The Experts below are selected from a list of 180 Experts worldwide ranked by ideXlab platform
Qingyou Xia - One of the best experts on this subject based on the ideXlab platform.
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Transcriptome Analysis of Integument Differentially Expressed Genes in the Pigment Mutant (quail) during Molting of Silkworm, Bombyx mori
PloS one, 2014Co-Authors: Hongyi Nie, Chun Liu, Tingcai Cheng, Mengting Zhou, Yinxia Zhang, Wu Yuqian, Qingyou XiaAbstract:In the silkworm Bombyx mori, pigment mutants with diverse body colors have been maintained throughout domestication for about 5000 years. The silkworm larval body color is formed through the mutual interaction of melanin, ommochromes, Pteridines and uric acid. These pigments/compounds are synthesized by the cooperative action of various genes and enzymes. Previous reports showed that melanin, ommochrome and Pteridine are increased in silkworm quail (q) mutants. To understand the pigment increase and alterations in pigment synthesis in q mutant, transcriptome profiles of the silkworm integument were investigated at 16 h after head capsule slippage in the fourth molt in q mutants and wild-type (Dazao). Compared to the wild-type, 1161 genes were differentially expressed in the q mutant. Of these modulated genes, 62.4% (725 genes) were upregulated and 37.6% (436 genes) were downregulated in the q mutant. The molecular function of differently expressed genes was analyzed by Blast2GO. The results showed that upregulated genes were mainly involved in protein binding, small molecule binding, transferase activity, nucleic acid binding, specific DNA-binding transcription factor activity and chromatin binding, while exclusively down-expressed genes functioned in oxidoreductase activity, cofactor binding, tetrapyrrole binding, peroxidase activity and pigment binding. We focused on genes related to melanin, Pteridine and ommochrome biosynthesis; transport of uric acid; and juvenile hormone metabolism because of their importance in integument coloration during molting. This study identified differently expressed genes implicated in silkworm integument formation and pigmentation using silkworm q mutant. The results estimated the number and types of genes that drive new integument formation.
Stephen M. Beverley - One of the best experts on this subject based on the ideXlab platform.
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Pteridine salvage throughout the Leishmania infectious cycle: implications for antifolate chemotherapy.
Molecular and biochemical parasitology, 2001Co-Authors: Mark Cunningham, Stephen M. BeverleyAbstract:Protozoan parasites of the trypanosomatid genus Leishmania are Pteridine auxotrophs, and have evolved an elaborate and versatile Pteridine salvage network capable of accumulating and reducing Pteridines. This includes biopterin and folate transporters (BT1 and FT1), Pteridine reductase (PTR1), and dihydrofolate reductase‐thymidylate synthase (DHFR-TS). Notably, PTR1 is a novel alternative Pteridine reductase whose activity is resistant to inhibition by standard antifolates. In cultured promastigote parasites, PTR1 can function as a metabolic by-pass under conditions of DHFR inhibition and thus reduce the efficacy of chemotherapy. To test whether Pteridine salvage occurred in the infectious stage of the parasite, we examined several pathogenic species of Leishmania and the disease-causing amastigote stage that resides within human macrophages. To accomplish this we developed a new sensitive HPLC-based assay for PTR1 activity. These studies established the existence of the Pteridine salvage pathway throughout the infectious cycle of Leishmania, including amastigotes. In general, activities were not well correlated with RNA transcript levels, suggesting the occurrence of at least two different modes of post-transcriptional regulation. Thus, Pteridine salvage by amastigotes may account for the clinical inefficacy of antifolates against leishmaniasis, and ultimately provide insights into how this may be overcome in the future. © 2001 Elsevier Science B.V. All rights reserved.
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new approaches to leishmania chemotherapy Pteridine reductase 1 ptr1 as a target and modulator of antifolate sensitivity
Parasitology, 1997Co-Authors: Bakela Nare, Larry W. Hardy, James Luba, Stephen M. BeverleyAbstract:summary Leishmania and other trypanosomatid protozoa require reduced Pteridines (pterins and folates) for growth, suggesting that inhibition of these pathways could be targeted for eective chemotherapy. This goal has not yet been realized, indicating that Pteridine metabolism may be unusual in this lower eukaryote. We have investigated this possibility using both wild type and laboratory-selected antifolate-resistant strains, and with defined genetic knockouts of several Pteridine metabolic genes. In Leishmania, resistance to the antifolate methotrexate is mediated through several mechanisms singly or in combination, including alterations in transport leading to reduced drug influx, overproduction (R-region amplification) or point mutation of dihydrofolate reductase-thymidylate synthase (DHFR-TS), and amplification of a novel Pteridine reductase (PTR 1, encoded by the H-region). All of the proteins involved are potential targets for antifolate chemotherapy. Notably, parasites in which the gene encoding dihydrofolate reductase (DHFR) has been deleted (dhfr-ts’ knockouts) do not survive in animal models, validating this enzyme as a target for eective chemotherapy. However, the properties of Pteridine reductase 1 (PTR1) suggest a reason why antifolate chemotherapy has so far not been successful in trypanosomatids. PTR1, by its ability to provide reduced pterins and folates, has the potential to act as a by-pass and}or modulator of DHFR inhibition under physiological conditions. Moreover, PTR1 is less sensitive to many antifolates targeted primarily against DHFR. These findings suggest that successful antifolate chemotherapy in Leishmania will have to target simultaneously both DHFR and PTR1.
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The roles of Pteridine reductase 1 and dihydrofolate reductase-thymidylate synthase in Pteridine metabolism in the protozoan parasite Leishmania major.
The Journal of biological chemistry, 1997Co-Authors: Bakela Nare, Larry W. Hardy, Stephen M. BeverleyAbstract:Trypanosomatid protozoans depend upon exogenous sources of Pteridines (pterins or folates) for growth. A broad spectrum Pteridine reductase (PTR1) was recently identified in Leishmania major, whose sequence places it in the short chain alcohol dehydrogenase protein family although its enzymatic activities resemble dihydrofolate reductases. The properties of PTR1 suggested a role in essential Pteridine salvage as well as in antifolate resistance. To prove this, we have characterized further the properties and relative roles of PTR1 and dihydrofolate reductase-thymidylate synthase in Leishmania Pteridine metabolism, using purified enzymes and knockout mutants. Recombinant L. major and Leishmania tarentolae, and native L. major PTR1s, were tetramers of 30-kDa subunits and showed similar catalytic properties with pterins and folates (pH dependence, substrate inhibition with H2Pteridines). Unlike PTR1, dihydrofolate reductase-thymidylate synthase showed weak activity with folate and no activity with pterins. Correspondingly, studies of ptr1 2 and dhfr-ts 2 mutants implicated only PTR1 in the ability of L. major to grow on a wide array of pterins. PTR1 exhibited 2000-fold less sensitivity to inhibition by methotrexate than dihydrofolate reductase-thymidylate synthase, suggesting several mechanisms by which PTR1 may compromise antifolate inhibition in wild-type Leishmania and lines bearing PTR1 amplifications. We incorporate these results into a comprehensive model of Pteridine metabolism and discuss its implications in chemotherapy of this important human pathogen.
Hongyi Nie - One of the best experts on this subject based on the ideXlab platform.
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Transcriptome Analysis of Integument Differentially Expressed Genes in the Pigment Mutant (quail) during Molting of Silkworm, Bombyx mori
2016Co-Authors: Hongyi Nie, Chun Liu, Tingcai Cheng, Mengting Zhou, Yinxia ZhangAbstract:In the silkworm Bombyx mori, pigment mutants with diverse body colors have been maintained throughout domestication for about 5000 years. The silkworm larval body color is formed through the mutual interaction of melanin, ommochromes, Pteridines and uric acid. These pigments/compounds are synthesized by the cooperative action of various genes and enzymes. Previous reports showed that melanin, ommochrome and Pteridine are increased in silkworm quail (q) mutants. To understand the pigment increase and alterations in pigment synthesis in q mutant, transcriptome profiles of the silkworm integument were investigated at 16 h after head capsule slippage in the fourth molt in q mutants and wild-type (Dazao). Compared to the wild-type, 1161 genes were differentially expressed in the q mutant. Of these modulated genes, 62.4% (725 genes) were upregulated and 37.6 % (436 genes) were downregulated in the q mutant. The molecular function of differently expressed genes was analyzed by Blast2GO. The results showed that upregulated genes were mainly involved in protein binding, small molecule binding, transferase activity, nucleic acid binding, specific DNA-binding transcription factor activity and chromatin binding, while exclusively down-expressed genes functioned in oxidoreductase activity, cofactor binding, tetrapyrrole binding, peroxidase activity and pigment binding. We focused on genes related to melanin, Pteridine and ommochrome biosynthesis; transport of uric acid; and juvenile hormone metabolism because of their importance in integument coloration during molting. This study identified differently expressed genes implicated in silkworm integumen
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Transcriptome Analysis of Integument Differentially Expressed Genes in the Pigment Mutant (quail) during Molting of Silkworm, Bombyx mori
PloS one, 2014Co-Authors: Hongyi Nie, Chun Liu, Tingcai Cheng, Mengting Zhou, Yinxia Zhang, Wu Yuqian, Qingyou XiaAbstract:In the silkworm Bombyx mori, pigment mutants with diverse body colors have been maintained throughout domestication for about 5000 years. The silkworm larval body color is formed through the mutual interaction of melanin, ommochromes, Pteridines and uric acid. These pigments/compounds are synthesized by the cooperative action of various genes and enzymes. Previous reports showed that melanin, ommochrome and Pteridine are increased in silkworm quail (q) mutants. To understand the pigment increase and alterations in pigment synthesis in q mutant, transcriptome profiles of the silkworm integument were investigated at 16 h after head capsule slippage in the fourth molt in q mutants and wild-type (Dazao). Compared to the wild-type, 1161 genes were differentially expressed in the q mutant. Of these modulated genes, 62.4% (725 genes) were upregulated and 37.6% (436 genes) were downregulated in the q mutant. The molecular function of differently expressed genes was analyzed by Blast2GO. The results showed that upregulated genes were mainly involved in protein binding, small molecule binding, transferase activity, nucleic acid binding, specific DNA-binding transcription factor activity and chromatin binding, while exclusively down-expressed genes functioned in oxidoreductase activity, cofactor binding, tetrapyrrole binding, peroxidase activity and pigment binding. We focused on genes related to melanin, Pteridine and ommochrome biosynthesis; transport of uric acid; and juvenile hormone metabolism because of their importance in integument coloration during molting. This study identified differently expressed genes implicated in silkworm integument formation and pigmentation using silkworm q mutant. The results estimated the number and types of genes that drive new integument formation.
Bakela Nare - One of the best experts on this subject based on the ideXlab platform.
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new approaches to leishmania chemotherapy Pteridine reductase 1 ptr1 as a target and modulator of antifolate sensitivity
Parasitology, 1997Co-Authors: Bakela Nare, Larry W. Hardy, James Luba, Stephen M. BeverleyAbstract:summary Leishmania and other trypanosomatid protozoa require reduced Pteridines (pterins and folates) for growth, suggesting that inhibition of these pathways could be targeted for eective chemotherapy. This goal has not yet been realized, indicating that Pteridine metabolism may be unusual in this lower eukaryote. We have investigated this possibility using both wild type and laboratory-selected antifolate-resistant strains, and with defined genetic knockouts of several Pteridine metabolic genes. In Leishmania, resistance to the antifolate methotrexate is mediated through several mechanisms singly or in combination, including alterations in transport leading to reduced drug influx, overproduction (R-region amplification) or point mutation of dihydrofolate reductase-thymidylate synthase (DHFR-TS), and amplification of a novel Pteridine reductase (PTR 1, encoded by the H-region). All of the proteins involved are potential targets for antifolate chemotherapy. Notably, parasites in which the gene encoding dihydrofolate reductase (DHFR) has been deleted (dhfr-ts’ knockouts) do not survive in animal models, validating this enzyme as a target for eective chemotherapy. However, the properties of Pteridine reductase 1 (PTR1) suggest a reason why antifolate chemotherapy has so far not been successful in trypanosomatids. PTR1, by its ability to provide reduced pterins and folates, has the potential to act as a by-pass and}or modulator of DHFR inhibition under physiological conditions. Moreover, PTR1 is less sensitive to many antifolates targeted primarily against DHFR. These findings suggest that successful antifolate chemotherapy in Leishmania will have to target simultaneously both DHFR and PTR1.
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The roles of Pteridine reductase 1 and dihydrofolate reductase-thymidylate synthase in Pteridine metabolism in the protozoan parasite Leishmania major.
The Journal of biological chemistry, 1997Co-Authors: Bakela Nare, Larry W. Hardy, Stephen M. BeverleyAbstract:Trypanosomatid protozoans depend upon exogenous sources of Pteridines (pterins or folates) for growth. A broad spectrum Pteridine reductase (PTR1) was recently identified in Leishmania major, whose sequence places it in the short chain alcohol dehydrogenase protein family although its enzymatic activities resemble dihydrofolate reductases. The properties of PTR1 suggested a role in essential Pteridine salvage as well as in antifolate resistance. To prove this, we have characterized further the properties and relative roles of PTR1 and dihydrofolate reductase-thymidylate synthase in Leishmania Pteridine metabolism, using purified enzymes and knockout mutants. Recombinant L. major and Leishmania tarentolae, and native L. major PTR1s, were tetramers of 30-kDa subunits and showed similar catalytic properties with pterins and folates (pH dependence, substrate inhibition with H2Pteridines). Unlike PTR1, dihydrofolate reductase-thymidylate synthase showed weak activity with folate and no activity with pterins. Correspondingly, studies of ptr1 2 and dhfr-ts 2 mutants implicated only PTR1 in the ability of L. major to grow on a wide array of pterins. PTR1 exhibited 2000-fold less sensitivity to inhibition by methotrexate than dihydrofolate reductase-thymidylate synthase, suggesting several mechanisms by which PTR1 may compromise antifolate inhibition in wild-type Leishmania and lines bearing PTR1 amplifications. We incorporate these results into a comprehensive model of Pteridine metabolism and discuss its implications in chemotherapy of this important human pathogen.
Yinxia Zhang - One of the best experts on this subject based on the ideXlab platform.
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Transcriptome Analysis of Integument Differentially Expressed Genes in the Pigment Mutant (quail) during Molting of Silkworm, Bombyx mori
2016Co-Authors: Hongyi Nie, Chun Liu, Tingcai Cheng, Mengting Zhou, Yinxia ZhangAbstract:In the silkworm Bombyx mori, pigment mutants with diverse body colors have been maintained throughout domestication for about 5000 years. The silkworm larval body color is formed through the mutual interaction of melanin, ommochromes, Pteridines and uric acid. These pigments/compounds are synthesized by the cooperative action of various genes and enzymes. Previous reports showed that melanin, ommochrome and Pteridine are increased in silkworm quail (q) mutants. To understand the pigment increase and alterations in pigment synthesis in q mutant, transcriptome profiles of the silkworm integument were investigated at 16 h after head capsule slippage in the fourth molt in q mutants and wild-type (Dazao). Compared to the wild-type, 1161 genes were differentially expressed in the q mutant. Of these modulated genes, 62.4% (725 genes) were upregulated and 37.6 % (436 genes) were downregulated in the q mutant. The molecular function of differently expressed genes was analyzed by Blast2GO. The results showed that upregulated genes were mainly involved in protein binding, small molecule binding, transferase activity, nucleic acid binding, specific DNA-binding transcription factor activity and chromatin binding, while exclusively down-expressed genes functioned in oxidoreductase activity, cofactor binding, tetrapyrrole binding, peroxidase activity and pigment binding. We focused on genes related to melanin, Pteridine and ommochrome biosynthesis; transport of uric acid; and juvenile hormone metabolism because of their importance in integument coloration during molting. This study identified differently expressed genes implicated in silkworm integumen
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Transcriptome Analysis of Integument Differentially Expressed Genes in the Pigment Mutant (quail) during Molting of Silkworm, Bombyx mori
PloS one, 2014Co-Authors: Hongyi Nie, Chun Liu, Tingcai Cheng, Mengting Zhou, Yinxia Zhang, Wu Yuqian, Qingyou XiaAbstract:In the silkworm Bombyx mori, pigment mutants with diverse body colors have been maintained throughout domestication for about 5000 years. The silkworm larval body color is formed through the mutual interaction of melanin, ommochromes, Pteridines and uric acid. These pigments/compounds are synthesized by the cooperative action of various genes and enzymes. Previous reports showed that melanin, ommochrome and Pteridine are increased in silkworm quail (q) mutants. To understand the pigment increase and alterations in pigment synthesis in q mutant, transcriptome profiles of the silkworm integument were investigated at 16 h after head capsule slippage in the fourth molt in q mutants and wild-type (Dazao). Compared to the wild-type, 1161 genes were differentially expressed in the q mutant. Of these modulated genes, 62.4% (725 genes) were upregulated and 37.6% (436 genes) were downregulated in the q mutant. The molecular function of differently expressed genes was analyzed by Blast2GO. The results showed that upregulated genes were mainly involved in protein binding, small molecule binding, transferase activity, nucleic acid binding, specific DNA-binding transcription factor activity and chromatin binding, while exclusively down-expressed genes functioned in oxidoreductase activity, cofactor binding, tetrapyrrole binding, peroxidase activity and pigment binding. We focused on genes related to melanin, Pteridine and ommochrome biosynthesis; transport of uric acid; and juvenile hormone metabolism because of their importance in integument coloration during molting. This study identified differently expressed genes implicated in silkworm integument formation and pigmentation using silkworm q mutant. The results estimated the number and types of genes that drive new integument formation.
