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[
Am J Trop Med Hyg,
2003]
We have followed a population in an area endemic for Brugia malayi for three years after intensive treatment with diethylcarbamazine (DEC). Microfilariae were cleared from the circulation within four months in all eligible study participants (n = 60). There appeared to be a strong correlation between the maximum reduction in specific IgG4 and the number of days drug was taken under supervision (p = 0.41, P < 0.001), indicating that high total dosage of DEC is necessary for optimal reduction of active infection. In individuals with good compliance (at least 180 mg/kg of body weight, n = 34), we observed variable IgG4 patterns. All pre-treatment IgG4+ children (9-14 years old) and 40% of the IgG4+ adult population (> or = 15 years old) showed a gradual decrease in anti-filarial IgG4; 53% of these showed complete clearance of worm burden by the end of the study. In contrast, another group of male IgG4+ adults showed IgG4 patterns that started to increase between nine months and two years after treatment, indicating either a partial efficacy of DEC that allowed recovery of resident adult worms or reinfection.
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[
Mol Cell,
2009]
Three recent papers (Gu et al., 2009; Claycomb et al., 2009; van Wolfswinkel et al., 2009) provide evidence that links a new class of small RNAs and Argonaute-associated complexes to centromere function and genome surveillance.
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[
Int Microbiol,
2019]
Considering the emergence of multidrug resistance (MDR) in prevalent human pathogen, Mycobacterium tuberculosis (MTB), there is parallel spurt in development of novel strategies aimed to disrupt MDR. The cell envelope of MTB comprises a wealth of lipid moieties contributing towards long-term survival of pathogen that could be exploited as efficient antitubercular target owing to advancements made in mass spectrometry-based lipidomics technology. This study aimed to utilize the lipidomics approach to unveil several lipid associated changes in response to natural antimycobacterial compound vanillin (Van) in Mycobacterium smegmatis, a surrogate for MTB. Lipidomic analyses revealed that that Van alters the composition of fatty acid (FA), glycerolipid (GL), glycerophospholipid (GP), and saccharolipids (SL). Furthermore, Van leads to potentiation of ampicillin and displayed additive effect. The differential expressions of various lipid biosynthetic pathway genes by RT-PCR corroborated with the lipidomics data. Lastly, we demonstrated enhanced survival of Mycobacterium-infected Caenorhabditis elegans model in presence of Van. Thus, lipidomics approach provided detailed insight into mechanisms of membrane disruption by Van in Mycobacterium smegmatis. Our work offers the basis of further understanding the regulation of lipid homeostasis in MTB so that better therapeutic targets could be identified to combat MDR.
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[
Curr Med Mycol,
2020]
Background and Purpose: . Materials and Methods: nematode model. Results: infection. The results also confirmed negligible hemolytic activity on erythrocytes. Conclusion: As the findings of the present study indicated, Van is a persuasive natural compound that warrants further attention to exploit its anticandidal potential.
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[
Development,
2023]
Sequential rosettes are a type of collective cell behavior recently discovered in the C. elegans embryo that mediates directional cell migration through sequential formation and resolution of multicellular rosettes involving the migrating cell and its neighboring cells along the way. Here we show that a Planar Cell Polarity (PCP)-based polarity scheme regulates sequential rosettes, which is distinct from the known mode of PCP regulation in multicellular rosettes during the process of convergent extension. Specifically, non-muscle myosin (NMY) localization and edge contraction are perpendicular to that of Van Gogh as opposed to colocalizing with Van Gogh. Further analyses suggest a two-component polarity scheme: one being the canonical PCP pathway with MIG-1/Frizzled and VANG-1/Van Gogh localized to the vertical edges, the other being MIG-1/Frizzled and NMY-2 localized to the midline/contracting edges. The NMY-2 localization and contraction of the midline edges are also required LAT-1/Latrophilin, an adhesion G protein-coupled receptor which has not been shown to regulate multicellular rosettes. Our results establish a distinct mode of PCP-mediated cell intercalation and shed light on the versatile nature of PCP pathway.
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[
Methods Mol Biol,
2012]
This chapter was written as a guide to using the long-amplicon quantitative PCR (QPCR) assay for the measurement of DNA damage in mammalian as well as nonmammalian species such as Caenorhabditis elegans (nematodes), Drosophila melanogaster (fruit flies), and two species of fish (Fundulus heteroclitus and Danio rerio). Since its development in the early 1990s (Kalinowski et al., Nucleic Acids Res 20:3485-3494, 1992; Salazar and Van Houten, Mutat Res 385:139-149, 1997; Yakes and Van Houten, Proc Natl Acad Sci USA 94:514-519, 1997), the QPCR assay has been widely used to measure DNA damage and repair kinetics in nuclear and mitochondrial genomes after genotoxin exposure (Yakes and Van Houten, Proc Natl Acad Sci USA 94:514-519, 1997; Santos et al., J Biol Chem 278:1728-1734, 2003; Mandavilli et al., Mol Brain Res 133:215-223, 2005). One of the main strengths of the assay is that the labor-intensive and artifact-generating step of mitochondrial isolation is not needed for the accurate measurement of mitochondrial DNA copy number and damage. Below we present the advantages and limitations of using QPCR to assay DNA damage in animal cells and provide a detailed protocol of the QPCR assay that integrates its usage in newly developed animal systems.
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[
Science,
2002]
The chromodomain of the HP1 family of proteins recognizes histone tails with specifically methylated lysines. Here, we present structural, energetic, and mutational analyses of the complex between the Drosophila HP1 chromodomain and the histone H3 tail with a methyllysine at residue 9, a modification associated with epigenetic silencing. The histone tail inserts as a beta strand, completing the beta-sandwich architecture of the chromodomain. The methylammonium group is caged by three aromatic side chains, whereas adjacent residues form discerning contacts with one face of the chromodomain. Comparison of dimethyl- and trimethyllysine-containing complexes suggests a role for cation-pi and van der Waals interactions, with trimethylation slightly improving the binding affinity.
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[
Nature,
1992]
Sex and death are two fundamental but poorly understood aspects of life. They are often thought to be linked because reproduction requires the diversion of limited resources from somatic growth and maintenance. This diversion of resources in mated animals, often called a cost of reproduction, is usually expressed as a reduction of lifespan in mated animals, although some debate exists on the best way to measure this cost. I report here that in the soil nematode, Caenorhabiditis elegans, sex significantly decreases male lifespan without reducing hermaphrodite lifespan. The reduction of mated male lifespan seems to be caused by additional sperm production and not by the physical activity of mating. This conclusion is supported by observations that a mutation reducing sperm production increased mean lifespan by about 65% in both mated males and hermaphrodites. This suggests that spermatogenesis, rather than oogenesis or the physical act of mating, is a major factor reducing lifespan in C. elegans. This contradicts the traditional biological assumption that large oocytes are much costlier to produce than small sperm.AD - Department of Ecology and Evolutionary Biology, University of Arizona, Tucson 85721.FAU - Van Voorhies, W AAU - Van Voorhies WALA - engPT - Journal ArticleCY - ENGLANDTA - NatureJID - 0410462SB - IM
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[
Biochemistry,
1987]
The major intestinal esterase from the nematode Caenorhabditis elegans has been purified to essential homogeneity. Starting from whole worms, the overall purification is 9000-fold with a 10% recovery of activity. The esterase is a single polypeptide chain of Mr 60,000 and is stoichiometrically inhibited by organophosphates. Substrate preferences and inhibition patterns classify the enzyme as a carboxylesterase (EC 3.1.1.1), but the physiological function is unknown. The sequence of 13 amino acid residues at the esterase N- terminus has been determined. This partial sequence shows a surprisingly high degree of similarity to the N-terminal sequence of two carboxylesterases recently isolated from Drosophila mojavensis [Pen, J., van Beeumen, J., & Beintema, J. J. (1986) Biochem. J. 238, 691-699].
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[
J Am Chem Soc,
2001]
The Src-homology-3 (SH3) domain of the Caenorhabditis elegans protein Sem-5 binds proline-rich sequences. It is reported that the SH3 domains broadly accept amide: N-substituted residues instead of only recognizing prolines on the basis of side chain shape or rigidity. We have studied the interactions between Sem-5 and its ligands using molecular dynamics (MD), free energy calculations, and sequence analysis. Relative binding free energies, estimated by a method called MM/PBSA, between different substitutions at sites - 1, 0, and +2 of the peptide are consistent with the experimental data. A new method to calculate atomic partial charges. AM1-BCC method, is also used in the binding foe energy calculations for different N-substitutions at site -1. The results are very similar to those obtained from widely used RESP charges in the AMBER force field. AM1-BCC charges can be calculated more rapidly for any organic molecule than can the RESP charges. Therefore, their use can enable a broader and more efficient application of the MM/PBSA method in drug design. Examination of each component of the free energy leads to the construction of van der Weals interaction energy profiles for each ligand as well as for wild-type and mutant Sem-5 proteins. The profiles and free energy calculations indicate that the van der Waals interactions between the ligands and the receptor determine whether an N- or a C alpha -substituted residue is favored at each site. A VC value (defined as a product of the conservation percentage of each residue and its van der WaaIs interaction energy with the ligand) is used to identify several residues on the receptor that are critical for specificity and binding affinity. This VC value may have a potential use in identifying crucial residues for any Ligand-protein or protein-protein system. h Mutations at two of those crucial residues, N190 and N206, are examined. One mutation, N190I, is predicted to reduce the selectivity of the N-substituted residue at site -1 of the ligand and is shown to bind similarly with N- and C alpha -substituted residues at that site.