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Query: UNIPROT:P06889 (Mol)
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The sterol carrier protein-x (SCP-x), a peroxisomal thiolase/nonspecific lipid binding protein, was characterized in the yellow fever mosquito, Aedes aegypti. The Aedes aegypti SCP-x (AeSCP-x) has 83% and 75% similarities to Drosophila and mammalian SCP-x, respectively. However, the AeSCP-x gene did not produce multiple transcripts, which is characteristic of the vertebrate SCP-x gene. Levels of AeSCP-x transcription were higher in larvae and pupae. Gut tissue showed the highest level of AeSCP-x mRNA in larvae. In adults, low levels of AeSCP-x transcription were detected in both sexes. Polyclonal antibodies against the sterol carrier protein-2 (SCP-2) domain of AeSCP-x detected two proteins of 62 kDa and 13 kDa. The results indicate that AeSCP-x is proteolytically cleaved after translation to produce a smaller protein that contains only the SCP-2 domain, which is similar to post-translational modification of the vertebrate's SCP-x to produce multiple products.
Insect Mol Biol 2004 Oct
PMID:Expression of a sterol carrier protein-x gene in the yellow fever mosquito, Aedes aegypti. 1537 8

Population reduction of mosquitoes is an effective method for controlling dengue fever and malaria transmission. Recent developments in control techniques include proposals to construct transgenic strains of mosquitoes carrying dominant, conditional-lethal genes under the control of sex- and stage-specific promoters. In order to identify such promoters, subtractive cDNA libraries derived from male and female pupal mRNA of the yellow fever mosquito, Aedes aegypti, were constructed and screened. A cDNA clone, F49, corresponds to a gene expressed specifically in female pupae. Sequence analyses revealed that this gene belongs to the actin gene family, and therefore was designated Aedes Actin-4 (AeAct-4). Transcription analyses demonstrated that this gene is expressed predominantly in the indirect flight muscles and, to a lesser extent, the legs of developing female mosquitoes. The promoter of this gene may be a useful tool for developing conditional lethal strains of mosquitoes.
Insect Mol Biol 2004 Oct
PMID:The AeAct-4 gene is expressed in the developing flight muscles of female Aedes aegypti. 1537 13

Acambis, in collaboration with Aventis Pasteur, is developing a chimeric vaccine based on a recombinant yellow fever vaccine for the potential prevention of dengue virus infection. The vaccine is undergoing phase I clinical trials.
Curr Opin Mol Ther 2004 Aug
PMID:Technology evaluation: ChimeriVax-DEN, Acambis/Aventis. 1546 3

Insects transmit the causative agents for such debilitating diseases as malaria, lymphatic filariases, sleeping sickness, Chagas' disease, leishmaniasis, river blindness, Dengue, and yellow fever. The persistence of these diseases provides testimony to the genetic capacity of parasites to evolve strategies that ensure their successful development in two genetically diverse host species: insects and mammals. Current efforts to address the problems posed by insect-borne diseases benefit from a growing understanding of insect and mammalian immunity. Of considerable interest are recent genomic investigations that show several similarities in the innate immune effector responses and associated regulatory mechanisms manifested by insects and mammals. One notable exception, however, is the nearly universal presence of a brown-black pigment accompanying cellular innate immunity in insects. This response, which is unique to arthropods and certain other invertebrates, has focused attention on the elements involved in pigment synthesis as causing or contributing to the death of the parasite, and has even prompted speculation that the enzyme cascade mediating melanogenesis constitutes an ill-defined recognition mechanism. Experimental evidence defining the role of melanin and its precursors in insect innate immunity is severely lacking. A great deal of what is known about melanogenesis comes from studies of the process occurring in mammalian systems, where the pigment is synthesized by such diverse cells as those comprising portions of the skin, hair, inner ear, brain, and retinal epithelium. Fortunately, many of the components in the metabolic pathways leading to the formation of melanin have been found to be common to both insects and mammals. This review examines some of the factors that influence enzyme-mediated melanogenic responses, and how these responses likely contribute to blood cell-mediated, target-specific cytotoxicity in immune challenged insects.
Insect Biochem Mol Biol 2005 May
PMID:Melanogenesis and associated cytotoxic reactions: applications to insect innate immunity. 1580 78

In the yellow fever mosquito Aedes aegypti, the ferritin heavy-chain homologue (HCH) gene is induced by blood feeding. This suggests that ferritin may serve as a cytotoxic protector against the oxidative challenge of the blood meal and may be essential for the survival of the insect. In this study, various cis-acting elements for the gene were identified and mapped. Transfection assays showed that the strength and activity of a subset of these elements are orientation-dependent. The shift observed for the ferritin HCH cis-acting elements is unique among known ferritin genes. DNase I footprinting data together with Transfac analyses identified a number of putative sites known for their involvement in developmental and cell proliferation processes.
Insect Mol Biol 2005 Jun
PMID:Regulation of the ferritin heavy-chain homologue gene in the yellow fever mosquito, Aedes aegypti. 1592 91

The effect of gene expression knockdown was used to study the function of the sterol carrier protein-2 (AeSCP-2) in the yellow fever mosquito, Aedes aegypti. Injection of small double stranded AeSCP-2 RNAs into mosquito larvae resulted in the knockdown of gene products. The lack of AeSCP-2 in larvae coincided with a reduction in accumulated cholesterol in pupae, supporting the hypothesis that AeSCP-2 may be involved in cholesterol uptake in mosquito larvae. Knockdown of AeSCP-2 caused a high mortality rate in developing adult and reduced egg viability. Results from this study indicate that AeSCP-2 is important for adult development and for the viability of the eggs.
Insect Mol Biol 2005 Jun
PMID:Functional analysis of AeSCP-2 using gene expression knockdown in the yellow fever mosquito, Aedes aegypti. 1592 99

A small cDNA library was constructed from antennae of 100 adult male Aedes aegypti yellow fever mosquitoes. Sequencing of 80 clones identified 49 unique gene products, including a member of the Odorant Binding Protein family (Aaeg-OBP10), a homologue of Takeout (Aaeg-TO), and transposable elements of the LINE, SINE and MITE classes. Aaeg-OBP10 encodes a 140 amino acid protein including a predicted 25 amino acid signal peptide. Aaeg-OBP10 expression was adult male enriched, increased with adult age, and greatest in antennae and wings but also present in maxillary palps, proboscis and leg. Aaeg-OBP10 is a likely orthologue of Agam-OBP10 of the malaria mosquito Anopheles gambiae and shares significant similarity with members of the OBP56 gene cluster of Drosophila melanogaster. These OBP genes may represent a unified class of OBPs with unique roles in chemodetection; the expression pattern of Aaeg-OBP10 suggests it may play a role in adult male chemosensory behavior. Aaeg-TO encodes a 248 amino acid protein including a predicted 22 amino acid signal peptide. Aaeg-TO is homologous with the circadian/feeding regulated D. melanogaster Takeout protein (Dmel-TO) and a subclass of Juvenile Hormone Binding Proteins (JHBP) characterized by Moling from Manduca sexta; both Dmel-TO and Moling are sensitive to feeding, suggesting Aaeg-TO might regulate the antennal response to food, host or pheromonal odors in a JH sensitive manner. Aaeg-TO was used to identify 25 D. melanogaster and 13 A. gambiae homologues by Blast analysis suggesting these may comprise a relatively large class of protein involved in the hormonal regulation of behavior.
Insect Biochem Mol Biol 2005 Sep
PMID:Antennal expressed genes of the yellow fever mosquito (Aedes aegypti L.); characterization of odorant-binding protein 10 and takeout. 1597 98

The precise mechanism by which the broad-spectrum anti-RNA virus agent ribavirin elicits its in vitro antiviral effect has remained a matter of debate. We have demonstrated that inhibition of cellular inosine monophosphate dehydrogenase (IMPDH) activity, and thus depletion of intracellular GTP pools, is the predominant mechanism by which ribavirin inhibits the replication of four flavi- and two paramyxoviruses (J Virol 79:1943-1947, 2005). As a consequence, induction of error catastrophe, which has been proposed as a mechanism by which ribavirin may elicit its anti-RNA virus activity, may be expected to have little, if any, impact on its antiviral effect. The flavivirus yellow fever virus (17D vaccine strain) was cultured for five consecutive passages in the presence of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin), 5-ethynyl-1-beta-D-ribo-furanosylimidazole-4-carboxamide (EICAR) (the 5-ethynyl analog of ribavirin), or mycophenolic acid (MPA; a compound that exclusively inhibits IMPDH). The reduction in infectious virus yield brought about by ribavirin (as well as MPA and EICAR) was paralleled by a similar reduction in viral RNA yield; in case of error-prone replication, the infectious virus yield is expected to decrease significantly faster than the viral RNA yield. In addition, pre-extinction populations of the virus that has suffered a maximum impact of treatment with ribavirin did not accumulate an increased number of mutations. Very similar observations were obtained with EICAR and with MPA, a molecule that cannot be incorporated into viral RNA. These data thus allow us to conclude that the in vitro anti-yellow fever virus activity of ribavirin is independent of error-prone replication.
Mol Pharmacol 2006 Apr
PMID:The anti-yellow fever virus activity of ribavirin is independent of error-prone replication. 1642 Dec 90

The yellow fever mosquito, Aedes aegypti, must blood feed in order to complete her life cycle. The blood meal provides a high level of iron that is required for egg development. We are interested in developing control strategies that interfere with this process. We show that A. aegypti larval cells synthesize and secrete ferritin in response to iron exposure. Cytoplasmic ferritin is maximal at low levels of iron, consists of both the light chain (LCH) and heavy chain (HCH) subunits and reflects cytoplasmic iron levels. Secreted ferritin increases in direct linear relationship to iron dose and consists primarily of HCH subunits. Although the messages for both subunits increase with iron treatment, our data indicate that mosquito HCH synthesis could be partially controlled at the translational level as well. Importantly, we show that exposure of mosquito cells to iron at low concentrations increases cytoplasmic iron, while higher iron levels results in a decline in cytoplasmic iron levels indicating that excess iron is removed from mosquito cells. Our work indicates that HCH synthesis and ferritin secretion are key factors in the response of mosquito cells to iron exposure and could be the primary mechanisms that allow these insects to defend against an intracellular iron overload.
Insect Biochem Mol Biol 2006 Mar
PMID:Secreted ferritin: mosquito defense against iron overload? 1650 79

Current techniques for the genetic engineering of insect genomes utilize transposable genetic elements, which are inefficient, have limited carrying capacity and give rise to position effects and insertional mutagenesis. As an alternative, we investigated two site-specific integration mechanisms in the yellow fever mosquito, Aedes aegypti. One was a modified CRE/lox system from phage P1 and the other a viral integrase system from Streptomyces phage phi C31. The modified CRE/lox system consistently failed to produce stable germline transformants but the phi C31 system was highly successful, increasing integration efficiency by up to 7.9-fold. The ability to efficiently target transgenes to specific chromosomal locations and the potential to integrate very large transgenes has broad applicability to research on many medically and economically important species.
Insect Mol Biol 2006 Apr
PMID:High efficiency site-specific genetic engineering of the mosquito genome. 1664 Jul 23


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