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Autophagosomes and lysosomes work in tandem to conduct autophagy, an intracellular degradation system which is crucial for cellular homeostasis. Altered autophagy contributes to the pathophysiology of various diseases, including cancers and metabolic diseases. Although many studies have investigated autophagy to elucidate disease pathogenesis, specific identification of the various components of the cellular degradation machinery remains difficult. The goal of this paper is to describe an approach to reproducibly identify and distinguish subcellular structures involved in autophagy. We provide methods that avoid common pitfalls, including a detailed explanation for how to distinguish lysosomes and lipid droplets and discuss the differences between autophagosomes and inclusion bodies. These methods are based on using transmission electron microscopy (TEM), capable of generating nanometer-scale micrographs of cellular degradation components in a fixed sample. In addition to TEM, we discuss other imaging techniques, such as immunofluorescence and immunogold labeling, which can be utilized for the reliable and accurate classification of cellular organelles. Our results show how these methods may be employed to accurately quantify the cellular degradation machinery under various conditions, such as treatment with the endoplasmic reticulum stressor thapsigargin or the ablation of dynamin-related protein 1. 

Abstract We present a measurement of the high-energy astrophysical muon–neutrino flux with the IceCube Neutrino Observatory. The measurement uses a high-purity selection of 650k neutrino-induced muon tracks from the northern celestial hemisphere, corresponding to 9.5 yr of experimental data. With respect to previous publications, the measurement is improved by the increased size of the event sample and the extended model testing beyond simple power-law hypotheses. An updated treatment of systematic uncertainties and atmospheric background fluxes has been implemented based on recent models. The best-fit single power-law parameterization for the astrophysical energy spectrum results in a normalization of ϕ @ 100 TeV ν μ + ν ¯ μ = 1.44 − 0.26 + 0.25 × 10 − 18 GeV − 1 cm − 2 s − 1 sr − 1 and a spectral index γ SPL = 2.37 − 0.09 + 0.09 , constrained in the energy range from 15 TeV to 5 PeV. The model tests include a single power law with a spectral cutoff at high energies, a log-parabola model, several source-class-specific flux predictions from the literature, and a model-independent spectral unfolding. The data are consistent with a single power-law hypothesis, however, spectra with softening above one PeV are statistically more favorable at a two-sigma level. 

Abstract For several decades, the origin of ultra-high-energy cosmic rays (UHECRs) has been an unsolved question of high-energy astrophysics. One approach for solving this puzzle is to correlate UHECRs with high-energy neutrinos, since neutrinos are a direct probe of hadronic interactions of cosmic rays and are not deflected by magnetic fields. In this paper, we present three different approaches for correlating the arrival directions of neutrinos with the arrival directions of UHECRs. The neutrino data are provided by the IceCube Neutrino Observatory and ANTARES, while the UHECR data with energies above ∼50 EeV are provided by the Pierre Auger Observatory and the Telescope Array. All experiments provide increased statistics and improved reconstructions with respect to our previous results reported in 2015. The first analysis uses a high-statistics neutrino sample optimized for point-source searches to search for excesses of neutrino clustering in the vicinity of UHECR directions. The second analysis searches for an excess of UHECRs in the direction of the highest-energy neutrinos. The third analysis searches for an excess of pairs of UHECRs and highest-energy neutrinos on different angular scales. None of the analyses have found a significant excess, and previously reported overfluctuations are reduced in significance. Based on these results, we further constrain the neutrino flux spatially correlated with UHECRs.