Structure-function relationship of thiazolide-induced apoptosis in colorectal tumor cells.

Thiazolides are a novel class of anti-infectious agents against intestinal intracellular and extracellular protozoan parasites, bacteria, and viruses. While the parent compound nitazoxanide (NTZ; 2-(acetolyloxy)-N-(5-nitro-2-thiazolyl)benzamide) has potent antimicrobial activity, the bromo-thiazolide RM4819 (N-(5-bromothiazol-2-yl)-2-hydroxy-3-methylbenzamide) shows only reduced activity. Interestingly, both molecules are able to induce cell death in colon carcinoma cell lines, indicating that the molecular target in intestinal pathogens and in colon cancer cells is different.

Expanding the scope of human DNA polymerase λ and β inhibitors.

The exact biological functions of individual DNA polymerases still await clarification, and therefore appropriate reagents to probe their respective functions are required. In the present study, we report the development of a highly potent series of human DNA polymerase λ and β (pol λ and β) inhibitors based on the rhodanine scaffold. Both enzymes are involved in DNA repair and are thus considered as future drug targets.

A Hh-driven gene network controls specification, pattern and size of the Drosophila simple eyes.

During development, extracellular signaling molecules interact with intracellular gene networks to control the specification, pattern and size of organs. One such signaling molecule is Hedgehog (Hh). Hh is known to act as a morphogen, instructing different fates depending on the distance to its source.

Regulation of ocellar specification and size by twin of eyeless and homothorax.

The retinal determination gene network (RDGN) constitutes a paradigm of a gene network controlling organ specification and growth. In this study, we probed the RDGN in the Drosophila ocelli, a set of simple eyes located on the fly's dorsal head, by studying the expression, regulation, and function of toy, hth, eya, and so, members of the Pax6, Meis, Eya, and Six gene families. Our results highlight the role of the pax6 gene toy, together with the hh signaling pathway, in the initiation of eya and so expression; the engagement of eya and so in a feedback loop necessary for their full expression; and the interplay between hh signaling and hth as a mechanism of organ size control, as general regulatory steps in the specification of visual organs.