The sequence of 13.9 kilobases (kb) of the 17.1-kb mitochondrial genome of Mytilus edulis has been determined, and the arrangement of all genes has been deduced. Mytilus mitochondrial DNA (mtDNA) contains 37 genes, all of which are transcribed from the same DNA strand. The gene content of Mytilus is typically metazoan in that it includes genes for large and small ribosomal RNAs, for a complete set of transfer RNAs and for 12 proteins. The protein genes encode the cytochrome b apoenzyme, cytochrome c oxidase (CO) subunits I-III, NADH dehydrogenase (ND) subunits 1-6 and 4L, and ATP synthetase (ATPase) subunit 6. No gene for ATPase subunit 8 could be found. The reading frames for the ND1, COI, and COIII genes contain long extensions relative to those genes in other metazoan mtDNAs. There are 23 tRNA genes, one more than previously found in any metazoan mtDNA. The additional tRNA appears to specify methionine, making Mytilus mtDNA unique in having two tRNA(Met) genes. Five lengthy unassigned intergenic sequences are present, four of which vary in length from 79 to 119 nucleotides and the largest of which is 1.2 kb. The base compositions of these are unremarkable and do not differ significantly from that of the remainder of the mtDNA. The arrangement of genes in Mytilus mtDNA is remarkably unlike that found in any other known metazoan mtDNA.

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractEvasion of cell death by overexpression of anti-apoptotic proteins, such as Bcl-2, is commonly observed in cancer cells leading to a lack of response to chemotherapy.Hence, there is a need to find new chemotherapeutic agents that are able to overcome chemoresistance mediated by Bcl-2 and to understand their mechanisms of action. Helenalin, a sesquiterpene lactone ( and free intracellular iron as mediators of helenalin-induced cell death whereas activation of JNK and abrogation of Akt activity did not contribute to helenalin-elicited cell death. Our results highlight the NF-κB inhibitor helenalin as a promising chemotherapeutic agent to overcome Bcl-2-induced cell death resistance.

The aim of the present study was to prove a correlation between the calmodulin-dependent increase in the rate of calcium transport by dog cardiac sarcoplasmic reticulum and calmodulin-dependent phosphorylation.The dependence of phosphorylation on the total calmodulin concentration at 75 pM and 1 pM free calcium gave apparent calmodulin half-saturation constants K,,,(CaM) of 9.4 nM and 181 nM, respectively, whilst the apparent k ( C a M ) for the rate of calmodulin-stimulated calcium transport carried out at 1 pM calcium, but phosphorylated prior to the calcium uptake at 75 pM or 1 pM calcium, were 12.5 nM and 127 nM, respectively. A positive correlation was obtained between calmodulin-dependent increase in the rate of calcium transport and hydroxylamine-insensitive phosphoester formed by the calcium/calmodulin-regulated, membrane-bound protein kinase. More than 90 % of incorporated [32P]phosphate is confined to a 26 -28-kDa or 9 -1 I-kDa protein as determined by polyacrylamide gel electrophoresis following solubilization in sodium dodecyl sulfate at 37 'C and at 100 C, respectively, similar to the results obtained by phosphorylation with CAMP-dependent protein kinase. The data indicate that calmodulindependent phosphorylation of the above protein(s) is causally related to the stimulation of the rate of calcium transport by cardiac sarcoplasmic reticulum, which is at least partially due to a shift in the calcium dependence of the rate of calcium transport to lower free calcium concentrations, K(Ca), of 1.25 pM and 0.61 pM in controls and calmodulin-dependent phosphorylation, respectively.Activation of calmodulin-dependent phosphorylation by free calcium at total calmodulin concentrations of 300 nM, 100 nM and 30 nM gave apparent K(Ca) values of 0.53 pM, 1.44 pM and 2.3 pM and Hill coefficients of 4.13, 3.76 and 3.79, respectively, indicating that all four calcium binding sites of calmodulin have to be saturated to obtain activation of the calcium/calmodulin-regulated protein kinase. The calmodulin-dependent modulation of calcium transport in vivo is, therefore, determined to great extent by the total calmodulin concentration present in the sarcoplasm.Calmodulin stimulates the rate of calciym transport by cardiac sarcoplasmic reticulum [l -71 and the rate of calciumactivated ATP hydrolysis of the calcium transport ATPase [6,7]. Furthermore, calcium/calmodulin-dependent phosphorylation of several proteins present in crude sarcoplasmic reticulum fractions has been demonstrated [6,7]. The most prominently labelled proteins are a 22-27-kDA protein and its subunits [3, 5-7 . Since the identical protein and subunits appear to be phosphorylated by the CAMP-dependent p-otein kinase it was suggested by Le Peuch et al. [3] that calmodulindependent stimulation of the rate of calcium transport is due to calmodulin-dependent phosphorylation of phosphf3-lamban. Although this follows from the close correlation between CAMP-stimulation of calcium transport and CAMPdependent phosphorylation of a 22 -24-kDa protein (designated pho...