Glucose represses the transcription of many genes in bakers yeast (Saccharomyces cerevisiae). Mig1 is a Cys2-His2 zinc finger protein that mediates glucose repression of several genes by binding to their promoters and recruiting the general repression complex Ssn6-Tup1. We have found that the subcellular localization of Mig1 is regulated by glucose. Mig1 is imported into the nucleus within minutes after the addition of glucose and is just as rapidly transported back to the cytoplasm when glucose is removed. This regulated nuclear localization requires components of the glucose repression signal transduction pathway. An internal region of the protein separate from the DNA binding and repression domains is necessary and sufficient for glucose-regulated nuclear import and export. Changes in the phosphorylation status of Mig1 are coincident with the changes in its localization, suggesting a possible regulatory role for phosphorylation. Our results suggest that a glucose-regulated nuclear import and/or export mechanism controls the activity of Mig1.

Magnetic resonance imaging using fluorinated contrast agents (F MRI) enables to achive highcontrast in images due to the negligible fluorine background in living tissues. In this pilot study, we developed new biocompatible, temperature-responsive, and easily synthesized polymeric nanogels containing a sufficient concentration of magnetically equivalent fluorine atoms for F MRI purposes. The structure of the nanogels is based on amphiphilic copolymers containing two blocks, a hydrophilic poly[ N-(2-hydroxypropyl)methacrylamide] (PHPMA) or poly(2-methyl-2-oxazoline) (PMeOx) block, and a thermoresponsive poly[ N(2,2difluoroethyl)acrylamide] (PDFEA) block. The thermoresponsive properties of the PDFEA block allow us to control the process of nanogel self-assembly upon its heating in an aqueous solution. Particle size depends on the copolymer composition, and the most promising copolymers with longer thermoresponsive blocks form nanogels of suitable size for angiogenesis imaging or the labeling of cells (approximately 120 nm). The in vitroF MRI experiments reveal good sensitivity of the copolymer contrast agents, while the nanogels were proven to be noncytotoxic for several cell lines.

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Recently, 19F magnetic resonance imaging (MRI) emerged as a powerful noninvasive diagnostic tool in modern medicine. Fluorinated polymer materials represent an attractive class of MRI contrast agents (CAs) due to their structural variability and tunable properties. Herein, we describe for the first time the 19F MRI of CAs based on fluorinated water-soluble poly­(2-oxazoline)­s (PAOx), a polymer class with increasing popularity in biomedical sciences. A series of fluorinated PAOx with increasing fluorine content were synthesized by controlled side-chain hydrolysis of poly­(2-methyl-2-oxazoline) followed by reacylation of its ethylenimine units by difluoroacetic anhydride. As the increasing fluorine content leads to the copolymer hydrophobization, their composition was optimized for maximal 19F MRI performance while retaining good solubility in water. The magnetic properties of the water-soluble polymers were studied in vitro by 19F NMR and MRI, revealing their outstanding relaxation properties and imaging sensitivity. All CAs were found to be noncytotoxic for HeLa cells in vitro. Finally, the diagnostic potential of the new CAs was demonstrated by a successful in vivo 19F MRI visualization of the selected fluorinated polymer in rats.