A systemic risk assessment of OTC derivatives reforms and skin-in-the-game for CCPs

The G20 OTC (over-the-counter) derivatives reforms impose large collateral/liquidity demands on clearing members of Central Counterparty (CCP) clearing platforms in the form of initial margins, variation margins and contributions to the default fund. In Heath et al. (2016), it was shown how this introduces a trade-off between liquidity risk and solvency risk with the system manifesting considerable systemic risk from these two sources of risk while CCP penetration is at current levels. The authors extend this analysis to include the European Market Infrastructure Regulation (EMIR) skin-in-the-game requirements for CCPs, which aim to ameliorate the contributions to the default fund by clearing members and also to prevent moral hazard problems associated with the too-interconnected-to-fail (TITF) status of CCPs as more and more derivatives are centrally cleared. The authors provide a systemic risk assessment of these features of the OTC derivatives reforms using network analysis based on 2015-end data on the derivatives positions for 40 globally systemically important banks (G-SIBs)

Climacteric Lowers Plasma Levels of Platelet-Derived Microparticles: A Pilot Study in Pre-versus Postmenopausal Women

Background: Climacteric increases the risk of thrombotic events by alteration of plasmatic coagulation. Up to now, less is known about changes in platelet-(PMP) and endothelial cell-derived microparticles (EMP). Methods: In this prospective study, plasma levels of microparticles (MP) were compared in 21 premenopausal and 19 postmenopausal women. Results: No altered numbers of total MP or EMP were measured within the study groups. However, the plasma values of CD61-exposing MP from platelets/megakaryocytes were higher in premenopausal women (5,364 x 10(6)/l, range 4,384-17,167) as compared to postmenopausal women (3,808 x 10(6)/l, range 2,009-8,850; p = 0.020). This differentiation was also significant for the subgroup of premenopausal women without hormonal contraceptives (5,364 x 10(6)/l, range 4,223-15,916; p = 0.047; n = 15). Furthermore, in premenopausal women, higher plasma levels of PMP exposing CD62P were also present as compared to postmenopausal women (288 x 10(6)/l, range 139-462, vs. 121 x 10(6)/l, range 74-284; p = 0.024). This difference was also true for CD63+ PMP levels (281 x 10(6)/l, range 182-551, vs. 137 x 10(6)/l, range 64-432; p = 0.015). Conclusion: Climacteric lowers the level of PMP but has no impact on the number of EMP in women. These data suggest that PMP and EMP do not play a significant role in enhancing the risk of thrombotic events in healthy, postmenopausal women. Copyright (C) 2012 S. Karger AG, Base

APache Is an AP2-Interacting Protein Involved in Synaptic Vesicle Trafficking and Neuronal Development

Synaptic transmission is critically dependent on synaptic vesicle (SV) recycling. Although the precise mechanisms of SV retrieval are still debated, it is widely accepted that a fundamental role is played by clathrin-mediated endocytosis, a form of endocytosis that capitalizes on the clathrin/adaptor protein complex 2 (AP2) coat and several accessory factors. Here, we show that the previously uncharacterized protein KIAA1107, predicted by bioinformatics analysis to be involved in the SV cycle, is an AP2-interacting clathrin-endocytosis protein (APache). We found that APache is highly enriched in the CNS and is associated with clathrin-coated vesicles via interaction with AP2. APache-silenced neurons exhibit a severe impairment of maturation at early developmental stages, reduced SV density, enlarged endosome-like structures, and defects in synaptic transmission, consistent with an impaired clathrin/AP2-mediated SV recycling. Our data implicate APache as an actor in the complex regulation of SV trafficking, neuronal development, and synaptic plasticity

PRRT2 controls neuronal excitability by negatively modulating Na+ channel 1.2/1.6 activity

Proline-rich transmembrane protein 2 (PRRT2) is the causative gene for a heterogeneous group of familial paroxysmal neurological disorders that include seizures with onset in the first year of life (benign familial infantile seizures), paroxysmal kinesigenic dyskinesia or a combination of both. Most of the PRRT2 mutations are loss-of-function leading to haploinsufficiency and 80% of the patients carry the same frameshift mutation (c.649dupC; p.Arg217Profs*8), which leads to a premature stop codon. To model the disease and dissect the physiological role of PRRT2, we studied the phenotype of neurons differentiated from induced pluripotent stem cells from previously described heterozygous and homozygous siblings carrying the c.649dupC mutation. Singlecell patch-clamp experiments on induced pluripotent stem cell-derived neurons from homozygous patients showed increased Na+ currents that were fully rescued by expression of wild-type PRRT2. Closely similar electrophysiological features were observed in primary neurons obtained from the recently characterized PRRT2 knockout mouse. This phenotype was associated with an increased length of the axon initial segment and with markedly augmented spontaneous and evoked firing and bursting activities evaluated, at the network level, by multi-electrode array electrophysiology. Using HEK-293 cells stably expressing Nav channel subtypes, we demonstrated that the expression of PRRT2 decreases the membrane exposure and Na+ current of Nav1.2/Nav1.6, but not Nav1.1, channels. Moreover, PRRT2 directly interacted with Nav1.2/Nav1.6 channels and induced a negative shift in the voltage-dependence of inactivation and a slow-down in the recovery from inactivation. In addition, by co-immunoprecipitation assays, we showed that the PRRT2-Nav interaction also occurs in brain tissue. The study demonstrates that the lack of PRRT2 leads to a hyperactivity of voltage-dependent Na+ channels in homozygous PRRT2 knockout human and mouse neurons and that, in addition to the reported synaptic functions, PRRT2 is an important negative modulator of Nav1.2 and Nav1.6 channels. Given the predominant paroxysmal character of PRRT2-linked diseases, the disturbance in cellular excitability by lack of negative modulation of Na+ channels appears as the key pathogenetic mechanism

High-resolution patterning of colloidal quantum dots via non-destructive, light-driven ligand crosslinking

Establishing multi-colour patterning technology for colloidal quantum dots is critical for realising high-resolution displays based on the material. Here, we report a solution-based processing method to form patterns of quantum dots using a light-driven ligand crosslinker, ethane-1,2-diyl bis(4-azido-2,3,5,6-tetrafluorobenzoate). The crosslinker with two azide end groups can interlock the ligands of neighbouring quantum dots upon exposure to UV, yielding chemically robust quantum dot films. Exploiting the light-driven crosslinking process, different colour CdSe-based core-shell quantum dots can be photo-patterned; quantum dot patterns of red, green and blue primary colours with a sub-pixel size of 4 mu mx16 mu m, corresponding to a resolution of >1400 pixels per inch, are demonstrated. The process is non-destructive, such that photoluminescence and electroluminescence characteristics of quantum dot films are preserved after crosslinking. We demonstrate that red crosslinked quantum dot light-emitting diodes exhibiting an external quantum efficiency as high as 14.6% can be obtained. Designing high-resolution displays based on colloidal quantum dots remains a challenge. Here, the authors demonstrate a photo-patterning method to develop CdSe-based core-shell quantum dots patterns of red, green and blue colours with diameters ranging from 7 to 20nm and resolution of 1400 pixels per inch