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[
Development,
2022]
In multicellular systems, cells communicate with adjacent cells to determine their positions and fates, an arrangement important for cellular development. Orientation of cell division, cell-cell interactions (i.e. attraction and repulsion) and geometric constraints are three major factors that define cell arrangement. In particular, geometric constraints are difficult to reveal in experiments, and the contribution of the local contour of the boundary has remained elusive. In this study, we developed a multicellular morphology model based on the phase-field method so that precise geometric constraints can be incorporated. Our application of the model to nematode embryos predicted that the amount of extra-embryonic space, the empty space within the eggshell that is not occupied by embryonic cells, affects cell arrangement in a manner dependent on the local contour and other factors. The prediction was validated experimentally by increasing the extra-embryonic space in the Caenorhabditis elegans embryo. Overall, our analyses characterized the roles of geometrical contributors, specifically the amount of extra-embryonic space and the local contour, on cell arrangements. These factors should be considered for multicellular systems.
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Ecotoxicol Environ Saf,
2019]
Microbial community of an organism plays an important role on its fitness, including stress responses. In this study, we investigated the effect of the culturable subset of soil microbial community (SMB) on the stress response of the soil nematode Caenorhabditis elegans, upon exposure to one of the major soil contaminants, cadmium (Cd). Life history traits and the stress responses to Cd exposure were compared between SMB- and Escherichia coli strain OP50-fed worms. SMB-fed worms showed higher reproduction rates and longer lifespans. Also, the SMB-fed worms showed more tolerant response to Cd exposure. Gene expression profiling suggested that the chemical stress and immune response of worms were boosted upon SMB feeding. Finally, we investigated C. elegans gut microbial communities in the presence and absence of Cd in OP50- and SMB-fed C. elegans. In the OP50-fed worms, changes in microbial community by Cd exposure was severe, whereas in the SMB-fed worms, it was comparatively weak. Our results suggest that the SMB affects the response of C. elegans to Cd exposure and highlight the importance of the gut microbiome in host stress response.
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[
Int J Mol Sci,
2021]
The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using <i>Caenorhabditis elegans</i> expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in <i>
dpy-23</i> that encodes the 2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for <i>
dpy-23</i> revealed the <i>
lon-2</i> mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the <i>
cav-1</i> gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of <i>
cav-1</i>, the reduced TGF- signal was significantly restored in the <i>
dpy-23</i> mutant. In conclusion, the <i>
dpy-23</i> mutation upregulated <i>
cav-1</i> expression in the hypodermis, and increased CAV-1 resulted in a decrease of TRI. Finally, the reduction of collagen expression including <i>
rol-6</i> by the reduced TGF- signal influenced the cuticle formation of the <i>
dpy-23</i> mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions.
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J Virol,
2001]
The human herpes simplex virus (HSV) protein VP16 induces formation of a transcriptional regulatory complex with two cellular factors-the POU homeodomain transcription factor Oct-1 and the cell proliferation factor HCF-1-to activate viral immediate-early-gene transcription. Although the cellular role of Oct-1 in transcription is relatively well understood, the cellular role of HCF-1 in cell proliferation is enigmatic. HCF-1 and the related protein HCF-2 form an HCF protein family in humans that is related to a Caenorhabditis elegans homolog called CeHCF. In this study, we show that all three proteins can promote VP16-induced-complex formation, indicating that VP16 targets a highly conserved function of HCF proteins. The resulting VP16-induced complexes, however, display different transcriptional activities. In contrast to HCF-1 and CeHCF, HCF-2 fails to support VP16 activation of transcription effectively. These results suggest that, along with HCF-1, HCF-2 could have a role, albeit probably a different role, in HSV infection. CeHCF can mimic HCF-1 for both association with viral and cellular proteins and transcriptional activation, suggesting that the function(s) of HCF-1 targeted by VP16 has been highly conserved throughout metazoan evolution.
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MicroPubl Biol,
2019]
One barrier to communication at large face-to-face meetings, especially those focusing on scientific or technical topics, is a rapid way to understand what a person knows and thinks about before initiating a conversation. We have devised and reduced to practice an effective way to accomplish this task, the wearable microPoster.
In our experience, we observed that at most scientific meetings, especially once the number of participants passed 100, it is difficult to get productive conversations started with strangers. Thus, conversations tend to initiate among people that already know one another. This tends to exclude newer participants and those who do not have formal speaking slots. The difficulty increases at informal aspects of meetings: coffee breaks, lines for meals, social events, outdoor events in which a prominent speaker might have different clothes and sunglasses and is thus rendered unknown.
Poster sessions have long provided a venue for rapid communication and finding participants. These are usually the most productive parts of meetings. Our thinking evolved from jokes about sandwich board posters, in which one walks around with large posters on the front and back, to shirts with printed information. The advent of printed cloth posters provides a practical solution in which a microPoster is cut from the larger poster (ideally cloth), or printed on one or more sheets of standard paper, which are then taped together. A microPoster comprises your name, affiliation (with appropriate granularity determined by the meeting), and a graphical abstract. The goal is to identify yourself in a much more informative way than a nametag.
One convenient way to present the microPoster is pinned on your back like a bib number (e.g., as in marathons or dances). We carried out a pilot with ten microPosters at a meeting of 1500 people (Figure 1), and found them to be effective at attracting useful conversation.
The addition of a machine readable QR code (e.g., Salt, 2019) is a possible useful addition but we note that the expense in time, money and carbon footprint of a face-to-face meeting is better spent on face-to-face conversations.
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J Math Biol,
2020]
Cell polarity is an important cellular process that cells use for various cellular functions such as asymmetric division, cell migration, and directionality determination. In asymmetric cell division, a mother cell creates multiple polarities of various proteins simultaneously within her membrane and cytosol to generate two different daughter cells. The formation of multiple polarities in asymmetric cell division has been found to be controlled via the regulatory system by upstream polarity of the membrane to downstream polarity of the cytosol, which is involved in not only polarity establishment but also polarity positioning. However, the mechanism for polarity positioning remains unclear. In this study, we found a general mechanism and mathematical structure for the multiple streams of polarities to determine their relative position via conceptional models based on the biological example of the asymmetric cell division process of C. elegans embryo. Using conceptional modeling and model reductions, we show that the positional relation of polarities is determined by a contrasting role of regulation by upstream polarity proteins on the transition process of diffusion dynamics of downstream proteins. We analytically prove that our findings hold under the general mathematical conditions, suggesting that the mechanism of relative position between upstream and downstream dynamics could be understood without depending on a specific type of bio-chemical reaction, and it could be the universal mechanism in multiple streams of polarity dynamics of the cell.
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[
PLoS One,
2007]
BACKGROUND: The human herpes simplex virus (HSV) host cell factor HCF-1 is a transcriptional coregulator that associates with both histone methyl- and acetyltransferases, and a histone deacetylase and regulates cell proliferation and division. In HSV-infected cells, HCF-1 associates with the viral protein VP16 to promote formation of a multiprotein-DNA transcriptional activator complex. The ability of HCF proteins to stabilize this VP16-induced complex has been conserved in diverse animal species including Drosophila melanogaster and Caenorhabditis elegans suggesting that VP16 targets a conserved cellular function of HCF-1. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of HCF proteins in animal development, we have characterized the effects of loss of the HCF-1 homolog in C. elegans, called Ce HCF-1. Two large
hcf-1 deletion mutants (
pk924 and
ok559) are viable but display reduced fertility. Loss of Ce HCF-1 protein at reduced temperatures (e.g., 12 degrees C), however, leads to a high incidence of embryonic lethality and early embryonic mitotic and cytokinetic defects reminiscent of mammalian cell-division defects upon loss of HCF-1 function. Even when viable, however, at normal temperature, mutant embryos display reduced levels of phospho-histone H3 serine 10 (H3S10P), a modification implicated in both transcriptional and mitotic regulation. Mammalian cells with defective HCF-1 also display defects in mitotic H3S10P status. CONCLUSIONS/SIGNIFICANCE: These results suggest that HCF-1 proteins possess conserved roles in the regulation of cell division and mitotic histone phosphorylation.
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Mech Ageing Dev,
2007]
An explanation is offered for the increased lifespan of Caenorhabditis elegans when mRNA translation is inhibited due to loss of the initiation factor IFE-2 [Hansen, M., Taubert, T., Crawford, D., Libina, N., Lee, S.-J., Kenyon, C., 2007. Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Ageing Cell 6, 95-110; Pan, K.Z., Palter, J.E., Rogers, A.N., Olsen, A., Chen, D., Lithgow, G.J., Kapahi, P., 2007. Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Ageing Cell 6, 111-119; Syntichaki, P., Troulinaki, K., Tavernarakis, N., 2007. eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans. Nature 445, 922-926]. It is suggested that the general reduction of protein synthesis, due to the decreased frequency of mRNA translation, also lowers the cellular load of erroneously synthesized polypeptides which the constitutive protein homeostatic apparatus (proteases and chaperones proteins) normally eliminates. This situation results in "spare" proteolytic and chaperone function which can then deal with those proteins modified post-synthetically, e.g. by oxidation and/or glycation, which are thought to contribute to the senescent phenotype. This increased availability of proteolytic and chaperone functions may thereby contribute to the observed increase in organism stress resistance and lifespan.
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[
Bio Protoc,
2017]
Single-molecule RNA fluorescence <i>in situ</i> hybridization (smFISH) is a technique to visualize individual RNA molecules using multiple fluorescently-labeled oligonucleotide probes specific to the target RNA ( Raj <i>et al.</i>, 2008 ; Lee <i>et al.</i>, 2016a ). We adapted this technique to visualize RNAs in the <i>C. elegans</i> whole adult worm or its germline, which enabled simultaneous recording of nascent transcripts at active transcription sites and mature mRNAs in the cytoplasm ( Lee <i>et al.</i>, 2013 and 2016b). Here we describe each step of the smFISH procedure, reagents, and microscope settings optimized for <i>C. elegans</i> extruded gonads.
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J Biol Chem,
2007]
The biological methyl donor, S adenosylmethionine (AdoMet), can exist in two diastereoisomeric states with respect to its sulfonium ion. The "S" configuration, (S,S)AdoMet, is the only form that is produced enzymatically as well as the only form used in almost all biological methylation reactions. Under physiological conditions, however, the sulfonium ion can spontaneously racemize to the "R" form, producing (R,S)AdoMet. As of yet, (R,S)AdoMet has no known physiological function and may inhibit cellular reactions. In this study, two enzymes have been found in Saccharomyces cerevisiae that are capable of recognizing (R,S)AdoMet and using it to methylate homocysteine to form methionine. These enzymes are the products of the SAM4 and MHT1 genes, previously identified as homocysteine methyltransferases dependent upon AdoMet and S-methylmethionine respectively. We find here that Sam4 recognizes both (S,S) and (R,S)AdoMet, but its activity is much higher with the R,S form. Mht1 reacts with only the R,S form of AdoMet while no activity is seen with the S,S form. R,S-specific homocysteine methyltransferase activity is also shown here to occur in extracts of Arabidopsis thaliana, Drosophila melanogaster, and Caenorhabditis elegans, but has not been detected in several tissue extracts of Mus musculus. Such activity may function to prevent the accumulation of (R,S)AdoMet in these organisms.