What if Haecceity is not a Property?

In some sense, both ontological and epistemological problems related to individuation have been the focal issues in the philosophy of mathematics ever since Frege. However, such an interest becomes manifest in the rise of structuralism as one of the most promising positions in recent philosophy of mathematics. The most recent controversy between Keränen and Shapiro seems to be the culmination of this phenomenon. Rather than taking sides, in this paper, I propose to critically examine some common assumptions shared by both parties. In particular, I shall focus on their assumptions on (1) haecceity as an individual essence, (2) haecceity as a property, (3) the classification of properties, and thereby (4) the search for the principle of individuation in terms of properties. I shall argue that all these assumptions are mistaken and ungrounded from Scotus’ point of view. Further, I will fathom what consequences would follow, if we reject each of these assumptions.     

A metal complex that binds alpha-amino acids with high and predictable stereospecificity.

Molecular recognition is the key step in a wide range of controlled separation and chemical transformation processes, with enzymes performing this task with an unsurpassed degree of selectivity. Enzymes contain only 20 simple amino acids, yet it remains difficult to rationalize or even predict these stereospecific recognition events. Nonetheless, the rational design of receptors able to recognize amino acids stereospecifically is attracting considerable interest because therapeutic drugs, that may be developed from chiral amino acid intermediates, are increasingly required in enantiomerically pure form. Early work has stimulated the development of efficient receptors based on small molecules, but binding of amino acids with high and predictable stereospecificity remains difficult to achieve. Directed molecular evolution, on the other hand, does select for RNA sequences or antibodies that bind amino acids with high specificity, but typically without providing insights into the molecular recognition mechanisms involved. Here we show that a rationally designed metal complex formed from a trivalent cobalt ion and a tetradentate ligand binds natural amino acids, including the simple yet challenging amino acid alanine, with high and predictable regio- and stereospecificity. We expect that our approach will allow the binding as well as separation and stereospecific catalytic formation of its target amino acids.     

Indole-3-carbinol enhances ultraviolet B-induced apoptosis by sensitizing human melanoma cells

Indole-3-carbinol (I3C) has been found to act against several types of cancer, while ultraviolet B (UVB) is known to induce the apoptosis of human melanoma cells. Here, we investigated whether I3C can sensitize G361 human melanoma cells to UVB-induced apoptosis. We examined the effects of combined I3C and UVB (I3C/UVB) at various dosages. I3C (200 μM)/UVB (50 mJ/cm²) synergistically reduced melanoma cell viability, whereas I3C (200 μM) or UVB (50 mJ/cm²), separately, had little effect on cell viability. DNA fragmentation assays indicated that I3C/UVB induced apoptosis. Further results show that I3C/UVB activates caspase-8, −3, and Bid and causes the cleavage of poly(ADP-ribose) polymerase. Moreover, I3C decreased the expression of the anti-apoptotic protein, Bcl-2, whereas UVB increased the translocation of Bax to mitochondria. Thus, an increased Bax/Bcl-2 ratio by I3C/UVB may result in melanoma apoptosis. In conclusion, our study demonstrated that I3C sensitizes human melanoma cells by down-regulating Bcl-2. Received 5 July 2006; received after revision 25 August 2006; accepted 11 September 2006     

Polo-box domain: a versatile mediator of polo-like kinase function

Members of the polo subfamily of protein kinases have emerged as important regulators in diverse aspects of the cell cycle and cell proliferation. A large body of evidence suggests that a highly conserved polo-box domain (PBD) present in the C-terminal non-catalytic region of polo kinases plays a pivotal role in the function of these enzymes. Recent advances in our comprehension of the mechanisms underlying mammalian polo-like kinase 1 (Plk1)-dependent protein–protein interactions revealed that the PBD serves as an essential molecular mediator that brings the kinase domain of Plk1 into proximity with its substrates, mainly through phospho-dependent interactions with its target proteins. In this review, current understanding of the structure and functions of PBD, mode of PBD-dependent interactions and substrate phosphorylation, and other phospho-independent functions of PBD are discussed.     

Interaction of galectin-1 with caveolae induces mouse embryonic stem cell proliferation through the Src, ERas, Akt and mTOR signaling pathways

Galectins have the potential to provide a promising alternative for unveiling the complexity of embryonic stem (ES) cell self-renewal, although the mechanism by which galectins maintain ES cell self-renewal has yet to be identified. Galectin-1 increased [³H]-thymidine incorporation as well as cyclin expression and decreased p27^kip1 expression. Src and caveolin-1 phosphorylation was increased by galectin-1, and phospho-caveolin-1 was inhibited by PP2. In addition, inhibition of caveolin-1 by small interfering RNA and methyl-β-cyclodextrin (Mβ-CD) decreased galectin-1-induced cyclin expression and [³H]-thymidine incorporation. Galectin-1 caused Akt and mTOR phosphorylation, which is involved in cyclin expression. Galectin-1-induced phospho-Akt and -mTOR was inhibited by PP2, ERas siRNA, caveolin-1 siRNA and Mβ-CD. Furthermore, mTOR phosphorylation was decreased by LY294002 and Akt inhibitor. Galectin-1-induced increase in cyclin expression and decrease in p27^kip1 was blocked by Akt inhibitor and rapamycin. In conclusion, galectin-1 increased DNA synthesis in mouse ES cells via Src, caveolin-1 Akt, and mTOR signaling pathways. Received 30 October 2008; received after revision 18 February 2009; accepted 24 February 2009