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1
Han, Bingqing, Chongjiao Ren, Wenda Wang, Jiashan Li und Xinqi Gong. „Computational Prediction of Protein Intrinsically Disordered Region Related Interactions and Functions“. Genes 14, Nr. 2 (08.02.2023): 432. http://dx.doi.org/10.3390/genes14020432.
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Intrinsically Disordered Proteins (IDPs) and Regions (IDRs) exist widely. Although without well-defined structures, they participate in many important biological processes. In addition, they are also widely related to human diseases and have become potential targets in drug discovery. However, there is a big gap between the experimental annotations related to IDPs/IDRs and their actual number. In recent decades, the computational methods related to IDPs/IDRs have been developed vigorously, including predicting IDPs/IDRs, the binding modes of IDPs/IDRs, the binding sites of IDPs/IDRs, and the molecular functions of IDPs/IDRs according to different tasks. In view of the correlation between these predictors, we have reviewed these prediction methods uniformly for the first time, summarized their computational methods and predictive performance, and discussed some problems and perspectives.
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Coskuner-Weber, Orkid, und Vladimir N. Uversky. „Current Stage and Future Perspectives for Homology Modeling, Molecular Dynamics Simulations, Machine Learning with Molecular Dynamics, and Quantum Computing for Intrinsically Disordered Proteins and Proteins with Intrinsically Disordered Regions“. Current Protein & Peptide Science 25, Nr. 2 (Februar 2024): 163–71. http://dx.doi.org/10.2174/0113892037281184231123111223.
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Abstract:: The structural ensembles of intrinsically disordered proteins (IDPs) and proteins with intrinsically disordered regions (IDRs) cannot be easily characterized using conventional experimental techniques. Computational techniques complement experiments and provide useful insights into the structural ensembles of IDPs and proteins with IDRs. Herein, we discuss computational techniques such as homology modeling, molecular dynamics simulations, machine learning with molecular dynamics, and quantum computing that can be applied to the studies of IDPs and hybrid proteins with IDRs. We also provide useful future perspectives for computational techniques that can be applied to IDPs and hybrid proteins containing ordered domains and IDRs.
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Liu, Meili, Akshaya K. Das, James Lincoff, Sukanya Sasmal, Sara Y. Cheng, Robert M. Vernon, Julie D. Forman-Kay und Teresa Head-Gordon. „Configurational Entropy of Folded Proteins and Its Importance for Intrinsically Disordered Proteins“. International Journal of Molecular Sciences 22, Nr. 7 (26.03.2021): 3420. http://dx.doi.org/10.3390/ijms22073420.
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Many pairwise additive force fields are in active use for intrinsically disordered proteins (IDPs) and regions (IDRs), some of which modify energetic terms to improve the description of IDPs/IDRs but are largely in disagreement with solution experiments for the disordered states. This work considers a new direction—the connection to configurational entropy—and how it might change the nature of our understanding of protein force field development to equally well encompass globular proteins, IDRs/IDPs, and disorder-to-order transitions. We have evaluated representative pairwise and many-body protein and water force fields against experimental data on representative IDPs and IDRs, a peptide that undergoes a disorder-to-order transition, for seven globular proteins ranging in size from 130 to 266 amino acids. We find that force fields with the largest statistical fluctuations consistent with the radius of gyration and universal Lindemann values for folded states simultaneously better describe IDPs and IDRs and disorder-to-order transitions. Hence, the crux of what a force field should exhibit to well describe IDRs/IDPs is not just the balance between protein and water energetics but the balance between energetic effects and configurational entropy of folded states of globular proteins.
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Ahmed, Shehab S., Zaara T. Rifat, Ruchi Lohia, Arthur J. Campbell, A. Keith Dunker, M. Sohel Rahman und Sumaiya Iqbal. „Characterization of intrinsically disordered regions in proteins informed by human genetic diversity“. PLOS Computational Biology 18, Nr. 3 (11.03.2022): e1009911. http://dx.doi.org/10.1371/journal.pcbi.1009911.
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All proteomes contain both proteins and polypeptide segments that don’t form a defined three-dimensional structure yet are biologically active—called intrinsically disordered proteins and regions (IDPs and IDRs). Most of these IDPs/IDRs lack useful functional annotation limiting our understanding of their importance for organism fitness. Here we characterized IDRs using protein sequence annotations of functional sites and regions available in the UniProt knowledgebase (“UniProt features”: active site, ligand-binding pocket, regions mediating protein-protein interactions, etc.). By measuring the statistical enrichment of twenty-five UniProt features in 981 IDRs of 561 human proteins, we identified eight features that are commonly located in IDRs. We then collected the genetic variant data from the general population and patient-based databases and evaluated the prevalence of population and pathogenic variations in IDPs/IDRs. We observed that some IDRs tolerate 2 to 12-times more single amino acid-substituting missense mutations than synonymous changes in the general population. However, we also found that 37% of all germline pathogenic mutations are located in disordered regions of 96 proteins. Based on the observed-to-expected frequency of mutations, we categorized 34 IDRs in 20 proteins (DDX3X, KIT, RB1, etc.) as intolerant to mutation. Finally, using statistical analysis and a machine learning approach, we demonstrate that mutation-intolerant IDRs carry a distinct signature of functional features. Our study presents a novel approach to assign functional importance to IDRs by leveraging the wealth of available genetic data, which will aid in a deeper understating of the role of IDRs in biological processes and disease mechanisms.
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Medvedev, Kirill E., Jimin Pei und Nick V. Grishin. „DisEnrich: database of enriched regions in human dark proteome“. Bioinformatics 38, Nr. 7 (30.01.2022): 1870–76. http://dx.doi.org/10.1093/bioinformatics/btac051.
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Abstract Motivation Intrinsically disordered proteins (IDPs) are involved in numerous processes crucial for living organisms. Bias in amino acid composition of these proteins determines their unique biophysical and functional features. Distinct intrinsically disordered regions (IDRs) with compositional bias play different important roles in various biological processes. IDRs enriched in particular amino acids in human proteome have not been described consistently. Results We developed DisEnrich—the database of human proteome IDRs that are significantly enriched in particular amino acids. Each human protein is described using Gene Ontology (GO) function terms, disorder prediction for the full-length sequence using three methods, enriched IDR composition and ranks of human proteins with similar enriched IDRs. Distribution analysis of enriched IDRs among broad functional categories revealed significant overrepresentation of R- and Y-enriched IDRs in metabolic and enzymatic activities and F-enriched IDRs in transport. About 75% of functional categories contain IDPs with IDRs significantly enriched in hydrophobic residues that are important for protein–protein interactions. Availability and implementation The database is available at http://prodata.swmed.edu/DisEnrichDB/. Supplementary information Supplementary data are available at Bioinformatics Advances online.
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Felli, Isabella C., Wolfgang Bermel und Roberta Pierattelli. „Exclusively heteronuclear NMR experiments for the investigation of intrinsically disordered proteins: focusing on proline residues“. Magnetic Resonance 2, Nr. 1 (01.07.2021): 511–22. http://dx.doi.org/10.5194/mr-2-511-2021.
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Abstract. NMR represents a key spectroscopic technique that contributes to the emerging field of highly flexible, intrinsically disordered proteins (IDPs) or protein regions (IDRs) that lack a stable three-dimensional structure. A set of exclusively heteronuclear NMR experiments tailored for proline residues, highly abundant in IDPs/IDRs, are presented here. They provide a valuable complement to the widely used approach based on amide proton detection, filling the gap introduced by the lack of amide protons in proline residues within polypeptide chains. The novel experiments have very interesting properties for the investigations of IDPs/IDRs of increasing complexity.
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Saito, Akatsuki, Maya Shofa, Hirotaka Ode, Maho Yumiya, Junki Hirano, Toru Okamoto und Shige H. Yoshimura. „How Do Flaviviruses Hijack Host Cell Functions by Phase Separation?“ Viruses 13, Nr. 8 (28.07.2021): 1479. http://dx.doi.org/10.3390/v13081479.
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Viral proteins interact with different sets of host cell components throughout the viral life cycle and are known to localize to the intracellular membraneless organelles (MLOs) of the host cell, where formation/dissolution is regulated by phase separation of intrinsically disordered proteins and regions (IDPs/IDRs). Viral proteins are rich in IDRs, implying that viruses utilize IDRs to regulate phase separation of the host cell organelles and augment replication by commandeering the functions of the organelles and/or sneaking into the organelles to evade the host immune response. This review aims to integrate current knowledge of the structural properties and intracellular localizations of viral IDPs to understand viral strategies in the host cell. First, the properties of viral IDRs are reviewed and similarities and differences with those of eukaryotes are described. The higher IDR content in viruses with smaller genomes suggests that IDRs are essential characteristics of viral proteins. Then, the interactions of the IDRs of flaviviruses with the MLOs of the host cell are investigated with emphasis on the viral proteins localized in the nucleoli and stress granules. Finally, the possible roles of viral IDRs in regulation of the phase separation of organelles and future possibilities for antiviral drug development are discussed.
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Kastano, Kristina, Gábor Erdős, Pablo Mier, Gregorio Alanis-Lobato, Vasilis J. Promponas, Zsuzsanna Dosztányi und Miguel A. Andrade-Navarro. „Evolutionary Study of Disorder in Protein Sequences“. Biomolecules 10, Nr. 10 (06.10.2020): 1413. http://dx.doi.org/10.3390/biom10101413.
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Intrinsically disordered proteins (IDPs) contain regions lacking intrinsic globular structure (intrinsically disordered regions, IDRs). IDPs are present across the tree of life, with great variability of IDR type and frequency even between closely related taxa. To investigate the function of IDRs, we evaluated and compared the distribution of disorder content in 10,695 reference proteomes, confirming its high variability and finding certain correlation along the Euteleostomi (bony vertebrates) lineage to number of cell types. We used the comparison of orthologs to study the function of disorder related to increase in cell types, observing that multiple interacting subunits of protein complexes might gain IDRs in evolution, thus stressing the function of IDRs in modulating protein-protein interactions, particularly in the cell nucleus. Interestingly, the conservation of local compositional biases of IDPs follows residue-type specific patterns, with E- and K-rich regions being evolutionarily stable and Q- and A-rich regions being more dynamic. We provide a framework for targeted evolutionary studies of the emergence of IDRs. We believe that, given the large variability of IDR distributions in different species, studies using this evolutionary perspective are required.
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Alshehri, Manal A., Manee M. Manee, Mohamed B. Al-Fageeh und Badr M. Al-Shomrani. „Genomic Analysis of Intrinsically Disordered Proteins in the Genus Camelus“. International Journal of Molecular Sciences 21, Nr. 11 (03.06.2020): 4010. http://dx.doi.org/10.3390/ijms21114010.
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Intrinsically disordered proteins/regions (IDPs/IDRs) fail to fold completely into 3D structures, but have major roles in determining protein function. While natively disordered proteins/regions have been found to fulfill a wide variety of primary cellular roles, the functions of many disordered proteins in numerous species remain to be uncovered. Here, we perform the first large-scale study of IDPs/IDRs in the genus Camelus, one of the most important mammalians in Asia and North Africa, in order to explore the biological roles of these proteins. The study includes the prediction of disordered proteins/regions in Camelus species and in humans using multiple state-of-the-art prediction tools. Additionally, we provide a comparative analysis of Camelus and Homo sapiens IDPs/IDRs for the sake of highlighting the distinctive use of disorder in each genus. Our findings indicate that the human proteome is more disordered than the Camelus proteome. Gene Ontology analysis also revealed that Camelus IDPs are enriched in glutathione catabolism and lactose biosynthesis.
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Chiang, Wan-Chin, Ming-Hsuan Lee, Tsai-Chen Chen und Jie-rong Huang. „Interactions between the Intrinsically Disordered Regions of hnRNP-A2 and TDP-43 Accelerate TDP-43′s Conformational Transition“. International Journal of Molecular Sciences 21, Nr. 16 (18.08.2020): 5930. http://dx.doi.org/10.3390/ijms21165930.
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Most biological functions involve protein–protein interactions. Our understanding of these interactions is based mainly on those of structured proteins, because encounters between intrinsically disordered proteins (IDPs) or proteins with intrinsically disordered regions (IDRs) are much less studied, regardless of the fact that more than half eukaryotic proteins contain IDRs. RNA-binding proteins (RBPs) are a large family whose members almost all have IDRs in addition to RNA binding domains. These IDRs, having low sequence similarity, interact, but structural details on these interactions are still lacking. Here, using the IDRs of two RBPs (hnRNA-A2 and TDP-43) as a model, we demonstrate that the rate at which TDP-43′s IDR undergoes the neurodegenerative disease related α-helix-to-β-sheet transition increases in relation to the amount of hnRNP-A2′s IDR that is present. There are more than 1500 RBPs in human cells and most of them have IDRs. RBPs often join the same complexes to regulate genes. In addition to the structured RNA-recognition motifs, our study demonstrates a general mechanism through which RBPs may regulate each other’s functions through their IDRs.
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Gill, Michelle L., R. Andrew Byrd und Arthur G. Palmer, III. „Dynamics of GCN4 facilitate DNA interaction: a model-free analysis of an intrinsically disordered region“. Physical Chemistry Chemical Physics 18, Nr. 8 (2016): 5839–49. http://dx.doi.org/10.1039/c5cp06197k.
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McFadden, William M., und Judith L. Yanowitz. „idpr: A package for profiling and analyzing Intrinsically Disordered Proteins in R“. PLOS ONE 17, Nr. 4 (18.04.2022): e0266929. http://dx.doi.org/10.1371/journal.pone.0266929.
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Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) are proteins or protein-domains that do not have a single native structure, rather, they are a class of flexible peptides that can rapidly adopt multiple conformations. IDPs are quite abundant, and their dynamic characteristics provide unique advantages for various biological processes. The field of “unstructured biology” has emerged, in part, because of numerous computational studies that had identified the unique characteristics of IDPs and IDRs. The package ‘idpr’, short for Intrinsically Disordered Proteins in R, implements several R functions that match the established characteristics of IDPs to protein sequences of interest. This includes calculations of residue composition, charge-hydropathy relationships, and predictions of intrinsic disorder. Additionally, idpr integrates several amino acid substitution matrices and calculators to supplement IDP-based workflows. Overall, idpr aims to integrate tools for the computational analysis of IDPs within R, facilitating the analysis of these important, yet under-characterized, proteins. The idpr package can be downloaded from Bioconductor (https://bioconductor.org/packages/idpr/).
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Fujiwara, Satoru. „Dynamical Behavior of Disordered Regions in Disease-Related Proteins Revealed by Quasielastic Neutron Scattering“. Medicina 58, Nr. 6 (13.06.2022): 795. http://dx.doi.org/10.3390/medicina58060795.
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Background and Objectives: Intrinsically disordered proteins (IDPs) and proteins containing intrinsically disordered regions (IDRs) are known to be involved in various human diseases. Since the IDPs/IDRs are fluctuating between many structural substrates, the dynamical behavior of the disease-related IDPs/IDRs needs to be characterized to elucidate the mechanisms of the pathogenesis of the diseases. As protein motions have a hierarchy ranging from local side-chain motions, through segmental motions of loops or disordered regions, to diffusive motions of entire molecules, segmental motions, as well as local motions, need to be characterized. Materials and Methods: Combined analysis of quasielastic neutron scattering (QENS) spectra with the structural data provides information on both the segmental motions and the local motions of the IDPs/IDRs. Here, this method is applied to re-analyze the QENS spectra of the troponin core domain (Tn-CD), various mutants of which cause the pathogenesis of familial cardiomyopathy (FCM), and α-synuclein (αSyn), amyloid fibril formation of which is closely related to the pathogenesis of Parkinson’s disease, collected in the previous studies. The dynamical behavior of wild-type Tn-CD, FCM-related mutant Tn-CD, and αSyn in the different propensity states for fibril formation is characterized. Results: In the Tn-CD, the behavior of the segmental motions is shown to be different between the wild type and the mutant. This difference is likely to arise from changes in the intramolecular interactions, which are suggested to be related to the functional aberration of the mutant Tn-CD. In αSyn, concerted enhancement of the segmental motions and the local motions is observed with an increased propensity for fibril formation, suggesting the importance of these motions in fibril formation. Conclusions: Characterization of the segmental motions as well as the local motions is thus useful for discussing how the changes in dynamical behavior caused by the disease-related mutations and/or environmental changes could be related to the functional and/or behavioral aberrations of these proteins.
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Brocca, Stefania, Rita Grandori, Sonia Longhi und Vladimir Uversky. „Liquid–Liquid Phase Separation by Intrinsically Disordered Protein Regions of Viruses: Roles in Viral Life Cycle and Control of Virus–Host Interactions“. International Journal of Molecular Sciences 21, Nr. 23 (28.11.2020): 9045. http://dx.doi.org/10.3390/ijms21239045.
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Intrinsically disordered proteins (IDPs) are unable to adopt a unique 3D structure under physiological conditions and thus exist as highly dynamic conformational ensembles. IDPs are ubiquitous and widely spread in the protein realm. In the last decade, compelling experimental evidence has been gathered, pointing to the ability of IDPs and intrinsically disordered regions (IDRs) to undergo liquid–liquid phase separation (LLPS), a phenomenon driving the formation of membrane-less organelles (MLOs). These biological condensates play a critical role in the spatio-temporal organization of the cell, where they exert a multitude of key biological functions, ranging from transcriptional regulation and silencing to control of signal transduction networks. After introducing IDPs and LLPS, we herein survey available data on LLPS by IDPs/IDRs of viral origin and discuss their functional implications. We distinguish LLPS associated with viral replication and trafficking of viral components, from the LLPS-mediated interference of viruses with host cell functions. We discuss emerging evidence on the ability of plant virus proteins to interfere with the regulation of MLOs of the host and propose that bacteriophages can interfere with bacterial LLPS, as well. We conclude by discussing how LLPS could be targeted to treat phase separation-associated diseases, including viral infections.
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Kastano, Kristina, Pablo Mier, Zsuzsanna Dosztányi, Vasilis J. Promponas und Miguel A. Andrade-Navarro. „Functional Tuning of Intrinsically Disordered Regions in Human Proteins by Composition Bias“. Biomolecules 12, Nr. 10 (15.10.2022): 1486. http://dx.doi.org/10.3390/biom12101486.
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Intrinsically disordered regions (IDRs) in protein sequences are flexible, have low structural constraints and as a result have faster rates of evolution. This lack of evolutionary conservation greatly limits the use of sequence homology for the classification and functional assessment of IDRs, as opposed to globular domains. The study of IDRs requires other properties for their classification and functional prediction. While composition bias is not a necessary property of IDRs, compositionally biased regions (CBRs) have been noted as frequent part of IDRs. We hypothesized that to characterize IDRs, it could be helpful to study their overlap with particular types of CBRs. Here, we evaluate this overlap in the human proteome. A total of 2/3 of residues in IDRs overlap CBRs. Considering CBRs enriched in one type of amino acid, we can distinguish CBRs that tend to be fully included within long IDRs (R, H, N, D, P, G), from those that partially overlap shorter IDRs (S, E, K, T), and others that tend to overlap IDR terminals (Q, A). CBRs overlap more often IDRs in nuclear proteins and in proteins involved in liquid-liquid phase separation (LLPS). Study of protein interaction networks reveals the enrichment of CBRs in IDRs by tandem repetition of short linear motifs (rich in S or P), and the existence of E-rich polar regions that could support specific protein interactions with non-specific interactions. Our results open ways to pin down the function of IDRs from their partial compositional biases.
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Tarantino, Adriana, Giuseppe Ciconte, Andrea Ghiroldi, Flavio Mastrocinque, Emanuele Micaglio, Antonio Boccellino, Gabriele Negro et al. „Challenges in Brugada Syndrome Stratification: Investigating SCN5A Mutation Localization and Clinical Phenotypes“. International Journal of Molecular Sciences 24, Nr. 23 (23.11.2023): 16658. http://dx.doi.org/10.3390/ijms242316658.
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Brugada Syndrome (BrS) is a genetic heart condition linked to sudden cardiac death. Though the SCN5A gene is primarily associated with BrS, there is a lack of comprehensive studies exploring the connection between SCN5A mutation locations and the clinical presentations of the syndrome. This study aimed to address this gap and gain further understanding of the syndrome. The investigation classified 36 high-risk BrS patients based on SCN5A mutations within the transmembrane/structured (TD) and intra-domain loops (IDLs) lacking a 3D structure. We characterized the intrinsically disordered regions (IDRs) abundant in IDLs, using bioinformatics tools to predict IDRs and post-translational modifications (PTMs) in NaV1.5. Interestingly, it was found that current predictive tools often underestimate the impacts of mutations in IDLs and disordered regions. Moreover, patients with SCN5A mutations confined to IDL regions—previously deemed ‘benign’—displayed clinical symptoms similar to those carrying ‘damaging’ variants. Our research illuminates the difficulty in stratifying patients based on SCN5A mutation locations, emphasizing the vital role of IDLs in the NaV1.5 channel’s functioning and protein interactions. We advocate for caution when using predictive tools for mutation evaluation in these regions and call for the development of improved strategies in accurately assessing BrS risk
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Gonçalves-Kulik, Mariane, Pablo Mier, Kristina Kastano, Juan Cortés, Pau Bernadó, Friederike Schmid und Miguel A. Andrade-Navarro. „Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered“. Biomolecules 12, Nr. 8 (10.08.2022): 1098. http://dx.doi.org/10.3390/biom12081098.
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There is increasing evidence that many intrinsically disordered regions (IDRs) in proteins play key functional roles through interactions with other proteins or nucleic acids. These interactions often exhibit a context-dependent structural behavior. We hypothesize that low complexity regions (LCRs), often found within IDRs, could have a role in inducing local structure in IDRs. To test this, we predicted IDRs in the human proteome and analyzed their structures or those of homologous sequences in the Protein Data Bank (PDB). We then identified two types of simple LCRs within IDRs: regions with only one (polyX or homorepeats) or with only two types of amino acids (polyXY). We were able to assign structural information from the PDB more often to these LCRs than to the surrounding IDRs (polyX 61.8% > polyXY 50.5% > IDRs 39.7%). The most frequently observed polyX and polyXY within IDRs contained E (Glu) or G (Gly). Structural analyses of these sequences and of homologs indicate that polyEK regions induce helical conformations, while the other most frequent LCRs induce coil structures. Our work proposes bioinformatics methods to help in the study of the structural behavior of IDRs and provides a solid basis suggesting a structuring role of LCRs within them.
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Pintado-Grima, Carlos, Oriol Bárcenas und Salvador Ventura. „In-Silico Analysis of pH-Dependent Liquid-Liquid Phase Separation in Intrinsically Disordered Proteins“. Biomolecules 12, Nr. 7 (12.07.2022): 974. http://dx.doi.org/10.3390/biom12070974.
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Intrinsically disordered proteins (IDPs) are essential players in the assembly of biomolecular condensates during liquid–liquid phase separation (LLPS). Disordered regions (IDRs) are significantly exposed to the solvent and, therefore, highly influenced by fluctuations in the microenvironment. Extrinsic factors, such as pH, modify the solubility and disorder state of IDPs, which in turn may impact the formation of liquid condensates. However, little attention has been paid to how the solution pH influences LLPS, despite knowing that this process is context-dependent. Here, we have conducted a large-scale in-silico analysis of pH-dependent solubility and disorder in IDRs known to be involved in LLPS (LLPS-DRs). We found that LLPS-DRs present maximum solubility around physiological pH, where LLPS often occurs, and identified significant differences in solubility and disorder between proteins that can phase-separate by themselves or those that require a partner. We also analyzed the effect of mutations in the resulting solubility profiles of LLPS-DRs and discussed how, as a general trend, LLPS-DRs display physicochemical properties that permit their LLPS at physiologically relevant pHs.
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Watson, Matthew, und Katherine Stott. „Disordered domains in chromatin-binding proteins“. Essays in Biochemistry 63, Nr. 1 (April 2019): 147–56. http://dx.doi.org/10.1042/ebc20180068.
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Abstract Chromatin comprises proteins, DNA and RNA, and its function is to condense and package the genome in a way that allows the necessary transactions such as transcription, replication and repair to occur in a highly organised and regulated manner. The packaging of chromatin is often thought of in a hierarchical fashion starting from the most basic unit of DNA packaging, the nucleosome, to the condensation of nucleosomal ‘beads on a string’ by linker histones to form the 30-nm fibre and eventually large chromatin domains. However, a picture of a more heterogeneous, dynamic and liquid-like assembly is emerging, in which intrinsically disordered proteins (IDPs) and proteins containing intrinsically disordered regions (IDRs) play a central role. Disorder features at all levels of chromatin organisation, from the histone tails, which are sites of extensive post-translational modification (PTM) that change the fate of the underlying genomic information, right through to transcription hubs, and the recently elucidated roles of IDPs and IDRs in the condensation of large regions of the genome through liquid–liquid phase separation.
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Jain, Mayank, Vinod Kumar, Manish Jain, Kapil Garg, Ravi Shekhawat und Pankaj Kumar Gupta. „Indian Diabetes Risk Score (IDRS) as a strong predictor of diabetes mellitus: A cross sectional study among urban population of Jhalawar, Rajasthan“. Indian Journal of Community Health 34, Nr. 1 (31.03.2022): 60–66. http://dx.doi.org/10.47203/ijch.2022.v34i01.012.
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Introduction: The patients with Type 2 diabetes Mellitus may often remain asymptomatic for a longer period of time. The Indian Diabetes Risk Score (IDRS), a simple screening tool for prediction of undiagnosed diabetes. Objective: Validation of IDRS with standard test for type 2 diabetes among urban population of Jhalawar, Rajasthan. Material and Methods: A Community based Cross-sectional study was carried out in urban field practice area of Department of Community Medicine, Jhalawar Medical College, Jhalawar, Rajasthan. The study was conducted using a two-stage sampling design. A predesigned, pretested proforma and Indian Diabetes Risk Score (IDRS) sheet was used to collect data from the study participants. The IDRS is based on four parameters: age, family history of diabetes, waist circumference and physical inactivity. Data was collected using the World Health Organization stepwise approach to surveillance (STEPS). Results: Among 450 participants, 12.7% participants were in low risk, 59.1% were in moderate risk and 28.2% were in high risk of developing diabetes according to IDRS score. IDRS score of ?60 turned out to be the best cut point for identifying undiagnosed diabetes with sensitivity 92.3% and specificity 82.6%. Positive Predictive value and Negative Predictive value were 47.3% and 98.5% respectively. Conclusion: Association of IDRS was found significant with diabetes. IDRS score of ?60 turned out to be the best cut point for identifying undiagnosed diabetes. IDRS is found valid screening tool for early detection of Diabetes.
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Vovk, Andrei, und Anton Zilman. „Effects of Sequence Composition, Patterning and Hydrodynamics on the Conformation and Dynamics of Intrinsically Disordered Proteins“. International Journal of Molecular Sciences 24, Nr. 2 (11.01.2023): 1444. http://dx.doi.org/10.3390/ijms24021444.
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Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) perform diverse functions in cellular organization, transport and signaling. Unlike the well-defined structures of the classical natively folded proteins, IDPs and IDRs dynamically span large conformational and structural ensembles. This dynamic disorder impedes the study of the relationship between the amino acid sequences of the IDPs and their spatial structures and dynamics, with different experimental techniques often offering seemingly contradictory results. Although experimental and theoretical evidence indicates that some IDP properties can be understood based on their average biophysical properties and amino acid composition, other aspects of IDP function are dictated by the specifics of the amino acid sequence. We investigate the effects of several key variables on the dimensions and the dynamics of IDPs using coarse-grained polymer models. We focus on the sequence “patchiness” informed by the sequence and biophysical properties of different classes of IDPs—and in particular FG nucleoporins of the nuclear pore complex (NPC). We show that the sequence composition and patterning are well reflected in the global conformational variables such as the radius of gyration and hydrodynamic radius, while the end-to-end distance and dynamics are highly sequence-specific. We find that in good solvent conditions highly heterogeneous sequences of IDPs can be well mapped onto averaged minimal polymer models for the purpose of prediction of the IDPs dimensions and dynamic relaxation times. The coarse-grained simulations are in a good agreement with the results of atomistic MD. We discuss the implications of these results for the interpretation of the recent experimental measurements, and for the further applications of mesoscopic models of FG nucleoporins and IDPs more broadly.
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Pritišanac, Iva, Robert Vernon, Alan Moses und Julie Forman Kay. „Entropy and Information within Intrinsically Disordered Protein Regions“. Entropy 21, Nr. 7 (06.07.2019): 662. http://dx.doi.org/10.3390/e21070662.
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Bioinformatics and biophysical studies of intrinsically disordered proteins and regions (IDRs) note the high entropy at individual sequence positions and in conformations sampled in solution. This prevents application of the canonical sequence-structure-function paradigm to IDRs and motivates the development of new methods to extract information from IDR sequences. We argue that the information in IDR sequences cannot be fully revealed through positional conservation, which largely measures stable structural contacts and interaction motifs. Instead, considerations of evolutionary conservation of molecular features can reveal the full extent of information in IDRs. Experimental quantification of the large conformational entropy of IDRs is challenging but can be approximated through the extent of conformational sampling measured by a combination of NMR spectroscopy and lower-resolution structural biology techniques, which can be further interpreted with simulations. Conformational entropy and other biophysical features can be modulated by post-translational modifications that provide functional advantages to IDRs by tuning their energy landscapes and enabling a variety of functional interactions and modes of regulation. The diverse mosaic of functional states of IDRs and their conformational features within complexes demands novel metrics of information, which will reflect the complicated sequence-conformational ensemble-function relationship of IDRs.
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Singleton, Marc D., und Michael B. Eisen. „Evolutionary analyses of intrinsically disordered regions reveal widespread signals of conservation“. PLOS Computational Biology 20, Nr. 4 (25.04.2024): e1012028. http://dx.doi.org/10.1371/journal.pcbi.1012028.
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Intrinsically disordered regions (IDRs) are segments of proteins without stable three-dimensional structures. As this flexibility allows them to interact with diverse binding partners, IDRs play key roles in cell signaling and gene expression. Despite the prevalence and importance of IDRs in eukaryotic proteomes and various biological processes, associating them with specific molecular functions remains a significant challenge due to their high rates of sequence evolution. However, by comparing the observed values of various IDR-associated properties against those generated under a simulated model of evolution, a recent study found most IDRs across the entire yeast proteome contain conserved features. Furthermore, it showed clusters of IDRs with common “evolutionary signatures,” i.e. patterns of conserved features, were associated with specific biological functions. To determine if similar patterns of conservation are found in the IDRs of other systems, in this work we applied a series of phylogenetic models to over 7,500 orthologous IDRs identified in the Drosophila genome to dissect the forces driving their evolution. By comparing models of constrained and unconstrained continuous trait evolution using the Brownian motion and Ornstein-Uhlenbeck models, respectively, we identified signals of widespread constraint, indicating conservation of distributed features is mechanism of IDR evolution common to multiple biological systems. In contrast to the previous study in yeast, however, we observed limited evidence of IDR clusters with specific biological functions, which suggests a more complex relationship between evolutionary constraints and function in the IDRs of multicellular organisms.
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Gupta, Manoj Kumar, Gitashree Dutta, Sridevi G., Pankaja Raghav, Akhil Dhanesh Goel, Pankaj Bhardwaj, Suman Saurabh et al. „Application of Indian Diabetic Risk Score (IDRS) and Community Based Assessment Checklist (CBAC) as Metabolic Syndrome prediction tools“. PLOS ONE 18, Nr. 3 (27.03.2023): e0283263. http://dx.doi.org/10.1371/journal.pone.0283263.
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Background Indian Diabetic Risk Score (IDRS) and Community Based Assessment Checklist (CBAC) are easy, inexpensive, and non-invasive tools that can be used to screen people for Metabolic Syndrome (Met S). The study aimed to explore the prediction abilities of IDRS and CBAC tools for Met S. Methods All the people of age ≥30 years attending the selected rural health centers were screened for Met S. We used the International Diabetes Federation (IDF) criteria to diagnose the Met S. ROC curves were plotted by taking Met S as dependent variables, and IDRS and CBAC scores as independent/prediction variables. Sensitivity (SN), specificity (SP), Positive and Negative Predictive Value (PPV and NPV), Likelihood Ratio for positive and negative tests (LR+ and LR-), Accuracy, and Youden’s index were calculated for different IDRS and CBAC scores cut-offs. Data were analyzed using SPSS v.23 and MedCalc v.20.111. Results A total of 942 participants underwent the screening process. Out of them, 59 (6.4%, 95% CI: 4.90–8.12) were found to have Met S. Area Under the Curve (AUC) for IDRS in predicting Met S was 0.73 (95%CI: 0.67–0.79), with 76.3% (64.0%-85.3%) sensitivity and 54.6% (51.2%-57.8%) specificity at the cut-off of ≥60. For the CBAC score, AUC was 0.73 (95%CI: 0.66–0.79), with 84.7% (73.5%-91.7%) sensitivity and 48.8% (45.5%-52.1%) specificity at the cut-off of ≥4 (Youden’s Index, 2.1). The AUCs of both parameters (IDRS and CBAC scores) were statistically significant. There was no significant difference (p = 0.833) in the AUCs of IDRS and CBAC [Difference between AUC = 0.00571]. Conclusion The current study provides scientific evidence that both IDRS and CBAC have almost 73% prediction ability for Met S. Though CBAC holds relatively greater sensitivity (84.7%) than IDRS (76.3%), the difference in prediction abilities is not statistically significant. The prediction abilities of IDRS and CBAC found in this study are inadequate to qualify as Met S screening tools.
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Zhao, Bi, und Lukasz Kurgan. „Compositional Bias of Intrinsically Disordered Proteins and Regions and Their Predictions“. Biomolecules 12, Nr. 7 (25.06.2022): 888. http://dx.doi.org/10.3390/biom12070888.
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Intrinsically disordered regions (IDRs) carry out many cellular functions and vary in length and placement in protein sequences. This diversity leads to variations in the underlying compositional biases, which were demonstrated for the short vs. long IDRs. We analyze compositional biases across four classes of disorder: fully disordered proteins; short IDRs; long IDRs; and binding IDRs. We identify three distinct biases: for the fully disordered proteins, the short IDRs and the long and binding IDRs combined. We also investigate compositional bias for putative disorder produced by leading disorder predictors and find that it is similar to the bias of the native disorder. Interestingly, the accuracy of disorder predictions across different methods is correlated with the correctness of the compositional bias of their predictions highlighting the importance of the compositional bias. The predictive quality is relatively low for the disorder classes with compositional bias that is the most different from the “generic” disorder bias, while being much higher for the classes with the most similar bias. We discover that different predictors perform best across different classes of disorder. This suggests that no single predictor is universally best and motivates the development of new architectures that combine models that target specific disorder classes.
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Homma, Keiichi, Hiroto Anbo, Tamotsu Noguchi und Satoshi Fukuchi. „Both Intrinsically Disordered Regions and Structural Domains Evolve Rapidly in Immune-Related Mammalian Proteins“. International Journal of Molecular Sciences 19, Nr. 12 (04.12.2018): 3860. http://dx.doi.org/10.3390/ijms19123860.
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Eukaryotic proteins consist of structural domains (SDs) and intrinsically disordered regions (IDRs), i.e., regions that by themselves do not assume unique three-dimensional structures. IDRs are generally subject to less constraint and evolve more rapidly than SDs. Proteins with a lower number of protein-to-protein interactions (PPIs) are also less constrained and tend to evolve fast. Extracellular proteins of mammals, especially immune-related extracellular proteins, on average have relatively high evolution rates. This article aims to examine if a high evolution rate in IDRs or that in SDs accounts for the rapid evolution of extracellular proteins. To this end, we classified eukaryotic proteins based on their cellular localizations and analyzed them. Moreover, we divided proteins into SDs and IDRs and calculated the respective evolution rate. Fractional IDR content is positively correlated with evolution rate. For their fractional IDR content, immune-related extracellular proteins show an aberrantly high evolution rate. IDRs evolve more rapidly than SDs in most subcellular localizations. In extracellular proteins, however, the difference is diminished. For immune-related proteins in mammals in particular, the evolution rates in SDs come close to those in IDRs. Thus high evolution rates in both IDRs and SDs account for the rapid evolution of immune-related proteins.
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Sharma, Kanupriya, Priya Battu, Akshay Anand, Raghuram Nagarathna, Navneet Kaur, Neeru Malik, Amit Singh und Hongasandhra R. Nagendra. „Management of Type II Diabetes by Modulating the Modifiable Risk Factors: A Future Roadmap for Prevention of Cerebrovascular Complications“. Annals of Neurosciences 27, Nr. 3-4 (Juli 2020): 266–72. http://dx.doi.org/10.1177/09727531211000041.
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Background: Indian Diabetes Risk Score (IDRS) is a screening tool for quantifying the risk of diabetes mellitus (DM) development in the Indian population. The present study has evaluated the level of risk of developing DM in Chandigarh and Panchkula based on the IDRS score. Methods: As a part of a national diabetes control trial funded by the Ministry of Health and Family Welfare (MoHFW) and the Ministry of AYUSH, Government of India, 1,916 participants from the Chandigarh and Panchkula regions were assessed for the risk of developing DM. Risk assessment was done on the basis of the IDRS score which includes age, family history, waist circumference, and physical activity as its contributing factors. Participants with an IDRS score <30 were in the low-risk category, those with 30 to 50 were in the moderate-risk category, and those with >60 were in the high-risk category for DM. Results: Out of the 1,916 screened respondents (59.86% females and 40.14% males), 894 participants (46.65%) were at a high risk for DM (IDRS >60), 764 (39.87%) were at a moderate risk (IDRS = 30–60), and 258 (13.46%) were at a low risk (IDRS <30). Waist circumference contributed to 35.90% of the high-risk category followed by age (19.67%) and physical activity (11.67%). Age and waist circumference also showed a strong correlation with the total IDRS score. Conclusion: The Chandigarh and Panchkula population showed a high tendency to develop DM based on the IDRS score. Modifiable risk factors such as waist circumference and physical activity were the major contributing factors. Apart from the modifiable risk factors, age was also another major contributing risk factor. Based on these outcomes, lifestyle modifications like yoga and exercise can be proposed for this population as a preventive approach to reduce the risk of developing DM and other associated cerebrovascular complications.
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Namdev, Garima, und Vinod Narkhede. „A study on validity of Indian Diabetes Risk Score for screening of diabetes mellitus among rural adult population at Rural Health Training Centre, Bhouri, under Department of Community Medicine“. International Journal Of Community Medicine And Public Health 5, Nr. 12 (24.11.2018): 5295. http://dx.doi.org/10.18203/2394-6040.ijcmph20184806.
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Background: Diabetes mellitus is a major public health problem in India and many of them remain undetected throughout years. This scenario becomes worse in rural setup where limited heath care facilities are available. So, to detect risk of diabetes earlier, Indian diabetes risk score (IDRS) is to be used. There is also various socio demographic and anthropometric factors associated with the risk of occurring diabetes. The aims and objectives of the study were to study the validity of IDRS method as a screening tool in community as well as to determine the association of IDRS with socio demographic factors and body mass index (BMI).Methods: A cross sectional study was conducted on 270 study participants at rural health training centre (RHTC) for a period of around 7 months. All of them were being measured weight, height, waist circumference and calculated BMI. Along with it, they were categorized by applying IDRS method and measured blood sugar by glucometer also.Results: Out of 270 study subjects, 29% found to have high score. By applying IDRS, at score > 60, we found 32% sensitivity and 97% specificity. A statistically significant association of IDRS with age, gender, religion, socioeconomic status (SES), education, occupation and BMI was seen.Conclusions: In present study, IDRS method proved to be a good screening tool for detecting diabetes mellitus at rural set up with minimum cost.
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M., Sumana, Hanamantappa Kudachi und M. Sundar. „Prediction of risk of development of type 2 diabetes mellitus using Indian diabetic risk score in rural areas of Hassan“. International Journal Of Community Medicine And Public Health 5, Nr. 3 (24.02.2018): 948. http://dx.doi.org/10.18203/2394-6040.ijcmph20180443.
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Background: It has been estimated by International Diabetic Federation (IDF) that globally as many as 193million people with diabetes, are unaware of their disease, the use of a simple easy to use, non-invasive and cost effective screening tool for community based screening is the need of the hour. This study was taken with objective to assess the risk of development of type 2 diabetes mellitus using Indian diabetic risk score (IDRS), and to determine the association of IDRS with socio-demographic factors.Methods: Cross sectional study was conducted for 3 months in rural areas of Hassan. 480 subjects were chosen by systematic random sampling considering inclusion and exclusion criterions. Data was collected from individuals who were more than 30 years old and not having diabetes. IDRS components were assessed along with other socio demographic components.Results: Out of 480 participants, 256 (53.4%) were females, mean age of the participants 42.38±18.6. 47% belong to class III socioeconomic status, 63%of them are educated, 49% of participants having BMI ≥25, 41% (>0.8) female and 33% (>0.9) male having abnormal waist hip ratio (WHR), 49% of the participants having IDRS score >50 among these high risk participants 35% were having RBS >200. All 24 (100%) morbid obese individuals were having high IDRS score; among these 66.6% have abnormal RBS. IDRS predicted the risk of DM with sensitivity 81% and specificity 59%.Conclusions: As the study finds that percentage random blood glucose is more among participants of high IDRS, thus a simple IDRS tool can be used in the field for mass screening and early intervention.
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Guarna, Marta, Haiyan Yang, Natalie Glavas, Yanshen Deng, Edie Dullaghan, Neeloffer Mookherjee, Jennifer Bishop et al. „IDRs as Novel Immunomodulators (B208)“. Journal of Immunology 178, Nr. 1_Supplement (01.04.2007): LB43. http://dx.doi.org/10.4049/jimmunol.178.supp.b208.
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Abstract Inimex Innate Defence Regulators (IDRs) are novel, synthetic immunomodulatory peptides that protect against infections by selectively activating the innate immune system while regulating inflammation. The multi-faceted effects of IDRs are mediated primarily by monocytes and macrophages. These cells respond to IDRs by selectively increasing the expression of cell surface receptors, and cytokines and chemokines (MCP-1, MCP-3 and CCL-5) which trigger the recruitment and activation of immune cells to the site of the infection. In addition, IDRs control inflammation by enhancing the expression of the anti-inflammatory cytokine IL-10, and down-regulating the release of pro-inflammatory cytokines TNF-α and IL-6 in response to pathogen-associated stimuli. As a result, IDRs selectively activate the immune system without concomitant up-regulation of inflammatory responses. This combination of IDR effects is a distinctive quality of these agents since they are able to maintain a balance between immunostimulatory and inflammatory responses to an invading pathogen. Haiyan Yang is the recipient of an NSERC Industrial R&D Fellowship. Funded in part by a grant from the FNIH and the CIHR through the Grand Challenges in Global Health initiative
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Shashikantha SK, Sheethal MP und Chandana S. „Diabetes risk assessment with Indian Diabetes Risk Score: A cross-sectional study among adults in rural Mandya, Karnataka“. Asian Journal of Medical Sciences 15, Nr. 3 (01.03.2024): 103–7. http://dx.doi.org/10.3126/ajms.v15i3.59238.
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Background: Screening for diabetes using the Indian Diabetes Risk Score (IDRS) is an inexpensive yet effective way of early diagnosis. Aims and Objectives: The present study was conducted to assess the risk of developing diabetes among individuals in rural field practice areas using IDRS. Materials and Methods: A community-based observational study was conducted among persons aged 20 years and older in the rural field practice area for 2 months. A semi-structured interview schedule, including the “IDRS” questionnaire, was used to obtain the data. Results: Out of 1100 subjects, around 50% were above 50 years, only 38.6% of the subjects had a waist circumference within the normal limits; 73.8% did moderate exercise; 86% of the subjects had no history of diabetes in their parents. The mean IDRS score of the subjects was 44.12±14.33, ranging from 10 to 90. Nearly 2/3rd (69.6%) of them were at moderate risk, and 21.2% were at high risk for developing diabetes. The IDRS score was significantly higher among those with diabetes and hypertension. Conclusion: The majority of the subjects in our study had a moderate to high risk of developing diabetes as per the IDRS.
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Akter, Nazma. „Assessment of Risk Score for Developing Type 2 Diabetes Mellitus among Bangladeshi Adults Using Indian Diabetes Risk Score“. Delta Medical College Journal 9, Nr. 1 (07.02.2024): 9–16. http://dx.doi.org/10.3329/dmcj.v9i1.71331.
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Background: Different studies support the utilization of risk-assessment scoring systems in quantifying individual’s risk for developing type 2 diabetes mellitus (T2DM). Thus, a simple risk-assessment scoring system for early screening of T2DM among Bangladeshi adults would be beneficial to identify the high-risk adults and thus taking adequate preventive measures in combating DM. Objective: The purpose of the study was to calculate the risk assessment score for developing type 2 DM among Bangladeshi adults using IDRS (Indian Diabetes Risk Score) tool and to assess the association of different risk factors of IDRS tool with the risk score. Materials and method: The cross sectional observational study was conducted among randomly sampled 482 adult Bangladeshi male and female subjects. The study population consisted of non-diabetic adults visiting the outpatient department (OPD) of Medicine, MARKS Medical College & Hospital, a tertiary care hospital in Dhaka, Bangladesh, from June 2018 to May 2019. A Semi-structured questionnaire consisting of demographic characteristics, risk factor profile of Indian Diabetes Risk Score (IDRS) was used. All the participants were assessed and categorized as high (IDRS ≥60), moderate (IDRS 30-50) and low risk (IDRS <30) based on the risk score of IDRS questionnaire. Data were entered andanalyzed in SPSS. Results: Out of 482 subjects, female were 53.3%. The Mean (±SD) age of the study subjects was 38.92±1.12 years. According to IDRS score, 50.4% of the study subjects were at moderate risk and 37.3% were at high risk of developing diabetes; (p<0.05). The mean IDRS was significantly higher among female than male subjects (p<0.001). A statistically significant association of diabetes risk with different age group, waist circumference, level of exercise and positive family history for diabetes were seen. Conclusion: About 88% of the study subjects were at moderate to high risk of having diabetes, hence screening for risk factors is of utmost importance so thatinterventions can be initiated at an early stage. Delta Med Col J. Jan 2021;9(1):9-16
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Piovesan, Damiano, Alexander Miguel Monzon, Federica Quaglia und Silvio C. E. Tosatto. „Databases for intrinsically disordered proteins“. Acta Crystallographica Section D Structural Biology 78, Nr. 2 (21.01.2022): 144–51. http://dx.doi.org/10.1107/s2059798321012109.
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Intrinsically disordered regions (IDRs) lacking a fixed three-dimensional protein structure are widespread and play a central role in cell regulation. Only a small fraction of IDRs have been functionally characterized, with heterogeneous experimental evidence that is largely buried in the literature. Predictions of IDRs are still difficult to estimate and are poorly characterized. Here, an overview of the publicly available knowledge about IDRs is reported, including manually curated resources, deposition databases and prediction repositories. The types, scopes and availability of the various resources are analyzed, and their complementarity and overlap are highlighted. The volume of information included and the relevance to the field of structural biology are compared.
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Bianchi, Greta, Sonia Longhi, Rita Grandori und Stefania Brocca. „Relevance of Electrostatic Charges in Compactness, Aggregation, and Phase Separation of Intrinsically Disordered Proteins“. International Journal of Molecular Sciences 21, Nr. 17 (27.08.2020): 6208. http://dx.doi.org/10.3390/ijms21176208.
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The abundance of intrinsic disorder in the protein realm and its role in a variety of physiological and pathological cellular events have strengthened the interest of the scientific community in understanding the structural and dynamical properties of intrinsically disordered proteins (IDPs) and regions (IDRs). Attempts at rationalizing the general principles underlying both conformational properties and transitions of IDPs/IDRs must consider the abundance of charged residues (Asp, Glu, Lys, and Arg) that typifies these proteins, rendering them assimilable to polyampholytes or polyelectrolytes. Their conformation strongly depends on both the charge density and distribution along the sequence (i.e., charge decoration) as highlighted by recent experimental and theoretical studies that have introduced novel descriptors. Published experimental data are revisited herein in the frame of this formalism, in a new and possibly unitary perspective. The physicochemical properties most directly affected by charge density and distribution are compaction and solubility, which can be described in a relatively simplified way by tools of polymer physics. Dissecting factors controlling such properties could contribute to better understanding complex biological phenomena, such as fibrillation and phase separation. Furthermore, this knowledge is expected to have enormous practical implications for the design, synthesis, and exploitation of bio-derived materials and the control of natural biological processes.
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Avramov, Miloš, Éva Schád, Ágnes Révész, Lilla Turiák, Iva Uzelac, Ágnes Tantos, László Drahos und Željko D. Popović. „Identification of Intrinsically Disordered Proteins and Regions in a Non-Model Insect Species Ostrinia nubilalis (Hbn.)“. Biomolecules 12, Nr. 4 (18.04.2022): 592. http://dx.doi.org/10.3390/biom12040592.
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Research in previous decades has shown that intrinsically disordered proteins (IDPs) and regions in proteins (IDRs) are as ubiquitous as highly ordered proteins. Despite this, research on IDPs and IDRs still has many gaps left to fill. Here, we present an approach that combines wet lab methods with bioinformatics tools to identify and analyze intrinsically disordered proteins in a non-model insect species that is cold-hardy. Due to their known resilience to the effects of extreme temperatures, these proteins likely play important roles in this insect’s adaptive mechanisms to sub-zero temperatures. The approach involves IDP enrichment by sample heating and double-digestion of proteins, followed by peptide and protein identification. Next, proteins are bioinformatically analyzed for disorder content, presence of long disordered regions, amino acid composition, and processes they are involved in. Finally, IDP detection is validated with an in-house 2D PAGE. In total, 608 unique proteins were identified, with 39 being mostly disordered, 100 partially disordered, 95 nearly ordered, and 374 ordered. One-third contain at least one long disordered segment. Functional information was available for only 90 proteins with intrinsic disorders out of 312 characterized proteins. Around half of the 90 proteins are cytoskeletal elements or involved in translational processes.
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Kumaran, K. Myl, D. R. Vedapriya, Aravind Manoharan und A. Y. Nirupama. „Indian diabetic risk score screening of rural adults in Tamil Nadu“. IHOPE Journal of Ophthalmology 2 (06.05.2023): 31–35. http://dx.doi.org/10.25259/ihopejo_2_2023.
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Objectives: Diabetes is acknowledged as a key public health problem with the prevalence rate increasing globally and reaching epidemic proportions. It is high time that screening programs are implemented at the community level for early detection of the population, who are at risk of having diabetes mellitus. Materials and Methods: A community-based and cross-sectional study was conducted in the rural field practice area of a tertiary care hospital in Chengalpattu district, Tamil Nadu. The screening tool used to assess the risk status was the Indian diabetes risk score (IDRS) and the body mass index (BMI) of the participants was also calculated. Results: A total of 396 formed the study population with the males constituting 47.2% of the study population. The majority were more than 50 years of age. Evaluating the risk status of study subjects using IDRS, the higher IDRS risk score was seen in 48.2% of participants, 47.2% had moderate risk, while only 3.5% had low risk. About 54.2% (n = 198) of participants were found to have a BMI within the normal range, 18.4% were underweight, 20.5% were overweight, and obesity was seen in 6.8% of the participants. A statistically significant association was found between gender and IDRS risk status, whereas no significant association was found between BMI category and IDRS risk status. Conclusions: Almost half of the study participants belonged to the high-risk category using IDRS screening. For the mass screening of diabetes, IDRS seems practically feasible and acceptable.
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Widarjono, Agus, Md Mahmudul ALAM und Abdur Rafik. „The Dynamic Link Between Islamic and Conventional Deposit Rates in a Dual Banking System“. ISRA International Journal of Islamic Finance 15, Nr. 1 (06.03.2023): 91–108. http://dx.doi.org/10.55188/ijif.v15i1.487.
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Purpose — This study empirically assesses the extent to which the conventional deposit rate (CDR) affects the Islamic deposit rate (IDR) in Indonesia and Malaysia within the dual banking system.
Design/Methodology/Approach — This study uses non-linear autoregressive distributed lag (NARDL) and panel cointegration. Monthly data are employed, but the time period for the two countries examined is different because of data availability. The study thus covers the period 2009:M1 to 2020:M12 for Indonesia and 2000:M1 to 2020:M12 for Malaysia.
Findings — The findings confirm evidence of the long-run link between IDR and CDR, where the IDRs in Indonesia and Malaysia asymmetrically respond to changes in CDRs. In addition, Indonesia’s IDRs adjust faster in response to the decline in CDRs compared to increases in CDRs. However, Malaysia’s IDRs adapt faster in response to increases in CDRs than their decreases. The panel cointegration results reinforce the asymmetric findings.
Originality/Value — To the best of our knowledge, this paper is the first study to examine the extent to which IDRs asymmetrically respond to CDRs in a dual baking system in Indonesia and Malaysia.
Practical Implications — Islamic banks (IBs) follow CDRs in determining IDRs due to uncompetitive IDRs, implying that IBs suffer from displaced commercial risk. Therefore, IBs may adopt a policy to address liquidity issues through investment risk reserves (IRR) and profit equalization reserves (PER) to reduce the distinctive gap between IDRs and CDRs.
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Ahmed, Mansoor, und Amrutha A. M. „Association of socio-demographic variables and risk of type 2 diabetes using Indian diabetes risk score: a cross-sectional study in urban Mysuru“. International Journal Of Community Medicine And Public Health 5, Nr. 2 (24.01.2018): 740. http://dx.doi.org/10.18203/2394-6040.ijcmph20180260.
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Background: About 422 million people worldwide have diabetes. India has 69.2 million people living with diabetes out of a population of 1.3 billion (8.7%) as per the 2015 data. Of these, it remained undiagnosed in more than 36 million people. Early identification of at-risk individuals and appropriate lifestyle intervention would help in preventing or postponing the onset of diabetes mellitus. Present study aimed to study the association of IDRS components with socio demographic and anthropometric variables among adults in urban area of Mysore.Methods: A community-based cross sectional study was conducted in the urban areas of the field practice area of Mysore Medical College and Research Institute. The study was conducted between March and July 2015. Using the estimation set up technique for proportion, the sample size was calculated to be 872 rounded off to 900, with level of significance of 5% and precision of 10%. Risk level for diabetes was assessed using Indian Diabetic Risk Score (IDRS) and sociodemographic and anthropometric factors were assessed through a semi structured pretested questionnaire.Results: Of 900 participants, 197 (21.9%) had a high risk score (IDRS ≥60), the majority of participants (383; 42.5%) were in the moderate-risk category (IDRS 30–50). There was statistically significant difference between type of family and different risk categories under age component of IDRS (p<0.0005). Statistical significance was observed for marital status and SES among different age groups. Association was found significant between family history of diabetes component of IDRS and gender. There was also statistically significant difference between SES and different risk categories under family history of diabetes component of IDRS (p<0.0005).Conclusions: IDRS should be used routinely in community-based screening to find out high risk category of population for diabetes.
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Hsu, Ian S., Bob Strome, Emma Lash, Nicole Robbins, Leah E. Cowen und Alan M. Moses. „A functionally divergent intrinsically disordered region underlying the conservation of stochastic signaling“. PLOS Genetics 17, Nr. 9 (10.09.2021): e1009629. http://dx.doi.org/10.1371/journal.pgen.1009629.
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Stochastic signaling dynamics expand living cells’ information processing capabilities. An increasing number of studies report that regulators encode information in their pulsatile dynamics. The evolutionary mechanisms that lead to complex signaling dynamics remain uncharacterized, perhaps because key interactions of signaling proteins are encoded in intrinsically disordered regions (IDRs), whose evolution is difficult to analyze. Here we focused on the IDR that controls the stochastic pulsing dynamics of Crz1, a transcription factor in fungi downstream of the widely conserved calcium signaling pathway. We find that Crz1 IDRs from anciently diverged fungi can all respond transiently to calcium stress; however, only Crz1 IDRs from the Saccharomyces clade support pulsatility, encode extra information, and rescue fitness in competition assays, while the Crz1 IDRs from distantly related fungi do none of the three. On the other hand, we find that Crz1 pulsing is conserved in the distantly related fungi, consistent with the evolutionary model of stabilizing selection on the signaling phenotype. Further, we show that a calcineurin docking site in a specific part of the IDRs appears to be sufficient for pulsing and show evidence for a beneficial increase in the relative calcineurin affinity of this docking site. We propose that evolutionary flexibility of functionally divergent IDRs underlies the conservation of stochastic signaling by stabilizing selection.
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Arumugam, Balaji, Aadarshna R. und Suganya E. „Neck circumference as a risk indicator for type 2 diabetes mellitus: a community based cross-sectional study“. International Journal Of Community Medicine And Public Health 6, Nr. 11 (24.10.2019): 4624. http://dx.doi.org/10.18203/2394-6040.ijcmph20195032.
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Background: Diabetes mellitus is a metabolic syndrome due to insulin deficiency, characterized by hyperglycaemia. Indian diabetes risk score (IDRS) is the most commonly used one to determine the risk status. However there is lot of inconvenience and possible errors in measuring the waist circumference to determine the IDRS, hence the study was planned to evaluate if neck circumference could replace waist circumference in determining the diabetes risk.Methods: This cross sectional study was conducted among 300 study participants fulfilling the eligible criteria. Socio-demographic variables, parameters required for determining the IDRS was assessed, in addition, neck circumference (NC) was measured using standard protocol. Another risk score was calculated by replacing waist circumference (WC) with neck circumference and scoring was named as IDRS-NC. Pearson correlation and Wilcoxan sign rank test was done to find out the relationship between WC and NC and also to determine if IDRS-NC could replace IDRS.Results: Out of 300 study population, majority of the participants are in the age group of <35 years 129 (43%) and around 2/3rd of the participants were females. Among the study participants proportion of participants belonging to low risk, medium risk and high risk assessed using IDRS and IDRS-NC was 18.7%, 41%, 40.3% and 31.7%, 38%, 30.3% respectively. There was a strong positive correlation (r=0.837) between the neck circumference and waist circumference. Wilcoxan sign rank test was significant between the 2 scores having a p value of <0.05.Conclusions: In our study there was a positive correlation between neck circumference and waist circumference.
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Hall, Wayne, und Louisa Degenhardt. „The Australian Illicit Drug Reporting System: Monitoring Trends in Illicit Drug Availability, Use and Drug-Related Harm in Australia 1996–2006“. Contemporary Drug Problems 36, Nr. 3-4 (September 2009): 643–61. http://dx.doi.org/10.1177/009145090903600317.
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We describe trends in illicit drug use revealed by the Australian Illicit Drug Reporting System (IDRS) between 1996 and 2006. We begin by briefly outlining the rationale, development, and testing of the IDRS, which integrates information from: interviews with a sentinel population of injecting drug users (IDU); key experts in health and law enforcement; and indicators that include information on drug purity and price, plus indicators of drug-related harm, such as fatal and nonfatal overdoses. These sources of information are critically discussed at annual meetings of researchers, policy makers and practitioners in the field. We describe what the IDRS has revealed about the use of heroin, cocaine, methamphetamines, and injected pharmaceutical preparations (opioids and benzodiazepines) over the period 1996–2006. We also illustrate how IDRS data can be combined with pharmaceutical prescription data to evaluate the effectiveness of policies designed to reduce benzodiazepine injecting. We also very briefly describe recent experience with monitoring trends on “dance party” drug use that extends the methods of IDRS by combining data from interviews with party drug users, key experts, and leading indicators of drug use.
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Garaizar, Adiran, Ignacio Sanchez-Burgos, Rosana Collepardo-Guevara und Jorge R. Espinosa. „Expansion of Intrinsically Disordered Proteins Increases the Range of Stability of Liquid–Liquid Phase Separation“. Molecules 25, Nr. 20 (15.10.2020): 4705. http://dx.doi.org/10.3390/molecules25204705.
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Proteins containing intrinsically disordered regions (IDRs) are ubiquitous within biomolecular condensates, which are liquid-like compartments within cells formed through liquid–liquid phase separation (LLPS). The sequence of amino acids of a protein encodes its phase behaviour, not only by establishing the patterning and chemical nature (e.g., hydrophobic, polar, charged) of the various binding sites that facilitate multivalent interactions, but also by dictating the protein conformational dynamics. Besides behaving as random coils, IDRs can exhibit a wide-range of structural behaviours, including conformational switching, where they transition between alternate conformational ensembles. Using Molecular Dynamics simulations of a minimal coarse-grained model for IDRs, we show that the role of protein conformation has a non-trivial effect in the liquid–liquid phase behaviour of IDRs. When an IDR transitions to a conformational ensemble enriched in disordered extended states, LLPS is enhanced. In contrast, IDRs that switch to ensembles that preferentially sample more compact and structured states show inhibited LLPS. This occurs because extended and disordered protein conformations facilitate LLPS-stabilising multivalent protein–protein interactions by reducing steric hindrance; thereby, such conformations maximize the molecular connectivity of the condensed liquid network. Extended protein configurations promote phase separation regardless of whether LLPS is driven by homotypic and/or heterotypic protein–protein interactions. This study sheds light on the link between the dynamic conformational plasticity of IDRs and their liquid–liquid phase behaviour.
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Cohen, Dalya. „The Point By Ysuf Idrs“. Journal of Arabic Literature 22, Nr. 1 (01.01.1991): 47–52. http://dx.doi.org/10.1163/157006491x00043.
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McDermott, Michael, Corey Kemper, William Barone, Gregor Jost und Jan Endrikat. „Impact of CT Injector Technology and Contrast Media Viscosity on Vascular Enhancement: Evaluation in a Circulation Phantom“. British Journal of Radiology 93, Nr. 1109 (01.05.2020): 20190868. http://dx.doi.org/10.1259/bjr.20190868.
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Objective: To assess the impact of piston-based vs peristaltic injection system technology and contrast media viscosity on achievable iodine delivery rates (IDRs) and vascular enhancement in a pre-clinical study. Methods: Four injectors were tested: MEDRAD® Centargo, MEDRAD® Stellant, CT Exprès®, and CT motion™ using five contrast media [iopromide (300 and 370 mgI ml−1), iodixanol 320 mgI ml−1, iohexol 350 mgI ml−1, iomeprol 400 mgI ml−1]. Three experiments were performed evaluating achievable IDR and corresponding enhancement in a circulation phantom. Results: Experiment I: Centargo provided the highest achievable IDRs with all tested contrast media (p < 0.05). Iopromide 370 yielded the highest IDR with an 18G catheter (3.15 gI/s); iopromide 300 yielded the highest IDR with 20G (2.70 gI/s) and 22G (1.65 gI/s) catheters (p < 0.05). Experiment II: with higher achievable IDRs, piston-based injectors provided significantly higher peak vascular enhancement (up to 48% increase) than the peristaltic injectors with programmed IDRs from 1.8 to 2.4 gI/s (p < 0.05). Experiment III: with programmed IDRs (e.g. 1.5 gI/s) achievable by all injection systems, Centargo, with sharper measured bolus shape, provided significant increases in enhancement of 34–73 HU in the pulmonary artery with iopromide 370 (p < 0.05). Conclusion: The tested piston-based injection systems combined with low viscosity contrast media provide higher achievable IDRs and higher peak vascular enhancement than the tested peristaltic-based injectors. With equivalent IDRs, Centargo provides higher peak vascular enhancement due to improved bolus shape. Advances in knowledge: This paper introduces a new parameter to compare expected performance among contrast media: the concentration/viscosity ratio. Additionally, it demonstrates previously unexplored impacts of bolus shape on vascular enhancement.
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Narayanamurthy, M. R. „Screening for Diabetes Mellitus risk using Indian Diabetic risk score in an urban slum in Mysuru“. International Journal of Preclinical and Clinical Research 1, Nr. 1 (21.12.2020): 12–16. http://dx.doi.org/10.51131/ijpccr/v1i1.5.
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Globalization of risk factors is the new trend leading to non-communicable diseases and Diabetes ranks fourth. Diabetes owes its major importance to the fact that it is a silent killer which leads to serious sequel reducing the quality of life. Early detection of diabetes by suitable screening methods helps to delay the micro and macrovascular complications, thereby reducing the clinical, social, and economic burden of the diseases. To assess diabetes risk using IDRS and other associated factors. A cross-sectional study was done in an urban slum in Mysuru with 136 participants aged >18 years and no history of diabetes. Data was collected using a pre-designed questionnaire after taking written informed consent. Diabetes risk was assessed using MDRF’s IDRS. Data was entered in MS Excel and analysed using IBM SPSS v24. P<0.05 was considered statistically significant. Mean age of the study participants was 45.24±15.59 years. BPL card holders were 99 (72.8%). As per IDRS 49 (36.0%), 41 (30.1%) and 46 (33.8%) had a low, moderate and high risk for diabetes mellitus. Age, marital status, education, having BPL card and IDRS score of study participants were statistically significantly associated. According to IDRS 49 (36.0%), 41 (30.1%) and 46 (33.8%) had a low, moderate and high risk for diabetes mellitus, which is moderate to high. Measures like yoga and creating awareness about risk factors need to be taken to reduce the risk. Keywords: Diabetes mellitus; IDRS; risk factor
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Kajino, Tatsuo, Shogo Ichiyanagi und Hiromi Kako. „Utilizing the integrated dual recording system to enhance documentation and analysis of airway management in children with difficult airway: A case report“. Saudi Journal of Anaesthesia 18, Nr. 2 (2024): 293–95. http://dx.doi.org/10.4103/sja.sja_841_23.
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This case report highlights the use of an integrated Dual Recording System (iDRS) to document and analyze airway management. The iDRS combines video laryngoscopy and a wide-angle camera to capture dual-view recordings of the larynx and operating room during airway procedures. We utilized this system in a 5-month-old boy with a difficult airway who underwent pulmonary artery banding under general anesthesia. Retrospective video analysis showed discrepancies between written information and iDRS video findings, including differences in the desaturation cause, description of airway procedures, and effectiveness of interventions. Video analysis facilitated a revised airway management strategy for subsequent anesthesia for cardiac catheterization. This emphasizes the value of the comprehensive information provided by iDRS recordings that facilitate effective post-procedure analysis and better planning of airway management strategies for subsequent care, which ultimately improves clinical decision-making and patient care.
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Qin, Sanbo, Alan Hicks, Souvik Dey, Ramesh Prasad und Huan-Xiang Zhou. „ReSMAP: Web Server for Predicting Residue-Specific Membrane-Association Propensities of Intrinsically Disordered Proteins“. Membranes 12, Nr. 8 (11.08.2022): 773. http://dx.doi.org/10.3390/membranes12080773.
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The functional processes of many proteins involve the association of their intrinsically disordered regions (IDRs) with acidic membranes. We have identified the membrane-association characteristics of IDRs using extensive molecular dynamics (MD) simulations and validated them with NMR spectroscopy. These studies have led to not only deep insight into functional mechanisms of IDRs but also to intimate knowledge regarding the sequence determinants of membrane-association propensities. Here we turned this knowledge into a web server called ReSMAP, for predicting the residue-specific membrane-association propensities from IDR sequences. The membrane-association propensities are calculated from a sequence-based partition function, trained on the MD simulation results of seven IDRs. Robustness of the prediction is demonstrated by leaving one IDR out of the training set. We anticipate there will be many applications for the ReSMAP web server, including rapid screening of IDR sequences for membrane association.
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Shaik, Nazia N., Swapna M. Jaswanth und Shashikala Manjunatha. „Assessment of risk of developing diabetes using Indian diabetes risk score in the urban field practice area of Rajarajeswari Medical College and Hospital, Bangalore“. International Journal Of Community Medicine And Public Health 7, Nr. 1 (25.12.2019): 170. http://dx.doi.org/10.18203/2394-6040.ijcmph20195849.
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Background: Diabetes is one of the largest global health emergencies of the 21st century. As per International Federation of Diabetes some 425 million people worldwide are estimated to have diabetes. The prevalence is higher in urban versus rural (10.2% vs 6.9%). India had 72.9 million people living with diabetes of which, 57.9% remained undiagnosed as per the 2017 data. The objectives of the present study were to identify subjects who at risk of developing Diabetes by using Indian diabetes risk score (IDRS) in the Urban field practice area of Rajarajeswari Medical College and Hospital (RRMCH).Methods: A cross sectional study was conducted using a Standard questionnaire of IDRS on 150 individuals aged ≥20 years residing in the Urban field practice area of RRMCH. The subjects with score <30, 30-50, >or =60 were categorized as having low risk, moderate risk and high risk for developing diabetes type-2 respectively.Results: Out of total 150 participants, 36 (24%) were in high-risk category (IDRS≥60), the majority of participants 61 (41%) were in the moderate-risk category (IDRS 30–50) and 53 (35%) participants were found to be at low-risk (<30) for diabetes. Statistical significant asssociation was found between IDRS and gender, literacy status, body mass index (p<0.0000l).Conclusions: It is essential to implement IDRS which is a simple tool for identifying subjects who are at risk for developing diabetes so that proper intervention can be carried out at the earliest to reduce the burden of diabetes.
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Lafforgue, Guillaume, Thierry Michon und Justine Charon. „Analysis of the Contribution of Intrinsic Disorder in Shaping Potyvirus Genetic Diversity“. Viruses 14, Nr. 9 (03.09.2022): 1959. http://dx.doi.org/10.3390/v14091959.
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Intrinsically disordered regions (IDRs) are abundant in the proteome of RNA viruses. The multifunctional properties of these regions are widely documented and their structural flexibility is associated with the low constraint in their amino acid positions. Therefore, from an evolutionary stand point, these regions could have a greater propensity to accumulate non-synonymous mutations (NS) than highly structured regions (ORs, or ‘ordered regions’). To address this hypothesis, we compared the distribution of non-synonymous mutations (NS), which we relate here to mutational robustness, in IDRs and ORs in the genome of potyviruses, a major genus of plant viruses. For this purpose, a simulation model was built and used to distinguish a possible selection phenomenon in the biological datasets from randomly generated mutations. We analyzed several short-term experimental evolution datasets. An analysis was also performed on the natural diversity of three different species of potyviruses reflecting their long-term evolution. We observed that the mutational robustness of IDRs is significantly higher than that of ORs. Moreover, the substitutions in the ORs are very constrained by the conservation of the physico-chemical properties of the amino acids. This feature is not found in the IDRs where the substitutions tend to be more random. This reflects the weak structural constraints in these regions, wherein an amino acid polymorphism is naturally conserved. In the course of evolution, potyvirus IDRs and ORs follow different evolutive paths with respect to their mutational robustness. These results have forced the authors to consider the hypothesis that IDRs and their associated amino acid polymorphism could constitute a potential adaptive reservoir.
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Ashtekar, Shyam V., Aryaman Singh, Manasi S. Padhyegurjar, Sidrah M. Shaikh, Abhimanyu R. Kapse, Devendra R. Thorat, Rahul R. Bele, Pushpak D. Dhatare, Ashhar Ahmed Sharif und Abhimanyu Rajput. „Indian diabetes risk profile of employees in a tertiary care facility in north Maharashtra: a cross sectional study“. International Journal Of Community Medicine And Public Health 8, Nr. 10 (27.09.2021): 4944. http://dx.doi.org/10.18203/2394-6040.ijcmph20213799.
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Background: The rising prevalence of type 2 diabetes (T2D) in India calls for screening of at-risk adults. Objectives were to assess IDRS (Indian diabetes risk score) of T2D in staff in tertiary care hospital, and to assess covariates random blood sugar (RBS), BMI, skinfold thickness (SFT), pre-existing T2D in the employees.Methods: In this cross sectional study, IDRS was used to assess all staff in a tertiary care institute. Anthropometric measurements, BP and RBS were done. Information on parental T2D, cereal intake and weekly physical activity (PA) was obtained in interview.Results: 370 subjects (F-117, M-273) with mean age 30.81 (7.99), BMI 22.89 (14.13) years were screened. Subjects in moderate and sedentary work were 185 each, 15% women and 39% men had higher waist size. Total 5.4% subjects had T2D including known diabetics. RBS in women and men was 113.1 (27.87), 114.7 (27.66), with IDRS score high in 29 (7.84%) and moderate in 144 (38.92%). Parental T2D was present in 19.5% subjects. IDRS risk was strongly associated with type of work (Chi-square 79.0283, df=4, p=0.00). Multiple logistic regression for IDRS risk outcome showed association of age (OR 1.4), BMI (OR1.3), parental T2D (OR 9.6) with highly significant p values. Multiple linear regression for RBS outcome was associated with age (OR 1.3) and BMI (OR 1.4) but the results were statistically not significant.Conclusions: Pooled IDRS risk was present in 47% subjects despite younger age of study population. Improvements in physical activity and reduction in waist size is the need of the hour.