Complex I dysfunction underlies the glycolytic switch in pulmonary hypertensive smooth muscle cells.

ATP is essential for cellular function and is usually produced through oxidative phosphorylation. However, mitochondrial dysfunction is now being recognized as an important contributing factor in the development cardiovascular diseases, such as pulmonary hypertension (PH). In PH there is a metabolic change from oxidative phosphorylation to mainly glycolysis for energy production. However, the mechanisms underlying this glycolytic switch are only poorly understood. In particular the role of the respiratory Complexes in the mitochondrial dysfunction associated with PH is unresolved and was the focus of our investigations. We report that smooth muscle cells isolated from the pulmonary vessels of rats with PH (PH-PASMC), induced by a single injection of monocrotaline, have attenuated mitochondrial function and enhanced glycolysis. Further, utilizing a novel live cell assay, we were able to demonstrate that the mitochondrial dysfunction in PH-PASMC correlates with deficiencies in the activities of Complexes I-III. Further, we observed that there was an increase in mitochondrial reactive oxygen species generation and mitochondrial membrane potential in the PASMC isolated from rats with PH. We further found that the defect in Complex I activity was due to a loss of Complex I assembly, although the assembly of Complexes II and III were both maintained. Thus, we conclude that loss of Complex I assembly may be involved in the switch of energy metabolism in smooth muscle cells to glycolysis and that maintaining Complex I activity may be a potential therapeutic target for the treatment of PH

Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung.

There is increasing interest in the potential for metabolic profiling to evaluate the progression of pulmonary hypertension (PH). However, a detailed analysis of the metabolic changes in lungs at the early stage of PH, characterized by increased pulmonary artery pressure but prior to the development of right ventricle hypertrophy and failure, is lacking in a preclinical animal model of PH. Thus, we undertook a study using rats 14 days after exposure to monocrotaline (MCT), to determine whether we could identify early stage metabolic changes prior to the manifestation of developed PH. We observed changes in multiple pathways associated with the development of PH, including activated glycolysis, increased markers of proliferation, disruptions in carnitine homeostasis, increased inflammatory and fibrosis biomarkers, and a reduction in glutathione biosynthesis. Further, our global metabolic profile data compare favorably with prior work carried out in humans with PH. We conclude that despite the MCT-model not recapitulating all the structural changes associated with humans with advanced PH, including endothelial cell proliferation and the formation of plexiform lesions, it is very similar at a metabolic level. Thus, we suggest that despite its limitations it can still serve as a useful preclinical model for the study of PH

Emotions in business-to-business service relationships

Emotion in business-to-business service relationships regarding cargo services is explored. The service relationship is characterised by mutual trust and cooperation. Contact is mainly via telephone or e-mail with some face-to-face interactions and participants providing a complex, multi-skilled seamless service. Experience rather than training plays a vital role with long-term service relationships built up and maintained. Emotional sensitivity is acquired partly by experience and a repeat customer base but mainly through a genuine desire to help and get to know others. In contrast to the view of emotional labour bringing managerial control or adverse affects to service staff, the emotion engendered by this work is authentic expression bringing personal satisfaction

Recording advances for neural prosthetics

An important challenge for neural prosthetics research is to record from populations of neurons over long periods of time, ideally for the lifetime of the patient. Two new advances toward this goal are described, the use of local field potentials (LFPs) and autonomously positioned recording electrodes. LFPs are the composite extracellular potential field from several hundreds of neurons around the electrode tip. LFP recordings can be maintained for longer periods of time than single cell recordings. We find that similar information can be decoded from LFP and spike recordings, with better performance for state decodes with LFPs and, depending on the area, equivalent or slightly less than equivalent performance for signaling the direction of planned movements. Movable electrodes in microdrives can be adjusted in the tissue to optimize recordings, but their movements must be automated to be a practical benefit to patients. We have developed automation algorithms and a meso-scale autonomous electrode testbed, and demonstrated that this system can autonomously isolate and maintain the recorded signal quality of single cells in the cortex of awake, behaving monkeys. These two advances show promise for developing very long term recording for neural prosthetic applications

More than a cognitive experience: unfamiliarity, invalidation, and emotion in organizational learning

Literature on organizational learning (OL) lacks an integrative framework that captures the emotions involved as OL proceeds. Drawing on personal construct theory, we suggest that organizations learn where their members reconstrue meaning around questions of strategic significance for the organization. In this 5-year study of an electronics company, we explore the way in which emotions change as members perceive progress or a lack of progress around strategic themes. Our framework also takes into account whether OL involves experiences that are familiar or unfamiliar and the implications for emotions. We detected similar patterns of emotion arising over time for three different themes in our data, thereby adding to OL perspectives that are predominantly cognitive in orientation

Organizational learning and emotion: constructing collective meaning in support of strategic themes

Missing in the organizational learning literature is an integrative framework that reflects the emotional as well as the cognitive dynamics involved. Here, we take a step in this direction by focusing in depth over time (five years) on a selected organization which manufactures electronic equipment for the office industry. Drawing on personal construct theory, we define organizational learning as the collective re-construal of meaning in the direction of strategically significant themes. We suggest that emotions arise as members reflect on progress or lack of progress in achieving organizational learning. Our evidence suggests that invalidation – where organizational learning fails to correspond with expectations – gives rise to anxiety and frustration, while validation – where organizational learning is aligned with or exceeds expectations – evokes comfort or excitement. Our work aims to capture the key emotions involved as organizational learning proceeds

The golden circle: A way of arguing and acting about technology in the London ambulance service

This paper analyses the way in which the London Ambulance Service recovered from the events of October 1992, when it implemented a computer-aided despatch system (LASCAD) that remained in service for less than two weeks. It examines the enactment of a programme of long-term organizational change, focusing on the implementation of an alternative computer system in 1996. The analysis in this paper is informed by actor-network theory, both by an early statement of this approach developed by Callon in the sociology of translation, and also by concepts and ideas from Latour’s more recent restatement of his own position. The paper examines how alternative interests emerged and were stabilized over time, in a way of arguing and acting among key players in the change programme, christened the Golden Circle. The story traces four years in the history of the London Ambulance Service, from the aftermath of October 1992 through the birth of the Golden Circle to the achievement of National Health Service (NHS) trust status. LASCAD was the beginning of the story, this is the middle, an end lies in the future, when the remaining elements of the change programme are enacted beyond the Golden Circle

Surveillance sanitaire des cocoteraies adultes en Afrique de l'Ouest. I. Contrôles ordinaires

La plupart des ravageurs connus dans les cocoteraies d'Afrique de l'Ouest passent le plus souvent inaperçus, bien qu'ils soient toujours présents. Dans certaines conditions, difficiles à définir, il y a pullulation d'un ou de plusieurs d'entre eux et, en conséquence, des dégâts importants peuvent alors se produire. Des contrôles sanitaires fréquents sont nécessaires pour la conduite de la méthode de lutte intégrée, généralement adoptée à présent en défense des cultures, ce qui suppose une bonne connaissance des ravageurs, de leur biologie et de leurs ennemis naturels. Comme pour le palmier à huile, il y a deux types de contrôles phytosanitaires : - les contrôles ordinaires, décrits dans ces " Conseils ", qui permettent de suivre l'ensemble des populations de ravageurs, d'insectes auxiliaires, et de détecter toute anomalie susceptible de se traduire par des dégâts préjudiciables ; - les contrôles spéciaux, spécifiques d'un ravageur donné, qui feront l'objet d'une autre page de Pratique agricole (1 ), et sont réalisés sur un échantillon d'observation plus important. Ils permettent de suivre plus précisément l'évolution de ce ravageur, l'intensité et l'étendue des dégâts qu'il provoque. Toutefois, la décision d'intervention par traitement ne peut être prise à bon escient qu'après examen attentif des résultats d'un ou de plusieurs contrôles spéciaux réalisés après détection de l'attaque par un contrôle ordinaire. La présente " Page de pratique agricole " traite de la conduite des contrôles phytosanitaires en cocoteraie de plus de quatre ans, entrée en production. La surveillance des jeunes cocoteraies, beaucoup plus vulnérables, fera également l'objet d'autres " Conseils ". (Résumé d'auteur