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71.
Vanessa Gonzalez‐Covarrubias Marian Beekman Hae‐Won Uh Adrie Dane Jorne Troost Iryna Paliukhovich Frans M. van der Kloet Jeanine Houwing‐Duistermaat Rob J. Vreeken Thomas Hankemeier Eline P. Slagboom 《Aging cell》2013,12(3):426-434
Middle‐aged offspring of nonagenarians, as compared to their spouses (controls), show a favorable lipid metabolism marked by larger LDL particle size in men and lower total triglyceride levels in women. To investigate which specific lipids associate with familial longevity, we explore the plasma lipidome by measuring 128 lipid species using liquid chromatography coupled to mass spectrometry in 1526 offspring of nonagenarians (59 years ± 6.6) and 675 (59 years ± 7.4) controls from the Leiden Longevity Study. In men, no significant differences were observed between offspring and controls. In women, however, 19 lipid species associated with familial longevity. Female offspring showed higher levels of ether phosphocholine (PC) and sphingomyelin (SM) species (3.5–8.7%) and lower levels of phosphoethanolamine PE (38:6) and long‐chain triglycerides (TG) (9.4–12.4%). The association with familial longevity of two ether PC and four SM species was independent of total triglyceride levels. In addition, the longevity‐associated lipid profile was characterized by a higher ratio of monounsaturated (MUFA) over polyunsaturated (PUFA) lipid species, suggesting that female offspring have a plasma lipidome less prone to oxidative stress. Ether PC and SM species were identified as novel longevity markers in females, independent of total triglycerides levels. Several longevity‐associated lipids correlated with a lower risk of hypertension and diabetes in the Leiden Longevity Study cohort. This sex‐specific lipid signature marks familial longevity and may suggest a plasma lipidome with a better antioxidant capacity, lower lipid peroxidation and inflammatory precursors, and an efficient beta‐oxidation function. 相似文献
72.
Stella Manta Vanessa Parmenopoulou Christos Kiritsis Athina Dimopoulou Nikolaos Kollatos Ioannis Papasotiriou 《Nucleosides, nucleotides & nucleic acids》2013,32(7):522-535
This article describes the synthesis of (3 ′S) and (3 ′R)-3 ′-amino-3 ′-deoxy pyranonucleosides and their precursors (3 ′S) and (3 ′R)-3 ′-azido-3 ′-deoxy pyranonucleosides. Azidation of 1,2:5,6-di-O-isopropylidene-3-O-toluenesulfonyl-α-D-allofuranose followed by hydrolysis and subsequent acetylation afforded 3-azido-3-deoxy-1,2,4,6-tetra-O-acetyl-D-glucopyranose, which upon coupling with the proper silylated bases, deacetylation, and catalytic hydrogenation, obtained the target 3 ′-amino-3 ′-deoxy-β-D-glucopyranonucleosides. The desired 1-(3 ′-amino-3 ′-deoxy-β-D-allopyranosyl)5-fluorouracil was readily prepared from the suitable imidazylate sugar after azidation followed by a protection/deprotection sequence and reduction of the unprotected azido precursor. No antiviral activity was observed for the novel nucleosides. Moderate cytostatic activity was recorded for the 5-fluorouracil derivatives. 相似文献
73.
Vanessa A.R.O. Vieira Tiago G. CorreiaRenata G. Moreira 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2013,157(1):1-8
We investigated the effects of acidic pH and acute aluminum (Al) exposure on the metabolic substrates of Astyanax bimaculatus, and on the ability of these animals to recover in clean water. After an acclimation period, sexually mature A. bimaculatus females were sorted into six glass aquaria with three experimental groups: control in neutral pH (7.0), acidic pH (5.5), and Al (0.5 mg·L− 1) in acidic pH (5.5). After a 96 h treatment, 10 animals from each experimental group were sampled and the rest were returned to clean water in neutral pH without Al for a recovery period of 96 h. The acidic pH, either alone or combined with Al, decreased T4 levels, whereas Al exposure increased T3 levels. Recovery of T3 levels occurred after 96 h. Al exposure decreased ovary and plasma proteins, muscle glycogen contents, and hepatic lipids due to lipoperoxidation. In the recovery phase, lipids decreased in most tissues, probably to re-establish ovary protein and hepatic glycogen. A. bimaculatus prioritized the use of energetic resources during acclimatization to Al instead of prioritizing reproduction, thereby avoiding the ovulation of impaired eggs. 相似文献
74.
Isabelle Vanessa Mohrenz Patrick Antonietti Stefan Pusch David Capper Jörg Balss Sophia Voigt Susanne Weissert Alicia Mukrowsky Jan Frank Christian Senft Volker Seifert Andreas von Deimling Donat Kögel 《Apoptosis : an international journal on programmed cell death》2013,18(11):1416-1425
Isocitrate dehydrogenase 1 (IDH1) decarboxylates isocitrate to α-ketoglutarate (α-KG) leading to generation of NADPH, which is required to regenerate reduced glutathione (GSH), the major cellular ROS scavenger. Mutation of R132 of IDH1 abrogates generation of α-KG and leads to conversion of α-KG to 2-hydroxyglutarate. We hypothesized that glioma cells expressing mutant IDH1 have a diminished antioxidative capacity and therefore may encounter an ensuing loss of cytoprotection under conditions of oxidative stress. Our study was performed with LN229 cells stably overexpressing IDH1 R132H and wild type IDH1 or with a lentiviral IDH1 knockdown. Quantification of GSH under basal conditions and following treatment with the glutathione reductase inhibitor BCNU revealed significantly lower GSH levels in IDH1 R132H expressing cells and IDH1 KD cells compared to their respective controls. FACS analysis of cell death and ROS production also demonstrated an increased sensitivity of IDH1-R132H-expressing cells and IDH1 KD cells to BCNU, but not to temozolomide. The sensitivity of IDH1-R132H-expressing cells and IDH1 KD cells to ROS induction and cell death was further enhanced with the transaminase inhibitor aminooxyacetic acid and under glutamine free conditions, indicating that these cells were more addicted to glutaminolysis. Increased sensitivity to BCNU-induced ROS production and cell death was confirmed in HEK293 cells inducibly expressing the IDH1 mutants R132H, R132C and R132L. Based on these findings we propose that in addition to its established pro-tumorigenic effects, mutant IDH1 may also limit the resistance of gliomas to specific death stimuli, therefore opening new perspectives for therapy. 相似文献
75.
Vanessa Dutra Silva Jeferson Schneider Carletto Eduardo Carasek Boris Ugarte Stambuk Maria da Graça Nascimento 《Process Biochemistry》2013,48(8):1159-1165
The α,β-unsaturated carbonyl compound (4S)-(+)-carvone was selectively reduced to (1R,2R,4S)-iso-dihydrocarveol using baker's yeasts. The conversion of the bioreduction reaction was monitored using a green hollow-fiber liquid–liquid–liquid microextraction (HF-LLLME) technique. Several parameters which may affect the bioreduction of (4S)-(+)-carvone, such as temperature, time, substrate/enzyme ratio, pH and buffer concentration, were evaluated. The effect of some additives, such as trehalose, DMSO and the ionic liquid [BMIm][PF6], was also studied. The (1R,2R,4S)-iso-dihydrocarveol was recovered with 52.7% conversion and diastereoisomeric excess >99% after 48 h of reaction at 40 °C in an aqueous monophasic system, with 0.1 mol L?1 buffer concentration (pH 7.5) and a substrate/yeast cell mass ratio of 8.0 mg g?1. The HF-LLLME microextraction technique allowed the optimization of the reaction with a reduction of over 99.5% in relation to the use of organic solvents. 相似文献
76.
77.
Marcelo de Oliveira Barbosa Rubens Rodrigues da Silva Vanessa Carolina de Sena Correia Luana Pereira dos Santos Analía del Valle Garnero Ricardo José Gunski 《Genetics and molecular biology》2013,36(1):70-73
Cytogenetic studies in birds are still scarce compared to other vertebrates. Woodcreepers (Dendrocolaptidae) are part of a highly specialized group within the Suboscines of the New World. They are forest birds exclusive to the Neotropical region and similar to woodpeckers, at a comparable evolutionary stage. This paper describes for the first time the karyotypes of the Olivaceous and the Narrow-billed Woodcreeper using conventional staining with Giemsa and silver nitrate staining of the nucleolar organizer regions (Ag-NORs). Metaphases were obtained by fibular bone marrow culture. The chromosome number of the Olivaceous Woodcreeper was 2n = 82 and of the Narrow-billed Woodcreeper, 2n = 82. Ag-NORs in the largest macrochromosome pair and evidence of a chromosome inversion are described herein for the first time for this group. 相似文献
78.
Jamie Bryant Vanessa M McDonald Allison Boyes Rob Sanson-Fisher Christine Paul Jessica Melville 《Respiratory research》2013,14(1):109
Adherence to medication among individuals with chronic obstructive pulmonary disease (COPD) is suboptimal and has negative impacts on survival and health care costs. No systematic review has examined the effectiveness of interventions designed to improve medication adherence. Electronic databases Medline and Cochrane were searched using a combination of MeSH and keywords. Eligible studies were interventions with a primary or secondary aim to improve medication adherence among individuals with COPD published in English. Included studies were assessed for methodological quality using the Effective Practice and Organisation of Care (EPOC) criteria. Of the 1,186 papers identified, seven studies met inclusion criteria. Methodological quality of the studies was variable. Five studies identified effective interventions. Strategies included: brief counselling; monitoring and feedback about inhaler use through electronic medication delivery devices; and multi-component interventions consisting of self-management and care co-ordination delivered by pharmacists and primary care teams. Further research is needed to establish the most effective and cost effective interventions. Special attention should be given to increasing patient sample size and using a common measure of adherence to overcome methodological limitations. Interventions that involve caregivers and target the healthcare provider as well as the patient should be further explored. 相似文献
79.
Matthew Maddocks Vanessa Halliday Alpna Chauhan Victoria Taylor Annmarie Nelson Cathy Sampson Anthony Byrne Gareth Griffiths Andrew Wilcock 《PloS one》2013,8(12)
Background
A reduced exercise capacity is associated with increased morbidity and mortality in patients with advanced non-small cell lung cancer (NSCLC). Therapeutic exercise can be beneficial and neuromuscular electrical stimulation (NMES) of the quadriceps muscles may represent a practical approach. The primary aim of this study was to determine the acceptability of NMES of the quadriceps to patients with NSCLC used alongside palliative chemotherapy. Secondary aims explored aspects of safety and efficacy of NMES in this setting.Methods
Patients with advanced NSCLC due to receive first-line palliative chemotherapy were randomized to usual care with or without NMES. They were asked to undertake 30 minute sessions of NMES, ideally daily, but as a minimum, three times weekly. For NMES to be considered acceptable, it was predetermined that ≥80% of patients should achieve this minimum level of adherence. Qualitative interviews were held with a subset of patients to explore factors influencing adherence. Safety was assessed according to the Common Terminology Criteria for Adverse Events. Quadriceps muscle strength, thigh lean mass, and physical activity level were assessed at baseline and after three cycles of chemotherapy.Results
49 patients (28 male, median (IQR) age 69 (64−75) years) participated. Of 30 randomized to NMES, 18 were eligible for the primary endpoint, of whom 9 (50% [90% CI, 29 to 71]) met the minimum level of adherence. Adherence was enhanced by incorporating sessions into a daily routine and hindered by undesirable effects of chemotherapy. There were no serious adverse events related to NMES, nor significant differences in quadriceps muscle strength, thigh lean mass or physical activity level between groups.Conclusions
NMES is not acceptable in this setting, nor was there a suggestion of benefit. The need remains to explore NMES in patients with cancer in other settings.Trial Registration
Current Controlled Trials ISRCTN 42944026 www.controlled-trials.com/ISRCTN42944026 相似文献80.
Hianara A. Bustamante Andrés Rivera-Dictter Viviana A. Cavieres Vanessa C. Mu?oz Alexis González Yimo Lin Gonzalo A. Mardones Patricia V. Burgos 《PloS one》2013,8(12)
Alzheimer’s disease (AD) is characterized by the buildup of amyloid-β peptides (Aβ) aggregates derived from proteolytic processing of the β-amyloid precursor protein (APP). Amyloidogenic cleavage of APP by β-secretase/BACE1 generates the C-terminal fragment C99/CTFβ that can be subsequently cleaved by γ-secretase to produce Aβ. Growing evidence indicates that high levels of C99/CTFβ are determinant for AD. Although it has been postulated that γ-secretase-independent pathways must control C99/CTFβ levels, the contribution of organelles with degradative functions, such as the endoplasmic reticulum (ER) or lysosomes, is unclear. In this report, we investigated the turnover and amyloidogenic processing of C99/CTFβ in human H4 neuroglioma cells, and found that C99/CTFβ is localized at the Golgi apparatus in contrast to APP, which is mostly found in endosomes. Conditions that localized C99/CTFβ to the ER resulted in its degradation in a proteasome-dependent manner that first required polyubiquitination, consistent with an active role of the ER associated degradation (ERAD) in this process. Furthermore, when proteasomal activity was inhibited C99/CTFβ was degraded in a chloroquine (CQ)-sensitive compartment, implicating lysosomes as alternative sites for its degradation. Our results highlight a crosstalk between degradation pathways within the ER and lysosomes to avoid protein accumulation and toxicity. 相似文献