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IUBMB Life,
2000]
In the past decade, important advances have been made in our knowledge of the composition of human RNase MRP and RNase P complexes. Both ribonucleoprotein particles function as endonucleases and contain RNA components that are structurally related. RNase MRP has been suggested to be involved in the processing of precursor rRNA; RNase P, in the maturation of tRNA. Here we give an overview of current data on the structure and function of human RNase MRP and RNase P particles, with emphasis on their molecular composition. At present, seven protein subunits, probably all associated with both ribonucleoprotein particles, have been isolated and their corresponding cDNAs cloned. Although no known structural motifs can be identified in the amino acid sequences of these proteins, the majority is clearly rich in basic residues. For two protein subunits, a cluster of basic amino acids have been shown to be involved in nucleolar accumulation, whereas another protein, which lacks such a region, probably enters the nucleolus by way of a piggyback mechanism. The binding regions for several of the protein subunits on the RNA have been identified, and the data have been used to create a putative structural model for the RNase MRP particle. The rather obscure situation concerning the association of the autoantigenic Th-40 protein and its possible relationship with one of the subunits, Rpp38, is discussed.
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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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Pediatr Res,
2007]
The n-3 polyunsaturated fatty acid (PUFA) status of the neonatal brain has been associated with cognitive capability in mice. Previously, transgenic mice expressing the Caenorhabditis elegans (C. elegans) n-3 fatty acid (FA) desaturase gene under the control of a lactation-induced mammary gland promoter were found to produce milk containing significantly elevated levels of alpha-linolenic (ALA) and eicosapentaenoic (20:5n-3) (EPA) acid. In this study, the preweaning growth rate and development of mouse pups consuming elevated n-3 PUFA milk produced by transgenic dams were evaluated using the Wahlsten observational test battery and the object novelty preference test. Brains were collected at weaning and analyzed for FA composition. Pups nursed on transgenic dams had earlier eye opening, higher visual placement scores, and 1.6-fold more docosahexaenoic acid (DHA) in their brains compared with pups raised on wild-type dams. There was no significant effect of milk treatment (transgenic versus control) on other developmental parameters or novelty preference behavior. The pups consuming the elevated n-3 PUFA transgenic milk had slower preweaning growth rates such that pups reared on wild-type dams producing control milk [pups reared on wild-type dams producing control milk (wild type-fed)] were heavier than pups reared on transgenic dams producing high n-3 PUFA milk [pups reared on transgenic dams producing high n-3 PUFA milk (transgenic-fed)] by postnatal day (PND) 18. This transgenic model enables the provision of a high n-3 PUFA lactational environment independent of maternal diet or gestational FA status.
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Lipids,
2006]
The brain contains high levels of the long-chain n-3 FA DHA (22:6n-3), mainly in the gray matter and synaptosomes. Adequate intake of DHA is crucial for optimal nervous system function, particularly in infants. Supplementation of infant formulas with DHA at levels similar to human breast milk is recommended for biochemical and functional benefits to neonates. We generated transgenic mice that produce elevated levels of n-3 PUFA in their milk by expressing the Caenorhabditis elegans n-3 FA desaturase under the control of a lactation-induced goat beta-casein promoter. To examine the postnatal effects of consuming the n-3-enriched milk, we compared the growth and brain and plasma FA composition of mouse pups raised on milk from transgenic dams with those observed for pups raised on milk from nontransgenic dams. A significant decrease in arachidonic acid (ARA, 20:4n-6) and concomitant increases in n-3 PUFA were observed in the phospholipid fraction of transgenic mouse milk. The n-6:n-3 FA ratios were 4.7 and 34.5 for the transgenic and control milk phospholipid fractions, respectively. DHA and DPA (22:5n-6) comprised 15.1% and 2.8% of brain FA from weanling mice nursed on transgenic dams, as compared with 6.9% and 9.2% for weanling mice nursed on control dams, respectively. This transgenic mouse model offers a unique approach to disassociate the effects and fetal programming resulting from a high n-6:n-3 FA ratio gestational environment from the postnatal nutritional effects of providing milk with differing n-6:n-3 FA ratios.
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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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Aging Cell,
2002]
The papers by Van Voorhies in Free Radical Biology & Medicine (33, 587-596, 2002) and in this journal claim that the major longevity-extending mutations in C. elegans essentially act by reducing metabolic rate as predicted by the rate-of-living theory, and do not alter any metabolically independent mechanism specific to aging. In contrast, we found no evidence of a reduction in metabolic rate in these mutants using different experimental approaches. Now, Van Voorhies challenges the accuracy of our experimental results.
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[
International C. elegans Meeting,
1995]
The strain Bristol N2 has no endogenous Tc3 transposition activity, but forced expression of Tc3 transposase results in somatic transposition of endogenous Tc3 elements as well as Tc3 elements located on a transgene (Van Luenen et al. 1993 EMBO J. 12:2513-2520). This provides us with an assay for the requirements of Tc3 transposition in vivo.
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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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PLoS Biol,
2022]
In this issue of PLOS Biology, van Rijnberk and colleagues show how polyploidy, via binucleation, enables Caenorhabditis elegans intestinal cells to ramp up gene expression supplying the oocytes with the necessary lipids for optimal organismal growth and reproductive fitness.
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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.