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Zeitschriftenartikel zum Thema "Translation regulatory network"
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Pérez-Morales, Deyanira, Jessica Nava-Galeana, Roberto Rosales-Reyes, et al. "An incoherent feedforward loop formed by SirA/BarA, HilE and HilD is involved in controlling the growth cost of virulence factor expression by Salmonella Typhimurium." PLOS Pathogens 17, no. 5 (2021): e1009630. http://dx.doi.org/10.1371/journal.ppat.1009630.
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An intricate regulatory network controls the expression of Salmonella virulence genes. The transcriptional regulator HilD plays a central role in this network by controlling the expression of tens of genes mainly required for intestinal colonization. Accordingly, the expression/activity of HilD is highly regulated by multiple factors, such as the SirA/BarA two-component system and the Hcp-like protein HilE. SirA/BarA positively regulates translation of hilD mRNA through a regulatory cascade involving the small RNAs CsrB and CsrC, and the RNA-binding protein CsrA, whereas HilE inhibits HilD activity by protein-protein interaction. In this study, we show that SirA/BarA also positively regulates translation of hilE mRNA through the same mentioned regulatory cascade. Thus, our results reveal a paradoxical regulation exerted by SirA/BarA-Csr on HilD, which involves simultaneous opposite effects, direct positive control and indirect negative control through HilE. This kind of regulation is called an incoherent type-1 feedforward loop (I1-FFL), which is a motif present in certain regulatory networks and represents a complex biological problem to decipher. Interestingly, our results, together with those from a previous study, indicate that HilE, the repressor component of the I1-FFL reported here (I1-FFLSirA/BarA-HilE-HilD), is required to reduce the growth cost imposed by the expression of the genes regulated by HilD. Moreover, we and others found that HilE is necessary for successful intestinal colonization by Salmonella. Thus, these findings support that I1-FFLSirA/BarA-HilE-HilD cooperates to control the precise amount and activity of HilD, for an appropriate balance between the growth cost and the virulence benefit generated by the expression of the genes induced by this regulator. I1-FFLSirA/BarA-HilE-HilD represents a complex regulatory I1-FFL that involves multiple regulators acting at distinct levels of gene expression, as well as showing different connections to the rest of the regulatory network governing Salmonella virulence.
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Barbuti, Roberto, Pasquale Bove, Roberta Gori, Damas Gruska, Francesca Levi, and Paolo Milazzo. "Encoding Threshold Boolean Networks into Reaction Systems for the Analysis of Gene Regulatory Networks." Fundamenta Informaticae 179, no. 2 (2021): 205–25. http://dx.doi.org/10.3233/fi-2021-2021.
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Gene regulatory networks represent the interactions among genes regulating the activation of specific cell functionalities and they have been successfully modeled using threshold Boolean networks. In this paper we propose a systematic translation of threshold Boolean networks into reaction systems. Our translation produces a non redundant set of rules with a minimal number of objects. This translation allows us to simulate the behavior of a Boolean network simply by executing the (closed) reaction system we obtain. This can be very useful for investigating the role of different genes simply by “playing” with the rules. We developed a tool able to systematically translate a threshold Boolean network into a reaction system. We use our tool to translate two well known Boolean networks modelling biological systems: the yeast-cell cycle and the SOS response in Escherichia coli. The resulting reaction systems can be used for investigating dynamic causalities among genes.
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Kalous, Jaroslav, and Daria Aleshkina. "Multiple Roles of PLK1 in Mitosis and Meiosis." Cells 12, no. 1 (2023): 187. http://dx.doi.org/10.3390/cells12010187.
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Cells are equipped with a diverse network of signaling and regulatory proteins that function as cell cycle regulators and checkpoint proteins to ensure the proper progression of cell division. A key regulator of cell division is polo-like kinase 1 (PLK1), a member of the serine/threonine kinase family that plays an important role in regulating the mitotic and meiotic cell cycle. The phosphorylation of specific substrates mediated by PLK1 controls nuclear envelope breakdown (NEBD), centrosome maturation, proper spindle assembly, chromosome segregation, and cytokinesis. In mammalian oogenesis, PLK1 is essential for resuming meiosis before ovulation and for establishing the meiotic spindle. Among other potential roles, PLK1 regulates the localized translation of spindle-enriched mRNAs by phosphorylating and thereby inhibiting the translational repressor 4E-BP1, a downstream target of the mTOR (mammalian target of rapamycin) pathway. In this review, we summarize the functions of PLK1 in mitosis, meiosis, and cytokinesis and focus on the role of PLK1 in regulating mRNA translation. However, knowledge of the role of PLK1 in the regulation of meiosis remains limited.
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Chang, Lynne, Yaron Shav-Tal, Tatjana Trcek, Robert H. Singer, and Robert D. Goldman. "Assembling an intermediate filament network by dynamic cotranslation." Journal of Cell Biology 172, no. 5 (2006): 747–58. http://dx.doi.org/10.1083/jcb.200511033.
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We have been able to observe the dynamic interactions between a specific messenger RNA (mRNA) and its protein product in vivo by studying the synthesis and assembly of peripherin intermediate filaments (IFs). The results show that peripherin mRNA-containing particles (messenger ribonucleoproteins [mRNPs]) move mainly along microtubules (MT). These mRNPs are translationally silent, initiating translation when they cease moving. Many peripherin mRNPs contain multiple mRNAs, possibly amplifying the total amount of protein synthesized within these “translation factories.” This mRNA clustering is dependent on MT, regulatory sequences within the RNA and the nascent protein. Peripherin is cotranslationally assembled into insoluble, nonfilamentous particles that are precursors to the long IF that form extensive cytoskeletal networks. The results show that the motility and targeting of peripherin mRNPs, their translational control, and the assembly of an IF cytoskeletal system are linked together in a process we have termed dynamic cotranslation.
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Goldenkova-Pavlova, Irina, Olga Pavlenko, Orkhan Mustafaev, Igor Deyneko, Ksenya Kabardaeva, and Alexander Tyurin. "Computational and Experimental Tools to Monitor the Changes in Translation Efficiency of Plant mRNA on a Genome-Wide Scale: Advantages, Limitations, and Solutions." International Journal of Molecular Sciences 20, no. 1 (2018): 33. http://dx.doi.org/10.3390/ijms20010033.
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The control of translation in the course of gene expression regulation plays a crucial role in plants’ cellular events and, particularly, in responses to environmental factors. The paradox of the great variance between levels of mRNAs and their protein products in eukaryotic cells, including plants, requires thorough investigation of the regulatory mechanisms of translation. A wide and amazingly complex network of mechanisms decoding the plant genome into proteome challenges researchers to design new methods for genome-wide analysis of translational control, develop computational algorithms detecting regulatory mRNA contexts, and to establish rules underlying differential translation. The aims of this review are to (i) describe the experimental approaches for investigation of differential translation in plants on a genome-wide scale; (ii) summarize the current data on computational algorithms for detection of specific structure–function features and key determinants in plant mRNAs and their correlation with translation efficiency; (iii) highlight the methods for experimental verification of existed and theoretically predicted features within plant mRNAs important for their differential translation; and finally (iv) to discuss the perspectives of discovering the specific structural features of plant mRNA that mediate differential translation control by the combination of computational and experimental approaches.
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Sudalagunta, Praneeth Reddy, Rafael Renatino Canevarolo, Mark Meads, et al. "Abstract 4313: A novel gene regulatory network model identifies master regulators in cancer." Cancer Research 83, no. 7_Supplement (2023): 4313. http://dx.doi.org/10.1158/1538-7445.am2023-4313.
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Abstract Small-scale regulatory networks can model known biological processes; while large-scale genome-wide datasets can identify novel mechanisms. We developed a biophysical modeling framework that combines the accuracy of small-scale networks with the power of large-scale datasets. As a proof of principle, we implemented this framework on a cohort of 844 multiple myeloma (MM) patients’ (and 1092 TCGA breast cancer patients) z-normalized RNAseq data using t-Distributed Stochastic Neighbor Embedding to construct a disease-specific transcriptomic map, where genes closer to each other co-express within the cohort. Fuzzy c-means clustering is carried out to identify clusters of genes that are likely regulated by a common transcription factor (TF). We construct a gene regulatory network (GRN) for each cluster of co-expressing genes on a disease-specific transcriptomic map by identifying upstream TFs for each cluster using publicly available databases ENCODE and ChEA, and kinases that phosphorylate these TFs using PhosphoSitePlus and PhosphoPoint. An exhaustive list of TFs and kinases are reduced to a few key predictor variables using regression tree modeling for each gene in that cluster. This leads to a cascading network of kinases that phosphorylate TFs, which regulate expression of genes in a cluster. We derived a mechanistic model from first-principles to define functional relationships governing the GRN; where transcription, translation, and post-translational modifications are modeled using first-order reversible reaction kinetic equations. The patient-specific rate constants of the model are parametrized by single sample gene set enrichment analysis scores of key KEGG pathways like ribosome, protein synthesis, RNA degradation, etc. The system of differential equations, under steady-state, reduce to an algebraic equation that can predict the expression of every gene in a cluster from the expression of its upstream TFs and kinases alone, which is fitted to RNAseq data of 422 MM patients to estimate undetermined parameters. The remaining patients’ data is used to estimate the accuracy of the model using Pearson’s correlation (model predicted vs actual) coefficient, r. Out of 16,738 genes, 7,936 were predicted accurately (r>0.5), while the remaining genes were shown to have a significant overlap (hypergeometric test; p-value<1e-48 and representation factor = 7.27) with genes that have high variability in chromatin accessibility across patients. A reduced GRN with only accurately predicted genes is obtained for each cluster, followed by linking GRNs to each other through TFs and kinases that are featured in other GRNs; where betweenness centrality measures of the resulting directed graph identifies disease-specific master regulators. MYC, STAT3, CREB1, POLR2A, PLK1, and TP53 are found to be key hubs in MM network; similar analyses are being conducted for other cancers featured in TCGA. Citation Format: Praneeth Reddy Sudalagunta, Rafael Renatino Canevarolo, Mark Meads, Maria Coelho Silva, Xiaohong Zhao, Raghunandan Reddy Alugubelli, Joon-hyun Song, Erez Persi, Mehdi Damaghi, Kenneth H. Shain, Ariosto Silva. A novel gene regulatory network model identifies master regulators in cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4313.
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Farley, Brian M., and Sean P. Ryder. "POS-1 and GLD-1 repress glp-1 translation through a conserved binding-site cluster." Molecular Biology of the Cell 23, no. 23 (2012): 4473–83. http://dx.doi.org/10.1091/mbc.e12-03-0216.
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RNA-binding proteins (RBPs) coordinate cell fate specification and differentiation in a variety of systems. RNA regulation is critical during oocyte development and early embryogenesis, in which RBPs control expression from maternal mRNAs encoding key cell fate determinants. The Caenorhabditis elegans Notch homologue glp-1 coordinates germline progenitor cell proliferation and anterior fate specification in embryos. A network of sequence-specific RBPs is required to pattern GLP-1 translation. Here, we map the cis-regulatory elements that guide glp-1 regulation by the CCCH-type tandem zinc finger protein POS-1 and the STAR-domain protein GLD-1. Our results demonstrate that both proteins recognize the glp-1 3′ untranslated region (UTR) through adjacent, overlapping binding sites and that POS-1 binding excludes GLD-1 binding. Both factors are required to repress glp-1 translation in the embryo, suggesting that they function in parallel regulatory pathways. It is intriguing that two equivalent POS-1–binding sites are present in the glp-1 3′ UTR, but only one, which overlaps with a translational derepression element, is functional in vivo. We propose that POS-1 regulates glp-1 mRNA translation by blocking access of other RBPs to a key regulatory sequence.
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Zamani, Zahra, Amirhossein Hajihosseini, and Ali Masoudi-Nejad. "Computational Methodologies for Analyzing, Modeling and Controlling Gene Regulatory Networks." Biomedical Engineering and Computational Biology 2 (January 2010): BECB.S5594. http://dx.doi.org/10.4137/becb.s5594.
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Molecular biology focuses on genes and their interactions at the transcription, regulation and protein level. Finding genes that cause certain behaviors can make therapeutic interventions more effective. Although biological tools can extract the genes and perform some analyses, without the help of computational methods, deep insight of the genetic function and its effects will not occur. On the other hand, complex systems can be modeled by networks, introducing the main data as nodes and the links in-between as the transactions occurring within the network. Gene regulatory networks are examples that are modeled and analyzed in order to gain insight of their exact functions. Since a cell's specific functionality is greatly determined by the genes it expresses, translation or the act of converting mRNA to proteins is highly regulated by the control network that directs cellular activities. This paper briefly reviews the most important computational methods for analyzing, modeling and controlling the gene regulatory networks.
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Spirov, Alexander V., Ekaterina M. Myasnikova, and David M. Holloway. "Sequential construction of a model for modular gene expression control, applied to spatial patterning of theDrosophilagenehunchback." Journal of Bioinformatics and Computational Biology 14, no. 02 (2016): 1641005. http://dx.doi.org/10.1142/s0219720016410055.
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Gene network simulations are increasingly used to quantify mutual gene regulation in biological tissues. These are generally based on linear interactions between single-entity regulatory and target genes. Biological genes, by contrast, commonly have multiple, partially independent, cis-regulatory modules (CRMs) for regulator binding, and can produce variant transcription and translation products. We present a modeling framework to address some of the gene regulatory dynamics implied by this biological complexity. Spatial patterning of the hunchback (hb) gene in Drosophila development involves control by three CRMs producing two distinct mRNA transcripts. We use this example to develop a differential equations model for transcription which takes into account the cis-regulatory architecture of the gene. Potential regulatory interactions are screened by a genetic algorithms (GAs) approach and compared to biological expression data.
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Alshabi, Ali Mohamed, Basavaraj Vastrad, Ibrahim Ahmed Shaikh, and Chanabasayya Vastrad. "Identification of Crucial Candidate Genes and Pathways in Glioblastoma Multiform by Bioinformatics Analysis." Biomolecules 9, no. 5 (2019): 201. http://dx.doi.org/10.3390/biom9050201.
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The present study aimed to investigate the molecular mechanisms underlying glioblastoma multiform (GBM) and its biomarkers. The differentially expressed genes (DEGs) were diagnosed using the limma software package. The ToppGene (ToppFun) was used to perform pathway and Gene Ontology (GO) enrichment analysis of the DEGs. Protein-protein interaction (PPI) networks, extracted modules, miRNA-target genes regulatory network and TF-target genes regulatory network were used to obtain insight into the actions of DEGs. Survival analysis for DEGs was carried out. A total of 590 DEGs, including 243 up regulated and 347 down regulated genes, were diagnosed between scrambled shRNA expression and Lin7A knock down. The up-regulated genes were enriched in ribosome, mitochondrial translation termination, translation, and peptide biosynthetic process. The down-regulated genes were enriched in focal adhesion, VEGFR3 signaling in lymphatic endothelium, extracellular matrix organization, and extracellular matrix. The current study screened the genes in the PPI network, extracted modules, miRNA-target genes regulatory network, and TF-target genes regulatory network with higher degrees as hub genes, which included NPM1, CUL4A, YIPF1, SHC1, AKT1, VLDLR, RPL14, P3H2, DTNA, FAM126B, RPL34, and MYL5. Survival analysis indicated that the high expression of RPL36A and MRPL35 were predicting longer survival of GBM, while high expression of AP1S1 and AKAP12 were predicting shorter survival of GBM. High expression of RPL36A and AP1S1 were associated with pathogenesis of GBM, while low expression of ALPL was associated with pathogenesis of GBM. In conclusion, the current study diagnosed DEGs between scrambled shRNA expression and Lin7A knock down samples, which could improve our understanding of the molecular mechanisms in the progression of GBM, and these crucial as well as new diagnostic markers might be used as therapeutic targets for GBM.
Dissertationen zum Thema "Translation regulatory network"
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Freschi, Luca. "Post-translational modifications regulatory networks : evolution, mechanisms et implications." Doctoral thesis, Université Laval, 2015. http://hdl.handle.net/20.500.11794/25812.
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Les modifications post-traductionnelles (PTM) sont des modifications chimiques des protéines qui permettent à la cellule de réguler finement ses fonctions ainsi que de coder et d’intégrer des signaux environnementaux. Les progrès récents en ce qui a trait aux techniques expérimentales et bioinformatiques nous ont permis de determiner les profils de PTM pour des protéomes entiers ainsi que d’identifier les molécules qui sont responsables d’ « écrire » ou d’« effacer » ces PTM. Avec ces donnés, il a été possible de commencer à definir des réseaux de régulation cellulaire par PTM. Ici, nous avons étudié l’évolution de ces réseaux pour mieux comprendre comment ils peuvent contribuer à expliquer la complexité et la diversité des organismes ainsi que pour mieux comprendre leurs mecanismes d’action. Avant tout, nous avons abordé la question de comment les réseaux de régulation des PTM peuvent être recablés après un évenement de duplication des gènes en étudiant comment le réseau de phosphorégulation de la levure bourgeonnante a été récablé après un évenement de duplication complète du génome qui a eu lieu il y a 100 milions d’années. Nos résultats mettent en évidence le rôle de la duplication des gènes comme mécanisme clé pour l’innovation et la complexification des réseaux de régulation par PTM. Par la suite, nous avons abordé la question de comment les PTM peuvent contribuer à la diversité des organismes en comparant les profils de phosphorylation de l’homme et de la souris. Nous avons trouvé des différences substantielles dans les profils de PTM de ces deux espèces qui ont le potentiel d’expliquer, au moins en partie, les différences phénotypiques observées entre eux. Nous avons aussi trouvé des évidences qui supportent l’idée que les PTM peuvent « sauter » vers des nouvelles localisations et quand même réguler les mêmes fonctions biologiques. Ce phénomène doit être pris en considération dans les comparaisons des profils de PTM qui appartiennent à des espèces différentes, pour éviter de surestimer la divergence causée par la régulation par les PTM. Enfin, nous avons investigué comment plusieures PTM alternatives pour un même residu pouvent interagir pour réguler des fonctions cellulaires. Nous avons examiné deux des PTM les plus connus, la phosphorylation et la O-GlcNAcylation, qui modifient les sérines et les thréonines, et nous avons étudié les mécanismes potentiels d’interaction entre ces deux PTM. Nos résultats supportent l’hypothèse que ces deux PTM contrôlent plusieurs fonctions biologiques plutôt qu’une seule fonction. Globalement, les résultats présentés dans cette thèse permettent d’élucider les dynamiques évolutives, les mécanismes de fonctionnement et les implications biologiques des PTM.<br>Post-translational modifications (PTMs) are chemical modification of proteins that allow the cell to finely tune its functions as well as to encode and integrate environmental signals. The recent advancements in the experimental and bioinformatic techniques have allowed us to determine the PTM profiles of entire proteomes as well as to identify the molecules that write or erase PTMs to/from each protein. This data have made possible to define cellular PTM regulatory networks. Here, we study the evolution of these networks to get new insights about how they may contribute to increase organismal complexity and diversity and to better understand their molecular mechanisms of functioning. We first address the question of how and to which extent a PTM network can be rewired after a gene duplication event, by studying how the budding yeast phosphoregulatory network was rewired after a whole genome duplication event that occurred 100 million years ago. Our results highlight the role of gene duplication as a key mechanism to innovate and complexify PTM regulatory networks. Then, we address the question of how PTM networks may contribute to organismal diversity by comparing the human and mouse phosphorylation profiles. We find that there are substantial differences in the PTM profiles of these two species that have the potential to explain, at least in part, the phenotypic differences observed between them. Moreover, we find evidence supporting the idea that PTMs can jump to new positions during evolution and still regulate the same biological functions. This phenomenon should be taken into account when comparing the PTM profiles of different species, in order to avoid overestimating the divergence in PTM regulation. Finally, we investigate how multiple and alternative PTMs that affect the same residues interact with each other to control proteins functions. We focus on two of the most studied PTMs, protein phosphorylation and O-GlcNAcylation, that affect serine and threonine residues and we study their potential mechanisms of interactions in human and mouse. Our results support the hypothesis that these two PTMs control multiple biological functions rather than a single one. Globally this work provides new findings that elucidate the evolutionary dynamics, the functional mechanisms and the biological implications of PTMs.
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Pontheaux, Florian. "Activité traductionnelle et dynamique mitotique induites par la fécondation chez l’oursin." Electronic Thesis or Diss., Sorbonne université, 2022. http://www.theses.fr/2022SORUS209.
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La régulation fine de la traduction pour la dynamique du cycle cellulaire est un sujet important dans la recherche cellulaire. Au cours de ma thèse, j'ai analysé les relations entre l’activité traductionnelle des ARNm et les divisions embryonnaires mitotiques d'oursins. La fécondation de l'œuf déclenche l'activation de la machinerie traductionnelle nécessaire à la reprise des divisions mitotiques. Un réseau de régulation traductionnelle (TlRN), indépendant de la transcription, reste à identifier et à caractériser en amont des acteurs du cycle cellulaire. A la recherche d'activités mitotiques pour visualiser la dynamique spatiale à l'intérieur d'œufs, j'ai obtenu des données originales montrant l'activité dynamique et spatiale du complexe mitotique CyclinB/CDK1 et la phosphorylation de l'histone H3 sur la thréonine 3 (pH3T3) pendant la mitose embryonnaire. Ensuite, j'ai analysé le rôle in vivo de 5'UTR spécifiques pour contrôler le recrutement d'ARNm dans les polysomes actifs après la fécondation. Enfin, j'ai montré que la traduction de l'ARNm codant pour eIF4B (facteur d'initiation eucaryote 4B) contrôle l'activité traductionnelle et la dynamique des deux premières divisions mitotiques induites par la fécondation. Je propose qu'eIF4B agisse comme un régulateur positif au sein du TlRN. Ces données permettront d'étudier l'effet potentiel d'eIF4B sur les activités CDK1 et pH3T3<br>Fine tuning of translation for cell cycle dynamics remains an important topic in cell research. During my thesis, I analyzed the relationships between mRNA translational activity and mitotic cell division using sea urchin embryos. Egg fertilization triggers the activation of the translational machinery, which is required for resuming the first mitotic division, independently of any transcription. A Translational Regulatory Network (TlRN) remains to be identified and characterized upstream of the cell cycle actors. Seeking mitotic activities that can help visualize spatial dynamics inside isolated eggs, I obtained original data showing the spatial and dynamic activity of the mitotic complex CyclinB/CDK1 and the phosphorylation of histone H3 at threonine 3 (pH3T3) during embryonic mitosis. Then, I analyzed the in vivo role of specific 5’UTR for controlling the mRNA recruitment onto active polysome following fertilization. Finally, I showed that the translation of the mRNA encoding for eIF4B (eukaryotic Initiation Factor 4B) controls the translational activity and dynamics of the first two mitotic divisions induced by fertilization. I propose that eIF4B acts as a positive regulator within the TlRN. These data will allow to study the potential effect of eIF4B acting upstream the spatial dynamics of CDK1 and pH3T3 activities
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Tan, Elizabeth E.-Lyn. "Immuno-metabolism in Metabolic (dysfunction) associated fatty liver disease (MAFLD)." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/27978.
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The findings from chronic complex diseases modelled in animals are difficult to extrapolate to humans. In metabolic (dysfunction) associated fatty liver disease (MAFLD), dietary models are commonly used to study the mechanisms for disease progression. The current dogma is that diets rich in fat, simple carbohydrates, and cholesterol can lead to systemic alterations in metabolism that leads to the accumulation of lipids in the adipose and liver tissues. This leads to lipotoxicity and a vicious cycle of inflammation and liver injury which can drive disease progression. Hence, there has been a considerable interest to model and comprehend the role of metabolism and the immune response in this disease. However, our knowledge of the underlying mechanisms in MAFLD is still limited. A major caveat is that pre-clinical models do not represent the full spectrum of human diseases. This has been a major source of failure in clinical trials. Understanding the impact of dietary challenges in animal models and where they resemble or diverge from human disease can help to resolve the current dilemmas that have hampered progress in the field.
In this thesis, I used different dietary models in mice and characterised liver pathology, the liver immune profile, and the landscape of liver gene expression. Initially, we used multiple dietary models containing simple (sucrose) or complex carbohydrates, with/without cholesterol (2%), and with/without an added bile acid (cholic acid): A) normal chow (NC); B) high sucrose (HS); C) high sucrose and high cholesterol (HS_Chol2%); D) high sucrose, high cholesterol (2%) and cholic acid (HS_Chol2%_CA); E) high cholesterol (2%) and cholic acid (Chol2%_CA); F) cholic acid (CA). From a liver pathology perspective, diets containing cholesterol (Diets C to E) induced a dramatic change in liver pathology. Consistently, immune profiling of the liver of mice fed these diets induced infiltration of a broad range of immune cells including myeloid and lymphoid cells (diets C to E). Of note, the combination of cholesterol and cholate (diets D and E) had synergistic effects and dramatically enhanced liver immune cell infiltration. Subsequently, we performed RNA sequencing on the liver of mice fed these 6 diets. In agreement, we detected the highest differentially expressed genes in diets containing cholesterol and cholate (diets D and E). We conclude that this combination disturbs liver homeostatic functions the greatest.
To gain a systems perspective of perturbations in liver homeostatic function, we undertook a systems approach and applied weighted gene co-expression network analysis (WGCNA) on liver transcriptomes. We noticed several gene expression modules (networks) that were associated with diets. Most of these modules were enriched for metabolic pathways and immune responses. Of interest, there was a negative correlation between immune and metabolic-related modules. This was reminiscent of immunometabolism and a co-variance in gene regulatory networks between metabolic and immune modules. The up-regulation of immune responses and down-regulation of metabolic networks within the liver were prominent in mice exposed to cholesterol and cholate. A published report and our unpublished data (not the subject of this thesis) indicated that diets containing cholesterol and cholate induce a heightened immune response with anti-tumorigenic properties. Thus, from a phenotypic perspective, this immune response and the outcomes are divergent from human fatty liver that increases the risk of liver cancer.
One caveat in our dietary models was that they contained supra-physiological levels of cholesterol (2%). I detected a suppression in the expression of genes in cholesterol biosynthesis pathway in all diets that contained cholesterol (Diet C) or cholic acid (Diets D to F). This was in contrast with a study on clinical fatty liver disease (in humans) which reported up-regulation of genes in cholesterol biosynthesis pathways. I hypothesised that reduction in cholesterol biosynthesis could be related to a higher immune response. Hence, I omitted cholic acid and reduced the amount of cholesterol to 0.2% and investigated the liver pathology in mice exposed to a HS_Chol0.2% diet. This diet also induced minimal liver pathology similar to the HS diet. Despite a reduction in the cholesterol content, I detected a suppression in the expression of genes in cholesterol biosynthesis in mice exposed to the 0.2% cholesterol in the diet. This indicates a diverged response in cholesterol metabolism between mice and human liver. This diet did not induce pathological features resembling human MAFLD, however it resembled some characteristics of metabolic syndrome such as adiposity with systemic glucose intolerance.
One of the models that is often used to simulate MAFLD is the MCD (methionine choline deficient) diet. This diet induced pathological features resembling human MAFLD, however, our analysis of liver transcriptome data on mice fed with MCD diet indicated down-regulation in metabolic pathways and cholesterol biosynthesis. Indeed, the behaviour of these modules in mice on the MCD diet resembles those in mice exposed to high levels of cholesterol, which are divergent from human fatty liver disease. Overall, my results have shown that mice dietary models do not fully resemble clinical fatty liver either phenotypically or at the gene expression level. A possible strategy to overcome these limitations is to use multiple models in which each model could represent a specific aspect of the disease. At the molecular level, undertaking a module-based approach to understand the link between the behaviour of preserved modules (e.g., between mice and humans) to phenotypic outcome is an alternative strategy. One unmet need in human fatty liver is dissociating liver tissue inflammation from protective immune responses (immunosurveillance), which I would like to delve into in my future endeavours.
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Eckmann, Christian R., Mark Schmid, Adam P. Kupinski, Britta Jedamzik, Martin Harterink, and Agata Rybarska. "GLS-1, a novel P granule component, modulates a network of conserved RNA regulators to influence germ cell fate decisions." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-184095.
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Post-transcriptional regulatory mechanisms are widely used to influence cell fate decisions in germ cells, early embryos, and neurons. Many conserved cytoplasmic RNA regulatory proteins associate with each other and assemble on target mRNAs, forming ribonucleoprotein (RNP) complexes, to control the mRNAs translational output. How these RNA regulatory networks are orchestrated during development to regulate cell fate decisions remains elusive. We addressed this problem by focusing on Caenorhabditis elegans germline development, an exemplar of post-transcriptional control mechanisms. Here, we report the discovery of GLS-1, a new factor required for many aspects of germline development, including the oocyte cell fate in hermaphrodites and germline survival. We find that GLS-1 is a cytoplasmic protein that localizes in germ cells dynamically to germplasm (P) granules. Furthermore, its functions depend on its ability to form a protein complex with the RNA-binding Bicaudal-C ortholog GLD-3, a translational activator and P granule component important for similar germ cell fate decisions. Based on genetic epistasis experiments and in vitro competition experiments, we suggest that GLS-1 releases FBF/Pumilio from GLD-3 repression. This facilitates the sperm-to-oocyte switch, as liberated FBF represses the translation of mRNAs encoding spermatogenesis-promoting factors. Our proposed molecular mechanism is based on the GLS-1 protein acting as a molecular mimic of FBF/Pumilio. Furthermore, we suggest that a maternal GLS-1/GLD-3 complex in early embryos promotes the expression of mRNAs encoding germline survival factors. Our work identifies GLS-1 as a fundamental regulator of germline development. GLS-1 directs germ cell fate decisions by modulating the availability and activity of a single translational network component, GLD-3. Hence, the elucidation of the mechanisms underlying GLS-1 functions provides a new example of how conserved machinery can be developmentally manipulated to influence cell fate decisions and tissue development.
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Eckmann, Christian R., Mark Schmid, Adam P. Kupinski, Britta Jedamzik, Martin Harterink, and Agata Rybarska. "GLS-1, a novel P granule component, modulates a network of conserved RNA regulators to influence germ cell fate decisions." PLOS Genetics, 2009. https://tud.qucosa.de/id/qucosa%3A28993.
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Post-transcriptional regulatory mechanisms are widely used to influence cell fate decisions in germ cells, early embryos, and neurons. Many conserved cytoplasmic RNA regulatory proteins associate with each other and assemble on target mRNAs, forming ribonucleoprotein (RNP) complexes, to control the mRNAs translational output. How these RNA regulatory networks are orchestrated during development to regulate cell fate decisions remains elusive. We addressed this problem by focusing on Caenorhabditis elegans germline development, an exemplar of post-transcriptional control mechanisms. Here, we report the discovery of GLS-1, a new factor required for many aspects of germline development, including the oocyte cell fate in hermaphrodites and germline survival. We find that GLS-1 is a cytoplasmic protein that localizes in germ cells dynamically to germplasm (P) granules. Furthermore, its functions depend on its ability to form a protein complex with the RNA-binding Bicaudal-C ortholog GLD-3, a translational activator and P granule component important for similar germ cell fate decisions. Based on genetic epistasis experiments and in vitro competition experiments, we suggest that GLS-1 releases FBF/Pumilio from GLD-3 repression. This facilitates the sperm-to-oocyte switch, as liberated FBF represses the translation of mRNAs encoding spermatogenesis-promoting factors. Our proposed molecular mechanism is based on the GLS-1 protein acting as a molecular mimic of FBF/Pumilio. Furthermore, we suggest that a maternal GLS-1/GLD-3 complex in early embryos promotes the expression of mRNAs encoding germline survival factors. Our work identifies GLS-1 as a fundamental regulator of germline development. GLS-1 directs germ cell fate decisions by modulating the availability and activity of a single translational network component, GLD-3. Hence, the elucidation of the mechanisms underlying GLS-1 functions provides a new example of how conserved machinery can be developmentally manipulated to influence cell fate decisions and tissue development.
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Campbell, Pearl. "Pou5f1 Post-translational Modifications Modulate Gene Expression and Cell Fate." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23607.
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Embryonic stem cells (ESCs) are characterized by their unlimited capacity for self-renewal and the ability to contribute to every lineage of the developing embryo. The promoters of developmentally regulated loci within these cells are marked by coincident epigenetic modifications of gene activation and repression, termed bivalent domains. Trithorax group (TrxG) and Polycomb Group (PcG) proteins respectively place these epigenetic marks on chromatin and extensively colocalize with Oct4 in ESCs. Although it appears that these cells are poised and ready for differentiation, the switch that permits this transition is critically held in check. The derepression of bivalent domains upon knockdown of Oct4 or PcG underscores their respective roles in maintaining the pluripotent state through epigenetic regulation of chromatin structure. The mechanisms that facilitate the recruitment and retention of Oct4, TrxG, and PcG proteins at developmentally regulated loci to maintain the pluripotent state, however, remain unknown. Oct4 may function as either a transcriptional activator or repressor. Prevailing thought holds that both of these activities are required to maintain the pluripotent state through activation of genes implicated in pluripotency and cell-cycle control with concomitant repression of genes required for differentiation and lineage-specific differentiation. More recent evidence however, suggests that the activator function of Oct4 may play a more critical role in maintaining the pluripotent state (Hammachi et al., 2012). The purpose of the studies described in this dissertation was to clarify the underlying mechanisms by which Oct4 functions in transcriptional activation and repression. By so doing, we wished to contextualize its role in pluripotent cells, and to provide insight into how changes in Oct4 function might account for its ability to facilitate cell fate transitions. As a result of our studies we find that Oct4 function is dependent upon post-translational modifications (PTMs). We find through a combination of experimental approaches, including genome-wide microarray analysis, bioinformatics, chromatin immunoprecipitation, functional molecular, and biochemical analyses, that in the pluripotent state Oct4, Akt, and Hmgb2 participate in a regulatory feedback loop. Akt-mediated phosphorylation of Oct4 facilitates interaction with PcG recruiter Hmgb2. Consequently, Hmgb2 functions as a context dependent modulator of Akt and Oct4 function, promoting transcriptional poise at Oct4 bound loci. Sumoylation of Oct4 is then required to maintain Hmgb2 enrichment at repressed loci and to transmit the H3K27me3 mark in daughter progeny. The expression of Oct4 phosphorylation mutants however, leads to Akt inactivation and initiates the DNA Damage Checkpoint response. Our results suggest that this may subsequently facilitate chromatin reorganization and cell fate transitions. In summary, our results suggest that controlled modulation of Oct4, Akt, and Hmgb2 function is required to maintain pluripotency and for the faithful induction of transcriptional programs required for lineage specific differentiation.
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Surappa-Narayanappa, Ananth Prakash. "The evolution, modifications and interactions of proteins and RNAs." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/269851.
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Proteins and RNAs are two of the most versatile macromolecules that carry out almost all functions within living organisms. In this thesis I have explored evolutionary and regulatory aspects of proteins and RNAs by studying their structures, modifications and interactions. In the first chapter of my thesis I investigate domain atrophy, a term I coined to describe large-scale deletions of core structural elements within protein domains. By looking into truncated domain boundaries across several domain families using Pfam, I was able to identify rare cases of domains that showed atrophy. Given that even point mutations can be deleterious, it is surprising that proteins can tolerate such large-scale deletions. Some of the structures of atrophied domains show novel protein-protein interaction interfaces that appear to compensate and stabilise their folds. Protein-protein interactions are largely influenced by the surface and charge complementarity, while RNA-RNA interactions are governed by base-pair complementarity; both interaction types are inherently different and these differences might be observed in their interaction networks. Based on this hypothesis I have explored the protein-protein, RNA-protein and the RNA-RNA interaction networks of yeast in the second chapter. By analysing the three networks I found no major differences in their network properties, which indicates an underlying uniformity in their interactomes despite their individual differences. In the third chapter I focus on RNA-protein interactions by investigating post-translational modifications (PTMs) in RNA-binding proteins (RBPs). By comparing occurrences of PTMs, I observe that RBPs significantly undergo more PTMs than non-RBPs. I also found that within RBPs, PTMs are more frequently targeted at regions that directly interact with RNA compared to regions that do not. Moreover disorderedness and amino acid composition were not observed to significantly influence the differential PTMs observed between RBPs and nonRBPs. The results point to a direct regulatory role of PTMs in RNA-protein interactions of RBPs. In the last chapter, I explore regulatory RNA-RNA interactions. Using differential expression data of mRNAs and lncRNAs from mouse models of hereditary hemochromatosis, I investigated competing regulatory interactions between mRNA, lncRNA and miRNA. A mutual interaction network was created from the predicted miRNA interaction sites on mRNAs and lncRNAs to identify regulatory RNAs in the disease. I also observed interesting relations between the sense-antisense mRNA-lncRNA pairs that indicate mutual regulation of expression levels through a yet unknown mechanism.
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Ghaffari, Noushin. "Genomic Regulatory Networks, Reduction Mappings and Control." Thesis, 2012. http://hdl.handle.net/1969.1/ETD-TAMU-2012-05-10726.
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All high-level living organisms are made of small cell units, containing DNA,
RNA, genes, proteins etc. Genes are important components of the cells and it is
necessary to understand the inter-gene relations, in order to comprehend, predict and
ultimately intervene in the cells’ dynamics. Genetic regulatory networks (GRN) represent
the gene interactions that dictate the cell behavior. Translational genomics
aims to mathematically model GRNs and one of the main goals is to alter the networks’
behavior away from undesirable phenotypes such as cancer.
The mathematical framework that has been often used for modeling GRNs is the
probabilistic Boolean network (PBN), which is a collection of constituent Boolean
networks with perturbation, BNp. This dissertation uses BNps, to model gene regulatory
networks with an intent of designing stationary control policies (CP) for the
networks to shift their dynamics toward more desirable states. Markov Chains (MC)
are used to represent the PBNs and stochastic control has been employed to find
stationary control policies to affect steady-state distribution of the MC. However,
as the number of genes increases, it becomes computationally burdensome, or even
infeasible, to derive optimal or greedy intervention policies.
This dissertation considers the problem of modeling and intervening in large GRNs.
To overcome the computational challenges associated with large networks, two approaches
are proposed: first, a reduction mapping that deletes genes from the network;
and second, a greedy control policy that can be directly designed on large networks.
Simulation results show that these methods achieve the goal of controlling large networks
by shifting the steady-state distribution of the networks toward more desirable
states.
Furthermore, a new inference method is used to derive a large 17-gene Boolean network
from microarray experiments on gastrointestinal cancer samples. The new algorithm
has similarities to a previously developed well-known inference method, which
uses seed genes to grow subnetworks, out of a large network; however, it has major
differences with that algorithm. Most importantly, the objective of the new algorithm
is to infer a network from a seed gene with an intention to derive the Gene Activity
Profile toward more desirable phenotypes. The newly introduced reduction mappings
approach is used to delete genes from the 17-gene GRN and when the network is
small enough, an intervention policy is designed for the reduced network and induced
back to the original network. In another experiment, the greedy control policy approach
is used to directly design an intervention policy on the large 17-gene network
to beneficially change the long-run behavior of the network.
Finally, a novel algorithm is developed for selecting only non-isomorphic BNs, while
generating synthetic networks, using a method that generates synthetic BNs, with a
prescribed set of attractors. The goal of the new method described in this dissertation
is to discard isomorphic networks.
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Dey, Souvik. "Transcriptional regulation of ATF4 is critical for controlling the Integrated Stress Response during eIF2 phosphorylation." Thesis, 2012. http://hdl.handle.net/1805/3041.
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Indiana University-Purdue University Indianapolis (IUPUI)<br>In response to different environmental stresses, phosphorylation of eIF2 (eIF2P) represses global translation coincident with preferential translation of ATF4. ATF4 is a transcriptional activator of the integrated stress response, a program of gene expression involved in metabolism, nutrient uptake, anti-oxidation, and the activation of additional transcription factors, such as CHOP/GADD153, that can induce apoptosis. Although eIF2P elicits translational control in response to many different stress arrangements, there are selected stresses, such as exposure to UV irradiation, that do not increase ATF4 expression despite robust eIF2P. In this study we addressed the underlying mechanism for variable expression of ATF4 in response to eIF2P during different stress conditions and the biological significance of omission of enhanced ATF4 function. We show that in addition to translational control, ATF4 expression is subject to transcriptional regulation. Stress conditions such as endoplasmic reticulum stress induce both transcription and translation of ATF4, which together enhance expression of ATF4 and its target genes in response to eIF2P. By contrast, UV irradiation represses ATF4 transcription, which diminishes ATF4 mRNA available for translation during eIF2∼P. eIF2P enhances cell survival in response to UV irradiation. However, forced expression of ATF4 and its target gene CHOP leads to increased sensitivity to UV irradiation. In this study, we also show that C/EBPβ is a transcriptional repressor of ATF4 during UV stress. C/EBPβ binds to critical elements in the ATF4 promoter resulting in its transcriptional repression. The LIP isoform of C/EBPβ, but not the LAP version is regulated following UV exposure and directly represses ATF4 transcription. Loss of the LIP isoform results in increased ATF4 mRNA levels in response to UV irradiation, and subsequent recovery of ATF4 translation, leading to enhanced expression of its target genes. Together these results illustrate how eIF2P and translational control, combined with transcription factors regulated by alternative signaling pathways, can direct programs of gene expression that are specifically tailored to each environmental stress.
Buchteile zum Thema "Translation regulatory network"
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Miyamoto-Sato, Etsuko. "Next-Generation Sequencing Coupled with a Cell-Free Display Technology for Reliable Interactome of Translational Factors." In Transcription Factor Regulatory Networks. Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0805-9_3.
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2
Cheok, Yi Ying, Suhailah Abdullah, and Won Feng Wong. "Transcriptional regulatory network associated with multiple sclerosis pathogenesis." In Transcription and Translation in Health and Disease. Elsevier, 2023. http://dx.doi.org/10.1016/b978-0-323-99521-4.00018-0.
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3
Yousefi, Mohammadmahdi Rezaei. "Optimal Intervention Methods for Markovian Gene Regulatory Networks." In Data Analytics in Medicine. IGI Global, 2020. http://dx.doi.org/10.4018/978-1-7998-1204-3.ch057.
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A central problem in translational medicine is to provide a framework for deriving and studying effective intervention methods to elicit desired steady-state behavior for a gene regulatory network of interest with Markovian dynamics. Heretofore, two rather different external control approaches have been taken. The first optimizes a subjectively defined cost function while modeling treatment constraints; therefore, desirable shift of the steady-state mass is a by-product. The second approach, on the other hand, focuses solely on the steady-state behavior of the network and provides the maximal shift achievable. Although both approaches are optimal with respect to their objectives, the choice of which to use depends on the treatment goals.
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Carvalho, P., G. Elias da Silva, and N. J. M. Saibo. "Understanding the genetics of C3 photosynthesis in crop plants." In Understanding and improving crop photosynthesis. Burleigh Dodds Science Publishing, 2023. http://dx.doi.org/10.19103/as.2022.0119.03.
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Understanding the genetics of C3 photosynthesis, particularly its regulation, is essential to undertake photosynthetic improvement. The expression of the photosynthesis-associated genes is regulated at different levels (transcriptional, post-transcriptional, post-translational), but very little is known about the regulatory networks involved. This chapter introduces the photosynthesis-associated core genes encoded either in the nucleus or in the chloroplast and discusses how different internal (e.g. redox state, circadian rhythm) and external (e.g. abiotic stresses, light) signals regulate their transcription, particularly in crop plants. Since the molecular mechanisms underlying the regulation of photosynthesis-associated genes is poorly understood, this chapter also discusses what is known regarding the transcriptional regulation of photosynthesis in C3 crops, mainly rice and tomato. Among the regulators described, few were shown in the field to have the potential to improve photosynthesis. How the state-of-the-art knowledge can be used for photosynthesis improvement and future work perspectives, including the use of transplastomics, is also discussed.
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Dang, Nitika. "Current Practice of Sleep Medicine in India." In The Practice of Sleep Medicine Around The World: Challenges, Knowledge Gaps and Unique Needs. BENTHAM SCIENCE PUBLISHERS, 2023. http://dx.doi.org/10.2174/9789815049367123010018.
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The history of sleep medicine dates back to millennia, carrying centuries of wisdom, decades of myths and challenges through the many years of struggle. Having been recognised as a body of knowledge in the last two decades and a formal branch of medicine in modern-day India. The burden of impending clinical practice, research and disproportionate health indices has allowed the tide of sleep medicine to be surfed by multiple specialties. With research interest dating back to 1965, the practice laid its formal beginning with the first sleep lab set up in New Delhi in 1995. The regulatory practices are thin on the ground that impedes the standardization of clinical research, labs or training of personnel in India. Initiatives at the behest of physicians have led to the setup of self-structured regulatory bodies, expanding the network of sleep labs in the country, albeit still very limited in comparison to the size of its populace. Increasing awareness about healthy sleep habits, bridging gaps in research, quality training and standards, improved regulatory frameworks, and translating knowledge from evidence-based medicine will drive the desired public health outcomes as well as the growth of standards and the future of sleep medicine practice in India.
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Ross, John, Igor Schreiber, and Marcel O. Vlad. "Mini-Introduction to Bioinformatics." In Determination of Complex Reaction Mechanisms. Oxford University Press, 2006. http://dx.doi.org/10.1093/oso/9780195178685.003.0015.
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There is enormous interest in the biology of complex reaction systems, be it in metabolism, signal transduction, gene regulatory networks, protein synthesis, and many others. The field of the interpretation of experiments on such systems by application of the methods of information science, computer science, and biostatistics is called bioinformatics (see for a presentation of this subject). Part of it is an extension of the chemical approaches that we have discussed for obtaining information on the reaction mechanisms of complex chemical systems to complex biological and genetic systems. We present here a very brief introduction to this field, which is exploding with scientific and technical activity. No review is intended, only an indication of several approaches on the subject of our book, with apologies for the omission of vast numbers of publications. A few reminders: The entire complement of DNA molecules constitute the genome, which consists of many genes. RNA is generated from DNA in a process called transcription; the RNA that codes for proteins is known as messenger RNA, abbreviated tomRNA. Other RNAs code for functional molecules such as transfer RNAs, ribosomal components, and regulatory molecules, or even have enzymatic function. Protein synthesis is regulated by many mechanisms, including that for transcription initiation, RNA splicing (in eukaryotes), mRNA transport, translation initiation, post-translational modifications, and degradation of mRNA. Proteins perform perhaps most cellular functions. Advances in microarray technology, with the use of cDNA or oligonucleotides immobilized in a predefined organization on a solid phase, have led to measurements of mRNA expression levels on a genome-wide scale (see chapter 3). The results of the measurements can be displayed on a plot on which a row represents one gene at various times, a column the whole set of genes, and the time of gene expression is plotted along the axis of rows. The changes in expression levels, as measured by fluorescence, are indicated by colors, for example green for decreased expression, black for no change in expression, and red for increased expression. Responses in expression levels have been measured for various biochemical and physiological conditions. We turn now to a few methods of obtaining information on genomic networks from microarray measurements.
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Amenta, Valentina, Adriana Lazzaroni, and Laura Abba. "Internet Identity and the Right to be Forgotten." In Handbook of Research on Redesigning the Future of Internet Architectures. IGI Global, 2015. http://dx.doi.org/10.4018/978-1-4666-8371-6.ch002.
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In this chapter, the analysis will focus on the concept of digital identity which is evolving and changing, based on the experiences that every individual lives. The chapter further highlights how the digital identity includes the fundamental human rights such as the right to a name, the right of reply, the right to protection of personal data and the right to an image. In translating the right to personal identity to our digitalized era, with its massive use of social networks, we have added to the related decalogue of rights the right to oblivion, equally called right to be forgotten. Given the complexity of the subject, the chapter develops an analysis of the actual international regulatory trends.
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Tong, Ling, Shuanghao Yong, Wei Li, Xiao Yang, and Xing Wang. "ARES-Kcr: A New Network Model Utilizing Attention Mechanism and Residual Structure for the Prediction of Lysine Crotonylation Sites." In Studies in Health Technology and Informatics. IOS Press, 2023. http://dx.doi.org/10.3233/shti230877.
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Lysine crotonylation (Kcr), as a significant post-translational modification of protein, exists in the core histones and some non histones of many organisms, and plays a crucial regulatory role in many biological processes such as gene expression, cell development, and disease treatment. Due to the high cost, time-consuming and labor-intensive nature of traditional biological experimental methods, it is necessary to develop efficient, low-cost and accurate calculation methods for identifying crotonylation sites. Therefore, we propose a new network model called ARES-Kcr, which extracts three types of features from different perspectives and integrates convolutional modules, attention mechanisms, and residual modules for feature fusion to improve prediction ability in this paper. Our model performs significantly better than other models on the benchmark dataset, with an average AUC of 92% in the independent test set, demonstrating its excellent predictive ability.
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Altay, Halit Yusuf, Fatma Özdemir, İskalen Cansu Topçu Okan, Yeşim Tütüncü, and Cavit Ağca. "Gen Düzenleyici Araçlar ve Bunların Translasyonel Yönleri." In Moleküler Biyoloji ve Genetik. Türkiye Bilimler Akademisi, 2023. http://dx.doi.org/10.53478/tuba.978-625-8352-48-1.ch08.
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Recent discoveries and advancements of gene editing tools and artificial transcription factors as well as delivery vectors are extending the frontiers for potential applications in the gene therapy field. Gene-editing tools like CRISPR (Clustered Regularly Interspaced Palindromic Repeats)-Cas9, transcription activator-like effector nucleases (TALENs), and zinc-finger nucleases (ZFNs) are mainly used for correcting disease mutations or modifying genome for research purposes. However, artificial transcription factors (non-cutting gene-editing tools) together with transcriptional activators or repressors are mostly used for establishing synthetic gene regulatory networks that will either overexpress or repress several genes in a controlled manner. Applications of gene editing tools and artificial transcription factors in humans have been the focus of research for years, however, the required efficiency, safety, and applicability were not achieved until recently. Moreover, the number of human trials using these tools for gene therapy applications is increasing tremendously. With the recent discovery of a highly efficient protein delivery method, we can now further benefit from gene regulatory and gene editing tools in a transient fashion, which will minimize the undesired side effects and off-target modifications. In this chapter, we summarized the origins, mechanisms, and recent progress on gene regulation and gene editing tools with a focus on the recent translational applications.
Konferenzberichte zum Thema "Translation regulatory network"
1
Liu, Yu, Yang Liu, Zhengtao Xiao, and Xuerui Yang. "Abstract A2-54: DNA methylation-dependent transcription regulatory networks elucidate dynamics of transcription regulatory circuitry in cancers." In Abstracts: AACR Special Conference: Translation of the Cancer Genome; February 7-9, 2015; San Francisco, CA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.transcagen-a2-54.
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2
Wu, Daniel Duanqing, Xiaohua Hu, and Tingting He. "Exploratory Analysis of Protein Translation Regulatory Networks Using Hierarchical Random Graphs." In 2009 IEEE International Conference on Bioinformatics and Biomedicine (BIBM). IEEE, 2009. http://dx.doi.org/10.1109/bibm.2009.38.
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3
Singh, Abhyudai, and Joao Pedro Hespanha. "Reducing noise through translational control in an auto-regulatory gene network." In 2009 American Control Conference. IEEE, 2009. http://dx.doi.org/10.1109/acc.2009.5160206.
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Fujita, Andre, Carme Camps, Jiannis Ragoussis, Satoru Miyano, and Patricia Severino. "Abstract A18: Assessing microRNA regulatory networks for biomarker discovery in cancer." In Abstracts: AACR International Conference on Translational Cancer Medicine-- Jul 11-14, 2010; San Francisco, CA. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1078-0432.tcmusa10-a18.
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Pires, Bruno R. B., Gerson M. Ferreira, Renata Binato, and Eliana Abdelhay. "Abstract A45: Regulatory network of the metastatic process in breast cancer." In Abstracts: AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1557-3265.tcm17-a45.
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Abate-Shen, Cory. "Abstract IA5: Using cross-species analysis of genome-wide regulatory networks to identify drivers of cancer malignancy." In Abstracts: AACR Special Conference: The Translational Impact of Model Organisms in Cancer; November 5-8, 2013; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1557-3125.modorg-ia5.
Der volle Inhalt der QuelleBerichte der Organisationen zum Thema "Translation regulatory network"
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Chen, Junping, Zach Adam, and Arie Admon. The Role of FtsH11 Protease in Chloroplast Biogenesis and Maintenance at Elevated Temperatures in Model and Crop Plants. United States Department of Agriculture, 2013. http://dx.doi.org/10.32747/2013.7699845.bard.
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specific objectives of this proposal were to: 1) determine the location, topology, and oligomerization of FtsH11 protease; 2) identify the substrate/s of FtsH11 and the downstream components involved in maintaining thermostability of chloroplasts; 3) identify new elements involved in FtsH11 protease regulatory network related to HT adaptation processes in chloroplast; 4) Study the role of FtsH11 homologs from crop species in HT tolerance. Background to the topic: HT-tolerant varieties that maintain high photosynthetic efficiency at HT, and cope better with daily and seasonal temperature fluctuations are in great need to alleviate the effect of global warming on food production. Photosynthesis is a very complex process requiring accurate coordination of many complex systems and constant adjustments to the changing environments. Proteolytic activities mediated by various proteases in chloroplast are essential part of this process and critical for maintaining normal chloroplast functions under HT. However, little is known about mechanisms that contribute to adaptation of photosynthetic processes to HT. Our study has shown that a chloroplast-targeted Arabidopsis FtsH11 protease plays an essential and specific role in maintaining thermostability of thylakoids and normal photosynthesis at moderate HT. We hypothesized that FtsH11 homologs recently identified in other plant species might have roles similarly to that of AtFtsH1. Thus, dissecting the underlying mechanisms of FtsH11 in the adaptation mechanisms in chloroplasts to HT stress and other elements involved will aid our effort to produce more agricultural products in less favorable environments. Major conclusions, solutions, achievements - Identified the chloroplast inner envelope membrane localization of FtsH11. - Revealed a specific association of FtsH11 with the a and b subunits of CPN60. - Identified the involvement of ARC6, a protein coordinates chloroplast division machineries in plants, in FtsH11 mediated HT adaptation process in chloroplast. -Reveal possible association of a polyribonucleotide nucleotidyltransferase (cpPNPase), coded by At3G03710, with FtsH11 mediated HT adaptation process in chloroplast. - Mapped 4 additional loci in FtsH11 mediated HT adaptation network in chloroplast. - Demonstrated importance of the proteolytic activity of FtsH11 for thermotolerance, in addition to the ATPase activity. - Demonstrated a conserved role of plant FtsH11 proteases in chloroplast biogenesis and in maintaining structural and functional thermostability of chloroplast at elevated temperatures. Implications, both scientific and agricultural:Three different components interacting with FtsH11 were identified during the course of this study. At present, it is not known whether these proteins are directly involved in FtsH11mediated thermotolerance network in chloroplast and/or how these elements are interrelated. Studies aiming to connect the dot among biological functions of these networks are underway in both labs. Nevertheless, in bacteria where it was first studied, FtsH functions in heat shock response by regulating transcription level of σ32, a heat chock factor regulates HSPsexpression. FtsH also involves in control of biosynthesis of membrane components and quality control of membrane proteins etc. In plants, both Arc 6 and CPN60 identified in this study are essential in chloroplast division and developments as mutation of either one impairs chloroplast division in Arabidopsis. The facts that we have found the specific association of both α and β CPN60 with FtsH11 protein biochemically, the suppression/ enhancement of ftsh11 thermosensitive phenotype by arc6 /pnp allele genetically, implicate inter-connection of these networks via FtsH11 mediated network(s) in regulating the dynamic adaptation processes of chloroplast to temperature increases at transcriptional, translational and post-translational levels. The conserved role of FtsH11 proteases in maintaining thermostability of chloroplast at HT demonstrated here provides a foundation for improving crop photosynthetic performance at high temperatures.
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Shale Gas: Strategic, Technical, Environmental and Regulatory Issues. Universidad de Deusto, 2016. http://dx.doi.org/10.18543/tszi1191.
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In January 2016, the book Gas no convencional: shale gas. Aspectos estratégicos, técnicos, medioambientales y regulatorios was published. As we pointed out in the prologue of the book, the study of unconventional gas is within the lines of knowledge of the Energy Chair of Orkestra of the University of Deusto. In fact, three main lines of study are currently covered. Namely Energy markets, Energy Industry and Technology, and Energy Policy. The approach to the shale gas study that the reader has in his hands, in our view, covers a wide scope of topics, including the strategic aspects, the technical topics related to the exploration, drilling and hydraulic fracturing, as well as the environmental aspects and the regulation processes for exploration. One of the characteristics of the research of the Energy Chair is to try to work with a network of institutions, universities and professionals with experience and knowledge in the specific topics that we analyze. In this case, from the very beginning, it was though that the creation and implementation of a group of experts would be particularly valuable, so an Advisory Group and a Reviewers Group were put in place. The relevant professionals and institutions that we have the honor to count on are reflected in this study. Given the participation of the members of the Advisory Group and the Reviewers Group, the first draft of the study was written in English. At the beginning of the project, Nerea Álvarez, mining engineer, produced a first draft. The English version was translated into Spanish and later, when Claudia Suárez joined the Energy Chair of Orkestra, she was fully involved to revise, extend and improve the study. In the process, we decided to focus our improvements in the Spanish version and to publish a book in Spanish. This study does not cover exactly all aspects and details dealt with in the book. Therefore, the document cannot be considered, in strict sense, a full and complete translation of the book, although many improvements of the Spanish book have been incorporated to the first draft in English.