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Igbe M, Anyaike C, Griswold E, Noland GS, Mafuyai H, Kahansim B, Danboyi J, Miri E, Adelamo S, Umaru J, Unnasch TR, Kadimbo J, Rakers L, Richards FO, Nwoke BEB, Saka Y, Eigege A
[
Am J Trop Med Hyg,
2020]
Plateau and Nasarawa states in central Nigeria were endemic for onchocerciasis. The rural populations of these two states received annual ivermectin mass drug administration (MDA) for a period of 8-26 years (1992-2017). Ivermectin combined with albendazole was given for 8-13 of these years for lymphatic filariasis (LF); the LF MDA program successfully concluded in 2012, but ivermectin MDA continued in areas known to have a baseline meso-/hyperendemic onchocerciasis. In 2017, serological and entomological assessments were undertaken to determine if MDA for onchocerciasis could be stopped in accordance with the current WHO guidelines. Surveys were conducted in 39 sites that included testing 5- to < 10-year-old resident children by using ELISA for OV16 IgG4 antibodies, and <i>Onchocerca volvulus</i> O150 pooled polymerase chain reaction (PCR) testing of <i>Simulium damnosum</i> s.l. vector heads. Only two of 6,262 children were OV16 positive, and none of 19,056 vector heads were positive for parasite DNA. Therefore, both states were able to meet WHO stop-MDA thresholds of an infection rate in children of < 0.1% and a rate of infective blackflies of <1/2,000, with 95% statistical confidence. Transmission of onchocerciasis was declared interrupted in Plateau and Nasarawa states by the Federal Ministry of Health, and 2.2 million ivermectin treatments/year were stopped in 2018. Post-treatment Surveillance was launched focusing on entomological monitoring on borders with neighboring onchocerciasis-endemic states. An apparent positive impact of the LF MDA program on eliminating hypo-endemic onchocerciasis was observed. This is the first stop-MDA decision for onchocerciasis in Nigeria and the largest single stop-MDA decision for onchocerciasis yet reported. This achievement, along with the process used in adapting and implementing the 2016 WHO stop-MDA guidelines, will be important as a potential model for decision makers and national onchocerciasis elimination committees in other African countries that are charged with advancing their programs.
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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).
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[
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.
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[
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.
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[
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.
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[
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.
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[
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.
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[
Curr Biol,
2020]
How protein homeostasis is maintained in the extracellular space remains poorly studied. A recent study employed a Caenorhabditis elegans model to carry out a systematic analysis of the extracellular proteostasis network and uncovered its role in combating a pathogenic attack.
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[
Lab Chip,
2008]
A droplet-based microfluidic system integrating a droplet generator and a droplet trap array is described for encapsulating individual Caenorhabditis elegans into a parallel series of droplets, enabling characterization of the worm behavior in response to neurotoxin at single-animal resolution.
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[
Curr Biol,
2021]
In a C.elegans model of host-microbiome interactions, interrogation of a genetically diverse panel of host strains with a defined, complex bacterial community reveals an important role for a conserved insulin-like signaling pathway in shaping the phylogenetic composition of the gut microbiome.