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1.
Anna Nilsson Thomas E. Fehniger Lena Gustavsson Malin Andersson Kerstin Kenne Gy?rgy Marko-Varga Per E. Andrén 《PloS one》2010,5(7)
Readouts that define the physiological distributions of drugs in tissues are an unmet challenge and at best imprecise, but are needed in order to understand both the pharmacokinetic and pharmacodynamic properties associated with efficacy. Here we demonstrate that it is feasible to follow the in vivo transport of unlabeled drugs within specific organ and tissue compartments on a platform that applies MALDI imaging mass spectrometry to tissue sections characterized with high definition histology. We have tracked and quantified the distribution of an inhaled reference compound, tiotropium, within the lungs of dosed rats, using systematic point by point MS and MS/MS sampling at 200 µm intervals. By comparing drug ion distribution patterns in adjacent tissue sections, we observed that within 15 min following exposure, tiotropium parent MS ions (mass-to-charge; m/z 392.1) and fragmented daughter MS/MS ions (m/z 170.1 and 152.1) were dispersed in a concentration gradient (80 fmol-5 pmol) away from the central airways into the lung parenchyma and pleura. These drug levels agreed well with amounts detected in lung compartments by chemical extraction. Moreover, the simultaneous global definition of molecular ion signatures localized within 2-D tissue space provides accurate assignment of ion identities within histological landmarks, providing context to dynamic biological processes occurring at sites of drug presence. Our results highlight an important emerging technology allowing specific high resolution identification of unlabeled drugs at sites of in vivo uptake and retention. 相似文献
2.
Yanyan Han Elfriede Eppinger Ingrid G. Schuster Luise U. Weigand Xiaoling Liang Elisabeth Kremmer Christian Peschel Angela M. Krackhardt 《The Journal of biological chemistry》2009,284(48):33409-33417
The formin protein formin-like 1 (FMNL1) is highly restrictedly expressed in hematopoietic lineage-derived cells and has been previously identified as a tumor-associated antigen. However, function and regulation of FMNL1 are not well defined. We have identified a novel splice variant (FMNL1γ) containing an intron retention at the C terminus affecting the diaphanous autoinhibitory domain (DAD). FMNL1γ is specifically located at the cell membrane and cortex in diverse cell lines. Similar localization of FMNL1 was observed for a mutant lacking the DAD domain (FMNL1ΔDAD), indicating that deregulation of autoinhibition is effective in FMNL1γ. Expression of both FMNL1γ and FMNL1ΔDAD induces polarized nonapoptotic blebbing that is dependent on N-terminal myristoylation of FMNL1 but independent of Src and ROCK activity. Thus, our results describe N-myristoylation as a regulative mechanism of FMNL1 responsible for membrane trafficking potentially involved in a diversity of polarized processes of hematopoietic lineage-derived cells. 相似文献
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5.
Summary Phenylalanine production from E. coli KA 197/pJN6 (plasmid harboring genes for aro F, phe AFBR, AmpR and TcR) was studied under varying nutritional conditions in batch and continuous cultures. In batch culture experiments where growth was deliberately interrupted by limiting concentrations of sulphate and phosphate the phenylalanine production continued from the non-growing cells. However, the depletion of phosphate resulted in an immediate cessation of phenylalanine production but thereafter a low specific rate of phenylalanine formation resumed, while the decrease in specific rate of product formation was less after sulphate depletion. In the chemostat experiments, however, phosphate limitation was the only case where the specific rate of phenylalanine formation remained constant, while at the corresponding time in sulphate and glucose limited chemostats it was declining respectively had ceased. 相似文献
6.
Lena Kautsky 《Ecography》1990,13(2):143-148
Sediment samples from 5 stations in the northern Baltic proper, 6.5 o/oo S, were collected in April 1987 and the emergence of seedlings was recorded over 120 days in a greenhouse at 20°C. Total seedling densities varied from 0 to 3328 m-2 : and of seven species, Zannichellia palustris and Chara spp. were the most abundant among seedlings and sporelings, respectively. Several common macrophytes in the area were rare as seedlings and no seedlings were recorded for the most abundant angiosperms, Potamogeton pectinatus, Potamogeton perfoliatus and Ranunculus baudotii. Except for the few annual species, reproduction by seeds contributed little to the dynamics of the vegetation in the area and no correlation was found between vegetation composition and the seed bank. For perennial species the winter survival of vegetative propagules is the most important factor for vegetation dynamics. 相似文献
7.
Lena Lewin Mats-Olof Mattsson David K. Rassin Åke Sellström 《Neurochemical research》1992,17(4):333-337
The uptake of radioactive -aminobutyric acid (GABA) andd-aspartate and the effect of SKF 89976-A, a non-substrate inhibitor of the GABA transporter, on this uptake have been investigated. Neuronal cultures from eight-day-old chick embryos grown for three or six days in vitro, were used as a model. For comparison, we also used the P2-fraction from rat. Neuronal cultures grown for three and six days expressed high-affinity uptake systems for [3H]GABA and ford-[3H]aspartate with an increasing Vmax during this period. The lipophilic non-substrate GABA uptake inhibitor, SKF 89976-A, inhibited transporter mediated uptake of GABA both in cell cultures from chicken, and in P2-fractions from rat. The results also showed that SKF 89976-A was a poor inhibitor of the uptake ofd-aspartate. We found no non-saturable uptake ofd-aspartate. 相似文献
8.
Summary
Pleurotus florida was grown in submerged culture with different concentrations of sugar beet pulp with a view to its nutritional upgrading.
Micelial growth, protein enrichment and dry weight loss of the solid residues of cultures, as well as the evolution of reducing
sugars in the liquid medium, were followed for 14 days. A product with 45% (w/w) protein and a saccharification extent as
high as 35% (w/w) were obtained after 7 days with 1% (w/v) sugar beet pulp. 相似文献
9.
Summary The production of -linolenic acid (GLA) by the fungus Mucor rouxii CBS 416.77 was studied on low budget nitrogen and carbon sources, i.e. rape meal, cocos expeller and two types of yeast extract (nitrogen sources), and starch, starch hydrolysate, beet molasses and cocos expeller (carbon sources). As references, Difco yeast extract and glucose were used. In flask cultivations the three yeast extracts were fully interchangeable, while the Difco yeast extract (the most expensive of those tested) gave a higher productivity of GLA in fermentor cultures (14 mg·l–1·h–1). The yield of lipids and GLA were increased in the order yeast extract < rape meal < cocos expeller. Thus the amount of lipid increased from 0.56 to 2.8 g·l–1, and that of GLA from 0.15 to 0.33 g·l–1. Use of beet molasses or cocos expeller as carbon sources gave poor growth. Starch and starch hydrolysate resulted in better productivity of GLA than glucose (4.7 and 4.9 compared to 3.4 mg·l–1·h–1).
Offsprint requests to: A.-M. Lindberg 相似文献
10.
Mouse soleus muscle Na-K pump activity: direct correlation with in vitro and in vivo oxygen consumption 总被引:1,自引:0,他引:1
To evaluate the contribution of active sodium-potassium transport to energy utilization, measurements of sodium-potassium pump activity in isolated soleus muscles of normal mice were carried out and related to measurements of oxygen consumption by the tissue. A highly significant positive correlation (r = 0.89, p less than 0.001) was found between these two parameters. In addition, both the in vitro oxygen consumption and Na-K pump activity of the muscles were found to correlate with whole body oxygen utilization by the experimental animals. The results support a role for the sodium-potassium pump in the determination of energy turnover. 相似文献