Distinctive effects of G-CSF, GM-CSF and TNFalpha on neutrophil apoptosis in systemic lupus erythematosus.

OBJECTIVE: To investigate the influence of culture with G-CSF GM-CSF and TNFalpha on neutrophil apoptosis, comparing neutrophils from SLE patients with rheumatoid arthritis (RA) patients and healthy control subjects. METHODS: Neutrophils were isolated from SLE (n= 10), RA (n= 10) and healthy control subjects (n= 10), and cultured with two different concentrations of G-CSF, GM-CSF and TNFalpha. Proportion of apoptotic neutrophils at T=0, T=2hrs and T=24hrs was measured using FITC-labelled annexinV and flow cytometry. RESULTS: Significantly more neutrophils were apoptotic at T=0 in the SLE subjects than in the other groups (median, range--Control 3.5% (0.3-7.9) SLE 9.5% (2.9-29.1) RA 3.0% (0.4-23.0) p

Multiplicative spectra of Banach spaces

The multiplicative spectrum of a complex Banach space X is the class K(X) of all (automatically compact and Hausdorff) topological spaces appearing as spectra of Banach algebras (X,*) for all possible continuous multiplications on X turning X into a commutative associative complex algebra with the unity. The properties of the multiplicative spectrum are studied. In particular, we show that K(X^n) consists of countable compact spaces with at most n non-isolated points for any separable hereditarily indecomposable Banach space X. We prove that K(C[0,1]) coincides with the class of all metrizable compact spaces.

Index of sources of stress in nursing students: a confirmatory factor analysis.

Aim. This paper is a report of a study to test the proposed factor structure of the Index of Sources of Stress in Nursing Students. Background. Research across many countries has identified a number of sources of distress in nursing students but little attempt has been made to understand and measure sources of eustress or those stressors likely to enhance performance and well-being. The Index of Sources of Stress in Nursing Students was developed to do this. Exploratory factor analysis suggested a three-factor structure, the factors being labelled: learning and teaching; placement-related and course organization. It is important, however, to subject the instrument to confirmatory factor analysis as a further test of construct validity. Method. A convenience sample of final year nursing students (n = 176) was surveyed in one university in Northern Ireland in 2007. The Index of Sources of Stress in Nursing Students, which measures sources of stress likely to contribute to distress and eustress, was completed electronically. The LISREL programme was used to carry out the confirmatory factor analysis and test the factor structure suggested in the exploratory analysis. Findings. The proposed factor structure for the items measuring ‘Uplifts’ proved to be a good fit to the data and the proposed factor structure for the items measuring ‘Hassles’ showed adequate fit. Conclusion. In nursing programmes adopting the academic model and combining university-based learning with placement experience, this instrument can be used to help identify the sources of stress or course demands that students rate as distressing and those that help them to achieve. The validity of the ISSN could be further evaluated in other education settings.

Cohomology of Banach algebras of operators and geometry of Banach spaces.

In the paper we give an exposition of the major results concerning the relation between first order cohomology of Banach algebras of operators on a Banach space with coefficients in specified modules and the geometry of the underlying Banach space. In particular we shall compare the properties weak amenability and amenability for Banach algebras A(X), the approximable operators on a Banach space X. Whereas amenability is a local property of the Banach space X, weak amenability is often the consequence of properties of large scale geometry.

Rhodopsin and the Others: A Historical Perspective on Structural Studies of G Protein-Coupled Receptors

The role of rhodopsin as a structural prototype for the study of the whole superfamily of G protein-coupled receptors (GPCRs) is reviewed in an historical perspective. Discovered at the end of the nineteenth century, fully sequenced since the early 1980s, and with direct three-dimensional information available since the 1990s, rhodopsin has served as a platform to gather indirect information on the structure of the other superfamily members. Recent breakthroughs have elicited the solution of the structures of additional receptors, namely the beta 1- and beta 2-adrenergic receptors and the A(2A) adenosine receptor, now providing an opportunity to gauge the accuracy of homology modeling and molecular docking techniques and to perfect the computational protocol. Notably, in coordination with the solution of the structure of the A(2A) adenosine receptor, the first "critical assessment of GPCR structural modeling and docking" has been organized, the results of which highlighted that the construction of accurate models, although challenging, is certainly achievable. The docking of the ligands and the scoring of the poses clearly emerged as the most difficult components. A further goal in the field is certainly to derive the structure of receptors in their signaling state, possibly in complex with agonists. These advances, coupled with the introduction of more sophisticated modeling algorithms and the increase in computer power, raise the expectation for a substantial boost of the robustness and accuracy of computer-aided drug discovery techniques in the coming years.

Evidence for a Direct and Functional Interaction between the Regulators of G Protein Signaling-2 and Phosphorylated C Terminus of Cholecystokinin-2 Receptor

Signaling of G protein-coupled receptors (GPCRs) is regulated by different mechanisms. One of these involves regulators of G protein signaling (RGS), which are diverse and multifunctional proteins that bind to active G alpha subunits of G proteins and act as GTPase-activating proteins. Little is known about the molecular mechanisms that govern the selective use of RGS proteins in living cells. We first demonstrated that CCK2R-mediated inositol phosphate production, known to be G(q-)dependent, is more sensitive to RGS2 than to RGS4 and is insensitive to RGS8. Both basal and agonist-stimulated activities of the CCK2R are regulated by RGS2. By combining biochemical functional, and in silico structural approaches, we demonstrate that a direct and functional interaction occurs between RGS2 and agonist-stimulated cholecystokinin receptor-2 (CCK2R) and identified the precise residues involved: phosphorylated Ser434 and Thr439 located in the C-terminal tail of CCK2R and Lys62, Lys63, and Gln67, located in the N-terminal domain of RGS2. These findings confirm previous reports that RGS proteins can interact with GPCRs to modulate their signaling and provide a molecular basis for RGS2 recognition by the CCK2R.