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排序方式: 共有1287条查询结果,搜索用时 15 毫秒
41.
Vishal M. Gohil Lin Zhu Charli D. Baker Valentin Cracan Abbas Yaseen Mohit Jain Clary B. Clish Paul S. Brookes Marica Bakovic Vamsi K. Mootha 《The Journal of biological chemistry》2013,288(49):35387-35395
We recently identified meclizine, an over-the-counter drug, as an inhibitor of mitochondrial respiration. Curiously, meclizine blunted respiration in intact cells but not in isolated mitochondria, suggesting an unorthodox mechanism. Using a metabolic profiling approach, we now show that treatment with meclizine leads to a sharp elevation of cellular phosphoethanolamine, an intermediate in the ethanolamine branch of the Kennedy pathway of phosphatidylethanolamine biosynthesis. Metabolic labeling and in vitro enzyme assays confirmed direct inhibition of the cytosolic enzyme CTP:phosphoethanolamine cytidylyltransferase (PCYT2). Inhibition of PCYT2 by meclizine led to rapid accumulation of its substrate, phosphoethanolamine, which is itself an inhibitor of mitochondrial respiration. Our work identifies the first pharmacologic inhibitor of the Kennedy pathway, demonstrates that its biosynthetic intermediate is an endogenous inhibitor of respiration, and provides key mechanistic insights that may facilitate repurposing meclizine for disorders of energy metabolism. 相似文献
42.
Adam C. Levine Richard M. Munyaneza Justin Glavis-Bloom Vanessa Redditt Hannah C. Cockrell Bantu Kalimba Valentin Kabemba Juvenal Musavuli Mathias Gakwerere Jean Paul de Charles Umurungi Sachita P. Shah Peter C. Drobac 《PloS one》2013,8(12)
Objective
To investigate the accuracy of three clinical scales for predicting severe disease (severe dehydration or death) in children with diarrhea in a resource-limited setting.Methods
Participants included 178 children admitted to three Rwandan hospitals with diarrhea. A local physician or nurse assessed each child on arrival using the World Health Organization (WHO) severe dehydration scale and the Centers for Disease Control (CDC) scale. Children were weighed on arrival and daily until they achieved a stable weight, with a 10% increase between admission weight and stable weight considered severe dehydration. The Clinical Dehydration Scale was then constructed post-hoc using the data collected for the other two scales. Receiver Operator Characteristic (ROC) curves were constructed for each scale compared to the composite outcome of severe dehydration or death.Results
The WHO severe dehydration scale, CDC scale, and Clinical Dehydration Scale had areas under the ROC curves (AUCs) of 0.72 (95% CI 0.60, 0.85), 0.73 (95% CI 0.62, 0.84), and 0.80 (95% CI 0.71, 0.89), respectively, in the full cohort. Only the Clinical Dehydration Scale was a significant predictor of severe disease when used in infants, with an AUC of 0.77 (95% CI 0.61, 0.93), and when used by nurses, with an AUC of 0.78 (95% CI 0.63, 0.93).Conclusions
While all three scales were moderate predictors of severe disease in children with diarrhea, scale accuracy varied based on provider training and age of the child. Future research should focus on developing or validating clinical tools that can be used accurately by nurses and other less-skilled providers to assess all children with diarrhea in resource-limited settings. 相似文献43.
Late Pleistocene origin of the entire circumarctic range of the arctic‐alpine plant Kalmia procumbens 下载免费PDF全文
Hajime Ikeda Pernille Bronken Eidesen Valentin Yakubov Vyacheslav Barkalov Christian Brochmann Hiroaki Setoguchi 《Molecular ecology》2017,26(20):5773-5783
The circumarctic ranges of arctic‐alpine plants are thought to have been established in the late Pliocene/early Pleistocene, when the modern arctic tundra was formed in response to climate cooling. Previous findings of range‐wide genetic structure in arctic‐alpine plants have been thought to support this hypothesis, but few studies have explicitly addressed the temporal framework of the genetic structure. Here, we estimated the demographic history of the genetic structure in the circumarctic Kalmia procumbens using sequences of multiple nuclear loci and examined whether its genetic structure reflects prolonged isolation throughout the Pleistocene. Both Bayesian clustering and phylogenetic analyses revealed genetic distinction between alpine and arctic regions, whereas detailed groupings were somewhat discordant between the analyses. By assuming a population grouping based on the phylogenetic analyses, which likely reflects a deeper intraspecific divergence, we conducted model‐based analyses and demonstrated that the intraspecific genetic divergence in K. procumbens likely originated during the last glacial period. Thus, there is no need to postulate range separation throughout the Pleistocene to explain the current genetic structure in this species. This study demonstrates that range‐wide genetic structure in arctic‐alpine plants does not necessarily result from the late Pliocene/early Pleistocene origin of their circumarctic ranges and emphasizes the importance of a temporal framework of the current genetic structure for understanding the biogeographic history of the arctic flora. 相似文献
44.
A series of 5-substituted derivatives of the potent phenylalanine ammonia-lyase (PAL) inhibitor 2-aminoindane-2-phosphonic acid (AIP; 2) were synthesized. The AIP analogues 3-7, with additional NO2, NH2, Me, Br, and OH groups, respectively, were tested as in vitro inhibitors of buckwheat PAL, and as in vivo inhibitors of anthocyanin biosynthesis. Within this series, the racemic 5-bromo (6) and 5-methyl (7) congeners were biologically most active (Table), although being ca. one order of magnitude less potent than AIP proper. 相似文献
45.
46.
Rolf Frischknecht Christian Bauer Christof Bucher Linda Ager-Wick Ellingsen Lukas Gutzwiller Britta Heimbach René Itten Xun Liao Evangelos Panos Stephan Pfister Tobias Schmidt Valentin Stahel Philippe Stolz Peter Toggweiler Karin Treyer Jacques Villeneuve Andreas Wade Marcel Weil 《The International Journal of Life Cycle Assessment》2018,23(8):1716-1721
47.
48.
Antonov AS Kalinovsky AI Dmitrenok PS Kalinin VI Stonik VA Mollo E Cimino G 《Carbohydrate research》2011,346(14):2182-2192
Seven new triterpene glycosides, erylosides R1 (1), T1 (3), T2 (4), T3 (5), T4 (6), T5 (7), and T6 (8) along with the known formoside (2) were isolated from the sponge Erylus formosus collected along the Caribbean coast of Mexico. Glycoside 1 was determined as a trisaccharide, glycoside 2 as a tetrasaccharide while glycosides 3–8 were hexasaccharide. Their carbohydrate chains were unprecedented and have never been found in oligosaccharides from other biological sources, except Erylus spp. Three carbohydrate chains in the glycosides 3 and 6, 4 and 7, 5 and 8 correspondingly are new. The glycosides 1–5 have penasterol as aglycone while glycosides 6–8 proved to be glycoconjugates of 24-methylene-14-carboxy-lanost-8(9)-en-3β-ol. 相似文献
49.
Ruslan Hlushchuk Daniel Br?nnimann Carlos Correa Shokiche Laura Schaad Ramona Triet Anna Jazwinska Stefan A. Tschanz Valentin Djonov 《PloS one》2016,11(3)
Background
Researchers evaluating angiomodulating compounds as a part of scientific projects or pre-clinical studies are often confronted with limitations of applied animal models. The rough and insufficient early-stage compound assessment without reliable quantification of the vascular response counts, at least partially, to the low transition rate to clinics.Objective
To establish an advanced, rapid and cost-effective angiogenesis assay for the precise and sensitive assessment of angiomodulating compounds using zebrafish caudal fin regeneration. It should provide information regarding the angiogenic mechanisms involved and should include qualitative and quantitative data of drug effects in a non-biased and time-efficient way.Approach & Results
Basic vascular parameters (total regenerated area, vascular projection area, contour length, vessel area density) were extracted from in vivo fluorescence microscopy images using a stereological approach. Skeletonization of the vasculature by our custom-made software Skelios provided additional parameters including “graph energy” and “distance to farthest node”. The latter gave important insights into the complexity, connectivity and maturation status of the regenerating vascular network. The employment of a reference point (vascular parameters prior amputation) is unique for the model and crucial for a proper assessment. Additionally, the assay provides exceptional possibilities for correlative microscopy by combining in vivo-imaging and morphological investigation of the area of interest. The 3-way correlative microscopy links the dynamic changes in vivo with their structural substrate at the subcellular level.Conclusions
The improved zebrafish fin regeneration model with advanced quantitative analysis and optional 3-way correlative morphology is a promising in vivo angiogenesis assay, well-suitable for basic research and preclinical investigations. 相似文献50.