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[
Autophagy,
2016]
Lysosomes are highly acidic cellular organelles traditionally viewed as sacs of enzymes involved in digesting extracellular or intracellular macromolecules for the regeneration of basic building blocks, cellular housekeeping, or pathogen degradation. Bound by a single lipid bilayer, lysosomes receive their substrates by fusing with endosomes or autophagosomes, or through specialized translocation mechanisms such as chaperone-mediated autophagy or microautophagy. Lysosomes degrade their substrates using up to 60 different soluble hydrolases and release their products either to the cytosol through poorly defined exporting and efflux mechanisms or to the extracellular space by fusing with the plasma membrane. However, it is becoming evident that the role of the lysosome in nutrient homeostasis goes beyond the disposal of waste or the recycling of building blocks. The lysosome is emerging as a signaling hub that can integrate and relay external and internal nutritional information to promote cellular and organismal homeostasis, as well as a major contributor to the processing of energy-dense molecules like glycogen and triglycerides. Here we describe the current knowledge of the nutrient signaling pathways governing lysosomal function, the role of the lysosome in nutrient mobilization, and how lysosomes signal other organelles, distant tissues, and even themselves to ensure energy homeostasis in spite of fluctuations in energy intake. At the same time, we highlight the value of genomics approaches to the past and future discoveries of how the lysosome simultaneously executes and controls cellular homeostasis.
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[
Anim Cells Syst (Seoul),
2012]
Food is important to any animal, and a large part of the behavioral repertoire is concerned with ensuring adequate nutrition. Two main nutritional sensations, hunger and satiety, produce opposite behaviors. Hungry animals seek food, increase exploratory behavior and continue feeding once they encounter food. Satiated animals decrease exploratory behavior, take rest, and stop feeding. The signals of hunger or satiety and their effects on physiology and behavior will depend not only on the animal's current nutritional status but also on its experience and the environment in which the animal evolved. In our novel, nutritionally rich environment, improper control of appetite contributes to diseases from anorexia to the current epidemic of obesity. Despite extraordinary recent advances, genetic contribution to appetite control is still poorly understood partly due to lack of simple genetic model systems. In this review, we will discuss current understanding of molecular and cellular mechanisms by which animals regulate food intake depending on their nutritional status. Then, focusing on relatively less known muscarinic and cGMP signals, we will discuss how the molecular and behavioral aspects of hunger and satiety are conserved in a simple invertebrate model system, C. elegans so as for us to use it to understand the genetics of appetite control.
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Sternberg PW, Davis P, Wang X, Ozersky P, Raciti D, Schedl T, Li Y, Stein L, Berriman M, Williams G, Kersey P, Wong JD, Chen WJ, Muller HM, Baran J, Howe K, Schindelman G, Wang D, Van Auken K, Spieth J, Lee R, Chan J, Grove C, Nakamura C, Done J, Harris TW, Tuli MA, Paulini M, Kishore R, Bieri T, Yook K, Cabunoc A, Hodgkin J
[
Nucleic Acids Res,
2014]
WormBase
(http://www.wormbase.org/) is a highly curated resource dedicated to supporting research using the model organism Caenorhabditis elegans. With an electronic history predating the World Wide Web, WormBase contains information ranging from the sequence and phenotype of individual alleles to genome-wide studies generated using next-generation sequencing technologies. In recent years, we have expanded the contents to include data on additional nematodes of agricultural and medical significance, bringing the knowledge of C. elegans to bear on these systems and providing support for underserved research communities. Manual curation of the primary literature remains a central focus of the WormBase project, providing users with reliable, up-to-date and highly cross-linked information. In this update, we describe efforts to organize the original atomized and highly contextualized curated data into integrated syntheses of discrete biological topics. Next, we discuss our experiences coping with the vast increase in available genome sequences made possible through next-generation sequencing platforms. Finally, we describe some of the features and tools of the new WormBase Web site that help users better find and explore data of interest.
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[
Anemia,
2012]
C. elegans provides an excellent model system for the study of the Fanconi Anemia (FA), one of the hallmarks of which is sensitivity to interstrand crosslinking agents. Central to our understanding of FA has been the investigation of DOG-1, the functional ortholog of the deadbox helicase FANCJ. Here we review the current understanding of the unique role of DOG-1 in maintaining stability of G-rich DNA in C. elegans and explore the question of why DOG-1 animals are crosslink sensitive. We propose a dynamic model in which noncovalently linked G-rich structures form and un-form in the presence of DOG-1. When DOG-1 is absent but crosslinking agents are present the G-rich structures are readily covalently crosslinked, resulting in increased crosslinks formation and thus giving increased crosslink sensitivity. In this interpretation DOG-1 is neither upstream nor downstream in the FA pathway, but works alongside it to limit the availability of crosslink substrates. This model reconciles the crosslink sensitivity observed in the absence of DOG-1 function with its unique role in maintaining G-Rich DNA and will help to formulate experiments to test this hypothesis.
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[
Elife,
2022]
Low complexity regions (LCRs) play a role in a variety of important biological processes, yet we lack a unified view of their sequences, features, relationships, and functions. Here, we use dotplots and dimensionality reduction to systematically define LCR type/copy relationships and create a map of LCR sequence space capable of integrating LCR features and functions. By defining LCR relationships across the proteome, we provide insight into how LCR type and copy number contribute to higher order assemblies, such as the importance of K-rich LCR copy number for assembly of the nucleolar protein RPA43 in vivo and in vitro. With LCR maps, we reveal the underlying structure of LCR sequence space, and relate differential occupancy in this space to the conservation and emergence of higher order assemblies, including the metazoan extracellular matrix and plant cell wall. Together, LCR relationships and maps uncover and identify scaffold-client relationships among E-rich LCR-containing proteins in the nucleolus, and revealed previously undescribed regions of LCR sequence space with signatures of higher order assemblies, including a teleost-specific T/H-rich sequence space. Thus, this unified view of LCRs enables discovery of how LCRs encode higher order assemblies of organisms.
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[
Cad Saude Publica
]
Lymphatic filariasis is caused by the nematodes Brugia malayi, Brugia timori, and Wuchereria bancrofti. The disease occurs in developing countries and is more frequent in urban areas. An estimated 4 billion people live in at-risk areas. In Brazil the endemic is caused by W. bancrofti and was first documented in 1878. It was first detected in Recife in 1952. Currently, Recife and Belem are the only cities in Brazil where the endemic is considered a public health problem. The objectives of this study are to discuss the epidemiology and control of lymphatic filariasis and review its control since it was reported by Rachou in 1952. We analyze the "campanhista" or campaign-oriented model employed by the Sucam/FNS institutional program, as well as several proposed innovative methods. We present available strategies for control of filariasis through primary health care services, decentralization to the local level (or "municipalization"), and community-based health programs.
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[
Tissue Cell,
1995]
At ultrastructural level, the Caenorhabditis elegans (C. elegans) cuticle shows the presence of well-defined layers, one of them is a membrane-like structure designated as epicuticle, always present on the outermost surface of nematodes. Freeze-fracture replicas revealed the existance of two faces of the epicuticle: a inner face containing numerous particles, and a almost smooth outer face. Deep etching replicas confirmed the existance of these two faces of the epicuticle showing in some replicas two particle populations on the outer face of L4 and adult forms of C. elegans. Also a previously unrecognized structure was noted in the cuticle of C. elegans, a matrix composed by network of globular and filamentous structures, leaving in between them spaces, which probably are occupied by water in the living adult and L4 larvae specimen. This network demonstrates either a compact nature or loose nature according to their cuticle location. Deep etching replicas of the adults nematode revealed large spaces between the cortical and basal layers which are regularly interrupted by struts connecting each other by fibers in a particular arrangement.
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[
J Genet,
2018]
The inappropriate genetic expansion of various repetitive DNA sequences underlies over 20 distinct inherited diseases. The genetic context of these repeats in exons, introns and untranslated regions has played a major role in thinking about the mechanisms by which various repeat expansions might cause disease. Repeat expansions in exons are thought to give rise to expanded toxic protein repeats (i.e. polyQ). Repeat expansions in introns and UTRs (i.e. FXTAS) are thought to produce aberrant repeat-bearing RNAs that interact with and sequester a wide variety of essential proteins, resulting in cellular toxicity. However, a new phenomenon termed 'repeat-associated nonAUG dependent (RAN) translation' paints a new and unifying picture of how distinct repeat expansion-bearing RNAs might act as substrates for this noncanonical form of translation, leading to the production of a wide range of repeat sequence-specific-encoded toxic proteins. Here, we review how the model system <i>Caenorhabditis elegans</i> has been utilized to model many repeat disorders and discuss how RAN translation could be a previously unappreciated contributor to the toxicity associated with these different models.
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Rondeau G, Colon-Ramos DA, Gandler W, Bokinsky A, Kumar A, McCreedy E, Christensen R, McAuliffe M, Wu Y, Shroff H, Bao Z, Chandris P
[
Nat Protoc,
2014]
We describe the construction and use of a compact dual-view inverted selective plane illumination microscope (diSPIM) for time-lapse volumetric (4D) imaging of living samples at subcellular resolution. Our protocol enables a biologist with some prior microscopy experience to assemble a diSPIM from commercially available parts, to align optics and test system performance, to prepare samples, and to control hardware and data processing with our software. Unlike existing light sheet microscopy protocols, our method does not require the sample to be embedded in agarose; instead, samples are prepared conventionally on glass coverslips. Tissue culture cells and Caenorhabditis elegans embryos are used as examples in this protocol; successful implementation of the protocol results in isotropic resolution and acquisition speeds up to several volumes per s on these samples. Assembling and verifying diSPIM performance takes 6 d, sample preparation and data acquisition take up to 5 d and postprocessing takes 3-8 h, depending on the size of the data.
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[
Biochem Soc Trans,
2021]
The simple notion 'infection causes an immune response' is being progressively refined as it becomes clear that immune mechanisms cannot be understood in isolation, but need to be considered in a more global context with other cellular and physiological processes. In part, this reflects the deployment by pathogens of virulence factors that target diverse cellular processes, such as translation or mitochondrial respiration, often with great molecular specificity. It also reflects molecular cross-talk between a broad range of host signalling pathways. Studies with the model animal C. elegans have uncovered a range of examples wherein innate immune responses are intimately connected with different homeostatic mechanisms, and can influence reproduction, ageing and neurodegeneration, as well as various other aspects of its biology. Here we provide a short overview of a number of such connections, highlighting recent discoveries that further the construction of a fully integrated view of innate immunity.