Efficient synthesis and in vitro cytostatic activity of 4-substituted triazolyl-nucleosides

We report herein an efficient synthesis of 4-substituted triazolyl-nucleosides and their in vitro cytostatic activity. The synthesis is based on a straightforward 1,3-dipolar cycloaddition between 1-azido-ribose 2 and terminal alkynes under a cooperative effect of microwave activation and copper (I) catalysis. All cycloadducts were obtained in nearly quantitative yield after a short reaction time (1 to 2min). After removal of acetyl protecting groups, the free nucleosides were evaluated against L1210, Molt4/C8, and CEM tumor cell lines. Structure-activity relationship study shows that the substituent on the triazole ring has a major effect since nucleosides 4c and 4g, containing, respectively, a long alkyl chain and an aryl donor group are the most active compounds in this series.     

Prawn lipocalin: characteristics and expressional pattern in subepidermal adipose tissue during reproductive molting cycle

In crustaceans, the fascinating processes of maturation, reproductive molting and carapace coloration are regulated by hydrophobic molecules. Interestingly, most of the molecules are ligands of lipocalin. To understand the role of lipocalin in the aforementioned processes at molecular level, we isolated a cDNA that belongs to the lipocalin family, from a central nervous system cDNA library of Macrobrachium rosenbergii. We monitored the spatial and temporal distributions of the mRNA by using Northern Blotting analysis. Our results demonstrated that this gene expresses abundantly in the subepidermal adipose tissue, while faintly in the hepatopancreas and central nervous system. However, no signal was detected in other tissues including muscle, gill and ovary. Its expression levels in subepidermal adipose tissue during various stages of maturation as well as through the whole molting cycle showed that prawn lipocalin is involved in sexual maturation, as the maximal level was observed just after molt.     

Differential response of etiolated pea seedlings to inoculation with rhizobacteria capable of utilizing 1-aminocyclopropane-1-carboxylate or L-methionine

The majority of soil microorganisms can derive ethylene from L-methionine (L-MET), while some rhizobacteria can hydrolyze 1-aminocyclopropane-1-carboxylate (ACC) due to their ACC-deaminase activity. In this study, three strains having either ACC-deaminase activity (Pseudomonas putida biotype A, A7), or the ability to produce ethylene from L-MET (Acinetobacter calcoaceticus, M9) or both (Pseudomonas fluorescens, AM3) were used for inoculation. The highly ethylene specific bioassay of a classical "triple" response in pea seedlings was used to investigate the effect of the inoculation with the rhizobacteria in the presence of 10 mM ACC or L-MET. The exogenous application of ACC had a concentration-dependent effect on the etiolated pea seedlings in creating the classical "triple" response. The inoculation with P. putida diluted the effect of ACC, which was most likely due to its ACC-deaminase activity. Similarly, the application of Co2+ reduced the ACC-imposed effect on etiolated pea seedlings. In contrast, the inoculation of A. calcoaceticus or P. fluorescens in the presence of L-MET caused a stronger classical "triple" response in etiolated pea seedlings; most likely by producing ethylene from L-MET. This is the first study, to our knowledge, reporting on the comparative effect of rhizobacteria capable of utilizing ACC vs L-MET on etiolated pea seedlings.     

Biodegradation of α- and β-endosulfan by soil bacteria

Extensive applications of persistent organochlorine pesticides like endosulfan on cotton have led to the contamination of soil and water environments at several sites in Pakistan. Microbial degradation offers an effective approach to remove such toxicants from the environment. This study reports the isolation of highly efficient endosulfan degrading bacterial strains from soil. A total of 29 bacterial strains were isolated through enrichment technique from 15 specific sites using endosulfan as sole sulfur source. The strains differed substantially in their potential to degrade endosulfan in vitro ranging from 40 to 93% of the spiked amount (100 mg l⁻¹). During the initial 3 days of incubation, there was very little degradation but it got accelerated as the incubation period proceeded. Biodegradation of endosulfan by these bacteria also resulted in substantial decrease in pH of the broth from 8.2 to 3.7 within 14 days of incubation. The utilization of endosulfan was accompanied by increased optical densities (OD₅₉₅) of the broth ranging from 0.511 to 0.890. High performance liquid chromatography analyses revealed that endosulfan diol and endosulfan ether were among the products of endosulfan metabolism by these bacterial strains while endosulfan sulfate, a persistent and toxic metabolite of endosulfan, was not detected in any case. The presence of endosulfan diol and endosulfan ether in the bacterial metabolites was further confirmed by GC-MS. Abiotic degradation contributed up to 21% of the spiked amount. The three bacterial strains, Pseudomonas spinosa, P. aeruginosa, and Burkholderia cepacia, were the most efficient degraders of both α- and β-endosulfan as they consumed more than 90% of the spiked amount (100 mg l⁻¹) in the broth within 14 days of incubation. Maximum biodegradation by these three selected efficient bacterial strains was observed at an initial pH of 8.0 and at an incubation temperature of 30°C. The results of this study may imply that these bacterial strains could be employed for bioremediation of endosulfan polluted soil and water environments.     

Improved production of biosurfactant by a <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> mutant using vegetable oil refinery wastes

Biosurfactant production by Pseudomonas aeruginosa EBN-8 mutant was studied in shake flasks on separate wastes from canola, soybean and corn oil refineries. Of the substrates tested, canola oil refinery waste (COD=20 g l⁻¹) supplemented with sodium nitrate (at COD/N=20) showed the best microbial growth (4.50 g l⁻¹) and rhamnolipid production (8.50 g l⁻¹), at 10 d of incubation with the specific growth rate of 0.316 h⁻¹ and specific product yield of 0.597 g g⁻¹ h. Its cell-free supernatant showed the critical micelle dilution (CMD) of 150 and surface tension (ST) of 28.5 mN m⁻¹.     

Rosiglitazone treatment improves cardiac efficiency in hearts from diabetic mice

Isolated perfused hearts from type 2 diabetic (db/db) mice show impaired ventricular function, as well as altered cardiac metabolism. Assessment of the relationship between myocardial oxygen consumption (MVO(2)) and ventricular pressure-volume area (PVA) has also demonstrated reduced cardiac efficiency in db/db hearts. We hypothesized that lowering the plasma fatty acid supply and subsequent normalization of altered cardiac metabolism by chronic treatment with a peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist will improve cardiac efficiency in db/db hearts. Rosiglitazone (23 mg/kg body weight/day) was administered as a food admixture to db/db mice for five weeks. Ventricular function and PVA were assessed using a miniaturized (1.4 Fr) pressure-volume catheter; MVO(2) was measured using a fibre-optic oxygen sensor. Chronic rosiglitazone treatment of db/db mice normalized plasma glucose and lipid concentrations, restored rates of cardiac glucose and fatty acid oxidation, and improved cardiac efficiency. The improved cardiac efficiency was due to a significant decrease in unloaded MVO(2), while contractile efficiency was unchanged. Rosiglitazone treatment also improved functional recovery after low-flow ischemia. In conclusion, the present study demonstrates that in vivo PPARgamma-treatment restores cardiac efficiency and improves ventricular function in perfused hearts from type 2 diabetic mice.     

Evaluation of antitumor effects of VEGFR-2 inhibitor F16 in a colorectal xenograft model

Biotechnology Letters - Colorectal cancer&nbsp;(CRC) is the third most prevalent type of cancer in the United States. The treatment options for cancer include surgery, chemotherapy, radiation,...     

Molecular Simulations of Gram-Negative Bacterial Membranes: A Vignette of Some Recent Successes

In the following review we use recent examples from the literature to discuss progress in the area of atomistic and coarse-grained molecular dynamics simulations of selected bacterial membranes and proteins, with a particular focus on Gram-negative bacteria. As structural biology continues to provide increasingly high-resolution data on the proteins that reside within these membranes, simulations have an important role to play in linking these data with the dynamical behavior and function of these proteins. In particular, in the last few years there has been significant progress in addressing the issue of biochemical complexity of bacterial membranes such that the heterogeneity of the lipid and protein components of these membranes are now being incorporated into molecular-level models. Thus, in future we can look forward to complementary data from structural biology and molecular simulations combining to provide key details of structure-dynamics-function relationships in bacterial membranes.