Pleckstrin Homology (PH) Domain Leucine-Rich Repeat Protein Phosphatase Controls Cell Polarity by Negatively Regulating the Activity of Atypical Protein Kinase C

The proper establishment of epithelial polarity allows cells to sense and respond to signals that arise from the microenvironment in a spatiotemporally controlled manner. Atypical PKCs (aPKCs) are implicated as key regulators of epithelial polarity. However, the molecular mechanism underlying the negative regulation of aPKCs remains largely unknown. In this study, we demonstrated that PH domain leucine-rich repeat protein phosphatase (PHLPP), a novel family of Ser/Thr protein phosphatases, plays an important role in regulating epithelial polarity by controlling the phosphorylation of both aPKC isoforms. Altered expression of PHLPP1 or PHLPP2 disrupted polarization of Caco2 cells grown in 3D cell cultures as indicated by the formation of aberrant multi-lumen structures. Overexpression of PHLPP resulted in a decrease in aPKC phosphorylation at both the activation loop and the turn motif sites; conversely, knockdown of PHLPP increased aPKC phosphorylation. Moreover, in vitro dephosphorylation experiments revealed that both aPKC isoforms were substrates of PHLPP. Interestingly, knockdown of PKCζ, but not PKCι, led to similar disruption of the polarized lumen structure, suggesting that PKCζ likely controls the polarization process of Caco2 cells. Furthermore, knockdown of PHLPP altered the apical membrane localization of aPKCs and reduced the formation of aPKC-Par3 complex. Taken together, our results identify a novel role of PHLPP in regulating aPKC and cell polarity

Prescribing Gaussian curvature on surfaces with conical singularities and geodesic boundary

We study conformal metrics with prescribed Gaussian curvature on surfaces with conical singularities and geodesic boundary in supercritical regimes. Exploiting a variational argument, we derive a general existence result for surfaces with at least two boundary components. This seems to be the first result in this setting. Moreover, we allow to have conical singularities with both positive and negative orders, that is cone angles both less and grater than $2\pi$

Rigid vortices in MgB2

Magnetic relaxation of high-pressure synthesized MgB$_2$ bulks with different thickness is investigated. It is found that the superconducting dia-magnetic moment depends on time in a logarithmic way; the flux-creep activation energy decreases linearly with the current density (as expected by Kim-Anderson model); and the activation energy increases linearly with the thickness of sample when it is thinner than about 1 mm. These features suggest that the vortices in the MgB$_2$ are rather rigid, and the pinning and creep can be well described by Kim-Anderson model.Comment: Typo corrected & reference adde

Leveraging Team Correlation for Approximating Equilibrium in Two-Team Zero-Sum Games

Two-team zero-sum games are one of the most important paradigms in game theory. In this paper, we focus on finding an unexploitable equilibrium in large team games. An unexploitable equilibrium is a worst-case policy, where members in the opponent team cannot increase their team reward by taking any policy, e.g., cooperatively changing to other joint policies. As an optimal unexploitable equilibrium in two-team zero-sum games, correlated-team maxmin equilibrium remains unexploitable even in the worst case where players in the opponent team can achieve arbitrary cooperation through a joint team policy. However, finding such an equilibrium in large games is challenging due to the impracticality of evaluating the exponentially large number of joint policies. To solve this problem, we first introduce a general solution concept called restricted correlated-team maxmin equilibrium, which solves the problem of being impossible to evaluate all joint policy by a sample factor while avoiding an exploitation problem under the incomplete joint policy evaluation. We then develop an efficient sequential correlation mechanism, and based on which we propose an algorithm for approximating the unexploitable equilibrium in large games. We show that our approach achieves lower exploitability than the state-of-the-art baseline when encountering opponent teams with different exploitation ability in large team games including Google Research Football

Minimum average-case queries of q + 1 -ary search game with small sets

Given a search space S={1,2,...,n}, an unknown element x*∈S and fixed integers ℓ≥1 and q≥1, a q+1-ary ℓ-restricted query is of the following form: which one of the set {A 0,A 1,...,A q} is the x* in?, where (A 0,A 1,...,A q) is a partition of S and | Ai|≤ℓ for i=1,2,...,q. The problem of finding x* from S with q+1-ary size-restricted queries is called as a q+1-ary search game with small sets. In this paper, we consider sequential algorithms for the above problem, and establish the minimum number of average-case sequential queries when x* satisfies the uniform distribution on S. © 2011 Elsevier B.V. All rights reserved

The chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) controls cellular quiescence by hyperpolarizing the cell membrane during diapause in the crustacean Artemia

Cellular quiescence, a reversible state in which growth, proliferation, and other cellular activities are arrested, is important for self-renewal, differentiation, development, regeneration, and stress resistance. However, the physiological mechanisms underlying cellular quiescence remain largely unknown. In the present study, we used embryos of the crustacean Artemia in the diapause stage, in which these embryos remain quiescent for prolonged periods, as a model to explore the relationship between cell-membrane potential (V-mem) and quiescence. We found that V-mem is hyperpolarized and that the intracellular chloride concentration is high in diapause embryos, whereas V-mem is depolarized and intracellular chloride concentration is reduced in postdiapause embryos and during further embryonic development. We identified and characterized the chloride ion channel protein cystic fibrosis transmembrane conductance regulator (CFTR) of Artemia (Ar-CFTR) and found that its expression is silenced in quiescent cells of Artemia diapause embryos but remains constant in all other embryonic stages. Ar-CFTR knockdown and GlyH-101-mediated chemical inhibition of Ar-CFTR produced diapause embryos having a high V-mem and intracellular chloride concentration, whereas control Artemia embryos released free-swimming nauplius larvae. Transcriptome analysis of embryos at different developmental stages revealed that proliferation, differentiation, and metabolism are suppressed in diapause embryos and restored in postdiapause embryos. Combined with RNA sequencing (RNA-Seq) of GlyH-101-treated MCF-7 breast cancer cells, these analyses revealed that CFTR inhibition down-regulates the Wnt and Aurora Kinase A (AURKA) signaling pathways and up-regulates the p53 signaling pathway. Our findings provide insight into CFTR-mediated regulation of cellular quiescence and V-mem in the Artemia model