Epigenetic modifications as outcomes of exercise interventions related to specific metabolic alterations: a systematic review

Background: Chronic diseases arise as a consequence of an unhealthy lifestyle primarily characterized by physical inactivity and unbalanced diets. Regular physical activity can improve health, and there is consistent evidence that these improvements may be the result of epigenetic modifications. Objective: To identify epigenetic modificationsas outcomes of exercise interventions related to specific metabolic alterations. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) methodology for manuscript research and preparation was followed using PubMed and EBSCO databases for literature review. Out of 2,638 articles identified, only 34 articles met the inclusion criteria. Results: The sections of the review were organized by metabolic alterations in which studies were grouped according to healthy, diseased, and trained individuals. Resistance exercise in humans induced epigenetic changes in pathways associated with energy metabolism and insulin sensitivity, contributing to healthy skeletal muscle. Endurance exercise also caused modifications in biomarkers associated to metabolic alterations through changes in DNA methylation and the expression of specific miRNAs. However, both resistance and endurance exercise are necessary to obtain a better physiological adaptation and a combination of both seems to be needed to properly tackle the increasing prevalence of non-communicable pathologies. Conclusion: Given the heterogeneity and complexity of the existing literature, it is currently not possible to propose a specific recommendation about the type, intensity, or duration of exercise that could be beneficial for different subsets of the population (healthy, diseased, and/or trained). Nevertheless, this review highlights the importance of exercise for health and shows the need to perform more research in this emerging area to identify epigenetic biomarkers that could serve as indicators of exercise adaptations

Flat Spectrum Radio Quasars through the MAGIC glasses

The detection of Flat Spectrum Radio Quasars (FSRQs) in the Very High Energy (VHE, E > 100 GeV) range is challenging, mainly because of their steep spectra in this energy band. Up to now, only five FSRQs are known to be VHE γ-ray emitters, all of them have been detected by the MAGIC telescopes, that discovered four of them in the VHE band. The observations in the VHE band are crucial to understand their emission, specially to constrain the location of the emitting region within the jet due to the absorption from their broad line region (BLR). Typically, FSRQs are detected during high flux states, enhancing the probability of detection with the current instruments sensitivities. However, the last observation campaigns performed with the MAGIC telescopes show emission during moderate states, thus challenging our understanding of the emission mechanisms in FSRQs. In this contribution, we give an overview and present the most recent results of the three FSRQs 3C279, PKS1222+21 and PKS1510-089 in a multi-wavelength context with special focus on MAGIC and Fermi-LAT simultaneous observations

Biochemical and structural characterization of a novel thermophilic esterase EstD11 provide catalytic insights for the HSL family

19 pags., 12 figs., 2 tabs.A novel esterase, EstD11, has been discovered in a hot spring metagenomic library. It is a thermophilic and thermostable esterase with an optimum temperature of 60°C. A detailed substrate preference analysis of EstD11 was done using a library of chromogenic ester substrate that revealed the broad substrate specificity of EstD11 with significant measurable activity against 16 substrates with varied chain length, steric hindrance, aromaticity and flexibility of the linker between the carboxyl and the alcohol moiety of the ester. The tridimensional structures of EstD11 and the inactive mutant have been determined at atomic resolutions. Structural and bioinformatic analysis, confirm that EstD11 belongs to the family IV, the hormone-sensitive lipase (HSL) family, from the α/β-hydrolase superfamily. The canonical α/β-hydrolase domain is completed by a cap domain, composed by two subdomains that can unmask of the active site to allow the substrate to enter. Eight crystallographic complexes were solved with different substrates and reaction products that allowed identification of the hot-spots in the active site underlying the specificity of the protein. Crystallization and/or incubation of EstD11 at high temperature provided unique information on cap dynamics and a first glimpse of enzymatic activity in vivo. Very interestingly, we have discovered a unique Met zipper lining the active site and the cap domains that could be essential in pivotal aspects as thermo-stability and substrate promiscuity in EstD11.We thank the staff from ALBA synchrotron facility (Barcelona, Spain) for support during crystallographic data collection. This work was funded by the UE through the HotDrops Project (FP7- PEOPLE-2012-IAPP, project number 324439). Additionally, this work was supported by the BFU2017-90030-P grant to J.A.H. from the Spanish Ministry of Science and Innovatio

The afterglow and kilonova of the short GRB 160821B

GRB 160821B is a short duration gamma-ray burst (GRB) detected and localized by the Neil Gehrels Swift Observatory in the outskirts of a spiral galaxy at z=0.1613, at a projected physical offset of 16 kpc from the galaxy's center. We present X-ray, optical/nIR and radio observations of its counterpart and model them with two distinct components of emission: a standard afterglow, arising from the interaction of the relativistic jet with the surrounding medium, and a kilonova, powered by the radioactive decay of the sub-relativistic ejecta. Broadband modeling of the afterglow data reveals a weak reverse shock propagating backward into the jet, and a likely jet-break at 3.5 d. This is consistent with a structured jet seen slightly off-axis while expanding into a low-density medium. Analysis of the kilonova properties suggests a rapid evolution toward red colors, similar to AT2017gfo, and a low nIR luminosity, possibly due to the presence of a long-lived neutron star. The global properties of the environment, the inferred low mass (M_ej < 0.006 Msun) and velocities (v > 0.05 c) of lanthanide-rich ejecta are consistent with a binary neutron star merger progenitor.Comment: 14 pages, 6 figures, MNRAS, in press. Moderate revision, added Figure 5 and X-ray data to Table

Detection of bridge emission above 50 GeV from the Crab pulsar with the MAGIC telescopes

The Crab pulsar is the only astronomical pulsed source detected at very high energy (VHE, E>100GeV) gamma-rays. The emission mechanism of VHE pulsation is not yet fully understood, although several theoretical models have been proposed. In order to test the new models, we measured the light curve and the spectra of the Crab pulsar with high precision by means of deep observations. We analyzed 135 hours of selected MAGIC data taken between 2009 and 2013 in stereoscopic mode. In order to discuss the spectral shape in connection with lower energies, 4.6 years of {\it Fermi}-LAT data were also analyzed. The known two pulses per period were detected with a significance of $8.0 \sigma$ and $12.6 \sigma$. In addition, significant emission was found between the two pulses with $6.2 \sigma$. We discovered the bridge emission above 50 GeV between the two main pulses. This emission can not be explained with the existing theories. These data can be used for testing new theoretical models.Comment: 5 pages, 4 figure

MAGIC detection of short-term variability of the high-peaked BL Lac object 1ES 0806+524

The high-frequency-peaked BL Lac (HBL) 1ES 0806+524 (z = 0.138) was discovered in VHE $\gamma$ rays in 2008. Until now, the broad-band spectrum of 1ES 0806+524 has been only poorly characterized, in particular at high energies. We analysed multiwavelength observations from $\gamma$ rays to radio performed from 2011 January to March, which were triggered by the high activity detected at optical frequencies. These observations constitute the most precise determination of the broad-band emission of 1ES 0806+524 to date. The stereoscopic MAGIC observations yielded a $\gamma$-ray signal above 250 GeV of $(3.7 \pm 0.7)$ per cent of the Crab Nebula flux with a statistical significance of 9.9 $\sigma$. The multiwavelength observations showed significant variability in essentially all energy bands, including a VHE $\gamma$-ray flare that lasted less than one night, which provided unprecedented evidence for short-term variability in 1ES 0806+524. The spectrum of this flare is well described by a power law with a photon index of $2.97 \pm 0.29$ between $\sim$150 GeV and 1 TeV and an integral flux of $(9.3 \pm 1.9)$ per cent of the Crab Nebula flux above 250 GeV. The spectrum during the non-flaring VHE activity is compatible with the only available VHE observation performed in 2008 with VERITAS when the source was in a low optical state. The broad-band spectral energy distribution can be described with a one-zone Synchrotron Self Compton model with parameters typical for HBLs, indicating that 1ES 0806+524 is not substantially different from the HBLs previously detected.Comment: 12 pages, 8 figures, 3 tables, accepted 2015 April 20 for publication in Monthly Notices of the Royal Astronomical Society Main Journa

Measurement of the Crab Nebula spectrum over three decades in energy with the MAGIC telescopes

The MAGIC stereoscopic system collected 69 hours of Crab Nebula data between October 2009 and April 2011. Analysis of this data sample using the latest improvements in the MAGIC stereoscopic software provided an unprecedented precision of spectral and night-by-night light curve determination at gamma rays. We derived a differential spectrum with a single instrument from 50 GeV up to almost 30 TeV with 5 bins per energy decade. At low energies, MAGIC results, combined with Fermi-LAT data, show a flat and broad Inverse Compton peak. The overall fit to the data between 1 GeV and 30 TeV is not well described by a log-parabola function. We find that a modified log-parabola function with an exponent of 2.5 instead of 2 provides a good description of the data ($\chi^2=35/26$). Using systematic uncertainties of red the MAGIC and Fermi-LAT measurements we determine the position of the Inverse Compton peak to be at (53 $\pm$ 3stat + 31syst -13syst) GeV, which is the most precise estimation up to date and is dominated by the systematic effects. There is no hint of the integral flux variability on daily scales at energies above 300 GeV when systematic uncertainties are included in the flux measurement. We consider three state- of-the-art theoretical models to describe the overall spectral energy distribution of the Crab Nebula. The constant B-field model cannot satisfactorily reproduce the VHE spectral measurements presented in this work, having particular difficulty reproducing the broadness of the observed IC peak. Most probably this implies that the assumption of the homogeneity of the magnetic field inside the nebula is incorrect. On the other hand, the time-dependent 1D spectral model provides a good fit of the new VHE results when considering a 80 {\mu}G magnetic field. However, it fails to match the data when including the morphology of the nebula at lower wavelengths.Comment: accepted by JHEAp, 9 pages, 6 figure

MAGIC observations of MWC 656, the only known Be/BH system

Context: MWC 656 has recently been established as the first observationally detected high-mass X-ray binary system containing a Be star and a black hole (BH). The system has been associated with a gamma-ray flaring event detected by the AGILE satellite in July 2010. Aims: Our aim is to evaluate if the MWC 656 gamma-ray emission extends to very high energy (VHE > 100 GeV) gamma rays. Methods. We have observed MWC 656 with the MAGIC telescopes for $\sim$23 hours during two observation periods: between May and June 2012 and June 2013. During the last period, observations were performed contemporaneously with X-ray (XMM-Newton) and optical (STELLA) instruments. Results: We have not detected the MWC 656 binary system at TeV energies with the MAGIC Telescopes in either of the two campaigns carried out. Upper limits (ULs) to the integral flux above 300 GeV have been set, as well as differential ULs at a level of $\sim$5% of the Crab Nebula flux. The results obtained from the MAGIC observations do not support persistent emission of very high energy gamma rays from this system at a level of 2.4% the Crab flux.Comment: Accepted for publication in A&A. 5 pages, 2 figures, 2 table

Limits to dark matter annihilation cross-section from a combined analysis of MAGIC and Fermi-LAT observations of dwarf satellite galaxies

We present the first joint analysis of gamma-ray data from the MAGIC Cherenkov telescopes and the Fermi Large Area Telescope (LAT) to search for gamma-ray signals from dark matter annihilation in dwarf satellite galaxies. We combine 158 hours of Segue 1 observations with MAGIC with 6-year observations of 15 dwarf satellite galaxies by the Fermi-LAT. We obtain limits on the annihilation cross-section for dark matter particle masses between 10 GeV and 100 TeV - the widest mass range ever explored by a single gamma-ray analysis. These limits improve on previously published Fermi-LAT and MAGIC results by up to a factor of two at certain masses. Our new inclusive analysis approach is completely generic and can be used to perform a global, sensitivity-optimized dark matter search by combining data from present and future gamma-ray and neutrino detectors.Comment: 19 pages, 3 figures. V2: Few typos corrected and references added. Matches published version JCAP 02 (2016) 03