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Avian migration is an exceptionally high-energy-demanding process, which is met by the accumulation and utilization of fuel stores as well as the alterations in muscle physiology prior to their flight. Pre-migratory fattening coupled with changes in flight muscle metabolic enzymes and proteome is required to provide the necessary fuel and muscle performance required for migration. We studied how the serum metabolites (urea, uric acid, and creatinine), pectoralis muscle metabolites (glycogen, glucose, and cholesterol), muscle metabolic enzymes (CPT, HOAD, CS, MDH, CCO, CK, LDH, PFK, MLPL, and PK), liver lipogenic enzyme (FAS), and pectoralis muscle proteins get altered in pre-migratory and non-migratory buntings. Significantly increased pectoralis muscle fatty acid oxidation (CPT and HOAD activity), aerobic/anaerobic capacity (CS, CCO, and MDH activity), glycolytic capacity (PFK and PK activity), lipolysis (muscle LPL), and burst power (CK activity) were observed prior to the spring migration in pre-migratory buntings, whereas significantly increased pectoralis muscle anaerobic capacity (LDH activity) was observed in non-migratory buntings. Significant increase in the liver FAS showed profound lipogenesis prior to the spring migration. In this study, we have also investigated whether muscle has differential protein content during the pre-migratory and non-migratory phases of the annual migratory cycle. Twenty-nine proteins are identified and well characterized varying in expression significantly during the pre-migratory and non-migratory phases. These findings indicate that significant pre-migratory fattening and alterations in flight (pectoralis) muscle biochemistry and proteome in between the non- and pre-migratory phases may play a significant role in pre-migratory flight muscle preparation in these long-route migrants. [ABSTRACT FROM AUTHOR]

Abstract: The expression of PR-1a gene in tobacco is accompanied by changes in the chromatin architecture over its promoter region. The transcription initiates when the gene is induced in defense response, a condition that can be simulated experimentally by external application of salicylic acid. Mutagenesis of the core promoter sequence established that the TATA-box was critical to the expression of PR-1a gene. In order to study functional specificity between the core promoter and upstream activator region, the native core promoter was exchanged with that of a heterologous salicylic acid inducible promoter, Pcec. The core promoter and the activator region of PR-1a together determine its tightly regulated expression, slow kinetics of induction by SA and several fold induction of expression. In uninduced state, a single nucleosome was present over the core promoter of PR-1a. It masked both the TATA-box and the transcription initiation region. The transcriptional activation of the promoter by SA was accompanied by shift in the position of this nucleosome. The chimeric promoters failed to show inducibility or gave very low level of induction. They showed failure in shifting the nucleosome from the core promoter region. The promoter Pcec expressed constitutively at a high uninduced level in spite of a nucleosome over the TATA-box region. However, in this case, the nucleosome did not mask the transcript initiation region. The TATA-box nucleosome was shifted as the expression increased further, following induction by SA. A fully induced Pcec had the TATA-box fully exposed, though a weak nucleosome appeared on the +1 region. The results support a close relationship among promoter sequence architecture, nucleosome positioning and PR-1a expression. [Copyright &y& Elsevier]

Advanced glycation end products (AGEs) trigger intracellular reactive oxygen species (ROS) generation, activation of receptor for AGEs (RAGE) expression/functionality and RAGE-associated signalling pathways which influence the diabetic-cum-atherosclerotic complications, whereas, the atherosclerosis progression is greatly influenced by hepatic β-Hydroxy-β-methyl-glutaryl-Co-A reductase (HMG-R) activity. The present report was premeditated to uncover the regulatory role of HMG-R inhibitors and ezetimibe (EZ) in attenuating the LDL-AGEs-induced pathogenicity via targeting cellular-ROS and RAGE-associated signalling in HEK-293 cells. The MTT assay was used to assess either the cytotoxic or cytoprotective impact of each HMG-R inhibitors, EZ, and LDL-AGEs, whereas, quantification of ROS was performed by DCFDA method. The qRT-PCR was used to detect the mRNA level of RAGE, neuropilin-1 (NRP-1) and other RAGE-associated genes like MMP-2, NF-κB, and TGFβ-1. The HMG-R inhibitors do not exert any cytotoxicity in HEK-293 cells, whereas, and LDL-AGEs negatively affected the cell viability of HEK-293 cells. However, viability of LDL-AGEs-treated HEK-293was markedly retained after simultaneous treatment with our test inhibitors. Further, DCFDA staining showed that LDL-AGEs-induced ROS was also suppressed upon treatment with our test inhibitors in HEK-293 cells. qRT-PCR analysis reflected that these inhibitors suppress the RAGE, NF-κB, TGFβ-1, and MMP-2 expression, whereas, the NRP-1 was up-regulated by these compounds in LDL-AGEs-exposed HEK-293 cells. The above pharmacological effects signify that HMG-R inhibitors and EZ (alone or in combination) may implied in the treatment of AGEs-induced oxidative stress and tissue damage in diabetic complications via targeting intracellular-ROS, NRP-1 functionality and RAGE-associated genes i.e. NF-κB, TGFβ-1, and MMP-2. Unlabelled Image [ABSTRACT FROM AUTHOR]