Crystallization of calcite from amorphous calcium carbonate: earthworms show the way

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Soil pH governs production rate of calcium carbonate secreted by the earthworm Lumbricus terrestris

Lumbricus terrestris earthworms exposed to 11 soils of contrasting properties produced, on average, 0.8 ± 0.1 mgCaCO3 earthworm−1 day−1 in the form of granules up to 2 mm in diameter. Production rate increased with soil pH (r2 = 0.68, p < 0.01). Earthworms could be a significant source of calcite in soils

Vitamin E as Adjuvant in Emulsified Vaccine for Chicks

Abstract Mineral oil was partially replaced with D, L-α-tocopheryl acetate (vitamin E) in bacterial and viral inactivated emulsified vaccines. Vitamin E increased the immune response to the viral antigen (Newcastle disease virus) used but not to the bacterial antigen (Escherichia coli) when its presence in the oil phase did not exceed 30%. Inoculated vitamin E may have enhanced the immune response by interacting with the immune-competent cells involved in the inflammatory reaction that followed inoculation of emulsified vaccines

Low doses of cisplatin or gemcitabine plus Photofrin/photodynamic therapy: Disjointed cell cycle phase-related activity accounts for synergistic outcome in metastatic non-small cell lung cancer cells (H1299).

We compared the effects of monotherapy (photodynamic therapy or chemotherapy) versus combination therapy (photodynamic therapy plus a specific drug) on the non-small cell lung cancer cell line H1299. Our aim was to evaluate whether the additive/synergistic effects of combination treatment were such that the cytostatic dose could be reduced without affecting treatment efficacy. Photodynamic therapy was done by irradiating Photofrin-preloaded H1299 p53/p16-null cells with a halogen lamp equipped with a bandpass filter. The cytotoxic drugs used were cis-diammine-dichloroplatinum [II] (CDDP or cisplatin) and 2',2'-difluoro-2'-deoxycytidine (gemcitabine). Various treatment combinations yielded therapeutic effects (trypan blue dye exclusion test) ranging from additive to clearly synergistic, the most effective being a combination of photodynamic therapy and CDDP. To gain insight into the cellular response mechanisms underlying favorable outcomes, we analyzed the H1299 cell cycle profiles and the expression patterns of several key proteins after monotherapy. In our conditions, we found that photodynamic therapy with Photofrin targeted G0-G1 cells, thereby causing cells to accumulate in S phase. In contrast, low-dose CDDP killed cells in S phase, thereby causing an accumulation of G0-G1 cells (and increased p21 expression). Like photodynamic therapy, low-dose gemcitabine targeted G0-G1 cells, which caused a massive accumulation of cells in S phase (and increased cyclin A expression). Although we observed therapeutic reinforcement with both drugs and photodynamic therapy, reinforcement was more pronounced when the drug (CDDP) and photodynamic therapy exert disjointed phase-related cytotoxic activity. Thus, if photodynamic therapy is appropriately tuned, the dose of the cytostatic drug can be reduced without compromising the therapeutic response

DTIC xenogenized lines obtained from an L1210 clone: clonal analysis of cytotoxic T lymphocyte reactivity.

Antineoplastic compounds can induce on tumour cells new antigens that undetectable on parental cells and which are transmissible as a genetic character. In this study mouse leukaemia L1210 was cloned in vitro by limiting dilution and one cloned line was recloned in vivo. Four subcloned tumour cell lines (A,D,R,S) were xenogenized in vivo by DTIC treatment (A/DTIC, D/DTIC, R/DTIC, S/DTIC) following a schedule previously described. Up to 10(7) cells of these xenogenized subclones, injected i.p., were rejected by syngeneic hosts, although they grew in immunosuppressed hosts. The DTIC treated subclones were lysed by in vivo-primed, in vitro-restimulated (with the relevant subclone) lymphocytes. The cytotoxic lymphocyte activity was not strictly specific since parental, DTIC-untreated cells were also lysed, although less efficiently. CTL directed against the D/DTIC subclone were cloned by limiting dilution. Ninety-four CTL clones were assayed against L1210 subcloned cells, DTIC-treated and untreated, and against different murine tumours (syngeneic or allogenic). Three specific antigens could be identified in the 51Cr release assay. The DTIC subclones expressed one antigen that was specifically recognized by a set of CTL clones. A number of CTL clones were able to lyse the L1210 subcloned cell exclusively, targetting a tumour-associated antigen that did not appear to be modified in the DTIC-treated subclones. A third antigen was demonstrated in the parental and DTIC treated D subclone. On the basis of these results it was postulated that there was at least one common DTIC-inducible antigen specific and reproducible within an identical cell population. Moreover, DTIC treatment did not modify histocompatibility antigens or TAA pre-existing in L1210 cells. The findings discussed here provide new information about permanent xenogenization of tumour cells, which might be exploited for experimental chemo-immunotherapy of cancer

Earthworm-produced calcite granules: a new terrestrial palaeothermometer?

In this paper we show for the first time that calcite granules, produced by the earthworm Lumbricus terrestris, and commonly recorded at sites of archaeological interest, accurately reflect temperature and soil water δ18O values. Earthworms were cultivated in an orthogonal combination of two different (granule-free) soils moistened by three types of mineral water and kept at three temperatures (10, 16 and 20 ºC) for an acclimatisation period of three weeks followed by transfer to identical treatments and cultivation for a further four weeks. Earthworm-secreted calcite granules were collected from the second set of soils. δ18O values were determined on individual calcite granules (δ18Oc) and the soil solution (δ18Ow). The δ18Oc values reflect soil solution δ18Ow values and temperature, but are consistently enriched by 1.51 (±0.12) ‰ in comparison to equilibrium in synthetic carbonates. The data fit the equation 1000 ln α = [20.21 ± 0.92] (103 T-1) - [38.58 ± 3.18] (R2 = 0.95; n = 96; p < 0.0005). As the granules are abundant in modern soils, buried soils and archaeological contexts, and can be dated using U-Th disequilibria, the developed palaeotemperature relationship has enormous potential for application to Holocene and Pleistocene time intervals

Melatonin Analogue Antiproliferative and Cytotoxic Effects on Human Prostate Cancer Cells

Melatonin has been indicated as a possible oncostatic agent in different types of cancer, its antiproliferative role being demonstrated in several in vitro and in vivo experimental models of tumors. Specifically, melatonin was proven to inhibit cell growth of both androgen-dependent and independent prostate cancer cells, through various mechanisms. A number of melatonin derivatives have been developed and tested for their role in the prevention and treatment of neoplastic diseases. We recently proved the in vitro and in vivo anticancer activity of UCM 1037, a newly-synthetized melatonin analogue, on melanoma and breast cancer cells. In this study we evaluated UCM 1037 effects on cell proliferation, cell cycle distribution, and cytotoxicity in LNCaP, PC3, DU145, and 22Rv1 prostate cancer cells. We demonstrated significant dose- and time-dependent UCM 1037 antiproliferative effects in androgen-sensitive LNCaP and 22Rv1 cells. Data from flow cytometric studies suggest that UCM 1037 is highly cytotoxic in androgen-sensitive prostate cancer cells, although no substantial increase in the apoptotic cell fraction has been observed. UCM 1037 cytotoxic effects were much less evident in androgen-insensitive PC3 and DU145 cells. Experiments performed to gain insights into the possible mechanism of action of the melatonin derivative revealed that UCM 1037 down-regulates androgen receptor levels and Akt activation in LNCaP and 22Rv1 cells

Determinants of the voltage dependence of G protein modulation within calcium channel β subunits

CaVβ subunits of voltage-gated calcium channels contain two conserved domains, a src-homology-3 (SH3) domain and a guanylate kinase-like (GK) domain with an intervening HOOK domain. We have shown in a previous study that, although Gβγ-mediated inhibitory modulation of CaV2.2 channels did not require the interaction of a CaVβ subunit with the CaVα1 subunit, when such interaction was prevented by a mutation in the α1 subunit, G protein modulation could not be removed by a large depolarization and showed voltage-independent properties (Leroy et al., J Neurosci 25:6984–6996, 2005). In this study, we have investigated the ability of mutant and truncated CaVβ subunits to support voltage-dependent G protein modulation in order to determine the minimal domain of the CaVβ subunit that is required for this process. We have coexpressed the CaVβ subunit constructs with CaV2.2 and α2δ-2, studied modulation by the activation of the dopamine D2 receptor, and also examined basal tonic modulation. Our main finding is that the CaVβ subunit GK domains, from either β1b or β2, are sufficient to restore voltage dependence to G protein modulation. We also found that the removal of the variable HOOK region from β2a promotes tonic voltage-dependent G protein modulation. We propose that the absence of the HOOK region enhances Gβγ binding affinity, leading to greater tonic modulation by basal levels of Gβγ. This tonic modulation requires the presence of an SH3 domain, as tonic modulation is not supported by any of the CaVβ subunit GK domains alone

Computational modeling of the metabolic states regulated by the kinase Akt

Signal transduction and gene regulation determine a major reorganization of metabolic activities in order to support cell proliferation. Protein Kinase B (PKB), also known as Akt, participates in the PI3K/Akt/mTOR pathway, a master regulator of aerobic glycolysis and cellular biosynthesis, two activities shown by both normal and cancer proliferating cells. Not surprisingly considering its relevance for cellular metabolism, Akt/PKB is often found hyperactive in cancer cells. In the last decade, many efforts have been made to improve the understanding of the control of glucose metabolism and the identification of a therapeutic window between proliferating cancer cells and proliferating normal cells. In this context, we have modeled the link between the PI3K/Akt/mTOR pathway, glycolysis, lactic acid production, and nucleotide biosynthesis. We used a computational model to compare two metabolic states generated by two different levels of signaling through the PI3K/Akt/mTOR pathway: one of the two states represents the metabolism of a growing cancer cell characterized by aerobic glycolysis and cellular biosynthesis, while the other state represents the same metabolic network with a reduced glycolytic rate and a higher mitochondrial pyruvate metabolism. Biochemical reactions that link glycolysis and pentose phosphate pathway revealed their importance for controlling the dynamics of cancer glucose metabolism