Michael WM (2017) MicroPubl Biol "Asymmetric distribution of cyb-3 in 4-cell stage embryos."

Michael WM

[MicroPubl Biol, 2017]

Early embryos were fixed and stained with Mab F2F4 (green), shown to recognize CYB-3 (Michael, 2016), and DAPI, to illuminate the DNA (blue). Either wild type or par-4 mutant embryos were examined, after 24-hour incubation at 25C (the non-permissive temperature for the it47 allele of par-4). Anterior is to the left in all images. The data presented here reveals previously not shown data that depicts CYB-3 as asymmetrically distributed at the 4-cell stage. These data further support reported findings in Michael, 2016. There is more CYB-3 in the AB cell relative to its sister P1. In 4-cell embryos there is more CYB-3 in the EMS cell relative to its sister, P2. Thus, during P-lineage divisions, CYB-3 is asymmetrically distributed such that the somatic precursor receives more than its germline precursor sister cell. This asymmetry is abolished in par-4 mutant embryos, where all blastomeres contain equivalent amounts of CYB-3.

Lieb JD et al. (1996) Science "DPY-26, a link between dosage compensation and meiotic chromosome segregation in the nematode."

Capowski EE, Meneely PM, Lieb JD, Meyer BJ

[Science, 1996]

The DPY-26 protein is required in the nematode Caenorhabditis elegans for X-chromosome dosage compensation as well as for proper meiotic chromosome segregation. DPY-26 was shown to mediate both processes through its association with chromosomes. In somatic cells, DPY-26 associates specifically with hermaphrodite X chromosomes to reduce their transcript levels. In germ cells, DPY-26 associates with all meiotic chromosomes to mediate its role in chromosome segregation. The X-specific localization of DPY-26 requires two dosage compensation proteins (DPY-27 and DPY-30) and two proteins that coordinately control both sex determination and dosage compensation (SDC-2 and SDC-3).AD - Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.FAU - Lieb, J DAU - Lieb JDFAU - Capowski, E EAU - Capowski EEFAU - Meneely, PAU - Meneely PFAU - Meyer, B JAU - Meyer BJLA - engSI - GENBANK/U43562SI - GENBANK/Z70680ID - GM30702/GM/NIGMSID - HD24324/HD/NICHDID - T32 GM07127/GM/NIGMSPT - Journal ArticleCY - UNITED STATESTA - ScienceJID - 0404511RN - 0 (Carrier Proteins)RN - 0 (DPY-27 protein)RN - 0 (Helminth Proteins)RN - 0 (Nuclear Proteins)SB - IM

Chuang P-T et al. (1996) Science "Sex-specific assembly of a dosage compensation complex on the nematode X chromosome."

Lieb JD, Meyer JB, Chuang P-T

[Science, 1996]

In nematodes, flies, and mammals, dosage compensation equalizes X-chromosome gene expression between the sexes through chromosome-wide regulatory mechanisms that function in one sex to adjust the levels of X-linked transcripts. Here, a dosage compensation complex was identified in the nematode Caenorhabditis elegans that reduces transcript levels from the two X chromosomes in hermaphrodites. This complex contains at least four proteins, including products of the dosage compensation genes dpy-26 and dpy-27. Specific localization of the complex to the hermaphrodite X chromosomes is conferred by XX-specific regulatory genes that coordinately control both sex determination and dosage compensation.AD - Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.FAU - Chuang, P TAU - Chuang PTFAU - Lieb, J DAU - Lieb JDFAU - Meyer, B JAU - Meyer BJLA - engID - GM30702/GM/NIGMSID - T32 GM07127/GM/NIGMSPT - Journal ArticleCY - UNITED STATESTA - ScienceJID - 0404511RN - 0 (Carrier Proteins)RN - 0 (DPY-27 protein)RN - 0 (Helminth Proteins)RN - 0 (Nuclear Proteins)RN - 0 (RNA, Helminth)RN - 0 (RNA, Messenger)SB - IM

Vairoletti F et al. (2019) Medchemcomm "Synthesis of bicyclic 1,4-thiazepines as novel anti-Trypanosoma brucei brucei agents."

Medeiros A, Fontan P, Jancik V, Melendrez J, Saiz C, Vairoletti F, Tabarez C, Mahler G, Franco J, Salinas G, Comini MA, Saldana J

[Medchemcomm, 2019]

1,4-Thiazepines derivatives are pharmacologically important heterocycles with different applications in medicinal chemistry. In the present work, we describe the preparation of new bicyclic thiazolidinyl-1,4-thiazepines <b>3</b> by reaction between azadithiane compounds and Michael acceptors. The reaction scope was explored and the yields were optimized. The activity of the new compounds was evaluated against <i>Nippostrongylus brasiliensis</i> and <i>Caenorhabditis elegans</i> as anthelmintic models and <i>Trypanosoma brucei brucei.</i> The most active compound was <b>3l</b>, showing an EC₅₀ = 2.8 +/- 0.7 M against <i>T. b. brucei</i> and a selectivity index &gt;71.

Roussell DL et al. (1994) Parasitol Today "Germ-line determination in Caenorhabditis and Ascaris: will a helicase begin to unravel the mystery?"

Bennett KL, Roussell DL, Gruidl ME

[Parasitol Today, 1994]

How cell lineages are established during development in higher eukaryotes is being addressed by geneticists and by developmental and molecular biologists. In Drosophila melanogaster, a gene corresponding to a germ-line-specific RNA helicase, vasa, has been shown to be a component o f the posteriorly localized germ granules o f the developing embryo. A putative RNA helicase, glh-I r which appears germ-line specific in its expression, has recently been reported from the free-living nematode Caenorhabditis elegans. Parasitologists studying the nematode Ascaris lumbricoides var. suum have found it to be a useful complement to Caenorhabditis. Deborah Roussell, Michael Gruidl and Karen Bennett predict that Ascaris will be valuable in determining the role played by germ-line helicases in development.

Carmi I et al. (1998) Nature "The nuclear hormone receptor SEX-1 is an X-chromosome signal that determines nematode sex."

Meyer BJ, Kopczynski JB, Carmi I

[Nature, 1998]

Organisms in many phyla determine sexual fate by distinguishing one X chromosome from two. Here we use the model organism Caenorhabditis elegans to dissect such an X-chromosome-counting mechanism in molecular detail. In this nematode, several genes on the X chromosome called X signal elements communicate X-chromosome dose by controlling the activity of the sex-determination gene xol-1. xol-1 specifies male (XO) fate when active and hermaphrodite (XX) fate when inactive. The only X signal element described so far represses xol-1 post-transcriptionally, but xol-1 is repressed in XX animals by transcriptional and post-transcriptional mechanisms. Here we identify a nuclear-hormone-receptor homologue, SEX-1, that regulates the transcription of xol-1. We show that sex-1 is vital to X-chromosome counting: changing sex-1 gene dose in XX or XO embryos causes sexual transformation and death from inadequate dosage compensation (the hermaphrodite-specific process that equalizes X-gene expression between the sexes). The SEX-1 protein acts directly on xol-1, associating with its promoter in vivo and repressing xol-1 transcription in XX embryos. Thus, xol-1 is the direct molecular target of the primary sex-determination signal, and the dose of a nuclear hormone receptor helps to communicate X-chromosome number to determine nematode sex.AD - Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley 94720-3204, USA.FAU - Carmi, IAU - Carmi IFAU - Kopczynski, J BAU - Kopczynski JBFAU - Meyer, B JAU - Meyer BJLA - engSI - GENBANK/AF049869PT - Journal ArticleCY - ENGLANDTA - NatureJID - 0410462RN - 0 (Helminth Proteins)RN - 0 (Receptors, Cytoplasmic and Nuclear)RN - 0 (Repressor Proteins)RN - 0 (sex-1 protein)RN - 161477-65-2 (XOL-1 protein)SB - IM

Wang J et al. (2023) Carbohydr Polym "A ginseng-derived rhamnogalacturonan I (RG-I) pectin promotes longevity via TOR signalling in Caenorhabditis elegans."

Wang Y, Li X, Yu Y, Xue D, Wang J, Zhou Y

[Carbohydr Polym, 2023]

Panax ginseng C. A. Meyer (ginseng), a traditional Chinese herb, is usually used to improve health and increase anti-aging activity for human. Polysaccharides are bioactive components of ginseng. Herein, using Caenorhabditis elegans as a model, we discovered a ginseng-derived rhamnogalacturonan I (RG-I) pectin WGPA-1-RG promoted longevity via TOR signalling pathway with transcription factors FOXO/DAF-16 and Nrf2/SKN-1 accumulated in the nucleus, where they activated target genes. And the WGPA-1-RG-mediated lifespan extension was dependent on endocytosis, rather than a bacterial metabolic process. Glycosidic linkage analyses combined with arabinose- and galactose-releasing enzyme hydrolyses identified the RG-I backbone of WGPA-1-RG was primarily substituted with &#x3b1;-1,5-linked arabinan, &#x3b2;-1,4-linked galactan and arabinogalactan II (AG-II) side chains. Feeding worms with the WGPA-1-RG-derived fractions which lost distinct structural elements by enzymatic digestions, we found the arabinan side chains prominently contributed to the longevity-promoting activity of WGPA-1-RG. These findings provide a novel ginseng-derived nutrient that potentially increases human longevity.

Zhang M et al. (2018) FEMS Yeast Res "Floricolin C elicits intracellular ROS accumulation and disrupts mitochondria to exert fungicidal action."

Zhang M, Shi H, Li Y, Chang W, Li W, Zheng S, Lou H

[FEMS Yeast Res, 2018]

Candida albicans, one most prevalent fungal pathogen, causes severe mucosal and invasive infections in predisposed individuals. The rise of fungal infection and drug-resistance demands the development of novel antifungal agents. In this study, we observed that floricolin C (FC), a p-terphenyl pigment from an endolichenic fungus, killed C. albicans cells at planktonic state or within biofilms through reactive oxygen species (ROS) accumulation. Further test revealed that FC could directly damage the mitochondria to cause ROS accumulation. In addition, FC can quench thiol-based agents through a Michael reaction involving the ,-unsaturated carbonyl group, whose effect may chelate intracellular thiol-based molecules or proteins in C. albicans, resulting in imbalance of redox homeostasis. Increased ROS generation led to mitochondria dysfunction, nuclear dispersion, and consequently cell death. We further demonstrated that FC could prevent biofilm formation of other Candida species and eradicate their pre-formed biofilms. In vivo study demonstrated that FC prolonged the survival of C. albicans-infected Caenorhabditis elegans. Taken together, our study provides a basis for the application of FC to combat Candida infections.

Brackman G et al. (2011) PLoS One "Structure-activity relationship of cinnamaldehyde analogs as inhibitors of AI-2 based quorum sensing and their effect on virulence of Vibrio spp."

Van Calenbergh S, Hillaert U, Cos P, Celen S, Nelis HJ, Brackman G, Coenye T, Maes L

[PLoS One, 2011]

BACKGROUND: Many bacteria, including Vibrio spp., regulate virulence gene expression in a cell-density dependent way through a communication process termed quorum sensing (QS). Hence, interfering with QS could be a valuable novel antipathogenic strategy. Cinnamaldehyde has previously been shown to inhibit QS-regulated virulence by decreasing the DNA-binding ability of the QS response regulator LuxR. However, little is known about the structure-activity relationship of cinnamaldehyde analogs. METHODOLOGY/PRINCIPAL FINDINGS: By evaluating the QS inhibitory activity of a series of cinnamaldehyde analogs, structural elements critical for autoinducer-2 QS inhibition were identified. These include an , unsaturated acyl group capable of reacting as Michael acceptor connected to a hydrophobic moiety and a partially negative charge. The most active cinnamaldehyde analogs were found to affect the starvation response, biofilm formation, pigment production and protease production in Vibrio spp in vitro, while exhibiting low cytotoxicity. In addition, these compounds significantly increased the survival of the nematode Caenorhabditis elegans infected with Vibrio anguillarum, Vibrio harveyi and Vibrio vulnificus. CONCLUSIONS/SIGNIFICANCE: Several new and more active cinnamaldehyde analogs were discovered and they were shown to affect Vibrio spp. virulence factor production in vitro and in vivo. Although ligands for LuxR have not been identified so far, the nature of different cinnamaldehyde analogs and their effect on the DNA binding ability of LuxR suggest that these compounds act as LuxR-ligands.

Levin ED et al. (2009) Neurotoxicology "Genetic aspects of behavioral neurotoxicology."

Kirshner A, Eddins D, French R, Helmcke K, Page GP, Linney E, Lnenicka G, Berger K, Welsh-Bohmer KA, Corl AB, Levin ED, Hirsch HV, Aschner M, Bartlett S, Possidente B, Hayden KM, Chen L, Possidente D, Ruden D, Heberlein U

[Neurotoxicology, 2009]

Considerable progress has been made over the past couple of decades concerning the molecular bases of neurobehavioral function and dysfunction. The field of neurobehavioral genetics is becoming mature. Genetic factors contributing to neurologic diseases such as Alzheimer's disease have been found and evidence for genetic factors contributing to other diseases such as schizophrenia and autism are likely. This genetic approach can also benefit the field of behavioral neurotoxicology. It is clear that there is substantial heterogeneity of response with behavioral impairments resulting from neurotoxicants. Many factors contribute to differential sensitivity, but it is likely that genetic variability plays a prominent role. Important discoveries concerning genetics and behavioral neurotoxicity are being made on a broad front from work with invertebrate and piscine mutant models to classic mouse knockout models and human epidemiologic studies of polymorphisms. Discovering genetic factors of susceptibility to neurobehavioral toxicity not only helps identify those at special risk, it also advances our understanding of the mechanisms by which toxicants impair neurobehavioral function in the larger population. This symposium organized by Edward Levin and Annette Kirshner, brought together researchers from the laboratories of Michael Aschner, Douglas Ruden, Ulrike Heberlein, Edward Levin and Kathleen Welsh-Bohmer conducting studies with Caenorhabditis elegans, Drosophila, fish, rodents and humans studies to determine the role of genetic factors in susceptibility to behavioral impairment from neurotoxic exposure.