Jamison DC et al. (1995) International C. elegans Meeting "WCS and Mosaic: The ENQUire System"

Jamison DC, Schatz BR, Mills B

[International C. elegans Meeting, 1995]

The Worm Community System (WCS) is a digital library that consists of an information space about C. elegans and a set of programs to manipulate the information space. WCS contains data from ACeDB and literature sources, including the WBG, selected meeting abstracts, and CGC bibliography abstracts. Information is retrieved from the CSL server and displayed by client software running on the user's local machine. A major shortcoming of WCS is the expense of the computer systems needed to run the local client. WCS requires a Sun SparcStation to run, and is very memory intensive. To answer this complaint, we have implemented the query portions of WCS as a Mosaic interface called ENQUire (Extensible Network Query Unifier). ENQUire users input a single query through a query-builder Mosaic form, then select multiple databases to submit the query to. The ENQUire program then translates the query into the proper query language and submits it to each of the selected databases. The responses are then collated and returned to the the user. At present there are query translators available for ACeDB, the WBG, and Genbank/Medline. Additionally, there is an interface to computational resources available at NCSA -- the thesaurus and a specialized BLAST program. ENQUire was designed to make adding additional translators simple, so in the future more databases will become available for searches. ENQUire is not meant to be a replacement search engine for these databases. Instead, it is designed to save time and energy by making it easier to search various databases, and to serve as a mechanism to aid data discovery.

Jamison DC et al. (1994) Worm Breeder's Gazette "The First Ever WCS Baby Picture Contest."

Jamison DC, Schatz BR

[Worm Breeder's Gazette, 1994]

Jamison DC et al. (1993) International C. elegans Meeting "Balancing the left arm of chromosome IV."

Riddle DL, Jamison DC

[International C. elegans Meeting, 1993]

Shoman LM et al. (1994) Worm Breeder's Gazette "Worm Community System Users Envision Future Application."

Grossman E, Shoman LM, Jamison DC, Schatz BR

[Worm Breeder's Gazette, 1994]

Worm Community System Users Envision Future Application. Laura Shoman, Curt Jamison, Ed Grossman, Bruce Schatz, Community Systems Laboratory, National Center for Supercomputing Applications, University of Illinois, Urbana- Champaign, 405 North Mathews, Urbana, IL 61801 (wcs@csl.ncsa.uiuc.edu)

RC Chan et al. (1999) International C. elegans Meeting "Immunoaffinity purification of the C. elegans dosage compensation complex"

RC Chan, M Albrecht, C Tsai, BJ Meyer

[International C. elegans Meeting, 1999]

Dosage compensation (DC) in C. elegans equalizes X expression between males (XO) and hermaphrodites (XX) by reducing transcription from both hermaphrodite X chromosomes. A large protein complex specifically localizes to the X chromosomes of XX animals to implement DC. Members of this DC complex include the SMC (structural maintenance of chromosome) proteins DPY-27 and MIX-1, and a non-SMC protein DPY-26. The latter two proteins also function in chromosome segregation during mitosis or meiosis, demonstrating the recruitment of chromosome segregation proteins to the regulation of gene expression. A second class of genes ( sdc ) that coordinately controls sex-determination and DC is required for the X localization of the DC complex. To gain an in-depth view of the interactions among these various DC proteins and to identify other DC proteins, we developed an immunoaffinity purification scheme to enrich for the DC proteins localized on DNA. To characterize the DC complex, peptide antibodies were raised against the carboxyl terminal (c-ter) sequences of DPY-26, MIX-1 and DPY-27, and were used to precipitate the complex from crude embryonic extracts. The benefit of this approach is that the precipitate can be eluted with c-ter peptides under non-denaturing conditions to allow further fractionation and biochemical analysis. Our analysis provided the following findings: (1) The product of the genetically characterized DC gene dpy-28 was shown to be a member of the complex. Besides DC, DPY-28 also functions in meiosis (see Chan et al.), further reinforcing the model that DC evolved by recruiting factors essential to chromosome segregation. The addition of DPY-28 to the DC complex revealed a striking overall similarity between the DC complex and the Xenopus 13S condensin, required for mitotic chromosome condensation in vitro . This result suggests that DC may be mechanistically similar to mitotic chromosome compaction. (2) The SDC-2 and SDC-3 proteins were also present in the precipitate, suggesting that SDC proteins directly recruit the DC complex to X (see Dawes et al.) (3) Two other proteins of 165- and 80-kD were found. Work is in progress to identify these two proteins and to further purify the DC complex for biochemical analysis.

Tiraihi A et al. (2007) Biosystems "Early onset of regionalization in EMS lineage of C. elegans embryo: a quantitative study."

Tiraihi A, Tiraihi T

[Biosystems, 2007]

Early localization of C. elegans founder cell descendents in certain regions of embryo has been documented. The purpose of this investigation is to evaluate the onset of ABp and EMS descendent cell regionalization in the embryo using the random motility coefficient as a quantitative parameter. The forward migration index (FMI) was also calculated in order to evaluate the chemotatic biases of ABp-dc and EMS-dc during regionalization. The results showed that the random motility coefficient declined as the cells tended to regionalize. The mean squared displacement (MSD) versus time plot showed a non-linear model which indicated non-random cell movement. FMI showed progressive increase as the cells tended to regionalized, and it was significantly higher in EMS-dc than ABp-dc, moreover the chemotatic biases were higher in EMS-dc than ABp-dc. The circular plots showed that the statistical differences between the two lineages were significant, while ABp-dc showed significant differences in xy, xz and yz planes; EMS derived cells showed no significant differences except in yz planes. The conclusion of this study is that the onset of early regionalization occurs in EMS-dc sooner than in ABp-dc.

Zhong F et al. (2011) Genes Dev "Disruption of telomerase trafficking by TCAB1 mutation causes dyskeratosis congenita."

Alter BP, Artandi SE, Shkreli M, Jessop L, Zhong F, Giri N, Savage SA, Chen R, Myers T

[Genes Dev, 2011]

Dyskeratosis congenita (DC) is a genetic disorder of defective tissue maintenance and cancer predisposition caused by short telomeres and impaired stem cell function. Telomerase mutations are thought to precipitate DC by reducing either the catalytic activity or the overall levels of the telomerase complex. However, the underlying genetic mutations and the mechanisms of telomere shortening remain unknown for as many as 50% of DC patients, who lack mutations in genes controlling telomere homeostasis. Here, we show that disruption of telomerase trafficking accounts for unknown cases of DC. We identify DC patients with missense mutations in TCAB1, a telomerase holoenzyme protein that facilitates trafficking of telomerase to Cajal bodies. Compound heterozygous mutations in TCAB1 disrupt telomerase localization to Cajal bodies, resulting in misdirection of telomerase RNA to nucleoli, which prevents telomerase from elongating telomeres. Our findings establish telomerase mislocalization as a novel cause of DC, and suggest that telomerase trafficking defects may contribute more broadly to the pathogenesis of telomere-related disease.

Sharma R et al. (2014) Genes Dev "Differential spatial and structural organization of the X chromosome underlies dosage compensation in C. elegans."

Kind J, Vaillant C, Meister P, Jost D, Askjaer P, Sharma R, Gomez-Saldivar G, van Steensel B

[Genes Dev, 2014]

The adjustment of X-linked gene expression to the X chromosome copy number (dosage compensation [DC]) has been widely studied as a model of chromosome-wide gene regulation. In Caenorhabditis elegans, DC is achieved by twofold down-regulation of gene expression from both Xs in hermaphrodites. We show that in males, the single X chromosome interacts with nuclear pore proteins, while in hermaphrodites, the DC complex (DCC) impairs this interaction and alters X localization. Our results put forward a structural model of DC in which X-specific sequences locate the X chromosome in transcriptionally active domains in males, while the DCC prevents this in hermaphrodites.

Rezai P et al. (2011) Biomicrofluidics "Effect of pulse direct current signals on electrotactic movement of nematodes Caenorhabditis elegans and Caenorhabditis briggsae."

Selvaganapathy PR, Gupta BP, Salam S, Rezai P

[Biomicrofluidics, 2011]

The nematodes (worms) Caenorhabditiselegans and Caenorhabditisbriggsae are well-known model organisms to study the basis of animal development and behaviour. Their sinusoidal pattern of movement is highly stereotypic and serves as a tool to monitor defects in neurons and muscles that control movement. Until recently, a simple yet robust method to initiate movement response on-demand did not exist. We have found that the electrical stimulation in a microfluidic channel, using constant DC electric field, induces movement (termed electrotaxis) that is instantaneous, precise, sensitive, and fully penetrant. We have further characterized this behaviour and, in this paper, demonstrate that electrotaxis can also be induced using a pulse DC electric signal. Worms responded to pulse DC signals with as low as 30% duty cycle by moving towards the negative electrode at the same speed as constant DC fields (average speed of C. elegans=296+/-43m/s and C. briggsae=356+/-20m/s, for both constant and pulse DC electric fields with various frequencies). C. briggsae was found to be more sensitive to electric signals compared to C. elegans. We also investigated the turning response of worms to a change in the direction of constant and pulse DC signals. The response for constant DC signal was found to be instantaneous and similar for most worms. However, in the case of pulse DC signal, alterations in duty cycle affected the turning response time as well as the number of responding worms. Our findings show that pulse DC method allows quantitative measurement of response behaviour of worms and suggest that it could be used as a tool to study the neuronal basis of such a behaviour that is not observed under constant DC conditions.

Semnani RT et al. (2008) J Immunol "Induction of TRAIL- and TNF-alpha-dependent apoptosis in human monocyte-derived dendritic cells by microfilariae of Brugia malayi."

Skinner JA, Venugopal PG, Chien D, Mahapatra L, Chaussabel D, Meylan F, Dorward DW, Nutman TB, Semnani RT, Siegel RM

[J Immunol, 2008]

Dysregulation of professional APC has been postulated as a major mechanism underlying Ag-specific T cell hyporesponsiveness in patients with patent filarial infection. To address the nature of this dysregulation, dendritic cells (DC) and macrophages generated from elutriated monocytes were exposed to live microfilariae (mf), the parasite stage that circulates in blood and is responsible for most immune dysregulation in filarial infections. DC exposed to mf for 24-96 h showed a marked increase in cell death and caspase-positive cells compared with unexposed DC, whereas mf exposure did not induce apoptosis in macrophages. Interestingly, 48-h exposure of DC to mf induced mRNA expression of the proapoptotic gene TRAIL and both mRNA and protein expression of TNF-alpha. mAb to TRAIL-R2, TNF-R1, or TNF-alpha partially reversed mf-induced cell death in DC, as did knocking down the receptor for TRAIL-R2 using small interfering RNA. The mf also induced gene expression of BH3-interacting domain death agonist and protein expression of cytochrome c in DC; mf-induced cleavage of BH3-interacting domain death agonist could be shown to induce release of cytochrome c, leading to activation of caspase 9. Our data suggest that mf induce DC apoptosis in a TRAIL- and TNF-alpha-dependent fashion.