Mitochondrial ultrastructure and markers of dynamics in hepatocytes from aged, calorie restricted mice fed with different dietary fats

PMCID: PMC4104696In this paper we analyzed changes in hepatocyte mitochondrial mass and ultrastructure as well as in mitochondrial markers of fission/fusion and biogenesis in mice subjected to 40% calorie restriction (CR) for 18. months versus ad libitum-fed controls. Animals subjected to CR were separated into three groups with different dietary fats: soybean oil (also in controls), fish oil and lard. Therefore, the effect of the dietary fat under CR was studied as well. Our results show that CR induced changes in hepatocyte and mitochondrial size, in the volume fraction occupied by mitochondria, and in the number of mitochondria per hepatocyte. Also, mean number of mitochondrial cristae and lengths were significantly higher in all CR groups compared with controls. Finally, CR had no remarkable effects on the expression levels of fission and fusion protein markers. However, considerable differences in many of these parameters were found when comparing the CR groups, supporting the idea that dietary fat plays a relevant role in the modulation of CR effects in aged mice.Supported by NIH grant 1R01AG028125-01A1 (to JJR, PN and JMV), Ministerio de Economía y Competitividad and European FEDERBFU2011-23578 (to JMV), Junta de Andalucía Proyectos de Excelencia grant P09-CVI-4887 (to JMV), Junta de Andalucía Proyectos Internacionales (to JMV), and BIO-276 (Junta de Andalucía and the University of Córdoba, to JMV and EGC). JALD and LFdR were funded by predoctoral fellowships of the Spanish Ministerio de Educación and by BIO-276. HK was funded by a predoctoral fellowship of the Agencia Española de Cooperación Internacional al Desarrollo and by BIO-276.Peer Reviewe

The influence of dietary fat source on liver and skeletal muscle mitochondrial modifications and lifespan changes in calorie-restricted mice

The Membrane Theory of Aging proposes that lifespan is inversely related to the level of unsaturation in membrane phospholipids. Calorie restriction (CR) without malnutrition extends lifespan in many model organisms, which may be related to alterations in membrane phospholipids fatty acids. During the last few years our research focused on studying how altering the predominant fat source affects the outcome of CR in mice. We have established four dietary groups: one control group fed 95 % of a pre-determined ad libitum intake (in order to prevent obesity), and three CR groups fed 40 % less than ad libitum intake. Lipid source for the control and one of the CR groups was soybean oil (high in n-6 PUFA) whereas the two remaining CR groups were fed diets containing fish oil (high in n-3 PUFA), or lard (high in saturated and monounsaturated fatty acids). Dietary intervention periods ranged from 1 to 18 months. We performed a longitudinal lifespan study and a cross-sectional study set up to evaluate several mitochondrial parameters which included fatty acid composition, H+ leak, activities of electron transport chain enzymes, ROS generation, lipid peroxidation, mitochondrial ultrastructure, and mitochondrial apoptotic signaling in liver and skeletal muscle. These approaches applied to different cohorts of mice have independently indicated that lard as a fat source often maximizes the effects of 40 % CR on mice. These effects could be due to significant increases of monounsaturated fatty acids levels, in accordance with the Membrane Theory of Aging.Supported by NIH grant 1R01AG028125 (to JJR, PN and JMV), Ministerio de Economía y Competitividad BFU2011-23578 (to JMV), Junta de Andalucía Proyectos de Excelencia grant P09-CVI-4887 (to JMV), Junta de Andalucía Proyectos Internacionales grant (to JMV), and BIO-276 (Junta de Andalucía and the University of Córdoba, to JMV). RdC is funded by the Intramural Research program of the NIA/NIH. JALD, JA, LFdR and EGC were funded by a predoctoral fellowship of the Spanish Ministerio de Educación and BIO-276. HK was funded by a predoctoral fellowship of the Agencia Española de Cooperación Internacional al Desarrollo and BIO-276. MCR and MdR were supported by BIO-276.Peer Reviewe

Valoración de la capacidad predictiva de la calculadora Garvan del riesgo de fractura a 10 años en una población española

Introduction: Several calculation tools or scales have been developed in recent years to assess the risk of fracture due to long-term fragility. The Garvan calculator has not been validated in the Spanish population. This study aims to observe their predictive capacity in a population sample of the Canary Islands and, therefore, of the Spanish population. Material and Methods: We included 121 patients who were followed up for 10 years in our consultations. All were assessed the risk of fracture using the Garvan calculator and based on the data obtained in the first visit. Results: Of the 121 patients, 30 suffered at least one osteoporotic fracture over the 10-year follow-up period. The group of patients with fractures had on the Garvan scale an average risk value to suffer any fracturing fracture of 27%, compared to 13% of those who did not suffer fracture (p<0.001). The area under the corresponding ROC curve was 0.718 (CI-95% = 0.613 ; 0.824). Based on this, the estimated optimal cut-off point to consider a high risk fracture was 18.5%. This value corresponded to a sensitivity of 0.67 (CI-95% = 0.47 ; 0.83) and a specificity of 0.67 (CI-95% = 0.56 ; 0.77). Conclusions: Our results show that the Garvan scale adequately predicts the risk of 10-year osteoporotic fracture in our population. A value lower than 18.5% would allow us to establish a low fracture risk and could be used as a screening tool.Introducción: En los últimos años se han desarrollado varias herramientas de cálculo o escalas para valorar el riesgo de fractura por fragilidad a largo plazo. La calculadora Garvan no ha sido validada en la población española. El objetivo de este estudio fue observar su capacidad predictiva en una muestra de la población canaria y, por tanto, de la española. Material y métodos: Se incluyó a 121 pacientes a los que se les realizó un seguimiento de 10 años en nuestras consultas. A todos se les valoró el riesgo de fractura usando la calculadora Garvan y basándonos en los datos obtenidos en la primera visita realizada. Resultados: De los 121 pacientes, 30 sufrieron al menos una fractura osteoporótica a lo largo de los 10 años de seguimiento. El grupo de pacientes fracturados tenían en la escala Garvan un valor medio de riesgo de sufrir cualquier fractura por fragilidad de 27%, frente al 13% de aquellos que no sufrieron fractura (p<0,001). El área bajo la correspondiente curva ROC fue de 0,718 (IC-95% = 0,613 ; 0,824). En base a ella, se estimó que el punto de corte óptimo para considerar un alto riesgo de fractura por fragilidad fue 18,5%. A este valor le correspondió una sensibilidad de 0,67 (IC-95% = 0,47 ; 0,83) y una especificidad de 0,67 (IC-95% = 0,56 ; 0,77). Conclusiones: Nuestros resultados muestran que la escala Garvan predice adecuadamente el riesgo de fractura osteoporótica a 10 años en nuestra población. Un valor inferior a 18,5% permitiría establecer un riesgo de fractura bajo, pudiendo ser utilizada como herramienta de cribado

Charge separation relative to the reaction plane in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}}= 2.76 TeV

Measurements of charge dependent azimuthal correlations with the ALICE detector at the LHC are reported for Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV. Two- and three-particle charge-dependent azimuthal correlations in the pseudo-rapidity range $|\eta| < 0.8$ are presented as a function of the collision centrality, particle separation in pseudo-rapidity, and transverse momentum. A clear signal compatible with a charge-dependent separation relative to the reaction plane is observed, which shows little or no collision energy dependence when compared to measurements at RHIC energies. This provides a new insight for understanding the nature of the charge dependent azimuthal correlations observed at RHIC and LHC energies.Comment: 12 pages, 3 captioned figures, authors from page 2 to 6, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/286

First broadband characterization and redshift determination of the VHE blazar MAGIC J2001+439

We aim to characterize the broadband emission from 2FGL J2001.1+4352, which has been associated with the unknown-redshift blazar MG4 J200112+4352. Based on its gamma-ray spectral properties, it was identified as a potential very high energy (VHE; E > 100 GeV) gamma-ray emitter. The source was observed with MAGIC first in 2009 and later in 2010 within a multi-instrument observation campaign. The MAGIC observations yielded 14.8 hours of good quality stereoscopic data. The object was monitored at radio, optical and gamma-ray energies during the years 2010 and 2011. The source, named MAGIC J2001+439, is detected for the first time at VHE with MAGIC at a statistical significance of 6.3 {\sigma} (E > 70 GeV) during a 1.3-hour long observation on 2010 July 16. The multi-instrument observations show variability in all energy bands with the highest amplitude of variability in the X-ray and VHE bands. We also organized deep imaging optical observations with the Nordic Optical Telescope in 2013 to determine the source redshift. We determine for the first time the redshift of this BL Lac object through the measurement of its host galaxy during low blazar activity. Using the observational evidence that the luminosities of BL Lac host galaxies are confined to a relatively narrow range, we obtain z = 0.18 +/- 0.04. Additionally, we use the Fermi-LAT and MAGIC gamma-ray spectra to provide an independent redshift estimation, z = 0.17 +/- 0.10. Using the former (more accurate) redshift value, we adequately describe the broadband emission with a one-zone SSC model for different activity states and interpret the few-day timescale variability as produced by changes in the high-energy component of the electron energy distribution.Comment: 17 pages, 15 figures, Accepted for publication in A&

A note on comonotonicity and positivity of the control components of decoupled quadratic FBSDE

In this small note we are concerned with the solution of Forward-Backward Stochastic Differential Equations (FBSDE) with drivers that grow quadratically in the control component (quadratic growth FBSDE or qgFBSDE). The main theorem is a comparison result that allows comparing componentwise the signs of the control processes of two different qgFBSDE. As a byproduct one obtains conditions that allow establishing the positivity of the control process.Comment: accepted for publicatio

Transverse sphericity of primary charged particles in minimum bias proton-proton collisions at s=0.9\sqrt{s}=0.9, 2.76 and 7 TeV

Measurements of the sphericity of primary charged particles in minimum bias proton--proton collisions at $\sqrt{s}=0.9$, 2.76 and 7 TeV with the ALICE detector at the LHC are presented. The observable is linearized to be collinear safe and is measured in the plane perpendicular to the beam direction using primary charged tracks with $p_{\rm T}\geq0.5$ GeV/c in $|\eta|\leq0.8$. The mean sphericity as a function of the charged particle multiplicity at mid-rapidity ($N_{\rm ch}$) is reported for events with different $p_{\rm T}$ scales ("soft" and "hard") defined by the transverse momentum of the leading particle. In addition, the mean charged particle transverse momentum versus multiplicity is presented for the different event classes, and the sphericity distributions in bins of multiplicity are presented. The data are compared with calculations of standard Monte Carlo event generators. The transverse sphericity is found to grow with multiplicity at all collision energies, with a steeper rise at low $N_{\rm ch}$, whereas the event generators show the opposite tendency. The combined study of the sphericity and the mean $p_{\rm T}$ with multiplicity indicates that most of the tested event generators produce events with higher multiplicity by generating more back-to-back jets resulting in decreased sphericity (and isotropy). The PYTHIA6 generator with tune PERUGIA-2011 exhibits a noticeable improvement in describing the data, compared to the other tested generators.Comment: 21 pages, 9 captioned figures, 3 tables, authors from page 16, published version, figures from http://aliceinfo.cern.ch/ArtSubmission/node/308

Simultaneous multi-frequency observation of the unknown redshift blazar PG 1553+113 in March-April 2008

The blazar PG 1553+113 is a well known TeV gamma-ray emitter. In this paper, we determine its spectral energy distribution using simultaneous multi-frequency data in order to study its emission processes. An extensive campaign was carried out between March and April 2008, where optical, X-ray, high-energy (HE) gamma-ray, and very-high-energy (VHE) gamma-ray data were obtained with the KVA, Abastumani, REM, RossiXTE/ASM, AGILE and MAGIC telescopes, respectively. This is the first simultaneous broad-band (i.e., HE+VHE) gamma-ray observation, though AGILE did not detect the source. We combine data to derive source's spectral energy distribution and interpret its double peaked shape within the framework of a synchrotron self compton modelComment: 5 pages, 2 figures, publishe

Centrality dependence of charged particle production at large transverse momentum in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm{NN}}} = 2.76 TeV

The inclusive transverse momentum ($p_{\rm T}$) distributions of primary charged particles are measured in the pseudo-rapidity range $|\eta|<0.8$ as a function of event centrality in Pb-Pb collisions at $\sqrt{s_{\rm{NN}}}=2.76$ TeV with ALICE at the LHC. The data are presented in the $p_{\rm T}$ range $0.15<p_{\rm T}<50$ GeV/$c$ for nine centrality intervals from 70-80% to 0-5%. The Pb-Pb spectra are presented in terms of the nuclear modification factor $R_{\rm{AA}}$ using a pp reference spectrum measured at the same collision energy. We observe that the suppression of high-$p_{\rm T}$ particles strongly depends on event centrality. In central collisions (0-5%) the yield is most suppressed with $R_{\rm{AA}}\approx0.13$ at $p_{\rm T}=6$-7 GeV/$c$. Above $p_{\rm T}=7$ GeV/$c$, there is a significant rise in the nuclear modification factor, which reaches $R_{\rm{AA}} \approx0.4$ for $p_{\rm T}>30$ GeV/$c$. In peripheral collisions (70-80%), the suppression is weaker with $R_{\rm{AA}} \approx 0.7$ almost independently of $p_{\rm T}$. The measured nuclear modification factors are compared to other measurements and model calculations.Comment: 17 pages, 4 captioned figures, 2 tables, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/284

Complex evolutionary history of the Mexican stoneroller Campostoma ornatum Girard, 1856 (Actinopterygii: Cyprinidae)

<p>Abstract</p> <p>Background</p> <p>Studies of the phylogeography of Mexican species are steadily revealing genetic patterns shared by different species, which will help to unravel the complex biogeographic history of the region. <it>Campostoma ornatum </it>is a freshwater fish endemic to montane and semiarid regions in northwest Mexico and southern Arizona. Its wide range of distribution and the previously observed morphological differentiation between populations in different watersheds make this species a useful model to investigate the biogeographic role of the Sierra Madre Occidental and to disentangle the actions of Pliocene tecto-volcanic processes <it>vs </it>Quaternary climatic change. Our phylogeographic study was based on DNA sequences from one mitochondrial gene (<it>cytb</it>, 1110 bp, n = 285) and two nuclear gene regions (S7 and RAG1, 1822 bp in total, n = 56 and 43, respectively) obtained from 18 to 29 localities, in addition to a morphological survey covering the entire distribution area. Such a dataset allowed us to assess whether any of the populations/lineages sampled deserve to be categorised as an evolutionarily significant unit.</p> <p>Results</p> <p>We found two morphologically and genetically well-differentiated groups within <it>C. ornatum</it>. One is located in the northern river drainages (Yaqui, Mayo, Fuerte, Sonora, Casas Grandes, Santa Clara and Conchos) and another one is found in the southern drainages (Nazas, Aguanaval and Piaxtla). The split between these two lineages took place about 3.9 Mya (CI = 2.1-5.9). Within the northern lineage, there was strong and significant inter-basin genetic differentiation and also several secondary dispersal episodes whit gene homogenization between drainages. Interestingly, three divergent mitochondrial lineages were found in sympatry in two northern localities from the Yaqui river basin.</p> <p>Conclusions</p> <p>Our results indicate that there was isolation between the northern and southern phylogroups since the Pliocene, which was related to the formation of the ancient Nazas River paleosystem, where the southern group originated. Within groups, a complex reticulate biogeographic history for <it>C. ornatum </it>populations emerges, following the taxon pulse theory and mainly related with Pliocene tecto-volcanic processes. In the northern group, several events of vicariance promoted by river or drainage isolation episodes were found, but within both groups, the phylogeographic patterns suggest the occurrence of several events of river capture and fauna interchange. The Yaqui River supports the most diverse populations of <it>C. ornatum</it>, with several events of dispersal and isolation within the basin. Based on our genetic results, we defined three ESUs within <it>C. ornatum </it>as a first attempt to promote the conservation of the evolutionary processes determining the genetic diversity of this species. They will likely be revealed as a valuable tool for freshwater conservation policies in northwest Mexico, where many environmental problems concerning the use of water have rapidly arisen in recent decades.</p