31 research outputs found

    Triose Phosphate Isomerase Deficiency Is Caused by Altered Dimerization–Not Catalytic Inactivity–of the Mutant Enzymes

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    Triosephosphate isomerase (TPI) deficiency is an autosomal recessive disorder caused by various mutations in the gene encoding the key glycolytic enzyme TPI. A drastic decrease in TPI activity and an increased level of its substrate, dihydroxyacetone phosphate, have been measured in unpurified cell extracts of affected individuals. These observations allowed concluding that the different mutations in the TPI alleles result in catalytically inactive enzymes. However, despite a high occurrence of TPI null alleles within several human populations, the frequency of this disorder is exceptionally rare. In order to address this apparent discrepancy, we generated a yeast model allowing us to perform comparative in vivo analyses of the enzymatic and functional properties of the different enzyme variants. We discovered that the majority of these variants exhibit no reduced catalytic activity per se. Instead, we observed, the dimerization behavior of TPI is influenced by the particular mutations investigated, and by the use of a potential alternative translation initiation site in the TPI gene. Additionally, we demonstrated that the overexpression of the most frequent TPI variant, Glu104Asp, which displays altered dimerization features, results in diminished endogenous TPI levels in mammalian cells. Thus, our results reveal that enzyme deregulation attributable to aberrant dimerization of TPI, rather than direct catalytic inactivation of the enzyme, underlies the pathogenesis of TPI deficiency. Finally, we discovered that yeast cells expressing a TPI variant exhibiting reduced catalytic activity are more resistant against oxidative stress caused by the thiol-oxidizing reagent diamide. This observed advantage might serve to explain the high allelic frequency of TPI null alleles detected among human populations

    Chitosan–Starch–Keratin composites: Improving thermo-mechanical and degradation properties through chemical modification

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    The lysozyme test shows an improved in the degradability rate, the weight loss of the films at 21 days is reduced from 73 % for chitosan-starch matrix up to 16 % for the composites with 5wt% of quill; but all films show a biodegradable character depending on keratin type and chemical modification. The outstanding properties related to the addition of treated keratin materials show that these natural composites are a remarkable alternative to potentiat-ing chitosan–starch films with sustainable featuresChitosan–starch polymers are reinforced with different keratin materials obtained from chicken feather. Keratin materials are treated with sodium hydroxide; the modified surfaces are rougher in comparison with untreated surfaces, observed by Scanning Electron Microscopy. The results obtained by Differential Scanning Calorimetry show an increase in the endothermic peak related to water evaporation of the films from 92 °C (matrix) up to 102–114 °C (reinforced composites). Glass transition temperature increases from 126 °C in the polymer matrix up to 170–200 °C for the composites. Additionally, the storage modulus in the composites is enhanced up to 1614 % for the composites with modified ground quill, 2522 % for composites with modified long fiber and 3206 % for the composites with modified short fiber. The lysozyme test shows an improved in the degradability rate, the weight loss of the films at 21 days is reduced from 73 % for chitosan-starch matrix up to 16 % for the composites with 5wt% of quill; but all films show a biodegradable character depending on keratin type and chemical modification. The outstanding properties related to the addition of treated keratin materials show that these natural composites are a remarkable alternative to potentiat-ing chitosan–starch films with sustainable featuresUniversidad Autónoma del Estado de México Tecnológico Nacional de México, Instituto Tecnológico de Querétaro Universidad Nacional Autónoma de México Tecnológico Nacional de México, Instituto Tecnológico de Celaya Universidad Autónoma de Cd. Juáre

    The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) consortium: A collaborative cognitive and neuroimaging genetics project

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    BACKGROUND: Schizophrenia has a large genetic component, and the pathways from genes to illness manifestation are beginning to be identified. The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) Consortium aims to clarify the role of genetic variation in brain abnormalities underlying schizophrenia. This article describes the GENUS Consortium sample collection. METHODS: We identified existing samples collected for schizophrenia studies consisting of patients, controls, and/or individuals at familial high-risk (FHR) for schizophrenia. Samples had single nucleotide polymorphism (SNP) array data or genomic DNA, clinical and demographic data, and neuropsychological and/or brain magnetic resonance imaging (MRI) data. Data were subjected to quality control procedures at a central site. RESULTS: Sixteen research groups contributed data from 5199 psychosis patients, 4877 controls, and 725 FHR individuals. All participants have relevant demographic data and all patients have relevant clinical data. The sex ratio is 56.5% male and 43.5% female. Significant differences exist between diagnostic groups for premorbid and current IQ (both p10,000 participants. The breadth of data across clinical, genetic, neuropsychological, and MRI modalities provides an important opportunity for elucidating the genetic basis of neural processes underlying schizophrenia
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