Structural Basis of the Autophagy-Related LC3/Atg13 LIR Complex: Recognition and Interaction Mechanism

SummaryAutophagy is a bulk degradation pathway that removes cytosolic materials to maintain cellular homeostasis. The autophagy-related gene 13 (Atg13) and microtubule associate protein 1 light chain 3 (LC3) proteins are required for autophagosome formation. We demonstrate that each of the human LC3 isoforms (LC3A, LC3B, and LC3C) interacts with Atg13 via the LC3 interacting region (LIR) of Atg13. Using X-ray crystallography, we solved the macromolecular structures of LC3A and LC3C, along with the complex structures of the LC3 isoforms with the Atg13 LIR. Together, our structural and binding analyses reveal that the side-chain of Lys49 of LC3 acts as a gatekeeper to regulate binding of the LIR. We verified this observation by mutation of Lys49 in LC3A, which significantly reduces LC3A positive puncta formation in cultured cells. Our results suggest that specific affinity of the LC3 isoforms to the Atg13 LIR is required for proper autophagosome formation

Radiative Decay of a Long-Lived Particle and Big-Bang Nucleosynthesis

The effects of radiatively decaying, long-lived particles on big-bang nucleosynthesis (BBN) are discussed. If high-energy photons are emitted after BBN, they may change the abundances of the light elements through photodissociation processes, which may result in a significant discrepancy between the BBN theory and observation. We calculate the abundances of the light elements, including the effects of photodissociation induced by a radiatively decaying particle, but neglecting the hadronic branching ratio. Using these calculated abundances, we derive a constraint on such particles by comparing our theoretical results with observations. Taking into account the recent controversies regarding the observations of the light-element abundances, we derive constraints for various combinations of the measurements. We also discuss several models which predict such radiatively decaying particles, and we derive constraints on such models.Comment: Published version in Phys. Rev. D. Typos in figure captions correcte

Constrained Markovian dynamics of random graphs

We introduce a statistical mechanics formalism for the study of constrained graph evolution as a Markovian stochastic process, in analogy with that available for spin systems, deriving its basic properties and highlighting the role of the `mobility' (the number of allowed moves for any given graph). As an application of the general theory we analyze the properties of degree-preserving Markov chains based on elementary edge switchings. We give an exact yet simple formula for the mobility in terms of the graph's adjacency matrix and its spectrum. This formula allows us to define acceptance probabilities for edge switchings, such that the Markov chains become controlled Glauber-type detailed balance processes, designed to evolve to any required invariant measure (representing the asymptotic frequencies with which the allowed graphs are visited during the process). As a corollary we also derive a condition in terms of simple degree statistics, sufficient to guarantee that, in the limit where the number of nodes diverges, even for state-independent acceptance probabilities of proposed moves the invariant measure of the process will be uniform. We test our theory on synthetic graphs and on realistic larger graphs as studied in cellular biology.Comment: 28 pages, 6 figure

An Inflationary Scenario Taking into Account of Possible Dark Energy Effects in the Early Universe

We investigate the possible effect of cosmological-constant type dark energy during the inflation period of the early universe. This is accommodated by a new dispersion relation in de Sitter space. The modified inflation model of a minimally-coupled scalar field is still able to yield an observation-compatible scale-invariant primordial spectrum, simultaneously having potential to generate a spectrum with lower power at large scales. A qualitative match to the WMAP 7-year data is presented. We obtain an $\Omega_\Lambda$ of the same order of that in the $\Lambda$-CDM model. Possible relations between the de Sitter scenario and the Doubly Special Relativity(DSR) are also discussed.Comment: 17 pages, 3 figuire

The IAXO Helioscope

The IAXO (International Axion Experiment) is a fourth generation helioscope with a sensitivity, in terms of detectable signal counts, at least 104 better than CAST phase-I, resulting in sensitivity on ga¿ one order of magnitude better. To achieve this performance IAXO will count on a 8-coil toroidal magnet with 60 cm diameter bores and equipped with X-ray focusing optics into 0.20 cm2 spots coupled to ultra-low background Micromegas X-ray detectors. The magnet will be on a platform that will allow solar tracking for 12 hours per day. The next short term objectives are to prepare a Technical Design Report and to construct the first prototypes of the hardware main ingredients: demonstration coil, X-ray optics and low background detector while refining the physics case and studying the feasibility studies for Dark Matter axions

The Next Generation of Axion Helioscopes: The International Axion Observatory (IAXO)

The International Axion Observatory (IAXO) is a proposed 4th-generation axion helioscope with the primary physics research goal to search for solar axions via their Primakoff conversion into photons of 1 \u2013 10 keV energies in a strong magnetic field. IAXO will achieve a sensitivity to the axion-photon coupling ga\u3b3 down to a few 710 1212 GeV 121 for a wide range of axion masses up to 3c 0.25 eV. This is an improvement over the currently best (3rd generation) axion helioscope, the CERN Axion Solar Telescope (CAST), of about 5 orders of magnitude in signal strength, corresponding to a factor 3c 20 in the axion photon coupling. IAXO's sensitivity relies on the construction of a large superconducting 8-coil toroidal magnet of 20 m length optimized for axion research. Each of the eight 60 cm diameter magnet bores is equipped with x-ray optics focusing the signal photons into 3c 0.2 cm2 spots that are imaged by very low background x-ray detectors. The magnet will be built into a structure with elevation and azimuth drives that will allow solar tracking for 12 hours each day. This contribution is a summary of our papers [1], [2] and [3] and we refer to these for further details

Antimatter Regions in the Early Universe and Big Bang Nucleosynthesis

We have studied big bang nucleosynthesis in the presence of regions of antimatter. Depending on the distance scale of the antimatter region, and thus the epoch of their annihilation, the amount of antimatter in the early universe is constrained by the observed abundances. Small regions, which annihilate after weak freezeout but before nucleosynthesis, lead to a reduction in the 4He yield, because of neutron annihilation. Large regions, which annihilate after nucleosynthesis, lead to an increased 3He yield. Deuterium production is also affected but not as much. The three most important production mechanisms of 3He are 1) photodisintegration of 4He by the annihilation radiation, 2) pbar-4He annihilation, and 3) nbar-4He annihilation by "secondary" antineutrons produced in anti-4He annihilation. Although pbar-4He annihilation produces more 3He than the secondary nbar-4He annihilation, the products of the latter survive later annihilation much better, since they are distributed further away from the annihilation zone.Comment: 15 pages, 9 figures. Minor changes to match the PRD versio

Flowcharts for the management of biliary tract and ampullary carcinomas

No strategies for the diagnosis and treatment of biliary tract carcinoma have been clearly described. We developed flowcharts for the diagnosis and treatment of biliary tract carcinoma on the basis of the best clinical evidence. Risk factors for bile duct carcinoma are a dilated type of pancreaticobiliary maljunction (PBM) and primary sclerosing cholangitis. A nondilated type of PBM is a risk factor for gallbladder carcinoma. Symptoms that may indicate biliary tract carcinoma are jaundice and pain in the upper right area of the abdomen. The first step of diagnosis is to carry out blood biochemistry tests and ultrasonography (US) of the abdomen. The second step of diagnosis is to find the local extension of the carcinoma by means of computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), percutaneous transhepatic cholangiography (PTC), and endoscopic retrograde cholangiopancreatography (ERCP). Because resection is the only way to completely cure biliary tract carcinoma, the indications for resection are determined first. In patients with resectable disease, the indications for biliary drainage or portal vein embolization (PVE) are checked. In those with nonresectable disease, biliary stenting, chemotherapy, radiotherapy, and/or best supportive care is selected

Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC-2020 March 27 17:00 UTC). We conduct two independent searches: A generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate. © 2022. The Author(s). Published by the American Astronomical Society

Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run

Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets. © 2022. The Author(s). Published by the American Astronomical Society