8 Papers found (0.076 seconds)

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

[

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.

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 3 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 Nippostrongylus brasiliensis and Caenorhabditis elegans as anthelmintic models and Trypanosoma brucei brucei. The most active compound was 3l, showing an EC50 = 2.8 +/- 0.7 M against T. b. brucei and a selectivity index >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.

Garcia, Jessica et al. (2019) MicroPubl Biol

Collins, Kevin M, Garcia, Jessica

[

MicroPubl Biol,

2019]

In our accompanying paper, we show that Ca2+ activity in the HSN egg-laying command motor neurons is associated with a delay in the frequency defecation motor program (DMP) in both late L4 juveniles and egg-laying adults (Ravi and Collins 2019). While optogenetic activation of the HSNs did not directly reduce the frequency of defecation, egg-laying adults did show a significant reduction in defecation frequency compared to younger animals, consistent with previous results (Bolanowski et al. 1981). As shown in Figure 1A, the egg-laying and defecation circuits are interconnected. The HSN command neurons and VC motor neurons that synapse onto the egg-laying vulval muscles also make and receive synapses from the excitatory GABAergic AVL and DVB motoneurons that innervate the enteric muscles that regulate defecation. We test the functional relationship between egg-laying and defecation behaviors, we measured DMP frequency in animals with altered HSN neurotransmitter signaling. We hypothesized that mutations that reduce HSN neurotransmitter signaling would increase DMP frequency because periods of elevated HSN Ca2+ activity were associated with decreased DMP frequency (Ravi and Collins 2019). Surprisingly, animals bearing two independent egl-1(dm) mutants that cause the HSNs to undergo premature cell death showed a decrease in DMP frequency (Figure 1B). While this delay was significant, it was mild compared to egl-8(sa47) null mutants that eliminate PLCbeta and IP3 signaling required for proper timing of the defecation motor program (Dal Santo et al. 1999; Lackner et al. 1999). These results show the HSNs are required for a normal DMP rhythm in adult animals. Interestingly, this delay in defecation frequency in HSN-deficient animals was not observed in egl-47(dm) mutant animals with strong defects in HSN neurotransmitter release and similar defects in egg-laying behavior as egl-1(dm) mutants (Moresco and Koelle 2004). We do not believe this egl-1(dm)-specific defect in defecation is caused by differences in bloating in response to egg accumulation in the uterus, as both mutants retain an indistinguishable number of embryos (Moresco and Koelle 2004) and show similar delays in the onset of egg laying (Ravi et al. 2018). Further, egl-47(dm) animals still have HSNs (Moresco and Koelle 2004) and show occasional HSN Ca2+ transients, so the reduced DMP frequency in egl-1(dm) animals suggests the HSNs are developmentally required for a normal DMP rhythm and/or that even low levels of serotonin or NLP-3 neuropeptide release from HSN are sufficient for a normal defecation rhythm (Brewer et al. 2019). We propose that animals coordinate egg-laying and defecation behaviors to direct changes in hydrostatic pressure used to drive expulsion of uterine or intestinal contents, but that HSN signaling is still required for full coordination of these behaviors. Consistent with this hypothesis, a common set of signaling molecules regulate activity of circuits that modulate egg-laying and defecation behaviors (Reiner et al. 1995).

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."

[

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.

Bhoj PS et al. (2019) Parasitol Res "In vitro apoptotic effect on human lymphatic filarial parasite by piperidine derivatives and thymidine reversal study."

Goswami K, Togre NS, Rao S, Patil MB, Sharma R, Agrawal NR, Chandak HS, Bahekar SP, Bhoj PS

[

Parasitol Res,

2019]

A novel library of synthetic piperidine derivatives was used to screen against human lymphatic filarial parasite Brugia malayi. Piperidine has earlier been reported to have effect against parasites including rodent filarial nematodes. Compounds with hydroxyl substitutions (4Q and 4H) showed marked antifilarial effect. Molecular docking of 4H derivative showed more favorable thermodynamic parameters against thymidylate synthase of B. malayi than human counterpart. A wide difference between IC50 and LD50 ensured the therapeutic safety of the candidates against the filarial parasites. Addition of thymidine to the treatment regimen led to a significant reversal of antifilarial effect of 4H that confirmed inhibition of thymidylate synthase as pharmacological rationale. Apoptosis induced in the parasite as a consequence of probable inhibition of thymidylate synthase was studied by acridine orange/ethidium bromide fluorescent staining and poly (ADP-ribose) polymerase activity inhibition. Involvement of mitochondria was confirmed by decreased 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) conversion and increased cytosolic cytochrome c level in 4H treated microfilariae, compared with the untreated microfilariae. Moreover, Michael adduct of chalcone targeting dihydrofolate reductase and piperidine targeting thymidylate synthase demonstrated synergistic effect on the parasite, indicating the importance of inhibition of DNA synthesis by combined effect. In conclusion, piperidine derivatives with hydroxyl substitution have a great therapeutic potential with an apoptotic rationale involving mitochondrial pathway, due to possible inhibition of parasitic thymidylate synthase.