Calmodulin/KCa3.1 channel interactions as determinant to the KCa3.1 Ca2+ dependent gating : theoretical and experimental analyses

Differentes études ont montré que la sensibilité au Ca2+ du canal KCa3.1, un canal potassique indépendant du voltage, était conférée par la protéine calmoduline (CaM) liée de façon constitutive au canal. Cette liaison impliquerait la région C-lobe de la CaM et un domaine de $\ikca$ directement relié au segment transmembranaire S6 du canal. La CaM pourrait égalment se lier au canal de façon Ca2+ dépendante via une interaction entre un domaine de KCa3.1 du C-terminal (CaMBD2) et la région N-lobe de la CaM. Une étude fut entreprise afin de déterminer la nature des résidus responsables de la liaison entre le domaine CaMBD2 de KCa3.1 et la région N-lobe de la CaM et leur rôle dans le processus d'ouverture du canal par le Ca2+. Une structure 3D du complexe KCa3.1/CaM a d'abord été générée par modélisation par homologie avec le logiciel MODELLER en utilisant comme référence la structure cristalline du complexe SK2.2/CaM (PDB: 1G4Y). Le modèle ainsi obtenu de KCa3.1 plus CaM prévoit que le segment L361-S372 dans KCa3.1 devrait être responsable de la liaison dépendante du Ca2+ du canal avec la région N-lobe de la CaM via les résidus L361 et Q364 de KCa3.1 et E45, E47 et D50 de la CaM. Pour tester ce modèle, les résidus dans le segment L361-S372 ont été mutés en Cys et l'action du MTSET+ (chargé positivement) et MTSACE (neutre) a été mesurée sur l'activité du canal. Des enregistrements en patch clamp en configuration ``inside-out`` ont montré que la liaison du réactif chargé MTSET+ au le mutant Q364C entraîne une forte augmentation du courant, un effet non observé avec le MTSACE. De plus les mutations E45A et E47A dans la CaM, ont empêché l'augmentation du courant initié par MTSET+ sur le mutant Q364C. Une analyse en canal unitaire a confirmé que la liaison MTSET+ à Q364C cause une augmentation de la probabilité d'ouverture de KCa3.1 par une déstabilisation de l'état fermé du canal. Nous concluons que nos résultats sont compatibles avec la formation de liaisons ioniques entre les complexes chargés positivement Cys-MTSET+ à la position 364 de KCa3.1 et les résidus chargés négativement E45 et E47 dans la CaM. Ces données confirment qu'une stabilisation électrostatique des interactions CaM/KCa3.1 peut conduire à une augmentation de la probabilité d'ouverture du canal en conditions de concentrations saturantes de Ca2+.

Emotional Intelligence As A Determinant Of Conflict Style Adoption Of Managers: A Theoretical Perspective

Successful management is dependent heavily on the manager’s ability to handle conflict effectively. The workforce has been increasingly becoming diversified vis-à-vis the gender, culture and ethnicity. The present work environment has in itself contributed to sowing seeds of conflict with greater diversity, hostility, complexity and newer business competencies in the work context.The classic study of Mintzberg’s Managerial roles approach (1973) also says that a manager has to spend sufficient time and energy in solving conflict as he has to take roles as a negotiator, and dispute handler. An understanding of the conflict and role that it plays in influencing employee behavior constructively or destructively is immense. Therefore conflict when left unmanaged can lead to diminished cohesiveness amongst employees, productivity and reduced organizational fitness. To manage conflict effective conflict resolution strategies that have constructive outcomes is called for. Conflict resolution style theorists opine that collaborative or integrative style, where there is high concern for task and people is considered to give positive individual and organizational outcomes, while the withdrawing /avoidance style and forcing / dominating style are considered to be ineffective in managing conflict. Though managers have typical preferences in the styles followed it need not necessarily be the typical response as it depends on the context, power relationships, emotions etc. The adoption of conflict styles of managers however is dependent on variables like gender orientation, cultural values, personality orientation, underlying relationships – public/private. The paper attempts to draw the importance of managing conflicts at workplace positively and the need for effective conflict resolution strategies. The conflict style adopted and the variables that affect the adoption of each style are discussed and possible interventions at the workplace are suggested

Disability as a determinant of access to health care services in Colombia

The relationship between disability and poverty has been described in different contexts. Nevertheless, the basic characteristics of this relationship have not yet been fully established. The social exclusion and discrimination against people with disabilities increase the risk of poverty and reduce the access to basic opportunities such as health and education. This study examines the impact of a health limitation and poverty in the access to health care services in Colombia. Data from the Colombian National Health Survey (2007) was used in the analysis. Variables related with health condition and socio economic characteristics were first generated. Then interactions between health limitations and the lower levels of the asset index were created. This variable gave information related to the relationship between disability and poverty. A probabilistic model was estimated to examine the impact of a health condition and the relation between poverty and disability on the access to health care. The results suggest that living with a physical limitation increases by 10% the probability of access to health care services in Colombia. However, people with a disability and in the lowest quartile of the asset index have a 5% less probability of access to health care services. We conclude that people who live with a physical, mental or sensorial limitation have a higher probability of access to health care services. However, poor and disabled people have a lower probability in access, which increases the risk of having a severe disease and become chronically poor.

Iron-regulated surface determinant protein a mediates adhesion of staphylococcus aureus to human corneocyte envelope proteins

The ability of Staphylococcus aureus to colonize the human nares is a crucial prerequisite for disease. IsdA is a major S. aureus surface protein that is expressed during human infection and required for nasal colonization and survival on human skin. In this work, we show that IsdA binds to involucrin, loricrin, and cytokeratin K10, proteins that are present in the cornified envelope of human desquamated epithelial cells. To measure the forces and dynamics of the interaction between IsdA and loricrin (the most abundant protein of the cornified envelope), single-molecule force spectroscopy was used, demonstrating high-specificity binding. IsdA acts as a cellular adhesin to the human ligands, promoting whole-cell binding to immobilized proteins, even in the absence of other S. aureus components (as shown by heterologous expression in Lactococcus lactis). Inhibition experiments revealed the binding of the human ligands to the same IsdA region. This region was mapped to the NEAT domain of IsdA. The NEAT domain also was found to be required for S. aureus whole-cell binding to the ligands as well as to human nasal cells. Thus, IsdA is an important adhesin to human ligands, which predominate in its primary ecological niche.

Mapping quantitative trait loci for flag leave senescence as a yield determinant in winter wheat under optimal and drought stressed environments

The timing of flag leaf senescence (FLS) is an important determinant of yield under stress and optimal environments. A doubled haploid population derived from crossing the photo period-sensitive variety Beaver,with the photo period-insensitive variety Soissons, varied significantly for this trait, measured as the percent green flag leaf area remaining at 14 days and 35 days after anthesis. This trait also showed a significantly positive correlation with yield under variable environmental regimes. QTL analysis based on a genetic map derived from 48 doubled haploid lines using amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) markers, revealed the genetic control of this trait. The coincidence of QTL for senescence on chromosomes 2B and 2D under drought-stressed and optimal environments, respectively, indicate a complex genetic mechanism of this trait involving the re-mobilisation of resources from the source to the sink during senescence.

Characterization of the alpha-haemolysin determinant from the human enteropathogenic Escherichia coli O26 plasmid pEO5

The 157-kb conjugative plasmid pEO5 encoding alpha-haemolysin in strains of human enteropathogenic Escherichia coli (EPEC) O26 was investigated for its relationship with EHEC-haemolysin-encoding plasmids of enterohaemorrhagic E. coli (EHEC) O26 and O157 strains. Plasmid pEO5 was found to be compatible with EHEC-virulence plasmids and did not hybridize in Southern blots with plasmid pO157 from the EHEC O157:H7 strain EDL933, indicating that both plasmids were unrelated. A 9227-bp stretch of pEO5 DNA encompassing the entire alpha-hlyCABD operon was sequenced and compared for similarity to plasmid and chromosomally inherited alpha-hly determinants. The alpha-hly determinant of pEO5 (7252 bp) and its upstream region was most similar to corresponding sequences of the murine E. coli alpha-hly plasmid pHly152, in particular, the structural alpha-hlyCABD genes (99.2% identity) and the regulatory hlyR regions (98.8% identity). pEO5 and alpha-hly plasmids of EPEC O26 strains from humans and cattle were very similar for the regions encompassing the structural alpha-hlyCABD genes. The major difference found between the hly regions of pHly152 and pEO5 is caused by the insertion of an IS2 element upstream of the hlyC gene in pHly152. The presence of transposon-like structures at both ends of the alpha-hly sequence indicates that this pEO5 virulence factor was probably acquired by horizontal gene transfer.

Molecular analysis of maltotriose active transport and fermentation by Saccharomyces cerevisiae reveals a determinant role for the AGT1 permease

Incomplete and/or sluggish maltotriose fermentation causes both quality and economic problems in the ale-brewing industry. Although it has been proposed previously that the sugar uptake must be responsible for these undesirable phenotypes, there have been conflicting reports on whether all the known alpha-glucoside transporters in Saccharomyces cerevisiae (MALx1, AGT1, and MPH2 and MPH3 transporters) allow efficient maltotriose utilization by yeast cells. We characterized the kinetics of yeast cell growth, sugar consumption, and ethanol production during maltose or maltotriose utilization by several S. cerevisiae yeast strains (both MAL constitutive and AM inducible) and by their isogenic counterparts with specific deletions of the AGT1 gene. Our results clearly showed that yeast strains carrying functional permeases encoded by the MAL21, MAL31, and/or MAL41 gene in their plasma membranes were unable to utilize maltotriose. While both high-and low-affinity transport activities were responsible for maltose uptake from the medium, in the case of maltotriose, the only low-affinity (K-m, 36 +/- 2 mM) transport activity was mediated by the AGT1 permease. In conclusion, the AGT1 transporter is required for efficient maltotriose fermentation by S. cerevisiae yeasts, highlighting the importance of this permease for breeding and/or selection programs aimed at improving sluggish maltotriose fermentations.

Education as a determinant of health and well-being

This chapter is concerned with education as a factor in shaping life opportunities.  Education affects, and is affected by, individual and collective health and well-being.  It is now well established that the health and well-being of students impacts on their educational experience and outcomes, and that those experiences and outcomes impact on students' occupational futures, their future health and well-being and their level of participation as citizens.  Policy makers and practitioners are incresingly attentive to the relationship between education and health because of evidence highlighting the cyclical relationship between the economic and social conttext of schools, poor health and the well-being of students, and educational under-acheivement.

Exchange as a determinant in corporate citizenship : exploratory action research into the social construction of corporate citizenship

This study attempts to achieve two things. Firstly it contextualizes corporate citizenship drawing on scholarly, government, media, legal and business discourses which when viewed as a whole, reveals the importance of exchange as a central determinant in how all the major themes or subfields of corporate citizenship function and subsequently become valued within public discourse. Secondly, it reports on exploratory action research where I as a researcher occupied a central role in understanding and contributing towards how organizational settings socially construct and evolve corporate citizenship in real time through various exchange behaviour, drawing from four years field research within BP and its interactions with the external world. This research contributes to new knowledge by building a rare contextual understanding into how cultural change evolves over time within an organization, from its public face, through policy, down into employee and stakeholder reactions, including identifying the crucial role played by Cultural bridges’ in shifting entrenched organizational culture towards embracing new, more sustainable ways of doing business, and additionally how practitioners can legitimately act as a researcher in facilitating this process by assisting an organization to move from simple, transactional relationships to more sustainable integrated social, financial and environmental exchange between business and its broader context. Importantly, this research develops entirely new theoretical models for understanding the social application and commercial value of corporate citizenship to both business and society.

The raft-promoting property of virion-associated cholesterol, but not the presence of virion-associated brij 98 rafts, is a determinant of human immunodeficiency virus type 1 infectivity

Lipid rafts are enriched in cholesterol and sphingomyelin and are isolated on the basis of insolubility in detergents, such as Brij 98 and Triton X-100. Recent work by Holm et al. has shown that rafts insoluble in Brig 98 can be found in human immunodeficiency virus type 1 (HIV-1) virus-like particles, although it is not known whether raft-like structures are present in authentic HIV-1 and it is unclear whether a virion-associated raft-like structure is required for HIV replication. Independently, it was previously reported that virion-associated cholesterol is critical for HIV-1 infectivity, although the specific requirement of virion cholesterol in HIV-1 was not examined. In the present study, we have demonstrated that infectious wild-type HIV-1 contains Brij 98 rafts but only minimal amounts of Triton X-100 rafts. To directly assess the functional requirement of virion-associated rafts and various features of cholesterol on HIV-1 replication, we replaced virion cholesterol with exogenous cholesterol analogues that have demonstrated either raft-promoting or -inhibiting capacity in model membranes. We observed that variable concentrations of exogenous analogues are required to replace a defined amount of virion-associated cholesterol, showing that structurally diverse cholesterol analogues have various affinities toward HIV-1. We found that replacement of 50% of virion cholesterol with these exogenous cholesterol analogues did not eliminate the presence of Brij 98 rafts in HIV-1. However, the infectivity levels of the lipid-modified HIV-1s directly correlate with the raft-promoting capacities of these cholesterol analogues. Our data provide the first direct assessment of virion-associated Brij 98 rafts in retroviral replication and illustrate the importance of the raft-promoting property of virion-associated cholesterol in HIV-1 replication.

Nonnegative blind source separation by sparse component analysis based on determinant measure

The problem of nonnegative blind source separation (NBSS) is addressed in this paper, where both the sources and the mixing matrix are nonnegative. Because many real-world signals are sparse, we deal with NBSS by sparse component analysis. First, a determinant-based sparseness measure, named D-measure, is introduced to gauge the temporal and spatial sparseness of signals. Based on this measure, a new NBSS model is derived, and an iterative sparseness maximization (ISM) approach is proposed to solve this model. In the ISM approach, the NBSS problem can be cast into row-to-row optimizations with respect to the unmixing matrix, and then the quadratic programming (QP) technique is used to optimize each row. Furthermore, we analyze the source identifiability and the computational complexity of the proposed ISM-QP method. The new method requires relatively weak conditions on the sources and the mixing matrix, has high computational efficiency, and is easy to implement. Simulation results demonstrate the effectiveness of our method.