710 results
Search Results
2. Metformin treatment of diverse Caenorhabditis species reveals the importance of genetic background in longevity and healthspan extension outcomes
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Gordon J. Lithgow, Patrick C. Phillips, Mackenzie L Morshead, Brian Onken, June Hope, Elizabeth A. Chao, Erik Johnson, David Hall, Stephen A. Banse, Christine A Sedore, Esteban Chen, Phu Huynh, Todd Plummer, Anna C. Foulger, Suzhen Guo, Eleanor Grace Jones, Max Guo, Monica Driscoll, Delaney Inman, Anna L. Coleman-Hulbert, Dipa Bhaumik, Jian Xue, and Girish Harinath
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Aging ,endocrine system diseases ,medicine.drug_class ,media_common.quotation_subject ,Longevity ,healthspan ,Disease ,biguanide ,Bioinformatics ,Genetic variation ,medicine ,Animals ,Humans ,Hypoglycemic Agents ,Genetic variability ,Caenorhabditis elegans ,media_common ,Original Paper ,biology ,Biguanide ,digestive, oral, and skin physiology ,nutritional and metabolic diseases ,genetic diversity ,Cell Biology ,biology.organism_classification ,Original Papers ,Metformin ,Caenorhabditis ,Clinical trial ,Treatment Outcome ,anti‐diabetes drug ,medicine.drug - Abstract
Metformin, the most commonly prescribed anti‐diabetes medication, has multiple reported health benefits, including lowering the risks of cardiovascular disease and cancer, improving cognitive function with age, extending survival in diabetic patients, and, in several animal models, promoting youthful physiology and lifespan. Due to its longevity and health effects, metformin is now the focus of the first proposed clinical trial of an anti‐aging drug—the Targeting Aging with Metformin (TAME) program. Genetic variation will likely influence outcomes when studying metformin health effects in human populations. To test for metformin impact in diverse genetic backgrounds, we measured lifespan and healthspan effects of metformin treatment in three Caenorhabditis species representing genetic variability greater than that between mice and humans. We show that metformin increases median survival in three C. elegans strains, but not in C. briggsae and C. tropicalis strains. In C. briggsae, metformin either has no impact on survival or decreases lifespan. In C. tropicalis, metformin decreases median survival in a dose‐dependent manner. We show that metformin prolongs the period of youthful vigor in all C. elegans strains and in two C. briggsae strains, but that metformin has a negative impact on the locomotion of C. tropicalis strains. Our data demonstrate that metformin can be a robust promoter of healthy aging across different genetic backgrounds, but that genetic variation can determine whether metformin has positive, neutral, or negative lifespan/healthspan impact. These results underscore the importance of tailoring treatment to individuals when testing for metformin health benefits in diverse human populations., We monitored metformin impact in nine strains spanning three Caenorhabditis species that feature a nucleotide diversity greater than that between mouse and humans. We find that metformin promotes healthy aging across diverse genetic backgrounds, but that genetic background can determine whether metformin has a positive, neutral, or negative effect. Data demonstrate the potential broad reach of metformin but also underscore that individual genetics will underlie efficacy over a diverse test set.
- Published
- 2021
3. G protein–coupled receptor kinase 2 modifies the ability of Caenorhabditis elegans to survive oxidative stress
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Ngoc S Hoang, Magdalena Cybulska, Johnathen F Woodward, Nasma Awada, Selina Crivello, Tina M. Nguyen, Christopher H. So, Stacy A. Henry, Mary Nguyen, Nazgol Emami, and Tajinder Badial
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0301 basic medicine ,G-Protein-Coupled Receptor Kinase 2 ,Serotonin reuptake inhibitor ,Longevity ,medicine.disease_cause ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Loss of Function Mutation ,medicine ,Animals ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,Original Paper ,G protein-coupled receptor kinase ,biology ,Chemistry ,Kinase ,Beta adrenergic receptor kinase ,Cell Biology ,biology.organism_classification ,Cell biology ,Caenorhabditis ,Oxidative Stress ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,Signal transduction ,Oxidative stress - Abstract
Survival and adaptation to oxidative stress is important for many organisms, and these occur through the activation of many different signaling pathways. In this report, we showed that Caenorhabditis (C.) elegans G protein-coupled receptor kinases modified the ability of the organism to resist oxidative stress. In acute oxidative stress studies using juglone, loss-of-function grk-2 mutants were more resistant to oxidative stress compared with loss-of-function grk-1 mutants and the wild-type N2 animals. This effect was Ce-AKT-1 dependent, suggesting that Ce-GRK2 adjusted C. elegans oxidative stress resistance through the IGF/insulin-like signaling (IIS) pathway. Treating C. elegans with a GRK2 inhibitor, the selective serotonin reuptake inhibitor paroxetine, resulted in increased acute oxidative stress resistance compared with another selective serotonin reuptake inhibitor, fluoxetine. In chronic oxidative stress studies with paraquat, both grk-1 and grk-2 mutants had longer lifespan compared with the wild-type N2 animals in stress. In summary, this research showed the importance of both GRKs, especially GRK2, in modifying oxidative stress resistance.
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- 2020
4. Experimentally induced intrasexual mating competition and sex‐specific evolution in female and male nematodes
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Elisabeth Bolund, Pilar Puimedon Moreno, Josefine Stångberg, and Elina Immonen
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Male ,0106 biological sciences ,0301 basic medicine ,life history ,Competitive Behavior ,media_common.quotation_subject ,Zoology ,Intralocus sexual conflict ,010603 evolutionary biology ,01 natural sciences ,Competition (biology) ,caenorhabditis remanei ,Life history theory ,Evolutionsbiologi ,Sexual Behavior, Animal ,03 medical and health sciences ,intralocus sexual conflict ,Animals ,Sex Ratio ,trade‐off ,experimental evolution ,Selection, Genetic ,Mating ,Life History Traits ,Ecology, Evolution, Behavior and Systematics ,media_common ,trade-off ,Evolutionary Biology ,biology ,Caenorhabditis remanei ,biology.organism_classification ,Research Papers ,Sexual dimorphism ,030104 developmental biology ,Sexual selection ,sexual dimorphism ,Caenorhabditis ,Female ,Genetic Fitness ,Sex ratio ,Research Paper - Abstract
Sexual dimorphism in life history traits and their trade‐offs is widespread among sexually reproducing animals and is strongly influenced by the differences in reproductive strategies between the sexes. We investigated how intrasexual competition influenced specific life history traits, important to fitness and their trade‐offs in the outcrossing nematode Caenorhabditis remanei. Here, we altered the strength of sex‐specific selection through experimental evolution with increased potential for intrasexual competition by skewing the adult sex ratio towards either females or males (1:10 or 10:1) over 30 generations and subsequently measured the phenotypic response to selection in three traits related to fitness: body size, fecundity and tolerance to heat stress. We observed a greater evolutionary change in females than males for body size and peak fitness, suggesting that females may experience stronger net selection and potentially harbour higher amounts of standing genetic variance compared to males. Our study highlights the importance of investigating direct and indirect effects of intrasexual competition in both sexes in order to capture sex‐specific responses and understand the evolution of sexual dimorphism in traits expressed by both sexes., Sex‐specific evolution of peak fitness in response to skewed sex ratios, with the ancestral (ANC) population compared to female‐biased (FB) and male‐biased (MB) treatment populations after 30 generations of experimental evolution in Caenorhabditis remanei. We found a significant interaction between sex and treatment, indicating sex‐specific evolutionary responses in peak fitness (λpeak). Thus, the increased potential for intrasexual competition in the common sex in each treatment leads to opposite responses in the two sexes.
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- 2020
5. In vitro and in vivo defensive effect of probiotic LAB against Pseudomonas aeruginosa using Caenorhabditis elegans model
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Se-Hun Kim, Jung-Gu Choi, Ramachandran Chelliah, Shuai Wei, Deog-Hwan Oh, Sudha Rani Ramakrishnan, Su-bin Hwang, Byung-Jae Park, and Eric Banan-Mwine Daliri
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0301 basic medicine ,Microbiology (medical) ,Longevity ,030106 microbiology ,Immunology ,Gut colonization ,Biology ,medicine.disease_cause ,Microbiology ,lcsh:Infectious and parasitic diseases ,law.invention ,03 medical and health sciences ,Probiotic ,chemistry.chemical_compound ,Lactobacillales ,law ,In vivo ,Pseudomonas aeruginosa ( PA 14) ,medicine ,Animals ,lcsh:RC109-216 ,Pediococcus ,Caenorhabditis elegans ,Pseudomonas aeruginosa ,Chemotaxis ,Probiotics ,food and beverages ,Korean soybean paste (KSP) ,biology.organism_classification ,Pepsin A ,Anti-Bacterial Agents ,Lactic acid ,Gastrointestinal Tract ,Intestines ,Caenorhabditis ,Infectious Diseases ,chemistry ,Microbial Interactions ,Parasitology ,Pseudomonas aeruginosa(PA 14) ,Fermented Foods ,Caenorhabditis elegans (C. elegans) ,Bacteria ,Research Paper - Abstract
This study aimed to investigate in vitro and in vivo the probiotic characteristics of lactic acid bacteria (LAB) isolated from Korean traditional fermented foods. Caenorhabditis elegans (C. elegans) was used for analytical assays of fertility, chemotaxis, life-span, worm-killing and bacterial colonization in the intestinal lumen of the worm. All 35 strains of LAB reduced fertility and slowed development in the worms. The worm-killing assay showed that LAB significantly increased the lifespan (P
- Published
- 2018
6. Comparative mitochondrial genomics reveals a possible role of a recent duplication of NADH dehydrogenase subunit 5 in gene regulation
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Bi Y, Ho Vws, Runsheng Li, Ren X, Zhongying Zhao, and Ding Q
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0301 basic medicine ,Male ,Mitochondrial DNA ,Genomics ,Genome ,DNA, Mitochondrial ,Evolution, Molecular ,03 medical and health sciences ,RNA, Transfer ,Gene Duplication ,Gene duplication ,Genetics ,Animals ,non-coding region (NCR) ,Molecular Biology ,Gene ,mitochondrial transcriptome ,biology ,NADH dehydrogenase ,NADH Dehydrogenase ,General Medicine ,Full Papers ,biology.organism_classification ,Caenorhabditis ,Protein Subunits ,030104 developmental biology ,Gene Expression Regulation ,mitochondrial genome ,Transfer RNA ,Genome, Mitochondrial ,biology.protein ,Female ,Software - Abstract
Mitochondrial genome (mtDNA) carries not only well-conserved protein coding, tRNA and rRNA genes, but also highly variable non-coding regions (NCRs). However, the NCRs show poor conservation across species, making their function and evolution elusive. Identification and functional characterization of NCRs across species would be critical for addressing these questions. To this end, we devised a computational pipeline and performed de novo assembly and annotation of mtDNA from 19 Caenorhabditis species using next-generation sequencing (NGS) data. The mtDNAs for 14 out of the 19 species are reported for the first time. Comparison of the 19 genomes reveals species-specific sampling of partial displacement-loop (D-loop) sequence as a novel NCR inserted into a unique tRNA cluster, suggesting an important role of the D-loop and the tRNA cluster in shaping NCR evolution. Intriguingly, RNA-Seq analysis suggests that a novel NCR resulting from a recent duplication of NADH dehydrogenase subunit 5 (ND5) could be utilized as a 3′ UTR for up-regulation of its upstream gene. The expression analysis shows a species- and sex-specific expression of mitochondrial genes encoded by mtDNA and nucleus, respectively. Our analyses provide important insights into the function and evolution of mitochondrial NCRs and pave the way for further studying the function and evolution of mitochondrial genome.
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- 2018
7. Transcriptomic analyses reveal groups of co-expressed, syntenic lncRNAs in four species of the genus Caenorhabditis
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Susana Iraola-Guzmán, Ewa Ksiezopolska, Ester Saus, Uciel Chorostecki, Cinta Pegueroles, and Toni Gabaldón
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Motifs ,motifs ,Lncrna ,Computational biology ,Synteny ,Evolution, Molecular ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Species Specificity ,Genus ,Secondary structure ,biology.animal ,Animals ,Nucleotide Motifs ,Molecular Biology ,Gene ,030304 developmental biology ,Sequence (medicine) ,0303 health sciences ,Base Sequence ,biology ,Gene Expression Profiling ,synteny ,Computational Biology ,Vertebrate ,secondary structure ,Molecular Sequence Annotation ,Cell Biology ,biology.organism_classification ,Caenorhabditis ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,RNA, Long Noncoding ,Sequence motif ,030217 neurology & neurosurgery ,Research Paper - Abstract
Long non-coding RNAs (lncRNAs) are a heterogeneous class of genes that do not code for proteins. Since lncRNAs (or a fraction thereof) are expected to be functional, many efforts have been dedicated to catalog lncRNAs in numerous organisms, but our knowledge of lncRNAs in non vertebrate species remains very limited. Here, we annotated lncRNAs using transcriptomic data from the same larval stage of four Caenorhabditis species. The number of annotated lncRNAs in self-fertile nematodes was lower than in out-crossing species. We used a combination of approaches to identify putatively homologous lncRNAs: synteny, sequence conservation, and structural conservation. We classified a total of 1,532 out of 7,635 genes from the four species into families of lncRNAs with conserved synteny and expression at the larval stage, suggesting that a large fraction of the predicted lncRNAs may be species specific. Despite both sequence and local secondary structure seem to be poorly conserved, sequences within families frequently shared BLASTn hits and short sequence motifs, which were more likely to be unpaired in the predicted structures. We provide the first multi-species catalog of lncRNAs in nematodes and identify groups of lncRNAs with conserved synteny and expression, that share exposed motifs. This work was supported by the Spanish Ministry of Economy,Industry, and Competitiveness (MEIC), INB Grant (PT17/0009/0023 - ISCIII-SGEFI/ERDF) by the EMBL partnership, and grants ‘Centro de Excelencia Severo Ochoa 2013–2017’ SEV-2012-0208, and BFU2015-67107 cofounded by European Regional 710 Development Fund (ERDF); by the CERCA Programme/Generalitat de Catalunya; from the Catalan Research Agency (AGAUR) SGR857, and grant from the European Union’s Horizon 2020 research and innovation programme under the grant agreement ERC-2016-724173 the Marie Sklodowska-Curie grant agreement No 715 H2020-MSCA-ITN-2014-642095 and the Marie Skłodowska-Curie Actions [H2020-MSCA-IF-2017-793699].
- Published
- 2018
8. SDNN-PPI: self-attention with deep neural network effect on protein-protein interaction prediction.
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Li, Xue, Han, Peifu, Wang, Gan, Chen, Wenqi, Wang, Shuang, and Song, Tao
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ARTIFICIAL neural networks ,NETWORK effect ,PROTEIN-protein interactions ,MICE ,DEEP learning ,GENETIC transcription regulation ,CAENORHABDITIS - Abstract
Background: Protein-protein interactions (PPIs) dominate intracellular molecules to perform a series of tasks such as transcriptional regulation, information transduction, and drug signalling. The traditional wet experiment method to obtain PPIs information is costly and time-consuming. Result: In this paper, SDNN-PPI, a PPI prediction method based on self-attention and deep learning is proposed. The method adopts amino acid composition (AAC), conjoint triad (CT), and auto covariance (AC) to extract global and local features of protein sequences, and leverages self-attention to enhance DNN feature extraction to more effectively accomplish the prediction of PPIs. In order to verify the generalization ability of SDNN-PPI, a 5-fold cross-validation on the intraspecific interactions dataset of Saccharomyces cerevisiae (core subset) and human is used to measure our model in which the accuracy reaches 95.48% and 98.94% respectively. The accuracy of 93.15% and 88.33% are obtained in the interspecific interactions dataset of human-Bacillus Anthracis and Human-Yersinia pestis, respectively. In the independent data set Caenorhabditis elegans, Escherichia coli, Homo sapiens, and Mus musculus, all prediction accuracy is 100%, which is higher than the previous PPIs prediction methods. To further evaluate the advantages and disadvantages of the model, the one-core and crossover network are conducted to predict PPIs, and the data show that the model correctly predicts the interaction pairs in the network. Conclusion: In this paper, AAC, CT and AC methods are used to encode the sequence, and SDNN-PPI method is proposed to predict PPIs based on self-attention deep learning neural network. Satisfactory results are obtained on interspecific and intraspecific data sets, and good performance is also achieved in cross-species prediction. It can also correctly predict the protein interaction of cell and tumor information contained in one-core network and crossover network.The SDNN-PPI proposed in this paper not only explores the mechanism of protein-protein interaction, but also provides new ideas for drug design and disease prevention. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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9. A Model for Evolutionary Ecology of Disease: The Case for Caenorhabditis Nematodes and Their Natural Parasites
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Levi T. Morran and Amanda K. Gibson
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0301 basic medicine ,Experimental evolution ,evolution and ecology of infectious disease ,biology ,Disease ecology ,Life Sciences ,Disease ,biology.organism_classification ,Natural (archaeology) ,Caenorhabditis ,Natural history ,03 medical and health sciences ,030104 developmental biology ,lcsh:Biology (General) ,Evolutionary biology ,coevolution ,Evolutionary ecology ,experimental evolution ,fungi ,bacteria ,lcsh:QH301-705.5 ,Coevolution ,Invited Symposium Papers: Nematode-Microbe Symbioses - Abstract
Many of the outstanding questions in disease ecology and evolution call for combining observation of natural host–parasite populations with experimental dissection of interactions in the field and the laboratory. The “rewilding” of model systems holds great promise for this endeavor. Here, we highlight the potential for development of the nematode Caenorhabditis elegans and its close relatives as a model for the study of disease ecology and evolution. This powerful laboratory model was disassociated from its natural habitat in the 1960s. Today, studies are uncovering that lost natural history, with several natural parasites described since 2008. Studies of these natural Caenorhabditis–parasite interactions can reap the benefits of the vast array of experimental and genetic tools developed for this laboratory model. In this review, we introduce the natural parasites of C. elegans characterized thus far and discuss resources available to study them, including experimental (co)evolution, cryopreservation, behavioral assays, and genomic tools. Throughout, we present avenues of research that are interesting and feasible to address with caenorhabditid nematodes and their natural parasites, ranging from the maintenance of outcrossing to the community dynamics of host-associated microbes. In combining natural relevance with the experimental power of a laboratory supermodel, these fledgling host–parasite systems can take on fundamental questions in evolutionary ecology of disease.
- Published
- 2017
10. Programmed ribosomal frameshifting in the expression of the regulator of intestinal stem cell proliferation, adenomatous polyposis coli (APC)
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Pavel V. Baranov, Molly C. Jud, Anthea Letsou, Norma M. Wills, Andrew E. Firth, Kathy A. Barriscale, John F. Atkins, and Gerard Manning
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Genes, APC ,Adenomatous polyposis coli ,Adenomatous Polyposis Coli Protein ,Reading frame ,Ribosomal frameshift ,Frameshift mutation ,Open Reading Frames ,Animals ,RNA, Messenger ,Intestinal Mucosa ,Frameshift Mutation ,Wnt Signaling Pathway ,Molecular Biology ,Phylogeny ,beta Catenin ,Cell Proliferation ,Sequence Deletion ,Genetics ,Translational frameshift ,biology ,Stem Cells ,Frameshifting, Ribosomal ,RNA ,Cell Biology ,Ribosomal RNA ,biology.organism_classification ,Caenorhabditis ,biology.protein ,Drosophila ,Sequence Alignment ,Research Paper - Abstract
A programmed ribosomal frameshift (PRF) in the decoding of APC (adenomatous polyposis coli) mRNA has been identified and characterized in Caenorhabditis worms, Drosophila and mosquitoes. The frameshift product lacks the C-terminal approximately one-third of the product of standard decoding and instead has a short sequence encoded by the -1 frame which is just 13 residues in C. elegans, but is 125 in D. melanogaster. The frameshift site is A_AA.A_AA.C in Caenorhabditids, fruit flies and the mosquitoes studied while a variant A_AA.A_AA.A is found in some other nematodes. The predicted secondary RNA structure of the downstream stimulators varies considerably in the species studied. In the twelve sequenced Drosophila genomes, it is a long stem with a four-way junction in its loop. In the five sequenced Caenorhabditis species, it is a short RNA pseudoknot with an additional stem in loop 1. The efficiency of frameshifting varies significantly, depending on the particular stimulator within the frameshift cassette, when tested with reporter constructs in rabbit reticulocyte lysates. Phylogenetic analysis of the distribution of APC programmed ribosomal frameshifting cassettes suggests it has an ancient origin and raises questions about a possibility of synthesis of alternative protein products during expression of APC in other organisms such as humans. The origin of APC as a PRF candidate emerged from a prior study of evolutionary signatures derived from comparative analysis of the 12 fly genomes. Three other proposed PRF candidates (Xbp1, CG32736, CG14047) with switches in conservation of reading frames are likely explained by mechanisms other than PRF.
- Published
- 2011
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11. A monolithic optimal control method for displacement tracking of Cosserat rod with application to reconstruction of C. elegans locomotion.
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Wang, Yongxing, Ranner, Thomas, Ilett, Thomas P., Xia, Yan, and Cohen, Netta
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ANIMAL locomotion ,CAENORHABDITIS elegans ,CAENORHABDITIS ,TORQUE control ,PARTIAL differential equations ,INVERSE problems ,REACTION forces - Abstract
This article considers an inverse problem for a Cosserat rod where we are given only the position of the centreline of the rod and must solve for external forces and torques as well as the orientation of the cross sections of the centreline. We formulate the inverse problem as an optimal control problem using the position of the centreline as an objective function with the external force and torque as control variables, with meaningful regularisation of the orientations. A monolithic, implicit numerical scheme is proposed in the sense that primal and adjoint equations are solved in a fully-coupled manner and all the nonlinear coefficients of the governing partial differential equations are updated to the current state variables. The forward formulation, determining rod configuration from external forces and torques, is first validated by a numerical benchmark; the solvability and stability of the inverse problem are then tested using data from forward simulations. The proposed optimal control method is motivated by reconstruction of the orientations of a rod's cross sections, with its centreline being captured through imaging protocols. As a case study, we take the locomotion of the nematode, Caenorhabditis elegans. In this study we take laboratory data for its centreline and infer its cross-section orientation (muscle locations) with the control force and torque being interpreted as the reaction force, activated by C. elegans' muscles, from the surrounding fluids. This method thus combines the mathematical modelling and laboratory data to study the locomotion of C. elegans, which gives us insights into the potential anatomical orientation of the worm beyond what can be observed through the laboratory data. The paper is completed with several additional remarks explaining the theoretical and technical details of the model. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Unproductively spliced ribosomal protein mRNAs are natural targets of mRNA surveillance in C. elegans
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Quinn M. Mitrovich and Philip Anderson
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Ribosomal Proteins ,DNA, Complementary ,RNA Splicing ,Molecular Sequence Data ,Nonsense-mediated decay ,Biology ,Animals, Genetically Modified ,Exon ,Transformation, Genetic ,Sequence Homology, Nucleic Acid ,Genetics ,Animals ,RNA, Messenger ,Cloning, Molecular ,Caenorhabditis elegans ,Codon ,Messenger RNA ,Base Sequence ,Models, Genetic ,Alternative splicing ,Intron ,Exons ,Blotting, Northern ,Introns ,Stop codon ,mRNA surveillance ,Alternative Splicing ,RNA splicing ,Caenorhabditis ,Mutagenesis, Site-Directed ,Ribosomes ,Research Paper ,Developmental Biology - Abstract
Messenger RNA surveillance, the selective and rapid degradation of mRNAs containing premature stop codons, occurs in all eukaryotes tested. The biological role of this decay pathway, however, is not well understood. To identify natural substrates of mRNA surveillance, we used a cDNA-based representational difference analysis to identify mRNAs whose abundance increases in Caenorhabditis elegans smg(−) mutants, which are deficient for mRNA surveillance. Alternatively spliced mRNAs of genes encoding ribosomal proteins L3, L7a, L10a, and L12 are abundant natural targets of mRNA surveillance. Each of these genes expresses two distinct mRNAs. A productively spliced mRNA, whose abundance does not change in smg(−)mutants, encodes a normal, full-length, ribosomal protein. An unproductively spliced mRNA, whose abundance increases dramatically insmg(−) mutants, contains premature stop codons because of incomplete removal of an alternatively spliced intron. In transgenic animals expressing elevated quantities of RPL-12, a greater proportion of endogenous rpl-12 transcript is spliced unproductively. Thus, RPL-12 appears to autoregulate its own splicing, with unproductively spliced mRNAs being degraded by mRNA surveillance. We demonstrate further that alternative splicing of rpl introns is conserved among widely diverged nematodes. Our results suggest that one important role of mRNA surveillance is to eliminate unproductive by-products of gene regulation.
- Published
- 2000
13. XOL-1, primary determinant of sexual fate in C. elegans, is a GHMP kinase family member and a structural prototype for a class of developmental regulators
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John G. Luz, Barbara J Meyer, Ian A. Wilson, Catherine S. Pickle, Adam Godzik, and Christian A. Hassig
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X Chromosome ,Phosphomevalonate kinase ,Protein Conformation ,Molecular Sequence Data ,Disorders of Sex Development ,Biology ,Y chromosome ,Crystallography, X-Ray ,Adenosine Triphosphate ,Dosage Compensation, Genetic ,Genetics ,Animals ,Amino Acid Sequence ,Cloning, Molecular ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,X chromosome ,Adenosine Triphosphatases ,Dosage compensation ,Phosphotransferases (Phosphate Group Acceptor) ,Sequence Homology, Amino Acid ,Helminth Proteins ,Sex Determination Processes ,Galactokinase ,Dosage compensation complex ,Protein Structure, Tertiary ,Phosphotransferases (Alcohol Group Acceptor) ,Spectrometry, Fluorescence ,GHMP kinase family ,Primary sex determination ,Caenorhabditis ,Crystallization ,Developmental Biology ,Protein Binding ,Signal Transduction ,Research Paper - Abstract
Sex determination is the critical and universal developmental pathway underlying sexual reproduction. Its manifestations are pervasive and often conspicuous. Whereas the presence or absence of the Y chromosome dictates male or female development in mammals, sexual fate in the fruit fly Drosophila melanogaster and the free-living nematode Caenorhabditis elegans is determined genetically by the number of X chromosomes relative to the number of sets of autosomes. In mammals, the primary sex determining gene is SRY, which is present only on the Y chromosome and encodes an HMG domain-containing transcription factor. In the fruit fly, the primary sex determination gene Sex-lethal (Sxl; Maine et al. 1985) is a female-specific trans-acting gene regulator that binds tra transcripts and directs alternative splicing (Inoue et al. 1990). The SRY (Werner et al. 1995) and SXL (Handa et al. 1999) interactions with polynucleotides have been characterized structurally. In C. elegans, sexual differentiation is regulated by the expression levels of the developmental switch gene xol-1. High and low levels of xol-1 result in male (XO) and hermaphrodite (XX) development (Fig. (Fig.1),1), respectively. XOL-1 activity is absolutely required for proper sexual differentiation and male viability (Rhind et al. 1995), but its mechanism of action is unknown. Figure 1 Genetic control of sex determination and dosage compensation in C. elegans. xol-1 is the primary sex-determination switch gene and the direct molecular target of the X-chromosome counting mechanism. (Top) Male (XO). High xol-1 activity specifies male ... The cooperative activity of at least four X-linked genes, termed X-signal elements, represses expression of xol-1 (for review, see Meyer 2000a). By doubling the number of X-signal elements, an XX embryo reduces xol-1 expression by ∼10-fold (Rhind et al. 1995), facilitating hermaphrodite development. Two C. elegans X-signal elements have been characterized molecularly as follows: FOX-1 (Hodgkin et al. 1994; Nicoll et al. 1997; Skipper et al. 1999), an RNA-binding protein that may regulate alternate splicing of xol-1 RNA, and SEX-1 (Carmi et al. 1998), a nuclear receptor and likely a transcription factor. Although hermaphrodites and males differ in X chromosome number, the expression of most X-linked genes must be equal to ensure viability. This is accomplished through dosage compensation, which reduces expression of X-linked genes in hermaphrodites to male levels (for reviews, see Wood et al. 1997; Hansen and Pilgrim 1999; Meyer 2000b; Boag et al. 2001). High levels of XOL-1 in males correlate with low SDC-2 expression, preventing dosage compensation (Miller et al. 1988; Rhind et al. 1995). Conversely, low levels of XOL-1 in hermaphrodites correlate with high SDC-2 expression and the assembly on the X chromosome of the dosage compensation complex, which is composed of sdc, dpy, and mix-1 gene products (Nonet and Meyer 1991; Chuang et al. 1996; Lieb et al. 1996, 1998; Davis and Meyer 1997; Dawes et al. 1999; Chu et al. 2002). Other genes downstream of xol-1, such as her, tra, and fem, whose activities are inversely related in hermaphrodites and males, coordinate sexual differentiation (Goodwin and Ellis 2002). Null mutants of xol-1 are XO-lethal, inappropriately activating dosage compensation where only one X chromosome is present, whereas XOL-1 overexpression is XX-lethal, deactivating the dosage compensation pathway and elevating the expression of X chromosome genes to lethal levels in hermaphrodites (Rhind et al. 1995). XOL-1 is an acidic 51-kD nuclear protein (pKa 4.6), whose transcript is expressed at high levels only in pre-comma stage XO embryos (Rhind et al. 1995). XOL-1 transcripts are present in low levels throughout other larval stages in XO animals, but are nearly undetectable in XX larvae and adults of both sexes (Rhind et al. 1995). Currently, XOL-1 is annotated as a subtilisin-like protease on the basis of primary sequence (http://www.wormbase.org). BLAST searches of Genbank failed to identify any homologs that may have provided additional clues as to the function of XOL-1. Thus, we used x-ray crystallography to investigate the function of XOL-1, hypothesizing that the three-dimensional structure of the protein would yield insights into its nature, largely uncharacterized biochemically. The resulting crystal structure of XOL-1 (Fig. (Fig.2A)2A) unambiguously and unexpectedly defines XOL-1 as a member of the GHMP kinase family, a family of proteins known to be involved in small molecule metabolism, but not known to participate directly in sexual differentiation or dosage compensation. Figure 2 Comparison of XOL-1 and GHMP kinase structures. (A) The structure of XOL-1. Ribbon diagram of XOL-1 (PDB ID: 1MG7). Domain 1 consists of β-strands 2–7 and 12 (cyan) and α-helices 1–5 (yellow). Domain 2 consists of β-strands ... Galactokinase, homoserine kinase, mevalonate kinase, and phosphomevalonate kinase were originally identified as prototypic members of the GHMP kinase family and observed to contain a conserved Pro–Xaa3–Gly–Leu–Gly–Ser–Ser–Ala–Ala motif (Fig, 3A) that was hypothesized (Tsay and Robinson 1991; Bork et al. 1993), and later proved (Zhou et al. 2000; Krishna et al. 2001; Fu et al. 2002) to be involved in ATP binding. The nucleotide fold of GHMP kinases is distinct from those of other kinases, that is, P-loop, protein, and Hsp70-like kinases (Zhou et al. 2000; Bonanno et al. 2001; Fu et al. 2002; Romanowski et al. 2002; Yang et al. 2002), and binds ATP in both syn and anti-conformations (Zhou et al. 2000; Fu et al. 2002). GHMP kinases are found in bacteria, archaea, and eukaryotes and contain an unusual left-handed β–α–β fold similar to that observed in domain IV of elongation factor G (Zhou et al. 2000). In humans, deficiency of galactokinase, which participates in the conversion of galactose to glucose, contributes to cataract formation (Monteleone et al. 1971; Beutler 1972; Harley et al. 1972; Levy et al. 1972). Mutations in mevalonate kinase, an enzyme involved in the synthesis of sterols from acetate, are associated with mevalonic aciduria (Hoffmann et al. 1986; Schafer et al. 1992; Houten et al. 1999b) and hyperimmunoglobulinemia D/periodic fever syndrome (Drenth et al. 1999; Houten et al. 1999a, 2001; Cuisset et al. 2001; Rios et al. 2001; Simon et al. 2001). To date, no GHMP kinases have been shown to function in developmental pathways unrelated to metabolism.
- Published
- 2003
14. Counts of mechanical, external configurations compared to computational, internal configurations in natural and artificial systems.
- Author
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LaViers, Amy
- Subjects
MOORE'S law ,ANIMAL mechanics ,ARTIFICIAL membranes ,ANIMAL behavior - Abstract
Animal movement encodes information that is meaningfully interpreted by natural counterparts. This is a behavior that roboticists are trying to replicate in artificial systems but that is not well understood even in natural systems. This paper presents a count on the cardinality of a discretized posture space—an aspect of expressivity—of articulated platforms. The paper uses an information-theoretic measure, Shannon entropy, to create observations analogous to Moore’s Law, providing a measure that complements traditional measures of the capacity of robots. This analysis, applied to a variety of natural and artificial systems, shows trends in increasing capacity in both internal and external complexity for natural systems while artificial, robotic systems have increased significantly in the capacity of computational (internal) states but remained more or less constant in mechanical (external) state capacity. The quantitative measure proposed in this paper provides an additional lens through which to compare natural and artificial systems. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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- View/download PDF
15. VirginCaenorhabditis remaneifemales are attracted to a coital pheromone released by con-specific copulating males
- Author
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Matthew J. Markert and Luis René García
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copulation ,Gonad ,biology ,Ecology ,Zoology ,biology.organism_classification ,Attraction ,Caenorhabditis ,medicine.anatomical_structure ,Mate choice ,pheromone attraction ,Sexual selection ,medicine ,sexual selection ,Pheromone ,Caenorhabditis remanei ,mate choice ,Mating ,mating receptivity ,Research Paper - Abstract
The gonochoristic soil nematode Caenorhabditis remanei strictly requires copulation for species propagation. Males of this species are sexually promiscuous with females of other species; therefore, we asked in this study whether virgin C. remanei females display evidence of mate choice. We digitally recorded and measured the locomotor behaviors of one or more virgin females in the presence of a single male on a 5 mm diameter mating lawn. We observed that initially only the male modifies his locomotor trajectory to another animal on the mating lawn; the virgin females showed no locomotor bias toward the mate-searching male. However, once a male started to copulate, females in the vicinity altered their movement trajectories toward the copulating couple. Newly inseminated females are refractive to the coital signal, but partially regain their attraction to copulating males after 24 h. We found only copulating males with an intact gonad can attract females, and that the coital signal can be broadcasted at least 1.5 mm through the air. Unlike males, which are also attracted to hetero-specific females, virgin C. remanei females will only crawl toward a copulating con-specific male. We suggest that Caenorhabditis females use the coital signal as a pheromone to identify a vigorous male of their own species.
- Published
- 2013
16. Genome-wide characterization, evolution, structure, and expression analysis of the F-box genes in Caenorhabditis
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Wang, Ailan, Chen, Wei, and Tao, Shiheng
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- 2021
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17. Imaging adult C. elegans live using light‐sheet microscopy.
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VAN KRUGTEN, J., TARIS, K.‐K.H., and PETERMAN, ERWIN J.G.
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OPTICAL brighteners ,FOCAL planes ,CAENORHABDITIS elegans ,MICROSCOPY ,PHENOMENOLOGICAL biology ,CAENORHABDITIS ,YOUNG adults ,FLUORESCENCE microscopy - Abstract
Summary: Live observation of biological phenomena in the context of living organisms can provide important insights in the mechanisms of these phenomena. However, the spatially complex and dynamic physiology of multicellular organisms can be a challenging environment to make observations with fluorescence microscopy. Due to the illumination of out‐of‐focus planes, confocal and particularly widefield fluorescence microscopy suffer from low signal‐to‐background ratio (SBR), photo toxicity and bleaching of fluorescent probes. In light‐sheet microscopy (LSM), solely the focal plane of the detection objective is illuminated, minimising out‐of‐focus fluorescence and photobleaching, thereby enhancing SBR, allowing for low laser intensities and longer acquisition periods. Here we present a straightforward light‐sheet microscope with a 1.0‐NA detection objective and a fast sample‐positioning stage that allows for four degrees of freedom. By imaging the sensory cilia and nervous system of living young adult C. elegans, we demonstrate that the instrument is well suited for relatively fast, volumetric imaging of larger (hundreds of micrometres cubed) living samples. These experiments demonstrate that such an instrument provides a valuable addition to commonly used widefield and confocal fluorescence microscopes. Lay description: In fluorescence microscopy, sharp images can only be obtained when the light obtained from the section of the image that is in focus is not overwhelmed by light emerging from elsewhere. In this paper, we present a light‐sheet fluorescence microscope, based on the OpenSPIM initiative, with a magnification of 90× and a sensitive sample positioning stage that allows for fast controlled linear movement and rotation. In a light‐sheet microscope (LSM), the sample is illuminated from the side, compared to the direction of detection, limiting illumination only to the part of the sample that is imaged in the focal plane (general resources: Wikipedia or MicroscopyU). This does not only limit background noise, but also reduces damage to the sample due to phototoxicity. This makes a LSM particularly suitable for imaging living samples at high resolution, in three dimensions, over long periods of time. Our instrument was specifically designed for imaging adult C. elegans nematodes. We show here how the instrument compares to a standard epifluorescence microscope, imaging neuronal structures in the animals. The instrument proved well suited for fast volumetric imaging of larger cellular structures such as C. elegans neuronal cell bodies. Our experiments show that the instrument provides a valuable addition to widefield and confocal fluorescence microscopes commonly used to image adult C. elegans. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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- View/download PDF
18. Xenobiotic metabolism and transport in Caenorhabditis elegans.
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Hartman, Jessica H., Widmayer, Samuel J., Bergemann, Christina M., King, Dillon E., Morton, Katherine S., Romersi, Riccardo F., Jameson, Laura E., Leung, Maxwell C. K., Andersen, Erik C., Taubert, Stefan, and Meyer, Joel N.
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CAENORHABDITIS elegans ,ENVIRONMENTAL toxicology ,CAENORHABDITIS ,METABOLIC regulation ,NUCLEAR receptors (Biochemistry) ,METABOLISM - Abstract
Caenorhabditis elegans has emerged as a major model in biomedical and environmental toxicology. Numerous papers on toxicology and pharmacology in C. elegans have been published, and this species has now been adopted by investigators in academic toxicology, pharmacology, and drug discovery labs. C. elegans has also attracted the interest of governmental regulatory agencies charged with evaluating the safety of chemicals. However, a major, fundamental aspect of toxicological science remains underdeveloped in C. elegans: xenobiotic metabolism and transport processes that are critical to understanding toxicokinetics and toxicodynamics, and extrapolation to other species. The aim of this review was to initially briefly describe the history and trajectory of the use of C. elegans in toxicological and pharmacological studies. Subsequently, physical barriers to chemical uptake and the role of the worm microbiome in xenobiotic transformation were described. Then a review of what is and is not known regarding the classic Phase I, Phase II, and Phase III processes was performed. In addition, the following were discussed (1) regulation of xenobiotic metabolism; (2) review of published toxicokinetics for specific chemicals; and (3) genetic diversity of these processes in C. elegans. Finally, worm xenobiotic transport and metabolism was placed in an evolutionary context; key areas for future research highlighted; and implications for extrapolating C. elegans toxicity results to other species discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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- View/download PDF
19. On‐Chip Rotation of Caenorhabditis elegans Using Microfluidic Vortices.
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Pan, Peng, Laver, John D., Qin, Zhen, Zhou, Yuxiao, Peng, Ran, Zhao, Lijun, Xie, Hui, Calarco, John A., and Liu, Xinyu
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CAENORHABDITIS elegans ,MICROFLUIDIC devices ,CAENORHABDITIS ,ROTATIONAL motion ,FLUORESCENT proteins ,BODY image - Abstract
Precise and controllable rotation of small biological samples is essential to many biological and medical applications. This paper reports, an easy‐to‐use microfluidic device to rotate single nematode worm Caenorhabditis elegans in a reliable and controllable fashion, which was enabled by on‐chip generation of stable microscale vortices inside a worm‐loaded microchannel by fluidic shear stress. To test the capability of the proposed device, single worms were successfully rotated in continuous and stepwise modes. Using this device, clear visualization of all dopaminergic neurons in the head of a C. elegans was demonstrated by capturing fluorescence images of the worm body at several rotational angles. Multiple perspectives of individual neurons of a multi‐color fluorescent transgenic worm were also obtained at high resolution using laser‐scanning confocal microscopy. The results show that this microfluidic rotation device provides a simple solution to overcoming limitations of confocal microscopy when imaging relatively thick tissue samples such as an adult C. elegans, and is compatible with multiple fluorescent proteins with different spectral properties. With its controllability, precision, and simplicity in fabrication and operation, this microfluidic device has important utility in model organism studies. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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- View/download PDF
20. Active backlight for automating visual monitoring: An analysis of a lighting control technique for Caenorhabditis elegans cultured on standard Petri plates.
- Author
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Puchalt, Joan Carles, Sánchez-Salmerón, Antonio-José, Martorell Guerola, Patricia, and Genovés Martínez, Salvador
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CAENORHABDITIS elegans ,LIGHTING ,IMAGE segmentation ,IMAGE processing ,ELECTROMAGNETIC radiation ,LIGHT intensity ,VISIBLE spectra - Abstract
Lifespan and healthspan machines can undergo C. elegans image segmentation errors due to changes in lighting conditions, which produce non-uniform images. Most C. elegans monitoring machines use backlight techniques based on the transparency of both the container and media. Backlight illumination obtains high-contrast images with dark C. elegans and a bright background. However, changes in illumination or media transparency conditions can produce non-uniform images, which are currently alleviated by image processing techniques. Besides, these machines should avoid C. elegans exposure to light as much as possible because light stresses worms, and can even affect their lifespan, mainly when using (1) long exposure times, (2) high intensities or (3) wavelengths that come close to ultraviolet. However, if short exposure of worms to light is required for visual monitoring, then light can also be used as a movement stimulus. In this paper, an active backlight method is analysed. The proposed method consists of controlling the light intensities and wavelengths of an illumination dots matrix with PID regulators. These regulators adapt illumination to some changing conditions. The experimental results shows that this method simplifies the image segmentation problem because it is able to automatically compensate not only changes in media transparency throughout assay days, but also changes in ambient conditions, such as smooth condensation on the lid and light derivatives of the illumination source during its lifetime. In addition, the strategic application of wavelengths could be adapted for the requirements of each assay. For instance, a specific control strategy has been proposed to minimise stress to worms and trying to stimulate C. elegans movement in lifespan assays. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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21. Common dace (Leuciscus leuciscus) - A new host of the myxozoan fish parasite, Myxobolus elegans (Cnidaria: Myxozoa) - Short communication.
- Author
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MOROZOVA, DARIA A., VORONIN, VLADIMIR N., and KATOKHIN, ALEXEY V.
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FISH parasites ,MYXOZOA ,CNIDARIA ,CAENORHABDITIS ,RECOMBINANT DNA - Abstract
This paper reports the detection of the myxozoan species Myxobolus elegans Kashkovsky 1966 in common dace (Leuciscus leuciscus) that has not been previously listed as its host. The problem of differentiation of phenotypically similar Myxobolus species is addressed. During parasitological survey of common dace from the desalinated part of the Gulf of Finland at the city of Sestroretsk, Russia, numerous oval-shaped plasmodia, 0.2-0.4 mm in size, filled with Myxobolus spores were found on the gills. Pear-shaped myxospores were 15.4 (14.8-16.0) x 10.2 (9.6-10.9) mm in size with a rib on each valve. On the basis of spore morphology, the species appeared to be similar to M. elegans and Myxobolus hungaricus Jaczó, 1940. In order to identify the species, molecular genetic analysis was performed, and the species was identified on the basis of morphological characteristics and 18S rDNA data. The results obtained indicate that the Myxobolus species observed on the gills of dace is M. elegans. Thus, common dace is another valid host of M. elegans besides the type host, ide (Leuciscus idus). [ABSTRACT FROM AUTHOR]
- Published
- 2020
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22. An atlas of Caenorhabditis elegans chemoreceptor expression.
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Vidal, Berta, Aghayeva, Ulkar, Sun, Haosheng, Wang, Chen, Glenwinkel, Lori, Bayer, Emily A., and Hobert, Oliver
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CHEMORECEPTORS ,GENE expression ,CAENORHABDITIS elegans genetics ,G protein coupled receptors ,SENSORY neurons - Abstract
One goal of modern day neuroscience is the establishment of molecular maps that assign unique features to individual neuron types. Such maps provide important starting points for neuron classification, for functional analysis, and for developmental studies aimed at defining the molecular mechanisms of neuron identity acquisition and neuron identity diversification. In this resource paper, we describe a nervous system-wide map of the potential expression sites of 244 members of the largest gene family in the C. elegans genome, rhodopsin-like (class A) G-protein-coupled receptor (GPCR) chemoreceptors, using classic gfp reporter gene technology. We cover representatives of all sequence families of chemoreceptor GPCRs, some of which were previously entirely uncharacterized. Most reporters are expressed in a very restricted number of cells, often just in single cells. We assign GPCR reporter expression to all but two of the 37 sensory neuron classes of the sex-shared, core nervous system. Some sensory neurons express a very small number of receptors, while others, particularly nociceptive neurons, coexpress several dozen GPCR reporter genes. GPCR reporters are also expressed in a wide range of inter- and motorneurons, as well as non-neuronal cells, suggesting that GPCRs may constitute receptors not just for environmental signals, but also for internal cues. We observe only one notable, frequent association of coexpression patterns, namely in one nociceptive amphid (ASH) and two nociceptive phasmid sensory neurons (PHA, PHB). We identified GPCRs with sexually dimorphic expression and several GPCR reporters that are expressed in a left/right asymmetric manner. We identified a substantial degree of GPCR expression plasticity; particularly in the context of the environmentally-induced dauer diapause stage when one third of all tested GPCRs alter the cellular specificity of their expression within and outside the nervous system. Intriguingly, in a number of cases, the dauer-specific alterations of GPCR reporter expression in specific neuron classes are maintained during postdauer life and in some case new patterns are induced post-dauer, demonstrating that GPCR gene expression may serve as traits of life history. Taken together, our resource provides an entry point for functional studies and also offers a host of molecular markers for studying molecular patterning and plasticity of the nervous system. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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23. Independent degradation in genes of the plastid ndh gene family in species of the orchid genus Cymbidium (Orchidaceae; Epidendroideae).
- Author
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Kim, Hyoung Tae and Chase, Mark W.
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CYMBIDIUM ,PLASTIDS ,GENE transfection ,MITOCHONDRIAL DNA ,CHROMOSOMAL translocation - Abstract
In this paper, we compare ndh genes in the plastid genome of many Cymbidium species and three closely related taxa in Orchidaceae looking for evidence of ndh gene degradation. Among the 11 ndh genes, there were frequently large deletions in directly repeated or AT-rich regions. Variation in these degraded ndh genes occurs between individual plants, apparently at population levels in these Cymbidium species. It is likely that ndh gene transfers from the plastome to mitochondrial genome (chondriome) occurred independently in Orchidaceae and that ndh genes in the chondriome were also relatively recently transferred between distantly related species in Orchidaceae. Four variants of the ycf1-rpl32 region, which normally includes the ndhF genes in the plastome, were identified, and some Cymbidium species contained at least two copies of that region in their organellar genomes. The four ycf1-rpl32 variants seem to have a clear pattern of close relationships. Patterns of ndh degradation between closely related taxa and translocation of ndh genes to the chondriome in Cymbidium suggest that there have been multiple bidirectional intracellular gene transfers between two organellar genomes, which have produced different levels of ndh gene degradation among even closely related species. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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24. Cornus officinalis Extract Enriched with Ursolic Acid Ameliorates UVB-Induced Photoaging in Caenorhabditis elegans.
- Author
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Yue, Zengwang, Liu, Han, Liu, Manqiu, Wang, Ning, Ye, Lin, Guo, Chaowan, and Zheng, Bisheng
- Subjects
URSOLIC acid ,CAENORHABDITIS elegans ,CAENORHABDITIS ,REACTIVE oxygen species ,GENE expression ,OXIDATIVE stress ,WATER use - Abstract
Ultraviolet B (UVB) exposure can contribute to photoaging of skin. Cornus officinalis is rich in ursolic acid (UA), which is beneficial to the prevention of photoaging. Because UA is hardly soluble in water, the Cornus officinalis extract (COE) was obtained using water as the antisolvent to separate the components containing UA from the crude extract of Cornus officinalis. The effect of COE on UVB damage was assessed using Caenorhabditis elegans. The results showed that COE could increase the lifespan and enhance the antioxidant enzyme activity of C. elegans exposed to UVB while decreasing the reactive oxygen species (ROS) level. At the same time, COE upregulated the expression of antioxidant-related genes and promoted the migration of SKN-1 to the nucleus. Moreover, COE inhibited the expression of the skn-1 downstream gene and the extension of the lifespan in skn-1 mutants exposed to UVB, indicating that SKN-1 was required for COE to function. Our findings indicate that COE mainly ameliorates the oxidative stress caused by UVB in C. elegans via the SKN-1/Nrf2 pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
25. The Probiotic Strain Lactobacillus acidophilus CL1285 Reduces Fat Deposition and Oxidative Stress and Increases Lifespan in Caenorhabditis elegans.
- Author
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Bouasker, Samir, Nodland, Sonja, and Millette, Mathieu
- Subjects
LACTOBACILLUS acidophilus ,CAENORHABDITIS ,OXIDATIVE stress ,CAENORHABDITIS elegans ,STAINS & staining (Microscopy) ,PROBIOTICS ,OLEIC acid ,FAT - Abstract
Caenorhabditis elegans was recently shown to be a powerful model for studying and identifying probiotics with specific functions. Lactobacillus acidophilus CL1285, Lacticaseibacillus casei LBC80R, and Lacticaseibacillus rhamnosus CLR2, which are three bacteria that were marketed by Bio-K+, were evaluated using the nematode C. elegans to study fat accumulation, lifespan, and resistance to oxidative stress. Although the general effects of probiotics in terms of protection against oxidative stress were highlighted, the CL1285 strain had an interesting and specific feature, namely its ability to prevent fat accumulation in nematodes; this effect was verified by both the Oil Red and Nile Red methods. This observed phenotype requires daf-16 and is affected by glucose levels. In addition, in a daf-16- and glucose-dependent manner, CL1285 extended the lifespan of C. elegans; this effect was unique to CL1285 and not found in the other L. acidophilus subtypes in this study. Our findings indicate that L. acidophilus CL1285 impacts fat/glucose metabolism in C. elegans and provides a basis to further study this probiotic, which could have potential health benefits in humans and/or in mammals. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
26. Rewiring the Sex-Determination Pathway During the Evolution of Self-Fertility.
- Author
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Shen, Yongquan, Lin, Shin-Yi, Harbin, Jonathan, Amin, Richa, Vassalotti, Allison, Romanowski, Joseph, Schmidt, Emily, Tierney, Alexis, and Ellis, Ronald E
- Subjects
SEX determination ,CAENORHABDITIS elegans ,SPERMATOGENESIS ,CAENORHABDITIS ,PROTEIN-protein interactions ,GENETIC sex determination - Abstract
Although evolution is driven by changes in how regulatory pathways control development, we know little about the molecular details underlying these transitions. The TRA-2 domain that mediates contact with TRA-1 is conserved in Caenorhabditis. By comparing the interaction of these proteins in two species, we identified a striking change in how sexual development is controlled. Identical mutations in this domain promote oogenesis in Caenorhabditis elegans but promote spermatogenesis in Caenorhabditis briggsae. Furthermore, the effects of these mutations involve the male-promoting gene fem-3 in C. elegans but are independent of fem-3 in C. briggsae. Finally, reciprocal mutations in these genes show that C. briggsae TRA-2 binds TRA-1 to prevent expression of spermatogenesis regulators. By contrast, in C. elegans TRA-1 sequesters TRA-2 in the germ line, allowing FEM-3 to initiate spermatogenesis. Thus, we propose that the flow of information within the sex determination pathway has switched directions during evolution. This result has important implications for how evolutionary change can occur. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
27. L-Theanine Prolongs the Lifespan by Activating Multiple Molecular Pathways in Ultraviolet C-Exposed Caenorhabditis elegans.
- Author
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Chen, Liangwen, Chen, Guijie, Gai, Tingting, Zhou, Xiuhong, Zhu, Jinchi, Wang, Ruiyi, Wang, Xuemei, Guo, Yujie, Wang, Yun, and Xie, Zhongwen
- Subjects
CAENORHABDITIS ,CAENORHABDITIS elegans ,EPIGALLOCATECHIN gallate ,UNFOLDED protein response ,MITOCHONDRIAL DNA ,MITOCHONDRIAL dynamics ,IMMUNOREGULATION ,GREEN tea - Abstract
L-theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effects, regulation of the immune response, relaxing neural tension, and reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPR
mt ) in UVC-exposed nematodes. In addition, L-theanine treatment also upregulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provides a theoretical basis for the possibility that tea drinking may prevent mitochondrial-related diseases. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
28. CDC-42 Orients Cell Migration during Epithelial Intercalation in the Caenorhabditis elegans Epidermis.
- Author
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Walck-Shannon, Elise, Cochran, Hunter, Bothfeld, William, Hardin, Jeff, Lucas, Bethany, Chin-Sang, Ian, Reiner, David, and Kumfer, Kraig
- Subjects
CELL migration ,EPITHELIAL cells ,INTERCALATION reactions ,EPIDERMIS ,MORPHOGENESIS - Abstract
Cell intercalation is a highly directed cell rearrangement that is essential for animal morphogenesis. As such, intercalation requires orchestration of cell polarity across the plane of the tissue. CDC-42 is a Rho family GTPase with key functions in cell polarity, yet its role during epithelial intercalation has not been established because its roles early in embryogenesis have historically made it difficult to study. To circumvent these early requirements, in this paper we use tissue-specific and conditional loss-of-function approaches to identify a role for CDC-42 during intercalation of the Caenorhabditis elegans dorsal embryonic epidermis. CDC-42 activity is enriched in the medial tips of intercalating cells, which extend as cells migrate past one another. Moreover, CDC-42 is involved in both the efficient formation and orientation of cell tips during cell rearrangement. Using conditional loss-of-function we also show that the PAR complex functions in tip formation and orientation. Additionally, we find that the sole C. elegans Eph receptor, VAB-1, functions during this process in an Ephrin-independent manner. Using epistasis analysis, we find that vab-1 lies in the same genetic pathway as cdc-42 and is responsible for polarizing CDC-42 activity to the medial tip. Together, these data establish a previously uncharacterized role for polarized CDC-42, in conjunction with PAR-6, PAR-3 and an Eph receptor, during epithelial intercalation. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
29. An Observation-Driven Agent-Based Modeling and Analysis Framework for C. elegans Embryogenesis.
- Author
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Wang, Zi, Ramsey, Benjamin J., Wang, Dali, Wong, Kwai, Li, Husheng, Wang, Eric, and Bao, Zhirong
- Subjects
MULTIAGENT systems ,CAENORHABDITIS elegans ,EMBRYOLOGY ,IMAGE analysis ,CELLS ,CELL motility ,CELL communication ,BEHAVIOR - Abstract
With cutting-edge live microscopy and image analysis, biologists can now systematically track individual cells in complex tissues and quantify cellular behavior over extended time windows. Computational approaches that utilize the systematic and quantitative data are needed to understand how cells interact in vivo to give rise to the different cell types and 3D morphology of tissues. An agent-based, minimum descriptive modeling and analysis framework is presented in this paper to study C. elegans embryogenesis. The framework is designed to incorporate the large amounts of experimental observations on cellular behavior and reserve data structures/interfaces that allow regulatory mechanisms to be added as more insights are gained. Observed cellular behaviors are organized into lineage identity, timing and direction of cell division, and path of cell movement. The framework also includes global parameters such as the eggshell and a clock. Division and movement behaviors are driven by statistical models of the observations. Data structures/interfaces are reserved for gene list, cell-cell interaction, cell fate and landscape, and other global parameters until the descriptive model is replaced by a regulatory mechanism. This approach provides a framework to handle the ongoing experiments of single-cell analysis of complex tissues where mechanistic insights lag data collection and need to be validated on complex observations. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
30. Editorial: C. elegans host-microbiome interactions: From medical to ecological and evolutionary model.
- Author
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Herman, Michael A., E. Irazoqui, Javier, Samuel, Buck S., and Vega, Nic
- Subjects
EVOLUTIONARY models ,ECOLOGICAL models ,CAENORHABDITIS elegans ,CAENORHABDITIS ,MOLECULAR microbiology ,CYTOLOGY ,MOLECULAR virology - Published
- 2022
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- View/download PDF
31. Embryogenesis in C. elegans after elimination of individual blastomeres or induced alteration of the cell division order.
- Author
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Junkersdorf, Bernd and Schierenberg, Einhard
- Abstract
Our earlier studies on embryonic arrest mutants of C. elegans had indicated that early deviations from the normal temporal and spatial pathway of development lead to monstrous terminal phenotypes with little resemblance to a hatched juvenile. To analyze more directly the roles of different parameters for cellular pattern formation, various experiments with a laser microbeam have now been performed and are described in this and the accompanying paper. By ablating early blastomeres we demonstrate here that the establishment of certain cell lineages is not necessary for the generation of a hatching juvenile. However, no replacement of missing cells was observed in these cases, and the resultant animals lacked those structures which are normally produced by the ablated cells. We found that retardation of cell cycle periods in certain cell lineages and thus a change in the normal order of cell divisions is compatible with development to a hatching juvenile. This is also true when, after irradiation of gut precursor cells, their inward migration is considerably delayed. Our results demonstrate that the invariant pattern of early nematode embryogenesis is not a necessary prerequisite for normal development. Studying parameters necessary for gastrulation we found that after irradiation leading to prolonged cell cycle periods the undivided gut founder cell itself rather than its two daughters moves into the center of the embryo. We removed individual early blastomeres and tested whether the typical inward movement of gut precursors still took place. Our results show that the presence of specific neighboring founder cells is not required, indicating that prospective gut cells reduce their cohesive contacts with adjacent blastomeres prior to the onset of gastrulation. [ABSTRACT FROM AUTHOR]
- Published
- 1992
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- View/download PDF
32. The effect of common paralytic agents used for fluorescence imaging on redox tone and ATP levels in Caenorhabditis elegans.
- Author
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Morton, Katherine S., Wahl, Ashlyn K., and Meyer, Joel N.
- Subjects
OXIDATION-reduction reaction ,CAENORHABDITIS ,RESTRAINT of patients ,CAENORHABDITIS elegans ,FLUORESCENCE ,ROTENONE ,PURINERGIC receptors - Abstract
One aspect of Caenorhabditis elegans that makes it a highly valuable model organism is the ease of use of in vivo genetic reporters, facilitated by its transparent cuticle and highly tractable genetics. Despite the rapid advancement of these technologies, worms must be paralyzed for most imaging applications, and few investigations have characterized the impacts of common chemical anesthetic methods on the parameters measured, in particular biochemical measurements such as cellular energetics and redox tone. Using two dynamic reporters, QUEEN-2m for relative ATP levels and reduction-oxidation sensitive GFP (roGFP) for redox tone, we assess the impact of commonly used chemical paralytics. We report that no chemical anesthetic is entirely effective at doses required for full paralysis without altering redox tone or ATP levels, and that anesthetic use alters the detected outcome of rotenone exposure on relative ATP levels and redox tone. We also assess the use of cold shock, commonly used in combination with physical restraint methods, and find that cold shock does not alter either ATP levels or redox tone. In addition to informing which paralytics are most appropriate for research in these topics, we highlight the need for tailoring the use of anesthetics to different endpoints and experimental questions. Further, we reinforce the need for developing less disruptive paralytic methods for optimal imaging of dynamic in vivo reporters. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
33. Reproductive system, temperature, and genetic background effects in experimentally evolving populations of Caenorhabditis elegans.
- Author
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Baran, Joanna K., Kosztyła, Paulina, Antoł, Weronika, Labocha, Marta K., Sychta, Karolina, Drobniak, Szymon M., and Prokop, Zofia M.
- Subjects
GENITALIA ,HEREDITY ,CAENORHABDITIS elegans ,CAENORHABDITIS ,TEMPERATURE - Abstract
Experimental evolution (EE) is a powerful research framework for gaining insights into many biological questions, including the evolution of reproductive systems. We designed a long-term and highly replicated EE project using the nematode C. elegans, with the main aim of investigating the impact of reproductive system on adaptation and diversification under environmental challenge. From the laboratory-adapted strain N2, we derived isogenic lines and introgressed the fog-2(q71) mutation, which changes the reproductive system from nearly exclusive selfing to obligatory outcrossing, independently into 3 of them. This way, we obtained 3 pairs of isogenic ancestral populations differing in reproductive system; from these, we derived replicate EE populations and let them evolve in either novel (increased temperature) or control conditions for over 100 generations. Subsequently, fitness of both EE and ancestral populations was assayed under the increased temperature conditions. Importantly, each population was assayed in 2–4 independent blocks, allowing us to gain insight into the reproducibility of fitness scores. We expected to find upward fitness divergence, compared to ancestors, in populations which had evolved in this treatment, particularly in the outcrossing ones due to the benefits of genetic shuffling. However, our data did not support these predictions. The first major finding was very strong effect of replicate block on populations' fitness scores. This indicates that despite standardization procedures, some important environmental effects were varying among blocks, and possibly compounded by epigenetic inheritance. Our second key finding was that patterns of EE populations' divergence from ancestors differed among the ancestral isolines, suggesting that research conclusions derived for any particular genetic background should never be generalized without sampling a wider set of backgrounds. Overall, our results support the calls to pay more attention to biological variability when designing studies and interpreting their results, and to avoid over-generalizations of outcomes obtained for specific genetic and/or environmental conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
34. Antibacterial activity of cinnamon essential oil and its main component of cinnamaldehyde and the underlying mechanism.
- Author
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Chengjie Shu, Ling Ge, Zhuohang Li, Bin Chen, Shengliang Liao, Lu Lu, Qinlin Wu, Xinyi Jiang, Yuhan An, Zongde Wang, and Man Qu
- Subjects
ESSENTIAL oils ,CAENORHABDITIS elegans ,ANTIBACTERIAL agents ,CAENORHABDITIS ,CINNAMON ,ANTIMICROBIAL peptides ,VEGETABLE oils - Abstract
Background: Plant essential oils have long been regarded as repositories of antimicrobial agents. In recent years, they have emerged as potential alternatives or supplements to antimicrobial drugs. Although literature reviews and previous studies have indicated that cinnamon essential oil (CIEO) and its major component, cinnamaldehyde (CID), possess potent antibacterial activities, their antibacterial mechanisms, especially the in vivo antibacterial mechanisms, remain elusive. Methods: In this study, we utilized the in vivo assessment system of Caenorhabditis elegans (C. elegans) to investigate the effects and mechanisms of high dose (100 mg/L) and low dose (10 mg/L) CIEO and CID in inhibiting Pseudomonas aeruginosa (P. aeruginosa). In addition, we also examined the in vitro antibacterial abilities of CIEO and CID against other common pathogens including P. aeruginosa and 4 other strains. Results: Our research revealed that both high (100 mg/L) and low doses (10 mg/L) of CIEO and CID treatment significantly alleviated the reduction in locomotion behavior, lifespan, and accumulation of P. aeruginosa in C. elegans infected with the bacteria. During P. aeruginosa infection, the transcriptional expression of antimicrobial peptide-related genes (lys-1 and lys-8) in C. elegans was upregulated with low-dose CIEO and CID treatment, while this trend was suppressed at high doses. Further investigation suggested that the PMK-1 mediated p38 signaling pathway may be involved in the regulation of CIEO and CID during nematode defense against P. aeruginosa infection. Furthermore, in vitro experimental results also revealed that CIEO and CID exhibit good antibacterial effects, which may be associated with their antioxidant properties. Conclusion: Our results indicated that low-dose CIEO and CID treatment could activate the p38 signaling pathway in C. elegans, thereby regulating antimicrobial peptides, and achieving antimicrobial effects. Meanwhile, high doses of CIEO and CID might directly participate in the internal antimicrobial processes of C. elegans. Our study provides research basis for the antibacterial properties of CIEO and CID both in vivo and in vitro. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
35. Effect of Different Edible Trichosanthes Germplasm on Its Seed Oil to Enhance Antioxidant and Anti-Aging Activity in Caenorhabditis elegans.
- Author
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Wang, Wenqian, Li, Shan, Zhu, Yunguo, Zhu, Ruilin, Du, Xiling, Cui, Xianghuan, Wang, Hongbing, and Cheng, Zhou
- Subjects
OILSEEDS ,CAENORHABDITIS elegans ,GERMPLASM ,CAENORHABDITIS ,AGING prevention ,UNSATURATED fatty acids - Abstract
The seeds of various Trichosanthes L. plants have been frequently used as snacks instead of for traditional medicinal purposes in China. However, there is still a need to identify the species based on seeds from Trichosanthes germplasm for the potential biological activities of their seed oil. In this study, 18 edible Trichosanthes germplasm from three species were identified and distinguished at a species level using a combination of seed morphological and microscopic characteristics and nrDNA-ITS sequences. Seed oil from the edible Trichosanthes germplasm significantly enhanced oxidative stress tolerance, extended lifespan, delayed aging, and improved healthspan in Caenorhabditis elegans. The antioxidant activity of the seed oil exhibits a significant positive correlation with its total unsaturated fatty acid content among the 18 edible Trichosanthes germplasm, suggesting a genetic basis for this trait. The biological activities of seed oil varied among species, with T. kirilowii Maxim. and T. rosthornii Harms showing stronger effects than T. laceribractea Hayata. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
36. The Effects of Caustic Soda and Benzocaine on Directed Grooming to the Eyestalk in the Glass Prawn, Palaemon elegans , Are Consistent with the Idea of Pain in Decapods.
- Author
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Barr, Stuart and Elwood, Robert W.
- Subjects
DECAPODA ,STARTLE reaction ,SODIUM hydroxide ,GLASS ,TISSUE wounds ,SHRIMPS ,CAENORHABDITIS ,ANESTHETICS - Abstract
Simple Summary: The possibility of pain occurring in animals is often accepted if various criteria are fulfilled. These criteria include prolonged grooming or rubbing at the site of a wound or tissue damage, or other behaviour involving the site of damage. We also expect to see a reduction in such activities if a local anaesthetic is applied. Here, we report on an experiment that applied caustic soda, a known irritant in humans, to one eyestalk of the glass prawn. This caused immediate escape responses and then nipping and picking at the treated eyestalk rather than at the untreated eyestalk. Prior application of a local anaesthetic reduced the amount of directed behaviour. However, the local anaesthetic also appeared to be an irritant as it too caused immediate escape responses and directed behaviour to the eyestalk. The results provide further support to the idea that these animals can experience pain. Acceptance of the possibility of pain in animals usually requires that various criteria are fulfilled. One such criterion is that a noxious stimulus or wound would elicit directed rubbing or grooming at the site of the stimulus. There is also an expectation that local anaesthetics would reduce these responses to damage. These expectations have been fulfilled in decapod crustaceans but there has been criticism of a lack of replication. Here, we report an experiment on the effects of a noxious chemical, sodium hydroxide, applied to one eyestalk of the glass prawn. This caused an immediate escape tail-flick response. It then caused nipping and picking with the chelipeds at the treated eyestalk but much less so at the alternative eyestalk. Prior treatment with benzocaine also caused an immediate tail-flick and directed behaviour, suggesting that this agent is aversive. Subsequently, however, it reduced the directed behaviour caused by caustic soda. We thus demonstrated responses that are consistent with the idea of pain in decapod crustaceans. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
37. Patterns of Genomic Diversity in a Fig-Associated Close Relative of Caenorhabditis elegans.
- Author
-
Woodruff, Gavin C, Willis, John H, and Phillips, Patrick C
- Subjects
CAENORHABDITIS elegans ,POPULATION differentiation ,DEVELOPMENTAL genetics ,POPULATION dynamics ,FIG ,CAENORHABDITIS - Abstract
The evolution of reproductive mode is expected to have profound impacts on the genetic composition of populations. At the same time, ecological interactions can generate close associations among species, which can in turn generate a high degree of overlap in their spatial distributions. Caenorhabditis elegans is a hermaphroditic nematode that has enabled extensive advances in developmental genetics. Caenorhabditis inopinata , the sister species of C. elegans , is a gonochoristic nematode that thrives in figs and obligately disperses on fig wasps. Here, we describe patterns of genomic diversity in C. inopinata. We performed RAD-seq on individual worms isolated from the field across three Okinawan island populations. C. inopinata is about five times more diverse than C. elegans. Additionally, C. inopinata harbors greater differences in diversity among functional genomic regions (such as between genic and intergenic sequences) than C. elegans. Conversely, C. elegans harbors greater differences in diversity between high-recombining chromosome arms and low-recombining chromosome centers than C. inopinata. F
ST is low among island population pairs, and clear population structure could not be easily detected among islands, suggesting frequent migration of wasps between islands. These patterns of population differentiation appear comparable with those previously reported in its fig wasp vector. These results confirm many theoretical population genetic predictions regarding the evolution of reproductive mode and suggest C. inopinata population dynamics may be driven by wasp dispersal. This work sets the stage for future evolutionary genomic studies aimed at understanding the evolution of sex as well as the evolution of ecological interactions. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
38. Using C. elegans Forward and Reverse Genetics to Identify New Compounds with Anthelmintic Activity.
- Author
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Mathew, Mark D., Mathew, Neal D., Miller, Angela, Simpson, Mike, Au, Vinci, Garland, Stephanie, Gestin, Marie, Edgley, Mark L., Flibotte, Stephane, Balgi, Aruna, Chiang, Jennifer, Giaever, Guri, Dean, Pamela, Tung, Audrey, Roberge, Michel, Roskelley, Calvin, Forge, Tom, Nislow, Corey, and Moerman, Donald
- Subjects
CAENORHABDITIS elegans genetics ,REVERSE genetics ,ANTHELMINTICS ,NEMATODES ,NEMATOCIDES ,DRUG resistance ,ANIMAL behavior - Abstract
Background: The lack of new anthelmintic agents is of growing concern because it affects human health and our food supply, as both livestock and plants are affected. Two principal factors contribute to this problem. First, nematode resistance to anthelmintic drugs is increasing worldwide and second, many effective nematicides pose environmental hazards. In this paper we address this problem by deploying a high throughput screening platform for anthelmintic drug discovery using the nematode Caenorhabditis elegans as a surrogate for infectious nematodes. This method offers the possibility of identifying new anthelmintics in a cost-effective and timely manner. Methods/Principal findings: Using our high throughput screening platform we have identified 14 new potential anthelmintics by screening more than 26,000 compounds from the Chembridge and Maybridge chemical libraries. Using phylogenetic profiling we identified a subset of the 14 compounds as potential anthelmintics based on the relative sensitivity of C. elegans when compared to yeast and mammalian cells in culture. We showed that a subset of these compounds might employ mechanisms distinct from currently used anthelmintics by testing diverse drug resistant strains of C. elegans. One of these newly identified compounds targets mitochondrial complex II, and we used structural analysis of the target to suggest how differential binding of this compound may account for its different effects in nematodes versus mammalian cells. Conclusions/Significance: The challenge of anthelmintic drug discovery is exacerbated by several factors; including, 1) the biochemical similarity between host and parasite genomes, 2) the geographic location of parasitic nematodes and 3) the rapid development of resistance. Accordingly, an approach that can screen large compound collections rapidly is required. C. elegans as a surrogate parasite offers the ability to screen compounds rapidly and, equally importantly, with specificity, thus reducing the potential toxicity of these compounds to the host and the environment. We believe this approach will help to replenish the pipeline of potential nematicides. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
39. Identifying Multi-Dimensional Co-Clusters in Tensors Based on Hyperplane Detection in Singular Vector Spaces.
- Author
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Zhao, Hongya, Wang, Debby D., Chen, Long, Liu, Xinyu, and Yan, Hong
- Subjects
MULTIDIMENSIONAL databases ,TENSOR algebra ,VECTOR spaces ,DATA analysis ,GENE expression - Abstract
Co-clustering, often called biclustering for two-dimensional data, has found many applications, such as gene expression data analysis and text mining. Nowadays, a variety of multi-dimensional arrays (tensors) frequently occur in data analysis tasks, and co-clustering techniques play a key role in dealing with such datasets. Co-clusters represent coherent patterns and exhibit important properties along all the modes. Development of robust co-clustering techniques is important for the detection and analysis of these patterns. In this paper, a co-clustering method based on hyperplane detection in singular vector spaces (HDSVS) is proposed. Specifically in this method, higher-order singular value decomposition (HOSVD) transforms a tensor into a core part and a singular vector matrix along each mode, whose row vectors can be clustered by a linear grouping algorithm (LGA). Meanwhile, hyperplanar patterns are extracted and successfully supported the identification of multi-dimensional co-clusters. To validate HDSVS, a number of synthetic and biological tensors were adopted. The synthetic tensors attested a favorable performance of this algorithm on noisy or overlapped data. Experiments with gene expression data and lineage data of embryonic cells further verified the reliability of HDSVS to practical problems. Moreover, the detected co-clusters are well consistent with important genetic pathways and gene ontology annotations. Finally, a series of comparisons between HDSVS and state-of-the-art methods on synthetic tensors and a yeast gene expression tensor were implemented, verifying the robust and stable performance of our method. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
40. Evolutionary conservation of the circadian gene timeout in Metazoa.
- Author
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Diyan Li, Yuan Su, Jianbo Tu, Ranlei Wei, Xiaolan Fan, Huadong Yin, Yaodong Hu, Huailiang Xu, Yongfang Yao, Deying Yang, and Mingyao Yang
- Subjects
METAZOA ,DROSOPHILIDAE ,FRUIT flies ,DROSOPHILA ,EMBRYOLOGY ,GENETICS ,BIOLOGICAL evolution ,CAENORHABDITIS - Abstract
Timeless (Tim) is considered to function as an essential circadian clock gene in Drosophila. Putative homologues of the Drosophila timeless gene have been identified in both mice and humans. While Drosophila contains two paralogs, timeless and timeout, acting in clock/light entrainment and chromosome integrity/photoreception, respectively, mammals contain only one Tim homolog. In this paper, we study the phylogeny of the timeless/timeout family in 48 species [including 1 protozoan (Guillardia theta), 1 nematode (Caenorhabditis elegans), 8 arthropods and 38 chordates], for which whole genome data are available by using MEGA (Molecular Evolutionary Genetics Analysis). Phylogenetic Analysis by Maximum Likelihood (PAML) was used to analyze the selective pressure acting on metazoan timeless/timeout genes. Our phylogeny clearly separates insect timeless and timeout lineages and shows that non-insect animal Tim genes are homologs of insect timeout. In this study, we explored the relatively rapidly evolving timeless lineage that was apparently lost from most deuterostomes, including chordates, and from Caenorhabditis elegans. In contrast, we found that the timeout protein, often confusingly called "timeless" in the vertebrate literature, is present throughout the available animal genomes. Selection results showed that timeout is under weaker negative selection than timeless. Finally, our phylogeny of timeless/timeout showed an evolutionary conservation of the circadian clock gene timeout in Metazoa. This conservation is in line with its multifunctionality, being essential for embryonic development and maintenance of chromosome integrity, among others. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
41. Disruption of O-GlcNAc cycling in C. elegans perturbs nucleotide sugar pools and complex glycans.
- Author
-
Ghosh, Salil K., Bond, Michelle R., Love, Dona C., Gilbert Ashwell, G., Krause, Michael W., and Hanover, John A.
- Subjects
N-acetylglucosamine ,GLUCOSAMINE ,CAENORHABDITIS elegans ,CAENORHABDITIS ,NUCLEOTIDES - Abstract
The carbohydrate modification of serine and threonine residues with O-linked beta- N-acetylglucosamine (O-GlcNAc) is ubiquitous and governs cellular processes ranging from cell signaling to apoptosis.The O-GlcNAc modification along with other carbohydrate modifications, including N-linked and O-linked glycans, glycolipids, and sugar polymers, all require the use of the nucleotide sugar UDP-GlcNAc, the end product of the hexosamine biosynthetic pathway (HBP). In this paper, we describe the biochemical consequences resulting from perturbation of the O-GlcNAc pathway in C. elegans lacking O-GlcNAc transferase and O-GlcNAcase activities. In ogt-1 null animals, steady-state levels of UDPGlcNAc/ UDP-GalNAc and UDP-glucose were substantially elevated. Transcripts of genes encoding for key members in the HBP (gfat-2, gna-2, C36A4.4) and trehalose metabolism (tre-1, tre-2, tps-2) were elevated in ogt-1 null animals. While there is no evidence to suggest changes in the profile of N-linked glycans in the ogt-1 and oga-1 mutants, glycans insensitive to PNGase digestion (including O-linked glycans, glycolipids, and glycopolymers) were altered in these strains. Our data support that changes in O-GlcNAcylation alters nucleotide sugar production, overall glycan composition, and transcription of genes encoding glycan processing enzymes. These data along with our previous findings that disruption in O-GlcNAc cycling alters macronutrient storage underscores the noteworthy influence this posttranslational modification plays in nutrient sensing. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
42. But can they learn? My accidental discovery of learning and memory in C. elegans.
- Author
-
Rankin, Catharine H.
- Subjects
CAENORHABDITIS elegans ,LEARNING by discovery ,MEMORY ,CAENORHABDITIS ,COLLEGE teachers - Abstract
I did not set out to study C. elegans. My undergraduate and graduate training was in Psychology. My postdoctoral work involved studying learning and memory in 1 mm diameter juvenile Aplysia californica. As a starting Assistant Professor when I attempted to continue my studies on Aplysia I encountered barriers to carrying out that work; at about the same time I was introduced to Caenorhabditis elegans and decided to investigate whether they could learn and remember. My laboratory was the first to demonstrate conclusively that C. elegans could learn and in the years since then my lab and many others have demonstrated that C. elegans is capable of a variety of forms of learning and memory. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
43. An in vivo microfluidic study of bacterial transit in C. elegans nematodes.
- Author
-
Viri, Vittorio, Cornaglia, Matteo, Atakan, Huseyin Baris, Lehnert, Thomas, and Gijs, Martin A. M.
- Subjects
CAENORHABDITIS ,CAENORHABDITIS elegans ,NEMATODES ,GREEN fluorescent protein ,IN vivo studies ,FLUORESCENT proteins ,FLUORESCENCE microscopy - Abstract
Caenorhabditis elegans (C. elegans) constitutes an important model organism for use in nutrition and aging studies. We report a novel method for studying the dynamics of Escherichia coli (E. coli) bacterial transit through the worms' intestine. A microfluidic chip was designed for alternating C. elegans on-chip culture and immobilization, thereby enabling periodic high-resolution time-lapse imaging at single-worm resolution over several days. Immobilization was achieved in a reversible way using arrays of tapered channels suitable for assay parallelization. Dedicated C. elegans feeding protocols were applied. Two E. coli bacterial strains, HT115 and OP50, respectively labeled with green fluorescent protein (GFP) and red fluorescent protein (RFP), were used as food source and imaged with fluorescence microscopy techniques to measure relevant parameters of the bacterial transit process. Feeding behavior and E. coli transit dynamics in the whole intestinal tract of the worms were characterized in an automated way over the first 3 days of adulthood, revealing both fast transit phenomena and variations in microbial accumulation. In particular, we studied the bacterial food transit periodicity in wild-type and eat-2 (ad465) mutant C. elegans strains in both trapped and free-swimming conditions. In order to further demonstrate the versatility of our microfluidic platform, we also studied drug-induced modifications of the bacterial transit by measuring the response of the worms' intestine to exposure to the neurotransmitter serotonin. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
44. Silver(I) complexes with different pyridine-4,5-dicarboxylate ligands as efficient agents for the control of cow mastitis associated pathogens.
- Author
-
Andrejević, Tina P., Milivojevic, Dusan, Glišić, Biljana Đ., Kljun, Jakob, Stevanović, Nevena Lj., Vojnovic, Sandra, Medic, Strahinja, Nikodinovic-Runic, Jasmina, Turel, Iztok, and Djuran, Miloš I.
- Subjects
CAENORHABDITIS elegans ,COWS ,CAENORHABDITIS ,BACTERIAL cell walls ,DAIRY industry ,SILVER ,SEARCH engines ,SILVER compounds - Abstract
Infections of the cow udder leading to mastitis and lower milk quality are one of the biggest problems in the dairy industry worldwide. Unfortunately, therapeutic options for the treatment of cow mastitis are limited as a consequence of the development of pathogens that are resistant to conventionally used antibiotics. In the search for agents that will be active against cow mastitis associated pathogens, in the present study, five new silver(I) complexes with different chelating pyridine-4,5-dicarboxylate types of ligands, [Ag(NO
3 )(py-2py)]n (1), [Ag(NO3 )(py-2metz)]n (2), [Ag(CH3 CN)(py-2py)]BF4 (3), [Ag(py-2tz)2 ]BF4 (4) and [Ag(py-2metz)2 ]BF4 (5), py-2py is dimethyl 2,2′-bipyridine-4,5-dicarboxylate, py-2metz is dimethyl 2-(4-methylthiazol-2-yl)pyridine-4,5-dicarboxylate and py-2tz is dimethyl 2-(thiazol-2-yl)pyridine-4,5-dicarboxylate, were synthesized, structurally characterized and assessed for in vitro antimicrobial activity using both standard bioassay and clinical isolates from a contaminated milk sample obtained from a cow with mastitis. These complexes showed remarkable activity against the standard panel of microorganisms and a selection of clinical isolates from the milk of the cow diagnosed with mastitis. With the aim of determining the therapeutic potential of silver(I) complexes, their toxicity in vivo against the model organism, Caenorhabditis elegans (C. elegans), was investigated. The complexes that had the best therapeutic profile, 2 and 5, induced bacterial membrane depolarization and the production of reactive oxygen species (ROS) in Candida albicans cells and inhibited the hyphae as well as the biofilm formation. Taken together, the presented data suggest that the silver(I) complexes with pyridine ligands could be considered for the treatment of microbial pathogens, which are causative agents of cow mastitis. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
45. Simira cordifolia protects against metal induced-toxicity in Caenorhabditis elegans.
- Author
-
Duran-Izquierdo, Margareth, Sierra-Marquez, Lucellys, Taboada-Alquerque, Maria, and Olivero-Verbel, Jesus
- Subjects
HEAVY metals ,CAENORHABDITIS ,CAENORHABDITIS elegans ,LEAD ,HEAVY metal toxicology ,METALS ,THERMAL stresses ,IRIDOIDS - Abstract
Simira cordifolia (Hook.f.) Steyerm (Rubiaceae) is a vascular plant used in Northern Colombia as a source of pigments and wood. However, there is a lack of information regarding its pharmacology and toxicity. This research aimed to study the hydroalcoholic extract of Simira cordifolia as a protector against metal-induced toxicity in Caenorhabditis elegans. Preliminary phytochemical screening of the hydroalcoholic extract of S. cordifolia (HAE-Sc) was conducted using HPLC-ESI-QTOF. Wild-type N2 C. elegans larvae were exposed to different concentrations of HAE-Sc evaluating lethality (50–5000 μg/mL), growth, lifespan, resistance to heat stress, and its protective effect against Mercury (Hg)-, Lead (Pb)- and Cadmium (Cd)-induced lethality (50–1000 μg/mL). The main metabolites present in the extract were iridoids, βcarboline-alkaloids and polyphenols. Bioassays demonstrated that HAE-Sc exhibited low toxicity, with significant lethality (4.2% and 9.4%) occurring at 2500–5000 μg/mL. Growth inhibition reached up to 23.3%, while reproduction declined 13% and 17% at concentrations 500 and 1000 μg/mL, respectively. HAESc enhanced the survival rate of the nematode under thermal stress by up to 79.8%, and extended the mean lifespan of worms by over 33% compared to control. The average lifespan was prolonged by 15.3% and 18.5% at 50 and 100 μg/ mL HAE-Sc, respectively. The extract (1000 μg/mL) was able to reduce the death of C. elegans in the presence of heavy metals up to 65.9, 96.8% and 87% for Pb, Hg, and Cd, respectively. In summary, S. cordifolia shows potential protective effects in C. elegans against toxicity caused by heavy metals and heat. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
46. On-demand optical immobilization of Caenorhabditis elegans for high-resolution imaging and microinjection.
- Author
-
Hwang, Hyundoo, Krajniak, Jan, Matsunaga, Yohei, Benian, Guy M., and Lu, Hang
- Subjects
CAENORHABDITIS ,CAENORHABDITIS elegans ,MICROINJECTIONS ,MICROINJECTION (Cytology) ,CYTOPROTECTION - Abstract
This paper describes a novel selective immobilization technique based on optical control of the sol–gel transition of thermoreversible Pluronic gel, which provides a simple, versatile, and biocompatible approach for high-resolution imaging and microinjection of Caenorhabditis elegans. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
47. Green tea aroma fraction reduces β-amyloid peptide-induced toxicity in Caenorhabditis elegans transfected with human β-amyloid minigene.
- Author
-
Atsushi Takahashi, Tatsuro Watanabe, Takashi Fujita, Toshio Hasegawa, Michio Saito, and Masami Suganuma
- Subjects
ALZHEIMER'S disease prevention ,GREEN tea ,CAENORHABDITIS ,FRACTIONS ,ANTIOXIDANTS ,THERAPEUTICS - Abstract
The article discusses a research paper which examines the preventive effects on Alzheimer's diseases (AD) of a unique aroma of Japanese green tea. Topics discussed include a transgenic Caenorhabditis elegans (C. elegans), fractionation of green tea into volatile and non-volatile fractions called roasty aroma, and antioxidant activity.
- Published
- 2014
- Full Text
- View/download PDF
48. The Laplacian spectrum of neural networks.
- Author
-
de Lange, Siemon C., de Reus, Marcel A., and van den Heuvel, Martijn P.
- Subjects
BRAIN research ,GRAPHIC methods ,CAENORHABDITIS ,MACAQUES ,NEURAL circuitry - Abstract
The brain is a complex network of neural interactions, both at the microscopic and macroscopic level. Graph theory is well suited to examine the global network architecture of these neural networks. Many popular graph metrics, however, encode average properties of individual network elements. Complementing these "conventional" graph metrics, the eigenvalue spectrum of the normalized Laplacian describes a network's structure directly at a systems level, without referring to individual nodes or connections. In this paper, the Laplacian spectra of the macroscopic anatomical neuronal networks of the macaque and cat, and the microscopic network of the Caenorhabditis elegans were examined. Consistent with conventional graph metrics, analysis of the Laplacian spectra revealed an integrative community structure in neural brain networks. Extending previous findings of overlap of network attributes across species, similarity of the Laplacian spectra across the cat, macaque and C. elegans neural networks suggests a certain level of consistency in the overall architecture of the anatomical neural networks of these species. Our results further suggest a specific network class for neural networks, distinct from conceptual small-world and scale-free models as well as several empirical networks. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
49. Conservation of large foci formation in arrested oocytes of Caenorhabditis nematodes.
- Author
-
Jud M, Razelun J, Bickel J, Czerwinski M, and Schisa JA
- Subjects
- Animals, Female, Nuclear Pore Complex Proteins metabolism, Ovulation, Caenorhabditis cytology, Oocytes cytology, Ribonucleoproteins metabolism
- Abstract
Within the rhabditid phylogeny of nematodes, the great majority of species are gonochoristic, having evolved as obligate male/female species. In contrast, the well-studied nematode model system, Caenorhabditis elegans, is androdioecious, utilizing a hermaphroditic/male reproductive system. We have previously determined that in the arrested oocytes of old-aged C. elegans hermaphrodites with depleted sperm, large cytoplasmic ribonucleoprotein foci form. The formation of these foci is reversible, as they dissociate within 3 h after a male mates with the hermaphrodite, resupplying it with sperm. The functional significance of these oocyte foci is not known and previously has not been clear for a hermaphroditic species in which oocytes of young adults wait only approximately 23 min to be fertilized. One hypothesis is that the foci function to maintain maternal mRNAs in oocytes while fertilization is delayed. In this paper, we examine four gonochoristic rhabditid species: Caenorhabditis remanei, Caenorhabditis sp. CB5161, Caenorhabditis sp. PS1010, and Rhabditella axei DF5006. We demonstrate that in three of these four species, ovulation arrests in unmated females until mating occurs and large cytoplasmic foci develop in arrested oocytes. The oocyte foci contain nuclear pore proteins and, in C. remanei at least, the RNA-binding protein MEX-3 as well as RNA. We speculate that these foci maintain the integrity of ooctyes, possibly maintaining the stability or translational repression of maternal mRNAs in unmated females. We further speculate that their presence in oocytes of old-aged C. elegans hermaphrodites is due to conservation from an ancestral gonochoristic state.
- Published
- 2007
- Full Text
- View/download PDF
50. Ant Colony Based Mechanism for Increasing Life Time of Critical Nodes.
- Author
-
Sandeep, J.
- Subjects
- *
AD hoc computer networks , *ANT algorithms , *THRESHOLD energy , *NETWORK performance , *ENERGY consumption , *ENERGY density , *PHEROMONES , *CAENORHABDITIS , *HYMENOPTERA - Abstract
MANET nodes act as a host as well as a router which increases the significance of every node for their participation in communication. Loss of any node in the network results in failure of links connected to the node which brings the importance of increased lifespan of a node. Some nodes during frequent transaction at critical network scenario consume more energy and become ill with critical energy level. Special attention towards these nodes can improve the lifespan of the node. In this paper an ant colony-based pheromone deposition mechanism was proposed to extend the lifetime of ill nodes. Pheromone deposited for the neighbor in the pheromone table helps in identifying frequently communicated neighbor. The proposed algorithm identifies the ill node and requests its frequently communicated neighbor for a tie up. The neighbor shares the workload of the ill node with mutual agreement. This method also improves the performance of a network by limiting pheromone deposition practice for low weighted nodes with low energy and high density (packet in queue). The proposed method increases lifespan of ill nodes and thereby increases the lifetime of entire network. The proposed work was also compared with existing protocol and the results have proved that the proposed mechanism has increased lifetime and reduced energy consumption of the entire network. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
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