Ma C et al. (2015) Molecules "Potent Activities of Roemerine against Candida albicans and the Underlying Mechanisms."

Yan L, Xu G, Wang C, He G, Du F, Jiang Y, Ma C, Rao G, He J

[Molecules, 2015]

Roemerine (RM) is an aporphine alkaloid isolated from the fresh rattan stem of Fibraurea recisa, and it has been demonstrated to have certain antifungal activity. This study aimed to investigate the antifungal activity of RM and the underlying mechanisms in Candida albicans (C. albicans). The in vitro antifungal activity of RM was evaluated by a series of experiments, including the XTT reduction assay, confocal laser scanning microscopy assay, scanning electron microscope assay. Results showed that 1 g/mL RM inhibited biofilm formation significantly (p < 0.01) both in Spider medium and Lee's medium. In addition, RM could inhibit yeast-to-hyphae transition of C. albicans in a dose-dependent manner. The biofilm-specific and hypha-specific genes such as YWP1, SAP5, SAP6, HWP1, ECE1 were up-regulated and EFG1 was down-regulated after 8 g/mL RM treatment. Furthermore, the toxicity of RM was investigated using C. elegans worms, three cancer cells and one normal cell. The date showed that RM had no significant toxicity. In conclusion, RM could inhibited the formation of C. albicans biofilm in vitro, but it had no fungicidal effect on planktonic C. albicans cells, and the anti-biofilm mechanism may be related to the cAMP pathway.

Gouveia GJ et al. (2021) Anal Chem "Long-Term Metabolomics Reference Material."

Andersen EC, Morse AM, Garcia BM, Edison AS, Shaver AO, Gouveia GJ, McIntyre LM

[Anal Chem, 2021]

The use of quality control samples in metabolomics ensures data quality, reproducibility, and comparability between studies, analytical platforms, and laboratories. Long-term, stable, and sustainable reference materials (RMs) are a critical component of the quality assurance/quality control (QA/QC) system; however, the limited selection of currently available matrix-matched RMs reduces their applicability for widespread use. To produce an RM in any context, for any matrix that is robust to changes over the course of time, we developed iterative batch averaging method (IBAT). To illustrate this method, we generated 11 independently grown <i>Escherichia coli</i> batches and made an RM over the course of 10 IBAT iterations. We measured the variance of these materials by nuclear magnetic resonance (NMR) and showed that IBAT produces a stable and sustainable RM over time. This <i>E. coli</i> RM was then used as a food source to produce a <i>Caenorhabditis elegans</i> RM for a metabolomics experiment. The metabolite extraction of this material, alongside 41 independently grown individual <i>C. elegans</i> samples of the same genotype, allowed us to estimate the proportion of sample variation in preanalytical steps. From the NMR data, we found that 40% of the metabolite variance is due to the metabolite extraction process and analysis and 60% is due to sample-to-sample variance. The availability of RMs in untargeted metabolomics is one of the predominant needs of the metabolomics community that reach beyond quality control practices. IBAT addresses this need by facilitating the production of biologically relevant RMs and increasing their widespread use.

Waterston RH et al. (1977) J Mol Biol "Mutants affecting paramyosin in Caenorhabditis elegans."

Brenner S, Fishpool RM, Waterston RH

[J Mol Biol, 1977]

Four mutants of Caenorhabditis elegans with abnormal muscle structure are described which are alleles of a single locus unc-15. In one of the mutants, E1214, paramyosin is completely absent from both body-wall and pharyngeal musculature. In the other three mutants paramyosin is present but does not assemble into thick filaments. Instead paramyosin paracrystals are formed in the body-wall muscle cells. Myosin filaments lacking paramyosin cores are present in all four mutants, but these filaments fail to integrate stably into the myofilament lattice. One mutant is temperature-sensitive; all four are semi-dominant in their effect on muscle structure. The hypothesis that unc-15 is the structural gene for paramyosin is discussed.

Birchall PS et al. (1995) Nat Genet "Expression patterns of predicted genes from the C. elegans genome sequence visualized by FISH in whole organisms."

Albertson DG, Fishpool RM, Birchall PS

[Nat Genet, 1995]

More than 10 megabases of contiguous genome sequence have been submitted to the databases by the Caenorhabditis elegans Genome Sequencing Consortium. To characterize the genes predicted from the sequence, we have developed high resolution FISH for visualization of mRNA distributions in whole animals. The high resolution and sensitivity afforded by the use of directly fluorescently labelled probes and confocal imaging permitted mRNA distributions to be recorded at the cellular and subcellular level. Expression patterns were obtained for 8 out of 10 genes in an initial test set of predicted gene sequences, indicating that FISH is an effective means of characterizing predicted genes in C. elegans.

MacLeod AR et al. (1977) J Mol Biol "Identification of the structural gene for a myosin heavy-chain in Caenorhabditis elegans."

Waterston RH, MacLeod AR, Brenner S, Fishpool RM

[J Mol Biol, 1977]

Mutants in the unc-54 gene of Caenorhabditis elegans have been characterized by cyanylation and sodium dodecyl sulphate/polyacrylamide gel electrophoresis of the total myosin present in each mutant. In the recessive mutants lacking a major fraction of the total myosin, the high molecular weight doublet of 15 X 10*4 and 14 X 10*4 which dominates the cyanylation pattern of the total wild-type myosin is absent. In the mutant E675, which possesses a novel heavy-chain with a molecular weight of 2 X 10*5, each component of the cyanylation doublet is reduced by 10*4 daltons, indicating that the doublet is derived from partial cleavage of a single polypeptide chain. This suggests that unc-54 is the structural gene for a myosin heavy-chain present in a major fraction of the total

Volpatti JR et al. (2020) Elife "Identification of drug modifiers for RYR1 related myopathy using a multi-species discovery pipeline."

Groom L, Endo Y, Volpatti JR, Zuercher WJ, Brennan S, Roy P, Dirksen RT, Dowling JJ, Knox J, Noche R

[Elife, 2020]

Ryanodine receptor type I-related myopathies (RYR1-RMs) are a common group of childhood muscle diseases associated with severe disabilities and early mortality for which there are no available treatments. The goal of this study is to identify new therapeutic targets for RYR1-RMs. To accomplish this, we developed a discovery pipeline using nematode, zebrafish, and mammalian cell models. We first performed large-scale drug screens in <i>C. elegans</i> which uncovered 74 hits. Targeted testing in zebrafish yielded positive results for two p38 inhibitors. Using mouse myotubes, we found that either pharmacological inhibition or siRNA silencing of p38 impaired caffeine-induced Ca²⁺ release from wild type cells while promoting intracellular Ca²⁺ release in <i>Ryr1</i> knockout cells. Lastly, we demonstrated that p38 inhibition blunts the aberrant temperature-dependent increase in resting Ca²⁺ in myotubes from an RYR1-RM mouse model. This unique platform for RYR1-RM therapy development is potentially applicable to a broad range of neuromuscular disorders.

Yu Z et al. (2011) J Environ Sci (China) "Behavior toxicity to Caenorhabditis elegans transferred to the progeny after exposure to sulfamethoxazole at environmentally relevant concentrations."

Yu Z, Jiang L, Yin D

[J Environ Sci (China), 2011]

Sulfamethoxazole (SMX) is one of the most common detected antibiotics in the environment. In order to study whether SMX can affect behavior and growth and whether these effects could be transferred to the progeny, Caenorhabditis elegans was exposed at environmentally relevant concentrations for 24, 48, 72 and 96 hr, respectively. After exposure, the exposed parent generation (P0) was measured for behavior and growth indicators, which were presented as percentage of controls (POC). Then their corresponding unexposed progeny (F1) was separated and measured for the same indicators. The lowest POC for P0 after 96 hr-exposure at 100 mg/L were 37.8%, 12.7%, 45.8% and 70.1% for body bending frequency (BBF), reversal movement (RM), Omega turns (OT) and body length (BL), respectively. And F1 suffered defects with the lowest POC as 55.8%, 24.1%, 48.5% and 60.7% for BBF, RM, OT and BL, respectively. Defects in both P0 and F1 showed a time- and concentration-dependent fashion and behavior indicators showed better sensitivity than growth indicator. The observed effects on F1 demonstrated the transferable properties of SMX. Defects of SMX at environmental concentrations suggested that it is necessary to perform further systematical studies on its ecological risk in actual conditions.

Zaridah MZ et al. (2001) J Ethnopharmacol "In vitro antifilarial effects of three plant species against adult worms of subperiodic Brugia malayi."

Omar AW, Idid SZ, Zaridah MZ, Khozirah S

[J Ethnopharmacol, 2001]

Five aqueous extracts from three plant species, i.e., dried husks (HX), dried seeds (SX) and dried leaves (LX) of Xylocarpus granatum (Meliaceae), dried stems (ST) of Tinospora crispa (Menispermaceae) and dried leaves (LA) of Andrographis paniculata (Acanthaceae) were tested in vitro against adult worms of subperiodic Brugia malayi. The relative movability (RM) value of the adult worms over the 24-h observation period was used as a measure of the antifilarial activity of the aqueous extracts. SX extract of X. granatum demonstrated the strongest activity, followed by the LA extract of A. paniculata, ST extract of T. crispa, HX extract and LX extract of X. granatum.

Rose AM et al. (1980) Genetics "Genetic organization of the region around UNC-15 (I), a gene affecting paramyosin in Caenorhabditis elegans."

Baillie DL, Rose AM

[Genetics, 1980]

In the nematode Caenorhabditis elegans mutants in the gene unc-15 (I) affect the muscle protein paramyosin (Waterston, Fishpool and Brenner 1977). We have characterized 20 ethyl methanesulfonate-induced mutations in essential genes closely linked to unc-15. These lethals defined 16 new complementation groups. In the 0.65 map-unit interval around unc-15 defined by dpy-14 and unc-56, seven newly identified genes have been mapped relative to five existing genes. At present, the average distance between genes in this region is approximately 0.05 map units. Two genes, unc-15 and unc-13, are only 0.025 map units apart. Partial fine-structures maps of alleles of these two genes have been constructed. This analysis of unc-15 and genes adjacent to it is the first in a series of genetic and biochemical studies directed towards understanding the control of unc-15 expression.

Wilson DL (1993) Mech Ageing Dev "A comparison of methods for estimating mortality parameters from survival data."

Wilson DL

[Mech Ageing Dev, 1993]

The Gompertz mortality function, Rm = R0e alpha t, is frequently used to describe changes in mortality rate (Rm) with time (t). In this paper, four methods for determining the best fit values of the two parameters, R0 and alpha, are compared. Three of the four methods use the Gompertz mortality function with mortality rate estimates derived from survival data to determine the best fit values for the two parameters. All three confront problems. The fourth method uses the Gompertz survival function, which can be derived from the Gompertz mortality function and which allows one to use survival data directly. It thereby avoids the problems and generally gives the best estimates for the two parameters. The use of the mortality function, with mortality rate estimates, confronts four distinct problems. One of these is caused by time intervals when zero organisms die. A second is caused by errors produced in estimating mortality rates from survival data. If too high a proportion of a population die in a given time interval, the mortality rate estimates are too low. A third problem is the sensitivity of the mortality-equation-based analyses to values at the end of the survival curve, where scatter in mortality values tends to be greater. A final problem occurs when time intervals greater than one time unit (day, week, year, etc.) are used in the analysis. Such problems with the use of mortality rates to estimate parameter values are revealed when the calculated parameters are used to produce a survival curve, or when known values of R0 and alpha are used to generate survival data. This paper introduces a non-linear regression analysis, using a Simplex algorithm to fit parameters R0 and alpha in the Gompertz Survival function and concludes that it gives more reliable and consistent results with a variety of data than do three methods that use the mortality function.