The Experts below are selected from a list of 186 Experts worldwide ranked by ideXlab platform
Phillip A Yates - One of the best experts on this subject based on the ideXlab platform.
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purine responsive expression of the leishmania donovani nt3 purine nucleobase transporter is mediated by a conserved rna stem loop
Journal of Biological Chemistry, 2020Co-Authors: Haley M Licon, Phillip A YatesAbstract:The ability to modulate gene expression in response to changes in the host environment is essential for survival of the kinetoplastid parasite Leishmania Unlike most eukaryotes, gene expression in kinetoplastids is predominately regulated posttranscriptionally. Consequently, RNA-binding proteins and mRNA-Encoded Sequence elements serve as primary determinants of gene regulation in these organisms; however, few have defined roles in specific stress response pathways. Leishmania species cannot synthesize purines de novo and must scavenge these essential nutrients from the host. Leishmania have evolved a robust stress response to withstand sustained periods of purine scarcity during their life cycle. The purine nucleobase transporter LdNT3 is among the most substantially up-regulated proteins in purine-starved Leishmania donovani parasites. Here we report that the posttranslational stability of the LdNT3 protein is unchanged in response to purine starvation. Instead, LdNT3 up-regulation is primarily mediated by a 33-nucleotide-long Sequence in the LdNT3 mRNA 3' UTR that is predicted to adopt a stem-loop structure. Although this Sequence is highly conserved within the mRNAs of orthologous transporters in multiple kinetoplastid species, putative stem-loops from L. donovani and Trypanosoma brucei nucleobase transporter mRNAs were not functionally interchangeable for purine-responsive regulation. Through mutational analysis of the element, we demonstrate that species specificity is attributable to just three variant bases within the predicted loop. Finally, we provide evidence that the abundance of the trans-acting factor that binds the LdNT3 stem-loop in vivo is substantially higher than required for regulation of LdNT3 alone, implying a potential role in regulating other purine-responsive genes.
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purine responsive expression of the leishmania donovani nt3 purine nucleobase transporter is mediated by a conserved rna stem loop
bioRxiv, 2020Co-Authors: Meredith H Licon, Phillip A YatesAbstract:The ability to modulate gene expression in response to changes in the host environment is essential for survival of the kinetoplastid parasite Leishmania. Unlike most eukaryotes, gene expression in kinetoplastids is predominately regulated post-transcriptionally. Consequently, RNA-binding proteins (RBPs) and mRNA-Encoded Sequence elements serve as primary determinants of gene regulation in these organisms; however, few have been ascribed roles in specific stress-response pathways. Leishmania lack the capacity for de novo purine synthesis and must scavenge these essential nutrients from the host. Leishmania have evolved a robust stress response to withstand sustained periods of purine scarcity during their lifecycle. The purine nucleobase transporter, LdNT3, is among the most substantially upregulated proteins in purine-starved L. donovani. Here we report that the post-translational stability of the LdNT3 protein is unchanged in response to purine starvation. Instead, LdNT3 upregulation is primarily mediated by a 33 nucleotide (nt) Sequence in the LdNT3 mRNA 39-untranslated region that is predicted to adopt a stem-loop structure. While this Sequence is highly conserved within the mRNAs of orthologous transporters in multiple kinetoplastid species, putative stem-loops from L. donovani and Trypanosoma brucei nucleobase transporter mRNAs are not functionally interchangeable for purine-responsive regulation. Through mutational analysis of the element, we demonstrate that species specificity is attributable to just three variant bases within the predicted loop. Finally, we provide evidence that the abundance of the trans-acting factor that binds the LdNT3 stem-loop in vivo is substantially higher than required for regulation of LdNT3 alone, implying a potential role in regulating other purine-responsive genes.
Mitchel Weintraub - One of the best experts on this subject based on the ideXlab platform.
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ICASSP - West: Word Encoded Sequence Transducers
ICASSP 2019 - 2019 IEEE International Conference on Acoustics Speech and Signal Processing (ICASSP), 2019Co-Authors: Ehsan Variani, Ananda Theertha Suresh, Mitchel WeintraubAbstract:Most of the parameters in large vocabulary models are used in embedding layer to map categorical features to vectors and in softmax layer for classification weights. This is a bottleneck in memory constraint on-device training applications like federated learning and on-device inference applications like automatic speech recognition (ASR). One way of compressing the embedding and softmax layers is to substitute larger units such as words with smaller sub-units such as characters. However, often the sub-unit models perform poorly compared to the larger unit models. We propose WEST, an algorithm for encoding categorical features and output classes with a Sequence of random or domain dependent sub-units and demonstrate that this transduction can lead to significant compression without compromising performance.
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WEST: Word Encoded Sequence Transducers
arXiv: Learning, 2018Co-Authors: Ehsan Variani, Ananda Theertha Suresh, Mitchel WeintraubAbstract:Most of the parameters in large vocabulary models are used in embedding layer to map categorical features to vectors and in softmax layer for classification weights. This is a bottle-neck in memory constraint on-device training applications like federated learning and on-device inference applications like automatic speech recognition (ASR). One way of compressing the embedding and softmax layers is to substitute larger units such as words with smaller sub-units such as characters. However, often the sub-unit models perform poorly compared to the larger unit models. We propose WEST, an algorithm for encoding categorical features and output classes with a Sequence of random or domain dependent sub-units and demonstrate that this transduction can lead to significant compression without compromising performance. WEST bridges the gap between larger unit and sub-unit models and can be interpreted as a MaxEnt model over sub-unit features, which can be of independent interest.
Adolfo Borges - One of the best experts on this subject based on the ideXlab platform.
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diversity of long chain toxins in tityus zulianus and tityus discrepans venoms scorpiones buthidae molecular immunological and mass spectral analyses
Comparative Biochemistry and Physiology C-toxicology & Pharmacology, 2006Co-Authors: Adolfo Borges, Marcelo J Alfonzo, Carmen C Garcia, Elizabeth Lugo, Michael J Jowers, Huub Op Den J M CampAbstract:In Venezuela, stings by Tityus zulianus scorpions produce cardiorespiratory arrest, whereas envenoming by Tityus discrepans involves gastrointestinal/pancreatic complications, suggesting structural and/or functional differences. We sought to compare their toxin repertoires through immunological, molecular, and mass spectral analyses. First, in vivo tests showed that neutralization of T. zulianus venom toxicity by the anti-T. discrepans antivenom was not complete. To compare T. discrepans and T. zulianus long-chain (sodium channel-active) toxins, their most toxic Sephadex® G-50 fractions, TdII and TzII, were subjected to acid–urea PAGE, which showed differences in composition. Amplification of toxin-encoding mRNAs using a leader peptide-based oligonucleotide rendered cDNAs representing twelve T. discrepans and two T. zulianus distinct toxin transcripts, including only one shared component, indicating divergence between T. zulianus and T. discrepans 5′ region-Encoded, toxin signal peptides. A 3′-UTR polymorphism was also noticed among the transcripts encoding shared components Tz1 and Td4. MALDI–TOF MS profiling of TdII and TzII produced species-specific spectra, with seven of the individual masses matching those predicted by cDNA sequencing. Phylogenetic analysis showed that the unique T. zulianus transcript-Encoded Sequence, Tz2, is structurally related to Tityus serrulatus and Centruroides toxins. Together with previous reports, this work indicates that T. zulianus and T. discrepans toxin repertoires differ structurally and functionally.
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isolation molecular cloning and functional characterization of a novel β toxin from the venezuelan scorpion tityus zulianus
Toxicon, 2004Co-Authors: Adolfo Borges, Marcelo J Alfonzo, Carmen C Garcia, Nena J Winand, Enrico Leipold, Stefan H HeinemannAbstract:Sting in children by Tityus zulianus scorpions (western Venezuela) often produces cardiorespiratory arrest and death by pulmonary oedema. To assess its toxicity, lethality in mice of T. zulianus soluble venom was determined. Toxin composition was studied by fractionating the crude venom through reversed-phase HPLC. The most abundant peptide, Tz1, was purified further and its N-terminal Sequence, amino acid composition and molecular mass (by electron-spray ionization mass spectrometry) determined. In the presence of Tz1, activation of recombinant rat skeletal muscle sodium channels (NaV1.4) was shifted about 35 mV in the hyperpolarizing direction in a prepulse-dependent manner. This typical β-toxin effect had an apparent EC50 of 3.5 μM. A cDNA Sequence encoding Tz1 was isolated from T. zulianus venom gland RNA using a combination of 5′- and 3′-RACE PCR. Analysis of the Encoded Sequence indicated that Tz1 is the processed product of a precursor containing: (i) a 20-residue long leader peptide; (ii) the amino acid Sequence of the mature toxin (64 residues); and (iii) an extra Gly-Lys tail at the C-terminus, probably removed post-translationally. A comparison of Tz1 with Tityus serrulatus β-toxin Ts1 revealed that some of the non-conservative replacements in Tz1 lie in regions potentially involved in receptor recognition.
Haley M Licon - One of the best experts on this subject based on the ideXlab platform.
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purine responsive expression of the leishmania donovani nt3 purine nucleobase transporter is mediated by a conserved rna stem loop
Journal of Biological Chemistry, 2020Co-Authors: Haley M Licon, Phillip A YatesAbstract:The ability to modulate gene expression in response to changes in the host environment is essential for survival of the kinetoplastid parasite Leishmania Unlike most eukaryotes, gene expression in kinetoplastids is predominately regulated posttranscriptionally. Consequently, RNA-binding proteins and mRNA-Encoded Sequence elements serve as primary determinants of gene regulation in these organisms; however, few have defined roles in specific stress response pathways. Leishmania species cannot synthesize purines de novo and must scavenge these essential nutrients from the host. Leishmania have evolved a robust stress response to withstand sustained periods of purine scarcity during their life cycle. The purine nucleobase transporter LdNT3 is among the most substantially up-regulated proteins in purine-starved Leishmania donovani parasites. Here we report that the posttranslational stability of the LdNT3 protein is unchanged in response to purine starvation. Instead, LdNT3 up-regulation is primarily mediated by a 33-nucleotide-long Sequence in the LdNT3 mRNA 3' UTR that is predicted to adopt a stem-loop structure. Although this Sequence is highly conserved within the mRNAs of orthologous transporters in multiple kinetoplastid species, putative stem-loops from L. donovani and Trypanosoma brucei nucleobase transporter mRNAs were not functionally interchangeable for purine-responsive regulation. Through mutational analysis of the element, we demonstrate that species specificity is attributable to just three variant bases within the predicted loop. Finally, we provide evidence that the abundance of the trans-acting factor that binds the LdNT3 stem-loop in vivo is substantially higher than required for regulation of LdNT3 alone, implying a potential role in regulating other purine-responsive genes.
Carmen C Garcia - One of the best experts on this subject based on the ideXlab platform.
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diversity of long chain toxins in tityus zulianus and tityus discrepans venoms scorpiones buthidae molecular immunological and mass spectral analyses
Comparative Biochemistry and Physiology C-toxicology & Pharmacology, 2006Co-Authors: Adolfo Borges, Marcelo J Alfonzo, Carmen C Garcia, Elizabeth Lugo, Michael J Jowers, Huub Op Den J M CampAbstract:In Venezuela, stings by Tityus zulianus scorpions produce cardiorespiratory arrest, whereas envenoming by Tityus discrepans involves gastrointestinal/pancreatic complications, suggesting structural and/or functional differences. We sought to compare their toxin repertoires through immunological, molecular, and mass spectral analyses. First, in vivo tests showed that neutralization of T. zulianus venom toxicity by the anti-T. discrepans antivenom was not complete. To compare T. discrepans and T. zulianus long-chain (sodium channel-active) toxins, their most toxic Sephadex® G-50 fractions, TdII and TzII, were subjected to acid–urea PAGE, which showed differences in composition. Amplification of toxin-encoding mRNAs using a leader peptide-based oligonucleotide rendered cDNAs representing twelve T. discrepans and two T. zulianus distinct toxin transcripts, including only one shared component, indicating divergence between T. zulianus and T. discrepans 5′ region-Encoded, toxin signal peptides. A 3′-UTR polymorphism was also noticed among the transcripts encoding shared components Tz1 and Td4. MALDI–TOF MS profiling of TdII and TzII produced species-specific spectra, with seven of the individual masses matching those predicted by cDNA sequencing. Phylogenetic analysis showed that the unique T. zulianus transcript-Encoded Sequence, Tz2, is structurally related to Tityus serrulatus and Centruroides toxins. Together with previous reports, this work indicates that T. zulianus and T. discrepans toxin repertoires differ structurally and functionally.
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isolation molecular cloning and functional characterization of a novel β toxin from the venezuelan scorpion tityus zulianus
Toxicon, 2004Co-Authors: Adolfo Borges, Marcelo J Alfonzo, Carmen C Garcia, Nena J Winand, Enrico Leipold, Stefan H HeinemannAbstract:Sting in children by Tityus zulianus scorpions (western Venezuela) often produces cardiorespiratory arrest and death by pulmonary oedema. To assess its toxicity, lethality in mice of T. zulianus soluble venom was determined. Toxin composition was studied by fractionating the crude venom through reversed-phase HPLC. The most abundant peptide, Tz1, was purified further and its N-terminal Sequence, amino acid composition and molecular mass (by electron-spray ionization mass spectrometry) determined. In the presence of Tz1, activation of recombinant rat skeletal muscle sodium channels (NaV1.4) was shifted about 35 mV in the hyperpolarizing direction in a prepulse-dependent manner. This typical β-toxin effect had an apparent EC50 of 3.5 μM. A cDNA Sequence encoding Tz1 was isolated from T. zulianus venom gland RNA using a combination of 5′- and 3′-RACE PCR. Analysis of the Encoded Sequence indicated that Tz1 is the processed product of a precursor containing: (i) a 20-residue long leader peptide; (ii) the amino acid Sequence of the mature toxin (64 residues); and (iii) an extra Gly-Lys tail at the C-terminus, probably removed post-translationally. A comparison of Tz1 with Tityus serrulatus β-toxin Ts1 revealed that some of the non-conservative replacements in Tz1 lie in regions potentially involved in receptor recognition.