Control of nuclear-cytoplasmic shuttling of Ankrd54 by PKCδ

AIM To identify and characterize the effect of phosphorylation on the subcellular localization of Ankrd54. METHODS HEK293T cells were treated with calyculin A, staurosporin or phorbol 12-myristate 13-acetate (PMA). Cells were transfected with eGFP-tagged Ankrd54 with or without Lyn tyrosine kinase (wild-type, Y397F mutant, or Y508F mutant). The subcellular localization was assessed by immunofluorescence imaging of cells, immunoblotting of subcellular fractionations. The phosphorylation of Ankrd54 was monitored using Phos-tagTM gel retardation. Phosphorylated peptides were analysed by multiple-reaction-monitoring (MRM) proteomic analysis. RESULTS Activation of PKC kinases using PMA promoted nuclear export of Ankrd54 and correlated with increased Ankrd54 phosphorylation, assayed using Phos-tagTM gel retardation. Co-expression of an active form of the PKCδ isoform specifically promoted both phosphorylation and cytoplasmic localization of Ankrd54, while PKCδ, Akt and PKA did not. Alanine mutation of several serine residues in the amino-terminal region of Ankrd54 (Ser14, Ser17, Ser18, Ser19) reduced both PMA induced cytoplasmic localization and phosphorylation of Ankrd54. Using MRM proteomic analysis, phosphorylation of the Ser18 residue of Ankrd54 was readily detectable in response to PMA stimulation. PMA stimulation of cells co-expressing Ankrd54 and Lyn tyrosine kinase displayed increased co-immunoprecipitation and enhanced co-localization in the cytoplasm. CONCLUSION We identify phosphorylation by PKCδ as a major regulator of nuclear-cytoplasmic shuttling of Ankrd54, and its interaction with the tyrosine kinase Lyn

Instability of vortex array and transitions to turbulent states in rotating helium II

We consider superfluid helium inside a container which rotates at constant angular velocity and investigate numerically the stability of the array of quantized vortices in the presence of an imposed axial counterflow. This problem was studied experimentally by Swanson {\it et al.}, who reported evidence of instabilities at increasing axial flow but were not able to explain their nature. We find that Kelvin waves on individual vortices become unstable and grow in amplitude, until the amplitude of the waves becomes large enough that vortex reconnections take place and the vortex array is destabilized. The eventual nonlinear saturation of the instability consists of a turbulent tangle of quantized vortices which is strongly polarized. The computed results compare well with the experiments. Finally we suggest a theoretical explanation for the second instability which was observed at higher values of the axial flow

Governance of microfinance institutions (MFIs) in Cameroon: What lessons can we learn?

The aim of this paper is to find out the effects of the COBAC regulations regulating the microfinance industry on the governance of microfinance institutions (MFIs) in Cameroon. The paper is based on 35 in-depth interviews carried out from May to June 2011 and June to July 2012 with managers and accountants from MFIs in Cameroon, MFI clients and non-clients, regulatory authorities in the Ministry of Finance, and accounting professionals. The findings show that the regulations have broken down the governance within the MFIs in Cameroon thus turning MFIs into hybrid organizations with managers striving to meet their shareholders' interests

Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained

Protein metabolism in the small intestine during cancer cachexia and chemotherapy in mice

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