The Harlequin ladybird continues to invade southeastern Europe

The ladybird Harmonia axyridis (Pallas) is considered one of the most serious invasive species around the globe. It has spread all over North America and Western Europe, while data from southeastern Europe, especially in the Mediterranean region, are scarce. In this study we present the first confirmed data of the spread of H. axyridis throughout Croatia. Specimens were sampled and identified during the period 2008–2010. The species was recorded at 18 localities in all three colour forms in various habitat types. Light trapping was found to be a satisfactory method for collecting H. axyridis. Since there is no evidence to suggest the deliberate introduction of H. axyridis in Croatia, it can be assumed that it has spread southwards from Central and Eastern Europe, and that it will probably continue to spread. Further investigations should focus on monitoring and detailed mapping of H. axyridis in Croatia and neighbouring countries, especially in the Mediterranean region, to determine whether stable populations are present.     

A toolbox for class I HDACs reveals isoform specific roles in gene regulation and protein acetylation

The class I histone deacetylases are essential regulators of cell fate decisions in health and disease. While pan- and class-specific HDAC inhibitors are available, these drugs do not allow a comprehensive understanding of individual HDAC function, or the therapeutic potential of isoform-specific targeting. To systematically compare the impact of individual catalytic functions of HDAC1, HDAC2 and HDAC3, we generated human HAP1 cell lines expressing catalytically inactive HDAC enzymes. Using this genetic toolbox we compare the effect of individual HDAC inhibition with the effects of class I specific inhibitors on cell viability, protein acetylation and gene expression. Individual inactivation of HDAC1 or HDAC2 has only mild effects on cell viability, while HDAC3 inactivation or loss results in DNA damage and apoptosis. Inactivation of HDAC1/HDAC2 led to increased acetylation of components of the COREST co-repressor complex, reduced deacetylase activity associated with this complex and derepression of neuronal genes. HDAC3 controls the acetylation of nuclear hormone receptor associated proteins and the expression of nuclear hormone receptor regulated genes. Acetylation of specific histone acetyltransferases and HDACs is sensitive to inactivation of HDAC1/HDAC2. Over a wide range of assays, we determined that in particular HDAC1 or HDAC2 catalytic inactivation mimics class I specific HDAC inhibitors. Importantly, we further demonstrate that catalytic inactivation of HDAC1 or HDAC2 sensitizes cells to specific cancer drugs. In summary, our systematic study revealed isoform-specific roles of HDAC1/2/3 catalytic functions. We suggest that targeted genetic inactivation of particular isoforms effectively mimics pharmacological HDAC inhibition allowing the identification of relevant HDACs as targets for therapeutic intervention.     

Calcium-binding protein in bull seminal vesicle secretion and seminal plasma.

A protein which showed high affinity for calcium ions was isolated from bull seminal vesicle secretion and seminal plasma. Its calcium-binding activity depended on the ionic strength and pH of the medium. The dissociation constant was 7-7 X 10(-7) M and there were 14 binding sites per protein molecule. The molecular weight of calcium-binding protein from bull seminal vesicle secretion, estimated by the gel filtration method, was 110,000. The protein may be involved in the regulation of the calcium ion level in seminal plasma.     

Human Health, Well-Being, and Global Ecological Scenarios

This article categorizes four kinds of adverse effects to human health caused by ecosystem change: direct, mediated, modulated, and systems failure. The effects are categorized on their scale, complexity, and lag-time. Some but not all of these can be classified as resulting from reduced ecosystem services. The articles also explores the impacts that different socioeconomic–ecologic scenarios are likely to have on human health and how changes to human health may, in turn, influence the unfolding of four different plausible future scenarios. We provide examples to show that our categorization is a useful taxonomy for understanding the complex relationships between ecosystems and human well-being and for predicting how future ecosystem changes may affect human health.Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the position of the World Health Organization. This article has been subjected to EPA review and approved for publication but does not necessarily reflect EPA policy.     

A monoclonal antibody-purified soluble target cell antigen inhibits nonspecific cytotoxic cell activity.

We have previously reported the characterization of mAb derived against NC-37 target cells. mAb 18C2 and 1E7 inhibit fish cytotoxicity by binding to target cells and thus preventing the formation of conjugates with fish nonspecific cytotoxic cells (NCC). It was therefore presumed that these inhibitory mAb were specific for the target cell Ag necessary for effector cell recognition. mAb 1D4 and 7C6 bind to NC-37 cells but do not inhibit fish cytotoxic activity. We now report the isolation and purification of the Ag recognized by mAb 18C2 (inhibitor) and 1D4 (noninhibitor) by affinity chromatography of solubilized NC-37 target cell extracts. The 18C2-purified soluble target Ag (STAg) caused inhibition of cytotoxicity when preincubated with fish NCC. This inhibitory activity was reversible and dose-dependent ranging from 20 to 70% inhibition with 25 to 100 micrograms 18C2 purified STAg/10(6) NCC. STAg purified by 1D4 affinity chromatography had no effect on fish cytotoxicity. mAb 18C2 and 1E7 preabsorbed with 18C2 STAg lost their inhibitory activity when tested in the fish NCC cytotoxicity assay. Preabsorption of the same mAb with 1D4 STAg had no effect on their activity.     

Inhibition of human natural killer cell activity by a synthetic peptide homologous to a conserved region in the retroviral protein, p15E

It has been shown previously that the retroviral envelope protein p15E suppresses certain monocyte and lymphocyte functions. In this paper, we describe the effects on natural killer (NK) activity of a synthetic peptide (CKS-17) with homology to a region of p15E conserved among numerous retroviruses. Enriched human NK cells were assayed against K562 tumor target cells in a 51Cr-release cytotoxicity assay. Pretreatment of NK cells with CKS-17 at concentrations as low as 1.5 microM, but not with equivalent concentrations of control materials, markedly and reproducibly suppressed NK lytic activity. Prior exposure of NK cells to interferon-alpha (IFN-alpha) at 1000 U/ml did not alter their sensitivity to CKS-17-induced inhibition. Pretreating NK cells with CKS-17 almost entirely diminished their responsiveness to IFN-alpha and IFN-gamma, but not to interleukin 2 (IL 2). Kinetics experiments demonstrated that CKS-17-mediated suppression of both endogenous and activated NK cells was reversible after 18 hr at 37 degrees C. Experiments designed to examine the CKS-17 mechanism of action revealed that the peptide bound to all Leu-11+ lymphocytes, as shown by two-color flow cytometry. CKS-17 did not, however, inhibit effector cell/target cell conjugate formation. These data suggest a new mechanism for immune suppression mediated by retroviruses; inhibition of NK function. They moreover imply that the CKS-17 peptide interferes with the lytic phase of NK cytolysis.     

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Human peripheral blood monocytes were reproducibly shown to lyse a variety of tumor cells in a 3- to 4-hr ⁵¹Cr release assay. Ficoll-Hypaque-purified mononuclear cells were suspended in medium supplemented with either 10% autologous serum or fetal calf serum (PCS). With either serum, highly purified (97–99%) and viable (>99%) monocyte suspensions were obtained by EDTA-reversible adherence to plastic surfaces which had been precoated with autologous serum. When used as effectors in cytotoxicity assays, the monocytes recovered from mononuclear cells suspended in FCS-supplemented medium exhibited higher cytolytic activity and were therefore used for further studies. Using FCS for both coating the plates and supplementing the suspension medium resulted in monocytes with low cytolytic activity. Tumor cell lysis measured by ⁵¹Cr release was detected within 2 hr of incubation and increased gradually with time. The level of lysis was dependent on the effector/target ratio and the tumor target cell employed. The involvement of natural killer lymphocytes in the observed tumoricidal activity was excluded. Detection of cytotoxic activity in a short-term assay will be very helpful in further studies of the mechanism of tumor cell killing by human monocytes since potential complicating effects of long-term in vitro cultivation will be minimized.