[
Curr Drug Targets,
2019]
BACKGROUND AND OBJECTIVES: Lymphatic filariasis is a neglected tropical disease caused by infection with filarial worms that are transmitted through mosquito bites. Globally, 120 million people are infected, with nearly 40 million people disfigured and disabled by complications such as severe swelling of the legs (elephantiasis) or scrotum (hydrocele). Current treatments (ivermectin, diethylcarbamazine) have limited effects on adult parasites and produce side effects; therefore, there is an urgent to search for new antifilarial agents. Numerous studies on the antifilarial activity of pure molecules have been reported accross the recent literature. The present study describes the current standings of potent antifilarial compounds against lymphatic filariasis. METHODS: A literature search was conducted for naturally occurring and synthetic antifilarial compounds by referencing textbooks and scientific databases (SciFinder, PubMed, Science Direct, Wiley, ACS, SciELO, Google Scholar, and Springer, among others) from their inception until September 2019. RESULTS: Numerous compounds have been reported to exhibit antifilarial acitivity in adult and microfilariae forms of the parasites responsible for lymphatic filariasis. In silico studies of active antifilarial compounds (ligands) showed molecular interactions over the protein targets (trehalose-6-phosphate phosphatase, thymidylate synthase, among others) of lymphatic filariasis, and supported the in vitro results. CONCLUSION: With reference to in vitro antifilarial studies, there is evidence that natural and synthetic products can serve as basic scaffolds for the development of antifilarial agents. The optimization of the most potent antifilarial compounds can be further performed, follow by their in vivo studies.
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Soft Matter,
2019]
Microorganisms often move through viscoelastic environments, as biological fluids frequently have a rich microstructure owing to the presence of large polymeric molecules. Research on the effect of fluid elasticity on the swimming kinematics of these organisms has usually been focused on those that move via cilia or flagellum. Experimentally, Shen (X. N. Shen et al., Phys. Rev. Lett., 2011, 106, 208101) reported that the nematode C. elegans, a model organism used to study undulatory motion, swims more slowly as the Deborah number describing the fluid's elasticity is increased. This phenomenon has not been thoroughly studied via a fully resolved three-dimensional simulation; moreover, the effect of fluid elasticity on the swimming speed of organisms moving via euglenoid movement, such as E. gracilis, is completely unknown. In this study, we discuss the simulation of the arbitrary motion of an undulating or pulsating swimmer that occupies finite volume in three dimensions, with the ability to specify any differential viscoelastic rheological model for the surrounding fluid. To accomplish this task, we use a modified version of the Immersed Finite Element Method presented in a previous paper by Guido and Saadat in 2018 (A. Saadat et al., Phys. Rev. E, 2018, 98, 063316). In particular, this version allows for the simulation of deformable swimmers such that they evolve through an arbitrary set of specified shapes via a conformation-driven force. From our analysis, we observe several key trends not found in previous two-dimensional simulations or theoretical analyses for C. elegans, as well as novel results for the amoeboid motion. In particular, we find that regions of high polymer stress concentrated at the head and tail of the swimming C. elegans are created by strong extensional flow fields and are associated with a decrease in swimming speed for a given swimming stroke. In contrast, in two dimensions these regions of stress are commonly found distributed along the entire body, likely owing to the lack of a third dimension for polymer relaxation. A comparison of swim speeds shows that the calculations in two-dimensional simulations result in an over-prediction of the speed reduction. We believe that our simulation tool accurately captures the swimming motion of the two aforementioned model swimmers and furthermore, allows for the simulation of multiple deformable swimmers, as well as more complex swimming geometries. This methodology opens many new possibilities for future studies of swimmers in viscoelastic fluids.
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Methods Mol Biol,
2015]
Optogenetics was introduced as a new technology in the neurosciences about a decade ago (Zemelman et al., Neuron 33:15-22, 2002; Boyden et al., Nat Neurosci 8:1263-1268, 2005; Nagel et al., Curr Biol 15:2279-2284, 2005; Zemelman et al., Proc Natl Acad Sci USA 100:1352-1357, 2003). It combines optics, genetics, and bioengineering to render neurons sensitive to light, in order to achieve a precise, exogenous, and noninvasive control of membrane potential, intracellular signaling, network activity, or behavior (Rein and Deussing, Mol Genet Genomics 287:95-109, 2012; Yizhar et al., Neuron 71:9-34, 2011). As C. elegans is transparent, genetically amenable, has a small nervous system mapped with synapse resolution, and exhibits a rich behavioral repertoire, it is especially open to optogenetic methods (White et al., Philos Trans R Soc Lond B Biol Sci 314:1-340, 1986; De Bono et al., Optogenetic actuation, inhibition, modulation and readout for neuronal networks generating behavior in the nematode Caenorhabditis elegans, In: Hegemann P, Sigrist SJ (eds) Optogenetics, De Gruyter, Berlin, 2013; Husson et al., Biol Cell 105:235-250, 2013; Xu and Kim, Nat Rev Genet 12:793-801, 2011). Optogenetics, by now an "exploding" field, comprises a repertoire of different tools ranging from transgenically expressed photo-sensor proteins (Boyden et al., Nat Neurosci 8:1263-1268, 2005; Nagel et al., Curr Biol 15:2279-2284, 2005) or cascades (Zemelman et al., Neuron 33:15-22, 2002) to chemical biology approaches, using photochromic ligands of endogenous channels (Szobota et al., Neuron 54:535-545, 2007). Here, we will focus only on optogenetics utilizing microbial rhodopsins, as these are most easily and most widely applied in C. elegans. For other optogenetic tools, for example the photoactivated adenylyl cyclases (PACs, that drive neuronal activity by increasing synaptic vesicle priming, thus exaggerating rather than overriding the intrinsic activity of a neuron, as occurs with rhodopsins), we refer to other literature (Weissenberger et al., J Neurochem 116:616-625, 2011; Steuer Costa et al., Photoactivated adenylyl cyclases as optogenetic modulators of neuronal activity, In: Cambridge S (ed) Photswitching proteins, Springer, New York, 2014). In this chapter, we will give an overview of rhodopsin-based optogenetic tools, their properties and function, as well as their combination with genetically encoded indicators of neuronal activity. As there is not "the" single optogenetic experiment we could describe here, we will focus more on general concepts and "dos and don'ts" when designing an optogenetic experiment. We will also give some guidelines on which hardware to use, and then describe a typical example of an optogenetic experiment to analyze the function of the neuromuscular junction, and another application, which is Ca(2+) imaging in body wall muscle, with upstream neuronal excitation using optogenetic stimulation. To obtain a more general overview of optogenetics and optogenetic tools, we refer the reader to an extensive collection of review articles, and in particular to volume 1148 of this book series, "Photoswitching Proteins."