Modifiers of solid RNP granules control normal RNP dynamics and mRNA activity in early development

Ribonucleoproteins (RNPs) often coassemble into supramolecular bodies with regulated dynamics. The factors controlling RNP bodies and connections to RNA regulation are unclear. During Caenorhabditis elegans oogenesis, cytoplasmic RNPs can transition among diffuse, liquid, and solid states linked to mRNA regulation. Loss of CGH-1/Ddx6 RNA helicase generates solid granules that are sensitive to mRNA regulators. Here, we identified 66 modifiers of RNP solids induced by cgh-1 mutation. A majority of genes promote or suppress normal RNP body assembly, dynamics, or metabolism. Surprisingly, polyadenylation factors promote RNP coassembly in vivo, suggesting new functions of poly(A) tail regulation in RNP dynamics. Many genes carry polyglutatmine (polyQ) motifs or modulate polyQ aggregation, indicating possible connections with neurodegenerative disorders induced by CAG/polyQ expansion. Several RNP body regulators repress translation of mRNA subsets, suggesting that mRNAs are repressed by multiple mechanisms. Collectively, these findings suggest new pathways of RNP modification that control large-scale coassembly and mRNA activity during development.

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Caenorhabditis elegans, a Host to Investigate the Probiotic Properties of Beneficial Microorganisms

Frontiers in Nutrition ◽

10.3389/fnut.2020.00135 ◽

2020 ◽

Vol 7 ◽

Author(s):

Cyril Poupet ◽

Christophe Chassard ◽

Adrien Nivoliez ◽

Stéphanie Bornes

Keyword(s):

Caenorhabditis Elegans ◽

High Throughput Screening ◽

Large Scale ◽

Molecular Mechanisms ◽

Probiotic Properties ◽

C Elegans ◽

Probiotic Potential ◽

Challenges And Opportunities ◽

Future Challenges

Caenorhabditis elegans, a non-parasitic nematode emerges as a relevant and powerful candidate as an in vivo model for microorganisms-microorganisms and microorganisms-host interactions studies. Experiments have demonstrated the probiotic potential of bacteria since they can provide to the worm a longer lifespan, an increased resistance to pathogens and to oxidative or heat stresses. Probiotics are used to prevent or treat microbiota dysbiosis and associated pathologies but the molecular mechanisms underlying their capacities are still unknown. Beyond safety and healthy aspects of probiotics, C. elegans represents a powerful way to design large-scale studies to explore transkingdom interactions and to solve questioning about the molecular aspect of these interactions. Future challenges and opportunities would be to validate C. elegans as an in vivo tool for high-throughput screening of microorganisms for their potential probiotic use on human health and to enlarge the panels of microorganisms studied as well as the human diseases investigated.

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Elevated CO2 regulates the Wnt signaling pathway in mammals, Drosophila melanogaster and Caenorhabditis elegans

Scientific Reports ◽

10.1038/s41598-019-54683-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Masahiko Shigemura ◽

Emilia Lecuona ◽

Martín Angulo ◽

Laura A. Dada ◽

Melanie B. Edwards ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Caenorhabditis Elegans ◽

Wnt Signaling ◽

Large Scale ◽

Wnt Pathway ◽

Wnt Signaling Pathway ◽

Secondary Analysis ◽

Evolutionarily Conserved ◽

Integrated Or

AbstractCarbon dioxide (CO2) is sensed by cells and can trigger signals to modify gene expression in different tissues leading to changes in organismal functions. Despite accumulating evidence that several pathways in various organisms are responsive to CO2 elevation (hypercapnia), it has yet to be elucidated how hypercapnia activates genes and signaling pathways, or whether they interact, are integrated, or are conserved across species. Here, we performed a large-scale transcriptomic study to explore the interaction/integration/conservation of hypercapnia-induced genomic responses in mammals (mice and humans) as well as invertebrates (Caenorhabditis elegans and Drosophila melanogaster). We found that hypercapnia activated genes that regulate Wnt signaling in mouse lungs and skeletal muscles in vivo and in several cell lines of different tissue origin. Hypercapnia-responsive Wnt pathway homologues were similarly observed in secondary analysis of available transcriptomic datasets of hypercapnia in a human bronchial cell line, flies and nematodes. Our data suggest the evolutionarily conserved role of high CO2 in regulating Wnt pathway genes.

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Whole integration of neural connectomics, dynamics and bio-mechanics for identification of behavioral sensorimotor pathways in Caenorhabditis elegans

10.1101/724328 ◽

2019 ◽

Author(s):

Jimin Kim ◽

Julia A. Santos ◽

Mark J. Alkema ◽

Eli Shlizerman

Keyword(s):

Nervous System ◽

Caenorhabditis Elegans ◽

Large Scale ◽

Neural Circuits ◽

The Body ◽

Neural Dynamics ◽

Neural Pathways ◽

Computational Approaches ◽

External Forces

AbstractThe ability to fully discern how the brain orchestrates behavior requires the development of successful computational approaches to integrate and inform in-vivo investigations of the nervous system. To effectively assist with such investigations, computational approaches must be generic, scalable and unbiased. We propose such a comprehensive framework to investigate the interaction between the nervous system and the body for the nematode Caenorhabditis elegans (C. elegans). Specifically, we introduce a model that computationally emulates the activity of the complete somatic nervous system and its response to stimuli. The model builds upon the full anatomical wiring diagram, the connectome, and integrates it with additional layers including intra-cellular and extra-cellular bio-physically relevant neural dynamics, layers translating neural activity to muscle forces and muscle impulses to body postures. In addition, it implements inverse integration which modulates neural dynamics according to external forces on the body. We validate the model by in-silico injection of currents into sensory- and inter-neurons known to play a role in locomotion behaviors (e.g. posterior/anterior touch) and by applying external forces on the body. We are able to generate characteristic baseline locomotion behaviors (forward and backward movements). Inclusion of proprioceptive feedback, implemented through inverse integration, shows that feedback can entrain and sustain movements initiated by neural or mechanical triggers. We further apply neural stimuli, experimentally known to modulate locomotion, and show that our model supports natural behavioral responses such as turns, reversals and avoidance. The proposed model can be utilized to infer neural circuits involved in sensorimotor behavior. For this purpose, we develop large-scale computational ablation approaches such as (i) ablation survey and (ii) conditional ablation. Our results show how an ablation survey can identify neurons required for a ventral turning behavior. We also show how conditional ablation can identify alternative novel neural pathways, e.g. propose neurons which facilitate steering behavior towards olfactory attractants. The outcomes of our study show that the framework can be utilized to identify neural circuits, which control, mediate and generate natural behavior.

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Maternal mRNAs are regulated by diverse P body–related mRNP granules during early Caenorhabditis elegans development

The Journal of Cell Biology ◽

10.1083/jcb.200802128 ◽

2008 ◽

Vol 182 (3) ◽

pp. 559-572 ◽

Cited By ~ 72

Author(s):

Scott L. Noble ◽

Brittany L. Allen ◽

Lai Kuan Goh ◽

Kristen Nordick ◽

Thomas C. Evans

Keyword(s):

Caenorhabditis Elegans ◽

Rna Binding ◽

Germ Line ◽

Processing Bodies ◽

Body Protein ◽

P Bodies ◽

Granule Morphology ◽

Maternal Mrnas ◽

Rnp Granules

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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Insights into amyloid disease from fly models

Essays in Biochemistry ◽

10.1042/bse0560069 ◽

2014 ◽

Vol 56 ◽

pp. 69-83 ◽

Cited By ~ 1

Author(s):

Ko-Fan Chen ◽

Damian C. Crowther

Keyword(s):

Drosophila Melanogaster ◽

Neurodegenerative Disorders ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Disease Pathogenesis ◽

Amyloid Aggregates ◽

Aβ Amyloid ◽

Polypeptide Chains ◽

Amyloid Diseases

The formation of amyloid aggregates is a feature of most, if not all, polypeptide chains. In vivo modelling of this process has been undertaken in the fruitfly Drosophila melanogaster with remarkable success. Models of both neurological and systemic amyloid diseases have been generated and have informed our understanding of disease pathogenesis in two main ways. First, the toxic amyloid species have been at least partially characterized, for example in the case of the Aβ (amyloid β-peptide) associated with Alzheimer's disease. Secondly, the genetic underpinning of model disease-linked phenotypes has been characterized for a number of neurodegenerative disorders. The current challenge is to integrate our understanding of disease-linked processes in the fly with our growing knowledge of human disease, for the benefit of patients.

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Purification of the Antihemophilic Factor by Gel Filtration on Agarose

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651394 ◽

1969 ◽

Vol 22 (03) ◽

pp. 577-583 ◽

Cited By ~ 3

Author(s):

M.M.P Paulssen ◽

A.C.M.G.B Wouterlood ◽

H.L.M.A Scheffers

Keyword(s):

Factor Viii ◽

Plasma Proteins ◽

Large Scale ◽

Gel Filtration ◽

Large Scale Preparation ◽

Scale Preparation ◽

Antihemophilic Factor

SummaryFactor VIII can be isolated from plasma proteins, including fibrinogen by chromatography on agarose. The best results were obtained with Sepharose 6B. Large scale preparation is also possible when cryoprecipitate is separated by chromatography. In most fractions containing factor VIII a turbidity is observed which may be due to the presence of chylomicrons.The purified factor VIII was active in vivo as well as in vitro.

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The Effect of Active Site-inhibited Factor VIIa on Tissue Factor-initiated Coagulation Using Platelets before and after Aspirin Administration

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657715 ◽

1997 ◽

Vol 78 (04) ◽

pp. 1202-1208 ◽

Cited By ~ 18

Author(s):

Marianne Kjalke ◽

Julie A Oliver ◽

Dougald M Monroe ◽

Maureane Hoffman ◽

Mirella Ezban ◽

...

Keyword(s):

Tissue Factor ◽

Active Site ◽

Large Scale ◽

Thrombin Generation ◽

Factor Viia ◽

Dependent Manner ◽

Antithrombotic Agent ◽

Before And After ◽

Ic50 Values

SummaryActive site-inactivated factor VIIa has potential as an antithrombotic agent. The effects of D-Phe-L-Phe-L-Arg-chloromethyl ketone-treated factor VIla (FFR-FVIIa) were evaluated in a cell-based system mimicking in vivo initiation of coagulation. FFR-FVIIa inhibited platelet activation (as measured by expression of P-selectin) and subsequent large-scale thrombin generation in a dose-dependent manner with IC50 values of 1.4 ± 0.8 nM (n = 8) and 0.9 ± 0.7 nM (n = 7), respectively. Kd for factor VIIa binding to monocytes ki for FFR-FVIIa competing with factor VIIa were similar (11.4 ± 0.8 pM and 10.6 ± 1.1 pM, respectively), showing that FFR-FVIIa binds to tissue factor in the tenase complex with the same affinity as factor VIIa. Using platelets from volunteers before and after ingestion of aspirin (1.3 g), there were no significant differences in the IC50 values of FFR-FVIIa [after aspirin ingestion, the IC50 values were 1.7 ± 0.9 nM (n = 8) for P-selectin expression, p = 0.37, and 1.4 ± 1.3 nM (n = 7) for thrombin generation, p = 0.38]. This shows that aspirin treatment of platelets does not influence the inhibition of tissue factor-initiated coagulation by FFR-FVIIa, probably because thrombin activation of platelets is not entirely dependent upon expression of thromboxane A2.

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