Design,synthesis and molecular docking of thiazolidinedione based benzene sulphonamide derivatives containing pyrazole core as potential anti-diabetic agents

We herein report the design, synthesis and molecular docking studies of 2,4-thiazolidinedione derivatives containing benzene sulphonyl group which are docked against the Peroxisome Proliferator Activated Receptor (PPARγ) target. Compound 7p was most effective in lowering the blood glucose level as compared to standard drugs pioglitazone and rosiglitazone. Compound 7p exhibited potent PPAR-γ transactivation of 61.2% with 1.9 folds increase in gene expression. In molecular docking studies 7p showed excellent interactions with amino acids TYR 473, SER 289, HIE 449, TYR 327, ARG 288, MET 329 and LEU 228. Compound 7p did not cause any damage to the liver without any noteworthy weight gain and may be considered as promising candidates for the development of new antidiabetic agents.     

mRNA degradation in bacteria

Messenger RNAs in prokaryotes exhibit short half-lives when compared with eukaryotic mRNAs. Considerable progress has been made during recent years in our understanding of mRNA degradation in bacteria. Two major aspects determine the life span of a messenger in the bacterial cell. On the side of the substrate, the structural features of mRNA have a profound influence on the stability of the molecule. On the other hand, there is the degradative machinery. Progress in the biochemical characterization of proteins involved in mRNA degradation has made clear that RNA degradation is a highly organized cellular process in which several protein components, and not only nucleases, are involved. In Escherichia coli, these proteins are organized in a high molecular mass complex, the degradosome. The key enzyme for initial events in mRNA degradation and for the assembly of the degradosome is endoribonuclease E. We discuss the identified components of the degradosome and its mode of action. Since research in mRNA degradation suffers from dominance of E. coli-related observations we also look to other organisms to ask whether they could possibly follow the E. coli standard model.     

1,25-Dihydroxyvitamin D3 inhibits parathyroid hormone-related peptide mRNA expression in fetal rat long bones in culture

Summary When fetal rat long bones are incubated in the presence of 10⁻⁸ M 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], steady-state parathyroid hormone-related peptide (PTHrP) mRNA levels are decreased. This decrease is temporary: it is observed as soon as after 3 h of exposure and reaches a nadir after 6 h. At that time, PTHrP mRNA levels are significantly lower in the experimental than in the control bones. However the inhibitory effect vanishes after 24 h, despite continuous exposure to 1,25(OH)₂D₃ for even 48 h. This is the first report showing that PTHrP mRNA expression can be regulated in rat fetal long bones in vitro by 1,25(OH)₂D₃.     

Phosphate metabolism during diel vertical migration in the raphidophycean alga, Chattonella antiqua

The ecological advantage of diel vertical migration on the nutrition and accumulation of Chattonella antiqua, which is one of the dominant red-tide forming phytoplankton species in the Seto Inland Sea of Japan, was examined using a large axenic culture tank, in which vertical stratification of salinity, temperature and nutrients was maintained, analogous to natural conditions observed when red tides occur. C. antiqua was capable of migrating through very sharp salinity and temperature gradients. At night the species migrated to the deep nutrient-rich water and assimilated nutrients. During the daytime it migrated to the nutrient-depleted surface water and used the accumulated nutrients for photosynthesis. Nitrogen uptake was synchronized with phosphate uptake. ³¹P-NMR spectroscopy during the migration experiment revealed that C. antiqua has the capability of nocturnal phosphate uptake in the deep nutrient-rich water, but no capability of synthesizing polyphosphate, which was considered to be the intracellular phosphate pool. These findings were compared with those reported for another raphidophycean, Heterosigma akashiwo. Although both species carry out vertical migration and nocturnal nutrient uptake, only H. akashiwo has the capability of making an intracellular polyphosphate pool. This revised version was published online in July 2006 with corrections to the Cover Date.     

Rapid bidirectional modulation of mRNA expression and export accompany long‐term facilitation and depression of Aplysia synapses

Serotonin (5‐HT) and the neuropeptide Phe‐Met‐Arg‐Phe‐amide (FMRFa) modulate synaptic efficacy of sensory neurons (SNs) of Aplysia in opposite directions and for long duration. Both long‐term responses require changes in mRNA and protein synthesis. The SN‐specific neuropeptide, sensorin A, is a gene product that appears to be increased by 5‐HT and decreased by FMRFa. We examined whether changes in sensorin A mRNA levels in the cell body and neurites of SNs accompany long‐term facilitation and depression. Both 5‐HT and FMRFa evoked rapid changes in sensorin A mRNA levels in the SN cell bodies: an increase with 5‐HT and a decrease with FMRFa. Parallel changes in sensorin A mRNA levels in SN neurites were detected 2 h and 4 h later. These rapid changes in mRNA expression and net export required the presence of the appropriate target motor cell L7. The neuromodulators failed to produce changes in mRNA expression or export when SNs were cultured alone or with the inappropriate target cell L11. The changes in mRNA expression were transient because mRNA levels returned to control values 24 h after treatment, while synaptic efficacy remained altered by the respective treatments. These results indicate that two neuromodulators produce distinct, but transient, target‐dependent effects on expression and export of a cell‐specific mRNA that correlate with changes in synaptic plasticity. © 2000 John Wiley & Sons, Inc. J Neurobiol 46: 41–47, 2001     

小麦赤霉病拮抗菌JB7的拮抗活性及鉴定

由禾谷镰刀菌(Fusarium graminearum, Fg)引起的赤霉病是限制小麦生产的主要病害之一。生物防治是一种高效且可持续的防治方法。【目的】从小麦种子内筛选具有抑制禾谷镰刀菌的菌株并对其生防潜力进行评估,为小麦赤霉病生防制剂的开发与利用提供菌种资源及理论支撑。【方法】采用平板对峙、孢子萌发法和无菌上清液抑菌试验筛选小麦种子内对禾谷镰刀菌具有拮抗活性的内生菌株;利用扫描电镜(scanning electron microscope, SEM)和共聚焦扫描电镜(confocal laser scanning microscope, CLSM)观察并分析无菌上清液对Fg的分生孢子形态、膜完整性以及胞内活性氧的影响;通过盆栽试验验证内生菌对小麦赤霉病的生防效果;应用二代Illumina HiSeq测序平台进行全基因组测序。【结果】从小麦种子中分离出一株高效抑制Fg生长的内生菌株JB7,其衰亡期无菌上清液对Fg孢子萌发抑制率高达85.23%。菌株JB7的无菌上清液使Fg孢子表面凹陷,破坏其细胞膜,造成核酸和蛋白质的渗漏,诱导Fg菌丝活性氧的累积,引起Fg菌丝可溶性蛋白和丙二醛含量的显著升高。该菌株具有分泌蛋白酶、纤维素酶、葡聚糖酶和产铁载体的能力。盆栽试验表明菌株JB7能显著降低小麦赤霉病的病情指数(P<0.05)。经全基因组学鉴定为甲基营养型芽孢杆菌(Bacillus methylotrophicus) JB7,该菌株基因组中含有12个抑菌功能的次级代谢产物合成基因簇。【结论】菌株JB7能抑制禾谷镰刀菌的生长,对小麦赤霉病有较强的防效,可作为生物防治小麦赤霉病的候选菌株。