Model sensitivity in the effect of Antarctic sea ice and stratification on atmospheric pCO2

Several recent papers have demonstrated a decrease in atmospheric pCO(2) resulting from barriers to communication between the deep sea and the atmosphere in the Southern Ocean. Stephens and Keeling [2000] decreased pCO(2) by increasing Antarctic sea ice in a seven-box model of the world ocean, and Toggweiler [1999] showed a similar response to Southern Ocean stratification. In box models the pCO(2) of the atmosphere is controlled by the region of the surface ocean that fills the deep sea [Archer et al., 2000a]. By severing the Southern Ocean link between the deep sea and the atmosphere, atmospheric pCO(2) in these models is controlled elsewhere and typically declines, although the models range widely in their responses. "Continuum models,'' such as three-dimensional (3-D) and 2-D general circulation models, control pCO(2) in a more distributed way and do not exhibit box model sensitivity to high-latitude sea ice or presumably stratification. There is still uncertainty about the high-latitude sensitivity of the real ocean. Until these model sensitivities can be resolved, glacial pCO(2) hypotheses and interpretations based on Southern Ocean barrier mechanisms (see above mentioned references plus Elderfield and Rickaby [2000], Francois et al. [1998], Gildor and Tziperman [2001], Sigman and Boyle [2000], and Watson et al. [2000]) are walking on thin ice

Environmental occurrence, analysis, and toxicology of toxaphene compounds.

Toxaphene production, in quantities similar to those of polychlorinated biphenyls, has resulted in high toxaphene levels in fish from the Great Lakes and in Arctic marine mammals (up to 10 and 16 microg g-1 lipid). Because of the large variabiliity in total toxaphene data, few reliable conclusions can be drawn about trends or geographic differences in toxaphene concentrations. New developments in mass spectrometric detection using either negative chemical ionization or electron impact modes as well as in multidimensional gas chromatography recently have led researchers to suggest congener-specific approaches. Recently, several nomenclature systems have been developed for toxaphene compounds. Although all systems have specific advantages and limitations, it is suggested that an international body such as the International Union of Pure and Applied Chemistry make an attempt to obtain uniformity in the literature. Toxicologic information on individual chlorobornanes is scarce, but some reports have recently appeared. Neurotoxic effects of toxaphene exposure such as those on behavior and learning have been reported. Technical toxaphene and some individual congeners were found to be weakly estrogenic in in vitro test systems; no evidence for endocrine effects in vivo has been reported. In vitro studies show technical toxaphene and toxaphene congeners to be mutagenic. However, in vivo studies have not shown genotoxicity; therefore, a nongenotoxic mechanism is proposed. Nevertheless, toxaphene is believed to present a potential carcinogenic risk to humans. Until now, only Germany has established a legal tolerance level for toxaphene--0.1 mg kg-1 wet weight for fish

Inhibition of Myogenesis by the H-Ras Oncogene: Implication of a Role for Protein Kinase C

Expression of the oncogenic form of H-ras p21 in the mouse myogenic cell line, 23A2, blocks myogenesis and inhibits expression of the myogenic regulatory factor gene, MyoD1. Previous studies from a number of laboratories have demonstrated that the activation of ras p21 is associated with changes in phospholipid metabolism that directly, or indirectly, lead to elevated levels of intracellular diacylglycerol and the subsequent activation of protein kinase C (PKC). To assess the importance of PKC activity to the ras-induced inhibition of skeletal myogenesis, we examined the levels of PKC activity associated with the terminal differentiation of wild-type myoblasts and with the differentiation-defective phenotype of 23A2 ras cells. We demonstrate that there is a 50% reduction in PKC activity during normal myogenesis and that PKC activity is required for myoblast fusion, but not for the transcriptional activation of muscle-specific genes. In contrast, we found that the differentiation-defective 23A2 ras cells possess two- to threefold more PKC activity than wild-type myofibers and that reducing the PKC activity in these cultures does not reverse their nonmyogenic phenotype. On the other hand, if PKC activity is downregulated in 23A2 cells before the expression of activated ras p21, myogenesis is not inhibited. These results suggest that activated ras p21 relies on a PKC-dependent signal transduction pathway to initiate, but not to sustain, its negative effects on 23A2 skeletal myogenesis and underscore the potential importance of PKC activity to the proper control of skeletal muscle differentiation

Evaluation of (2S,4S)/(2R,4R) and (2S,4R)/(2R,4S) 6,6-N,N-dimethyl-2-methyl-2-oxo-1,3-dioxa-4-hexadecyl-6,aza-2-phosphacyc looctane bromide as inhibitors for protein kinase C, carnitine octanoyltransferase, and carnitine palmitoyltransferase

(2S,4S)/(2R,4R) and (2S,4R)/(2R,4S) 6,6-N,N-dimethyl-2-methyl-2-oxo-1,3-dioxa-4-hexadecyl-6-aza-2-phosphacyc looctane bromide strongly inhibited protein kinase C and moderately inhibited carnitine octanoyltransferase and carnitine palmitoyltransferase.</p

Evaluation of (2S,4S)/(2R,4R) and (2S,4R)/(2R,4S) 6,6-N,N-dimethyl-2-methyl-2-oxo-1,3-dioxa-4-hexadecyl-6,aza-2-phosphacyc looctane bromide as inhibitors for protein kinase C, carnitine octanoyltransferase, and carnitine palmitoyltransferase

(2S,4S)/(2R,4R) and (2S,4R)/(2R,4S) 6,6-N,N-dimethyl-2-methyl-2-oxo-1,3-dioxa-4-hexadecyl-6-aza-2-phosphacyc looctane bromide strongly inhibited protein kinase C and moderately inhibited carnitine octanoyltransferase and carnitine palmitoyltransferase.</p

D-501036, a novel selenophene-based triheterocycle derivative, exhibits potent in vitro and in vivo antitumoral activity which involves DNA damage and ataxia telangiectasia-mutated nuclear protein kinase activation

[[abstract]]D-501036 [2,5-bis(5-hydroxymethyl-2-selenienyl)-3-hydroxymethyl-N-methylpyrrole] is herein identified as a novel antineoplastic agent with a broad spectrum of antitumoral activity against several human cancer cells and an IC50 value in the nanomolar range. The IC50 values for D-501036 in the renal proximal tubule, normal bronchial epithelial, and fibroblast cells were > 10 mu mol/L. D-501036 exhibited no cross-resistance with vincristine- and paclitaxel-resistant cell lines, whereas a low level of resistance toward the etoposide-resistant KB variant was observed. Cell cycle analysis established that D-501036 treatment resulted in a dose-dependent accumulation in S phase with concomitant loss of both the G(0)-G(1) and G(2)-M phase in both Hep 3B and A-498 cells. Pulsed-field gel electrophoresis showed D-501036-induced, concentration-dependent DNA breaks in both Hep 38 and A-498 cells. These breaks did not involve interference with either topoisomerase-I and topoisomerase-II function or DNA binding. Rapid reactive oxygen species production and formation of Se-DNA adducts were evident following exposure of cells to D-501036, indicating that D-501036-mediated DNA breaks were attributable to the induction of reactive oxygen species and DNA adduct formation. Moreover, D-501036-induced DNA damage activated ataxia telangiectasia-mutated nuclear protein kinase, leading to hyperphosphorylation of Chk1, Chk2, and p53, decreased expression of CDC25A, and up-regulation of p21(WAF1) in both p53-proficient and p53-deficient cells. Collectively, the results indicate that D-501036-induced cell death was associated with DNA damage-mediated induction of ataxia telangiectasia-mutated activation, and p53-dependent and -independent apoptosis pathways. Notably, D-501036 shows potent activity against the growth of xenograft tumors of human renal carcinoma A-498 cells. Thus, D-501036 is a promising anticancer compound that has strong potential for the management of human cancers