Benzylideneoxymorphone: A new lead for development of bifunctional mu/delta opioid receptor ligands

Opioid analgesic tolerance remains a considerable drawback to chronic pain management. The finding that concomitant administration of delta opioid receptor (DOR) antagonists attenuates the development of tolerance to mu opioid receptor (MOR) agonists has led to interest in producing bifunctional MOR agonist/DOR antagonist ligands. Herein, we present 7-benzylideneoxymorphone (6, UMB 246) displaying MOR partial agonist/DOR antagonist activity, representing a new lead for designing bifunctional MOR/DOR ligands.     

Lung injury caused by high tidal volume mechanical ventilation and hyperoxia is dependent on oxidant-mediated c-Jun NH2-terminal kinase activation

Both prolonged exposure to hyperoxia and large tidal volume mechanical ventilation can each independently cause lung injury. However, the combined impact of these insults is poorly understood. We recently reported that preexposure to hyperoxia for 12 h, followed by ventilation with large tidal volumes, induced significant lung injury and epithelial cell apoptosis compared with either stimulus alone (Makena et al. Am J Physiol Lung Cell Mol Physiol 299: L711-L719, 2010). The upstream mechanisms of this lung injury and apoptosis have not been clearly elucidated. We hypothesized that lung injury in this model was dependent on oxidative signaling via the c-Jun NH(2)-terminal kinases (JNK). We, therefore, evaluated lung injury and apoptosis in the presence of N-acetyl-cysteine (NAC) in both mouse and cell culture models, and we provide evidence that NAC significantly inhibited lung injury and apoptosis by reducing the production of ROS, activation of JNK, and apoptosis. To confirm JNK involvement in apoptosis, cells treated with a specific JNK inhibitor, SP600125, and subjected to preexposure to hyperoxia, followed by mechanical stretch, exhibited significantly reduced evidence of apoptosis. In conclusion, lung injury and apoptosis caused by preexposure to hyperoxia, followed by high tidal volume mechanical ventilation, induces ROS-mediated activation of JNK and mitochondrial-mediated apoptosis. NAC protects lung injury and apoptosis by inhibiting ROS-mediated activation of JNK and downstream proapoptotic signaling.     

Candida krusei : biotechnological potentials and concerns about its safety

Yeasts have a tradition in biotechnological applications, and Saccharomyces species are the most dominating representatives. Among the yeast species, Candida krusei has been isolated from different habitats, and in recent years, it has gained increased interest because of its diverse biotechnological role. It is found in many fermented food items and dairy products and has also been exploited for production of biochemicals and enzymes. However, because of its opportunistic pathogenic nature, it draws scientific attention regarding the safety of its industrial exploitation. Candida?krusei generally causes infections in immunocompromised patients, such as those suffering from Human immunodeficiency virus - acquired immune deficiency syndrome, and also in cancer patients. The recent increase in the use of immunosuppressive drugs has increased the chances of C.?krusei infections. Candida?krusei possesses an intrinsic resistance to many triazole antifungal drugs, especially fluconazole, which is a main drug used in antifungal therapy; therefore, there is serious concern regarding its safe industrial use.     

Development of single nucleotide polymorphism (SNP) markers for use in commercial maize (Zea mays L.) germplasm

The development of single nucleotide polymorphism (SNP) markers in maize offers the opportunity to utilize DNA markers in many new areas of population genetics, gene discovery, plant breeding and germplasm identification. However, the steps from sequencing and SNP discovery to SNP marker design and validation are lengthy and expensive. Access to a set of validated SNP markers is a significant advantage to maize researchers who wish to apply SNPs in scientific inquiry. We mined 1,088 loci sequenced across 60 public inbreds that have been used in maize breeding in North America and Europe. We then selected 640 SNPs using generalized marker design criteria that enable utilization with several SNP chemistries. While SNPs were found on average every 43 bases in 1,088 maize gene sequences, SNPs that were amenable to marker design were found on average every 623 bases; representing only 7% of the total SNPs discovered. We also describe the development of a 768 marker multiplex assay for use on the Illumina^® BeadArray? platform. SNP markers were mapped on the IBM2 intermated B73 × Mo17 high resolution genetic map using either the IBM2 segregating population, or segregation in multiple parent-progeny triplets. A high degree of colinearity was found with the genetic nested association map. For each SNP presented we give information on map location, polymorphism rates in different heterotic groups and performance on the Illumina^® platform.     

Production of alkaline protease with immobilized cells of bacillus subtilis PE-11 in various matrices by entrapment technique

The purpose of this investigation was to study the effect ofBacillus subtilis PE-11 cells immobilized in various matrices, such as calcium alginate, k-Carrageenan, ployacrylamide, agar-agar, and gelatin, for the production of alkaline protease. Calcium alginate was found to be an effective and suitable matrix for higher alkaline protease productivity compared to the other matrices studied. All the matrices were selected for repeated batch fermentation. The average specific volumetric productivity with calcium alginate was 15.11 U/mL/hour, which was 79.03% higher production over the conventional free-cell fermentation. Similarly, the specific volumetric productivity by repeated batch fermentation was 13.68 U/mL/hour with k-Carrageenan, 12.44 U/mL/hour with agar-agar, 11.71 U/mL/hour with polyacrylamide, and 10.32 U/mL/hour with gelatin. In the repeated batch fermentations of the shake flasks, an optimum level of enzyme was maintained for 9 days using calcium alginate immobilized cells. From the results, it is concluded that the immobilized cells ofB subtilis PE-11 in calcium alginate are more efficient for the production of alkaline protease with repeated batch fermentation. The alginate immobilized cells ofB subtilis PE-11 can be proposed as an effective biocatalyst for repeated usage for maximum production of alkaline protease. Published: October 21, 2005     

Simultaneous single-cell protein production and COD removal with characterization of residual protein and intermediate metabolites during whey fermentation by K. marxianus

Cheese whey fermentation with Kluyveromyces marxianus was carried out at 40 °C and pH 3.5 to examine simultaneous single-cell protein production and chemical oxygen demand (COD) removal, determine the fate of soluble whey protein and characterize intermediate metabolites. After 36 h of batch fermentation, the biomass concentration increased from 2.0 to 6.0 g/L with 55 % COD reduction (including protein), whereas soluble whey protein concentration decreased from 5.6 to 4.1 g/L. It was confirmed through electrophoresis (SDS-PAGE) that the fermented whey protein was different from native whey protein. HPLC and GC–MS analysis revealed a change in composition of organic compounds post-fermentation. High inoculum concentration in batch fermentation resulted in an increase in biomass concentration from 10.3 to 15.9 g/L with 80 % COD reduction (including protein) within 36 h with residual protein concentration of 4.5 g/L. In third batch fermentation, the biomass concentration increased from 7.3 to 12.4 g/L with 71 % of COD removal and residual protein concentration of 4.3 g/L after 22 h. After 22 h, the batch process was shifted to a continuous process with cell recycle, and the steady state was achieved after another 60 h with biomass yield of 0.19 g biomass/g lactose and productivity of 0.26 g/L h. COD removal efficiency was 78–79 % with residual protein concentration of 3.8–4.2 g/L. The aerobic continuous fermentation process with cell recycle could be applied to single-cell protein production with substantial COD removal at low pH and high temperature from cheese whey.