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Differential inactivation of plant lauric acid omega- and in-chain-hydroxylases by terminally unsaturated fatty acids 总被引:1,自引:0,他引:1
J P Salaün A Simon F Durst N O Reich P R Ortiz de Montellano 《Archives of biochemistry and biophysics》1988,260(2):540-545
The microsomal fraction from Vicia sativa L. cv. Septimane contains a cytochrome P-450-dependent lauric acid omega-hydroxylase that is inactivated in a time-dependent, pseudo-first-order manner when the microsomes are incubated with 11-dodecynoic acid. The rate constant for the inactivation is approximately 4.3-4.8 X 10(-3) s-1. In contrast, the olefinic analog 11-dodecenoic acid is primarily a time-independent inhibitor of the omega-hydroxylase. 1-Aminobenzotriazole, 3-phenoxy-1-propyne, and 3-(2,4-dichlorophenoxy)-1-propyne, mechanism-based inactivators of cinnamic acid 4-hydroxylase, and 9-decenoic acid, a mechanism-based inactivator of the lauric acid in-chain hydroxylase, are at best poor inactivators of the omega-hydroxylase. Conversely, cinnamic acid 4-hydroxylase is only slightly affected by concentrations of 11-dodecynoic acid that completely inactivate the omega-hydroxylase. 11-Dodecynoic acid is thus a potent, relatively specific, inactivator of the V. sativa lauric acid omega-hydroxylase. 相似文献
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Ana Marcia Escocard de Azevedo Manhaes Fausto Andres Ortiz-Morea Ping He Libo Shan 《植物学报(英文版)》2021,63(1):79-101
As sessile organisms, plants are exposed to pathogen invasions and environmental fluctuations. To overcome the challenges of their surroundings, plants acquire the potential to sense endogenous and exogenous cues, resulting in their adaptability. Hence, plants have evolved a large collection of plasma membrane-resident receptors, including RECEPTOR-LIKE KINASEs(RLKs) and RECEPTOR-LIKE PROTEINs(RLPs) to perceive those signals and regulate plant growth,development, and immunity. The ability of RLKs and RLPs to recognize distinct ligands relies on diverse categories of extracellular domains evolved. Co-regulatory receptors are often required to associate with RLKs and RLPs to facilitate cellular signal transduction. RECEPTOR-LIKE CYTOPLASMIC KINASEs(RLCKs) also associate with the complex, bifurcating the signal to key signaling hubs, such as MITOGEN-ACTIVATED PROTEIN KINASE(MAPK) cascades, to regulate diverse biological processes. Here, we discuss recent knowledge advances in understanding the roles of RLKs and RLPs in plant growth, development, and immunity, and their connection with co-regulatory receptors, leading to activation of diverse intracellular signaling pathways. 相似文献
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Mario Gimona Maria Felice Brizzi Andre Boon Hwa Choo Massimo Dominici Sean M. Davidson Johannes Grillari Dirk M. Hermann Andrew F. Hill Dominique de Kleijn Ruenn Chai Lai Charles P. Lai Rebecca Lim Marta Monguió-Tortajada Maurizio Muraca Takahiro Ochiya Luis A. Ortiz Wei Seong Toh Yong Weon Yi Sai Kiang Lim 《Cytotherapy》2021,23(5):373-380
Mesenchymal stromal/stem cells (MSCs) have been widely tested against many diseases, with more than 1000 registered clinical trials worldwide. Despite many setbacks, MSCs have been approved for the treatment of graft-versus-host disease and Crohn disease. However, it is increasingly clear that MSCs exert their therapeutic functions in a paracrine manner through the secretion of small extracellular vesicles (sEVs) of 50–200 nm in diameter. Unlike living cells that can persist long-term, sEVs are non-living and non-replicative and have a transient presence in the body. Their small size also renders sEV preparations highly amenable to sterilization by filtration. Together, acellular MSC-sEV preparations are potentially safer and easier to translate into the clinic than cellular MSC products. Nevertheless, there are inherent challenges in the development of MSC-sEV drug products. MSC-sEVs are products of living cells, and living cells are sensitive to changes in the external microenvironment. Consequently, quality control metrics to measure key identity and potency features of MSC-sEV preparations have to be specified during development of MSC-sEV therapeutics. The authors have previously described quantifiable assays to define the identity of MSC-sEVs. Here the authors discuss requirements for prospective potency assays to predict the therapeutic effectiveness of the drug substance in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines. Although potency assays should ideally reflect the mechanism of action (MoA), this is challenging because the MoA for the reported efficacy of MSC-sEV preparations against multiple diseases of diverse underlying pathology is likely to be complex and different for each disease and difficult to fully elucidate. Nevertheless, robust potency assays could be developed by identifying the EV attribute most relevant to the intended biological activity in EV-mediated therapy and quantifying the EV attribute. Specifically, the authors highlight challenges and mitigation measures to enhance the manufacture of consistent and reproducibly potent sEV preparations, to identify and select the appropriate EV attribute for potency assays despite a complex “work-in-progress” MoA and to develop assays likely to be compliant with regulatory guidance for assay validation. 相似文献
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We studied the population and feeding ecology of the kelp crab Taliepus marginatus in subtidal kelp forests dominated by either of two morphologically different kelp species (Macrocystis pyrifera or Lessonia trabeculata) in northern Chile. The sizes and abundances of T. marginatus differed between the two kelp habitats. Kelp crabs were more abundant in the M. pyrifera forest than in the L. trabeculata forest. Size‐frequency distributions showed that juvenile and immature crabs were more common in the M. pyrifera forest than in the L. trabeculata forest, where reproductive adults predominated. The smaller crabs in the M. pyrifera habitat also consumed a higher proportion of kelp tissues than the larger crabs in the L. trabeculata habitat, which had a higher proportion of animal food in their diet. In both kelp forests, individuals of T. marginatus showed a similar pattern of nocturnal feeding over a 24‐h period, consuming more food at night than during the day. The more complex and dense forests of M. pyrifera appear to present better nursery habitats for juvenile kelp crabs than the more open and less dense forests dominated by L. trabeculata. These results suggest that the role of the two kelp habitats for T. marginatus varies during the life cycle of the kelp crabs, with M. pyrifera tending to have nursery function and L. trabeculata being more suitable as a reproductive habitat. 相似文献
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Esther García‐Fernández Daniel J. Frank Beatriz Galán Petrea M. Kells Larissa M. Podust José L. García Paul R. Ortiz de Montellano 《Environmental microbiology》2013,15(8):2342-2359
Degradation of the cholesterol side‐chain in Mycobacterium tuberculosis is initiated by two cytochromes P450, CYP125A1 and CYP142A1, that sequentially oxidize C26 to the alcohol, aldehyde and acid metabolites. Here we report characterization of the homologous enzymes CYP125A3 and CYP142A2 from Mycobacterium smegmatis mc2 155. Heterologously expressed, purified CYP125A3 and CYP142A2 bound cholesterol, 4‐cholesten‐3‐one, and antifungal azole drugs. CYP125A3 or CYP142A2 reconstituted with spinach ferredoxin and ferredoxin reductase efficiently hydroxylated 4‐cholesten‐3‐one to the C‐26 alcohol and subsequently to the acid. The X‐ray structures of both substrate‐free CYP125A3 and CYP142A2 and of cholest‐4‐en‐3‐one‐bound CYP142A2 reveal significant differences in the substrate binding sites compared with the homologous M. tuberculosis proteins. Deletion only of cyp125A3 causes a reduction of both the alcohol and acid metabolites and a strong induction of cyp142 at the mRNA and protein levels, indicating that CYP142A2 serves as a functionally redundant back up enzyme for CYP125A3. In contrast to M. tuberculosis, the M. smegmatis Δcyp125Δcyp142 double mutant retains its ability to grow on cholesterol albeit with a diminished capacity, indicating an additional level of redundancy within its genome. 相似文献
69.
Emilio García García María-Ángeles Vázquez López Rafael Galera Martínez Irene Alias Manuel Martín González Antonio Bonillo Perales José Eugenio Cabrera Sevilla Icíar García Escobar Sara Gómez Bueno Encarnación López Ruzafa Francisco-Javier Muñoz Vico Patricia Oliva Pérez María Ortiz Pérez Juan Poveda González Marisa Rodríguez Lucenilla Firma-Isabel Rodríguez Sánchez Ana Ruiz Sánchez Lucía Ruiz Tudela Sara Torrico 《Endocrinología y nutrición》2013,60(3):121-126
ObjectivesTo estimate the prevalence of obesity and overweight in children and adolescents in our city and to investigate the associated factors.Subjects and methodsA cross-sectional study of 1317 children and adolescents aged 2-16 years. Multistage probability sampling was used to select three groups of subjects: 411 aged 12 to 16 years, 504 aged 6 to 12 years, and 402 aged 2 to 6 years. Body mass index was calculated, and obesity and overweight were diagnosed using the threshold levels of the International Obesity Task Force for children and adolescents. Parents were asked about eating habits, health, social, and demographic aspects. Results are given as percentages (95% confidence interval). The relationship between obesity and overweight and the different variables was studied using multiple logistic regression. The adjusted odds ratio (OR) was calculated.ResultsAmong children and adolescentes aged 2-16 years, 9.5% (8.0%-11.0%) were obese and 22.4% (23.3%-24.6%) were overweight. Of subjects aged 12-16 years, 8.5% (5.9%-11.2%) were obese and 20.5% (16.7%-24.3%) were overweight. In the groups aged 6-12 years and 2-6 years, rates of obesity and overweight were 11.6% (8.9% -14.3%) and 31.0% (27.0-35.0) and 8.0% (5.4%-10.6%) and 13.6% (10.3%-16.9%) respectively. Obesity or overweight was associated to age (OR 1.21; P< 0.001), maternal obesity (OR 10.99; P= 0.008), a birthweight higher than 4 kg (OR 2.91; p 0.002), and formula feeding (OR 1.82; P= 0.005).ConclusionObesity and overweight in children and adolescents are highly prevalent problems in our city. 相似文献
70.
J. Jaime Miranda Victor M. Herrera Julio A. Chirinos Luis F. Gómez Pablo Perel Rafael Pichardo Angel González José R. Sánchez Catterina Ferreccio Ximena Aguilera Eglé Silva Myriam Oróstegui Josefina Medina-Lezama Cynthia M. Pérez Erick Suárez Ana P. Ortiz Luis Rosero Noberto Schapochnik Zulma Ortiz Daniel Ferrante Juan P. Casas Leonelo E. Bautista 《PloS one》2013,8(1)