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931.
Birgit H M Meldal Carles Pons Livia Perfetto Noemi Del-Toro Edith Wong Patrick Aloy Henning Hermjakob Sandra Orchard Pablo Porras 《Nucleic acids research》2021,49(6):3156
The EMBL-EBI Complex Portal is a knowledgebase of macromolecular complexes providing persistent stable identifiers. Entries are linked to literature evidence and provide details of complex membership, function, structure and complex-specific Gene Ontology annotations. Data are freely available and downloadable in HUPO-PSI community standards and missing entries can be requested for curation. In collaboration with Saccharomyces Genome Database and UniProt, the yeast complexome, a compendium of all known heteromeric assemblies from the model organism Saccharomyces cerevisiae, was curated. This expansion of knowledge and scope has led to a 50% increase in curated complexes compared to the previously published dataset, CYC2008. The yeast complexome is used as a reference resource for the analysis of complexes from large-scale experiments. Our analysis showed that genes coding for proteins in complexes tend to have more genetic interactions, are co-expressed with more genes, are more multifunctional, localize more often in the nucleus, and are more often involved in nucleic acid-related metabolic processes and processes where large machineries are the predominant functional drivers. A comparison to genetic interactions showed that about 40% of expanded co-complex pairs also have genetic interactions, suggesting strong functional links between complex members. 相似文献
932.
Alex Zaufel Sandra M.W. van de Wiel Lu Yin Günter Fauler Daphne Chien Xinzhong Dong John F. Gilmer Jennifer K. Truong Paul A. Dawson Stan F.J. van de Graaf Peter Fickert Tarek Moustafa 《生物化学与生物物理学报:疾病的分子基础》2021,1867(8):166153
IsoBAs, stereoisomers of primary and secondary BAs, are found in feces and plasma of human individuals. BA signaling via the nuclear receptor FXR is crucial for regulation of hepatic and intestinal physiology/pathophysiology. Aim: Investigate the ability of BA-stereoisomers to bind and modulate FXR under physiological/pathological conditions. Methods: Expression-profiling, luciferase-assays, fluorescence-based coactivator-association assays, administration of (iso)-BAs to WT and cholestatic mice. Results: Compared to CDCA/isoCDCA, administration of DCA/isoDCA, UDCA/isoUDCA only slightly increased mRNA expression of FXR target genes; the induction was more evident looking at pre-mRNAs. Notably, almost 50% of isoBAs were metabolized to 3-oxo-BAs within 4 h in cell-based assays, making it difficult to study their actions. FRET-based real-time monitoring of FXR activity revealed that isoCDCA>CDCA stimulated FXR, and isoDCA and isoUDCA allowed fully activated FXR to be re-stimulated by a second dose of GW4064. In vivo co-administration of a single dose of isoBAs followed by GW4064 cooperatively activated FXR, as did feeding of UDCA in a background of endogenous FXR ligands. However, in animals with biliary obstruction and concomitant loss of intestinal BAs, UDCA was unable to increase intestinal Fgf15. In contrast, mice with an impaired enterohepatic circulation of BAs (Asbt?/?, Ostα?/?), administration of UDCA was still able to induce ileal Fgf15 and repress hepatic BA-synthesis, arguing that UDCA is only effective in the presence of endogenous FXR ligands. Conclusion: Secondary (iso)BAs cooperatively activate FXR in the presence of endogenous BAs, which is important to consider in diseases linked to disturbances in BA enterohepatic cycling. 相似文献
933.
934.
935.
Olwen M. Grace Oscar A. Pérez-Escobar Eve J. Lucas Maria S. Vorontsova Gwilym P. Lewis Barnaby E. Walker Lúcia G. Lohmann Sandra Knapp Peter Wilkie Tiina Sarkinen Iain Darbyshire Eimear Nic Lughadha Alexandre Monro Yannick Woudstra Sebsebe Demissew A. Muthama Muasya Sandra Díaz William J. Baker Alexandre Antonelli 《Trends in plant science》2021,26(5):433-441
936.
Sandra Y. Valencia C Carlos A. Isaza M Julieta Henao B Leonardo Beltrán A Nelsy Loango Patricia Landázuri 《Biochemistry and Biophysics Reports》2021
BackgroundControversy exists regarding the role of the subfractions of high-density lipoproteins (HDL2 and HDL3) in cardiovascular disease. The functionality of these particles, and their protective role, is due in part to the paraoxonase 1 (PON1) presence in them. The polymorphisms rs662 (Q192R, A/G), rs854560 (L55 M, T/A), and rs705379 (C-108T) of the PON1 gene have been related to enzyme activity and, with the anti-oxidative capacity of the HDL. The objective was to determine the arylesterase PON1 activity in HDL3 and HDL2 and its relationship with the polymorphisms mentioned, in a young population.MethodsThe polymorphisms were determined through mini-sequencing (SnaPshot). The HDL subpopulations were separated via ionic precipitation, cholesterol was measured with enzymatic methods, and PON1 activity was measured through spectrophotometry.ResultsThe results show that the PON1 polymorphisms do not influence the cholesterol in the HDL. A variation between 40.02 and 43.9 mg/dL was in all the polymorphisms without significant differences. Additionally, PON1 activity in the HDL3 subfractions was greater (62.83 ± 20 kU/L) than with HDL2 (35.8 ± 20.8 kU/L) in the whole population and in all the polymorphisms (p < 0.001), and it was independent of the polymorphism and differential arylesterase activity in the Q192R polymorphism (QQ > QR > RR). Thus, 115.90 ± 30.7, 88.78 ± 21.3, 65.29 ± 10.2, respectively, for total HDL, with identical behavior for HDL3 and HDL2.ConclusionsPON1 polymorphisms do not influence the HDL-c, and the PON activity is greater in the HDL3 than in the HDL2, independent of the polymorphism, but it is necessary to delve into the functionality of these findings in different populations. 相似文献
937.
Sandra A. DeSimone 《Restoration Ecology》2013,21(2):149-152
Researchers reexamining the relationship between restoration science and practice report a continuing scientist‐practitioner gap. As a land manager with scientific training, I offer my perspective of the chasm and describe a restoration practice infused with as much science as the realities of limited budget and time allow. The coastal sage scrub (CSS) restoration project at Starr Ranch, a 1,585 ha Audubon preserve in southern California, combines non‐chemical invasive species control, restoration, and applied research. Our practices evolve from modified scientific approaches and the scientific literature. Results from experiments with non‐optimum replication (on effects of seed rates, soil tamping, and timing of planting) nonetheless had value for management decisions. A critical practice came from academic research that encouraged cost‐effective passive restoration. Our passive restoration monitoring data showed 28–100% total native cover after 3–5 years. Another published study found that restoration success in semiarid regions is dependent on rainfall, a finding vital for understanding active restoration monitoring results that showed a range of 0–88% total native cover at the end of the first season. Work progresses through a combination of applied research, a watchful eye on the scientific literature, and “ecological intuition” informed by the scientific literature and our own findings. I suggest that it is less critical for academic scientists to address the basic questions on technique that are helpful to land managers but rather advocate practitioner training in methods to test alternative strategies and long‐term monitoring. 相似文献
938.
939.
Marcela S. Villaverde Cecilia E. Hanzel Sandra V. Verstraeten 《Free radical research》2013,47(9):977-984
We investigated the hypothesis that thallium (Tl) interactions with the glutathione-dependent antioxidant defence system could contribute to the oxidative stress associated with Tl toxicity. Working in vitro with reduced glutathione (GSH), glutathione reductase (GR) or glutathione peroxidase (GPx) in solution, we studied the effects of Tl+ and Tl3+ (1-25 μM) on: (a) the amount of free GSH, investigating whether the metal binds to GSH and/or oxidizes it; (b) the activity of the enzyme GR, that catalyzes GSH regeneration; and (c) the enzyme GPx, that reduces hydroperoxide at expense of GSH oxidation. We found that, while Tl+ had no effect on GSH concentration, Tl3+ oxidized it. Both cations inhibited the reduction of GSSG by GR and the diaphorase activity of this enzyme. In addition, Tl3+per se oxidized NADPH, the cofactor of GR. The effects of Tl on GPx activity depended on the metal charge: Tl+ inhibited GPx when cumene hydroperoxide (CuOOH) was the substrate, while Tl3+-mediated GPx inhibition occurred with both substrates. The present results show that Tl interacts with all the components of GSH/GSSG antioxidant defence system. Alterations of this protective pathway could be partially responsible for the oxidative stress associated with Tl toxicity. 相似文献
940.
Sandra L. Siedlak Gemma Casadesus Kate M. Webber Miguel A. Pappolla Craig S. Atwood Mark A. Smith 《Free radical research》2013,47(2):156-164
Oxidative modifications are a hallmark of oxidative imbalance in the brains of individuals with Alzheimer's, Parkinson's and prion diseases and their respective animal models. While the causes of oxidative stress are relatively well-documented, the effects of chronically reducing oxidative stress on cognition, pathology and biochemistry require further clarification. To address this, young and aged control and amyloid-β protein precursor-over-expressing mice were fed a diet with added R-alpha lipoic acid for 10 months to determine the effect of chronic antioxidant administration on the cognition and neuropathology and biochemistry of the brain. Both wild type and transgenic mice treated with R-alpha lipoic acid displayed significant reductions in markers of oxidative modifications. On the other hand, R-alpha lipoic acid had little effect on Y-maze performance throughout the study and did not decrease end-point amyloid-β load. These results suggest that, despite the clear role of oxidative stress in mediating amyloid pathology and cognitive decline in ageing and AβPP-transgenic mice, long-term antioxidant therapy, at levels within tolerable nutritional guidelines and which reduce oxidative modifications, have limited benefit. 相似文献