The free nucleoplasmic Ca2+ concentration ([Ca2+]n) may regulate many nuclear events, such as gene transcription. Since the nucleus may possess the enzymes necessary to generate the second messenger inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), and because the nuclear envelope may enclose an Ins(1,4,5)P3-releasable Ca2+ store, we tested the hypothesis that nuclear and/or cytosolic levels of Ins(1,4,5)P3 can control [Ca2+]n. To assay [Ca2+]n, we measured the fluorescence of the Ca2+ indicator fluo 3 in the nucleus of Xenopus oocytes by confocal microscopy. When we injected Ins(1,4,5)P3 into the cytosol, [Ca2+]n increased. This increase in [Ca2]n still occurred when heparin was present in the nucleus, but was abolished when heparin was present in the cytosol, indicating that cytosolic Ins(1,4,5)P3 levels could control [Ca2+]n. When we injected Ins(1,4,5)P3 directly into the nucleus, [Ca2+]n increased, even when heparin was present in the cytosol, indicating that Ins(1,4,5)P3 could control [Ca2+]n from within the nucleus. These results provide functional evidence for Ins(1,4,5)P3 receptors facing the nucleoplasm and raise the possibility that a phosphoinositide cycle situated at the nuclear membranes can control Ca(2+)-dependent nuclear functions.

The receptors for the second messenger inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] form a family of closely related proteins that play an important role in regulating the free intracellular Ca2+ concentration. To test the hypothesis that changing the expression level of Ins(1,4,5)P3 receptors could alter the Ins(1,4,5)P3-mediated Ca2+ signal, we overexpressed Ins(1,4,5)P3 receptor type 1 (InsP3R-1) or type 3 (InsP3R-3) in Xenopus laevis oocytes. Expression of InsP3R-1 increased the velocity of the propagating waves of intracellular Ca2+ release but did not affect the Ins(1,4,5)P3-induced entry of extracellular Ca2+ across the plasma membrane. In contrast, expression of intracellular Ca2+ but markedly increased the magnitude and duration of Ca2+ influx. Immunolocalization studied revealed InsP3R-3 at the endoplasmic reticulum, with a relatively stronger signal at or near the plasma membrane. The results suggest that changing the expression level of an InsP3R can alter the Ins(1,4,5)P3-mediated Ca2+ signal and that InsP3R-1 and InsP3R-3 may have different biological functions.

Although benchmarking has proven to be valuable for large businesses and organizations for quite sometime, up until recently, serious doubts existed as to its usefulness for smaller businesses. In this paper, we present the PDG ® , a benchmarking system meant to evaluate SMEs from an external perspective in order to produce a diagnosis of their performance and potential, complemented with relevant recommendations. Our research results show that benchmarking allows SMEs to improve their operational performance thus confirming the usefulness of benchmarking. These results also confirm the value of the recommendations included in the PDG ® report concerning short-term actions to be undertaken to modify management practices. We think the PDG ® system proves that if the benchmarking approach is tailored to SMEs' characteristics, an adequate tool can be devised and used to help SMEs increase their performance.

Calreticulin (CRT) is a highly conserved

Adenophostin A possesses the highest known affinity for the inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3 ) receptor (InsP 3 R). The compound shares with Ins(1,4,5)P 3 those structural elements essential for binding to the InsP 3 R. However, its adenosine 2-phosphate moiety has no counterpart in the Ins(1,4,5)P 3 molecule. To determine whether its unique structure conferred a distinctive biological activity, we characterized the adenophos- Stimulation of many plasma membrane receptors increases the intracellular concentration of the second messenger inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3 ).