Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic lowgrade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders

MAGIC observations provide compelling evidence of hadronic multi-TeV emission from the putative PeVatron SNR G106.3+2.7

Context. Certain types of supernova remnants (SNRs) in our Galaxy are assumed to be PeVatrons, capable of accelerating cosmic rays (CRs) to ∼ PeV energies. However, conclusive observational evidence for this has not yet been found. The SNR G106.3+2.7, detected at 1- 100 TeV energies by different γ-ray facilities, is one of the most promising PeVatron candidates. This SNR has a cometary shape, which can be divided into a head and a tail region with different physical conditions. However, in which region the 100 TeV emission is produced has not yet been identified because of the limited position accuracy and/or angular resolution of existing observational data. Additionally, it remains unclear as to whether the origin of the γ-ray emission is leptonic or hadronic. Aims. With the better angular resolution provided by new MAGIC data compared to earlier γ-ray datasets, we aim to reveal the acceleration site of PeV particles and the emission mechanism by resolving the SNR G106.3+2.7 with 0.1 resolution at TeV energies. Methods. We observed the SNR G106.3+2.7 using the MAGIC telescopes for 121.7 h in total - after quality cuts - between May 2017 and August 2019. The analysis energy threshold is ∼0.2 TeV, and the angular resolution is 0.07-0.1. We examined the γ-ray spectra of different parts of the emission, whilst benefitting from the unprecedented statistics and angular resolution at these energies provided by our new data. We also used measurements at other wavelengths such as radio, X-rays, GeV γ-rays, and 10 TeV γ-rays to model the emission mechanism precisely. Results. We detect extended γ-ray emission spatially coincident with the radio continuum emission at the head and tail of SNR G106.3+2.7. The fact that we detect a significant γ-ray emission with energies above 6.0 TeV from only the tail region suggests that the emissions above 10 TeV detected with air shower experiments (Milagro, HAWC, Tibet ASγ and LHAASO) are emitted only from the SNR tail. Under this assumption, the multi-wavelength spectrum of the head region can be explained with either hadronic or leptonic models, while the leptonic model for the tail region is in contradiction with the emission above 10 TeV and X-rays. In contrast, the hadronic model could reproduce the observed spectrum at the tail by assuming a proton spectrum with a cutoff energy of ∼1 PeV for that region. Such high-energy emission in this middle-aged SNR (4-10 kyr) can be explained by considering a scenario where protons escaping from the SNR in the past interact with surrounding dense gases at present. Conclusions. The γ-ray emission region detected with the MAGIC telescopes in the SNR G106.3+2.7 is extended and spatially coincident with the radio continuum morphology. The multi-wavelength spectrum of the emission from the tail region suggests proton acceleration up to ∼PeV, while the emission mechanism of the head region could either be hadronic or leptonic

Multimessenger Characterization of Markarian 501 during Historically Low X-Ray and γ-Ray Activity

We study the broadband emission of Mrk 501 using multiwavelength observations from 2017 to 2020 performed with a multitude of instruments, involving, among others, MAGIC, Fermi's Large Area Telescope (LAT), NuSTAR, Swift, GASP-WEBT, and the Owens Valley Radio Observatory. Mrk 501 showed an extremely low broadband activity, which may help to unravel its baseline emission. Nonetheless, significant flux variations are detected at all wave bands, with the highest occurring at X-rays and very-high-energy (VHE) 3-rays. A significant correlation (>3σ) between X-rays and VHE 3-rays is measured, supporting leptonic scenarios to explain the variable parts of the emission, also during low activity. This is further supported when we extend our data from 2008 to 2020, and identify, for the first time, significant correlations between the Swift X-Ray Telescope and Fermi-LAT. We additionally find correlations between high-energy 3-rays and radio, with the radio lagging by more than 100 days, placing the 3-ray emission zone upstream of the radio-bright regions in the jet. Furthermore, Mrk 501 showed a historically low activity in X-rays and VHE 3-rays from mid-2017 to mid-2019 with a stable VHE flux (>0.2 TeV) of 5% the emission of the Crab Nebula. The broadband spectral energy distribution (SED) of this 2 yr long low state, the potential baseline emission of Mrk 501, can be characterized with one-zone leptonic models, and with (lepto)-hadronic models fulfilling neutrino flux constraints from IceCube. We explore the time evolution of the SED toward the low state, revealing that the stable baseline emission may be ascribed to a standing shock, and the variable emission to an additional expanding or traveling shock. © 2023. The Author(s). Published by the American Astronomical Society

MAGIC observations provide compelling evidence of the hadronic multi-TeV emission from the putative PeVatron SNR G106.3+2.7

The SNR G106.3+2.7, detected at 1--100 TeV energies by different $\gamma$-ray facilities, is one of the most promising PeVatron candidates. This SNR has a cometary shape which can be divided into a head and a tail region with different physical conditions. However, it is not identified in which region the 100 TeV emission is produced due to the limited position accuracy and/or angular resolution of existing observational data. Additionally, it remains unclear whether the origin of the $\gamma$-ray emission is leptonic or hadronic. With the better angular resolution provided by these new MAGIC data compared to earlier $\gamma$-ray datasets, we aim to reveal the acceleration site of PeV particles and the emission mechanism by resolving the SNR G106.3+2.7 with 0.1$^\circ$ resolution at TeV energies. We detected extended $\gamma$-ray emission spatially coincident with the radio continuum emission at the head and tail of SNR G106.3+2.7. The fact that we detected a significant $\gamma$-ray emission with energies above 6.0 TeV from the tail region only suggests that the emissions above 10 TeV, detected with air shower experiments (Milagro, HAWC, Tibet AS$\gamma$ and LHAASO), are emitted only from the SNR tail. Under this assumption, the multi-wavelength spectrum of the head region can be explained with either hadronic or leptonic models, while the leptonic model for the tail region is in contradiction with the emission above 10 TeV and X-rays. In contrast, the hadronic model could reproduce the observed spectrum at the tail by assuming a proton spectrum with a cutoff energy of $\sim 1$ PeV for the tail region. Such a high energy emission in this middle-aged SNR (4--10 kyr) can be explained by considering the scenario that protons escaping from the SNR in the past interact with surrounding dense gases at present.Comment: 13 pages, 7 figures, Accepted for publication in A&

Multi-messenger characterization of Mrk 501 during historically low X-ray and γ\gamma-ray activity

We study the broadband emission of Mrk 501 using multi-wavelength observations from 2017 to 2020 performed with a multitude of instruments, involving, among others, MAGIC, Fermi-LAT, NuSTAR, Swift, GASP-WEBT, and OVRO. Mrk 501 showed an extremely low broadband activity, which may help to unravel its baseline emission. Nonetheless, significant flux variations are detected at all wavebands, with the highest occurring at X-rays and very-high-energy (VHE) $\gamma$-rays. A significant correlation ($>$3$\sigma$) between X-rays and VHE $\gamma$-rays is measured, supporting leptonic scenarios to explain the variable parts of the emission, also during low activity. This is further supported when we extend our data from 2008 to 2020, and identify, for the first time, significant correlations between Swift-XRT and Fermi-LAT. We additionally find correlations between high-energy $\gamma$-rays and radio, with the radio lagging by more than 100 days, placing the $\gamma$-ray emission zone upstream of the radio-bright regions in the jet. Furthermore, Mrk 501 showed a historically low activity in X-rays and VHE $\gamma$-rays from mid-2017 to mid-2019 with a stable VHE flux ($>$0.2 TeV) of 5% the emission of the Crab Nebula. The broadband spectral energy distribution (SED) of this 2-year-long low-state, the potential baseline emission of Mrk 501, can be characterized with one-zone leptonic models, and with (lepto)-hadronic models fulfilling neutrino flux constraints from IceCube. We explore the time evolution of the SED towards the low-state, revealing that the stable baseline emission may be ascribed to a standing shock, and the variable emission to an additional expanding or traveling shock.Comment: 56 pages, 30 figures, 14 tables, submitted. Corresponding authors are L. Heckmann, D. Paneque, S. Gasparyan, M. Cerruti, and N. Sahakya

Wavelet analysis and hierarchical clustering of ofm phenotypic population's variations originated from southern america and europe and attempts of a first relation to molecular divergence.

In this work we compare Grapholita molesta Busck (Lepidoptera: Tortricidae) populations originated from Brazil, Chile, Spain, Italy and Greece using power spectral density and phylogenetic analysis to detect any similarities between the population macro- and the molecular micro-level. Log-transformed population data were normalized and AR(p) models were developed to generate for each case population time series of equal lengths. The time-frequency/scale properties of the population data were further analyzed using wavelet analysis to detect any population dynamics frequency changes and cluster the populations. Based on the power spectral of each population time series and the hierarchical clustering schemes, populations originated from Southern America (Brazil and Chile) exhibit similar rhythmic properties and are both closer related with populations originated from Greece. Populations from Spain and especially Italy, have higher distance by terms of periodic changes on their population dynamics. Moreover, the members within the same cluster share similar spectral information, therefore they are supposed to participate in the same temporally regulated population process. On the contrary, the phylogenetic approach revealed a less structured pattern that bears indications of panmixia, as the two clusters contain individuals from both Europe and South America. This preliminary outcome will be further assessed by incorporating more individuals and likely employed a second molecular marker

Cross-calibration and combined analysis of the CTA-LST prototype and the MAGIC telescopes

The Cherenkov Telescope Array (CTA) is the next-generation gamma-ray observatory that is expected to reach one order of magnitude better sensitivity than that of current telescope arrays. The Large-Sized Telescopes (LSTs) have an essential role in extending the energy range down to 20 GeV. The prototype LST (LST-1) proposed for CTA was built in La Palma, the northern site of CTA, in 2018. LST-1 is currently in its commissioning phase and moving towards scientific observations. The LST-1 camera consists of 1855 photomultiplier tubes (PMTs) which are sensitive to Cherenkov light. PMT signals are recorded as waveforms sampled at 1 GHz rate with Domino Ring Sampler version 4 (DRS4) chips. Fast sampling is essential to achieve a low energy threshold by minimizing the integration of background light from the night sky. Absolute charge calibration can be performed by the so-called F-factor method, which allows calibration constants to be monitored even during observations. A calibration pipeline of the camera readout has been developed as part of the LST analysis chain. The pipeline performs DRS4 pedestal and timing corrections, as well as the extraction and calibration of charge and time of pulses for subsequent higher-level analysis. The performance of each calibration step is examined, and especially charge and time resolution of the camera readout are evaluated and compared to CTA requirements. We report on the current status of the calibration pipeline, including the performance of each step through to signal reconstruction, and the consistency with Monte Carlo simulation