Comber SD et al. (2006) Environ Pollut "Chronic toxicity of sediment-associated linear alkylbenzene sulphonates (LAS) to freshwater benthic organisms."

Hoss S, Webb S, Comber SD, Conrad AU, Marshall S

[Environ Pollut, 2006]

The toxicity of linear alkylbenzene sulphonates (LAS), to freshwater benthic organisms was assessed during exposure to spiked sediment. Lethal and sub-lethal end-points were monitored for two organisms (oligochaete Lumbriculus variegatus and nematode Caenorhabditis elegans). Results demonstrated relatively low toxicity (LOECs >100mg/kg dry weight). No observed effect concentrations (NOECs) of 81mg/kg dw (Lumbriculus) and 100mg/kg dw (Caenorhabditis) were determined. For the oligochaete, no specific endpoint was particularly sensitive to LAS. For the nematode, egg production was the most sensitive endpoint. Significant degradation was measured over the 28-day duration of the Lumbriculus study, equating to a half-life of 20days in sediment.

Titanji VP et al. (1988) Parasitol Res "Studies on glucose-6-phosphate dehydrogenase from the human parasite, Onchocerca volvulus."

Tchoupe JR, Muluh JP, Titanji VP

[Parasitol Res, 1988]

Glucose-6-phosphate dehydrogenase (E.C. 1.1.1.49) was partially purified from the extracts of adult Onchocerca volvulus by affinity chromatography on 2'5'ADP-Sepharose-4B. Kinetic studies revealed a typical bell-shaped pH profile with an optimum lying between pH 7.3 and 7.8. The apparent Km for glucose-6-phosphate was 5.66 x 10(-5) M, whereas that for NADP was 2.17 x 10(-6) M. Suramin, a filaricidal drug, inhibited the enzyme competitively with respect to NADP as a substrate: the apparent Ki values were 2.23 x 10(-6) M and 4.21 x 10(-7) M, respectively, for the crude and purified enzyme preparations. Glucose-6-phosphate dehydrogenase therefore, could be one of the targets of suramin in vivo.

Mitsui Y et al. (2017) J Helminthol "Chemoattractant activity of tris-(hydroxymethyl)aminomethane for Brugia pahangi infective third-stage larvae."

Urena-Tatis KE, Aoki Y, Mitsui Y

[J Helminthol, 2017]

Urocanic acid (UCA) is known as a major chemoattractant for Strongyloides stercoralis infective third-stage larvae (L3). Since Brugia pahangi is a skin-penetrating parasitic nematode similar to S. stercoralis, UCA was expected to be a chemoattractant for B. pahangi L3. Thus, the chemoattractant activity of UCA for B. pahangi L3 was assessed. The chemotactic responses of B. pahangi L3 to UCA or acetic acid (CH3COOH) dissolved in amine solutions were assessed using an agar-plate assay. A test solution of 200 mm UCA dissolved in aqueous 270 mm tris(hydroxymethyl)aminomethane (Tris) significantly attracted B. pahangi L3 compared with deionized water (DW), while neither a solution of 200 mm UCA dissolved in aqueous 230 mm ammonia (NH3) nor 290 mm triethylamine (TEA) significantly attracted L3. Similarly, a test solution of 200 mm CH3COOH dissolved with 200 mm Tris significantly attracted L3, but neither a test solution of 200 mm CH3COOH plus 200 mm NH3 nor 200 mm TEA attracted L3. Furthermore, L3 were significantly attracted to 200 mm Tris alone, compared with DW, but avoided 200 mm NH3 and 200 mm TEA. Moreover, the chemoattractant activity of Tris for L3 was observed even at a low concentration of 25 mm, and it was observed in a mild alkaline condition but not in an acidic condition. The present study reveals that Tris is a potential chemoattractant for B. pahangi L3 while UCA is not. This finding will contribute to an understanding of the mechanisms of skin-penetrating infection of filarial L3.

Freire SL et al. (2014) J Vis Exp "Taking advantage of reduced droplet-surface interaction to optimize transport of bioanalytes in digital microfluidics."

Freire SL, Dao S, Wutkowski M, Thorne N

[J Vis Exp, 2014]

Digital microfluidics (DMF), a technique for manipulation of droplets, is a promising alternative for the development of "lab-on-a-chip" platforms. Often, droplet motion relies on the wetting of a surface, directly associated with the application of an electric field; surface interactions, however, make motion dependent on droplet contents, limiting the breadth of applications of the technique. Some alternatives have been presented to minimize this dependence. However, they rely on the addition of extra chemical species to the droplet or its surroundings, which could potentially interact with droplet moieties. Addressing this challenge, our group recently developed Field-DW devices to allow the transport of cells and proteins in DMF, without extra additives. Here, the protocol for device fabrication and operation is provided, including the electronic interface for motion control. We also continue the studies with the devices, showing that multicellular, relatively large, model organisms can also be transported, arguably unaffected by the electric fields required for device operation.

Furuta T et al. (2023) MicroPubl Biol "sart-3 functions to regulate germline sex determination in C. elegans ."

Arur S, Furuta T

[MicroPubl Biol, 2023]

<i>Caenorhabditis elegans</i> gene <i>sart-3</i> was first identified as the homolog of human SART3 ( S quamous cell carcinoma A ntigen R ecognized by T -cells 3). In humans, expression of SART3 is associated with squamous cell carcinoma, thus most of the studies focus on its potential role as a target of cancer immunotherapy (Shichijo et al. 1998; Yang et al. 1999). Furthermore, SART3 is also known as Tip110 (Liu et al. 2002; Whitmill et al. 2016) in the context of HIV virus host activation pathway. Despite these disease related studies, the molecular function of this protein was not revealed until the yeast homolog was identified as spliceosome U4/U6 snRNP recycling factor (Bell et al. 2002). The function of SART3 in development, however, remains unknown. Here we report that the <i>C. elegans</i> <i>sart-3</i> mutant hermaphrodites exhibit a Mog ( M asculinization O f the G ermline) phenotype in adulthood suggesting that <i>sart-3</i> normally functions to regulate the switch from spermatogenic to oogenic gametic sex.

Yajnik V et al. (2003) Cell "DOCK4, a GTPase activator, is disrupted during tumorigenesis."

Settleman J, Haber DA, Saito M, Bell DW, Reynolds P, McClatchey AI, van den Heuvel S, Wahrer DC, Paulding C, Yajnik V, Lake R, Sordella R

[Cell, 2003]

We used representational difference analysis to identify homozygous genomic deletions selected during tumor progression in the mouse NF2 and TP53 tumor model. We describe a deletion targeting DOCK4, a member of the CDM gene family encoding regulators of small GTPases. DOCK4 specifically activates Rap GTPase, enhancing the formation of adherens junctions. DOCK4 mutations are present in a subset of human cancer cell lines; a recurrent missense mutant identified in human prostate and ovarian cancers encodes a protein that is defective in Rap1 activation. The engulfment defect of C. elegans mutants lacking the CDM gene ced-5 is rescued by wild-type DOCK4, but not by the mutant allele. Expression of wild-type, but not mutant, DOCK4 in mouse osteosarcoma cells with a deletion of the endogenous gene suppresses growth in soft agar and tumor invasion in vivo. DOCK4 therefore encodes a CDM family member that regulates intercellular junctions and is disrupted during tumorigenesis.

Schertzinger G et al. (2017) Environ Pollut "Assessment of sublethal endpoints after chronic exposure of the nematode Caenorhabditis elegans to palladium, platinum and rhodium."

Schertzinger G, Zimmermann S, Grabner D, Sures B

[Environ Pollut, 2017]

The aim of this study was to investigate chronic effects of the platinum-group elements (PGE) palladium (Pd), platinum (Pt) and rhodium (Rh) on the nematode Caenorhabditis elegans. Aquatic toxicity testing was carried out according to ISO 10872 by determining 96h EC50 values for sublethal endpoints, including growth, fertility and reproduction. Single PGE standard solutions were used as metal source. Based on the EC50 values for Pt, reproduction (96h EC50=497g/L) was the most sensitive endpoint followed by fertility (96h EC50=726g/L) and growth (96h EC50=808g/L). For Pd, no precise EC50 values could be calculated due to bell-shaped concentration response curves, but the 96h EC50 for reproduction ranged between 10 and 100g/L. Pd and Pt had effects on all endpoints. With raising element concentrations reproduction was inhibited first. At a certain concentration, fertility was also affected, which in turn had an additional effect on reproduction. Growth inhibition can also lead to a loss of fertility if the worms do not reach an appropriate body size to become fertile. Rhodium showed no inhibition of any endpoint between concentrations of 100 to 10,000g Rh/L. The results of this study allow the following order of PGE with respect to decreasing toxicity to C.elegans: Pd&gt;Pt"Rh.

Liu Q et al. (2006) J Biol Chem "Low conductance gap junctions mediate specific electrical coupling in body-wall muscle cells of Caenorhabditis elegans."

Gaier E, Wang ZW, Joshi J, Chen B, Liu Q

[J Biol Chem, 2006]

Invertebrate innexins and their mammalian homologues pannexins are gap junction proteins. Despite a large number of such proteins have been identified, few gap junctions that they form have been characterized with combined information of biophysical properties, coupling pattern, and molecular compositions. We adapted the dual whole-cell voltage clamp technique to in situ analysis of electrical coupling in C. elegans body-wall muscle. We found that body-wall muscle cells were electrically coupled in a highly organized and specific pattern. The coupling was characterized by small (350 pS or less) junctional conductance (Gj), which showed a bell-shaped relationship with junctional potential (Vj) but was independent of membrane potential (Vm). Injection of currents comparable to the junctional current (Ij) into body-wall muscle cells caused significant depolarization, suggesting important functional relevance. The innexin UNC-9 appeared to be a key component of the gap junctions. Both Myc- and GFP-tagged UNC-9 was localized to muscle intercellular junctions. Gj was greatly inhibited in unc-9(fc16), a putative null mutant. Specific inhibition of UNC-9 function in muscle cells reduced locomotion velocity. Despite UNC-9 expression in both motor neurons and body-wall muscle cells, analyses of miniature and evoked postsynaptic currents (mPSCs and ePSCs) in the unc-9 mutant showed normal neuromuscular transmission. These analyses provide a relatively detailed description of innexin-based gap junctions in a native tissue, and suggest that innexin-based small-conductance gap junctions can play an important role in processes such as locomotion.

Carmel L et al. (2009) Genome Biol Evol "A universal nonmonotonic relationship between gene compactness and expression levels in multicellular eukaryotes."

Koonin EV, Carmel L

[Genome Biol Evol, 2009]

Analysis of gene architecture and expression levels of four organisms, Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, and Arabidopsis thaliana, reveals a surprising, nonmonotonic, universal relationship between expression level and gene compactness. With increasing expression level, the genes tend at first to become longer but, from a certain level of expression, they become more and more compact, resulting in an approximate bell-shaped dependence. There are two leading hypotheses to explain the compactness of highly expressed genes. The selection hypothesis predicts that gene compactness is predominantly driven by the level of expression, whereas the genomic design hypothesis predicts that expression breadth across tissues is the driving force. We observed the connection between gene expression breadth in humans and gene compactness to be significantly weaker than the connection between expression level and compactness, a result that is compatible with the selection hypothesis but not the genome design hypothesis. The initial gene elongation with increasing expression level could be explained, at least in part, by accumulation of regulatory elements enhancing expression, in particular, in introns. This explanation is compatible with the observed positive correlation between intron density and expression level of a gene. Conversely, the trend toward increasing compactness for highly expressed genes could be caused by selection for minimization of energy and time expenditure during transcription and splicing and for increased fidelity of transcription, splicing, and/or translation that is likely to be particularly critical for highly expressed genes. Regardless of the exact nature of the forces that shape the gene architecture, we present evidence that, at least, in animals, coding and noncoding parts of genes show similar architectonic trends.

Garcia-Casas P et al. (2018) Front Pharmacol "Inhibition of Sarco-Endoplasmic Reticulum Ca2+ ATPase Extends the Lifespan in C. elegans Worms."

Fonteriz RI, Alvarez J, Arias-Del-Val J, Alvarez-Illera P, Garcia-Casas P, Montero M

[Front Pharmacol, 2018]

The sarco-endoplasmic reticulum Ca²⁺-ATPase (SERCA) refills the endoplasmic reticulum (ER) with Ca²⁺ up to the millimolar range and is therefore the main controller of the ER [Ca²⁺] level ([Ca²⁺]_ER), which has a key role in the modulation of cytosolic Ca²⁺ signaling and ER-mitochondria Ca²⁺ transfer. Given that both cytosolic and mitochondrial Ca²⁺ dynamics strongly interplay with energy metabolism and nutrient-sensitive pathways, both of them involved in the aging process, we have studied the effect of SERCA inhibitors on lifespan in <i>C. elegans</i>. We have used thapsigargin and 2,5-Di-tert-butylhydroquinone (2,5-BHQ) as SERCA inhibitors, and the inactive analog 2,6-Di-tert-butylhydroquinone (2,6-BHQ) as a control for 2,5-BHQ. Every drug was administered to the worms either directly in the agar or via an inclusion compound with -cyclodextrin. The results show that 2,6-BHQ produced a small but significant increase in survival, perhaps because of its antioxidant properties. However, 2,5-BHQ produced in all the conditions a much higher increase in lifespan, and the potent and specific SERCA inhibitor thapsigargin also extended the lifespan. The effects of 2,5-BHQ and thapsigargin had a bell-shaped concentration dependence, with a maximum effect at a certain dose and smaller or even toxic effects at higher concentrations. Our data show therefore that submaximal inhibition of SERCA pumps has a pro-longevity effect, suggesting that Ca²⁺ signaling plays an important role in the aging process and that it could be a promising novel target pathway to act on aging.