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141.
T Akerström J Crona A Delgado Verdugo LF Starker K Cupisti HS Willenberg WT Knoefel W Saeger A Feller J Ip P Soon M Anlauf PF Alesina KW Schmid M Decaussin P Levillain B Wängberg JL Peix B Robinson J Zedenius M Bäckdahl S Caramuta KA Iwen J Botling P Stålberg JL Kraimps H Dralle P Hellman S Sidhu G Westin H Lehnert MK Walz G Akerström T Carling M Choi RP Lifton P Björklund 《PloS one》2012,7(7):e41926
Background
Aldosterone producing lesions are a common cause of hypertension, but genetic alterations for tumorigenesis have been unclear. Recently, either of two recurrent somatic missense mutations (G151R or L168R) was found in the potassium channel KCNJ5 gene in aldosterone producing adenomas. These mutations alter the channel selectivity filter and result in Na+ conductance and cell depolarization, stimulating aldosterone production and cell proliferation. Because a similar mutation occurs in a Mendelian form of primary aldosteronism, these mutations appear to be sufficient for cell proliferation and aldosterone production. The prevalence and spectrum of KCNJ5 mutations in different entities of adrenocortical lesions remain to be defined.Materials and Methods
The coding region and flanking intronic segments of KCNJ5 were subjected to Sanger DNA sequencing in 351 aldosterone producing lesions, from patients with primary aldosteronism and 130 other adrenocortical lesions. The specimens had been collected from 10 different worldwide referral centers.Results
G151R or L168R somatic mutations were identified in 47% of aldosterone producing adenomas, each with similar frequency. A previously unreported somatic mutation near the selectivity filter, E145Q, was observed twice. Somatic G151R or L168R mutations were also found in 40% of aldosterone producing adenomas associated with marked hyperplasia, but not in specimens with merely unilateral hyperplasia. Mutations were absent in 130 non-aldosterone secreting lesions. KCNJ5 mutations were overrepresented in aldosterone producing adenomas from female compared to male patients (63 vs. 24%). Males with KCNJ5 mutations were significantly younger than those without (45 vs. 54, respectively; p<0.005) and their APAs with KCNJ5 mutations were larger than those without (27.1 mm vs. 17.1 mm; p<0.005).Discussion
Either of two somatic KCNJ5 mutations are highly prevalent and specific for aldosterone producing lesions. These findings provide new insight into the pathogenesis of primary aldosteronism. 相似文献142.
de Lima Prata K de Santis GC Orellana MD Palma PV Brassesco MS Covas DT 《Cytotherapy》2012,14(6):694-700
Background aimsMesenchymal stromal cells (MSC) are being used to treat and prevent a variety of clinical conditions. To be readily available, MSC must be cryopreserved until infusion. However, the optimal cryopreservation methods, cryoprotector solutions and MSC sensitivity to dimethyl sulfoxide (DMSO) exposure are unknown. This study investigated these issues.MethodsMSC samples were obtained from human umbilical cord (n = 15), expanded with Minimal Essential Medium-alpha (α-MEM) 10% human serum (HS), resuspended in 25 mL solution (HS, 10% DMSO, 20% hydroxyethyl starch) and cryopreserved using the BioArchive® system. After a mean of 18 ± 7 days, cell suspensions were thawed and diluted until a DMSO concentration of 2.5% was reached. Samples were tested for cell quantification and viability, immunophenotype and functional assays.ResultsPost-thaw cell recovery: 114 ± 2.90% (mean ± SEM). Recovery of viable cells: 93.46 ± 4.41%, 90.17 ± 4.55% and 81.03 ± 4.30% at 30 min, 120 min and 24 h post-thaw, respectively. Cell viability: 89.26 ± 1.56%, 72.71 ± 2.12%, 70.20 ± 2.39% and 63.02 ± 2.33% (P < 0.0001) pre-cryopreservation and 30 min, 120 min and 24 h post-thaw, respectively. All post-thaw samples had cells that adhered to culture bottles. Post-thaw cell expansion was 4.18 ± 0.17 ×, with a doubling time of 38 ± 1.69 h, and their capacity to inhibit peripheral blood mononuclear cells (PBMC) proliferation was similar to that observed before cryopreservation. Differentiation capacity, cell-surface marker profile and cytogenetics were not changed by the cryopreservation procedure.ConclusionsA method for cryopreservation of MSC in bags, in xenofree conditions, is described that facilitates their clinical use. The MSC functional and cytogenetic status and morphologic characteristics were not changed by cryopreservation. It was also demonstrated that MSC are relatively resistant to exposure to DMSO, but we recommend cell infusion as soon as possible. 相似文献
143.
Sajish M Zhou Q Kishi S Valdez DM Kapoor M Guo M Lee S Kim S Yang XL Schimmel P 《Nature chemical biology》2012,8(6):547-554
Interferon-γ (IFN-γ) engenders strong antiproliferative responses, in part through activation of p53. However, the long-known IFN-γ-dependent upregulation of human Trp-tRNA synthetase (TrpRS), a cytoplasmic enzyme that activates tryptophan to form Trp-AMP in the first step of protein synthesis, is unexplained. Here we report a nuclear complex of TrpRS with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and with poly(ADP-ribose) polymerase 1 (PARP-1), the major PARP in human cells. The IFN-γ-dependent poly(ADP-ribosyl)ation of DNA-PKcs (which activates its kinase function) and concomitant activation of the tumor suppressor p53 were specifically prevented by Trp-SA, an analog of Trp-AMP that disrupted the TrpRS-DNA-PKcs-PARP-1 complex. The connection of TrpRS to p53 signaling in vivo was confirmed in a vertebrate system. These and further results suggest an unexpected evolutionary expansion of the protein synthesis apparatus to a nuclear role that links major signaling pathways. 相似文献
144.
Acosta JC Ferrándiz N Bretones G Torrano V Blanco R Richard C O'Connell B Sedivy J Delgado MD León J 《Molecular and cellular biology》2008,28(24):7286-7295
145.
Rodrigo Delgado Pedro Fernndez-Llario Marisa Azevedo Albano Beja-Pereira Pedro Santos 《Mammalian Biology》2008,73(3):169-176
Multiple paternity within litters occurs in various groups of mammals exhibiting different mating systems. Using seven genetic markers (i.e., microsatellites), we investigated the paternity of littermates in free-ranging wild boar (Sus scrofa) in a Mediterranean habitat. Using the software CERVUS 2.0 we estimated the probability of detecting multiple paternity across all loci (D), the probability of paternity (W) and a statistic Δ that allows the assignment of paternity to the most likely male with strict and relaxed levels of confidence. Multiple paternity was inferred for one of the nine analysed litters at the 80% confidence level. This suggests that a single male may control the access to receptive adult females and it shows that multiple paternity is not very common in the studied free-ranging wild boar population. Despite the possible occurrence of sperm competition and/or female cryptic choice, mate guarding seems to play a significant role in sexual selection. To better understand the wild boar's mating strategies further studies analysing the reproductive success of both sexes and under different environmental conditions should be conducted. 相似文献
146.
Bedia C Canals D Matabosch X Harrak Y Casas J Llebaria A Delgado A Fabriás G 《Chemistry and physics of lipids》2008,156(1-2):33-40
The acid ceramidase (AC) inhibitory activity of octanoylamides, p-tert-butylbenzamides and pivaloylamides of several 2-substituted aminoethanols is reported. All the aminoethanol amides bearing a hexadecyl substituent (C16), as well as (S)-N-(1-(hexadecylthio)-3-hydroxypropan-2-yl)pivaloylamide (SC16-tb) were inhibitory in cell lysates overexpressing AC, while all other compounds were not inhibitors. Kinetic experiments with (R,E)-N-(1-hydroxyoctadec-3-en-2-yl)pivaloylamide (E-tb) and SC16-tb showed that inhibition was competitive, with K(i) values of 34 and 94.0 microM, respectively. None of the compounds inhibited neutral ceramidase. Compounds E-tb and E-c7 (the octanoylamide of the unsaturated base E), which elicited a dose-response inhibition with IC(50) values around 15 microM, were the only AC inhibitors in intact cells. Both compounds were toxic to A549 cells with LD(50) values nearly 40 microM. Flow cytometry studies with E-tb evidenced that this compound induced a concentration-dependent cell cycle arrest at G(1) and a 20-25% apoptosis/late apoptosis/necrosis after a 24-h incubation at 50 microM. In agreement with its activity as acidic ceramidase inhibitor, this effect was accompanied with an increase in the amounts of C14, C16 and C18 ceramides (LC-MS analyses), which suggested that these lipids may be responsible for the cytotoxic activity of E-tb. 相似文献
147.
Yurixhi Maldonado–López Edelmira Linares–Mazari Robert Bye Guillermo Delgado Francisco J. Espinosa–García 《Economic botany》2008,62(2):161-170
Mexican Arnica Anti–Inflammatory Action: Plant Age Is Correlated with the Concentration of Anti–inflammatory Sesquiterpenes
in the Medicinal Plant
Heterotheca inuloides
Cass. (Asteraceae). Mexican árnica (Heterotheca inuloides Cass.) is a widely used anti–inflammatory medicinal plant in Mexican folk medicine. Although it has been suggested that plant
age, fertilization, and harvesting regime influence the concentration of secondary compounds affecting the therapeutic activity
of the plant, the effect of these variables on the concentration of the Mexican árnica anti–inflammatory compounds was not
known. We quantified anti–inflammatory sesquiterpenes (caryolan–1, 9β–diol, cadalen–15–oic acid, 7–hydroxycadalene, 4–hydroxy–2–isopropyl–4,
7–dimethyl–1[4H] naftalinone, 7–hydroxy–4αH–3, 4–dihydrocadalene, β–caryophyllene, and β–caryophyllene epoxide) in Mexican
árnica plants subjected to fertilization and successive harvests of flowering stems, conditions that mimic the cultivation
and harvesting for árnica in México. Fertilization and successive harvesting and their interaction had no significant effect
on the concentration of anti–inflammatory compounds. However, the concentrations of these compounds were 60% higher in flowering
stems from 15–month–old plants than in those from 4– or 8–month–old plants and was independent of the number of harvests and
fertilization regime applied. 相似文献
148.
J.A. Delgado M. Shaffer C. Hu R. Lavado J. Cueto-Wong P. Joosse D. Sotomayor W. Colon R. Follett S. DelGrosso X. Li H. Rimski-Korsakov 《Ecological Engineering》2008,32(2):108-120
Nitrogen (N) losses from agriculture are negatively impacting groundwater, air, and surface water quality. New tools are needed to quickly assess these losses and provide nutrient managers and conservationists with effective tools to assess the effects of current and alternative management practices on N loss pathways. A new N-Index tool was developed in spreadsheet format, allowing prompt assessments of management practices on agricultural N losses. The N-Index tool was compared with experimental field data and shown to estimate the effects of management practices on N loss pathways (probability, P < 0.001). The N-Index correctly assessed the nitrate nitrogen (NO3-N) leaching losses when tested against measured NO3-N leaching data and atmospheric N losses collected over multiple years (annual basis) and locations. The N-Index tool was developed with international cooperation from several countries and there is potential to use this tool at the international level. 相似文献
149.
Is Shade Beneficial for Mediterranean Shrubs Experiencing Periods of Extreme Drought and Late-winter Frosts? 总被引:1,自引:0,他引:1
Valladares F Zaragoza-Castells J Sánchez-Gómez D Matesanz S Alonso B Portsmuth A Delgado A Atkin OK 《Annals of botany》2008,102(6):923-933