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61.
The short- and long-term pro-oxidant effect of protoporphyrin IX (PROTO) administration to mice was studied in liver. A peak of liver porphyrin accumulation was found 2 h after the injection of PROTO (3.5 mg/kg, i.p.); then the amount of porphyrins diminished due to biliar excretion. After several doses of PROTO (1 dose every 24 h up to 5 doses) a sustained enhancement of liver porphyrins was observed. The activity of δ-amino-levulinic acid synthetase was induced 70–90% over the control values 4 h after the first injection of PROTO and stayed at these high levels throughout the period of the assay. Administration of PROTO induced rapid liver damage, involving lipid peroxidation. Hepatic GSH content was increased 2 h after the first injection of PROTO, but then decreased below the control values which were maintained after several doses of porphyrin. After a single dose of PROTO, Cu-Zn superoxide dismutase (SOD) was rapidly induced, suggesting that superoxide radicals had been generated. Increased levels of hydrogen peroxide coming from the reaction catalyzed by SOD and lipid peroxides as a consequence of membrane peroxidation, induced the activity of catalase and glutathione peroxidase (GPx), while decreased GSH levels induced glutathione reductase (GRed) activity. However after 5 doses of PROTO, the activity of SOD was reduced reaching control values. GPx and catalase activities slowly went down, while GRed continued increasing as long as the levels of GSH were kept very low. TBARS values, although lower than those observed after a single dose of PROTO, remained above control values; Glutathione S-transferase activity was instead greatly diminished, indicating sustained liver damage.Our findings would indicate that accumulation of PROTO in liver induces oxidative stress, leading to rapid increase in the activity of the antioxidant enzymes to avoid or revert liver damage. However, constant accumulation of porphyrins provokes a liver damage so severe that the antioxidant system is compromised. 相似文献
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64.
Susana Freitas Anna Vavakou Marine Arakelyan Sergei V. Drovetski Jelka Crnobrnja-isailović Artem A. Kidov 《分类学与生物多样性》2013,11(2):184-197
Darevskia praticola differs from the other species of the genus in having a large but disjunct distribution, covering the Balkan and the Caucasus regions. Furthermore, most Darevskia species occupy saxicolous habitats, whereas D. praticola inhabits meadows and forest environments. Here we determine the phylogeographic and phylogenetic relationships of Darevskia praticola sensu lato and evaluate the current, morphology-based taxonomy. We sequenced two mtDNA genes (Cyt-b and ND4) and two nuclear loci (MC1R and RELN) for samples collected across the species range. Because our sequences amplified with the Cyt-b primers appear to represent a nuclear pseudogene we excluded this marker from the final analysis. Our results support monophyly of D. praticola and show its division into three clades. The first divergence, dated to the Late Pliocene, is between the Balkans and the Caucasus. The Caucasus lineage is further subdivided in a western Greater Caucasus and a Transcaucasia clade, likely due to subsequent differentiation during the Pleistocene. Our findings do not support the current taxonomic arrangement within D. praticola. The main geographic divergence likely happened due to a vicariance event associated with Plio-Pleistocene climatic and vegetation oscillations. 相似文献
65.
Ana B. Fagundo Rafael de la Torre Susana Jiménez-Murcia Zaida Agüera Antoni Pastor Felipe F. Casanueva Roser Granero Rosa Ba?os Cristina Botella Amparo del Pino-Gutierrez Jose M. Fernández-Real Jose C. Fernández-García Gema Frühbeck Javier Gómez-Ambrosi José M. Menchón Inés Moragrega Roser Rodríguez Salomé Tárrega Francisco J. Tinahones Fernando Fernández-Aranda 《PloS one》2013,8(6)
Animal studies point to an implication of the endocannabinoid system on executive functions. In humans, several studies have suggested an association between acute or chronic use of exogenous cannabinoids (Δ9-tetrahydrocannabinol) and executive impairments. However, to date, no published reports establish the relationship between endocannabinoids, as biomarkers of the cannabinoid neurotransmission system, and executive functioning in humans. The aim of the present study was to explore the association between circulating levels of plasma endocannabinoids N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) and executive functions (decision making, response inhibition and cognitive flexibility) in healthy subjects. One hundred and fifty seven subjects were included and assessed with the Wisconsin Card Sorting Test; Stroop Color and Word Test; and Iowa Gambling Task. All participants were female, aged between 18 and 60 years and spoke Spanish as their first language. Results showed a negative correlation between 2-AG and cognitive flexibility performance (r = −.37; p<.05). A positive correlation was found between AEA concentrations and both cognitive flexibility (r = .59; p<.05) and decision making performance (r = .23; P<.05). There was no significant correlation between either 2-AG (r = −.17) or AEA (r = −.08) concentrations and inhibition response. These results show, in humans, a relevant modulation of the endocannabinoid system on prefrontal-dependent cognitive functioning. The present study might have significant implications for the underlying executive alterations described in some psychiatric disorders currently associated with endocannabinoids deregulation (namely drug abuse/dependence, depression, obesity and eating disorders). Understanding the neurobiology of their dysexecutive profile might certainly contribute to the development of new treatments and pharmacological approaches. 相似文献
66.
Alicia Barbero Susana Astiz Clemente J. Lopez-Bote Maria L. Perez-Solana Miriam Ayuso Isabel Garcia-Real Antonio Gonzalez-Bulnes 《PloS one》2013,8(10)
The present study aimed to determine, in a swine model of leptin resistance, the effects of type and timing of maternal malnutrition on growth patterns, adiposity and metabolic features of the progeny when exposed to an obesogenic diet during their juvenile development and possible concomitant effects of the offspring sex. Thus, four groups were considered. A CONTROL group involved pigs born from sows fed with a diet fulfilling their daily maintenance requirements for pregnancy. The treated groups involved the progeny of females fed with the same diet but fulfilling either 160% or 50% of pregnancy requirements during the entire gestation (OVERFED and UNDERFED, respectively) or 100% of requirements until Day 35 of pregnancy and 50% of such amount from Day 36 onwards (LATE-UNDERFED). OVERFED and UNDERFED offspring were more prone to higher corpulence and fat deposition from early postnatal stages, during breast-feeding; adiposity increased significantly when exposed to obesogenic diets, especially in females. The effects of sex were even more remarkable in LATE-UNDERFED offspring, which had similar corpulence to CONTROL piglets; however, females showed a clear predisposition to obesity. Furthermore, the three groups of pigs with maternal malnutrition showed evidences of metabolic syndrome and, in the case of individuals born from OVERFED sows, even of insulin resistance and the prodrome of type-2 diabetes. These findings support the main role of early nutritional programming in the current rise of obesity and associated diseases in ethnics with leptin resistance. 相似文献
67.
Benjamin S. Aribisala Alan J. Gow Mark E. Bastin Maria del Carmen Valdés Hernández Catherine Murray Natalie A. Royle Susana Mu?oz Maniega John M. Starr Ian J. Deary Joanna M. Wardlaw 《PloS one》2013,8(11)
Background
Higher levels of fitness or physical function are positively associated with cognitive outcomes but the potential underlying mechanisms via brain structure are still to be elucidated in detail. We examined associations between brain structure and physical function (contemporaneous and change over the previous three years) in community-dwelling older adults.Methodology/Principal Findings
Participants from the Lothian Birth Cohort 1936 (N=694) underwent brain MRI at age 73 years to assess intracranial volume, and the volumes of total brain tissue, ventricles, grey matter, normal-appearing white matter, and white matter lesions. At ages 70 and 73, physical function was assessed by 6-meter walk, grip strength, and forced expiratory volume. A summary ‘physical function factor’ was derived from the individual measures using principal components analysis. Performance on each individual physical function measure declined across the three year interval (p<0.001). Higher level of physical function at ages 70 and 73 was associated with larger total brain tissue and white matter volumes, and smaller ventricular and white matter lesion volumes (standardized β ranged in magnitude from 0.07 to 0.17, p<0.001 to 0.034). Decline in physical function from age 70 to 73 was associated with smaller white matter volume (0.08, p<0.01, though not after correction for multiple testing), but not with any other brain volumetric measurements.Conclusions/Significance
Physical function was related to brain volumes in community-dwelling older adults: declining physical function was associated with less white matter tissue. Further study is required to explore the detailed mechanisms through which physical function might influence brain structure, and vice versa. 相似文献68.
Climate has been inherently linked to global diversity patterns, and yet no empirical data are available to put modern climate change into a millennial-scale context. High tropical species diversity has been linked to slow rates of climate change during the Quaternary, an assumption that lacks an empirical foundation. Thus, there is the need for quantifying the velocity at which the bioclimatic space changed during the Quaternary in the tropics. Here we present rates of climate change for the late Pleistocene and Holocene from Mexico and Guatemala. An extensive modern pollen survey and fossil pollen data from two long sedimentary records (30,000 and 86,000 years for highlands and lowlands, respectively) were used to estimate past temperatures. Derived temperature profiles show a parallel long-term trend and a similar cooling during the Last Glacial Maximum in the Guatemalan lowlands and the Mexican highlands. Temperature estimates and digital elevation models were used to calculate the velocity of isotherm displacement (temperature change velocity) for the time period contained in each record. Our analyses showed that temperature change velocities in Mesoamerica during the late Quaternary were at least four times slower than values reported for the last 50 years, but also at least twice as fast as those obtained from recent models. Our data demonstrate that, given extremely high temperature change velocities, species survival must have relied on either microrefugial populations or persistence of suppressed individuals. Contrary to the usual expectation of stable climates being associated with high diversity, our results suggest that Quaternary tropical diversity was probably maintained by centennial-scale oscillatory climatic variability that forestalled competitive exclusion. As humans have simplified modern landscapes, thereby removing potential microrefugia, and climate change is occurring monotonically at a very high velocity, extinction risk for tropical species is higher than at any time in the last 86,000 years. 相似文献
69.
It is widely agreed that complex diseases are typically caused by the joint effects of multiple instead of a single genetic variation. These genetic variations may show stronger effects when considered together than when considered individually, a phenomenon known as epistasis or multilocus interaction. In this work, we explore the applicability of information interaction to discover pairwise epistatic effects related with complex diseases. We start by showing that traditional approaches such as classification methods or greedy feature selection methods (such as the Fleuret method) do not perform well on this problem. We then compare our information interaction method with BEAM and SNPHarvester in artificial datasets simulating epistatic interactions and show that our method is more powerful to detect pairwise epistatic interactions than its competitors. We show results of the application of information interaction method to the WTCCC breast cancer dataset. Our results are validated using permutation tests. We were able to find 89 statistically significant pairwise interactions with a p-value lower than . Even though many recent algorithms have been designed to find epistasis with low marginals, we observed that all (except one) of the SNPs involved in statistically significant interactions have moderate or high marginals. We also report that the interactions found in this work were not present in gene-gene interaction network STRING. 相似文献
70.
Martha Lissete Morales Villarreal Marina Padilha Antonio Diogo Silva Vieira Bernadette Dora Gombossy de Melo Franco Rafael Chacon Ruiz Martinez Susana Marta Isay Saad 《PloS one》2013,8(12)
Species-specific Quantitative Real Time PCR (qPCR) alone and combined with the use of propidium monoazide (PMA) were used along with the plate count method to evaluate the survival of the probiotic strains Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12, and the bacteriocinogenic and potentially probiotic strain Lactobacillus sakei subsp. sakei 2a in synbiotic (F1) and probiotic (F2) petit-suisse cheeses exposed throughout shelf-life to in vitro simulated gastrointestinal tract conditions. The three strains studied showed a reduction in their viability after the 6 h assay. Bb-12 displayed the highest survival capacity, above 72.6 and 74.6% of the initial populations, respectively, by plate count and PMA-qPCR, maintaining population levels in the range or above 6 log CFU/g. The prebiotic mix of inulin and FOS did not offer any additional protection for the strains against the simulated gastrointestinal environment. The microorganisms'' populations were comparable among the three methods at the initial time of the assay, confirming the presence of mainly viable and culturable cells. However, with the intensification of the stress induced throughout the various stages of the in vitro test, the differences among the methods increased. The qPCR was not a reliable enumeration method for the quantification of intact bacterial populations, mixed with large numbers of injured and dead bacteria, as confirmed by the scanning electron microscopy results. Furthermore, bacteria plate counts were much lower (P<0.05) than with the PMA-qPCR method, suggesting the accumulation of stressed or dead microorganisms unable to form colonies. The use of PMA overcame the qPCR inability to differentiate between dead and alive cells. The combination of PMA and species-specific qPCR in this study allowed a quick and unequivocal way of enumeration of viable closely related species incorporated into probiotic and synbiotic petit-suisse cheeses and under stress conditions. 相似文献