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Pest Manag Sci,
2001]
Chitin is an abundant biologically important aminopolysaccharide composed of N-acetyl-D-glucosamine units. Individual polymers, which are synthesized intracellularly by chitin synthase (CS), a membrane-bound glycosyl transferase, are translocated across the plasma membrane and coalesce to form rigid crystallites. These crystallites, inter alia, are integral parts of septa and cell walls in yeast and filamentous fungi, respectively, and of cuticles in invertebrates, notably crustaceans and insects. Despite decades of intensive research, many events associated with the complexity of chitin formation and deposition are still obscure, or only partially understood. The list includes the hormonal control of CS at the transcriptional and translational levels as well as the post-translational CS packaging; trafficking and guidance of CS clusters to proper sites in the cells and their intricate insertion into the plasma membranes; activation of the catalytic step and its control or modulation; and translocation of chitin chains across cell membranes, their orientation, fibrillogenesis and association with other extracellular structural components such as polysaccharides (fungi) and cuticular proteins (insects). Also the precise biochemical lesions inflicted by CS inhibitors, such as the acylurea insect growth regulators, are largely unclear. The recent isolation and sequencing of insect CS genes should help in elucidating various aspects of chitin biochemistry and inhibition. In particular, the large number of transmembrane segments, characteristic of the insect CS, are speculated to be involved in chitin translocation and are expected to shed light on the mode of action of acylurea insecticides.
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Front Mol Biosci,
2023]
The protein homeostasis (proteostasis) network is a nexus of molecular mechanisms that act in concert to maintain the integrity of the proteome and ensure proper cellular and organismal functionality. Early in life the proteostasis network efficiently preserves the functionality of the proteome, however, as the organism ages, or due to mutations or environmental insults, subsets of inherently unstable proteins misfold and form insoluble aggregates that accrue within the cell. These aberrant protein aggregates jeopardize cellular viability and, in some cases, underlie the development of devastating illnesses. Hence, the accumulation of protein aggregates activates different nodes of the proteostasis network that refold aberrantly folded polypeptides, or direct them for degradation. The proteostasis network apparently functions within the cell, however, a myriad of studies indicate that this nexus of mechanisms is regulated at the organismal level by signaling pathways. It was also discovered that the proteostasis network differentially responds to dissimilar proteotoxic insults by tailoring its response according to the specific challenge that cells encounter. In this mini-review, we delineate the proteostasis-regulating neuronal mechanisms, describe the indications that the proteostasis network differentially responds to distinct proteotoxic challenges, and highlight possible future clinical prospects of these insights.
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Traffic,
2012]
Maintenance of proteome integrity (proteostasis) is essential for cellular and organismal survival. Various cellular mechanisms work to preserve proteostasis by ensuring correct protein maturation and efficient degradation of misfolded and damaged proteins. Despite this cellular effort, under certain circumstances subsets of aggregation-prone proteins escape the quality control surveillance, accumulate within the cell and form insoluble aggregates that can lead to the development of disorders including late-onset neurodegenerative diseases. Cells respond to the appearance of insoluble aggregates by actively transporting them to designated deposition sites where they often undergo degradation. Although several protein aggregate deposition sites have been described and extensively studied, key questions regarding their biological roles and how they are affected by aging remained unanswered. Here we review the recent advances in the field, describe the different subtypes of these cellular compartments and outline the evidence that these structures change their properties over time. Finally, we propose models to explain the possible mechanistic links between aggregate deposition sites, neurodegenerative disorders and the aging process.
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Ageing Res Rev,
2013]
We have conducted a comprehensive literature review regarding the effect of vitamin E on lifespan in model organisms including single-cell organisms, rotifers, Caenorhabditis elegans, Drosophila melanogaster and laboratory rodents. We searched Pubmed and ISI Web of knowledge for studies up to 2011 using the terms "tocopherols", "tocotrienols", "lifespan" and "longevity" in the above mentioned model organisms. Twenty-four studies were included in the final analysis. While some studies suggest an increase in lifespan due to vitamin E, other studies did not observe any vitamin E-mediated changes in lifespan in model organisms. Furthermore there are several studies reporting a decrease in lifespan in response to vitamin E supplementation. Different outcomes between studies may be partly related to species-specific differences, differences in vitamin E concentrations and the vitamin E congeners administered. The findings of our literature review suggest that there is no consistent beneficial effect of vitamin E on lifespan in model organisms which is consistent with reports in human intervention studies.
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Hermann, Editeurs des Sciences et des Arts. Paris, France.,
2002]
L'espce Caenorhabditis elegans fut dcrite en 1900 Alger par E. Maupas, qui s'intressait son mode de reproduction hermaphrodite. Plus tard, vers le milieu du vingtime sicle, V. Nigon et ses collaboratuers Lyon tudirent les reorganizations cellulaires accompagnant la fecundation et les premiers clivages. J. Brun isola les preiers mutants morpholgiques.
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Parasite,
1994]
Two genes coding for cuticlin components of Coenorhabditis elegans have been cloned and their structure is described. Recombinant proteins have been produced in E. coli and antibodies raised against them. Nucleic acid and specific antibodies are being used to isolate the homologues from the parasitic species Ascaris lumbricoides and Brugia pahangi.
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Seminars in Developmental Biology,
1994]
Gastrulation in Caenorhabditis elegans has been described by following the movements of individual nuclei in living embryos by Nomarski microscopy. Gastrulation starts in the 26-cell stage when the two gut precursors, Ea and Ep, move into the blastocoele. The migration of Ea and Ep does not depend on interactions with specific neighboring cells and appears to rely on the earlier fate specification of the E lineage. In particular, the long cell cycle length of Ea and Ep appears important for gastrulation. Later in embryogenesis, the precursors to the germline, muscle and pharynx join the E descendants in the interior. As in other organisms, the movement of gastrulation permit novel cell contacts that are important for the specification of certain cell fates.
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Wiley Interdiscip Rev Dev Biol,
2013]
The transcriptional regulatory hierarchy that controls development of the Caenorhabditis elegans endoderm begins with the maternally provided SKN-1 transcription factor, which determines the fate of the EMS blastomere of the four-cell embryo. EMS divides to produce the posterior E blastomere (the clonal progenitor of the intestine) and the anterior MS blastomere, a major contributor to mesoderm. This segregation of lineage fates is controlled by an intercellular signal from the neighboring P2 blastomere and centers on the HMG protein POP-1. POP-1 would normally repress the endoderm program in both E and MS but two consequences of the P2-to-EMS signal are that POP-1 is exported from the E-cell nucleus and the remaining POP-1 is converted to an endoderm activator by complexing with SYS-1, a highly diverged -catenin. In the single E cell, a pair of genes encoding small redundant GATA-type transcription factors, END-1 and END-3, are transcribed under the combined control of SKN-1, the POP-1/SYS-1 complex, as well as the redundant pair of MED-1/2 GATA factors, themselves direct zygotic targets of SKN-1 in the EMS cell. With the expression of END-1/END-3, the endoderm is specified. END-1 and END-3 then activate transcription of a further set of GATA-type transcription factors that drive intestine differentiation and function. One of these factors, ELT-2, appears predominant; a second factor, ELT-7, is partially redundant with ELT-2. The mature intestine expresses several thousand genes, apparently all controlled, at least in part, by cis-acting GATA-type motifs.
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Curr Opin Chem Biol,
2014]
The site specific, co-translational introduction of unnatural amino acids into proteins produced in cells has been facilitated by the development of the pyrrolysyl-tRNA synthetase/tRNACUA pair. This pair can now be used to direct the site-specific incorporation of designer amino acids in E. coli, yeast, mammalian cells, and animals (the worm, C. elegans and the fly, D. melanogaster). Developments in encoding components of rapid bioorthogonal reactions are providing new opportunities for labelling and visualising proteins. A new method called stochastic orthogonal recoding of translation with chemoselective modification (SORT-M) leverages advances in genetic code expansion and bioorthogonal chemistry to label proteomes with diverse chemistry at diverse codons in E. coli, mammalian cells, and in spatially and temporally defined sets of cells in the fly. Proteomes in targeted sets of cells have been visualised by SORT-M and proteins in targeted cells have been identified by SORT-M.
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Mol Reprod Dev,
2015]
Developmental robustness is the ability of an embryo to develop normally despite many sources of variation, from differences in the environment to stochastic cell-to-cell differences in gene expression. The nematode Caenorhabditis elegans exhibits an additional level of robustness: Unlike most other animals, the embryonic pattern of cell divisions is nearly identical from animal to animal. The endoderm (gut) lineage is an ideal model for studying such robustness as the juvenile gut has a simple anatomy, consisting of 20 cells that are derived from a single cell, E, and the gene regulatory network that controls E specification shares features with developmental regulatory networks in many other systems, including genetic redundancy, parallel pathways, and feed-forward loops. Early studies were initially concerned with identifying the genes in the network, whereas recent work has focused on understanding how the endoderm produces a robust developmental output in the face of many sources of variation. Genetic control exists at three levels of endoderm development: Progenitor specification, cell divisions within the developing gut, and maintenance of gut differentiation. Recent findings show that specification genes regulate all three of these aspects of gut development, and that mutant embryos can experience a "partial" specification state in which some, but not all, E descendants adopt a gut fate. Ongoing studies using newer quantitative and genome-wide methods promise further insights into how developmental gene-regulatory networks buffer variation. Mol. Reprod. Dev. 2015. 2015 Wiley Periodicals, Inc.