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Nematologica,
1978]
Moulting of Caenorhabditis elegans has been observed by Nomarski interference contrast microscopy, and by electron microscopy of animals at selected stages. The wild type, cell division mutants and animals in which cells had been ablated by a laser microbeam were examined. The median lateral hypodermis, or "seam", is required for the formation of alae and for dauer larva maturation. During cuticle deposition, large Golgi bodies are seen in the seam cells. The excretory system is not essential for moulting.
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Int J Nanomedicine,
2012]
PURPOSE: The currently available drug repertoire against lymphatic filariasis, a major health hazard in the developing world, is inadequate and is fraught with serious limitations. Thus, the development of an effective antifilarial strategy has become a global research thrust mandated by the World Health Organization. Nanoparticles of silver endowed with antibacterial potency are known to induce apoptosis in eukaryotic cells. The present study was designed to investigate the possible microfilaricidal efficacy of silver nanoparticles and to establish the validity of apoptotic rationale in antifilarial drug designing. METHODS: This report analyzed the effect of nanoparticles of silver as well as gold (size range: 10-15 nm) on the microfilariae of Brugia malayi obtained from the lavage of peritoneal cavities of infected jirds (Meriones unguiculatus). The study included a microfilarial motility assay, a trypan blue exclusion test, a poly(adenosine diphosphate-ribose) polymerase activity study, ethidium bromide/acridine orange differential staining, and transmission, as well as scanning electron microscopic evaluation of ultrastructural changes in microfilariae. RESULTS: The study demonstrates that nanoparticles of silver, but not of gold, elicited significant loss in microfilarial motility. Differential staining of parasites with ethidium bromide and acridine orange, poly(adenosine diphosphate-ribose) polymerase activity in microfilarial lysate, and electron microscopic findings underscored apoptotic death of parasites attributable to nanosilver. In a trypan blue exclusion test, the 50% lethal dose of nanosilver was measured to be 101.2 M, which was higher than the recorded complete inhibitory concentration value (50.6 M), thus supporting nanosilver as a potential drug candidate against lymphatic filariasis. CONCLUSION: The present report provides the first ever conclusive proof in support of apoptosis as a novel stratagem in antifilarial drug designing and nanoscale silver as a valid lead in research on antifilarial therapeutics. The main embargo about the current drug diethylcarbamazine citrate is its empirical use without rationale. Effective microfilaricidal activity of nanosilver at relatively low concentrations as reported in this study, with evidence of the induction of apoptosis in microfilariae, projects nanosilver as a potential drug adjuvant against lymphatic filariasis. The much higher 50% lethal dose value of nanosilver compared to the complete inhibitory concentration value reported in this study argues in favor of a safe therapeutic window of this agent in its antifilarial efficacy.
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Aging Cell,
2016]
Insulin/IGF-1-like signalling (IIS) and dietary restriction (DR) are the two major modulatory pathways controlling longevity across species. Here, we show that both pathways license a common chromatin modifier, ZFP-1/AF10. The downstream transcription factors of the IIS and select DR pathways, DAF-16/FOXO or PHA-4/FOXA, respectively, both transcriptionally regulate the expression of
zfp-1. ZFP-1, in turn, negatively regulates the expression of DAF-16/FOXO and PHA-4/FOXA target genes, apparently forming feed-forward loops that control the amplitude as well as the duration of gene expression. We show that ZFP-1 mediates this regulation by negatively influencing the recruitment of DAF-16/FOXO and PHA-4/FOXA to their target promoters. Consequently,
zfp-1 is required for the enhanced longevity observed during DR and on knockdown of IIS. Our data reveal how two distinct sensor pathways control an overlapping set of genes, using different downstream transcription factors, integrating potentially diverse and temporally distinct nutritional situations.
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Sci Rep,
2016]
The organization in brain networks shows highly modular features with weak inter-modular interaction. The topology of the networks involves emergence of modules and sub-modules at different levels of constitution governed by fractal laws that are signatures of self-organization in complex networks. The modular organization, in terms of modular mass, inter-modular, and intra-modular interaction, also obeys fractal nature. The parameters which characterize topological properties of brain networks follow one parameter scaling theory in all levels of network structure, which reveals the self-similar rules governing the network structure. Further, the calculated fractal dimensions of brain networks of different species are found to decrease when one goes from lower to higher level species which implicates the more ordered and self-organized topography at higher level species. The sparsely distributed hubs in brain networks may be most influencing nodes but their absence may not cause network breakdown, and centrality parameters characterizing them also follow one parameter scaling law indicating self-similar roles of these hubs at different levels of organization in brain networks. The local-community-paradigm decomposition plot and calculated local-community-paradigm-correlation co-efficient of brain networks also shows the evidence for self-organization in these networks.
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Parasitol Int,
2008]
5'' EST from filarial gene database has been subjected to 3'' rapid amplification of cDNA ends (RACE), semi-nested PCR and PCR to obtain full-length cDNA of Brugia malayi. Full-length hexokinase gene was obtained from cDNA using gene specific primers. The elicited PCR product was cloned, sequenced and expressed as an active enzyme in Escherichia coli. Sequence analysis of B. malayi hexokinase (BmHk) revealed 59% identity with nematode Caenorhabditis elegans but low similarity with all other available hexokinases including human. BmHk, an apparent tetramer with subunit molecular mass of 72 kDa, was able to phosphorylate glucose, fructose, mannose, maltose and galactose. The K(m) values for glucose, fructose and ATP were found to be 0.035+/-0.005, 75+/-0.3 and 1.09+/-0.5 mM respectively. BmHk was strongly inhibited by ADP, glucosamine, N-acetyl glucosamine and mannoheptulose. The recombinant enzyme was found to be activated by glucose-6-phosphate. ADP exhibited noncompetitive inhibition with the substrate glucose (K(i)=0.55 mM) while, mixed type of inhibition was observed with inorganic pyrophosphate (PPi) when ATP was used as substrate (K(i)=9.92 microM). The enzyme activity is highly dependent on maintenance of free sulfhydryl groups. CD analysis indicated that BmHk is composed of 37% alpha-helices and 26% beta-sheets. The observed differences in kinetic properties of BmHk as compared to host enzyme may facilitate designing of specific inhibitors against BmHk.
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MBio,
2019]
Female <i>Aedes aegypti</i> mosquitoes bite human hosts to obtain a blood meal and, in the process, act as vectors for many disease-causing viruses, including the dengue, chikungunya, yellow fever, and Zika viruses. After a complete meal, the female mosquitoes lose attraction to their hosts for several days. New research shows that pharmacological activation of neuropeptide Y-like receptor (NPYLR) signaling elicits host aversion in female mosquitoes. This behavior of mosquitoes shows remarkable similarities to a bacterial-aversion behavior of the nematode <i>Caenorhabditis elegans</i> Feeding on pathogenic bacteria causes bloating of the gut in <i>C. elegans</i> that leads to activation of NPYLR signaling and bacterial aversion. Several studies suggest that this newly discovered mechanism underlying foraging may be conserved across a large number of species. A better understanding of the regulation of NPYLR signaling pathways could provide molecular targets for the control of eating behaviors in different animals, including human-disease vectors.
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Commun Integr Biol,
2014]
Asymmetric cell divisions combine cell division with fate specification and one general model of how this is achieved was proposed already decades ago(1,2): During interphase, the cell polarity axis is specified, followed by orientation of the spindle along the polarity axis and segregation of fate determinants along the polarity axis during mitosis. In most cells, the polarity axis and the spindle will usually align with the long axis that the cell had before division, also called Hertwig's rule(3-6). In the C. elegans embryo, the first polarity axis also forms along the long axis of the embryo by enrichment of myosin in the anterior(7) and formation of mutually exclusive anterior and posterior cortical polarity domains, mediated through directional cortical contractile flow(8-10). The directionality of this flow is determined by an extrinsic cue, the entry of the sperm, which inhibits Rho-dependent myosin activation at the future posterior pole by bringing with it the Rho GTPase activating protein CYK-4(11,12). Moreover, since there is no previous division 'history' before the first cleavage, mechanisms have to ensure that the nucleus-centrosome complex undergoes a 90 degree rotation so that the spindle can subsequently elongate along the long axis(13-15). Additional mechanisms ensure that the site of cleavage is perpendicular to the long axis(16,17). Hence, tight coupling of an extrinsic cue to intrinsic polarity formation and spindle elongation enables alignment of the division orientation with the long axis of the organism and successful segregation of fate determinants.
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Genetics,
2005]
Comparing patterns of molecular evolution between autosomes and sex chromosomes (such as X and W chromosomes) can provide insight into the forces underlying genome evolution. Here we investigate patterns of codon bias evolution on the X chromosome and autosomes in Drosophila and Caenorhabditis. We demonstrate that X-linked genes have significantly higher codon bias compared to autosomal genes in both Drosophila and Caenorhabditis. Furthermore, genes that become X-linked evolve higher codon bias gradually, over tens of millions of years. We provide several lines of evidence that this elevation in codon bias is due exclusively to their chromosomal location and not to any other property of X-linked genes. We present-two possible explanations for these observations. One possibility is that natural selection is more efficient on the X chromosome due to effective haploidy of the X chromosomes in males and persistently low effective numbers of reproducing males compared to that of females. Alternatively, X-linked genes might experience stronger natural selection for higher codon bias as a result of maladaptive reduction of their dosage engendered by the loss of the Y-linked homologs.
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Elife,
2019]
The recognition of pathogens and subsequent activation of defense responses are critical for the survival of organisms. The nematode <i>Caenorhabditis elegans</i> recognizes pathogenic bacteria and elicits defense responses by activating immune pathways and pathogen avoidance. Here we show that chemosensation of phenazines produced by pathogenic <i>Pseudomonas aeruginosa</i>, which leads to rapid activation of DAF-7/TGF- in ASJ neurons, is insufficient for the elicitation of pathogen avoidance behavior. Instead, intestinal infection and bloating of the lumen, which depend on the virulence of <i>P. aeruginosa</i>, regulates both pathogen avoidance and aversive learning by modulating not only the DAF-7/TGF- pathway but also the G-protein coupled receptor NPR-1 pathway, which also controls aerotaxis behavior. Modulation of these neuroendocrine pathways by intestinal infection serves as a systemic feedback that enables animals to avoid virulent bacteria. These results reveal how feedback from the intestine during infection can modulate the behavior, learning, and microbial perception of the host.
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J Theor Biol,
2017]
We study brain network data of three species, namely, C. elegans, cat and macaque monkey within the framework of network theory and Potts Hamiltonian model, and explore rich fractal nature in it, which could be an important signature of self-organization, and a simple rule to be obeyed in complex patterns of brain networks. Further, this fractal behaviors in topological parameters of brain networks at various network levels could be an indicator of systems level organization in complicated brain functionality. Again, Rich-club formation of leading hubs in brain networks becomes unpredictable as one goes down to different levels of organization. The popularity of these leading hubs in main modules or sub-modules also gets changed at different network levels, with varied attitudes at each level. Moreover, distribution of edges, which involves intra- and inter-modular/sub-modular interactions, inherited from one level of organization to another level follows fractal law. In addition to this, the Hamiltonian function at each network level, which may correspond to the energy cost in network organization at that level, shows fractal nature. Significant motifs, which are building blocks of networks and related to basic functionalities, in brain networks is found to be triangular motif, and its probability distribution at various levels as a function of size of modules or sub-modules follows fractal law.