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Zeitschriftenartikel zum Thema "Granules RNP"
1
Krüger, Timothy, Mario Hofweber und Susanne Kramer. „SCD6 induces ribonucleoprotein granule formation in trypanosomes in a translation-independent manner, regulated by its Lsm and RGG domains“. Molecular Biology of the Cell 24, Nr. 13 (Juli 2013): 2098–111. http://dx.doi.org/10.1091/mbc.e13-01-0068.
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Ribonucleoprotein (RNP) granules are cytoplasmic, microscopically visible structures composed of RNA and protein with proposed functions in mRNA decay and storage. Trypanosomes have several types of RNP granules, but lack most of the granule core components identified in yeast and humans. The exception is SCD6/Rap55, which is essential for processing body (P-body) formation. In this study, we analyzed the role of trypanosome SCD6 in RNP granule formation. Upon overexpression, the majority of SCD6 aggregates to multiple granules enriched at the nuclear periphery that recruit both P-body and stress granule proteins, as well as mRNAs. Granule protein composition depends on granule distance to the nucleus. In contrast to findings in yeast and humans, granule formation does not correlate with translational repression and can also take place in the nucleus after nuclear targeting of SCD6. While the SCD6 Lsm domain alone is both necessary and sufficient for granule induction, the RGG motif determines granule type and number: the absence of an intact RGG motif results in the formation of fewer granules that resemble P-bodies. The differences in granule number remain after nuclear targeting, indicating translation-independent functions of the RGG domain. We propose that, in trypanosomes, a local increase in SCD6 concentration may be sufficient to induce granules by recruiting mRNA. Proteins that bind selectively to the RGG and/or Lsm domain of SCD6 could be responsible for regulating granule type and number.
2
An, Haiyan, Jing Tong Tan und Tatyana A. Shelkovnikova. „Stress granules regulate stress-induced paraspeckle assembly“. Journal of Cell Biology 218, Nr. 12 (21.10.2019): 4127–40. http://dx.doi.org/10.1083/jcb.201904098.
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Eukaryotic cells contain a variety of RNA-protein macrocomplexes termed RNP granules. Different types of granules share multiple protein components; however, the crosstalk between spatially separated granules remains unaddressed. Paraspeckles and stress granules (SGs) are prototypical RNP granules localized exclusively in the nucleus and cytoplasm, respectively. Both granules are implicated in human diseases, such as amyotrophic lateral sclerosis. We characterized the composition of affinity-purified paraspeckle-like structures and found a significant overlap between the proteomes of paraspeckles and SGs. We further show that paraspeckle hyperassembly is typical for cells subjected to SG-inducing stresses. Using chemical and genetic disruption of SGs, we demonstrate that formation of microscopically visible SGs is required to trigger and maintain stress-induced paraspeckle assembly. Mechanistically, SGs may sequester negative regulators of paraspeckle formation, such as UBAP2L, alleviating their inhibitory effect on paraspeckles. Our study reveals a novel function for SGs as positive regulators of nuclear RNP granule assembly and suggests a role for disturbed SG-paraspeckle crosstalk in human disease.
3
Hanazawa, Momoyo, Masafumi Yonetani und Asako Sugimoto. „PGL proteins self associate and bind RNPs to mediate germ granule assembly in C. elegans“. Journal of Cell Biology 192, Nr. 6 (14.03.2011): 929–37. http://dx.doi.org/10.1083/jcb.201010106.
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Germ granules are germ lineage–specific ribonucleoprotein (RNP) complexes, but how they are assembled and specifically segregated to germ lineage cells remains unclear. Here, we show that the PGL proteins PGL-1 and PGL-3 serve as the scaffold for germ granule formation in Caenorhabditis elegans. Using cultured mammalian cells, we found that PGL proteins have the ability to self-associate and recruit RNPs. Depletion of PGL proteins from early C. elegans embryos caused dispersal of other germ granule components in the cytoplasm, suggesting that PGL proteins are essential for the architecture of germ granules. Using a structure–function analysis in vivo, we found that two functional domains of PGL proteins contribute to germ granule assembly: an RGG box for recruiting RNA and RNA-binding proteins and a self-association domain for formation of globular granules. We propose that self-association of scaffold proteins that can bind to RNPs is a general mechanism by which large RNP granules are formed.
4
Davis, Michael, Andrea Montalbano, Megan P. Wood und Jennifer A. Schisa. „Biphasic adaptation to osmotic stress in the C. elegans germ line“. American Journal of Physiology-Cell Physiology 312, Nr. 6 (01.06.2017): C741—C748. http://dx.doi.org/10.1152/ajpcell.00364.2016.
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Cells respond to environmental stress in multiple ways. In the germ line, heat shock and nutritive stress trigger the assembly of large ribonucleoprotein (RNP) granules via liquid-liquid phase separation (LLPS). The RNP granules are hypothesized to maintain the quality of oocytes during stress. The goal of this study was to investigate the cellular response to glucose in the germ line and determine if it is an osmotic stress response. We found that exposure to 500 mM glucose induces the assembly of RNP granules in the germ line within 1 h. Interestingly, the RNP granules are maintained for up to 3 h; however, they dissociate after longer periods of stress. The RNP granules include processing body and stress granule proteins, suggesting shared functions. Based on several lines of evidence, the germ line response to glucose largely appears to be an osmotic stress response, thus identifying osmotic stress as a trigger of LLPS. Although RNP granules are not maintained beyond 3 h of osmotic stress, the quality of oocytes does not appear to decrease after longer periods of stress, suggesting a secondary adaptation in the germ line. We used an indirect marker of glycerol and observed high levels after 5 and 20 h of glucose exposure. Moreover, in gpdh-1;gpdh-2 germ lines, glycerol levels are reduced concomitant with RNP granules being maintained for an extended period. We speculate that increased glycerol levels may function as a secondary osmoregulatory adaptive response in the germ line, following a primary response of RNP granule assembly.
5
Aoki, Scott T., Aaron M. Kershner, Craig A. Bingman, Marvin Wickens und Judith Kimble. „PGL germ granule assembly protein is a base-specific, single-stranded RNase“. Proceedings of the National Academy of Sciences 113, Nr. 5 (19.01.2016): 1279–84. http://dx.doi.org/10.1073/pnas.1524400113.
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Cellular RNA-protein (RNP) granules are ubiquitous and have fundamental roles in biology and RNA metabolism, but the molecular basis of their structure, assembly, and function is poorly understood. Using nematode “P-granules” as a paradigm, we focus on the PGL granule scaffold protein to gain molecular insights into RNP granule structure and assembly. We first identify a PGL dimerization domain (DD) and determine its crystal structure. PGL-1 DD has a novel 13 α-helix fold that creates a positively charged channel as a homodimer. We investigate its capacity to bind RNA and discover unexpectedly that PGL-1 DD is a guanosine-specific, single-stranded endonuclease. Discovery of the PGL homodimer, together with previous results, suggests a model in which the PGL DD dimer forms a fundamental building block for P-granule assembly. Discovery of the PGL RNase activity expands the role of RNP granule assembly proteins to include enzymatic activity in addition to their job as structural scaffolds.
6
Van Treeck, Briana, David S. W. Protter, Tyler Matheny, Anthony Khong, Christopher D. Link und Roy Parker. „RNA self-assembly contributes to stress granule formation and defining the stress granule transcriptome“. Proceedings of the National Academy of Sciences 115, Nr. 11 (26.02.2018): 2734–39. http://dx.doi.org/10.1073/pnas.1800038115.
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Stress granules are higher order assemblies of nontranslating mRNAs and proteins that form when translation initiation is inhibited. Stress granules are thought to form by protein–protein interactions of RNA-binding proteins. We demonstrate RNA homopolymers or purified cellular RNA forms assemblies in vitro analogous to stress granules. Remarkably, under conditions representative of an intracellular stress response, the mRNAs enriched in assemblies from total yeast RNA largely recapitulate the stress granule transcriptome. We suggest stress granules are formed by a summation of protein–protein and RNA–RNA interactions, with RNA self-assembly likely to contribute to other RNP assemblies wherever there is a high local concentration of RNA. RNA assembly in vitro is also increased by GR and PR dipeptide repeats, which are known to increase stress granule formation in cells. Since GR and PR dipeptides are involved in neurodegenerative diseases, this suggests that perturbations increasing RNA–RNA assembly in cells could lead to disease.
7
An, Haiyan, und Tatyana A. Shelkovnikova. „Stress granules regulate paraspeckles: RNP granule continuum at work“. Cell Stress 3, Nr. 12 (09.12.2019): 385–87. http://dx.doi.org/10.15698/cst2019.12.207.
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Noble, Scott L., Brittany L. Allen, Lai Kuan Goh, Kristen Nordick und Thomas C. Evans. „Maternal mRNAs are regulated by diverse P body–related mRNP granules during early Caenorhabditis elegans development“. Journal of Cell Biology 182, Nr. 3 (11.08.2008): 559–72. http://dx.doi.org/10.1083/jcb.200802128.
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Processing bodies (P bodies) are conserved mRNA–protein (mRNP) granules that are thought to be cytoplasmic centers for mRNA repression and degradation. However, their specific functions in vivo remain poorly understood. We find that repressed maternal mRNAs and their regulators localize to P body–like mRNP granules in the Caenorhabditis elegans germ line. Surprisingly, several distinct types of regulated granules form during oocyte and embryo development. 3′ untranslated region elements direct mRNA targeting to one of these granule classes. The P body factor CAR-1/Rap55 promotes association of repressed mRNA with granules and contributes to repression of Notch/glp-1 mRNA. However, CAR-1 controls Notch/glp-1 only during late oogenesis, where it functions with the RNA-binding regulators PUF-5, PUF-6, and PUF-7. The P body protein CGH-1/Rck/Dhh1 differs from CAR-1 in control of granule morphology and promotes mRNP stability in arrested oocytes. Therefore, a system of diverse and regulated RNP granules elicits stage-specific functions that ensure proper mRNA control during early development.
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De Graeve, Fabienne, und Florence Besse. „Neuronal RNP granules: from physiological to pathological assemblies“. Biological Chemistry 399, Nr. 7 (27.06.2018): 623–35. http://dx.doi.org/10.1515/hsz-2018-0141.
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Abstract Neuronal cells rely on macro- and micro-cellular compartmentalization to rapidly process information, and respond locally to external stimuli. Such a cellular organization is achieved via the assembly of neuronal ribonucleoprotein (RNP) granules, dynamic membrane-less organelles enriched in RNAs and associated regulatory proteins. In this review, we discuss how these high-order structures transport mRNAs to dendrites and axons, and how they contribute to the spatio-temporal regulation of localized mRNA translation. We also highlight how recent biophysical studies have shed light on the mechanisms underlying neuronal RNP granule dynamic assembly, remodeling and maturation, in both physiological and pathological contexts.
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Corbet, Giulia Ada, und Roy Parker. „RNP Granule Formation: Lessons from P-Bodies and Stress Granules“. Cold Spring Harbor Symposia on Quantitative Biology 84 (2019): 203–15. http://dx.doi.org/10.1101/sqb.2019.84.040329.
Der volle Inhalt der QuelleDissertationen zum Thema "Granules RNP"
1
Cid, Samper Fernando 1991. „Computational approaches to characterize RNP granules“. Doctoral thesis, Universitat Pompeu Fabra, 2020. http://hdl.handle.net/10803/668449.
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Ribonucleoprotein granules (RNP granules) are liquid-liquid phase separated
complexes composed mainly by proteins and RNA. They are responsible of many
processes involved in RNA regulation. Alterations in the dynamics of these proteinRNA complexes are associated with the appearance of several neurodegenerative
disorders such as Amyotrophic Lateral Sclerosis ALS or Fragile X Tremor Ataxia
Syndrome FXTAS. Yet, many aspects of their organization as well as the specific
roles of the RNA on the formation and function of these complexes are still unknown.
In order to study RNP granules structure and formation, we integrated several state of
the art high-throughput datasets. This includes protein and RNA composition obtained
from RNP pull-downs, protein-RNA interaction data from eCLIP experiments and
transcriptome-wide secondary structure information (produced by PARS). We used
network analysis and clustering algorithms to understand the fundamental properties
of granule RNAs. By integrating these properties, we produced a model to identify
scaffolding RNA. Scaffolding RNAs are able to recruit many protein components into
RNP granules. We found that the main protein components of stress granules (a kind
of RNP granules) are connected through protein-RNA interactions. We also analyzed
the contribution of RNA-RNA interactions and RNA post-transcriptional
modifications on the granule internal organization.
We applied these findings to understand the biochemical pathophysiology of FXTAS
disease, employing as well some novel experimental data. In FXTAS, a mutation on
the FMR1 gene produces a 5´microsatellite repetition that enhances its scaffolding
ability. This mutated mRNA is able to sequester some important proteins into nuclear
RNP granules, such as TRA2A (i.e. a splicing factor), impeding their normal function
and therefore producing some symptoms associated with the progress of the disease.
The better understanding of the principles governing granules formation and structure
will enable to develop novel therapies (e.g. aptamers) to mitigate the development of
several neurodegenerative diseases.Los gránulos ribonucleoproteicos (gránulos RNP, por sus siglas en inglés) son complejos producidos mediante separación líquido-líquido y están constituidos principalmente por proteínas y ARN. Son responsables de numerosos procesos involucrados con la regulación del ARN. Alteraciones en la dinámica de estos complejos de proteínas y ARN están asociadas con la aparición de diversas enfermedades neurodegenerativas como el ELA o FXTAS. Sin embargo, todavía se desconocen muchos aspectos relativos a su organización interna así como las contribuciones específicas del RNA en la formación y funcionamiento de estos complejos. A fin de estudiar la estructura y formación de los gránulos RNP, hemos integrado varias bases de datos de alto rendimiento de reciente aparición. Esto incluye datos sobre la composición proteica y en ARN de los RNP, sobre la interacción de proteínas y ARN extraída de experimentos de eCLIP y sobre la estructura secundaria del transcriptoma (producida mediante PARS). Todos estos datos han sido procesados para comprender las propiedades fundamentales de los ARNs que integran los gránulos, mediante el empleo de métodos computacionales como el análisis de redes o algoritmos de agrupamiento. De esta manera, hemos producido un modelo que integra varias de estas propiedades e identifica candidatos denominados ARNs de andamiaje. Definimos ARNs de andamiaje como moléculas de ARN con una alta propensión a formar gránulos y reclutar un gran número de componentes proteicos a los gránulos RNP. También hemos encontrado que las interacciones proteína-ARN conectan los principales componentes proteicos de consenso de los gránulos de estrés (un tipo específico de gránulos RNP). También hemos estudiado la contribución de las interacciones ARN-ARN y las modificaciones post-transcriptionales del RNA en la organización interna del gránulo. Hemos aplicado estos resultados para la comprensión de la fisiopatología molecular de FXTAS, empleando también algunos datos experimentales originales. En FXTAS, una mutación en el gen FMR1 produce una repetición de microsatélite en 5´ que incrementa su capacidad como ARN de andamiaje. Este mARN mutado es capaz de secuestrar algunas proteínas importantes como TRA2A (un factor de ayuste alternativo) en gránulos RNP nucleares, impidiendo su normal funcionamiento y por consiguiente produciendo algunos síntomas asociados con el progreso de la enfermedad. Una mejor comprensión de los principios que gobiernan la formación y estructura de los gránulos puede permitir desarrollar nuevas terapias (ej: aptámeros) para mitigar el desarrollo de diversas enfermedades neurodegenerativas.
2
Vijayakumar, Jeshlee Cyril. „Rôle du domaine de type prion de Imp dans la régulation des granules RNP neuronaux“. Thesis, Université Côte d'Azur (ComUE), 2018. http://www.theses.fr/2018AZUR4099/document.
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Les ARNms des cellules eucaryotes sont liés à des protéines de liaison aux ARNs (RBPs) et empaquetés au sein d’assemblages macro-moléculaires appelés granules RNP. Dans les cellules neuronales, les granules RNP de transport sont impliqués dans le transport d’ARNms spécifiques jusqu’aux axones et dendrites, ainsi que dans leur traduction locale en réponse à des signaux externes. Bien que peu de choses soient connues sur l’assemblage et la régulation de ces granules in vivo, des résultats récents ont indiqué que la présence de domaines de type prion (PLDs) dans les RBPs facilite les interactions protéines-protéines et protéines-ARN, favorisant ainsi la condensation de complexes solubles en granules RNP. La RBP conservée Imp est un composant central de granules RNP qui sont transportés dans les axones lors du remodelage neuronal chez la drosophile. De plus, la fonction de Imp est nécessaire au remodelage des axones lors de la maturation du système nerveux de drosophile. Une analyse de la séquence de la protéine Imp a révélé qu’en plus de quatre domaines de liaison aux ARNs, Imp contient un domaine C-terminal désordonné enrichi en Glutamines et Serines, deux propriétés caractéristiques des domaines PLDs. Lors de ma thèse, j’ai étudié la fonction de ce PLD dans le contexte de l’assemblage et du transport des granules RNP. J’ai observé en culture de cellules que les granules Imp s’assemblent en absence de PLD, bien que leur nombre et leur taille soient augmentés. Des protéines présentant une séquence PLD mélangée, au contraire, s’accumulent dans des granules au nombre et à la taille normale, indiquant que l’état désordonné de ce domaine, et non sa séquence primaire, est essentiel à l’homéostasie des granules. De plus, des expériences de FRAP réalisées en culture de cellule et in vivo ont révélé que le domaine PLD de Imp favorise la dynamique des granules. In vivo, ce domaine est nécessaire et suffisant à l’accumulation axonale de Imp. Comme montré par une analyse en temps réel, l’absence de domaine PLD aboutit également à une diminution du nombre de granules axonaux motiles. Fonctionnellement, le domaine PLD de Imp est essentiel au remodelage neuronal car des protéines sans ce domaine ne sont pas capables de supprimer les défauts de repousse axonale observés après inactivation de imp. Enfin, la génération d’un variant de Imp dans lequel le domaine PLD a été déplacé en N-terminus a montré que les fonctions du PLD dans le transport des granules et dans leur assemblage sont découplées, et que la modulation des propriétés des granules Imp médiée par le domaine PLD n’est pas nécessaire au remodelage neuronal in vivo. En conclusion, mes résultats ont montré que le domaine PLD de Imp n’est pas nécessaire à l’assemblage des granules RNP Imp, mais régule leur nombre et leur dynamique. De plus, mon travail a mis en évidence une fonction inattendue pour un domaine PLD dans le transport axonal et le remodelage des neurones lors de la maturation du système nerveuxEukaryotic mRNAs are bound by RNA Binding Proteins (RBP) and packaged into diverse range of macromolecular assemblies named RNP granules. In neurons, transport RNP granules are implicated in the transport of specific mRNAs to axons or dendrites, and in their local translation in response to external cues. Although little is known about the assembly and regulation of these granules in vivo, growing evidence indicates that the presence of Prion Like domains (PLD) within RBPs favours multivalent protein–protein and protein-RNA interactions, promoting the transition of soluble complexes into RNP granules. The conserved RBP Imp is as a core component of RNP granules that are actively transported to axons upon neuronal remodelling in Drosophila. Furthermore, Imp function was shown to be required for axonal remodelling during Drosophila nervous system maturation. Analyses of the domain architecture of the Imp protein revealed that, in addition to four RNA binding domains (RBD), Imp contains a Cterminal domain showing a striking enrichment in Glutamines and Serines, which is one of the characteristics of a PLD. During my PhD, I explored the function of the PLD in the context of granule assembly and transport. In cultured cells, I observed that Imp granules assembled in the absence of the PLD, however their number and size were increased. Proteins with scrambled PLD sequence accumulated in granules of normal size and number, implying that the degree of disorder of this domain, and not its sequence, is essential for granule homeostasis. Moreover, FRAP experiments, performed on cultured cells and in vivo, revealed that Imp PLD is important to maintain the turnover of these granules. In vivo, this domain is both necessary and sufficient for efficient transport of Imp granules to axons. These defects are associated with a reduction on the number of motile granules in axons. Furthermore, mutant forms lacking the PLD do not rescue the axon remodelling defects observed upon imp loss of function. Finally, a swapping experiment in which I moved Imp PLD from the C-terminus to the N-terminus of the protein revealed that the functions of Imp PLD in granule transport and homeostasis are uncoupled, and that PLD-dependent modulation of Imp granule properties is dispensable in vivo. Together, my results show that Imp PLD of is not required for the assembly of RNP granules, but rather regulates granule number and dynamics. Furthermore, my work uncovered an unexpected in vivo function for a PLD in axonal transport and remodelling during nervous system maturation
3
Pushpalatha, Kavya Vinayan. „Remodelage des condensats RNP neuronaux au cours du vieillissement chez la drosophile“. Electronic Thesis or Diss., Université Côte d'Azur, 2021. http://theses.univ-cotedazur.fr/2021COAZ6007.
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Dans la cellule, les molécules d’ARN s’assemblent avec des protéines de liaison aux ARNs pour former des assemblages macromoléculaires très dynamiques appelés granules ribonucléoprotéiques (RNP). Ces assemblages régulent l’expression génique en contrôlant le transport, la stabilité et/ou la traduction des ARNs associés. Des travaux réalisés in vitro ont montré que la formation et la composition des granules RNP reposent sur l’établissement de réseaux denses d’interactions établis entre protéines et ARN, ainsi que sur leur stoechiométrie. Comment les propriétés des granules RNP sont régulées en contexte physiologique, et en particulier lors du vieillissement, est cependant actuellement peu connu. Mon projet de thèse visait à répondre à cette question par une étude in vivo des granules RNP présents dans les cellules neuronales du cerveau de drosophile.A cette fin, j’ai analysé dans des cerveaux d’âge croissant des granules RNP caractérisés par la présence de la protéine de liaison aux ARNs Imp/ZBP1 et de la DEAD-box hélicase Me31B/DDX6. Mes travaux ont révélé une augmentation progressive de la condensation de Imp et Me31B en larges granules au cours du vieillissement. Ces granules sont dynamiques et ne co-localisent pas avec des marqueurs d’agrégation, suggérant qu’ils ne correspondent pas à des agrégats protéiques statiques. Remarquablement, la condensation de Imp et Me31B est associée à la perte des granules Me31B+ Imp- observées dans les cerveaux jeunes, et à la coalescence de Me31B et Imp pour former des granules uniques Me31B+ Imp+. De plus, ce processus est accompagné d’une inhibition spécifique de la traduction des ARNms associés aux granules, parmi lesquels profilin. Par une analyse fonctionnelle, j’ai mis en évidence qu’une modification de la concentration en Me31B est responsable de la condensation de Me31B dans les cerveaux âgés. Alors qu’une augmentation de la quantité de Me31B est observée au cours du vieillissement, enlever une copie de me31B supprime la condensation age-dépendante de ce composant. Étant donné que la condensation de Imp n’est que partiellement affectée dans ce contexte, j’ai réalisé un crible génétique afin d’identifier des régulateurs de ce processus. Ceci m’a permis de montrer que l’activité de la kinase PKA est essentielle d’une part à la condensation de Imp chez les drosophiles âgées, et d’autre part à la répression traductionnelle des ARNms associés aux granules.En conclusion, mon travail a montré pour la première fois que les propriétés des granules RNP neuronaux sont modifiées au cours du vieillissement, un phénomène qui ne reflète pas une altération générale de l’homéostasie des ARNs, mais plutôt une modulation spécifique de la concentration en composants RNP combinée à l’activité de kinase conservée. Ces résultats démontrent comment les systèmes biologiques peuvent moduler des paramètres clés initialement identifiés dans des contextes in vitro, et ouvrent de nouvelles perspectives dans le domaine de la régulation de l’expression génique au cours du vieillissementNascent mRNAs complex with RNA binding proteins (RBPs) to form highly dynamic, phase-separated organelles termed ribonucleoprotein (RNP) granules. These macromolecular assemblies can regulate gene expression by controlling the transport, decay and/or translation of associated RNA molecules. As mostly shown in vitro, RNP granule assembly and function rely on the interaction networks established by individual components and on their stoichiometry. To date, how the properties of constitutive RNP granules are regulated in different physiological context is unclear. In particular, the impact of physiological aging is unclear. My PhD project aimed at addressing this question by analyzing in vivo in long-lived neuronal cells the properties of RNP granules. To this end, I have analysed in flies of increasing age RNP granules characterized by the presence of the conserved RBP Imp/ZBP1 and DEAD-box RNA helicase Me31B/DDX6. Strikingly, a progressive increase in the condensation of Imp and Me31B into granules was observed upon aging. The large granules observed in aged flies were dynamic, contained profilin mRNA, and did not colocalize with Ubiquitin or aggregation markers, suggesting that they do not correspond to static protein aggregates. Increased condensation also associated with the loss of Me31B+ Imp- granules observed in young brains and the collapse of RNP component into a unique class of Me31B+ Imp+ granule. Furthermore, it was accompanied by a specific inhibition of the translation of granule-associated mRNAs, among which the Imp RNA target profilin. Through functional analysis, I uncovered that changes in Me31B stoichiometry trigger Me31B condensation in aged flies. While an increase in Me31B protein levels was observed upon aging, decreasing the dosage of Me31B suppressed its age-dependent condensation. As Imp condensation was only partially suppressed in this context, I performed a selective screen to identify regulators of this process. This revealed that downregulating PKA activity by different genetic means both drastically reduced Imp recruitment and prevented the age-dependent translational repression of granule-associated mRNAs. Taken together, my work thus showed for the first time in vivo that the properties of neuronal RNP granules change upon aging, a phenomenon that does not reflect general alterations in RNA homeostasis but rather specific modulation of RNP component stoichiometry and kinase activity. These results demonstrate how biological systems can modulate key parameters initially defined based on in vitro framework, and also open new perspectives in the field of age-dependent regulation of gene expression
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Shah, Khyati H. „REGULATION, COMPOSITION AND FUNCTIONS OF RNP GRANULES IN QUIESCENT CELLS OF SACCHAROMYCES CEREVISIAE“. The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1417541239.
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Formicola, Nadia. „Remodelage des granules ARN en réponse à l’activité neuronale“. Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2019. http://theses.univ-cotedazur.fr/2019AZUR6008.
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Une des questions les plus fascinantes – et les plus ouvertes – en neuroscience est de comprendre comment les cellules neuronales contribuent à la formation, le maintien puis le rappel des souvenirs. Des travaux antérieurs ont montré que la formation de la mémoire à long-terme (MLT) requiert la synthèse de novo de protéines, impliquant non seulement la traduction d’ARNs nouvellement transcrits, mais aussi la traduction locale, induite par l’expérience, d’ARNms latents transportés et stockés dans les synapses. En vue de leur transport et du contrôle de leur traduction, les ARNms sont empaquetés avec des protéines de liaison aux ARNs (RBP), qui sont majoritairement des répresseurs de traduction, dans des granules ribonucléoprotéiques (RNP). La manière dont les granules RNP neuronaux sont remodelés en réponse à l’activité neuronale pour lever la répression traductionelle des ARNms est pour l’instant peu claire. En outre, l’impact fonctionnel d’un tel remodelage sur l’établissement de la MLT reste à démontrer in vivo. L’objectif de mon doctorat était 1) d’étudier les mécanismes in vivo qui sous-tendent le remodelage des granules RNP neuronaux ; 2) de tester l’hypothèse que les granules RNP pourraient être impliqués dans les mécanismes de renforcement de la MLT en régulant l’expression génétique. Dans cette optique, j’ai utilisé comme modèle des granules RNP contenant la RBP conservée Imp chez la drosophile. Tout d’abord, j’ai étudié l’impact de l’activité neuronale sur les propriétés des granules RNP Imp, en traitant des explants de cerveau soit avec du KCl, soit avec le neuromodulateur Tyramine. Dans les deux cas, un désassemblage des granules RNP Imp - caractérisé par une dé-granulation à la fois de Imp et d’autres composants – est observé. Le désassemblage des granules RNP est réversible après retrait de la tyramine, et n’a pas été observé dans les neurones hyperpolarisés. Il ne dépend pas strictement du domaine de type prion qui se trouve à l’extrémité carboxy-terminale de Imp, un domaine connu pour être impliqué dans l’homéostasie des granules RNP. De plus, mes données suggèrent que ce désassemblage soit lié à une augmentation de la traduction des ARNms associés, ce qui est cohérent avec un modèle dans lequel le remodelage des granules RNP induit par l’activité des neurones induit une dé-répression de la traduction. Ensuite, j’ai recherché les mécanismes contrôlant le remodelage des granules RNP. Un candidat pour cette régulation était CamkII, une kinase conservée activée par le calcium, et identifiée comme partenaire de Imp dans une analyse d’immunoprécipitation-spectrométrie de masse. Au cours de mon doctorat, j’ai pu valider l’intéraction Imp-CamkII et montrer qu’elle n’est pas médiée par l’ARN, mais dépend de l’activité de CamkII. De plus, j’ai montré qu’inhiber l’activité de CamkII empêche le désassemblage des granules RNP Imp observé lors de l’activation neuronale, suggérant que CamkII pourrait être impliquée dans le remodelage des granules RNP Imp induit par l’activité neuronale. Ces résutats sont particulièrement intéressants dans le contexte de l’établissement de la MLT, car CamkII est depuis longtemps reconnue comme y étant essentielle. Plus encore, nous avons récemment démontré chez la drosophile qu’inactiver la fonction de Imp dans une population de neurones du cerveau central impliquée dans l’apprentissage et la mémoire – les neurones du Mushroom Body – altère radicalement la MLT. En conclusion, mes résultats sont cohérents avec un modèle où le remodelage des granules RNP Imp en réponse à l’activation neuronale dépend de CamkII, et pourrait contribuer à la formation de la MLT in vivoOne of the most fascinating – and still open – questions in neuroscience is how neuronal cells can form, store and then recall memories. Previous work has shown that Long-term memory (LTM) formation requires de novo protein synthesis, involving not only translation of newly transcribed RNAs, but also local, experience-induced translation of quiescent mRNAs carried and stored at synapses. For their transport and translational control, mRNAs are packaged with regulatory RNA binding proteins (RBPs), mainly translational repressors, into ribonucleoprotein (RNP) granules. To date, how neuronal RNP granules are remodelled in response to neuronal activity to relieve translation repression of mRNAs is unclear. Furthermore, the functional impact of such a remodelling in the establishment of long-term memories remains to be demonstrated in vivo. The objective of my PhD was to 1) investigate the in vivo mechanisms underlying activity-dependent remodelling of neuronal RNP granules; 2) test the hypothesis that RNPs could be involved in LTM-underlying mechanisms by regulating gene expression. To this end, I used as paradigm RNPs containing the conserved RBP Imp in Drosophila. First, I studied the impact of neuronal activity on Imp RNP properties by treating Drosophila brain explants with either KCl or the tyramine neuropeptide. In both cases, a disassembly of Imp RNPs was observed, characterized by a loss of both Imp and other RNP-component granular patterns, and a de-clustering of RNP-associated mRNA molecules. RNP disassembly could be reverted upon Tyramine withdrawal and was not observed in hyperpolarized neurons. Furthermore, my data suggest that RNP-disassembly is linked to increased translation of associated mRNAs, consistent with a model in which activity-induced RNP remodelling would lead to translational de-repression. Second, I investigated the mechanisms controlling RNP remodelling. A candidate regulator was CamkII, a conserved Ca2+ -activated kinase identified as a partner of Imp in an IP-Mass Spectrometry analysis. During my PhD, I could validate the Imp-CamkII interaction and showed that it is not mediated by RNA but depends on CamkII activity. Furthermore, I showed that inactivating CamkII function prevents the disassembly of Imp RNPs observed upon neuronal activation of brain explants, suggesting that CamkII may be involved in the activity-dependent remodelling of Imp RNP granules. These results are particularly interesting in the context of establishment of LTM, as CamkII has long been recognized as essential for LTM. Moreover, we recently showed in Drosophila that interfering with Imp function in a population of CNS neurons involved in learning and memory – the Mushroom Body γ neurons -, dramatically impairs LTM and that this effect relies on Imp C-terminal Prion-like domain, a domain known to be involved in RNP homeostasis. Altogether, my thesis work suggests a model where CamkII-dependent remodelling of Imp RNPs in response to neuronal activation might underlie LTM formation in vivo
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Agostini, Federico 1985. „Predictions of RNA-binding ability and aggregation propensity of proteins“. Doctoral thesis, Universitat Pompeu Fabra, 2014. http://hdl.handle.net/10803/318159.
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RNA-binding proteins (RBPs) control the fate of a multitude of coding and non-coding transcripts. Formation of ribonucleoprotein (RNP) complexes fine-tunes regulation of post-transcriptional events and influences gene expression. Recently, it has been observed that non-canonical proteins with RNA-binding ability are enriched in structurally disordered and low-complexity regions that are generally involved in functional and dysfunctional associations. Therefore, it is possible that interactions with RNA protect unstructured protein domains from aberrant associations or aggregation. Nevertheless, the mechanisms that prevent protein aggregation and the role of RNA in such processes are not well understood. In this work, I will describe algorithms that I have developed to predict protein solubility and to estimate the ability of proteins and transcripts to interact. I will illustrate applications of computational methods and show how they can be integrated with high throughput approaches. The overarching goal of my work is to provide experimentalists with tools that facilitate the investigation of regulatory mechanisms controlling protein homeostasis.Las proteínas de unión de ARN son responsables de controlar el destino de una multitud de transcriptos codificantes y no codificantes. De hecho, la formación de complejos de ribonucleoproteínas (RNP) afina la regulación de una serie de eventos post-transcripcionales e influye en la expresión génica. Recientemente, se ha observado que las proteínas con capacidad no canónica de unión al ARN se enriquecen en las regiones estructuralmente desordenadas y de baja complejidad, que son las que participan generalmente en asociaciones funcionales y disfuncionales. Por lo tanto, es posible que interactuar con el ARN pudiera ser una manera de proteger las proteínas no estructuradas de asociaciones aberrantes o de agregación. Sin embargo, los mecanismos que impiden la agregación de proteínas y la función del ARN en tales procesos no están bien descritas. En este trabajo, se describen los me ́todos que he desarrollado para predecir la solubilidad de proteínas y para estimar la capacidad de transcriptos y proteínas de interactuar. De otra parte, voy a ilustrar sus aplicaciones y explicar como los métodos de bajo rendimiento han evolucionado a un mayor rendimiento. El objetivo final es proporcionar instrumentos a los investigadores experimentales que se pueden utilizar para facilitar la investigación de los mecanismos reguladores que controlan la homeostasis molecular.
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Al-Sailawi, Majid. „Investigating RNA granules formation during caliciviruses infection“. Thesis, University of Surrey, 2015. http://epubs.surrey.ac.uk/809289/.
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Human norovirus (HuNV) is a member of the calicivirus family and is a major cause of viral gastroenteritis worldwide. Due to the absence of a suitable cell culture system, HuNoV replication mechanisms are poorly understood, but two animal caliciviruses, Feline calicivirus (FCV) and Murine Norovirus (MNV) provide models to increase our understanding of norovirus biology. Unlike cellular mRNAs, the calicivirus RNA genome does not possess a 5' cap structure but instead has a 13–15 kDa viral protein, genome linked (VPg) directing translation, hijacking the host protein synthesis machinery. The viral life cycle requires separated events occurring at different times since viral transcripts are used as the template both for translation (mRNA) and replication (genomic RNA). Therefore mechanisms are required to control the viral RNA fate. In eukaryotes, during stress conditions, mRNAs can be stored in subcellular compartments such as stress granules to stall their translation or in processing bodies to be degraded. Recent evidence indicates that these compartments also play an important role during the viral life cycle. Therefore, using immunofluorescence microscopy we set out to investigate how FCV and MNV infection regulate the formation of G3BP1- and PABP-1-containing stress granules and DCP-1-containing processing bodies to address whether these cytoplasmic granules could play a role during the viral life cycle. We have now shown that FCV has the ability to prevent stress granules formation during infection and that this is important for replication in CRFK and FEA cells. Using FCV-free supernatant from infected CRFK cells and immunofluorescence microscopy, we have also shown that during infection, the formation of stress granules is induced in a paracrine manner in uninfected cells via a messenger molecule released from infected cells. We hypothesize that this could reflect a new antiviral role for stress granules. Furthermore, MNV and FCV infection also led to the disruption of processing-bodies assembly. Overall, this study revealed that caliciviruses modulate the RNA granules during infection and that this could be part of viral mechanism to counteract the antiviral response.
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Oh, Seong-Wook. „Functional Analysis of RIG-I and RNP Complexes in the Antiviral Interferon System“. 京都大学 (Kyoto University), 2016. http://hdl.handle.net/2433/215973.
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Pizzinga, Mariavittoria. „Granules of translation factor mRNAs and their potential role in the localisation of the translation machinery to regions of polarised growth“. Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/granules-of-translation-factor-mrnas-and-their-potential-role-in-the-localisation-of-the-translation-machinery-to-regions-of-polarised-growth(9cb42e69-3c8c-4f10-b79f-ba8261be4430).html.
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The subcellular localisation of mRNA is a widespread mechanism to determine the fate of mRNAs in eukaryotes. Translationally repressed mRNAs localise to P-bodies and stress granules where their decay and storage, respectively, are directed. In a study from the Ashe lab, specific mRNAs were identified to localise, in actively growing S. cerevisiae, to cytoplasmic granules that do not seem to be related to P-bodies or stress granules but appear to be associated with active translation (Lui et al., 2014).It is possible that this might represent a strategy to co-regulate the expression of proteins from the same pathway. In the work of this thesis, microscopy techniques to visualise RNAs in live cells were used to extend the localisation analysis to several mRNAs encoding translation factors. The investigated transcripts were all found to localise to mostly one or two cytoplasmic granules per cell and would sometimes overlap with other transcripts, suggesting that each granule contains a mixture of mRNAs. Granules tend to migrate to the bud tip and may provide the daughter cell with a "start-up kit" of transcripts essential for rapid growth. A similar pattern can be observed in yeast cells growing undergoing filamentous growth, with granules harbouring translation factor transcripts often found in the apical quarter of the elongated cell. Although the mechanism by which the granules form and their protein composition are not yet known, high-throughput genetic screens performed as part of this work offer some insight into factors that might be involved in granule assembly and proteins that partially overlap with the granules. We propose that granules containing translation factor mRNAs might be functioning as a specialised factory for the translation machinery and are possibly being directed to the point in the cell where the rhythm of protein production is highest.
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Kuznicki, Kathleen. „The function of the germline rna helicase (GLH) genes in caenorhabditis elegans“. free to MU campus, to others for purchase, 2000. http://wwwlib.umi.com/cr/mo/fullcit?p9988682.
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Jønson, Lars, Finn Cilius Nielsen und Jan Christiansen. „Isolation of RNP Granules“. In RNA, 265–73. Totowa, NJ: Humana Press, 2010. http://dx.doi.org/10.1007/978-1-59745-248-9_18.
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Mateju, Daniel, Laura Mediani, Federica F. Morelli, Simon Alberti und Serena Carra. „Molecular Chaperones Regulating the Dynamics, Composition and Functionality of RNP Granules: Implications for Age-Related Diseases“. In HSP70 in Human Diseases and Disorders, 205–22. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-89551-2_10.
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Sidibé, Hadjara, und Christine Vande Velde. „RNA Granules and Their Role in Neurodegenerative Diseases“. In Advances in Experimental Medicine and Biology, 195–245. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-31434-7_8.
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Fan, Alexander C., und Anthony K. L. Leung. „RNA Granules and Diseases: A Case Study of Stress Granules in ALS and FTLD“. In Advances in Experimental Medicine and Biology, 263–96. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-29073-7_11.
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Nakamura, Hideki. „Engineering Hydrogel Production in Mammalian Cells to Synthetically Mimic RNA Granules“. In Methods in Molecular Biology, 253–76. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1441-9_15.
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Sarkar, Jaya, und Sua Myong. „Single-Molecule and Ensemble Methods to Probe Initial Stages of RNP Granule Assembly“. In Methods in Molecular Biology, 325–38. New York, NY: Springer New York, 2018. http://dx.doi.org/10.1007/978-1-4939-8591-3_19.
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Xavier, Vanessa Joanne, und Jean-Claude Martinou. „Visualization of Mitochondrial RNA Granules in Cultured Cells Using 5-Bromouridine Labeling“. In Methods in Molecular Biology, 69–73. New York, NY: Springer US, 2020. http://dx.doi.org/10.1007/978-1-0716-0834-0_6.
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Nagamori, Ippei, Adam Cruickshank und Paolo Sassone-Corsi. „The Chromatoid Body: A Specialized RNA Granule of Male Germ Cells“. In Epigenetics and Human Reproduction, 311–28. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-642-14773-9_14.
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Saito, Makoto, Vytautas Iestamantavicius, Daniel Hess und Patrick Matthias. „Monitoring Acetylation of the RNA Helicase DDX3X, a Protein Critical for Formation of Stress Granules“. In Methods in Molecular Biology, 217–34. New York, NY: Springer US, 2020. http://dx.doi.org/10.1007/978-1-0716-0935-4_14.
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Benarroch, Eduardo E. „Messenger RNA Metabolism“. In Neuroscience for Clinicians, herausgegeben von Eduardo E. Benarroch, 62–84. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780190948894.003.0005.
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Metabolism of messenger RNA (mRNA) is critical for control of cell phenotype and includes several steps: transcription of DNA into a pre-mRNA, mRNA maturation, nucleocytoplasmic export and transport to specific cellular locations, translation into proteins, and decay. All these steps are seamlessly integrated and controlled by a large number of RNA-binding proteins that interact with RNA, forming messenger ribonucleoprotein particles. Several noncoding RNAs, such as microRNAs, also regulate mRNA metabolism. Activity-dependent control of mRNA transcription, splicing, and translation are critical for growth, plasticity, and repair in the nervous system. Disorders of RNA metabolism are a major disease pathway for a large number of neurologic disorders, many of them associated with accumulation of stress granules containing RNA and associated proteins. Elucidation of the pathophysiology of some of these disorders provides novel approaches for their treatment, including antisense oligonucleotide therapy.
Konferenzberichte zum Thema "Granules RNP"
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Arun, Vedant, Joseph Wiley, Zia Karim und Abhijit Guha. „Abstract 4023: Novel role of neurofibromin in transport of RNA granules“. In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-4023.
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Kolobova, Elena, M. Cecilia Larocca und James R. Goldenring. „Abstract 3560: Evaluation of RNA-stress granules formation as an indicator of response to Darinaparsin in cancer cell lines“. In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-3560.
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Mittelbach, Livia. „Numerical simulation of rip-raps with the distinct element method“. In POWDERS AND GRAINS 2013: Proceedings of the 7th International Conference on Micromechanics of Granular Media. AIP, 2013. http://dx.doi.org/10.1063/1.4812147.
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Gutierrez Klinsky, Luis Miguel, Mario Alexander Castañeda López, William Fedrigo, Thaís Radünz Kleinert, Washington Peres Núñez, Jorge Augusto Pereira Ceratti und Valeria Cristina De Faria. „Estudio de fatiga en mezclas asfálticas recicladas con cemento a través de ensayo en viga cuatro puntos“. In CIT2016. Congreso de Ingeniería del Transporte. Valencia: Universitat Politècnica València, 2016. http://dx.doi.org/10.4995/cit2016.2016.3486.
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El reciclaje profundo de pavimentos flexibles con cemento Portland es una técnica de recuperación estructural y funcional recurrente en la práctica vial Brasilera, ya que la reutilización de capas degradadas de revestimiento asfáltico o RAP (reclaimed asphalt pavement) y de base, permite reducir costos y tiempo de ejecución. Sin embargo, en Brasil no existe un criterio de dimensionamiento de pavimentos que considere este tipo de materiales. En este sentido, es aceptado que la capacidad estructural de capas cementadas es limitada por la deformación de tracción en su base. Con el objetivo de establecer esta relación, a través de modelos de fatiga, fue desarrollado un programa experimental basado en la experiencia australiana, buscando verificar su aplicabilidad a materiales reciclados de origen brasilero. Conforme al protocolo adoptado, el programa consistió de ensayos de flexión estáticos y dinámicos del tipo cuatro puntos en vigas, con edades de cura mayores a 28 días, moldadas en laboratorio usando energía de compactación modificada brasilera. Las mezclas consideradas están constituidas 4 % de cemento Portland, y por brita granular y RAP en proporciones 80:20, 50:50 y 30:70. El comportamiento mecánico fue evaluado a través de la Resistencia a la Tracción a la Flexión (RTF) y el Módulo Flexural Estático y Resiliente (MFE y MFR, respectivamente). Entre otras conclusiones, el comportamiento estático indica que el incremento de RAP reduce el MFE, incrementando la deformación de tracción de ruptura, mientras que la influencia del RAP en la RTF no fue notoria. De otra parte, la relación entre el exponente de daño y el porcentaje de RAP apunta a una dependencia del fenómeno de fatiga y el contenido de material reciclado. En general, puede concluirse que el protocolo australiano puede ser usado como modelo para el desarrollo de un método brasilero para este tipo de mezclas, con algunas modificaciones.DOI: http://dx.doi.org/10.4995/CIT2016.2016.3486
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Duarte de Barros, Guilherme, Juliana De Oliveira, Vitor Matheus Ferraz Pereira, Wesley Da Silva Pereira und André Luiz Maciel Santana. „Análise morfológica de nanofibras Uma abordagem por visão computacional e aprendizagem de máquina“. In Computer on the Beach. São José: Universidade do Vale do Itajaí, 2021. http://dx.doi.org/10.14210/cotb.v12.p537-539.
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The studies and applications of nanofibers have grown over the years. It was observed that the properties of the nanometer-scale yarns present advantages in applications in several areas, such as biomedical, energy storage and production, and applications involving water filtration. These materials are synthesized through a technical process and, for that reason, they are subject to the presentation of failures. The most common flaws are the formation of granules and pores. With the evolution of computing, applications that use machine learning resources can assist in detecting these failures. This work aims to evaluate and compare two different approaches to morphological analysis to see losses in nanofibers. Firstly, a data set was created using a Scanning Electron Microscope. After that, each image was analyzed by ImageJ software and by RNA solution. As a hypothesis, the article will assess whether the beads identification and the number of beads by the analog method are statistically similar (H0) or statistically different (H1) from the machine learning method. The preliminary results indicate that for the group that used 100 images and computer visualization, the analog method's accuracy was 7.23%. In order to accuracy increase, another test with 150 more distinct images was done, bringing a new result of 55.09%. The analysis time was considerably less when performed by the computational method. It was possible to conclude that the computational approach does not have the beads identification statistically similar to the analog way concerning the methodology used. Therefore, rejected H0. However, the directly proportional relationship of accuracy with the number of samples suggests that training with more various images can calibrate the algorithm.
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Basu, Debashis, Steve Green, Kaushik Das, Ron Janetzke und John Stamatakos. „Numerical Simulation of Surface Waves Generated by a Subaerial Landslide at Lituya Bay, Alaska“. In ASME 2009 28th International Conference on Ocean, Offshore and Arctic Engineering. ASMEDC, 2009. http://dx.doi.org/10.1115/omae2009-79595.
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This paper presents preliminary results of a computational study conducted to analyze the impulse waves generated by the subaerial landslide at Lituya Bay, Alaska. The volume of fluid (VOF) method is used to track the free surface and shoreline movements. The Renormalization Group (RNG) turbulence model and Detached Eddy Simulation (DES) multiscale model were used to simulate turbulence dissipation. The subaerial landslide is simulated using a sliding mass. Results from the two-dimensional (2-D) simulations are compared with results from a scaled-down experiment. The experiment is carried out at a 1:675 scale. In the experimental setup, the subaerial rockslide impact into the Gilbert Inlet, wave generation, propagation, and runup on the headland slope are considered in a geometrically undistorted Froude similarity model. The rockslide is simulated by a granular material driven by a pneumatic acceleration mechanism so that the impact characteristics can be controlled. Simulations are performed for different values of the landslide density to estimate the influence of slide deformation on the generated tsunami characteristics. Simulated results show the complex flow patterns in terms of the velocity field, shoreline evolution, and free surface profiles. The predicted wave runup height is in close agreement with both the observed wave runup height and that obtained from the scaled-down experimental model.
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Wang, Heyuan, Shun Li, Tengjiao Wang und Jiayi Zheng. „Hierarchical Adaptive Temporal-Relational Modeling for Stock Trend Prediction“. In Thirtieth International Joint Conference on Artificial Intelligence {IJCAI-21}. California: International Joint Conferences on Artificial Intelligence Organization, 2021. http://dx.doi.org/10.24963/ijcai.2021/508.
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Stock trend prediction is a challenging task due to the non-stationary dynamics and complex market dependencies. Existing methods usually regard each stock as isolated for prediction, or simply detect their correlations based on a fixed predefined graph structure. Genuinely, stock associations stem from diverse aspects, the underlying relation signals should be implicit in comprehensive graphs. On the other hand, the RNN network is mainly used to model stock historical data, while is hard to capture fine-granular volatility patterns implied in different time spans. In this paper, we propose a novel Hierarchical Adaptive Temporal-Relational Network (HATR) to characterize and predict stock evolutions. By stacking dilated causal convolutions and gating paths, short- and long-term transition features are gradually grasped from multi-scale local compositions of stock trading sequences. Particularly, a dual attention mechanism with Hawkes process and target-specific query is proposed to detect significant temporal points and scales conditioned on individual stock traits. Furthermore, we develop a multi-graph interaction module which consolidates prior domain knowledge and data-driven adaptive learning to capture interdependencies among stocks. All components are integrated seamlessly in a unified end-to-end framework. Experiments on three real-world stock market datasets validate the effectiveness of our model.
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Marquerie, G., A. Duperray, G. Uzan und R. Berthier. „BIOSYNTHETIC PATHWAYS OF THE PLATELET FIBRINOGEN RECEPTOR IN HUMAN MEGAKARYOCYTES“. In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642954.
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Interaction between cells and between cells and extracellular matrices are critical for a number of biological processes, including organ development, cell differenciation, cell motility, and the inimune' response. These interactions are mediated by a family of adhesion receptors that recognize short sequences such as Arg-Gly-Asp (RGD). These receptors share similar structural properties. They are heterodimers composed of a and B subunits and sometime express common epitopes. This suggests that the structural and functional relationship of these receptors may result from the transcription of related genes or may arise from cell specific post-transcriptional events. Thus, analysis of the biosynthesis and processing of these receptors would provide valuable insights into the molecular mechanism which control their expression at the surface,of different cells. Platelet membrane glycoprotein (GP) IIb-IIIa is a member of this receptor family. This protein is a non covalent heterodimer composed of two distinct polypeptides, Glib which consists of two subunits Ilba and IlbB (Mr = 116 kD, Mr = 25 kD) and GPIIIa (Mr = 100 kD, reduced). GPIIb-IIIa functions at site of platelet aggregation and serves as receptor for RGD containing factors including fibrinogen, fibronectin and von Willebrand factor. We report here on the investigation of the biosynthetic pathways of this RGD receptor in human megakaryocytes. High number of megakaryocytic cells from the megakaryoblastic stage to the polyploid mature megakaryocyte were obtained from liquid culture of cryopreserved leukocyte stem cell concentrates from patients with chronic myelogenous leukemia (CML). After sorting, using a FACS IV and indirect immunofluores-cent labeling with monoclonal antibodies anti-GPIIb-IIIa, 95 % of the cells in culture were of the megakaryocytic lineage. These megakarocytes represented an excellent tool to delineate at the molecular level events associated with the biosynthesis of GPIIb-IIIa.Metabolic labeling and pulse-chase experiments indicated that GPIIb and GPIIIa are synthesized from separate mRNA and that the two subunits of GPIIb derive from a common precursor. This was further confirmed by cell-free translation of megakaryocyte mRNA and the identification of separate cDNA containing sequences coding for the pro-GPIIb and for GPIIIa. These cDNA were isolated from a Xgt11 expression library constructed with purified megakaryocyte RNA, and were used to size the messengers coding for the two polypeptides. A single mRNA species of 3.9 kB was found to encode the pro-GPIIb, whereas two different mRNA species of 2.9 kB and 4. 1 kB were identified with the GPIIIa cDNA.The newly synthesized GPIIIa associates early with the pro-GPIIb in the rough endoplasmic reticulum. Examination of the glycosylation pathways with endoglycosidase H, tunicamycin and monensin indicated that high mannose oligosaccharides are added to the GPIIIa and pro-GPIIb polypeptide backbone. The pro-GPIIb is then processed with conversion of high mannose to the complex type carbohydrate, whereas GPIIIa remains endoH sensitive. Glycosylation of pro-GPIIb-IIIa and processing of oligosaccharides are prerequisite for proteolytic maturation of pro-GPIIb and the expression of the mature complex at the surface of the cell. Thus post-translational processing of GPIIb-IIIa requires an early assembly of the complex. This may have important implications in the maturation of megakaryocyte granules and in the molecular mechanism underlying the Glanzmann thrombastenic disease.
Berichte der Organisationen zum Thema "Granules RNP"
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Thembeka Ncube, Ayanda, und Antonio Bobet. Use of Recycled Asphalt. Purdue University, 2021. http://dx.doi.org/10.5703/1288284317316.
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The term Reclaimed Asphalt Pavement (RAP) is used to designate a material obtained from the removal of pavement materials. RAP is used across the US in multiple applications, largely on asphalt pavement layers. RAP can be described as a uniform granular non-plastic material, with a very low percentage of fines. It is formed by aggregate coated with a thin layer of asphalt. It is often used mixed with other granular materials. The addition of RAP to aggregates decreases the maximum dry unit weight of the mixture and decreases the optimum water content. It also increases the Resilient Modulus of the blend but decreases permeability. RAP can be used safely, as it does not pose any environmental concerns. The most important disadvantage of RAP is that it displays significant creep. It seems that this is caused by the presence of the asphaltic layer coating the aggregate. Creep increases with pressure and with temperature and decreases with the degree of compaction. Creep can be mitigated by either blending RAP with aggregate or by stabilization with chemical compounds. Fly ash and cement have shown to decrease, albeit not eliminate, the amount of creep. Mechanical stabilizing agents such as geotextiles may also be used.