Zervas CG et al. (2002) Curr Biol "Integrin adhesion: when is a kinase a kinase?"

Zervas CG, Brown NH

[Curr Biol, 2002]

Recent genetic studies in the worm Caenorhabditis elegans and fruitfly Drosophila have revealed the essential role integrin-linked kinase plays in integrin adhesion - but it apparently acts in this role as an adaptor rather than a kinase.

Zhang J et al. (2018) J Appl Toxicol "Multiple biological defects caused by calycosin-7-O--d-glucoside in the nematode Caenorhabditis elegans are associated with the activation of oxidative damage."

Yang Y, Ma W, Han Y, Zhang J, Qin X, Xue X

[J Appl Toxicol, 2018]

Calycosin-7-O--d-glucoside (CG) is an important active isoflavone compound in Radix Astragali that has many bioactivities. However, the toxicological effects and related toxicological mechanism of CG have been rarely documented. The purpose of the present study was to evaluate the toxicity effects of CG on the model organism Caenorhabditis elegans. Some characteristics of the nematode, including lifespan, movement behavior and reproductive capacity, were used to detect the toxic effects of CG on C. elegans. The results showed that CG could shorten the lifespan of C. elegans by up to 25.3% and severely damage the movement of N2 larvae compared with the control group. Moreover, CG could prolong the generation times and reduce the brood sizes. Furthermore, CG promoted the formation of reactive oxygen species (ROS), which caused oxidative stress, increased the mRNA expression of sod-1, sod-2, sod-3, sod-5, ctl-1, ctl-2 and ctl-3, and induced the antioxidant enzymes activities of superoxide dismutase and catalase to scavenge free radicals. However, antioxidant treatment experiments showed that Trolox could reduce the level of ROS caused by CG to the normal state of the control. These results suggested that the generation and elimination of ROS could not restore normal homeostasis in C. elegans treated by CG. These findings indicated that the activation of oxidative damage is one of the most important toxic mechanisms of CG in C. elegans.

Elkhedir A et al. (2022) Plant Foods Hum Nutr "Capsaicinoid-Glucosides of Fresh Hot Pepper Promotes Stress Resistance and Longevity in Caenorhabditis elegans."

Iqbal A, Albahi A, Rong L, Xu X, Tao M, Elkhedir A

[Plant Foods Hum Nutr, 2022]

In this study, capsaicin-glucoside and dihydro-capsaicin-glucoside derived from fresh hot-red pepper were isolated and identified using UPLC-ESI-Q-TOF-MS/PDA. Synchronized worms were treated with capsaicinoid-glucosides (CG), and then lifespan and stress resistance were examined. The 50g/ml concentration of CG-intake could effectively protect the Caenorhabditis elegans (C. elegans) against stresses factors including oxidation and heat as well as reactive oxygen species (ROS), thereby enhancing the survival of CG-treated worms under stress. Enhancing stress resistance in CG-treated worms could be due to the increased expressions of stress-related genes in C. elegans such as daf-16, skn-1 and their downstream target genes (sod-3, hsp-16.2, gst-4 and gcs-1). Lifespan study of different C. elegans strains and RT-PCR showed that the CG-mediated lifespan extension was dependent on DAF-16/FOXO and SKN-1/Nrf2 transcription factors. The study is a step forward in exploring the stress resistance and anti-aging properties of this beneficial extract. Thus, this study will be useful in formulating remedies for stresses factors and age associated disorders.

Minakuchi Y et al. (2004) Bioinformatics "SPI: a tool for incorporating gene expression data into a four-dimensional database of Caenorhabditis elegans embryogenesis."

Ito M, Minakuchi Y, Kohara Y

[Bioinformatics, 2004]

Motivation: A comprehensive gene expression database is essential for computer modeling and simulation of biological phenomena, including development. Development is a four-dimensional (4D; 3D structure and time course) phenomenon. We are constructing a 4D database of gene expression for the early embryogenesis of the nematode Caenorhabditis elegans. As a framework of the 4D database, we have constructed computer graphics (CG), into which we will incorporate the expression data of a number of genes at the subcellular level. However, the assignment of 3D distribution of gene products (protein, mRNA), of embryos at various developmental stages, is both difficult and tedious. We need to automate this process. For this purpose, we developed a new system, named SPI after superimposing fluorescent confocal microscopic data onto a CG framework. Results: The scheme of this system comprises the following: (1) acquirement of serial sections (40 slices) of fluorescent confocal images of three colors (4',6'-diamino-2-phenylindole (DAPI) for nuclei, indodicarbocyanine (Cy-3) for the internal marker, which is a germline-specific protein POS-1 and indocarbocyanine (Cy-5) for the gene product to be examined); (2) identification of several features of the stained embryos, such as contour, developmental stage and position of the internal marker; (3) selection of CG images of the corresponding stage for template matching; (4) superimposition of serial sections onto the CG; (5) assignment of the position of superimposed gene products. The Snakes algorithm identified the embryo contour. The detection accuracy of embryo contours was 92.1% when applied to 2- to 28-cell-stage embryos. The accuracy of the developmental stage prediction method was 81.2% for 2- to 8-cell-stage embryos. We manually judged only the later stage embryos because the accuracy for embryos at the later stages was unsatisfactory due to experimental noise effects. Finally, our system chose the optimal CG and performed the superposition and assignment of gene product distribution. We established an initial 4D gene expression database with 56 maternal gene products.

Zhang Q et al. (2015) J Theor Biol "Distribution bias of the sequence matching between exons and introns in exon joint and EJC binding region in C. elegans."

Zhou D, Zheng Y, Zhang Q, Li H, Zhao X

[J Theor Biol, 2015]

We propose a mechanism that there are matching relations between mRNA sequences and corresponding post-spliced introns, and introns play a significant role in the process of gene expression. In order to reveal the sequence matching features, Smith-Waterman local alignment method is used on C. elegans mRNA sequences to obtain optimal matched segments between exon-exon sequences and their corresponding introns. Distribution characters of matching frequency on exon-exon sequences and sequence characters of optimal matched segments are studied. Results show that distributions of matching frequency on exon-exon junction region have obvious differences, and the exon boundary is revealed. Distributions of the length and matching rate of optimal matched segments are consistent with sequence features of siRNA and miRNA. The optimal matched segments have special sequence characters compared with their host sequences. As for the first introns and long introns, matching frequency values of optimal matched segments with high GC content, rich CG dinucleotides and high CG values show the minimum distribution in exon junction complex (EJC) binding region. High CG values in optimal matched segments are main characters in distinguishing EJC binding region. Results indicate that EJC and introns have competitive and cooperative relations in the process of combining on protein coding sequences. Also intron sequences and protein coding sequences do have concerted evolution relations.

Masahiro Ito et al. (1999) International C. elegans Meeting "Toward four-dimensional database of gene expression in C. elegans"

Tomoko Motohashi, Masahiro Ito, Yohei Minakuchi, Yuji KOHARA

[International C. elegans Meeting, 1999]

One of the most challenging targets in the post genomics era is computer simulation of development. We feel C.elegans is the most suitable system for this purpose, since the complete parts list of cells has been identified and the expression patterns and functions of all genes are being analyzed systematically. Aiming at the final goal and at integrating such information, we are constructing a computer graphics (CG)-based four-dimensional (3D + time course) database of gene expression in C.elegans . Thus far, we have made a CG for early embryogenesis up to 100 cell stage based on 4D Nomarski image data including the data kindly supplied by Kevin O'Connel at the University of Wisconsin at Madison. Since it was very hard for conventional image processing software to extract the contour of cells from the Nomarski images, we adopted a 'low-tech' procedure; firstly we traced the contour of individual cells and nuclei by hand-writing on thousands of the original images of the 4D microscopic data and then reconstructed 3D structures by piling up and making relationship among the contour data from different focal planes. The resulting 3D structures of various stage embryos were arranged along the time course of development and connected each other by an interpolating method to finally generate the CG of early embryogenesis. The graphics is faithful to the real embryogenesis, thus, it provides various information such as the volume of individual cells, the extent of cell-cell contact and so on. To incorporate the information of gene expression patterns into the 4D graphics database, we have developed a procedure to superimpose a fluorescent-confocal data of the distribution of mRNA and proteins onto the CG. In the procedure, we use triple color staining, namely, DAPI and Cy-3 for nuclei and POS-1 (P-lineage specific) as internal markers for superimposing, respectively, and Cy-5 for a query gene product. By this fashion, we are incorporating the immunostaining patterns of maternal gene products. We are planning to make the 4D database accessible over the internet.

Wang Z et al. (2015) J Phys Chem B "Probing structural determinants of ATP-binding cassette exporter conformational transition using coarse-grained molecular dynamics."

Wang Z, Liao J

[J Phys Chem B, 2015]

ATP-binding cassette (ABC) exporters pump various substrates across the cell membrane by alternating between inward-facing (IF) and outward-facing (OF) conformations of the transmembrane domains (TMDs). However, the structural determinants of the conformational transition and their functional roles are not fully understood. In this study, we carried out coarse-grained molecular dynamics (CG-MD) simulations with umbrella sampling for the multidrug transporter P-glycoprotein from Caenorhabditis elegans in the presence of the membrane and explicit water molecules. The potential of mean force (PMF) is obtained to identify a reliable pathway where the predicted OF and IF structures are in good agreement with available experiments. The CG-MD simulations reveal that the different transmembrane (TM) helices play distinct but highly cooperative roles in the large-scale conformational changes. Most notably, the CG-MD trajectories show that the periplasmic gate is closed before the cytoplasmic gate is opened during the OF to IF conformational transition in response to the dissociation of the nucleotide-binding domains (NBDs), capturing the unidirectional feature of substrate translocation through the exporter. The structural and dynamical analyses identify the structural determinants and their functional roles in the structural transition. The present work sheds light on how the mechanical force generated upon the NBD dissociation is transferred to the periplasmic end at a distance over 70 A to close the gate, and subsequently to open the cytoplasmic gate. These results extend our understanding of the ABC transport mechanism.

Kanaya S et al. (2001) J Mol Evol "Codon usage and tRNA genes in eukaryotes: correlation of codon usage diversity with translation efficiency and with CG-dinucleotide usage as assessed by multivariate analysis."

Yamada Y, Kudo Y, Ikemura T, Kanaya S, Kinouchi M

[J Mol Evol, 2001]

The species-specific diversity of codon usage in five eukaryotes (Schizosaccharomyces pombe, Caenorhabditis elegans, Drosophila melanogaster, Xenopus laevis, and Homo sapiens) was investigated with principal component analysis. Optimal codons for translation were predicted on the basis of tRNA-gene copy numbers. Highly expressed genes, such as those encoding ribosomal proteins and histones in S. pombe, C. elegans, and D. melanogaster have biased patterns of codon usage which have been observed in a wide range of unicellular organisms. In S. pombe and C elegans, codons contributing positively to the principal component with the largest variance (Z(1)-parameter) corresponded to the optimal codons which were predicted on the basis of tRNA gene numbers. In D. melanogaster, this correlation was less evident, and the codons contributing positively to the Z(1)-parameter corresponded primarily to codons with a C or G in the codon third position. In X. laevis and H. sapiens, codon usage in the genes encoding ribosomal proteins and histones was not significantly biased, suggesting that the primary factor influencing codon-usage diversity in these species is not translation efficiency. Codon-usage diversity in these species is known to reflect primarily isochore structures. In the present study, the second additional factor was explained by the level of use of codons containing CG-dinucleotides, and this is discussed with respect to transcription regulation via methylation of CG-dinucleotides, which is observed in mammalian genomes.

Traboni C et al. (1984) Cell "Mutations in Box B of the promoter of a eucaryotic tRNAPro gene affect rate of transcription, processing, and stability of the transcripts."

Ciliberto G, Traboni C, Cortese R

[Cell, 1984]

We have constructed a series of single and double base-pair-substitution mutants in and around the second component (Box B) of the promoter of a tRNA(Pro) gene from C. elegans. Their analysis in in vivo and in vitro transcriptional systems establishes the importance of single nucleotides in the promotion of transcription. Most mutants in the region coding for the T*CG stem-loop show a reduced gene expression associated with lack of processing of the primary transcriptional products; in the oocytes these are rapidly degraded, with a half-life considerably shorter than that of wild-type tRNA molecules. In contrast, mutations in the DNA region coding for anticodon stem-loop do not alter the efficiency of transcription or the processing of the transcripts.

Borbolis F et al. (2020) Elife "mRNA decapping is an evolutionarily conserved modulator of neuroendocrine signaling that controls development and ageing."

Rallis J, Vakaloglou KM, Syntichaki P, Diallinas G, Vasileiou C, Borbolis F, Kanatouris G, Stravopodis DJ, Kokla N, Karamalegkos A, Zervas CG

[Elife, 2020]

Eukaryotic 5'-3' mRNA decay plays important roles during development and in response to stress, regulating gene expression post-transcriptionally. In <i>Caenorhabditis elegans</i>, deficiency of DCAP-1/DCP1, the essential co-factor of the major cytoplasmic mRNA decapping enzyme, impacts normal development, stress survival and ageing. Here, we show that overexpression of <i>dcap-1</i> in neurons of worms is sufficient to increase lifespan through the function of the insulin/IGF-like signaling and its effector DAF-16/FOXO transcription factor. Neuronal DCAP-1 affects basal levels of INS-7, an ageing-related insulin-like peptide, which acts in the intestine to determine lifespan. Short-lived <i>dcap-1</i> mutants exhibit a neurosecretion-dependent upregulation of intestinal <i>ins-7</i> transcription, and diminished nuclear localization of DAF-16/FOXO. Moreover, neuronal overexpression of DCP1 in <i>Drosophila melanogaster</i> confers longevity in adults, while neuronal DCP1 deficiency shortens lifespan and affects wing morphogenesis, cell non-autonomously. Our genetic analysis in two model-organisms suggests a critical and conserved function of DCAP-1/DCP1 in developmental events and lifespan modulation.