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  • 1
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    Impaired mitochondrial oxidative phosphorylation in the peroxisomal disease X-linked adrenoleukodystrophy (2013)
    Oxford University Press
    Details
    Publication Date: 2013-07-26
    Description: X-linked adrenoleukodystrophy (X-ALD) is an inherited metabolic disorder of the nervous system characterized by axonopathy in spinal cords and/or cerebral demyelination, adrenal insufficiency and accumulation of very long-chain fatty acids (VLCFAs) in plasma and tissues. The disease is caused by malfunction of the ABCD1 gene, which encodes a peroxisomal transporter of VLCFAs or VLCFA-CoA. In the mouse, Abcd1 loss causes late onset axonal degeneration in the spinal cord, associated with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. We have formerly shown that an excess of the VLCFA C26:0 induces oxidative damage, which underlies the axonal degeneration exhibited by the Abcd1 – mice. In the present study, we sought to investigate the noxious effects of C26:0 on mitochondria function. Our data indicate that in X-ALD patients' fibroblasts, excess of C26:0 generates mtDNA oxidation and specifically impairs oxidative phosphorylation (OXPHOS) triggering mitochondrial ROS production from electron transport chain complexes. This correlates with impaired complex V phosphorylative activity, as visualized by high-resolution respirometry on spinal cord slices of Abcd1 – mice. Further, we identified a marked oxidation of key OXPHOS system subunits in Abcd1 – mouse spinal cords at presymptomatic stages. Altogether, our results illustrate some of the mechanistic intricacies by which the excess of a fatty acid targeted to peroxisomes activates a deleterious process of oxidative damage to mitochondria, leading to a multifaceted dysfunction of this organelle. These findings may be of relevance for patient management while unveiling novel therapeutic targets for X-ALD.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 2
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    Relevance of silicate surface morphology in interstellar H2 formation. Insights from quantum chemical calculations (2015)
    Oxford University Press
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    Publication Date: 2015-08-24
    Description: The adsorption of H atoms and their recombination to form an H 2 molecule on slab models of the crystalline Mg 2 SiO 4 forsterite (001) and (110) surfaces was studied by means of quantum mechanical calculations based on periodic density functional theory (DFT). Present results are compared with those previously reported for the most stable (010) surface, showing the relevance of the surface morphology and their stability on the H 2 formation. Different H chemisorption states were identified, mostly on the outermost O atoms of the surfaces. In agreement with the higher instability of the (001) and (110) surfaces, the calculated adsorption energies are larger than those for the (010) surface. Computed energy barriers for the H hopping on these surfaces are exceedingly high to occur at the very low temperatures of deep space. For the adsorption of two H atoms, the most stable complexes are those in which the H atoms form Mg-H and SiOH surface groups. From these complexes, we did not identify energetically feasible paths for H 2 formation through a Langmuir–Hinshelwood mechanism on the (001) surface because the initial states are more stable than the final products. However, on the (110) surface one path was found to be exoergic with very low energy barriers. This differs to that observed for the (010) surface, for which two feasible Langmuir–Hinshelwood-based channels were identified. H 2 formation through the Eley–Rideal mechanism was also simulated, in which an incoming H atom impinges on a pre-adsorbed H atom at the (001) and (110) surfaces in a barrierless way.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 3
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    Lagrangian volume deformations around simulated galaxies (2015)
    Oxford University Press
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    Publication Date: 2015-05-30
    Description: We present a detailed analysis of the local evolution of 206 Lagrangian Volumes (LVs) selected at high redshift around galaxy seeds, identified in a large-volume cold dark matter (CDM) hydrodynamical simulation. The LVs have a mass range of 1–1500 10 10 M . We follow the dynamical evolution of the density field inside these initially spherical LVs from z  = 10 up to z low  = 0.05, witnessing highly non-linear, anisotropic mass rearrangements within them, leading to the emergence of the local cosmic web (CW). These mass arrangements have been analysed in terms of the reduced inertia tensor $I_{ij}^r$ , focusing on the evolution of the principal axes of inertia and their corresponding eigendirections, and paying particular attention to the times when the evolution of these two structural elements declines. In addition, mass and component effects along this process have also been investigated. We have found that deformations are led by dark matter dynamics and they transform most of the initially spherical LVs into prolate shapes, i.e. filamentary structures. An analysis of the individual freezing-out time distributions for shapes and eigendirections shows that first most of the LVs fix their three axes of symmetry (like a skeleton) early on, while accretion flows towards them still continue. Very remarkably, we have found that more massive LVs fix their skeleton earlier on than less massive ones. We briefly discuss the astrophysical implications our findings could have, including the galaxy mass–morphology relation and the effects on the galaxy–galaxy merger parameter space, among others.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 4
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    The BaLROG project - II. Quantifying the influence of bars on the stellar populations of nearby galaxies (2016)
    Oxford University Press
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    Publication Date: 2016-06-24
    Description: We continue the exploration of the BaLROG (Bars in Low Redshift Optical Galaxies) sample: 16 large mosaics of barred galaxies observed with the integral field unit Spectrographic Areal Unit for Research on Optical Nebulae. We quantify the influence of bars on the composition of the stellar component. We derive line-strength indices of H β, Fe5015 and Mg b . Based on single stellar population (SSP) models, we calculate ages, metallicities and [Mg/Fe] abundances and their gradients along the bar major and minor axes. The high spatial resolution of our data allows us to identify breaks among index and SSP profiles, commonly at 0.13 ± 0.06 bar length, consistent with kinematic features. Inner gradients are about 10 times steeper than outer gradients and become larger when there is a central rotating component, implying that the gradients are not independent of dynamics and orbits. Central ages appear to be younger for stronger bars. Yet, the bar regions are usually old. We find a flattening of the iron (Fe5015) and magnesium (Mg b ) outer gradients along the bar major axis, translating into a flattening of the metallicity gradient. This gradient is found to be 0.03 ± 0.07 dex kpc –1 along the bar major axis while the mean value of the bar minor axis compares well with that of an unbarred control sample and is significantly steeper, namely –0.20 ± 0.04 dex kpc –1 . These results confirm recent simulations and discern the important localized influence of bars. The elevated [Mg/Fe] abundances of bars and bulges compared to the lower values of discs suggest an early formation, in particular for early-type galaxies.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 5
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    The Aguacaliente Fault, source of the Cartago 1910 destructive earthquake (Costa Rica) (2013)
    Wiley
    Details
    Publication Date: 2013-04-02
    Description: On May 4, 1910, the most destructive earthquake in the history of Costa Rica (Ms 6.4) destroyed the city of Cartago, a major city located in the Valle Central of Costa Rica. Using both paleoseismological and morphotectonic analyses we have found evidence that points to the Aguacaliente Fault as the source of this earthquake. This structure is a N100 o E trending, strike-slip fault situated to the south of Cartago and within a wide band of deformation. We excavated two trenches near Bermejo, south of Cartago. We found evidence of three surface ruptures within the last 1,000 years on this fault. The age of the most recent rupture is consistent with the Cartago 1910 earthquake. The Aguacaliente fault is a seismogenic source capable of producing large earthquakes (Mw 6.5-6.9) with an estimated recurrence interval of about 500 years. © 2013 Blackwell Publishing Ltd
    Print ISSN: 0954-4879
    Electronic ISSN: 1365-3121
    Topics: Geosciences
    Published by Wiley
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  • 6
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    The role of defoliation and root rot pathogen infection in driving the mode of drought-related physiological decline in Scots pine (Pinus sylvestris L.) (2015)
    Oxford University Press
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    Publication Date: 2015-04-08
    Description: Drought-related tree die-off episodes have been observed in all vegetated continents. Despite much research effort, however, the multiple interactions between carbon starvation, hydraulic failure and biotic agents in driving tree mortality under field conditions are still not well understood. We analysed the seasonal variability of non-structural carbohydrates (NSCs) in four organs (leaves, branches, trunk and roots), the vulnerability to embolism in roots and branches, native embolism (percentage loss of hydraulic conductivity (PLC)) in branches and the presence of root rot pathogens in defoliated and non-defoliated individuals in a declining Scots pine ( Pinus sylvestris L.) population in the NE Iberian Peninsula in 2012, which included a particularly dry and warm summer. No differences were observed between defoliated and non-defoliated pines in hydraulic parameters, except for a higher vulnerability to embolism at pressures below –2 MPa in roots of defoliated pines. No differences were found between defoliation classes in branch PLC. Total NSC (TNSC, soluble sugars plus starch) values decreased during drought, particularly in leaves. Defoliation reduced TNSC levels across tree organs, especially just before (June) and during (August) drought. Root rot infection by the fungal pathogen Onnia P. Karst spp. was detected but it did not appear to be associated to tree defoliation. However, Onnia infection was associated with reduced leaf-specific hydraulic conductivity and sapwood depth, and thus contributed to hydraulic impairment, especially in defoliated pines. Infection was also associated with virtually depleted root starch reserves during and after drought in defoliated pines. Moreover, defoliated and infected trees tended to show lower basal area increment. Overall, our results show the intertwined nature of physiological mechanisms leading to drought-induced mortality and the inherent difficulty of isolating their contribution under field conditions.
    Print ISSN: 0829-318X
    Electronic ISSN: 1758-4469
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Published by Oxford University Press
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  • 7
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    Periodic eclipse variations in asynchronous polar V1432 Aql: evidence of a shifting threading region (2015)
    Oxford University Press
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    Publication Date: 2015-04-10
    Description: We report the results of a 28-month photometric campaign studying V1432 Aql, the only known eclipsing, asynchronous polar. Our data show that both the residual eclipse flux and eclipse O–C timings vary strongly as a function of the spin-orbit beat period. Relying upon a new model of the system, we show that cyclical changes in the location of the threading region along the ballistic trajectory of the accretion stream could produce both effects. This model predicts that the threading radius is variable, in contrast to previous studies which have assumed a constant threading radius. Additionally, we identify a very strong photometric maximum which is only visible for half of the beat cycle. The exact cause of this maximum is unclear, but we consider the possibility that it is the optical counterpart of the third accreting polecap proposed by Rana et al. Finally, the rate of change of the white dwarf's spin period is consistent with it being proportional to the difference between the spin and orbital periods, implying that the spin period is approaching the orbital period asymptotically.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 8
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    Historical trends in precipitation, temperature and drought in the Alabama–Coosa–Tallapoosa and Apalachicola–Chattahoochee–Flint river basins (2016)
    Wiley
    Details
    Publication Date: 2016-04-01
    Description: ABSTRACT Using station data from the United States Historical Climatology Network, we preformed a running trend analysis of temperature, precipitation and drought in the Alabama–Coosa–Tallapoosa and Apalachicola–Chattahoochee–Flint river basins for the time period 1895–2012 on annual and monthly timescales. Our study found that long-term precipitation and temperature trends were statistically detectible but relatively slight in the order of an increase at 3 mm per decade for precipitation and a decline of 0.02 °C per decade for temperature. Running trend analyses for the time period 1895–2012 found field-significant and relatively large annual precipitation increases and temperature decreases between the 1950s and early 1980s associated with the 'warming hole'. The magnitude of precipitation trends for the aforementioned period was in the range of 7 mm per year for precipitation and 0.6 °C per decade for temperature. For temperature, we observed generally decreasing maximum, minimum and mean temperatures in the 1960s and 1970s and increasing temperatures from the 1970s to present. Minimum temperatures particularly showed a strong increase in recent summer months in the range of 0.3 °C per decade. Trends in the diurnal temperature range showed a recent narrowing during summer and fall months. Differences in the standardized precipitation index (SPI) and standardized precipitation evapotranspiration index (SPEI) did not show a strong effect of temperature on drought for this region.
    Print ISSN: 0899-8418
    Electronic ISSN: 1097-0088
    Topics: Geosciences , Physics
    Published by Wiley
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  • 9
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    RNAiFold2T: Constraint Programming design of thermo-IRES switches (2016)
    Oxford University Press
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    Publication Date: 2016-06-16
    Description: Motivation: RNA thermometers (RNATs) are cis -regulatory elements that change secondary structure upon temperature shift. Often involved in the regulation of heat shock, cold shock and virulence genes, RNATs constitute an interesting potential resource in synthetic biology, where engineered RNATs could prove to be useful tools in biosensors and conditional gene regulation. Results: Solving the 2-temperature inverse folding problem is critical for RNAT engineering. Here we introduce RNAiFold2T, the first Constraint Programming (CP) and Large Neighborhood Search (LNS) algorithms to solve this problem. Benchmarking tests of RNAiFold2T against existent programs (adaptive walk and genetic algorithm) inverse folding show that our software generates two orders of magnitude more solutions, thus allowing ample exploration of the space of solutions. Subsequently, solutions can be prioritized by computing various measures, including probability of target structure in the ensemble, melting temperature, etc. Using this strategy, we rationally designed two thermosensor internal ribosome entry site ( thermo -IRES) elements, whose normalized cap-independent translation efficiency is approximately 50% greater at 42 °C than 30 °C, when tested in reticulocyte lysates. Translation efficiency is lower than that of the wild-type IRES element, which on the other hand is fully resistant to temperature shift-up. This appears to be the first purely computational design of functional RNA thermoswitches, and certainly the first purely computational design of functional thermo-IRES elements. Availability: RNAiFold2T is publicly available as part of the new release RNAiFold3.0 at https://github.com/clotelab/RNAiFold and http://bioinformatics.bc.edu/clotelab/RNAiFold , which latter has a web server as well. The software is written in C ++ and uses OR-Tools CP search engine. Contact: clote@bc.edu Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 10
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    Low-mass disc galaxies and the issue of stability: MOND versus dark matter (2016)
    Oxford University Press
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    Publication Date: 2016-09-03
    Description: We analyse the rotation curves and gravitational stability of a sample of six bulgeless galaxies for which detailed images reveal no evidence for strong bars. We explore two scenarios: Newtonian dark matter models and MOdified Newtonian Dynamics (MOND). By adjusting the stellar mass-to-light ratio, dark matter models can match simultaneously both the rotation curve and bar-stability requirements in these galaxies. To be consistent with stability constraints, in two of these galaxies, the stellar mass-to-light ratio is a factor of ~1.5–2 lower than the values suggested from galaxy colours. In contrast, MOND fits to the rotation curves are poor in three galaxies, perhaps because the gas tracer contains non-circular motions. The bar stability analysis provides a new observational test to MOND. We find that most of the galaxies under study require abnormally high levels of random stellar motions to be bar stable in MOND. In particular, for the only galaxy in the sample for which the line-of-sight stellar velocity dispersion has been measured (NGC 6503), the observed velocity dispersion is not consistent with MOND predictions because it is far below the required value to guarantee bar stability. Precise measurements of mass-weighted velocity dispersions in (unbarred and bulgeless) spiral galaxies are crucial to test the consistency of MOND.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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