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991.
Esther K. Schmitt D. Hoepfner P. Krastel 《Journal of industrial microbiology & biotechnology》2016,43(2-3):249-260
From the start of the pharmaceutical research natural products played a key role in drug discovery and development. Over time many discoveries of fundamental new biology were triggered by the unique biological activity of natural products. Unprecedented chemical structures, novel chemotypes, often pave the way to investigate new biology and to explore new pathways and targets. This review summarizes the recent results in the area with a focus on research done in the laboratories of Novartis Institutes for BioMedical Research. We aim to put the technological advances in target identification techniques in the context to the current revival of phenotypic screening and the increasingly complex biological questions related to drug discovery. 相似文献
992.
Fred R. Wolf Esther K. Nemethy Jonathan H. Blanding James A. Bassham 《Phytochemistry》1985,24(4):733-737
A ‘resting state’ isolate of the hydrocarbon-producing alga Botryococcus braunii photoassimilated sodium [14C]bicarbonate at rates comparable to fast growing algae, such as Chlorella (> 1.50 μg atoms 14C/mg chlorophyll·hr). Early in the reaction (up to several min), most of the radioactivity was associated with water-soluble metabolites. However, labelling of hexane-soluble compounds steadily from ca 3% at 15 sec to over 50% of the total incorporated 14C at 60 min. The purified hexane fraction, which consisted of a series of botryococcenes and squalene, constituted a relatively constant proportion (40–45%) of the total hexane-soluble radioactivity at all but the earliest time points (< 60 sec). This fraction initially consisted almost exclusively of a C30 botryococcene (ca 91%) and squalene (ca 8%); however, small amounts of radioactivity sequentially appeared in the C31, C32 and C34 botryococcenes. The results of pulse-chase experiments implicated the C30 botryococcene as the precursor of the higher homologues; during the chase, loss of radioactivity from the C30 compound was accompanied by a concomitant increase in the labelling of the C31 and C32 compounds. This study provides further evidence that the relatively slow growth of Botryococcus in culture may result, in part, from the diversion of a large proportion of reduced carbon into energetically expensive compounds and that the slower growth rate in the ‘resting state’ cannot be totally attributed to an impaired or intrinsically slow metabolism. 相似文献
993.
Griselda Vallejo Ana Cecilia Mestre-Citrinovitz Elke Winterhager Patricia Esther Saragüeta 《Journal of cellular physiology》2019,234(1):740-748
RNA-binding proteins (RBPs) have been described for cancer cell progression and differentiation, although there is still much to learn about their mechanisms. Here, using in vivo decidualization as a model, we describe the role of RBP cold shock domain containing C2 (CSDC2) in the endometrium. Csdc2 messenger RNA expression was differentially regulated depending on time and areas of decidua development, with the most variation in antimesometrium (AM) and, to a lesser degree, in the junctional zone (JZ). Immunohistochemistry of CSDC2 showed a preferentially cytoplasmic localization at AM and JZ, and nuclear localization in underneath myometrium and mesometrium (M). Cytoplasmic localization coincided with differentiated, DESMIN-marked areas, while nuclear localization coincides with proliferative zones. Uterine suppression of CSDC2 through intrauterine-injected-specific small interfering RNA (siRNA) led to abnormal decidualization in early pregnancy, with more extended antimesometrial area and with poor M development if compared with control siRNA-injected animals. These results suggest that CSDC2 could be a regulator during decidua development. 相似文献
994.
The rate of exchange of HCO3? with Cl? at 37°C in erythrocytes of ten mammalian species was studied. The rate constant increases from 7s?1 (ox) to 16s?1 (rat), and is inversely proportional to the body size (log10) of the species. It is found that the membrane permeability in different species is positively correlated to the red cell membrane phosphatidylcholine or arachidonate content, and is negatively correlated to the sphingomyelin or linoleate content. 相似文献
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Lihie Levin Ehud Zelzion Esther Nachliel Menachem Gutman Yossi Tsfadia Yulia Einav 《PloS one》2013,8(3)
The integrins are a family of membrane receptors that attach a cell to its surrounding and play a crucial function in cell signaling. The combination of internal and external stimuli alters a folded non-active state of these proteins to an extended active configuration. The β3 subunit of the platelet αIIbβ3 integrin is made of well-structured domains rich in disulfide bonds. During the activation process some of the disulfides are re-shuffled by a mechanism requiring partial reduction of some of these bonds; any disruption in this mechanism can lead to inherent blood clotting diseases. In the present study we employed Molecular Dynamics simulations for tracing the sequence of structural fluctuations initiated by a single cysteine mutation in the β3 subunit of the receptor. These simulations showed that in-silico protein mutants exhibit major conformational deformations leading to possible disulfide exchange reactions. We suggest that any mutation that prevents Cys560 from reacting with one of the Cys567–Cys581 bonded pair, thus disrupting its ability to participate in a disulfide exchange reaction, will damage the activation mechanism of the integrin. This suggestion is in full agreement with previously published experiments. Furthermore, we suggest that rearrangement of disulfide bonds could be a part of a natural cascade of thiol/disulfide exchange reactions in the αIIbβ3 integrin, which are essential for the native activation process. 相似文献