Abelian Monopole and Center Vortex Views at the Multi-Instanton Gas

We consider full non-Abelian, Abelian and center projected lattice field configurations built up from random instanton gas configurations in the continuum. We study the instanton contribution to the $\bar{Q}Q$ force with respect to ({\it i}) instanton density dependence, ({\it ii}) Casimir scaling and ({\it iii}) whether various versions of Abelian dominance hold. We check that the dilute gas formulation for the interaction potential gives an reliable approximation only for densities small compared to the phenomenological value. We find that Casimir scaling does not hold, confirming earlier statements in the literature. We show that the lattice used to discretize the instanton gas configurations has to be sufficiently coarse ($a \approx 2\bar{\rho}$ compared with the instanton size $\bar{\rho}$) such that maximal Abelian gauge projection and center projection as well as the monopole gas contribution to the $\bar{Q}Q$ force reproduce the non-Abelian instanton-mediated force in the intermediate range of linear quasi-confinement. We demonstrate that monopole clustering also depends critically on the discretization scale confirming earlier findings based on monopole blocking.Comment: 21 pages, 22 Postscript figure

Abelian-Projected Effective Gauge Theory of QCD with Asymptotic Freedom and Quark Confinement

We give an outline of a recent proof that the low-energy effective gauge theory exhibiting quark confinement due to magnetic monopole condensation can be derived from QCD without any specific assumption. We emphasize that the low-energy effective abelian gauge theories obtained here give the dual description of the same physics in the low-energy region. They show that the QCD vacuum is nothing but the dual (type II) superconductor.Comment: 15 pages, Latex, no figures, Talk given at YKIS'97, Non-perturbative QCD, Kyot

Abelian-Projected Effective Gauge Theory of QCD with Asymptotic Freedom and Quark Confinement

Starting from SU(2) Yang-Mills theory in 3+1 dimensions, we prove that the abelian-projected effective gauge theories are written in terms of the maximal abelian gauge field and the dual abelian gauge field interacting with monopole current. This is performed by integrating out all the remaining non-Abelian gauge field belonging to SU(2)/U(1). We show that the resulting abelian gauge theory recovers exactly the same one-loop beta function as the original Yang-Mills theory. Moreover, the dual abelian gauge field becomes massive if the monopole condensation occurs. This result supports the dual superconductor scenario for quark confinement in QCD. We give a criterion of dual superconductivity and point out that the monopole condensation can be estimated from the classical instanton configuration. Therefore there can exist the effective abelian gauge theory which shows both asymptotic freedom and quark confinement based on the dual Meissner mechanism. Inclusion of arbitrary number of fermion flavors is straightforward in this approach. Some implications to lower dimensional case will also be discussed.Comment: 39 pages, Latex, no figures, (2.2, 4.1, 4.3 are modified; 4.4, Appendices A,B,C and references are added. No change in conclusion

Structural insights into the catalysis and regulation of E3 ubiquitin ligases

Covalent attachment (conjugation) of one or more ubiquitin molecules to protein substrates governs numerous eukaryotic cellular processes, including apoptosis, cell division and immune responses. Ubiquitylation was originally associated with protein degradation, but it is now clear that ubiquitylation also mediates processes such as protein–protein interactions and cell signalling depending on the type of ubiquitin conjugation. Ubiquitin ligases (E3s) catalyse the final step of ubiquitin conjugation by transferring ubiquitin from ubiquitin-conjugating enzymes (E2s) to substrates. In humans, more than 600 E3s contribute to determining the fates of thousands of substrates; hence, E3s need to be tightly regulated to ensure accurate substrate ubiquitylation. Recent findings illustrate how E3s function on a structural level and how they coordinate with E2s and substrates to meticulously conjugate ubiquitin. Insights regarding the mechanisms of E3 regulation, including structural aspects of their autoinhibition and activation are also emerging

Specificity and disease in the ubiquitin system

Post-translational modification (PTM) of proteins by ubiquitination is an essential cellular regulatory process. Such regulation drives the cell cycle and cell division, signalling and secretory pathways, DNA replication and repair processes and protein quality control and degradation pathways. A huge range of ubiquitin signals can be generated depending on the specificity and catalytic activity of the enzymes required for attachment of ubiquitin to a given target. As a consequence of its importance to eukaryotic life, dysfunction in the ubiquitin system leads to many disease states, including cancers and neurodegeneration. This review takes a retrospective look at our progress in understanding the molecular mechanisms that govern the specificity of ubiquitin conjugation

Parkin–phosphoubiquitin complex reveals cryptic ubiquitin-binding site required for RBR ligase activity

RING-between-RING (RBR) E3 ligases are a class of ubiquitin ligases distinct from RING or HECT E3 ligases. An important RBR ligase is Parkin, mutations in which lead to early-onset hereditary Parkinsonism. Parkin and other RBR ligases share a catalytic RBR module but are usually autoinhibited and activated via distinct mechanisms. Recent insights into Parkin regulation predict large, unknown conformational changes during Parkin activation. However, current data on active RBR ligases reflect the absence of regulatory domains. Therefore, it remains unclear how individual RBR ligases are activated, and whether they share a common mechanism. We now report the crystal structure of a human Parkin–phosphoubiquitin complex, which shows that phosphoubiquitin binding induces movement in the 'in-between RING' (IBR) domain to reveal a cryptic ubiquitin-binding site. Mutation of this site negatively affects Parkin's activity. Furthermore, ubiquitin binding promotes cooperation between Parkin molecules, which suggests a role for interdomain association in the RBR ligase mechanism

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field