4K Papers found (0.019 seconds)

Gert de Voer et al. (2006) European Worm Meeting "Overexpression of Subunit C, the Main Component of the Storage Material in Juvenile Neuronal Ceroid Lipofuscinosis (JNCL), Causes Disruption of Mitochondria in C. Elegans and Subsequent Death"

Gert de Voer, Gert-Jan B. van Ommen, Ronald O.B. de Keizer, Peter E.M. Taschner, Paola van der Bent, Dorien J.M. Peters

[

European Worm Meeting,

2006]

Overexpression of Subunit C, the Main Component of the Storage Material in Juvenile Neuronal Ceroid Lipofuscinosis (JNCL), Causes Disruption of Mitochondria in C. Elegans and Subsequent Death. Gert de Voer, Ronald O.B. de Keizer, Paola van der Bent, Gert-Jan B. van Ommen, Dorien J.M. Peters, and Peter E.M. Taschner . Subunit c of the mitochondrial ATP synthase (subunit c) normally is present in the F0 part of the ATP synthase complex in mitochondria. The very hydrophobic subunit c also forms the main component of the lysosomal storage material found in many forms of the hereditary neurodegenerative disorders called Neuronal Ceroid Lipofuscinosis (NCL, Batten disease). The juvenile form of NCL is caused by mutations in the CLN3 gene, which has three homologs in C. elegans. In order to obtain more insight in the etiology of juvenile NCL and how the mitochondrial subunit c protein ends up in large quantities in lysosomes, we have constructed cln-3 triple mutants, in which all three cln-3 genes have been mutated. The cln-3 triple mutants had a decreased life span and brood size, but no lysosomal storage was observed, probably due to the relatively short life span of the worm. We hypothesized that overexpression of subunit c might directly or indirectly induce lysosomal storage in C. elegans and potentially lead to a phenotype useful for genetic screens. Therefore, we identified the atp-9 gene, which encodes the C. elegans subunit c protein, and generated transgenic worms carrying an hsp-16.2 promoter-atp-9 fusion construct. Induction of subunit c overexpression by a 2-hr heat shock causes the nematodes to disintegrate, presumably as a result of disrupted mitochondria. Electron micrographs of transgenic worms show altered mitochondria after induction of subunit c overexpression, but no lysosomal storage was detected irrespective of a wildtype or cln-3 triple mutant background. Milder induction of overexpression affects the reproduction and the morphology of the worms.. This work was financially supported by the Center for Biomedical Genetics, the Batten Disease Support and Research Association, and the European Union, EU project NCL models (EU LSHM-CT-2003-503051).

Gert de Voer et al. (2002) European Worm Meeting "Cln-3.3, one of the C. elegans homologues of the human CLN3 gene involved in neuronal ceroid lipofuscinosis, is expressed in the intestinal muscle"

Gert-Jan B Van Ommen, Dorien J M Peters, Gert de Voer, Peter E M Taschner

[

European Worm Meeting,

2002]

C. elegans has three genes of which the proteins are homologous to the human Cln3 protein. Mutations in the human CLN3 gene are the cause for a neurodegenerative disease called juvenile neuronal ceroid lipofuscinosis, j-NCL or Batten's disease. This devastating lysosomal storage illness is part of a group of common hereditary neurodegenerative disorders. The first symptom of the NCL's is progressive visual failure, and this group of diseases is also characterised by the accumulation of lipopigments in the lysosomes of neurons, and other cells. We focus on the juvenile form of the disease, since it is the most frequent form of NCL, and we set out to use C. elegans as a model organism to investigate this complicated disorder. The spatial and temporal expression patterns of the C. elegans cln-3 genes are being analysed by cloning the putative promoter regions in GFP expression vectors. Transgenic nematodes carrying the cln-3.1-GFP fusion construct show fluorescence suggesting cln-3.1 gene expression in the intestine. The absence of fluorescence in transgenic nematodes containing a construct consisting of the intergenic region upstream of cln-3.3 fused to the GFP gene may indicate the gene is part of an operon. The promoter region of the gene ZC190.2 upstream of cln-3.3 was fused to GFP and resulted in fluorescence signals, implying expression in head and tail neurons. Faint fluorescent signals in transgenic nematodes containing the entire cln-3.3 operon with the GFP gene fused to the cln-3.3 gene suggest cln-3.3 gene expression in the intestinal muscle. These results seem contradictory, but may be explained by the presence of additional regulatory sequences in the latter construct. Currently we are examining the cln-3 deletion mutants, and we expect that the determination of the spatial and temporal expression pattern of the cln-3 genes will be helpful in the characterization.

Gert de Voer et al. (2001) International C. elegans Meeting "Expression analysis of C. elegans homologues of the human CLN3 gene involved in neuronal ceroid lipofuscinosis"

Gert de Voer, Peter E M Taschner, Dorien J M Peters, Gert-Jan B Van Ommen

[

International C. elegans Meeting,

2001]

The neuronal ceroid lipofuscinoses (NCL) are the most common hereditary neurodegenerative disorders of childhood with an incidence as high as 1 in 12,500 in Northern Europe and the United States, and 1 in 100,000 elsewhere. Symptoms of this heterogenous group of devastating lysosomal storage diseases are progressive visual failure, seizures, and psychomotor deterioration. The different NCL types can be distinguished by age of onset, clinical signs and structural characteristics of the storage material. We focus on the juvenile form (Batten disease, gene symbol: CLN3), which is the most frequent form of the disease. Genetic studies have indicated that CLN3 encodes a novel integral membrane protein. The CLN3 protein has been localized to the lysosome, confirming that the primary defect in NCL is in lysosomal function, but the function of the CLN3 protein is still unknown. Homologues to the human CLN3 gene have been identified in several organisms, including the nematode Caenorhabditis elegans . In C. elegans three genes, cln-3.1 , cln-3.2 , and cln-3.3 , homologous to the human CLN3 gene have been identified by sequence comparison. We have decided to exploit the genetic power of C. elegans as a model for Batten disease in order to dissect the processes, in which the CLN3 proteins play a role, and to provide further insight into the function of the cln3 genes and in the mechanism of neurodegeneration in NCL. We have cloned the putative promotor regions of the CLN3 homologues in front of the GFP gene in C. elegans expression vectors and analyzed the spatial and temporal expression pattern of the cln3 genes in transgenic worms. Preliminary evidence suggests that the cln-3.1 -GFP fusion protein is expressed in the distal part of the gut. No fluorescent signals were observed with GFP fusion constructs containing the intergenic regions in front of the cln-3.2 and cln-3. 3 genes, suggesting that these genes are part of operons. We expect that the determination of the spatial and temporal expression pattern of the cln-3 genes will be helpful in the characterization of cln-3 deletion mutants.

Gert de Voer et al. (2003) International Worm Meeting "Overexpression of subunit c of the mitochondrial ATP synthase in Caenorhabditis elegans cln-3 triple mutants"

Gert de Voer, Ronald OB de Keizer, Peter EM Taschner, Dorien JM Peters, Gert-Jan B Van Ommen

[

International Worm Meeting,

2003]

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) or Battens disease is one of the most common hereditary neurodegenerative disorders of childhood with a severe progressive nature. JNCL is a lysosomal storage disease in which the major component of the stored material is subunit c of the mitochondrial ATP synthase (scMAS). Mutations in the CLN3 gene were identified as the cause of JNCL. In C. elegans three genes, cln-3.1, cln-3.2, and cln-3.3, homologous to the human CLN3 gene have been identified by sequence comparison. Single cln-3 deletion mutants do not have an obvious phenotype, which could be caused by functional redundancy. Therefore, all mutations have been crossed into the same background to obtain cln-3.1 cln-3.2 cln-3.3 triple mutants. This mutant is viable and phenotypically normal, suggesting that the cln-3 genes are not essential for normal development and functioning of C. elegans. In the cln-3 triple mutant we have not yet been able to detect several of the cellular features characterizing JNCL patients, such as accumulation of autofluorescent lipopigments, and specific lysosomal storage patterns. Therefore, we decided to investigate whether overexpression of scMAS could enhance a possible phenotype. We have generated transgenic worms, in which scMAS can be overexpressed under the control of heat shock promoter hsp-16.2. After a two-hour heat shock at 33 degrees C, in contrast to wildtype all transgenic animals had died, indicating that overexpression of scMAS has a deleterious effect on its own. Loss of mitochondrial staining by the fluorescent dye Mitotracker Red in transgenic worms after heat shock suggests that the mitochondria have disintegrated. Transgenic animals grown at 25 degrees C only show bulges of variable size at the tail section, and occasionally have abnormal embryos. We crossed the integrated scMAS overexpression array into the cln-3 triple mutant to test whether growth at 25 degrees C would result in an enhanced phenotype. We are currently testing different scMAS overexpression conditions to obtain a clear-cut phenotype in cln-3 triple mutants. This study was supported in part by the Batten Disease Support and Research Association.

Sharma S et al. (2019) Int Microbiol "Lipidomic insights to understand membrane dynamics in response to vanillin in Mycobacterium smegmatis."

Sharma S, Fatima Z, Hameed S

[

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.

Braeckman BP et al. (2002) Aging Cell "Rebuttal to Van Voorhies: 'the influence of metabolic rate on longevity in the nematode Caenorhabditis elegans'."

Braeckman BP, Houthoofd K, Vanfleteren JR

[

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.

Halic M et al. (2009) Mol Cell "22G-RNAs in transposon silencing and centromere function."

Moazed D, Halic M

[

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.

Dehn AS et al. (2022) PLoS Biol "Binucleation ramps up gene expression meeting the physiological demands of an organism."

Dehn AS, Losick VP

[

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.

Neupane RP et al. (2019) Mar Drugs "Cytotoxic Sesquiterpenoid Quinones and Quinols, and an 11-Membered Heterocycle, Kauamide, from the Hawaiian Marine Sponge Dactylospongia elegans."

Williams PG, Neupane JB, Yip MLR, Turkson J, Parrish SM, Yoshida WY, Head JD, Harper MK, Neupane RP

[

Mar Drugs,

2019]

Several known sesquiterpenoid quinones and quinols (1-9), and kauamide (10), a new polyketide-peptide containing an 11-membered heterocycle, were isolated from the extracts of the Hawaiian marine sponge Dactylospongiaelegans. The planar structure of 10 was determined from spectroscopic analyses, and its relative and absolute configurations were established from density functional theory (DFT) calculations of the GIAO NMR shielding tensors, and advanced Marfey's analysis of the N-MeLeu residue, respectively. Compounds 1 and 3 showed moderate inhibition of -secretase 1 (BACE1), whereas 1-9 exhibited moderate to potent inhibition of growth of human glioma (U251) cells. Compounds 1-2 and 4-7 were also active against human pancreatic carcinoma (Panc-1) cells.

Venkata S et al. (2020) Curr Med Mycol "Efficiency of vanillin in impeding metabolic adaptability and virulence of Candida albicans by inhibiting glyoxylate cycle, morphogenesis, and biofilm formation."

Saif H, Zeeshan F, Venkata S, Luqman AK, Kamal A

[

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.

load 10 more results