REGγ is associated with multiple oncogenic pathways in human cancers

<p>Abstract</p> <p>Background</p> <p>Recent studies suggest a role of the proteasome activator, REGγ, in cancer progression. Since there are limited numbers of known REGγ targets, it is not known which cancers and pathways are associated with REGγ.</p> <p>Methods</p> <p>REGγ protein expressions in four different cancers were investigated by immunohistochemistry (IHC) analysis. Following NCBI Gene Expression Omnibus (GEO) database search, microarray platform validation, differential expressions of REGγ in corresponding cancers were statistically analyzed. Genes highly correlated with REGγ were defined based on Pearson's correlation coefficient. Functional links were estimated by Ingenuity Core analysis. Finally, validation was performed by RT-PCR analysis in established cancer cell lines and IHC in human colon cancer tissues</p> <p>Results</p> <p>Here, we demonstrate overexpression of REGγ in four different cancer types by micro-tissue array analysis. Using meta-analysis of publicly available microarray databases and biological studies, we verified elevated REGγ gene expression in the four types of cancers and identified genes significantly correlated with REGγ expression, including genes in p53, Myc pathways, and multiple other cancer-related pathways. The predicted correlations were largely consistent with quantitative RT-PCR analysis.</p> <p>Conclusions</p> <p>This study provides us novel insights in REGγ gene expression profiles and its link to multiple cancer-related pathways in cancers. Our results indicate potentially important pathogenic roles of REGγ in multiple cancer types and implicate REGγ as a putative cancer marker.</p

A Leray-Serre spectral sequence for Lagrangian Floer theory

We consider symplectic fibrations as in Guillemin-Lerman-Sternberg, and derive a spectral sequence to compute the Floer cohomology of certain fibered Lagrangians sitting inside a compact symplectic fibration with small monotone fibers and a rational base. We show if the Floer cohomology with field coefficients of the fiber Lagrangian vanishes, then the Floer cohomology with field coefficients of the total Lagrangian also vanishes. We give an application to certain non-torus fibers of the Gelfand-Cetlin system in Flag manifolds, and show that their Floer cohomology vanishes.Comment: Final version, to appear in Algebraic and Geometric Topology. 59 pages, 4 figure

Non-abelian reciprocity laws on a Riemann surface

On a Riemann surface there are relations among the periods of holomorphic differential forms, called Riemann's relations. If one looks carefully in Riemann's proof, one notices that he uses iterated integrals. What I have done in this paper is to generalize these relations to relations among generating series of iterated integrals. Since the main result is formulated in terms of generating series, it gives infinitely many relations - one for each coefficient of the generating series. The lower order terms give the well known classical relations. The new result is reciprocity for the higher degree terms, which give non-trivial relations among iterated integrals on a Riemann surface. As an application we refine the definition of Manin's noncommutative modular symbol in order to include Eisenstein series. Finally, we have to point out that this paper contains some constructions needed for multidimensional reciprocity laws like a refinement of one of the Kato-Parshin reciprocity laws.Comment: 21 pages; Submitted to International Mathematics Research Notices

Pa28γ: New insights on an ancient proteasome activator

PA28 (also known as 11S, REG or PSME) is a family of proteasome regulators whose members are widely present in many of the eukaryotic supergroups. In jawed vertebrates they are represented by three paralogs, PA28α, PA28β, and PA28γ, which assemble as heptameric hetero (PA28αβ) or homo (PA28γ) rings on one or both extremities of the 20S proteasome cylindrical structure. While they share high sequence and structural similarities, the three isoforms significantly differ in terms of their biochemical and biological properties. In fact, PA28α and PA28β seem to have appeared more recently and to have evolved very rapidly to perform new functions that are specifically aimed at optimizing the process of MHC class I antigen presentation. In line with this, PA28αβ favors release of peptide products by proteasomes and is particularly suited to support adaptive immune responses without, however, affecting hydrolysis rates of protein substrates. On the contrary, PA28γ seems to be a slow-evolving gene that is most similar to the common ancestor of the PA28 activators family, and very likely retains its original functions. Notably, PA28γ has a prevalent nuclear localization and is involved in the regulation of several essential cellular processes including cell growth and proliferation, apoptosis, chromatin structure and organization, and response to DNA damage. In striking contrast with the activity of PA28αβ, most of these diverse biological functions of PA28γ seem to depend on its ability to markedly enhance degradation rates of regulatory protein by 20S proteasome. The present review will focus on the molecular mechanisms and biochemical properties of PA28γ, which are likely to account for its various and complex biological functions and highlight the common features with the PA28αβ paralog

First Class Futures: Specification and implementation of Update Strategies

International audienceA natural way to benefit from distribution is via asynchronous invocations to methods or services. Upon invocation, a request is enqueued at the destination side and the caller can continue its execution. But a question remains: “what if one wants to manipulate the result of an asynchronous invocation?” First-class futures provide a transparent and easy-to-program answer: a future acts as the placeholder for the result of an asynchronous invocation and can be safely transmitted between processes while its result is not needed. Synchronization occurs automatically upon an access to the result. As references to futures disseminate, a strategy is necessary to propagate the result of each request to the processes that need it. This paper studies the efficient transmission of results: it presents three strategies in a semi-formal manner, providing experimental results highlighting their benefits and drawbacks