Protection from experimental colitis by theaflavin-3,3'-digallate correlates with inhibition of IKK and NF-κB activation

Background and purpose: Inflammatory bowel disease (IBD) is associated with activation of nuclear factor κ B (NF-κB) involved in regulating the expression of inducible nitric oxide synthase (iNOS) and proinflammatory cytokine genes. As theaflavin-3,3'-digallate (TFDG), the most potent anti-oxidant polyphenol of black tea, down-regulates NF-κB activation, we investigated if TFDG is beneficial in colonic inflammation by suppressing iNOS and proinflammatory cytokines. Experimental approach: The in vivo efficacy of TFDG was assessed in mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis. Both mRNA and protein levels of proinflammatory cytokines and iNOS were analyzed in colon tissue treated with or without TFDG. NF-κB activation was determined by electrophoretic mobility shift assay and levels of NF-κB inhibitory protein (IκBα) were analyzed by Western blotting. Key results: Oral administration of TFDG (5 mg kg-1 daily i.g.) significantly improved TNBS-induced colitis associated with decreased mRNA and protein levels of TNF-α, IL-12, IFN- and iNOS in colonic mucosa. DNA binding and Western blotting revealed increase in NF-κB activation and IκB depletion in TNBS-treated mice from Day 2 through Day 8 with a maximum at Day 4, which resulted from increased phosphorylation of IκB and higher activity of IκB kinase (IKK). Pretreatment with TFDG markedly inhibited TNBS-induced increases in nuclear localization of NF-κBα, cytosolic IKK activity and preserved IκBα in colon tissue. Conclusions and Implications: TFDG exerts protective effects in experimental colitis and inhibits production of inflammatory mediators through a mechanism that, at least in part, involves inhibition of NF-κB activation

Affinity binding of non-histone chromatin proteins to the X chromosome of Drosophila by in situ chromatin reconstitution and its significance

Cytophotometric analysis of the in situ binding affinity of non-histone chromosomal protein (NHCP) to the polytenic X chromosome and autosome of Drosophila melanogaster has been carried out using Feulgen-Napthol Yellow S staining technique. The results reveal that the mean transformed absorbance ratio (male:female) with a 547nm interference band filter for the two specific segments of the X chromosome is close to 0-5, while for a specific segment of an autosome it is close to l"0, in the two sets of control; namely, the positive control (no treatment) and the negative control (treated with 1 M-urea+2M-NaCl) as well as in the reconstituted chromosomal preparations, which received 1 M-urea+2M-NaCl and the NHCP isolated from D. melanogaster. In contrast, the transformed absorbance ratios (male:female) with a 433 nm interference band filter yielded an interestingly different result. The ratios with a 433 nm filter for the X chromosome segments are significantly greater than 0-5 in all three sets of experiments. This finding by itself suggests that the NHCP binding affinity is dissimilar for the X chromosomes of male and female. When the 433 to 547 nm absorbance ratios were compared among the three sets, the data clearly revealed that in both positive control and NHCP reconstituted samples, the absorbance ratios (i.e. 433:547 nm) are significantly different between X chromosomes from males and those from females, while they are different between autosomes from males and females. The ratios are also not significantly different between male and female, either for the X chromosome or for the autosome in the negative control. These findings, therefore, suggest that there is a stronger binding affinity of NHCP for the male X chromosome of Drosophila, and reinstate the view that the X chromosomal hyperactivity in male Drosophila is the consequence of a regulated organizational change in the DNA template

Reconfiguration and load balancing in the LV and MV distribution networks for optimal performance

Abstract: To get the distribution network to operate at its optimum performance in an automated distribution system reconfiguration was been proposed and researched. Considering, however, that optimum performance implies minimum loss, no overloading of transformers and cables, correct voltage profile, and absence of phase voltage and current imbalances, network reconfiguration alone is insufficient. It has to be complemented with techniques for phase rearrangement between the distribution transformer banks and the specific primary feeder with a radial structure and dynamic phase and load balancing along a feeder with a radial structure. This paper contributes such a technique at the low-voltage and medium-voltage levels of a distribution network simultaneously with reconfiguration at both levels. While the neural network is adopted for the network reconfiguration problem, this paper introduces a heuristic method for the phase balancing/loss minimization problem. A comparison of the heuristic algorithm with that of the neural network shows the former to be more robust. The approach proposed here, therefore for the combined problem, uses the neural network in conjunction with a heuristic method which enables different reconfiguration switches to be turned on/off and connected consumers to be switched between different phases to keep the phases balanced. An application example of the proposed method using real data is presente