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GABA (γ-aminobutyric acid) is the major inhibitory neurotransmitter in the central nervous system (CNS). GABA reuptake by GABA transporters from the synaptic cleft is one important mechanism in the regulation of GABA activity, whose impairment is involved in the CNS diseases such as Parkinson disease, epilepsy, depression, and Alzheimer disease. The GABA transporter 1 (GAT1) belongs to a family of secondary active systems that are driven by the electrochemical gradients generated by Na+ and Cl− ions, respectively. GAT1 is a glycoprotein possessing three N-glycosylation sites. In this paper, we review our recent results of the biological role of N-glycosylation, peripheral trimming of the N-glycans, and sialylation of GAT1. The cotranslational N-glycosylation, but not the peripheral trimming of N-glycans, is involved in the regulation of the stability and trafficking of GAT1. The GABA uptake activity of GAT1 was found to be regulated by N-glycans. Specifically, the terminal sialic acid residues, the peripheral structures of N-glycans play a crucial regulatory role in the GABA transport process. The negative charge of sialic acids influences the binding of GAT1 to sodium ion, while the structure of sialic acids participates directly in the GABA translocation process of GAT1. [ABSTRACT FROM AUTHOR]

During growth and differentiation the plasma membrane has a key role not only in the reception and transmission of extracellular signals such as hormones and growth factors, but also in communicating cellular response to the cellular microenvironment. Cellular response to trophic stimuli includes alterations of cell shape and cell surface antigenicity, of cell-cell recognition and cellular adhesion, of cell matrix binding and the adaptation of cell surface receptors. The plasma membrane is therefore regarded as a 'central agency' for the integration of a single cell into the complex system of a tissue or of an organism. The numerous functions of the plasma membrane are mainly mediated by membrane integrated glycoproteins or glycolipids both sharing the common feature of covalently bound oligosaccharide side chains. Specific alterations of oligosaccharide structure and metabolism associated with growth, differentiation and various pathologic conditions suggest a specific role for the oligosaccharide moieties in the regulation of cell surface functions (Table 1). This review intends to focus on the role of plasma membrane glycoproteins describing briefly principles of glycoprotein structure and function, and characteristics of their biosynthesis and degradation. [ABSTRACT FROM PUBLISHER]

We have investigated the effect of the synthetic phospholipid analogue, hexadecylphosphocholine (HePC), a member of a new class of membrane-affecting antiproliferative drugs, on adhesion to extracellular matrix components, reorganization of three-dimensional collagen lattices, and proliferative activity of human keratinocyte populations in vitro. Six transformed keratinocyte lines were compared with their normal counterparts from interfollicular epidermis. Adhesion to collagen types I and IV, laminin, and fibronectin was weakest in normal keratinocytes (binding of 3-10% of the cells), followed by HaCaT and HaCaT-II/3 (25-30% binding), and the squamous carcinoma lines and SV-40 transformed keratinocyles (35-50% binding). Treatment with non-toxic doses of 10-20 μmol/l HePC led to a clear inhibition of the adhesive interactions by 50-75% in all populations. The impaired adhesion capacity was paralleled by a clear decrease of the ability of all keratinocyte populations to contract three-dimensional collagen lattices, an experimental model system for the reorganization of extracellular matrices. Histological examination revealed that these effects were due to a reduced cell number in the collagen lattices, a finding underscored by significant inhibition of proliferative activity of all keratinocyte populations by HePC. Furthermore, HePC led lo marked changes of cellular morphology in the contracted gels. FACS analysis revealed that the impaired interaction with components of the extracellular matrix was not due to a specific downregulation of β1-integrins, the major cell-surface receptors for the respective matrix proteins. In conclusion, our results provide new insights into the potential action of HePC in a variety of skin disorders. Decreased proliferative activity and changes of cellular morphology, combined with impaired interactions with extracellular matrix proteins and a consecutive loss of matrix organization capacity, may cause suppression of different hyper proliferative skin diseases. [ABSTRACT FROM AUTHOR]

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Constitutional politics seemingly corroborate the assumption that Germany is a Grand Coalition state. In this perspective German cooperative federalism and the supermajority required for any amendment to the constitution privilege bargaining and intertwined policy-making as modes of conflict resolution and thus support grand coalitions. In this paper I will explore whether this theory can explain constitutional politics in the German Länder. Firstly, I examine how far sub-national constitutional politics match the functioning of cooperative federalism that is a defining feature of the Grand Coalition state. Secondly, I examine sub-national constitutional politics in the five new Länder and bring the role parties played in this policy field to the fore. Overall, I conclude that cooperative federalism did not impact on constitutional politics in East Germany and that the features of consensus democracy are only partly able to explain law-making in this sector.

The specific activity of dipeptidyl peptidase IV (DPPIV E.C. 3.4.14.-) in the plasma membrane of Morris hepatoma 9121 or hepatoma 7777 was 3.5% and 2.9%, respectively, of that in the plasma membrane of rat liver. The enzyme activity in the serum of hepatoma-bearing rats was 141% (hepatoma 91219) and 162% (hepatoma 7777) of the normal value. cytochemical investigation showed that the DPP IV activity was almost completely absent from the hepatoma cell plasma membrane and was not sequestered within these cells. Indirect immunofluorescence staining with a polyclonal antibody directed against DPP IV indicated that the loss of activity was due to the absence of DPP IV molecules in the plasma membrane. The possibility that the enzyme is transferred from the membrane into the serum as a result of structural alterations is discussed. [ABSTRACT FROM AUTHOR]

This special issue of Perspectives on Federalism collects papers mostly presented at the General Conference of the European Consortium of Political Research in September 2014. The issue contains five papers dealing with the role, the status, the dynamics, and the functions of sub-national constitutional politics and sub-national constitutionalism in a number of member states of the EU as well as in a comparative, non-EU perspective. Even though the papers take different perspectives on the topic at hand, they all engage with the contribution sub-national constitutions can make to democracy and the nationstate within as well as outside of Europe.

Abstract Background Dipeptidyl peptidase IV (DPPIV) also known as the T cell activation marker CD26 is a multifunctional protein which is involved in various biological processes. The association of human-DPPIV with components of the human immunodeficiency virus type-1 (HIV1) is well documented and raised some discussions. Several reports implicated the interaction of human-DPPIV with the HIV1 transcription transactivator protein (HIV1-Tat) and the inhibition of the dipeptidyl peptidase activity of DPPIV by the HIV1-Tat protein. Furthermore, enzyme kinetic data implied another binding site for the HIV1-Tat other than the active centre of DPPIV. However, the biological significance of this interaction of the HIV1-Tat protein and human-DPPIV has not been studied, yet. Therefore, we focused on the interaction of HIV1-Tat protein with DPPIV and investigated the subsequent biological consequences of this interaction in Spodoptera frugiperda cells, using the BAC-TO-BAC baculovirus system. Results The HIV1-Tat protein (Tat-BRU) co-localized and co-immunoprecipitated with human-DPPIV protein, following co-expression in the baculovirus-driven Sf9 cell expression system. Furthermore, tyrosine phosphorylation of DPPIV protein was up-regulated in Tat/DPPIV-co-expressing cells after 72 h culturing and also in DPPIV-expressing Sf9 cells after application of purified recombinant Tat protein. As opposed to the expression of Tat alone, serine phosphorylation of the Tat protein was decreased when co-expressed with human-DPPIV protein. Conclusions We show for the first time that human-DPPIV and HIV1-Tat co-immunoprecipitate. Furthermore, our findings indicate that the interaction of HIV1-Tat and human-DPPIV may be involved in signalling platforms that regulate the biological function of both human-DPPIV and HIV1-Tat.