The highly conserved methionine of subunit I of the heme-copper oxidases is not at the heme-copper dinuclear center: Mutagenesis of M110 in subunit I of cytochrome bo3-type ubiquinol oxidase from Escherichia coli

AbstractA common feature within the heme-copper oxidase superfamily is the dinuclear heme-copper center. Analysis via extended X-ray absorption fine structure (EXAFS) has led to the proposal that sulfur may be bound to CUB, a component of the dinuclear center, and a highly conserved methionine (M110 in the E. coli oxidase) in subunit I has been proposed as the ligand. Recent models of subunit I, however, suggest that this residue is unlikely to be near CUB, but is predicted to be near the low spin heme component of the heme-copper oxidases. In this paper, the role of M110 is examined by spectroscopic analyses of site-directed mutants of the bo3-type oxidase from Escherichia coli. The results show that M110 is a non-essential residue and suggest that it is probably not near the heme-copper dinuclear center

Portrait des ressources en eau souterraine des îles de la Madeleine : atlas hydrogéologique

L’eau souterraine constitue l’unique source d’approvisionnement en eau potable des îles de la Madeleine. Elle est vulnérable à l’intrusion d’eau salée qui provient de la mer et aux nombreuses activités humaines qui peuvent avoir un impact sur la quantité ou la qualité de la ressource. Les changements climatiques pourraient aussi influer sur la disponibilité future de cette ressource. Une connaissance accrue sur l’eau souterraine et les aquifères qui la contiennent est nécessaire pour la mise en place de mesures de protection et de gestion durable de la ressource. La présente étude établit le Portrait des ressources en eau souterraine des îles de la Madeleine en recensant d’abord l’ensemble des connaissances existantes sur les eaux souterraines du territoire d’étude. Des données complémentaires de terrain ont ensuite été acquises. L’ensemble des informations récoltées ont enfin été intégrées et interprétées en format cartographique, principalement à l’aide d’une approche méthodologique basée sur la modélisation numérique des écoulements. Les aquifères au potentiel d’exploitation moyen à très élevé, composés principalement de grès, ont été identifiés. Ceux-ci contiennent la presque totalité de l’eau souterraine qui est actuellement exploitée et constituent la réserve principale en eau douce disponible pour les besoins futurs. Cette eau est de très bonne qualité et peut souvent être distribuée sans traitement particulier. Les aires d’alimentation de ces aquifères correspondent aux territoires qui devraient être ciblés par les mesures de protection et de gestion de la ressource. La consommation annuelle en eau douce est faible comparativement à la réalimentation annuelle des aquifères. Ainsi, la quantité d’eau contenue dans les aquifères suffit aux besoins en eau potable actuels. Les ressources en eau souterraine et les réseaux d'exploitation actuels semblent suffisants pour les besoins futurs de la municipalité selon les projections en 2050 de la hausse de la consommation et de la diminution du volume d’eau disponible causée par les changements climatiques

Portrait des ressources en eau souterraine des îles de la Madeleine : rapport scientifique

L’eau souterraine constitue l’unique source d’approvisionnement en eau potable des îles de la Madeleine. Elle est vulnérable à l’intrusion d’eau salée qui provient de la mer et aux nombreuses activités humaines qui peuvent avoir un impact sur la quantité ou la qualité de la ressource. Les changements climatiques pourraient aussi influer sur la disponibilité future de cette ressource. Une connaissance accrue sur l’eau souterraine et les aquifères qui la contiennent est nécessaire pour la mise en place de mesures de protection et de gestion durable de la ressource. La présente étude établit le Portrait des ressources en eau souterraine des îles de la Madeleine en recensant d’abord l’ensemble des connaissances existantes sur les eaux souterraines du territoire d’étude. Des données complémentaires de terrain ont ensuite été acquises. L’ensemble des informations récoltées ont enfin été intégrées et interprétées en format cartographique, principalement à l’aide d’une approche méthodologique basée sur la modélisation numérique des écoulements. Les aquifères au potentiel d’exploitation moyen à très élevé, composés principalement de grès, ont été identifiés. Ceux-ci contiennent la presque totalité de l’eau souterraine qui est actuellement exploitée et constituent la réserve principale en eau douce disponible pour les besoins futurs. Cette eau est de très bonne qualité et peut souvent être distribuée sans traitement particulier. Les aires d’alimentation de ces aquifères correspondent aux territoires qui devraient être ciblés par les mesures de protection et de gestion de la ressource. La consommation annuelle en eau douce est faible comparativement à la réalimentation annuelle des aquifères. Ainsi, la quantité d’eau contenue dans les aquifères suffit aux besoins en eau potable actuels. Les ressources en eau souterraine et les réseaux d'exploitation actuels semblent suffisants pour les besoins futurs de la municipalité selon les projections en 2050 de la hausse de la consommation et de la diminution du volume d’eau disponible causée par les changements climatiques

Consensus guidelines on analgesia and sedation in dying intensive care unit patients

BACKGROUND: Intensivists must provide enough analgesia and sedation to ensure dying patients receive good palliative care. However, if it is perceived that too much is given, they risk prosecution for committing euthanasia. The goal of this study is to develop consensus guidelines on analgesia and sedation in dying intensive care unit patients that help distinguish palliative care from euthanasia. METHODS: Using the Delphi technique, panelists rated levels of agreement with statements describing how analgesics and sedatives should be given to dying ICU patients and how palliative care should be distinguished from euthanasia. Participants were drawn from 3 panels: 1) Canadian Academic Adult Intensive Care Fellowship program directors and Intensive Care division chiefs (N = 9); 2) Deputy chief provincial coroners (N = 5); 3) Validation panel of Intensivists attending the Canadian Critical Care Trials Group meeting (N = 12). RESULTS: After three Delphi rounds, consensus was achieved on 16 statements encompassing the role of palliative care in the intensive care unit, the management of pain and suffering, current areas of controversy, and ways of improving palliative care in the ICU. CONCLUSION: Consensus guidelines were developed to guide the administration of analgesics and sedatives to dying ICU patients and to help distinguish palliative care from euthanasia

Genes, Education, and Labor Market Outcomes: Evidence from the Health and Retirement Study

Recent advances have led to the discovery of specific genetic variants that predict educational attainment. We study how these variants, summarized as a genetic score variable, are associated with human capital accumulation and labor market outcomes in the Health and Retirement Study (HRS). We demonstrate that the same genetic score that predicts education is also associated with higher wages, but only among individuals with a college education. Moreover, the genetic gradient in wages has grown in more recent birth cohorts, consistent with interactions between technological change and labor market ability. We also show that individuals who grew up in economically disadvantaged households are less likely to go to college when compared to individuals with the same genetic score, but from higher socioeconomic status households. Our findings provide support for the idea that childhood socioeconomic status is an important moderator of the economic returns to genetic endowments. Moreover, the finding that childhood poverty limits the educational attainment of high-ability individuals suggests the existence of unrealized human potential

Sirt1 Regulates Insulin Secretion by Repressing UCP2 in Pancreatic β Cells

Sir2 and insulin/IGF-1 are the major pathways that impinge upon aging in lower organisms. In Caenorhabditis elegans a possible genetic link between Sir2 and the insulin/IGF-1 pathway has been reported. Here we investigate such a link in mammals. We show that Sirt1 positively regulates insulin secretion in pancreatic β cells. Sirt1 represses the uncoupling protein (UCP) gene UCP2 by binding directly to the UCP2 promoter. In β cell lines in which Sirt1 is reduced by SiRNA, UCP2 levels are elevated and insulin secretion is blunted. The up-regulation of UCP2 is associated with a failure of cells to increase ATP levels after glucose stimulation. Knockdown of UCP2 restores the ability to secrete insulin in cells with reduced Sirt1, showing that UCP2 causes the defect in glucose-stimulated insulin secretion. Food deprivation induces UCP2 in mouse pancreas, which may occur via a reduction in NAD (a derivative of niacin) levels in the pancreas and down-regulation of Sirt1. Sirt1 knockout mice display constitutively high UCP2 expression. Our findings show that Sirt1 regulates UCP2 in β cells to affect insulin secretion

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery