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991.
992.
Legume phylogeny and the evolution of a unique contractile apparatus that regulates phloem transport
Protein bodies called forisomes undergo Ca(2+)-dependent deformations to occlude sieve tubes reversibly, providing a unique regulatory mechanism of phloem transport. Because forisomes are known exclusively from the Papilionoideae (Leguminosae), the evolution of forisome function may have played a role in the rapid radiation of this huge taxon. The unexpected discovery of a papilionoid species lacking forisomes led us to evaluate a representative set of species covering 33 of the 36 legume tribes traditionally recognized. We found forisomes in Papilionoideae but not in Caesalpinioideae and Mimosoideae. Forisomes were absent from several species of the papilionoid tribe Galegeae. Forisomes with tail-like protrusions occurred less frequently than tailless ones; their distribution correlated with taxonomic units but not sharply enough to render forisome type a reliable criterion for classification. Thus, the distribution of forisome types appeared to reflect physiological variability in the pathways of forisome assembly rather than the evolution of forisome genes. On the other hand, Ca(2+)-dependent forisome deformation and sieve tube plugging occurred in Bobgunnia madagascariensis, a member of the swartzioid clade that presumably is the sister group of all other papilionoids, suggesting that forisomes and their unique mechanism of deformation are a synapomorphy of the Papilionoideae. 相似文献
993.
994.
Secretory phospholipase A2 is involved in inflammatory processes and was previously shown to be inhibited by lipophilic tetracyclines such as minocycline (minoTc) and doxycycline. Lipophilic tetracyclines might be a new lead compound for the design of specific inhibitors of secretory phospholipase A2, which play a crucial role in inflammatory processes. Our X-ray crystal structure analysis at 1.65 Å resolution of the minoTc complex of phospholipase A2 (PLA2) of the Indian cobra (Naja naja naja) is the first example of nonantibiotic tetracycline interactions with a protein. MinoTc interferes with the conformation of the active-site Ca2+-binding loop, preventing Ca2+ binding, and shields the active site from substrate entrance, resulting in inhibition of the enzyme. MinoTc binding to PLA2 is dominated by hydrophobic interactions quite different from antibiotic recognition of tetracyclines by proteins or the ribosome. The affinity of minoTc for PLA2 was determined by surface plasmon resonance, resulting in a dissociation constant Kd = 1.8 × 10− 4 M. 相似文献
995.
André Mikolay Susanne Huggett Ladji Tikana Gregor Grass Jörg Braun Dietrich H. Nies 《Applied microbiology and biotechnology》2010,87(5):1875-1879
Basic chemistry of copper is responsible for its Janus-faced feature: on one hand, copper is an essential trace element required
to interact efficiently with molecular oxygen. On the other hand, interaction with reactive oxygen species in undesired Fenton-like
reactions leads to the production of hydroxyl radicals, which rapidly damage cellular macromolecules. Moreover, copper cations
strongly bind to thiol compounds disturbing redox-homeostasis and may also remove cations of other transition metals from
their native binding sites in enzymes. Nature has learned during evolution to deal with the dangerous yet important copper
cations. Bacterial cells use different efflux systems to detoxify the metal from the cytoplasm or periplasm. Despite this
ability, bacteria are rapidly killed on dry metallic copper surfaces. The mode of killing likely involves copper cations being
released from the metallic copper and reactive oxygen species. With all this knowledge about the interaction of copper and
its cations with cellular macromolecules in mind, experiments were moved to the next level, and the antimicrobial properties
of copper-containing alloys in an “everyday” hospital setting were investigated. The alloys tested decreased the number of
colony-forming units on metallic copper-containing surfaces by one third compared to control aluminum or plastic surfaces.
Moreover, after disinfection, repopulation of the surfaces was delayed on copper alloys. This study bridges a gap between
basic research concerning cellular copper homeostasis and application of this knowledge. It demonstrates that the use of copper-containing
alloys may limit the spread of multiple drug-resistant bacteria in hospitals. 相似文献
996.
Andrew F. Donnell Paul J. Dollings John A. Butera Arlene J. Dietrich Kerri K. Lipinski Afshin Ghavami Warren D. Hirst 《Bioorganic & medicinal chemistry letters》2010,20(7):2163-2167
Substituted pyridazino[4,5-b]indolizines were identified as potent and selective PDE4B inhibitors. We describe the structure–activity relationships generated around an HTS hit that led to a series of compounds with low nanomolar affinity for PDE4B and high selectivity over the PDE4D subtype. 相似文献
997.
998.
Stephan Steckelbroeck Dieter Lütjohann David R. Bauman Michael Ludwig Anke Friedl Volkmar H.J. Hans Trevor M. Penning Dietrich Klingmüller 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2010,1801(11):1221-1231
Cerebral 3α-hydroxysteroid dehydrogenase (3α-HSD) activity was suggested to be responsible for the local directed formation of neuroactive 5α,3α-tetrahydrosteroids (5α,3α-THSs) from 5α-dihydrosteroids. We show for the first time that within human brain tissue 5α-dihydroprogesterone and 5α-dihydrotestosterone are converted via non-stereo-selective 3-ketosteroid reductase activity to produce the respective 5α,3α-THSs and 5α,3β-THSs. Apart from this, we prove that within the human temporal lobe and limbic system cytochrome P450c17 and 3β-HSD/Δ5–4 ketosteroid isomerase are not expressed. Thus, it appears that these brain regions are unable to conduct de novo biosynthesis of Δ4-3-ketosteroids from Δ5-3β-hydroxysteroids. Consequently, the local formation of THSs will depend on the uptake of circulating Δ4-3-ketosteroids such as progesterone and testosterone. 3α- and 3β-HSD activity were (i) equally enriched in the cytosol, (ii) showed equal distribution between cerebral neocortex and subcortical white matter without sex- or age-dependency, (iii) demonstrated a strong and significant positive correlation when comparing 46 different specimens and (iv) exhibited similar sensitivities to different inhibitors of enzyme activity. These findings led to the assumption that cerebral 3-ketosteroid reductase activity might be catalyzed by a single enzyme and is possibly attributed to the expression of a soluble AKR1C aldo-keto reductase. AKR1Cs are known to act as non-stereo-selective 3-ketosteroid reductases; low AKR1C mRNA expression was detected. However, the cerebral 3-ketosteroid reductase was clearly refractory to inhibition by AKR1C inhibitors indicating the expression of a currently unidentified enzyme. Its lack of stereo-selectivity is of physiological significance, since only 5α,3α-THSs enhance the effect of GABA on the GABAA receptor, whereas 5α,3β-THSs are antagonists. 相似文献
999.
1000.
Shannon Kidd Lisa Caldwell Martin Dietrich Ismael Samudio Erika L Spaeth Keri Watson Yuexi Shi James Abbruzzese Marina Konopleva Michael Andreeff Frank C Marini 《Cytotherapy》2010,12(5):615-625
Background aimsBecause of the inflammatory nature and extensive stromal compartment in pancreatic tumors, we investigated the role of mesenchymal stromal cells (MSC) to engraft selectively in pancreatic carcinomas and serve as anti-tumor drug delivery vehicles to control pancreatic cancer progression.MethodsHuman pancreatic carcinoma cells, PANC-1, expressing renilla luciferase were orthotopically implanted into SCID mice and allowed to develop for 10 days. Firefly luciferase-transduced MSC or MSC expressing interferon (IFN)-β were then injected intraperitoneally weekly for 3 weeks. Mice were monitored by bioluminescent imaging for expression of renilla (PANC-1) and firefly (MSC) luciferase.ResultsMSC selectively homed to sites of primary and metastatic pancreatic tumors and inhibited tumor growth (P = 0.032). The production of IFN-β within the tumor site by MSC–IFN-β further suppressed tumor growth (P = 0.0000083). Prior studies indicated that MSC home to sites of inflammation; therefore, we sought to alter the tumor microenvironment through treatment with a potent anti-inflammatory agent. After treatment, inflammation-associated mediators were effectively down-regulated, including NFκB, vascular endothelial growth factor (VEGF) and interleukin (IL)-6 as well as chemokines involved in MSC migration (CCL3 and CCL25). Treatment with the anti-inflammatory agent CDDO-Me before and after MSC–IFN-β injections resulted in reduction of MSC in the tumors and reversed the positive effect of tumor inhibition by MSC–IFN-β alone (P = 0.041).ConclusionsThese results suggest that MSC exhibit innate anti-tumor effects against PANC-1 cells and can serve as delivery vehicles for IFN-β for the treatment of pancreatic cancer. However, these beneficial effects may be lost in therapies combining MSC with anti-inflammatory agents. 相似文献