Miller DM et al. (1992) Worm Breeder's Gazette "unc-4 LacZ Expression in A-Type Motor Neurons"

Miller DM, Niemeyer CJ

[Worm Breeder's Gazette, 1992]

unc-4 LacZ expression in A-type motor neurons David M. Miller and Charles J. Niemeyer, Dept. of Cell Biology, Duke Univ. Medical Ctr, Durham, NC 27710

Johnson, Christina K. et al. (2021) MicroPubl Biol

Miller III, David M., Johnson, Christina K., Bianchi, Laura

[MicroPubl Biol, 2021]

For Johnson, CK; Miller, DD; Bianchi, L (2021). Effect of the protease plasmin on C. elegans hyperactive DEG/ENaC channels MEC-4(d) and UNC-8(d). microPublication Biology. 10.17912/micropub.biology.000412.

Phukhamsakda C et al. (2019) J Nat Prod "Sparticolins A-G, Biologically Active Oxidized Spirodioxynaphthalene Derivatives from the Ascomycete Sparticola junci."

Hyde KD, Phukhamsakda C, Cheng T, Macabeo APG, Stadler M, Huch V

[J Nat Prod, 2019]

To explore the chemical diversity of metabolites from new species of Dothideomycetes, the ex-type strain of <i>Sparticola junci</i> was investigated. Seven highly oxygenated and functionalized spirodioxynaphthalene natural products incorporating carboxyalkylidene-cyclopentanoid (<b>1</b>-<b>4</b>), carboxyl-functionalized oxabicyclo[3.3.0]octane (<b>5</b>-<b>6</b>), and annelated 2-cyclopentenone/-lactone (<b>7</b>) units, sparticolins A-G, were isolated from submerged cultures of the fungus. Their chemical structures including their relative (and absolute) configurations were established through spectroscopic and X-ray crystallographic analyses. Sparticolin B (<b>2</b>) exhibited inhibitory activity against the Gram-positive bacteria <i>Bacillus subtilis</i>, <i>Micrococcus luteus</i>, and <i>Staphylococcus aureus</i>, while sparticolin G (<b>7</b>) showed antifungal activities against <i>Schizosaccharomyces pombe</i> and <i>Mucor hiemalis</i>. All other sparticolins were only weakly active against <i>S. aureus</i> and also showed weak activities against the nematode <i>Caenorhabditis elegans</i>. Compounds <b>2</b> and <b>7</b> also showed moderate cytotoxic activities against seven mammalian cell lines.

Richie CT et al. (2005) Curr Biol "Chromosome segregation: Aurora B gets Tousled."

Golden A, Richie CT

[Curr Biol, 2005]

Aurora B kinases play important roles during mitosis in eukaryotic cells; new work in Caenorhabditis elegans has identified the Tousled kinase TLK-1 as a substrate activator of the model nematode''''s Aurora B kinase AIR-2 which acts to ensure proper chromosome segregation during

Kitamura S et al. (1994) Worm Breeder's Gazette "The Troponin C Gene, tnc-1, of Caenorhabditis elegans: Genome Structure and Mutation Sites of pat-10"

Williams BD, Kitamura S, Kagawa H, Sakube Y, Matsumoto S

[Worm Breeder's Gazette, 1994]

The troponin C gene, tnc-1 of Caenorhabditis elegans: Genome structure and mutation sites of pat-10 S. KITAMURA, B. WILLIAMS*, Y. SAKUBE, S. MATSUMOTO and H. KAGAWA, Dept. of Biol., Fac. of Sci., Okayama University, Japan, 700. *;Dept. of Gen., Washington Univ. School of Med., St. Louis

Georgikou C et al. (2020) Biomolecules "Novel Broccoli Sulforaphane-Based Analogues Inhibit the Progression of Pancreatic Cancer without Side Effects."

Bremerich M, Herr I, Roubicek N, Bolm C, Buglioni L, Gross W, Georgikou C, Sticht C, Yin L

[Biomolecules, 2020]

The naturally occurring isothiocyanate sulforaphane, found in <i>Brassicaceae</i> vegetables, is promising in cancer treatment, e.g., by the normalization of enhanced levels of NF-B-signaling in tumor stem cells. We chemically synthesized seven sulforaphane analogues by substitution of the sulfinyl group (S(O)) to either sulfimidoyl (S(NR)) or sulfonimidoyl (S (O) (NR)) groups, and characterized them in the cell lines of pancreatic cancer and several other tumor entities, including the NCI-60 cell panel. MTT and colony forming assays, flow cytometry, immunohistochemistry, microRNA arrays, bioinformatics, tumor xenotransplantation, and Kaplan Meier survival curves were performed. Compared to sulforaphane, the analogue <b>SF102</b> was most efficient in inhibition of viability, colony formation, tumor growth, and the induction of apoptosis, followed by <b>SF134.</b> Side effects were not observed, as concluded from the body weight and liver histology of chick embryos and survival of <i>C. elegans</i> nematodes. Among 6659 differentially regulated microRNAs, miR29b-1-5p, and miR-27b-5p were downregulated by sulforaphane compared to controls, but upregulated by <b>SF102</b> and <b>SF134</b> compared to sulforaphane, suggesting differential signaling. Each substance was involved in the regulation of several NF-B-related target genes. In conclusion, sulforaphane analogues are promising for the development of highly active new drugs in cancer treatment.

Neupane RP et al. (2019) Mar Drugs "Cytotoxic Sesquiterpenoid Quinones and Quinols, and an 11-Membered Heterocycle, Kauamide, from the Hawaiian Marine Sponge Dactylospongia elegans."

Williams PG, Neupane JB, Yip MLR, Turkson J, Parrish SM, Yoshida WY, Head JD, Harper MK, Neupane RP

[Mar Drugs, 2019]

Several known sesquiterpenoid quinones and quinols (<b>1</b>-<b>9</b>), and kauamide (<b>10</b>), a new polyketide-peptide containing an 11-membered heterocycle, were isolated from the extracts of the Hawaiian marine sponge <i>Dactylospongia</i><i>elegans</i>. The planar structure of <b>10</b> was determined from spectroscopic analyses, and its relative and absolute configurations were established from density functional theory (DFT) calculations of the GIAO NMR shielding tensors, and advanced Marfey's analysis of the <i>N</i>-MeLeu residue, respectively. Compounds <b>1</b> and <b>3</b> showed moderate inhibition of -secretase 1 (BACE1), whereas <b>1</b>-<b>9</b> exhibited moderate to potent inhibition of growth of human glioma (U251) cells. Compounds <b>1</b>-<b>2</b> and <b>4</b>-<b>7</b> were also active against human pancreatic carcinoma (Panc-1) cells.

Song J et al. (2020) ACS Infect Dis "Discovery of Prenyltransferase Inhibitors with In Vitro and In Vivo Antibacterial Activity."

Gennis RB, Seleem MN, Pogorelov TV, Yang K, Feng X, Abutaleb NS, Gao Z, Vaidya GS, Malwal SR, Schurig-Briccio LA, Oldfield E, Song J, Baig N

[ACS Infect Dis, 2020]

<i>Cis</i>-prenyltransferases such as undecaprenyl diphosphate synthase (UPPS) and decaprenyl diphosphate synthase (DPPS) are essential enzymes in bacteria and are involved in cell wall biosynthesis. UPPS and DPPS are absent in the human genome, so they are of interest as targets for antibiotic development. Here, we screened a library of 750 compounds from National Cancer Institute Diversity Set V for the inhibition of <i>Mycobacterium tuberculosis</i> DPPS and found 17 hits, and then IC₅₀s were determined using dose-response curves. Compounds were tested for growth inhibition against a panel of bacteria, for <i>in vivo</i> activity in a <i>Staphylococcus aureus</i>/<i>Caenorhabditis elegans</i> model, and for mammalian cell toxicity. The most active DPPS inhibitor was the dicarboxylic acid redoxal (compound <b>10</b>), which also inhibited undecaprenyl diphosphate synthase (UPPS) as well as farnesyl diphosphate synthase. <b>10</b> was active against <i>S. aureus</i>, <i>Clostridiodes difficile</i>, <i>Bacillus anthracis</i> Sterne, and <i>Bacillus subtilis</i>, and there was a 3.4-fold increase in IC₅₀ on addition of a rescue agent, undecaprenyl monophosphate. We found that <b>10</b> was also a weak protonophore uncoupler, leading to the idea that it targets both isoprenoid biosynthesis and the proton motive force. In an <i>S. aureus</i>/<i>C. elegans in vivo</i> model, <b>10</b> reduced the <i>S. aureus</i> burden 3 times more effectively than did ampicillin.

Gupta S et al. (2005) Exp Parasitol "Setaria cervi: immunoprophylactic potential of glutathione-S-transferase against filarial parasite Brugia malayi."

Bhandari YP, Gupta S, Harinath BC, Reddy MV, Rathaur S

[Exp Parasitol, 2005]

Glutathione-S-transferase (GST) has been detected in the adult female Setaria cervi, a bovine filarial parasite. The role of S. cervi GST antigen in inducing immunity in the host against Brugia malayi microfilariae and infective larvae was studied by in vitro antibody dependent cell mediated reaction as well as in situ inoculation of filarial parasites within a microchamber in Mastomys. The immune sera from glutathione-S-transferase immunized Mastomys promoted the adherence of peritoneal exudate cells to B. malayi microfilariae and infective larvae in vitro inducing 80.7 and 77.6% cytotoxicity, respectively in 72 h. In the microchambers implanted in the immunized Mastomys host cells could migrate and adhere to the microfilariae and infective larvae and induced 77.8 and 75% cytotoxicity to B. malayi microfilariae and infective larvae in 72 h, respectively. These results suggest that native GST from S. cervi is effective in inducing protection against heterologous B. malayi filarial parasite and thus has potential in immunoprophylaxis.

Bito T et al. (2019) Metabolites "Involvement of Spermidine in the Reduced Lifespan of Caenorhabditis elegans During Vitamin B12 Deficiency."

Bito T, Arima J, Kawano T, Otsuka K, Okamoto N, Yabuta Y, Watanabe F

[Metabolites, 2019]

Vitamin B₁₂ deficiency leads to various symptoms such as neuropathy, growth retardation, and infertility. Vitamin B₁₂ functions as a coenzyme for two enzymes involved in amino acid metabolisms. However, there is limited information available on whether amino acid disorders caused by vitamin B₁₂ deficiency induce such symptoms. First, free amino acid levels were determined in vitamin B₁₂-deficient <i>Caenorhabditis elegans</i> to clarify the mechanisms underlying the symptoms caused by vitamin B₁₂ deficiency. Various amino acids (valine, leucine, isoleucine, methionine, and cystathionine, among others) metabolized by vitamin B₁₂-dependent enzymes were found to be significantly changed during conditions of B₁₂ deficiency, which indirectly affected certain amino acids metabolized by vitamin B₁₂-independent enzymes. For example, ornithine was significantly increased during vitamin B₁₂ deficiency, which also significantly increased arginase activity. The accumulation of ornithine during vitamin B₁₂ deficiency constitutes the first report. In addition, the biosynthesis of spermidine from ornithine was significantly decreased during vitamin B₁₂ deficiency, likely due to the reduction of <i>S</i>-adenosylmethionine as a substrate for <i>S</i>-adenosylmethionine decarboxylase, which catalyzes the formation of spermidine. Moreover, vitamin B₁₂ deficiency also demonstrated a significant reduction in worm lifespan, which was partially recovered by the addition of spermidine. Collectively, our findings suggest that decreased spermidine is one factor responsible for reduced lifespan in vitamin B₁₂-deficient worms.