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991.
992.
The purpose of the present study was to determine whether zinc and calcium could interact at the tissue level. In the first
part of the study, adult rats were injected with ZnCl2 dissolved in a physiological saline solution to determine the effects of Zn on Ca levels in various tissues. In the second
part of the study, weaned rats (at day 22 postnatally) were fed a diet supplemented with Zn until day 50 and were then sacrificed.
In both instances, blood, brain, heart, liver, and skeletal muscle were taken and analyzed. In the Zn-injected group, the
brain, heart, and liver showed no interaction between Zn and Ca. The skeletal muscle, in contrast, showed a decrease in Ca
in the homogenate, whereas Zn contents showed a significant increase at the sarcoplasmic reticulum (SR). Likewise, in the
Zn-supplemented group, the Zn content of the SR vesicle of the skeletal muscle showed an increase, whereas Ca content of the
pellet (14,000 g), which contains cell debris, nucleus, mitochondria, and SR vesicles of this group, showed a decrease. Current
findings suggest antagonistic effects between Zn and Ca on this tissue. Zn may play a critical role in cellular function through
the alteration of itnracellular distribution of Ca in skeletal muscle. 相似文献
993.
Juana Magdalena Mats Forsman Mauro V. Lenzini Alain Brans Jean Dusart 《FEMS microbiology letters》1992,99(1):101-105
Two beta-lactamase genes called blaL and blaU have been cloned independently in Liège and in Ume?, from Streptomyces cacaoi. Genes blaL and blaU were found to differ largely in their nucleotide sequences, although the encoded proteins both belonged to the class A of beta-lactamases (active-site serine penicillinases). DNA-hybridization and polymerase chain reaction assays have now demonstrated that both blaL and blaU genes were present in the S. cacaoi strains used in Liège and in Ume?. 相似文献
994.
Lucie Lorkova Michaela Scigelova Tabiwang Ndipanquang Arrey Ondrej Vit Jana Pospisilova Eliska Doktorova Magdalena Klanova Mahmudul Alam Petra Vockova Bokang Maswabi Klener Pavel Jr. Jiri Petrak 《PloS one》2015,10(8)
Mantle cell lymphoma (MCL) is a chronically relapsing aggressive type of B-cell non-Hodgkin lymphoma considered incurable by currently used treatment approaches. Fludarabine is a purine analog clinically still widely used in the therapy of relapsed MCL. Molecular mechanisms of fludarabine resistance have not, however, been studied in the setting of MCL so far. We therefore derived fludarabine-resistant MCL cells (Mino/FR) and performed their detailed functional and proteomic characterization compared to the original fludarabine sensitive cells (Mino). We demonstrated that Mino/FR were highly cross-resistant to other antinucleosides (cytarabine, cladribine, gemcitabine) and to an inhibitor of Bruton tyrosine kinase (BTK) ibrutinib. Sensitivity to other types of anti-lymphoma agents was altered only mildly (methotrexate, doxorubicin, bortezomib) or remained unaffacted (cisplatin, bendamustine). The detailed proteomic analysis of Mino/FR compared to Mino cells unveiled over 300 differentially expressed proteins. Mino/FR were characterized by the marked downregulation of deoxycytidine kinase (dCK) and BTK (thus explaining the observed crossresistance to antinucleosides and ibrutinib), but also by the upregulation of several enzymes of de novo nucleotide synthesis, as well as the up-regulation of the numerous proteins of DNA repair and replication. The significant upregulation of the key antiapoptotic protein Bcl-2 in Mino/FR cells was associated with the markedly increased sensitivity of the fludarabine-resistant MCL cells to Bcl-2-specific inhibitor ABT199 compared to fludarabine-sensitive cells. Our data thus demonstrate that a detailed molecular analysis of drug-resistant tumor cells can indeed open a way to personalized therapy of resistant malignancies. 相似文献
995.
996.
997.
Teresa Magdalena Lüffe Emérita R. Tirado Herrera Mirjam Nadjafzadeh Patricia Berles Andrew C. Smith Christoph Knogge Eckhard W. Heymann 《Primates; journal of primatology》2018,59(6):549-552
We report temporal variation and an “outbreak” of frog predation by moustached tamarins, Saguinus mystax, in north-eastern Peruvian Amazonia. Frog predation rates were generally very low, but strongly increased in October 2015. Other high rates, identified by outlier analyses, were also observed in September–November of other years. Over all study years, predation rates in this 3-month period were significantly higher than those in the remainder of the year, suggesting a seasonal pattern of frog predation by tamarins. Reduced fruit availability or increased frog abundance or a combination of both may be responsible for both the seasonal pattern and the specific “outbreak” of frog predation. 相似文献
998.
Katarzyna Szczepańska Tadeusz Karcz Magdalena Kotańska Agata Siwek Kamil J. Kuder Gniewomir Latacz Szczepan Mogilski Stefanie Hagenow Annamaria Lubelska Michał Sobolewski Holger Stark Katarzyna Kieć-Kononowicz 《Bioorganic & medicinal chemistry》2018,26(23-24):6056-6066
As a continuation of our search for novel histamine H3 receptor ligands, a series of new acetyl and propionyl phenoxyalkylamine derivatives (2–25) was synthesized. Compounds with three to four carbon atoms alkyl chain spacer, composed of six various 4N-substituted piperazine moieties were evaluated for their binding properties at human histamine H3 receptors (hH3R). In vitro test results proved the 4-pyridylpiperazine moiety as crucial element for high hH3R affinity (hH3R Ki?=?5.2–115?nM). Moreover introduction of carbonyl group containing residues in the lipophilic part of molecules instead of branched alkyl substituents resulted in increased affinity in correlation to previously described series, whereas propionyl derivatives showed slightly higher affinities than those of acetyl (16 and 22vs.4 and 10; hH3R Ki?=?5.2 and 15.4?nM vs. 10.2 and 115?nM, respectively). These findings were confirmed by molecular modelling studies, demonstrating multiple ligand-receptor interactions. Furthermore, pharmacological in vivo test results of compound 4 clearly indicate that it may affect the amount of calories consumed, thus act as an anorectic compound. Likewise, its protective action against hyperglycemia and the development of overweight has been shown. In order to estimate drug-likeness of compound 4, in silico and experimental evaluation of metabolic stability in human liver microsomes was performed. 相似文献
999.
Bert van Loo Markus Schober Eugene Valkov Magdalena Heberlein Erich Bornberg-Bauer Kurt Faber Marko Hyvönen Florian Hollfelder 《Journal of molecular biology》2018,430(7):1004-1023
Hydrolysis of organic sulfate esters proceeds by two distinct mechanisms, water attacking at either sulfur (S–O bond cleavage) or carbon (C–O bond cleavage). In primary and secondary alkyl sulfates, attack at carbon is favored, whereas in aromatic sulfates and sulfated sugars, attack at sulfur is preferred. This mechanistic distinction is mirrored in the classification of enzymes that catalyze sulfate ester hydrolysis: arylsulfatases (ASs) catalyze S–O cleavage in sulfate sugars and arylsulfates, and alkyl sulfatases break the C–O bond of alkyl sulfates. Sinorhizobium meliloti choline sulfatase (SmCS) efficiently catalyzes the hydrolysis of alkyl sulfate choline-O-sulfate (kcat/KM = 4.8 × 103 s? 1 M? 1) as well as arylsulfate 4-nitrophenyl sulfate (kcat/KM = 12 s? 1 M? 1). Its 2.8-Å resolution X-ray structure shows a buried, largely hydrophobic active site in which a conserved glutamate (Glu386) plays a role in recognition of the quaternary ammonium group of the choline substrate. SmCS structurally resembles members of the alkaline phosphatase superfamily, being most closely related to dimeric ASs and tetrameric phosphonate monoester hydrolases. Although > 70% of the amino acids between protomers align structurally (RMSDs 1.79–1.99 Å), the oligomeric structures show distinctly different packing and protomer–protomer interfaces. The latter also play an important role in active site formation. Mutagenesis of the conserved active site residues typical for ASs, H218O-labeling studies and the observation of catalytically promiscuous behavior toward phosphoesters confirm the close relation to alkaline phosphatase superfamily members and suggest that SmCS is an AS that catalyzes S–O cleavage in alkyl sulfate esters with extreme catalytic proficiency. 相似文献
1000.