Autophagy is a major route by which cytoplasmic contents are delivered to the lysosome for degradation. Many autophagyrelated (ATG) genes have been identified in yeast. Although most of them are conserved in human, the molecular composition of the Atg1 complex appears to differ between yeast and mammals. In yeast, Atg1 forms a complex with Atg11, Atg13, Atg17, Atg29 and Atg31, whereas mammalian Atg1 (ULK1/2) interacts with Atg13 and FIP200. Here, we identify a novel mammalian Atg13 binding protein, named Atg101. Atg101 shows no homology with other Atg proteins, and is conserved in various eukaryotes, but not in Saccharomyces cerevisiae. Atg101 associates with the ULK-Atg13-FIP200 complex, most likely through direct interaction with Atg13. In Atg13 siRNA-treated cells, Atg101 is present solely as a monomer. Interaction between Atg101 and the ULK-Atg13-FIP200 complex is stable, and is not regulated by nutrient conditions. GFP-Atg101 localizes to the isolation membrane/phagophore. GFP-LC3 dot formation is suppressed and endogenous LC3-I accumulates in Atg101 siRNA-treated cells, suggesting that Atg101 is a critical factor for autophagy. Furthermore, Atg101 is important for the stability and basal phosphorylation of Atg13 and ULK1. These data suggest that Atg101 is a novel Atg protein that functions together with ULK, Atg13 and FIP200. IntroductionAutophagy is an evolutionarily conserved cellular process responsible for the turnover of most long-lived proteins and some organelles. While basal autophagy is important for the quality control of cytoplasmic contents, autophagy can be upregulated by nutrient starvation to maintain the amino acid pool. Yeast genetic studies have identified 31 autophagy-related (ATG) genes. 1,2 Atg1-10, 12-14, 16-18, 29 and 31 are required for autophagosome formation. Although most yeast Atgs have mammalian counterparts, homologs of Atg17, Atg29 and Atg31 have not yet been identified. It should be noted that these three factors are included in the Atg1 kinase complex together with Atg11 and Atg13. While mammalian homologs of Atg1 and Atg13 have been identified as ULK1/2, 3-5 and mammalian Atg13, 6-9 respectively, homologs of the other complex subunits seem to be absent in mammals. We recently found that FIP200 (also known as RB1CC1) forms a complex with ULK1/2 and Atg13, but FIP200 does not have significant homology with Atg17, Atg29 or Atg31. 7,10 The yeast Atg1 complex functions at the most upstream step in the preautophagosomal structure (PAS) formation. [11][12][13] This complex appears to receive the nutrient signal from Tor, which suppresses autophagy. 14 In mammals and Drosophila melanogaster, it was also shown that (m)Tor regulates autophagy through the ULK-Atg13-FIP200 complex. 7,8,15 As PAS has only been described in yeast, the structure and function of the Atg1 protein complex may be quite different in mammals. These apparent differences prompted us to search for additional mammalian specific factors included in the ULK complex. In this study, we identify a novel Atg protein, At...

We extend the Polyakov-loop extended Nambu-Jona-Lasinio (PNJL) model by introducing an effective fourquark vertex depending on Polyakov loop. The effective vertex generates entanglement interactions between Polyakov loop and chiral condensate. The new model is consistent with lattice QCD data at imaginary quarknumber chemical potential and real and imaginary isospin chemical potentials, particularly on strong correlation between the chiral and deconfinement transitions and also on the quark-mass dependence of the order of the Roberge-Weiss endpoint. We investigate the influence of the entanglement interactions on the location of the tricritical point at real isospin chemical potential and on the location of the critical endpoint at real quark-number chemical potential.

Centenarians, or individuals who have lived more than a century, represent the ultimate model of successful longevity associated with decreased susceptibility to ageing-associated illness and chronic inflammation [1][2][3] . The gut microbiota is considered to be a critical determinant of human health and longevity [4][5][6][7][8] . Here we show that centenarians (average 107 yo) have a distinct gut microbiome enriched in microbes capable of generating unique secondary bile acids, including iso-, 3-oxo-, and isoallo-lithocholic acid (LCA), as compared to elderly (85-89 yo) and young (21-55 yo) controls. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from a centenarian's faecal microbiota, we identified Parabacteroides merdae and Odoribacteraceae strains as effective producers of isoalloLCA. Furthermore, we generated and tested mutant strains of P. merdae to show that the enzymes 5a-reductase (5AR) and 3bhydroxysteroid dehydrogenase (3bHSDH) were responsible for isoalloLCA production. This secondary bile acid derivative exerted the most potent antimicrobial effects among the tested bile acid compounds against gram-positive (but not gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and vancomycin-resistant Enterococcus faecium.These findings suggest that specific bile acid metabolism may be involved in reducing the risk of pathobiont infection, thereby potentially contributing to longevity. MainThe microbiome has long been recognized as a key player in determining the health status of ageing individuals through its role in controlling digestive functions, bone density, neuronal activity, immunity, and resistance to pathogen infection [9][10][11][12][13] . Microbial consortia in elderly individuals often show increased interindividual variability and reduced diversity, and are thus being linked to immunosenescence, chronic systemic inflammation, and frailty 6,14 . An integrated understanding of the dynamic balance and functions of microbial members with respect to ageing is essential for establishing a strategy toward rational manipulation of the microbiota for restoring and/or maintaining tissue homeostasis and overall health.Centenarians (aged 100 years and older) are known to be less susceptible to age-related diseases including hypertension, diabetes, obesity, and cancer 3,15 . Moreover, centenarians have likely survived periods of hunger and several bouts with infectious diseases such as influenza, tuberculosis, shigellosis, and salmonellosis 16 . It has been postulated that there are centenarian-specific members of the gut microbiota which, rather than representing a mere consequence of ageing, might actively contribute to maintaining homeostasis, resilience, and healthful ageing [4][5][6]8 . In this study, we aimed

We investigate quark–gluon thermodynamics with the symmetry. The flavor-dependent twist boundary condition (TBC) is imposed on Nc degenerate flavor quarks in the SU(Nc) gauge theory. This model is useful to understand the mechanism of color confinement. Thermodynamics of this quark–gluon system is studied by imposing the TBC on the Polyakov-loop extended Nambu–Jona–Lasinio (PNJL) model. The TBC model is applied to two- and three-color cases. The symmetry is preserved below some temperature Tc, but spontaneously broken above Tc. The color confinement below Tc preserves the flavor symmetry. Above Tc, the flavor symmetry is broken, but the breaking is suppressed by the entanglement between the Polyakov loop and the chiral condensate. Particularly at low temperature, dynamics of the TBC model is similar to that of the PNJL model with the standard fermion boundary condition, indicating that the symmetry is a good approximate concept in the latter model even if the current quark mass is small. The present prediction can be tested in future by lattice QCD, since the quark–gluon dynamics with a flavor-dependent imaginary chemical potential has no sign problem.

We draw the three-flavor phase diagram as a function of light-and strange-quark masses for both zero and imaginary quark-number chemical potential, using the Polyakov-loop extended Nambu-Jona-Lasinio model with an effective four-quark vertex depending on the Polyakov loop. The model prediction is qualitatively consistent with 2+1 flavor lattice QCD prediction at zero chemical potential and with degenerate three-flavor lattice QCD prediction at imaginary chemical potential.

Introduction: CT angiography has gained widespread acceptance for preoperative

Theta vacuum effects on the QCD phase structure in the \mu-T plane are studied by using the Polyakov-loop extended Nambu-Jona-Lasinio model and its extension, where \mu is the quark chemical potential and T is temperature, respectively. As the parameter \theta of the theta vacuum increases, the chiral transition becomes stronger. For large \theta, it eventually becomes first order even at zero \mu.Comment: 7 pages, 6 figure

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