Function of IRAG2 Is Modulated by NO/cGMP in Murine Platelets

Inositol 1,4,5-triphosphate receptor-associated 2 (IRAG2) is a type II membrane protein located at the endoplasmic reticulum. It is a homologue of inositol 1,4,5-triphosphate receptor-associated cGMP kinase substrate 1 (IRAG1), a substrate protein of cGMP-dependent protein kinase I (PKGI), and is among others expressed in platelets. Here, we studied if IRAG2 is also located in platelets and might be a substrate protein of PKGI. IRAG2 was detected in platelets of IRAG2-WT animals but not in those of IRAG2-KO animals. Next, we validated by co-immunoprecipitation studies that IRAG2 is associated with IP₃R1-3. No direct stable interaction with PKGIβ or with IRAG1 was observed. Phosphorylation of IRAG2 in murine platelets using a Ser/Thr-specific phospho-antibody was found in vitro and ex vivo upon cGMP stimulation. To gain insight into the function of IRAG2, platelet aggregation studies were performed using thrombin and collagen as agonists for treatment of isolated IRAG2-WT or IRAG2-KO platelets. Interestingly, platelet aggregation was reduced in the absence of IRAG2. Pretreatment of wild type or IRAG2-KO platelets with sodium nitroprusside (SNP) or 8-pCPT-cGMP revealed a further reduction in platelet aggregation in the absence of IRAG2. These results show that IRAG2 is a substrate of PKGI in murine platelets. Furthermore, our results indicate that IRAG2 is involved in the induction of thrombin- or collagen-induced platelet aggregation and that this effect is enhanced by cGMP-dependent phosphorylation of IRAG2. As IRAG1 was previously shown to inhibit platelet aggregation in a cGMP-dependent manner, it can be speculated that IRAG2 exerts an opposing function and might be an IRAG1 counterpart in murine platelets.     

Consideration of the BDNF gene in relation to two phenotypes: Hoarding and obesity.

The gene coding for the brain derived neurotrophic factor (BDNF) has emerged as an interesting candidate for multiple brain and brain disorder-related phenomena. The primary aim of the present investigation was to consider the relationship between the BDNF Val66Met variant and two phenotypes: compulsive hoarding as a symptom dimension of obsessive–compulsive disorder (OCD), and body mass index (BMI). We examined the BDNF gene in a large (N = 301) clinical sample of probands with OCD. Participants were classified as hoarding or nonhoarding using a strict, multimeasure grouping approach. Results revealed that the Val/Val genotype was linked with hoarding classification and more severe hoarding behaviors, as well as greater BMI levels. Hoarding status was also associated with greater BMI scores, with individuals in the hoarding group being far more likely to be classified as obese compared with the nonhoarding group. Our findings may provide a distinct avenue through which hoarding and BMI could be linked. These findings are suggestive of a complex gene, body weight, and psychopathology relationship wherein a primitive, survival “thrifty gene” strategy may be conserved and represented in a subgroup of humans manifesting severe hoarding symptoms. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

The E3 architecture: enabling future cellular networks with cognitive and self‐x capabilities

Future mobile networks are expected to be complex heterogeneous systems. On the one hand this will enable users to take advantage of a number of different access technologies. On the other hand it will seriously affect network management procedures since more extensive operations and decisions will have to be dealt with. To tackle these challenges a number of new dynamic mechanisms need to be designed. It is imperative that certain network management tasks have to be performed without human intervention to reduce the OPEX costs and achieve faster responses in different events. To achieve this goal, the introduction of self‐x functionalities, combined with cognitive mechanisms and the ability to reconfigure network entities and terminals, is required. Moreover, the introduction of a new pilot channel needs to be considered to assist the terminals in selecting the most suitable radio access technology according to their requirements. We present the functional architecture of an evolved network that was designed in the context of the EU‐funded IP project ‘E³: End‐to‐End Efficiency’. This architecture aims to enhance existing procedures usually performed in traditional operation and maintenance systems (e.g. spectrum management, network planning, configuration actions). We explain the rationale of our design and provide specific examples to illustrate the role of the different functional entities and their interfaces. A considerable part of this architecture has recently been approved as a feasibility study by the ETSI Committee Reconfigurable Radio System. Copyright © 2010 John Wiley & Sons, Ltd.     

Vacuolar and extracellular maturation of Saccharomyces cerevisiae proteinase A

The vacuolar aspartyl protease proteinase A (PrA) of Saccharomyces cerevisiae is encoded as a preproenzyme by the PEP4 gene and transported to the vacuole via the secretory route. Upon arrival of the proenzyme proPrA to the vacuole, active mature 42 kDa PrA is generated by specific proteolysis involving the vacuolar endoprotease proteinase B (PrB). Vacuolar activation of proPrA can also take place in mutants lacking PrB activity (prb1). Here an active 43 kDa species termed pseudoPrA is formed, probably by an autocatalytic process. When the PEP4 gene is overexpressed in wild-type cells, mature PrA can be found in the growth medium. We have found that prb1 strains overexpressing PEP4 can form pseudoPrA extracellularly. N-terminal amino acid sequence determination of extracellular, as well as vacuolar pseudoPrA showed that it contains nine amino acids of the propeptide, indicating a cleavage between Phe67 and Ser68 of the preproenzyme. This cleavage site is in accordance with the known substrate preference for PrA, supporting the notion that pseudoPrA is formed by autoactivation. When a multicopy PEP4 transformant of a prb1 mutant was grown in the presence of the aspartyl protease inhibitor pepstatin A, a significant level of proPrA was found in the growth medium. Our analyses show that overexpression of PEP4 leads to the secretion of proPrA to the growth medium where the zymogen is converted to pseudoPrA or mature PrA in a manner similar to the vacuolar processing reactions. Amino acid sequencing of secreted proPrA confirmed the predicted cleavage by signal peptidase between Ala22 and Lys23 of the preproenzyme.     

Merocyanine/C60 Planar Heterojunction Solar Cells: Effect of Dye Orientation on Exciton Dissociation and Solar Cell Performance

In this study the charge dissociation at the donor/acceptor heterointerface of thermally evaporated planar heterojunction merocyanine/C₆₀ organic solar cells is investigated. Deposition of the donor material on a heated substrate as well as post‐annealing of the complete devices at temperatures above the glass transition temperature of the donor material results in a twofold increase of the fill factor. An analytical model employing an electric‐field‐dependent exciton dissociation mechanism reveals that geminate recombination is limiting the performance of as‐deposited cells. Fourier‐transform infrared ellipsometry shows that, at temperatures above the glass transition temperature of the donor material, the orientation of the dye molecules in the donor films undergoes changes upon annealing. Based on this finding, the influence of the dye molecules’ orientations on the charge‐transfer state energies is calculated by quantum mechanical/molecular mechanics methods. The results of these detailed studies provide new insight into the exciton dissociation process in organic photovoltaic devices, and thus valuable guidelines for designing new donor materials.