Summary of recent advancesA family of small molecules called ascarosides act as pheromones to control multiple behaviors in the nematode Caenorhabditiselegans....Full Text Available
P granules are non-membrane-bound organelles found in the germ-line cytoplasm throughout Caenorhabditiselegans development. Like their “germ granule” counterparts in...Full Text Available
The nuo-6 and isp-1 genes of C. elegans encode, respectively, subunits of complex I and III of the mitochondrial respiratory chain. Partial loss-of-function...Full Text Available
Transient receptor potential (TRP) ion channels have been implicated in detecting chemical, thermal and mechanical stimuli in organisms ranging from mammals to Caenorhabditiselegans....Full Text Available
A common property of aging in all animals is that chronologically and genetically identical individuals age at different rates. To unveil mechanisms that influence aging variability, we identified markers...Full Text Available
Genetic defects in the dystrophin-associated protein complex (DAPC) are responsible for a variety of pathological conditions including muscular dystrophy, cardiomyopathy, and vasospasm. Conserved DAPC...Full Text Available
Although acetylated α-tubulin is known to be a marker of stable microtubules in neurons, precise factors that regulate α-tubulin acetylation are, to date, largely unknown. Therefore,...Full Text Available
Disorders of mitochondrial fat metabolism lead to sudden death in infants and children. Although survival is possible, the underlying molecular mechanisms which enable this outcome have not yet been...Full Text Available
Activation of the innate immune system results in a rapid microbicidal response against microorganisms, which needs to be fine-tuned because uncontrolled immune responses can lead to infection and cancer,...Full Text Available
Stem cells are expected to play a key role in the development and maintenance of organisms, and hold great therapeutic promises. However, a number of questions must be answered to achieve an...Full Text Available
The insulin/IGF-1 signaling (IIS) pathway is a conserved regulator of longevity, development, and metabolism. In Caenorhabditiselegans IIS involves activation of DAF-2 (insulin/IGF-1...Full Text Available
Cross-resistance to cefoxitin (FOX), chloramphenicol (CMP), and quinolones (nalidixic acid [NAL]) related to a putative efflux system overexpression has recently been reported for Klebsiella...Full Text Available
The decline in immune function with aging, known as immunosenescence, has been implicated in evolutionarily diverse species, but the underlying molecular mechanisms are not understood. During aging...Full Text Available
X-linked sideroblastic anemia with ataxia (XLSA/A) is a rare inherited disorder characterized by mild anemia and ataxia. XLSA/A is caused by mutations in the ABCB7 gene, which encodes...Full Text Available
The methylation of lysine 4 of Histone H3 (H3K4me) is an important component of epigenetic regulation. H3K4 methylation is a consequence of transcriptional activity, but also has been shown to contribute...Full Text Available
We review the application of C. elegans as a model system to understand key aspects of stem cell biology. The only bona fide stem cells in C. elegans...Full Text Available
PurposeHeavy metals and other forms of oxidative stress have been implicated as key factors in the formation of age-related cataract in humans. Metallothioneins are...Full Text Available
AIM: To investigate the role of metallothionein in colorectal tumours and the possible relation with other factors associated with tumour progression: expression of cathepsin D (CD), CD44, p53, Rb,...Full Text Available
Germline-specific granules of unknown function are found in a wide variety of organisms, including C. elegans, where they are called P granules. P granules are cytoplasmic bodies...Full Text Available
PurposeTo identify those metallothionein and α-crystallin/small heat-shock genes induced by toxic metals in human lens cells and to evaluate...Full Text Available
Motivation: Automatic recognition of cell identities is critical for quantitative measurement, targeting and manipulation of cells of model animals at single-cell resolution. It has been...Full Text Available
BackgroundHarbour porpoises Phocoena phocoena from the southern North Sea are known to display high levels of Zn and Hg in their tissues linked to their nutritional...Full Text Available
To define the import pathway for apoiso-1-cytochrome c in vivo, the coding region for bacterial chloramphenicol acetyltransferase (CAT) or yeast copper metallothionein (CuMT) was fused to the carboxy...Full Text Available
BackgroundMutations that impair mitochondrial functioning are associated with a variety of metabolic and age-related disorders. A barrier to rigorous tests of the role of mitochondrial...Full Text Available
SummaryThe life span of C. elegans can be increased via reduced function of the mitochondria; however, the extent to which mitochondrial alteration in a single,...Full Text Available
A mild reduction in mitochondrial respiration extends the life span of many species, including C. elegans. We recently showed that hypoxia-inducible factor 1 (HIF-1) is required for...Full Text Available
Many lifespan-modulating genes are involved in either generation of oxidative substrates and end-products, or their detoxification and removal. Among such metabolites, only lipoperoxides have the ability...Full Text Available
BackgroundA strong association between stress resistance and longevity in multicellular organisms has been established as many mutations that extend lifespan also show increased...Full Text Available
DYF-13, originally identified in C. elegans within a collection of dye-filling chemosensory mutants, is one of several proteins that have been classified as putatively involved...Full Text Available
Ataxin-3, the protein involved in Machado-Joseph disease, is able to bind ubiquitylated substrates and act as a deubiquitylating enzyme in vitro, and it has been involved in the modulation of protein...Full Text Available
BackgroundProteins may evolve through the recruitment and modification of discrete domains, and in many cases, protein action can be dissected at the domain level. PDZ domains are...Full Text Available
Mutations or multiplications in a-synuclein gene cause familial forms of Parkinson disease or dementia with Lewy bodies (LB), and the deposition of wild-type a-synuclein as LB occurs as a hallmark lesion of these disorders, collectively referred to as synucleinopathies, implicating a-synuclein in the pathogenesis of synucleinopathy. To identify modifier genes of a-synuclein-induced neurotoxicity, we conducted an RNAi screen in transgenic C. elegans (Tg worms) that overexpress human a-synuclein in a pan-neuronal manner. To enhance the RNAi effect in neurons, we crossed a-synuclein Tg worms with an RNAi-enhanced mutant eri-1 strain. We tested RNAi of 1673 genes related to nervous system or synaptic functions, and identified 10 genes that, upon knockdown, caused severe growth/motor abnormalit...
Glutathione (GSH) depletion sensitizes human lung carcinoma (A549-T27) cells to the cytotoxic effects of Cd++. The effects of GSH depletion on Cd++ accumulation and Cd++-induced metallothionein (MT) content were investigated to determine the possible role of these Cd++ responses in the sensitization process. Cellular GSH was depleted to 20% to 25% of control levels with buthionine sulfoximine (BSO), or diethyl maleate (DEM), respectively. Neither treatment significantly affected Cd++-induced accumulation of exogenous 35s-cysteine into intracellular MT in a dose-dependent fashion. The results indicate that neither enhanced Cd++ accumulation nor reduced MT synthesis plays a primary role in affecting enhanced Cd++ cytotoxicity in A549 cells with reduced GSH levels. Although BSO inhibition of GSH synthesis enhanced MT synthesis, it sensitized the cells to Cd++, which suggests an additive effect of GSH and MT in cadmium cytoprotection. This observation also raises the ...
To evaluate the role of phytochelatins and metallothioneins in heavy metal tolerance of black mangrove Avicennia germinans, 3-month-old seedlings were exposed to cadmium or copper for 30 h, under hydroponic conditions. Degenerate Mt2 and PCS primers were synthesized based on amino acid and nucleotide alignment sequences reported for Mt2 and PCS in other plant species found in GenBank. Total RNA was isolated from A. germinans leaves and two partial fragments of metallothionein and phytochelatin synthase genes were isolated. Gene expression was evaluated with reverse transcripatase-polymerase chain reaction (RT-PCR) amplification technique. Temporal analysis showed that low Cd{sup 2+} and Cu{sup 2+} concentrations caused a slight (but not significant) increase in AvMt2 expression after a 16 h exposure time, while AvPCS expression showed a significant increase under the same conditions but only after 4 h. Results strongly suggest that the rapid ...
To evaluate the role of phytochelatins and metallothioneins in heavy metal tolerance of black mangrove Avicennia germinans, 3-month-old seedlings were exposed to cadmium or copper for 30 h, under hydroponic conditions. Degenerate Mt2 and PCS primers were synthesized based on amino acid and nucleotide alignment sequences reported for Mt2 and PCS in other plant species found in GenBank. Total RNA was isolated from A. germinans leaves and two partial fragments of metallothionein and phytochelatin synthase genes were isolated. Gene expression was evaluated with reverse transcripatase-polymerase chain reaction (RT-PCR) amplification technique. Temporal analysis showed that low Cd"2"+ and Cu"2"+ concentrations caused a slight (but not significant) increase in AvMt2 expression after a 16 h exposure time, while AvPCS expression showed a significant increase under the same conditions but only after 4 h. Results strongly suggest that the rapid increase ...
A cDNA library was constructed using RNA isolated from the livers of chickens which had been treated with zinc. This library was screened with a RNA probe complementary to mouse metallothionein-I (MT), and eight chicken MT cDNA clones were obtained. All of the cDNA clones contained nucleotide sequences homologous to regions of the longest (375 bp) cDNA clone. The latter contained an open reading frame of 189 bp, and the deduced amino acid sequence indicates a protein of 63 amino acids of which 20 are cysteine residues. Amino acid composition and partial amino acid sequence analyses of purified chicken MT protein agreed with the amino acid composition and sequence deduced from the cloned cDNA. Amino acid sequence comparison establish that chicken MT shares extensive homology with mammalian MTs. Southern blot analysis of chicken DNA indicates that the chicken MT gene is not a part of a large family of related sequences, but rather is likely to be a unique gene ...
The effects of different exposure concentrations of palladium (Pd) on relative metallothionein (MT) response and bioaccumulation were investigated in zebra mussels (Dreissena polymorpha). The mussels were exposed to 0.05, 5, 50, and 500 ?g/L Pd2+ for 10 weeks under controlled temperature and fasting conditions. Relative MT contents were assessed by a modified Ag-saturation method, which allows to discriminate between MT bound to Pd (Pd-MT) and MT bound to unidentified metals (Ag-MT). Determination of metal contents resulted from atomic absorption spectrometry following a microwave digestion. For unexposed mussels and mussels exposed to 0.05 ?g/L Pd no metal accumulation could be detected. All other exposure concentrations resulted in detectable Pd accumulation in mussels with final tissue concentrations of 96 ?g/g (500 ?g/L), 45 ?g/g (50 ?g/L), and 9 ?g/g (5 ?g/L). Compared with initial levels Pd-MT concentrations at the end of the exposure period were 600 (500 ...
Perinatal exposure to cadmium (Cd) or methylmercury (MeHg) results in impaired neurodevelopment. Thyroid hormone is essential for normal brain development. However, the issue whether Cd or MeHg, especially at low doses, interrupts thyroid hormone action remains to be investigated. In the present study, effects of perinatal exposure to low levels of Cd or MeHg on thyroid hormone metabolism were examined using metallothionein I and II (MT-I/II) null or wild-type neonatal mice. Dams were exposed to 10 mg/L water of Cd or 5 mg/kg chow of MeHg from gestational day 0 to post-natal day 10 (PND 10). Sera, livers and brains were collected from neonates on PND 10. Iodothyronine deiodinase activities and serum thyroxine (T4) concentrations were measured. MeHg exposure failed to induce changes in serum T4 levels and liver type 1 deiodinase (D1) and brain type 2 deiodinase (D2) activities regardless of the MT genotype. However, exposure to MeHg resulted in a decrease in brain ...
We describe an efficient procedure for proving stabilization of biological systems modeled as qualitative networks or genetic regulatory networks. For scalability, our procedure uses modular proof techniques, where state-space exploration is applied only locally to small pieces of the system rather than the entire system as a whole. Our procedure exploits the observation that, in practice, the form of modular proofs can be restricted to a very limited set. For completeness, our technique falls back on a non-compositional counterexample search. Using our new procedure, we have solved a number of challenging published examples, including: a 3-D model of the mammalian epidermis; a model of metabolic networks operating in type-2 diabetes; a model of fate determination of vulval precursor cells in the C. elegans worm; and a model of pair-rule regulation during segmentation in the Drosophila embryo. Our results show many orders of magnitude speedup in cases where ...
The process of mouse skin tumor formation is subdivided into three operational stages. These stages include initiation, promotion and progression. Ionizing radiation has been found to be a weak initiating agent in the production of malignant squamous cell carcinomas, a complete carcinogen and an agent effective in causing tumor progression. Four skin tumor histologies have been seen with ionizing radiation: benign papillomas, squamous (SCC) and basal (BCC) cell carcinomas and fibrosarcomas. Distinct non-ras transforming genes have been detected in radiation initiated SCCs. A benign papilloma cell line (308) was used as a model system to study ionizing radiation induced progression. A variant 308 cell line (308 10 Gy 5) derived by irradiation of the parental 308 cell has been characterized. The 308 10 Gy 5 cells unlike the parental 308 cells from malignant tumors in athymic nude mice upon subcutaneous injection. The variant 308 10 Gy 5 cells unlike the parental cells also show by ...
Paraquat (1,1'-dimethyl-4,4'-bipyridinium) is a widely used herbicide known to induce skin toxicity. This is thought to be due to oxidative stress resulting from the generation of cytotoxic reactive oxygen intermediates (ROI) during paraquat redox cycling. The skin contains a diverse array of antioxidant enzymes which protect against oxidative stress including superoxide dismutase (SOD), catalase, glutathione peroxidase-1 (GPx-1), heme oxygenase-1 (HO-1), metallothionein-2 (MT-2), and glutathione-S-transferases (GST). In the present studies we compared paraquat redox cycling in primary cultures of undifferentiated and differentiated mouse keratinocytes and determined if this was associated with oxidative stress and altered expression of antioxidant enzymes. We found that paraquat readily undergoes redox cycling in both undifferentiated and differentiated keratinocytes, generating superoxide anion and hydrogen peroxide as well as increased protein oxidation which ...