Diabetes-induced activation of protein kinase C inhibits store-operated Ca2+ uptake in rat retinal microvascular smooth muscle.

AIMS/HYPOTHESIS: To assess the effects of diabetes-induced activation of protein kinase C (PKC) on voltage-dependent and voltage-independent Ca2+ influx pathways in retinal microvascular smooth muscle cells. METHODS: Cytosolic Ca2+ was estimated in freshly isolated rat retinal arterioles from streptozotocin-induced diabetic and non-diabetic rats using fura-2 microfluorimetry. Voltage-dependent Ca2+ influx was tested by measuring rises in [Ca2+]i with KCl (100 mmol/l) and store-operated Ca2+ influx was assessed by depleting [Ca2+]i stores with Ca2+ free medium containing 5 micromol/l cyclopiazonic acid over 10 min and subsequently measuring the rate of rise in Ca2+ on adding 2 mmol/l or 10 mmol/l Ca2+ solution. RESULTS: Ca2+ entry through voltage-dependent L-type Ca2+ channels was unaffected by diabetes. In contrast, store-operated Ca2+ influx was attenuated. In microvessels from non-diabetic rats 20 mmol/l D-mannitol had no effect on store-operated Ca2+ influx. Diabetic rats injected daily with insulin had store-operated Ca2+ influx rates similar to non-diabetic control rats. The reduced Ca2+ entry in diabetic microvessels was reversed by 2-h exposure to 100 nmol/l staurosporine, a non-specific PKC antagonist and was mimicked in microvessels from non-diabetic rats by 10-min exposure to the PKC activator phorbol myristate acetate (100 nmol/l). The specific PKCbeta antagonist LY379196 (100 nmol/l) also reversed the poor Ca2+ influx although its action was less efficacious than staurosporine. CONCLUSION/INTERPRETATION: These results show that store-operated Ca2+ influx is inhibited in retinal arterioles from rats having sustained increased blood glucose and that PKCbeta seems to play a role in mediating this effect.

Gas-liquid two phase flow through a vertical 90deg elbow bend

Pressure drop data are reported for two phase air-water flow through a vertical to horizontal 90° elbow bend set in 0.026 m i.d. pipe. The pressure drop in the vertical inlet tangent showed some significant differences to that found for straight vertical pipe. This was caused by the elbow bend partially choking the inflow resulting in a build-up of pressure and liquid in the vertical inlet riser and differences in the structure of the flow regimes when compared to the straight vertical pipe. The horizontal outlet tangent by contrast gave data in general agreement with literature even to exhibiting a drag reduction region at low liquid rates and gas velocities between 1 and 2 m s -1. The elbow bend pressure drop was best correlated in terms of le/d determined using the actual pressure loss in the inlet vertical riser. The data showed a general increase with fluid rates that tapered off at high fluid rates and exhibited a negative pressure region at low rates. The latter was attributed to the flow being smoothly accommodated by the bend when it passed from slug flow in the riser to smooth stratified flow in the outlet tangent. A general correlation was presented for the elbow bend pressure drop in terms of total Reynolds numbers. A modified Lockhart-Martinelli model gave prediction of the data.

Making 'party identification' more versatile: operationalising the concept for the multiparty setting

The conventional operationalisation of the concept of party identification is not appropriate for the multiparty setting. I offer new measures that facilitate multiple, and negative as well as positive, identities. Using survey evidence from Northern Ireland, these new measures are validated in a number of ways and their role in a comprehensive model of voting is illustrated.

Langerhans cells--revisiting the paradigm using genetically engineered mice.

Langerhans cells (LCs) are prominent dendritic cells (DCs) in epithelia, but their role in immunity and tolerance is poorly defined. 'Knockin' mice expressing enhanced green fluorescent protein (EGFP) under the control of the langerin (CD207) gene were recently developed in order to discriminate epidermal LCs from other DC subsets and at the same time to track their dynamics under steady-state or inflammatory conditions in vivo. Additional knockin mice expressing a diphtheria toxin receptor fused to EGFP were used to conditionally ablate LCs and assess their role in triggering hapten-specific T cell effectors through skin immunization. We review the insights that have been provided by these various knockin mice and discuss gaps in our knowledge of LCs that need to be filled.

Factores explicativos de las actitudes hacia el castigo juvenil. Evidencias de un diseño factorial

El rol desempeñado por la opinión pública en el desarrollo de la política criminal actual justifica el incremento de investigaciones destinadas a evaluar las actitudes de los ciudadanos hacia el castigo. No obstante, los avances en este ámbito han sido limitados debido a la utilización de rudimentarios instrumentos de medida. Por ello, el presente trabajo tiene como propósito explorar el efecto que generan en la opinión ciudadana ciertas variables referidas al hecho delictivo y al infractor, precisando su contribución relativa y la interacción existente entre ellas. Para satisfacer este objetivo se recurrió a un diseño factorial de la encuesta, creando una población de 256 casos-escenario fruto de la combinación de cuatro factores: la edad del joven, su historial delictivo, el grado de implicación en el hecho y el tipo de delito cometido. Los mismos fueron distribuidos en grupos de ocho casos ordenados aleatoriamente y fueron suministrados a 32 sujetos. Posteriormente se aplicaron análisis de regresión logística binaria. Los resultados obtenidos revelan que la naturaleza violenta de los hechos, la implicación activa de los jóvenes y el historial delictivo son predictores importantes de las condenas punitivas. Sin embargo la edad, una variable fundamental en la configuración de la justicia juvenil, no resulta significativa. De este modo, el trabajo muestra el potencial explicativo de este conjunto de factores y debate sus implicaciones teóricas y metodológicas para la investigación futura en este terreno.

Kinestatin: a novel bradykinin B2 receptor antagonist peptide from the skin secretion of the Chinese toad, Bombina maxima

We have isolated a novel bradykinin B2-receptor antagonist peptide, kinestatin, from toad (Bombina maxima) defensive skin secretion. Mass spectroscopy established a molecular mass of 931.56 Da and a provisional structure: pGlu-Leu/Ile-Pro-Gly-Leu/Ile-Gly-Pro-Leu/Ile-Arg.amide. The unmodified sequence, -QIPGLGPLRG-, was located at the C-terminus of a 116-amino-acid residue open-reading frame following interrogation of a sequenced B. maxima skin cDNA library database. This confirmed the presence of appropriate primary structural attributes for the observed post-translational modifications present on the mature peptide and established residue 2 as Ile and residues 5/8 as Leu. Kinestatin represents a prototype novel peptide from amphibian skin.