Deciphering the number and location of active sites in the monomeric glyoxalase I of Zea mays

Detoxification of methylglyoxal, a toxic by-product of central sugar metabolism, is a major issue for all forms of life. The glyoxalase pathway evolved to effectively convert methylglyoxal into d-lactate via a glutathione hemithioacetal intermediate. Recently, we have shown that the monomeric glyoxalase I from maize exhibits a symmetric fold with two cavities, potentially harboring two active sites, in analogy with homodimeric enzyme surrogates. Here we confirm that only one of the two cavities exhibits glyoxalase I activity and show that it adopts a tunnel-shaped structure upon substrate binding. Such conformational change gives rise to independent binding sites for glutathione and methylglyoxal in the same active site, with important implications for the molecular reaction mechanism, which has been a matter of debate for several decades. Database: Structural data are available in The Protein Data Bank database under the accession numbers 6BNN, 6BNX, and 6BNZ.Fil: Gonzalez, Javier Marcelo. Universidad Nacional de Santiago del Estero. Instituto de Bionanotecnología del Noa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Bionanotecnología del Noa; ArgentinaFil: Agostini, Romina Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro de Estudios Fotosintéticos y Bioquímicos. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Estudios Fotosintéticos y Bioquímicos; ArgentinaFil: Alvarez, Clarisa Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro de Estudios Fotosintéticos y Bioquímicos. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Estudios Fotosintéticos y Bioquímicos; ArgentinaFil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Andreo, Carlos Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro de Estudios Fotosintéticos y Bioquímicos. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Estudios Fotosintéticos y Bioquímicos; ArgentinaFil: Campos Bermudez, Valeria Alina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro de Estudios Fotosintéticos y Bioquímicos. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Estudios Fotosintéticos y Bioquímicos; Argentin

Montana Kaimin, November 6, 1980

Student newspaper of the University of Montana, Missoula.https://scholarworks.umt.edu/studentnewspaper/8136/thumbnail.jp

1964-04-30 Morehead News

Morehead News published on April 30, 1964

Evidências do uso da tecnologia na promoção do funcionamento e participação social de pessoas com comprometimento cognitivo leve: uma Scoping Review

Para pessoas de qualquer idade gerenciar o uso da tecnologia é fundamental para uma manter uma vida autónoma e participar ativamente da comunidade, uma vez que elas estão cada vez mais presentes na vida cotidiana. A incorporação da tecnologia nas atividades de vida diária, por exemplo ao fazer compras com o cartão de crédito/débito e PIN, elevadores, fechadura de banheiro publico, bomba de combustível, máquinas de vendas automáticas, self checkout, implica maior capacidade de adaptação, maior esforço e capacidade cognitiva. Tantas e tão variadas tecnologias podem representar um obstáculo, principalmente para pessoas com comprometimento cognitivo, no desempenho das atividades de vida diária, no funcionamento e na participação social. Este estudo tem como objetivo mapear as evidências disponíveis e quais os domínios estão associados ao uso da tecnologia diária na promoção do funcionamento e participação social de pessoas com comprometimento cognitivo leve. Esta revisão de escopo pesquisou sistematicamente as evidências publicadas em 5 bases de dados relevantes, registos de ensaios e literatura cinzenta, no intervalo entre 1999 e 2021. Foram incluídas as publicações que utilizaram a população com comprometimento cognitivo leve, àquelas que avaliaram a utilização da tecnologia diária, a participação social, as características psicossociais e ou perfis cognitivos dos participantes, sendo excluídos os estudos secundários, as publicações que utilizaram tecnologias assistivas, tecnologias que não se enquadrem como de uso diário por exemplo, realidade virtual ou serious games, e tecnologias para o auto gerenciamento da doença e promoção de saúde. Os resultados incluíram 44 evidências, sendo 15 delas publicadas nos últimos dois anos, que utilizaram 24 instrumentos de avaliação em 11 países. Revelaram entre outras características, a importância da avaliação do domínio psicológico e social no maior ou menor uso da tecnologia (95,6% dos estudos incluíram alguma variável destes domínios), para além dos aspetos da usabilidade, aceitabilidade e relevância da tecnologia nesta população. A contribuição única deste estudo é ampliar os conhecimentos acerca dos fatores cognitivos, sociais e ambientais que permeiam a utilização da tecnologia no funcionamento e a participação social, a fim de detectar precocemente mudanças comportamentais, de personalidade e os déficits funcionais oriundos quer do gerenciamento da tecnologia quer dos próprios déficits cognitivos.For people of any age, managing the use of technology is essential to maintain an autonomous life and actively participate in the community, as they are increasingly present in everyday life. For example, when shopping with credit/debit card and PIN, elevators, public restroom installation, fuel pump, vending machines, self checkout, adaptability, implies greater effort and cognitive ability. So many and so varied technologies can represent an obstacle, especially for people with cognitive impairment, in the performance of activities of daily living, functioning and social participation. This study aims to map the available research and which domains are associated with the use of everyday technology to promote functioning and participation at the mild cognitive impairment of people. This scoping review is done as analyzes published at intervals of 5 relevant databases, trial records and literature between 1999 and 2021, publications that used the population with mild cognitive impairment, those that evaluated the use of daily technology, social participation, psychosocial characteristics and/or cognitive profiles of the participants were included, excluding secondary studies, publications that used assistive technologies, that do not fit into daily use, for example, virtual reality or serious games, and technologies for self-management of the disease and health promotion. The results included 44 analyses, 15 of which were published in the last two years, which are using 24 assessment instruments in 11 countries. Among other characteristics, they reveal the importance of evaluating the neuropsychological domain and use technology (88.4% of the studies include some psychological variables), in addition to the aspects of usability, acceptability and technology in this population. The unique contribution of this study is to expand the knowledge of the cognitive, social and environmental factors that permeate the use of technology in functioning and social participation, in order to detect early behavioral changes, personality and functional deficits arising either from the management of technology. or from the cognitive deficits themselves. Keywords: Everyday Technology, Mild Cognitive Impairment, Social Cognition, Social Participation, Social Functionalit

The role of the kidney in diabetic thiamine deficiency

Diabetes is a chronic epidemic compounded by a burden of vascular complications including diabetic nephropathy. Diabetic nephropathy affects ~40% of patients and is characterised by increased urinary albumin excretion and decreased glomerular filtration rate. Diabetic patients exhibit ~75% decreased plasma thiamine concentration, linked to increased renal thiamine clearance. In streptozotocin-induced diabetic rats, decreased plasma thiamine concentration was also associated with a reduction in expression and activity of transketolase. Transketolase is a thiamine pyrophosphate-dependent enzyme and a critical component of the reductive pentose phosphate pathway, a metabolic pathway leading from glycolysis involved with the synthesis of ribose sugars. It is proposed that increasing the relative flux of glucose through the pentose phosphate pathway can ameliorate hyperglycaemic damage. This thesis investigates mechanisms mediating the increased renal thiamine clearance and the effects of thiamine therapy on type 2 diabetic patients with nephropathy. The hypothesis that hyperglycaemia increases flux through the hexosamine pathway, leading to increased O-glycosylation of the transcription factor Sp1 and subsequent decreased expression of thiamine transporters is investigated. Thiamine transporters in normal human kidney sections were found to be localised to the proximal tubule. Investigations in primary cultures of human proximal tubule epithelial cells and the HK-2 cell line have shown that there is a decreased expression (-48 to -80%) and abundance (-52 to -77%) of thiamine transporters in cells cultured in high glucose concentrations (26mM) with respect to low glucose concentrations (5 mM). There is only limited evidence supporting the involvement of the hexosamine pathway in these decreases. A double-blind, placebo-controlled study investigated the effect of thiamine supplementation on type 2 diabetic patients with microalbuminuria. Thiamine therapy restored plasma thiamine concentrations from 11nM to 98nM, exceeding the published median concentration observed in normal patients (64nM). After three months, thiamine therapy, but not placebo, caused a decrease in the urinary albumin excretion rate relative to baseline (-18 mg day-1). These results show promise for thiamine as a therapy for diabetic nephropathy

The role of the kidney in diabetic thiamine deficiency

Diabetes is a chronic epidemic compounded by a burden of vascular complications including diabetic nephropathy. Diabetic nephropathy affects ~40% of patients and is characterised by increased urinary albumin excretion and decreased glomerular filtration rate. Diabetic patients exhibit ~75% decreased plasma thiamine concentration, linked to increased renal thiamine clearance. In streptozotocin-induced diabetic rats, decreased plasma thiamine concentration was also associated with a reduction in expression and activity of transketolase. Transketolase is a thiamine pyrophosphate-dependent enzyme and a critical component of the reductive pentose phosphate pathway, a metabolic pathway leading from glycolysis involved with the synthesis of ribose sugars. It is proposed that increasing the relative flux of glucose through the pentose phosphate pathway can ameliorate hyperglycaemic damage. This thesis investigates mechanisms mediating the increased renal thiamine clearance and the effects of thiamine therapy on type 2 diabetic patients with nephropathy. The hypothesis that hyperglycaemia increases flux through the hexosamine pathway, leading to increased O-glycosylation of the transcription factor Sp1 and subsequent decreased expression of thiamine transporters is investigated. Thiamine transporters in normal human kidney sections were found to be localised to the proximal tubule. Investigations in primary cultures of human proximal tubule epithelial cells and the HK-2 cell line have shown that there is a decreased expression (-48 to -80%) and abundance (-52 to -77%) of thiamine transporters in cells cultured in high glucose concentrations (26mM) with respect to low glucose concentrations (5 mM). There is only limited evidence supporting the involvement of the hexosamine pathway in these decreases. A double-blind, placebo-controlled study investigated the effect of thiamine supplementation on type 2 diabetic patients with microalbuminuria. Thiamine therapy restored plasma thiamine concentrations from 11nM to 98nM, exceeding the published median concentration observed in normal patients (64nM). After three months, thiamine therapy, but not placebo, caused a decrease in the urinary albumin excretion rate relative to baseline (-18 mg day-1). These results show promise for thiamine as a therapy for diabetic nephropathy.EThOS - Electronic Theses Online ServiceGBUnited Kingdo