformatics approaches to cancer diagnostics and therapeutic efforts. In the current article, we review various components of cancer immunoinformatics applied to a series of fields of cancer research, including computational tools for cancer mutation detection, cancer mutation and immunological databases, and computational vaccinology.
View Article and Find Full Text PDFThe COVID-19 pandemic has revealed a range of disease phenotypes in infected patients with asymptomatic, mild, or severe clinical outcomes, but the mechanisms that determine such variable outcomes remain unresolved. In this study, we identified immunodominant CD8 T-cell epitopes in the spike antigen using a novel TCR-binding algorithm. The predicted epitopes induced robust T-cell activation in unexposed donors demonstrating pre-existing CD4 and CD8 T-cell immunity to SARS-CoV-2 antigen.
View Article and Find Full Text PDFThe adaptive immune system in vertebrates has evolved to recognize non-self antigens, such as proteins expressed by infectious agents and mutated cancer cells. T cells play an important role in antigen recognition by expressing a diverse repertoire of antigen-specific receptors, which bind epitopes to mount targeted immune responses. Recent advances in high-throughput sequencing have enabled the routine generation of T-cell receptor (TCR) repertoire data.
View Article and Find Full Text PDFFour 1-butyl-3-methylimidazolium halide ionic liquids were synthesized via metathesis and anion exchange reactions. Silver nanoparticles (AgNPs) colloids were synthesized in four ionic liquids in the pressurized reactor by reduction of silver nitrate with hydrogen gas, without adding solvents or stabilizing agents. Antibacterial activities of base ionic liquids and AgNPs colloids in ionic liquids were reviewed by well-diffusion method for gram-positive Bacillus cereus (NCIM-2155) and gram-negative Escherichia coli (NCIM-2931) bacteria.
View Article and Find Full Text PDFThe interaction between the class I major histocompatibility complex (MHC), the peptide presented by the MHC and the T-cell receptor (TCR) is a key determinant of the cellular immune response. Here, we present TCRpMHCmodels, a method for accurate structural modelling of the TCR-peptide-MHC (TCR-pMHC) complex. This TCR-pMHC modelling pipeline takes as input the amino acid sequence and generates models of the TCR-pMHC complex, with a median Cα RMSD of 2.
View Article and Find Full Text PDFBackground: The development of accurate epitope prediction tools is important in facilitating disease diagnostics, treatment and vaccine development. The advent of new approaches making use of antibody and TCR sequence information to predict receptor-specific epitopes have the potential to transform the epitope prediction field. Development and validation of these new generation of epitope prediction methods would benefit from regularly updated high-quality receptor-antigen complex datasets.
View Article and Find Full Text PDFEnteroviruses are potentially linked to the emergence of Acute Flaccid Myelitis (AFM), a rare but very serious condition that affects the nervous system. AFM has been associated with coxsackievirus A16, enterovirus A71 (EVA71) and enterovirus D68 (EVD68). Little is known about host-pathogen interactions for these viruses, and whether immune responses may have a protective or immunopathological role in disease presentations.
View Article and Find Full Text PDFThe Immune Epitope Database Analysis Resource (IEDB-AR, http://tools.iedb.org/) is a companion website to the IEDB that provides computational tools focused on the prediction and analysis of B and T cell epitopes.
View Article and Find Full Text PDFB-cells can neutralize pathogenic molecules by targeting them with extreme specificity using receptors secreted or expressed on their surface (antibodies). This is achieved via molecular interactions between the paratope (i.e.
View Article and Find Full Text PDFThe Immune Epitope Database (IEDB) is a free public resource which catalogs experiments characterizing immune epitopes. To accommodate data from next generation repertoire sequencing experiments, we recently updated how we capture and query epitope specific antibodies and T cell receptors. Specifically, we are now storing partial receptor sequences sufficient to determine CDRs and VDJ gene usage which are commonly identified by repertoire sequencing.
View Article and Find Full Text PDFThe Immune Epitope Database (IEDB, iedb.org) captures experimental data confined in figures, text and tables of the scientific literature, making it freely available and easily searchable to the public. The scope of the IEDB extends across immune epitope data related to all species studied and includes antibody, T cell, and MHC binding contexts associated with infectious, allergic, autoimmune, and transplant related diseases.
View Article and Find Full Text PDFDigital holographic microscopy is the state of the art quantitative phase imaging of micro-objects including living cells. It is an ideal tool to image and quantify cell thickness profiles with nanometer thickness resolution. Digital holographic techniques usually are implemented using a two-beam setup that may be bulky and may not be field portable.
View Article and Find Full Text PDFQuantitative three-dimensional (3-D) imaging of living cells provides important information about the cell morphology and its time variation. Off-axis, digital holographic interference microscopy is an ideal tool for 3-D imaging, parameter extraction, and classification of living cells. Two-beam digital holographic microscopes, which are usually employed, provide high-quality 3-D images of micro-objects, albeit with lower temporal stability.
View Article and Find Full Text PDFLibraries of structural prototypes that abstract protein local structures are known as structural alphabets and have proven to be very useful in various aspects of protein structure analyses and predictions. One such library, Protein Blocks, is composed of 16 standard 5-residues long structural prototypes. This form of analyzing proteins involves drafting its structure as a string of Protein Blocks.
View Article and Find Full Text PDFThe relationship between the normal modes of a protein and its functional conformational change has been studied for decades. However, using this relationship in a predictive context remains a challenge. In this work, we demonstrate that, starting from a given protein conformer, it is possible to generate in a single step model conformers that are less than 1 Å (C -RMSD) from the conformer which is the known endpoint of the conformational change, particularly when the conformational change is collective in nature.
View Article and Find Full Text PDFRev Bras Anestesiol
April 2019
Gastroschisis is a congenital anomaly characterized by a defect in the anterior abdominal wall with protrusion of abdominal viscera. Perioperative mortality is very high in these patients. Traditionally gastroschisis repair has been performed under general anesthesia with endotracheal intubation, requiring postoperative intensive care admission and mechanical ventilation.
View Article and Find Full Text PDFThe task of epitope discovery and vaccine design is increasingly reliant on bioinformatics analytic tools and access to depositories of curated data relevant to immune reactions and specific pathogens. The Immune Epitope Database and Analysis Resource (IEDB) was indeed created to assist biomedical researchers in the development of new vaccines, diagnostics, and therapeutics. The Analysis Resource is freely available to all researchers and provides access to a variety of epitope analysis and prediction tools.
View Article and Find Full Text PDFInterferometric microscopy has grown into a very potent tool for quantitative phase imaging of biological samples. Among the interfermetric methods, microscopy by digital holography is one of the most effective techniques, especially for studying dynamics of cells. Imaging of cell fluctuations requires digital holographic setups with high temporal stability.
View Article and Find Full Text PDFNormal mode analysis is a computational technique that allows to study the dynamics of biological macromolecules. It was first applied to small protein cases, more than thirty years ago. The interest in this technique then raised when it was realized that it can provide insights about the large-scale conformational changes a protein can experience, for instance upon ligand binding.
View Article and Find Full Text PDFThe structural annotation of proteins with no detectable homologs of known 3D structure identified using sequence-search methods is a major challenge today. We propose an original method that computes the conditional probabilities for the amino-acid sequence of a protein to fit to known protein 3D structures using a structural alphabet, known as "Protein Blocks" (PBs). PBs constitute a library of 16 local structural prototypes that approximate every part of protein backbone structures.
View Article and Find Full Text PDFProtein structure alignment is a crucial step in protein structure-function analysis. Despite the advances in protein structure alignment algorithms, some of the local conformationally similar regions are mislabeled as structurally variable regions (SVRs). These regions are not well superimposed because of differences in their spatial orientations.
View Article and Find Full Text PDFConformational changes in proteins are extremely important for their biochemical functions. Correlation between inherent conformational variations in a protein and conformational differences in its homologues of known structure is still unclear. In this study, we have used a structural alphabet called Protein Blocks (PBs).
View Article and Find Full Text PDFBackground: Most signalling and regulatory proteins participate in transient protein-protein interactions during biological processes. They usually serve as key regulators of various cellular processes and are often stable in both protein-bound and unbound forms. Availability of high-resolution structures of their unbound and bound forms provides an opportunity to understand the molecular mechanisms involved.
View Article and Find Full Text PDFProtein structures are classically described in terms of secondary structures. Even if the regular secondary structures have relevant physical meaning, their recognition from atomic coordinates has some important limitations such as uncertainties in the assignment of boundaries of helical and β-strand regions. Further, on an average about 50% of all residues are assigned to an irregular state, i.
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