Seydoux G (2013) Nat Cell Biol "'Goldilocks' suppressor screen identifies web of polarity regulators."

Seydoux G

[Nat Cell Biol, 2013]

Genome sequencing and RNAi have been powerful allies in the quest to assign function to every gene. Systematic RNAi screens identify essential genes efficiently, but are less effective with pleiotropic or redundant genes. A common trick used by geneticists to overcome this problem is to screen for genetic interactors - mutations that enhance or suppress the phenotype of a starting mutation. Now, this classic approach has been combined with the versatility of RNAi to generate an expanded gene network for cell polarity.

Rouhanifard SH et al. (2013) Chem Soc Rev "Chemical probing of glycans in cells and organisms."

Rouhanifard SH, Nordstrom LU, Zheng T, Wu P

[Chem Soc Rev, 2013]

Among the four major building blocks of life, glycans play essential roles in numerous physiological and pathological processes. Due to their non-templated biosynthesis, advances towards elucidating the molecular details of glycan functions are relatively slow compared with the pace of protein and nucleic acid research. Over the past 30 years, chemical tools have emerged as powerful allies to genetics and molecular biology in the study of glycans in their native environment. This tutorial review will provide an overview of the recent technological developments in the field, as well as the progress in the application of these techniques to probe glycans in cells and organisms.

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.

Gharib S et al. (2000) Worm Breeder's Gazette "Correlating the C. elegans and C. briggsae genetic maps"

Gharib S, Ally A, Baillie DL, Sternberg PW, Johnsen B, Brown KB

[Worm Breeder's Gazette, 2000]

We are developing a genetic map of Caenorhabditis briggsae in order to facilitate comparative studies with Caenorhabditis elegans. The two nematode species are morphologically similar but are approximately 25 - 40 million years apart. The comparison of the genetic maps of the two species should reveal how selective pressure constrains evolution of the linkage groups. For example, in C. elegans chromosomes there are regions of low and high rates of recombination (R. Johnsen Ph.D Thesis 1990, Simon Fraser University, Burnaby, Canada; S. Jones Ph.D. Thesis 1999 Cambridge Eng.). It has been postulated that highly conserved genes are more likely to be in regions of low recombination whereas rapidly evolving genes more likely reside in regions of high recombination. If this were true we would expect a similar gene distribution in C. briggsae. Our studies should also prove valuable for researchers who are comparing specific genes in in two nemotode species. As part of our investigations we want to identify which C. elegans genes correspond to each of the C. briggsae genes. So far we have identified 15 cby, 7 mip, 1 rot and 1 sml genes (the C. briggsae versions of dpy, unc, rol and sma respectively). Five of the cby genes, three of the mips and the rot are on the X-chromosome while the other 10 cbys, 4 mips and the sml gene map to autosomes. We have concluded that mip-1 is the C. briggsae version of unc-22 and cby-4 is dpy-1. We have also shown that mip-1, mip-3, mip-6, cby-7 and cby-8 are linked. In order to correlate the two genetic maps in an efficacious manner we request any help that the members of the worm community can afford us. Either by way of rescuing DNA or by helping with the identification of phenotypes that requires special knowledge or conditions to identify.

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).

Danielle Thierry-Mieg et al. (2003) Worm Breeder's Gazette "www.wormgenes.org , a new gene centered database"

Vahan Simonyan, Michel Potdevin, Mark Sienkiewicz, Yuji KOHARA, Jean Thierry-Mieg, Danielle Thierry-Mieg, Tadasu SHIN-I

[Worm Breeder's Gazette, 2003]

Wormgenes is a new resource for C.elegans offering a detailed summary about each gene and a powerful query system.

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.