MM-102

We studied sixteen morphometric and eight meristic characteristics of forty-five goldside loaches from two rivers in central Croatia, the Bijela and the Petrinjcica, belonging to the Sava River basin. We found significant differences (P<0.01) in all the morphometric characteristics of the populations from these two rivers. While the mean total length (TL) of the goldside loache population from Petrinjcica (mean TL = 60.4 mm, min-max = 52.8 - 70.2 mm) is comparable with TL in other populations described in Europe, individuals from the Bijela seem to be significantly larger (mean TL = 91.8 mm; min-max = 76.4 mm- 102.4 mm) and are among the longest specimens in Europe. Although we can not be sure if this is a result of phenotype variability or some specific taxonomic quality, the position of the Bijela on the old isolated massif of Mt Papuk may have led to the specific morphometric characteristics of this goldside loach population.

Diabetes nephropathy (DN) is the leading cause of end stage renal disease and it affects up to 40% of diabetic patients. In addition to hyperglycemia, genetic factors are thought to contribute to the development of DN, but few if any genetic factors have been convincingly linked to DN. Other possible mechanisms may involve epigenetic regulation of glucose-stimulated gene activity which was suggested to explain long-term effects of poor glycemic control on risk of diabetic complications, often referred to as metabolic memory. Osteopontin (OPN) is one of the genes upregulated in kidneys from diabetic mouse models as well as humans with DN, and suggested to play an important role in the pathogenesis of DN. In this study, we demonstrated that OPN gene expression is upregulated in the kidneys of a hyperglycemia diabetes mouse model SUR1-E1506K, and glucose-stimulated OPN gene expression is strongly associated with increases in activating histone marks H3K9ac, H3K4me1 and H3K4me3 and decrease in inactivating mark H3K27me3 in the promoter region of OPN gene.

Mixed lineage leukemia 1 (MLL1) is a histone H3 lysine 4 (H3K4) methyltransferase, and targeting the MLL1 enzymatic activity has been proposed as a novel therapeutic strategy for the treatment of acute leukemia harboring MLL1 fusion proteins. The MLL1/WDR5 protein-protein interaction is essential for MLL1 enzymatic activity. In the present study, we designed a large number of peptidomimetics to target the MLL1/WDR5 interaction based upon -CO-ARA-NH-, the minimum binding motif derived from MLL1. Our study led to the design of high-affinity peptidomimetics, which bind to WDR5 with K(i) < 1 nM and function as potent antagonists of MLL1 activity in a fully reconstituted in vitro H3K4 methyltransferase assay. Determination of co-crystal structures of two potent peptidomimetics in complex with WDR5 establishes their structural basis for high-affinity binding to WDR5. Evaluation of one such peptidomimetic, MM-102, in bone marrow cells transduced with MLL1-AF9 fusion construct shows that the compound effectively decreases the expression of HoxA9 and Meis-1, two critical MLL1 target genes in MLL1 fusion protein mediated leukemogenesis.

PURPOSE: One important reconstruction procedure following pelvic tumor resection is ipsilateral femoral autograft reconstruction in which the autograft is transposed onto the defect and a conventional total hip replacement is implanted in the autograft. The purpose of this study is to provide anatomical evidence for this reconstruction by measurement of proximal femoral autografts.