Assessment of the antifungal activity of the violacein-forming strain Janthinobacterium sp. B-3515 against the mould fungus Alternaria brassicicola F-1864

A study of antifungal properties of violacein-forming strain Janthinobacterium sp. B-3515 as well as its secondary metabolite, violacein, against Alternaria brassicicola F-1864 is presented. Regardless of the presence of bacteria, mycelium growth in the first two days proceeded at the same rate. The effect of the bacterial strain was manifested after the third day of incubation. In general, during co-culture, the bacterial strain statistically significantly reduced the average growth of the mycelium of the mould fungus by 10

A New Mixed-Backbone Oligonucleotide against Glucosylceramide Synthase Sensitizes Multidrug-Resistant Tumors to Apoptosis

Enhanced ceramide glycosylation catalyzed by glucosylceramide synthase (GCS) limits therapeutic efficiencies of antineoplastic agents including doxorubicin in drug-resistant cancer cells. Aimed to determine the role of GCS in tumor response to chemotherapy, a new mixed-backbone oligonucleotide (MBO-asGCS) with higher stability and efficiency has been generated to silence human GCS gene. MBO-asGCS was taken up efficiently in both drug-sensitive and drug-resistant cells, but it selectively suppressed GCS overexpression, and sensitized drug-resistant cells. MBO-asGCS increased doxorubicin sensitivity by 83-fold in human NCI/ADR-RES, and 43-fold in murine EMT6/AR1 breast cancer cells, respectively. In tumor-bearing mice, MBO-asGCS treatment dramatically inhibited the growth of multidrug-resistant NCI/ADR-RE tumors, decreasing tumor volume to 37%, as compared with scrambled control. Furthermore, MBO-asGCS sensitized multidrug-resistant tumors to chemotherapy, increasing doxorubicin efficiency greater than 2-fold. The sensitization effects of MBO-asGCS relied on the decreases of gene expression and enzyme activity of GCS, and on the increases of C18-ceramide and of caspase-executed apoptosis. MBO-asGCS was accumulation in tumor xenografts was greater in other tissues, excepting liver and kidneys; but MBO-asGCS did not exert significant toxic effects on liver and kidneys. This study, for the first time in vivo, has demonstrated that GCS is a promising therapeutic target for cancer drug resistance, and MBO-asGCS has the potential to be developed as an antineoplastic agent

Collapse of extended deoxyribonucleoprotein molecules upon increase of the ionic strength of solution

The increase of the ionic strength of extremely dilute deoxyribonucleo protein (DNP) solution from 0.001 to 0.1 results in an intramolecular structural transition, which is reflected by a 2.5-fold increase of the sedimentation coefficient of the DNP and by the electron microscopic appearance of DNP molecules. The rate of this structural transition is considerably higher at 37° than at 0°. Both sedimentation and electron microscopic data allow one to suggest the existence of a supercoiled DNA in collapsed DNP molecules. Removal of the very lysine-rich histone (F1) and of some nonhistone proteins from the DNP results in the loss of its ability to undergo the above structural transition