Hendrickx K (2022) EMBO Rep "Keep biology weird: On disobedient worms and scientific freedom: On disobedient worms and scientific freedom."

Hendrickx K

[EMBO Rep, 2022]

Caenorhabditis elegans embodies the expectations of a solution-driven take on biology on the one hand, and the mysteries and wonders of life that drives biologists to go to their labs on the other hand.

Kumar M et al. (2012) PLoS One "In silico prediction and analysis of Caenorhabditis EF-hand containing proteins."

Kumar M, Ahmad S, Saifi MA, Ahmad E, Khan RH

[PLoS One, 2012]

Calcium (Ca) is a ubiquitous messenger in eukaryotes including Caenorhabditis. Ca-mediated signalling processes are usually carried out through well characterized proteins like calmodulin (CaM) and other Ca binding proteins (CaBP). These proteins interact with different targets and activate it by bringing conformational changes. Majority of the EF-hand proteins in Caenorhabditis contain Ca binding motifs. Here, we have performed homology modelling of CaM-like proteins using the crystal structure of Drosophila melanogaster CaM as a template. Molecular docking was applied to explore the binding mechanism of CaM-like proteins and IQ1 motif which is a 25 residues and conform to the consensus sequence (I, L, V)QXXXRXXXX(R,K) to serve as a binding site for different EF hand proteins. We made an attempt to identify all the EF-hand (a helix-loop-helix structure characterized by a 12 residues loop sequence involved in metal coordination) containing proteins and their Ca binding affinity in Caenorhabditis by analysing the complete genome sequence. Docking studies revealed that F165, F169, L29, E33, F44, L57, M61, M96, M97, M108, G65, V115, F93, N104, E144 of CaM-like protein is involved in the interaction with IQ1 motif. A maximum of 170 EF-hand proteins and 39 non-EF-hand proteins with Ca/metal binding motif were identified. Diverse proteins including enzyme, transcription, translation and large number of unknown proteins have one or more putative EF-hands. Phylogenetic analysis revealed seven major classes/groups that contain some families of proteins. Various domains that we identified in the EF-hand proteins (uncharacterized) would help in elucidating their functions. It is the first report of its kind where calcium binding loop sequences of EF-hand proteins were analyzed to decipher their calcium affinities. Variation in Ca-binding affinity of EF-hand CaBP could be further used to study the behaviour of these proteins. Our analyses postulated that Ca is likely to be key player in Caenorhabditis cell signalling.

Malik AN et al. (1995) International C. elegans Meeting "IDENTIFICATION OF THE LEADING EDGE CELLS DURING VENTRAL HYPODERMAL ENCLOSURE"

Malik AN, Hardin JD

[International C. elegans Meeting, 1995]

The morphogenesis of the external epithelium (hypodermis) of the Caenorhabditis elegans embryo drives ventral hypodermal enclosure and the subsequent elongation of the embryo. The presumptive ventral hypodermal cells arise on the dorsal surface of the embryo, and eventually spread laterally and then ventrally to establish junctional connections at the ventral midline. Time-lapse video microscopy as well as immunofluorescence has revealed that this enclosure process is led by the descendants of ABplaapp and ABpraapp. ABpraapppa and ABpraappap (the "leading" right-hand hypodermal cells) as well as ABplaapppa and ABplaappap (the "leading" left-hand hypodermal cells) appear to be pulling the rest of the ventral hypodermis along. We have investigated the role(s) of these leading cells during ventral enclosure using laser ablation. Ablation of the leading right-hand hypodermal cells (ABpraapppa and ABpraappap) causes the leading left-hand hypodermal cells (ABplaapppa and ABplaappap) to extend beyond the ventral midline, resulting in enclosure and elongation of the embryo. Likewise, ablation of the leading left-hand hypodermal cells has the same effect on the leading right-hand hypodermal cells. Ablation of all four cells early in enclosure causes the other ventral hypodermal cells to retract back towards the dorsal side of the embryo, resulting in interrupted elongation due to enclosure defects. Ablation of the anterior leading left and right-hand hypodermal cells still results in ventral enclosure, yet the embryo explodes during elongation (a similar result is seen when the two posterior cells are ablated). Ablation of one anterior leading left-hand hypodermal cell and one posterior leading right-hand hypodermal cell also results in wild-type enclosure with eventual irregular elongation. Ablation of ventral hypodermal cells which are posterior to the "leading" cells causes an immediate retraction of the hypodermis back towards the dorsal side of the embryo. We are currently recovering embryos after ablation and staining with the antibody MH27 in order visualize the apices of individual cells. We are also interested in analyzing the ventral enclosure process in the deficiency sDF23 (isolated by D. Baillie) because its "leading" cells do not migrate properly, while the rest of the hypodermis migrates around the embryo. Scanning electron microscopy is another technique which will be used to better elucidate the ventral enclosure process.

Galindo-Malagn XA et al. (2022) Zootaxa "New species, synonymies and records in the genus Rhagovelia Mayr, 1865 (Hemiptera: Heteroptera: Veliidae) from Colombia."

Moreira FFF, Morales I, Mondragn-F SP, Galindo-Malagn XA

[Zootaxa, 2022]

Rhagovelia medinae sp. nov., of the hambletoni group (angustipes complex), and R. utria sp. nov., of the hirtipes group (robusta complex), are described, illustrated, and compared with similar congeners. Based on the examination of type specimens, six new synonymies are proposed: R. elegans Uhler, 1894 = R. pediformis Padilla-Gil, 2010, syn. nov.; R. cauca Polhemus, 1997 = R. azulita Padilla-Gil, 2009, syn. nov., R. huila Padilla-Gil, 2009, syn. nov., R. oporapa Padilla-Gil, 2009, syn. nov, R. quilichaensis Padilla-Gil, 2011, syn. nov.; and R. gaigei, Drake Hussey, 1947 = R. victoria Padilla-Gil, 2012 syn. nov. The first record from Colombia is presented for R. trailii (White, 1879), and the distributions of the following species are extended in the country: R. cali Polhemus, 1997, R. castanea Gould, 1931, R. cauca Polhemus, 1997, R. gaigei Drake Hussey, 1957, R. elegans Uhler, 1894, R. femoralis Champion, 1898, R. malkini Polhemus, 1997, R. perija Polhemus, 1997, R. sinuata Gould, 1931, R. venezuelana Polhemus, 1997, R. williamsi Gould, 1931, and R. zeteki Drake, 1953.

Dutting S et al. (2011) Cell Commun Signal "Fraternal twins: Swiprosin-1/EFhd2 and Swiprosin-2/EFhd1, two homologous EF-hand containing calcium binding adaptor proteins with distinct functions."

Mielenz D, Brachs S, Dutting S

[Cell Commun Signal, 2011]

ABSTRACT: Changes in the intracellular calcium concentration govern cytoskeletal rearrangement, mitosis, apoptosis, transcriptional regulation or synaptic transmission, thereby, regulating cellular effector and organ functions. Calcium binding proteins respond to changes in the intracellular calcium concentration with structural changes, triggering enzymatic activation and association with downstream proteins. One type of calcium binding proteins are EF-hand super family proteins. Here, we describe two recently discovered homologous EF-hand containing adaptor proteins, Swiprosin-1/EF-hand domain containing 2 (EFhd2) and Swiprosin-2/EF-hand domain containing 1 (EFhd1), which are related to allograft inflammatory factor-1 (AIF-1). For reasons of simplicity and concision we propose to name Swiprosin-1/EFhd2 and Swiprosin-2/EFhd1 from now on EFhd2 and EFhd1, according to their respective gene symbols. AIF-1 and Swiprosin-1/EFhd2 are already present in Bilateria, for instance in Drosophila melanogaster and Caenhorhabditis elegans. Swiprosin-2/EFhd1 arose later from gene duplication in the tetrapodal lineage. Secondary structure prediction of AIF-1 reveals disordered regions and one functional EF-hand. Swiprosin-1/EFhd2 and Swiprosin-2/EFhd1 exhibit a disordered region at the N-terminus, followed by two EF-hands and a coiled-coil domain. Whereas both proteins are similar in their predicted overall structure they differ in a non-homologous stretch of 60 amino acids just in front of the EF-hands. AIF-1 controls calcium-dependent cytoskeletal rearrangement in innate immune cells by means of its functional EF-hand. We propose that Swiprosin-1/EFhd2 as well is a cytoskeleton associated adaptor protein involved in immune and brain cell function. Pro-inflammatory conditions are likely to modulate expression and function of Swiprosin-1/EFhd2. Swiprosin-2/EFhd1, on the other hand, modulates apoptosis and differentiation of neuronal and muscle precursor cells, probably through an association with mitochondria. We suggest furthermore that Swiprosin-2/EFhd1 is part of a cellular response to oxidative stress, which could explain its pro-survival activity in neuronal, muscle and perhaps some malignant tissues.

Qiang Liu et al. (2005) International Worm Meeting "Role of Ryanodine Receptors in Synaptic Release at the C. elegans Neuromuscular Junction"

Michael L Nonet, Ed Maryon, D Kent Morest, Bojun Chen, Arthur R Hand, Zhao-Wen Wang, Qiang Liu, Maya Yankova

[International Worm Meeting, 2005]

Quantal size (amount of neurotransmitter released from exocytosis of a single synaptic vesicle) is highly variable at many synapses. However, little is known about the regulation of quantal size. At the C. elegans neuromuscular junction, amplitudes of miniature postsynaptic currents (mPSCs) varied greatly. Mutations of the ryanodine receptor (RYR) gene unc-68 essentially abolished large-amplitude mPSCs. The amplitude of evoked postsynaptic currents (ePSCs) was also suppressed. These defects were completely rescued by expressing wild-type UNC-68 specifically in neurons but not in muscle cells. A combination of UNC-68 dysfunction and zero extracellular Ca2+ eliminated mPSCs, suggesting that synaptic exocytosis may have an obligatory requirement for Ca2+, and that Ca2+ influx and ryanodine receptor-mediated release are likely the exclusive sources of Ca2+, for synaptic exocytosis. The fraction of large-amplitude mPSCs remained constant following removal of extracellular Ca2+, suggesting that they were not endogenous ePSCs. Large-amplitude mPSCs at vertebrate central synapses are thought to result from synchronized multivesicular release ((Llano et al., 2000; Sharma and Vijayaraghavan, 2003). In contrast, large-amplitude mPSCs at the C. elegans NMJ appear to be monoquantal because (1) large-amplitude events remained after removal of extracellular Ca2+, (2) there was no correlation between the rise time and the amplitude of mPSCs, (3) the rise time of ePSCs, which represent synchronized multivesicular release, was much longer than that of mPSCs, (4) the fraction of large-amplitude mPSCs did not decrease in mutants (unc-64 and ric-4) that are defective in synchronized synaptic exocytosis. Electron microscopy showed that neither the synaptic vesicle size nor the numbers of total and morphologically docked vesicles per synapse were different between the wild-type and the unc-68 mutant, suggesting that the inhibition of mPSCs and ePSCs by RYR mutation was not due to decreased vesicle size or number. Thus we conclude that (1) all mPSCs at the C. elegans NMJ are monoquantal; (2) RYRs are required for the normal quantal size, and are potential regulators of quantal size; (3) synaptic exocytosis, including spontaneous events, appears to have an obligatory requirement for Ca2+. Influx of extracellular Ca2+ and RYR-mediated release from the ER are likely the exclusive sources of Ca2+ for synaptic exocytosis.

Fay DS (2013) Curr Biol "Cancer metabolism: feeding a worm to starve a tumor."

Fay DS

[Curr Biol, 2013]

The tumor suppressor Rb is known to have its hand in many pots. New findings have added another pot to the mix - cell metabolism. This may lead to a better understanding of Rb mutant phenotypes and Rb's roles in oncogenesis.

Gbary AR et al. Med Trop (Mars) "[Filarial multiparasitism in the savannah zone in Burkina Faso]."

Lechuga P, Gbary AR, Guiguemde TR, Ouedraogo JB

[Med Trop (Mars)]

From june 1985 to may 1986, 1.209 consulting patients were examined for filariae in skin and blood. Among patients with microfilariae 17% had associations of filarial infections. The multiple infections rate seemed more important in man than woman and increased with age. The results showed that associations were not due to chance only. The frequencies of associations between Dipetalonema perstans and Onchocerca volvulus at one hand, Dipetalonema perstans and Wuchereria bancrofti on the other hand were highly significant. Symptoms of filarial associations were studied and subsequent therapeutic attitude discussed.

Koyiloth M et al. (2020) Eur Biophys J "Molecular cloning and biochemical characterization of the phospholipid scramblase SCRM-1 from Caenorhabditis elegans."

Koyiloth M, Gummadi SN

[Eur Biophys J, 2020]

In this study, the SCRM-1 gene from Caenorhabditis elegans was cloned and overexpressed in E. coli to study the biochemical properties of scramblase. This is the first report showing that this scramblase from C. elegans possesses a Ca²⁺-dependent and head group-independent scramblase activity. The SCRM-1 of C.elegans possesses functional domains including a single EF-hand-like Ca²⁺ binding domain, as human scramblases do. A point mutation in the EF-hand-like Ca²⁺ binding motif results in loss of scramblase activity. Other biochemical assays like carbocyanine staining, Tb³⁺ luminescence, Tryptophan fluorescence, and CD spectroscopy strongly proved the role of the EF-hand motif for functional activity. The increase in protein size in solution upon incubating with Ca²⁺ shows ligand-dependent oligomerization and conformational changes.

Zeinolabediny Y et al. (2017) Sci Rep "HIV-1 matrix protein p17 misfolding forms toxic amyloidogenic assemblies that induce neurocognitive disorders."

Airoldi C, Weston R, Romeo M, Sarroca S, Morelli F, Slevin M, Caruso A, Donghui L, Garcia-Lara E, Rossi A, Colombo L, Ciaramelli C, Zeinolabediny Y, Caccuri F, Sanfeliu C, Corpas R, Salmona M, Krupinski J, Diomede L, Schiarea S

[Sci Rep, 2017]

Human immunodeficiency virus type-1 (HIV-1)-associated neurocognitive disorder (HAND) remains an important neurological manifestation that adversely affects a patient's quality of life. HIV-1 matrix protein p17 (p17) has been detected in autoptic brain tissue of HAND individuals who presented early with severe AIDS encephalopathy. We hypothesised that the ability of p17 to misfold may result in the generation of toxic assemblies in the brain and may be relevant for HAND pathogenesis. A multidisciplinary integrated approach has been applied to determine the ability of p17 to form soluble amyloidogenic assemblies in vitro. To provide new information into the potential pathogenic role of soluble p17 species in HAND, their toxicological capability was evaluated in vivo. In C. elegans, capable of recognising toxic assemblies of amyloidogenic proteins, p17 induces a specific toxic effect which can be counteracted by tetracyclines, drugs able to hinder the formation of large oligomers and consequently amyloid fibrils. The intrahippocampal injection of p17 in mice reduces their cognitive function and induces behavioral deficiencies. These findings offer a new way of thinking about the possible cause of neurodegeneration in HIV-1-seropositive patients, which engages the ability of p17 to form soluble toxic assemblies.