Drechsler C (1944) Mycologia "Three hyphomycetes that capture nematodes in adhesive networks."

Drechsler C

[Mycologia, 1944]

In several previous papers descriptive treatment was given to 22 interrelated hyphomycetes found subsisting by the capture and destruction of eelworms infesting transparent agar plate cultures started from diseased rootlets or from other decaying vegetable materials. Similar treatment is devoted herein to 3 additional fungi of like biological habit and manifestly belonging to the same predaceous series. Capture of eelworms is accomplished, in all 3 fungi, by means of adhesive bail-like hyphal loops, which, as in allied forms, may occur singly, or may be compounded into networks of variable intricacy. Two of the fungi are referred to Arthrobotrys, one being presented as a new variety, while the other is identified with a long-established though somewhat unfamiliar species of that genus. The third fungus is described as a new species of Dactylaria. In relation to a subsidiary spore form apparently connected with the new species, preliminary discussion is devoted to a delicate Trichothecium found producing stalked adhesive knob-cells.

Maqbool M et al. (2020) Bioorg Med Chem "Deciphering the robustness of pyrazolo-pyridine carboxylate core structure-based compounds for inhibiting -synuclein in transgenic C. elegans model of Synucleinopathy."

Rajvansh R, Maqbool M, Srividya K, Hoda N

[Bioorg Med Chem, 2020]

Parkinson's disease (PD), a calamitous neurodegenerative disorder with no cure till date, is closely allied with the misfolding and aggregation of -Synuclein ( -Syn). Inhibition of -Syn aggregation is one of the optimistic approaches for the treatment for PD. Here, we carried out hypothesis-driven studies towards synthesising a series of pyrazolo-pyridine carboxylate containing compounds (7a-7m) targeted at reducing deleterious -Syn aggregation. The target compounds were synthesized through multi-step organic synthesis reactions. From docking studies, compounds 7b, 7g and 7i displayed better interaction with the key residues of -Syn with values: -6.8, -8.9 and -7.2 Kcal/mol, respectively. In vivo transgenic C. elegans model of Synucleinopathy was used to evaluate the ability of the designed and synthesized compounds to inhibit -Syn aggregation. These lead compounds 7b, 7g and 7i displayed 1.7, 2.4 and 1.5-fold inhibition of -Syn with respect to the control. Further, the strategy of employing pyrazolo-pyridine-based compounds worked with success and these scaffolds could be further modified and validated for betterment of endpoints associated with PD.

Budel RG et al. (2019) Colloids Surf B Biointerfaces "Toxicological evaluation of naringin-loaded nanocapsules in vitro and in vivo."

Boeck CR, da Silva RS, Lopes LQS, Budel RG, Nazario LR, Majolo JH, Santos RCV, da Silva DA, Gomes P, Moreira MP, Dalcin AJF, Antunes Soares FA, da Silva AF

[Colloids Surf B Biointerfaces, 2019]

Naringin is a flavonoid widely known for its pharmacological properties, such as: anti-inflammatory and antioxidant ones, being an ally to avoid oxidative damage. Although naringin is an active easily found in citrus fruits, it has low bioavailability, biodistribution and also undergoes biotransformation in naringenin, limiting the described effects. The use of nanocapsules as drug carriers may increase solubility, improve biodistribution, impede the biotransformation thereof, and thus could improve the performance of naringin for use in treating neurological diseases. Therefore, the objective of this work is to produce a nanocapsule containing naringin, validate an analytical method by RP-HPLC to determination of the drug in nanoparticle and evaluate the toxicity. To that end, the blank nanocapsules (NB, without the drug) or naringin-loaded nanocapsules (NN) at the concentration of 2mg/mL were prepared by interfacial deposition of the preformed polymer and the quantification of naringin by HPLC. Toxicity of the formulations was evaluated in vitro in rat hippocampal slices and in vivo models with C. elegans and Danio rerio (zebrafish). The analytical parameters evaluated (linearity, limit of detection and quantification, specificity, precision, accuracy and robustness) indicated adequate method to assay of naringin in nanocapsules by HPLC. There was no indication of toxicity by the nanocapsules in the evaluated biological assays.

Boatin B (2008) Ann Trop Med Parasitol "The Onchocerciasis Control Programme in West Africa (OCP)."

Boatin B

[Ann Trop Med Parasitol, 2008]

The Onchocerciasis Control Programme in West Africa (OCP) started operations in 1975. Its main objectives were to eliminate human onchocerciasis, as a disease of public-health importance and an obstacle to socio-economic development, from the Programme area. By the end of 2002, the OCP covered 11 West African countries, and had introduced large-scale Mectizan (ivermectin) distribution to about 10 million people, through the communitydirected treatment approach, with treatment coverages ranging from 51%-81%. Research on large-scale Mectizan use illustrated the importance of evidence-based results, the power of multicountry studies, the need for social science in community-driven endeavours and operations research, and the value of empowering communities as allies in disease control. The generous donation of Mectizan by Merck & Co., Inc., has increased general interest in health-related public-private partnerships and generated the momentum for other donations to tackle other diseases. The vector control on which the OCP was initially based successfully interrupted the transmission of the parasite causing human onchocerciasis, Onchocerca volvulus, in many areas. The introduction of Mectizan led to the decline in anterior-segment lesions in the eye and the arrest of posterior-segment lesions. The drug continues to be highly effective in morbidity control, although recently there have been reports of sub-optimal responses in some adult O. volvulus, albeit in a few, very small and isolated foci.

Quartey MO et al. (2021) Sci Rep "The A(1-38) peptide is a negative regulator of the A(1-42) peptide implicated in Alzheimer disease progression."

Pennington PR, Heistad RM, Nyarko JNK, Barnes JR, Bolanos MAC, Parsons MP, Knudsen KJ, De Carvalho CE, Leary SC, Mousseau DD, Buttigieg J, Maley JM, Quartey MO

[Sci Rep, 2021]

The pool of -Amyloid (A) length variants detected in preclinical and clinical Alzheimer disease (AD) samples suggests a diversity of roles for A peptides. We examined how a naturally occurring variant, e.g. A(1-38), interacts with the AD-related variant, A(1-42), and the predominant physiological variant, A(1-40). Atomic force microscopy, Thioflavin T fluorescence, circular dichroism, dynamic light scattering, and surface plasmon resonance reveal that A(1-38) interacts differently with A(1-40) and A(1-42) and, in general, A(1-38) interferes with the conversion of A(1-42) to a -sheet-rich aggregate. Functionally, A(1-38) reverses the negative impact of A(1-42) on long-term potentiation in acute hippocampal slices and on membrane conductance in primary neurons, and mitigates an A(1-42) phenotype in Caenorhabditis elegans. A(1-38) also reverses any loss of MTT conversion induced by A(1-40) and A(1-42) in HT-22 hippocampal neurons and APOE 4-positive human fibroblasts, although the combination of A(1-38) and A(1-42) inhibits MTT conversion in APOE 4-negative fibroblasts. A greater ratio of soluble A(1-42)/A(1-38) [and A(1-42)/A(1-40)] in autopsied brain extracts correlates with an earlier age-at-death in males (but not females) with a diagnosis of AD. These results suggest that A(1-38) is capable of physically counteracting, potentially in a sex-dependent manner, the neuropathological effects of the AD-relevant A(1-42).

Tangrodchanapong T et al. (2020) Front Pharmacol "Frondoside A Attenuates Amyloid- Proteotoxicity in Transgenic Caenorhabditis elegans by Suppressing Its Formation."

Tangrodchanapong T, Sobhon P, Meemon K

[Front Pharmacol, 2020]

Oligomeric assembly of Amyloid- (A) is the main toxic species that contribute to early cognitive impairment in Alzheimer's patients. Therefore, drugs that reduce the formation of A oligomers could halt the disease progression. In this study, by using transgenic <i>Caenorhabditis elegans</i> model of Alzheimer's disease, we investigated the effects of frondoside A, a well-known sea cucumber <i>Cucumaria frondosa</i> saponin with anti-cancer activity, on A aggregation and proteotoxicity. The results showed that frondoside A at a low concentration of 1 M significantly delayed the worm paralysis caused by A aggregation as compared with control group. In addition, the number of A plaque deposits in transgenic worm tissues was significantly decreased. Frondoside A was more effective in these activities than ginsenoside-Rg3, a comparable ginseng saponin. Immunoblot analysis revealed that the level of small oligomers as well as various high molecular weights of A species in the transgenic <i>C. elegans</i> were significantly reduced upon treatment with frondoside A, whereas the level of A monomers was not altered. This suggested that frondoside A may primarily reduce the level of small oligomeric forms, the most toxic species of A. Frondoside A also protected the worms from oxidative stress and rescued chemotaxis dysfunction in a transgenic strain whose neurons express A. Taken together, these data suggested that low dose of frondoside A could protect against A-induced toxicity by primarily suppressing the formation of A oligomers. Thus, the molecular mechanism of how frondoside A exerts its anti-A aggregation should be studied and elucidated in the future.

Viney ME et al. (2004) Naturwissenschaften "Is dauer pheromone of Caenorhabditis elegans really a pheromone?"

Viney ME, Franks NR

[Naturwissenschaften, 2004]

Animals respond to signals and cues in their environment. The difference between a signal (e.g. a pheromone) and a cue (e.g. a waste product) is that the information content of a signal is subject to natural selection, whereas that of a cue is not. The model free-living nematode Caenorhabditis elegans forms an alternative developmental morph (the dauer larva) in response to a so-called 'dauer pheromone', produced by all worms. We suggest that the production of 'dauer pheromone' has no fitness advantage for an individual worm and therefore we propose that 'dauer pheromone' is not a signal, but a cue. Thus, it should not be called a pheromone.

Schaeffer JM et al. (1990) J Antibiot (Tokyo) "Cochlioquinone A, a nematocidal agent which competes for specific [3H]ivermectin binding sites."

Williamson JM, Schaeffer JM, Bergstrom AR, Liesch JM, Goetz MA, Frazier EG

[J Antibiot (Tokyo), 1990]

Cochlioquinone A, isolated from the fungus Helminthosporium sativum, was found to have nematocidal activity. Cochlioquinone A is a competitive inhibitor of specific [3H]ivermectin binding suggesting that cochlioquinone A and ivermectin interact with the same membrane receptor.

Desta IT et al. (2016) J Lab Autom "Detecting and Trapping of a Single C. elegans Worm in a Microfluidic Chip for Automated Microplate Dispensing."

Giakoumidis N, Mustafa N, AlGharibeh N, Orozaliev A, Al-Sharif A, Song YA, Desta IT, Gunsalus KC

[J Lab Autom, 2016]

Microfluidic devices offer new technical possibilities for a precise manipulation of Caenorhabditis elegans due to the comparable length scale. C. elegans is a small, free-living nematode worm that is a popular model system for genetic, genomic, and high-throughput experimental studies of animal development and neurobiology. In this paper, we demonstrate a microfluidic system in polydimethylsiloxane (PDMS) for dispensing of a single C. elegans worm into a 96-well plate. It consists of two PDMS layers, a flow and a control layer. Using five microfluidic pneumatic valves in the control layer, a single worm is trapped upon optical detection with a pair of optical fibers integrated perpendicular to the constriction channel and then dispensed into a microplate well with a dispensing tip attached to a robotic handling system. Due to its simple design and facile fabrication, we expect that our microfluidic chip can be expanded to a multiplexed dispensation system of C. elegans worms for high-throughput drug screening.

Ailion M et al. (2017) Curr Biol "Genetics: Master Regulator or Master of Disguise?"

Malik HS, Ailion M

[Curr Biol, 2017]

The pha-1 gene of Caenorhabditis elegans was originally heralded as a master regulator of organ differentiation. A new study suggests instead that pha-1 actually serves no role in development and instead is a component of a selfish genetic element.