Schmidt GD et al. (1972) Proc. Helminthological Society of Washington "Nematode parasites of Oceanica. XVIII. C. avicola sp. n. (Rhabditidae) found in a bird from Taiwan."

Schmidt GD, Kuntz RE

[Proc. Helminthological Society of Washington, 1972]

Caenorhabditis avicola sp. n. is described from one male and three female nematodes from the intestine of a plumbeous water redstart, Rhyacornis fuliginosus (Passeriformes, Turdidae), from Taiwan. It is characterized by the extension of the anterior margins of the peloderan bursa into sharp points, giving the male posterior end an arrowheadlike shape in ventral view, and by the spicules, which are 95 u long. It is postulated that the worms were pseudoparasites, possibly symbionts of an insect ingested by the bird.

Zhang W et al. (2011) Nanoscale "Biosafety assessment of Gd@C82(OH)22 nanoparticles on Caenorhabditis elegans."

Zhao B, Zhang W, Zhang L, Sun B, Zhao Y, Nie G

[Nanoscale, 2011]

Gd@C(82)(OH)(22), a water-soluble endohedral metallofullerene derivative, has been proven to possess significant antineoplastic activity in mice. Toxicity studies of the nanoparticle have shown some evidence of low or non toxicity in mice and cell models. Here we employed Caenorhabditis elegans (C. elegans) as a model organism to further evaluate the short- and long-term toxicity of Gd@C(82)(OH)(22) and possible behavior changes under normal and stress culture conditions. With treatment of Gd@C(82)(OH)(22) at 0.01, 0.1, 1.0 and 10 g ml(-1) within one generation (short-term), C. elegans showed no significant decrease in longevity or thermotolerance compared to the controls. Furthermore, when Gd@C(82)(OH)(22) treatment was extended up to six generations (long-term), non-toxic effects to the nematodes were found. In addition, data from body length measurement, feeding rate and egg-laying assays with short-term treatment demonstrated that the nanoparticles have no significant impact on the individual growth, feeding behavior and reproductive ability, respectively. In summary, this work has shown that Gd@C(82)(OH)(22) is tolerated well by worms and it has no apparent toxic effects on longevity, stress resistance, growth and behaviors that were observed in both adult and young worms. Our work lays the foundations for further developments of this anti-neoplastic agent for clinical applications.

Van Brempt N et al. (2023) Biochim Biophys Acta Proteins Proteom "The effect of pH and nitrite on the haem pocket of GLB-33, a globin-coupled neuronal transmembrane receptor of Caenorhabditis elegans."

Herrebout W, Dewilde S, Hammerschmid D, Sobott F, Van Brempt N, Sgammato R, Johannessen C, Van Doorslaer S, Moens L, Beirinckx Q

[Biochim Biophys Acta Proteins Proteom, 2023]

Out of the 34 globins in Caenorhabditis elegans, GLB-33 is a putative globin-coupled transmembrane receptor with a yet unknown function. The globin domain (GD) contains a particularly hydrophobic haem pocket, that rapidly oxidizes to a low-spin hydroxide ligated haem state at physiological pH. Moreover, the GD has one of the fastest nitrite reductase activity ever reported for globins. Here, we use a combination of electronic circular dichroism, resonance Raman and electron paramagnetic resonance (EPR) spectroscopy with mass spectrometry to study the pH dependence of the ferric form of the recombinantly over-expressed GD in the presence and absence of nitrite. The competitive binding of nitrite and hydroxide is examined as well as nitrite-induced haem modifications at acidic pH. Comparison of the spectroscopic results with data from other haem proteins allows to deduce the important effect of Arg at position E10 in stabilization of exogenous ligands. Furthermore, continuous-wave and pulsed EPR indicate that ligation of nitrite occurs in a nitrito mode at pH 5.0 and above. At pH 4.0, an additional formation of a nitro-bound haem form is observed along with fast formation of a nitri-globin.

Tilleman L et al. (2015) J Biol Chem "A globin domain in a neuronal transmembrane receptor of Caenorhabditis elegans and Ascaris suum: molecular modeling and functional properties."

Desmet F, Moens L, Dewilde S, Tilleman L, Van Doorslaer S, Schoofs L, Braeckman BP, Germani F, Helbo S, Berghmans H, Hoogewijs D, Fago A, De Henau S

[J Biol Chem, 2015]

We report the structural and biochemical characterization of GLB-33, a putative neuropeptide receptor that is exclusively expressed in the nervous system of the nematode Caenorhabditis elegans. This unique chimeric protein is composed of a 7-transmembrane domain (7TM), GLB-33 7TM, typical of a G-protein-coupled receptor, and of a globin domain (GD), GLB-33 GD. Comprehensive sequence similarity searches in the genome of the parasitic nematode, Ascaris suum, revealed a chimeric protein that is similar to a Phe-Met-Arg-Phe-amide neuropeptide receptor. The three-dimensional structures of the separate domains of both species and of the full-length proteins were modeled. The 7TM domains of both proteins appeared very similar, but the globin domain of the A. suum receptor surprisingly seemed to lack several helices, suggesting a novel truncated globin fold. The globin domain of C. elegans GLB-33, however, was very similar to a genuine myoglobin-type molecule. Spectroscopic analysis of the recombinant GLB-33 GD showed that the heme is pentacoordinate when ferrous and in the hydroxide-ligated form when ferric, even at neutral pH. Flash-photolysis experiments showed overall fast biphasic CO rebinding kinetics. In its ferrous deoxy form, GLB-33 GD is capable of reversibly binding O2 with a very high affinity and of reducing nitrite to nitric oxide faster than other globins. Collectively, these properties suggest that the globin domain of GLB-33 may serve as a highly sensitive oxygen sensor and/or as a nitrite reductase. Both properties are potentially able to modulate the neuropeptide sensitivity of the neuronal transmembrane receptor.

Mazzulli JR et al. (2011) Cell "Gaucher disease glucocerebrosidase and -synuclein form a bidirectional pathogenic loop in synucleinopathies."

Caldwell GA, Grabowski GA, Mazzulli JR, Krainc D, Knight AL, Sidransky E, Xu YH, McLean PJ, Sun Y

[Cell, 2011]

Parkinson's disease (PD), an adult neurodegenerative disorder, has been clinically linked to the lysosomal storage disorder Gaucher disease (GD), but the mechanistic connection is not known. Here, we show that functional loss of GD-linked glucocerebrosidase (GCase) in primary cultures or human iPS neurons compromises lysosomal protein degradation, causes accumulation of -synuclein (-syn), and results in neurotoxicity through aggregation-dependent mechanisms. Glucosylceramide (GlcCer), the GCase substrate, directly influenced amyloid formation of purified -syn by stabilizing soluble oligomeric intermediates. We further demonstrate that -syn inhibits the lysosomal activity of normal GCase in neurons and idiopathic PD brain, suggesting that GCase depletion contributes to the pathogenesis of sporadic synucleinopathies. These findings suggest that the bidirectional effect of -syn and GCase forms a positive feedback loop that may lead to a self-propagating disease. Therefore, improved targeting of GCase to lysosomes may represent a specific therapeutic approach for PD and other synucleinopathies.

Peng H et al. (2010) Bioinformatics "Automatic reconstruction of 3D neuron structures using a graph-augmented deformable model."

Sternson S, Atasoy D, Peng H, Ruan Z

[Bioinformatics, 2010]

MOTIVATION: Digital reconstruction of 3D neuron structures is an important step toward reverse engineering the wiring and functions of a brain. However, despite a number of existing studies, this task is still challenging, especially when a 3D microscopic image has low single-to-noise ratio and discontinued segments of neurite patterns. RESULTS: We developed a graph-augmented deformable model (GD) to reconstruct (trace) the 3D structure of a neuron when it has a broken structure and/or fuzzy boundary. We formulated a variational problem using the geodesic shortest path, which is defined as a combination of Euclidean distance, exponent of inverse intensity of pixels along the path and closeness to local centers of image intensity distribution. We solved it in two steps. We first used a shortest path graph algorithm to guarantee that we find the global optimal solution of this step. Then we optimized a discrete deformable curve model to achieve visually more satisfactory reconstructions. Within our framework, it is also easy to define an optional prior curve that reflects the domain knowledge of a user. We investigated the performance of our method using a number of challenging 3D neuronal image datasets of different model organisms including fruit fly, Caenorhabditis elegans, and mouse. In our experiments, the GD method outperformed several comparison methods in reconstruction accuracy, consistency, robustness and speed. We further used GD in two real applications, namely cataloging neurite morphology of fruit fly to build a 3D 'standard' digital neurite atlas, and estimating the synaptic bouton density along the axons for a mouse brain. AVAILABILITY: The software is provided as part of the V3D-Neuron 1.0 package freely available at http://penglab.janelia.org/proj/v3d.

chen, Y. et al. (2013) International Worm Meeting "The Effect of Hydrolysable Tannins from Eucalyptus Leaves on C. elegans Lifespan."

Huang, Q., Driscoll, M., Chen, H., Cao, Y., Onken, B., Chen, Y., Xiao, S.

[International Worm Meeting, 2013]

To identify potential pharmacological compounds that delay the progression of age-related degenerative changes and illness, we monitored the effects of six hydrolysable tannins with high antioxidant activities isolated from Eucalyptus leaves (Oenothein B (OEB), 1,2,3,4,6-penta-O-galloyl-b-D-glucose (PGG), Tellimagrandin I (T1), Tellimagrandin II(T2), Pedunculagin (Ped) and Gemin D (GD) ) on C. elegans lifespan at four different concentrations. We found that of the six, OEB and PGG extended lifespan in a dose-dependent manner and increased median lifespan by up to 22%. OEB significantly prolonged youthful locomotory ability. We also found that the survival curves of T1-treated animals at all tested concentrations were significantly increased, although median lifespan was not significantly improved. OEB, PGG and T1 did not significantly affect the age-associated physiological functions of reproduction, pharyngeal pumping rate, or age pigment accumulation. Animals treated with 40 mM Ped significantly extended median lifespan by 11%, but we did not observe any significant benefits at other Ped concentrations. T2 and GD did not cause significant lifespan extension at any tested concentration. To further determine how OEB and PGG prolong C. elegans lifespan, we investigated the genetic requirements for these benefits. Strikingly, we found that lifespan extension with OEB and PGG treatment was driven by the insulin signaling, dietary restriction, and mitochondrial function pathways, indicating that these compounds target multiple longevity mechanisms to promote lifespan. Together, our results demonstrate broad-based aging benefits with these botanical compounds, which may be exploited in novel therapies to promote healthy aging.

J Bellanger et al. (2004) European Worm Meeting "ZYG-9, TAC-1 AND ZYG-8 REGULATE MICROTUBULE BEHAVIOR IN ONE-CELL STAGE C. ELEGANS EMBRYOS"

A Debant, P Gonczy, J Bellanger

[European Worm Meeting, 2004]

Proper spatial and temporal control of microtubule dynamics by microtubule associated proteins (MAPs) is essential for successful cell division. In C. elegans one-cell stage embryos, the conserved MAPs ZYG-9 and ZYG-8 are required for pronuclear migration and anaphase spindle positioning, respectively (Matthews, Carter et al. 1998; Gnczy, Bellanger et al. 2001). To better understand how ZYG-8 activity is regulated during the cell cycle, we sought molecular partners through a two-hybrid screen. In doing so, we identified TAC-1, the sole Transforming and Acidic Coiled-Coil (TACC) protein of C. elegans (Bellanger and Gnczy 2003). We found that (i) pronuclear migration does not take place in tac-1 (RNAi) one-cell stage embryos, (ii) tac-1 promotes microtubule assembly in vivo, (iii) TAC-1 localizes to the cytoplasm and is enriched at spindle poles, (iv) TAC-1 physically interacts with both ZYG-8 and ZYG-9 in vitro and associates with the two MAPs in distinct complexes in vivo and (v) zyg-8 and zyg-9 functionally cooperate, acting in a partly redundant manner during meiosis, pronuclear migration and mitosis. Together, our data suggest that TAC-1 binds both ZYG-9 and ZYG-8 for proper microtubule stabilization throughout the cell cycle. The poster will also present a new project by J-MB and AD aiming at identifying the molecular complexes associated with the Guanine-nucleotide Exchange Factor (GEF) UNC-73 (Trio) in the developing nervous system of C. elegans. Several studies have indeed established Trio as a key transducer of extracellular guidance cues to the motile machinery during neuroblast migration, axon outgrowth and axon guidance (Steven, Kubiseski et al. 1998; Newsome, Schmidt et al. 2000; Estrach, Schmidt et al. 2002). However, the nature and the dynamics of the molecular complexes Trio assembles with remain elusive in vivo.

Li Y et al. (2014) Langmuir "Size-dependent MRI relaxivity and dual imaging with Eu0.2Gd0.8PO4-H2O nanoparticles."

Talham DR, Li Y, Tan W, Chen T

[Langmuir, 2014]

Three different sizes of Eu0.2Gd0.8PO4-H2O nanoparticles have been prepared to investigate the particle size influence on water proton relaxivity. Longitudinal relaxivity (r1) values increase for smaller particles, reaching as high as r1 = 6.13 mM(-1) s(-1) for a sample of 40 +/- 4 nm particles, which, with a ratio of transverse/longitudinal relaxivity, r2/r1 = 1.27, are shown to be effective positive contrast agents. The correlation between relaxivity and the surface-to-volume ratio implies that access to surface Gd(3+) sites is the principal factor affecting relaxivity. On the other hand, although ionic molar relaxivity decreases for larger particles, the relaxivity per particle can be significantly greater. Gadolinium-based nanoparticles doped with fluorescent lanthanide elements have attracted attention for their dual-imaging abilities, combining magnetic resonance imaging (MRI) and fluorescence imaging agents. In both in vitro experiments with HeLa cells and in vivo experiments with C. elegans, strong red fluorescence is observed from Eu0.2Gd0.8PO4-H2O with high resolution, demonstrating the parallel use of the particles as fluorescence imaging agents.

Katherine M Walstrom et al. (2005) International Worm Meeting "Transcription regulation of endogenous genes by C. elegans RNA Helicase A"

Deborah Schmidt, Christopher R Bauer, Katherine M Walstrom

[International Worm Meeting, 2005]

Transcriptional silencing is an important process required for early germline development in some organisms such as C. elegans and Drosophila (Leatherman and Jongens (2003) BioEssays 25, 326-335). RNA helicase A (RHA) is a conserved protein with roles in transcription regulation and histone modification in numerous organisms such as flies and humans. We are studying the role of C. elegans RHA (RHA-1) in transcription regulation and germline development. A null mutant, rha-1(tm329), has a temperature-dependent defect in germline transcriptional silencing of transgene arrays (Walstrom, Schmidt, Bean, and Kelly (2005) Mech. Dev. In press.). In addition, histone modifications are mis-localized on the transgene arrays, on autosomes, and on the single male X chromosome. These defects in gene regulation lead to a sterile phenotype in hermaphrodite and male worms. We are using real-time RT-PCR to determine if endogenous genes have altered expression in the mutants, and we are focusing on the X chromosome in the mutant males. The rha-1 mutant also has a temperature-dependent sterile phenotype, and we hope to identify genes with altered expression that could lead to the sterile phenotype. Recent results will be presented at the meeting.