Cassini ISS astrometry of the Saturnian satellites: Tethys, Dione, Rhea, Iapetus, and Phoebe 2004-2012

This work was mainly funded by European Community’s Seventh Framework Program (FP7/2007-2013) under grant agreement 263466 for the FP7-ESPaCE, and partially by UPMC-EMERGENCE (contract number EME0911), for which R.T. and V.L. are grateful. R.T. was also supported by the Cassini mission. In addition, this work was supported by the Science and Technology Facilites Council (Grant No. ST/F007566/1) and C.D.M. and N.J.C. are grateful to them for financial assistance. C.D.M. is also grateful to the Leverhulme Trust for the award of a Research Fellowship

Cassini ISS mutual event astrometry of the mid-sized Saturnian satellites 2005-2012

Reproduced with permission from Astronomy & Astrophysics, © ES

Activation of TRPC1 Channel by Metabotropic Glutamate Receptor mGluR5 Modulates Synaptic Plasticity and Spatial Working Memory

Group I metabotropic glutamate receptors, in particular mGluR5, have been implicated in various forms of synaptic plasticity that are believed to underlie declarative memory. We observed that mGluR5 specifically activated a channel containing TRPC1, an isoform of the canonical family of transient receptor potential (TRPC) channels highly expressed in CA1-3 regions of the hippocampus. TRPC1 is able to form tetrameric complexes with TRPC4 and/or TRPC5 isoforms. TRPC1/4/5 complexes have recently been involved in the efficiency of synaptic transmission in the hippocampus. We therefore used a mouse model devoid of TRPC1 expression to investigate the involvement of mGluR5-TRPC1 pathway in synaptic plasticity and memory formation. Trpc1-/- mice showed alterations in spatial working memory and fear conditioning. Activation of mGluR increased synaptic excitability in neurons from WT but not from Trpc1-/- mice. LTP triggered by a theta burst could not maintain over time in brain slices from Trpc1-/- mice. mGluR-induced LTD was also impaired in these mice. Finally, acute inhibition of TRPC1 by Pico145 on isolated neurons or on brain slices mimicked the genetic depletion of Trpc1 and inhibited mGluR-induced entry of cations and subsequent effects on synaptic plasticity, excluding developmental or compensatory mechanisms in Trpc1-/- mice. In summary, our results indicate that TRPC1 plays a role in synaptic plasticity and spatial working memory processes

Involvement of VDAC, Bax and Ceramides in the Efflux of AIF from Mitochondria during Curcumin-Induced Apoptosis

Contains fulltext : 80085.pdf (publisher's version ) (Open Access)BACKGROUND: We previously identified curcumin as a potent inducer of fibroblast apoptosis, which could be used to treat hypertrophic scar formation. Here we investigated the underlying mechanism of this process. PRINCIPAL FINDINGS: Curcumin-induced apoptosis could not be blocked by caspase-inhibitors and we could not detect any caspase-3/7 activity. Curcumin predominantly induced mitochondria-mediated ROS formation and stimulated the expression of the redox-sensitive pro-apoptotic factor p53. Inhibition of the pro-apoptotic signaling enzyme glycogen synthase kinase-3beta (GSK-3beta) blocked curcumin-induced apoptosis. Apoptosis was associated with high molecular weight DNA damage, a possible indicator of apoptosis-inducing factor (AIF) activity. Indeed, curcumin caused nuclear translocation of AIF, which could be blocked by the antioxidant N-acetyl cysteine. We next investigated how AIF is effluxed from mitochondria in more detail. The permeability transition pore complex (PTPC), of which the voltage-dependent anion channel (VDAC) is a component, could be involved since the VDAC-inhibitor DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) efficiently blocked AIF translocation. However, PTPC is not involved in AIF release since cyclosporine A, a specific inhibitor of the complex did not block apoptosis. Alternatively, the pro-apoptotic protein Bax could have formed mitochondrial channels and interacted with VDAC. Curcumin caused mitochondrial translocation of Bax, which was blocked by DIDS, suggesting a Bax-VDAC interaction. Interestingly, ceramide channels can also release apoptogenic factors from mitochondria and we found that addition of ceramide induced caspase-independent apoptosis. Surprisingly, this process could also be blocked by DIDS, suggesting the concerted action of Bax, VDAC and ceramide in the efflux of AIF from the mitochondrion. CONCLUSIONS: Curcumin-induced fibroblast apoptosis is totally caspase-independent and relies on the mitochondrial formation of ROS and the subsequent nuclear translocation of AIF, which is released from a mitochondrial pore that involves VDAC, Bax and possibly ceramides. The composition of the AIF-releasing channel seems to be much more complex than previously thought

Effects of cell seeding density on real-time monitoring of anti-proliferative effects of transient gene silencing

WOS: 000390112500001PubMed ID: 27981039Background: Real-time cellular analysis systems enable impedance-based label-free and dynamic monitoring of various cellular events such as proliferation. In this study, we describe the effects of initial cell seeding density on the anti-proliferative effects of transient gene silencing monitored via real-time cellular analysis. We monitored the realtime changes in proliferation of Huh7 hepatocellular carcinoma and A7r5 vascular smooth muscle cells with different initial seeding densities following transient receptor potential canonical 1 (TRPC1) silencing using xCELLigence system. Huh7 and A7r5 cells were seeded on E-plate 96 at 10,000, 5000, 1250 and 5000, 2500 cells well(-1), respectively, following silencing vector transfection. The inhibitory effects of transient silencing on cell proliferation monitored every 30 min for 72 h. Results: TRPC1 silencing did not inhibit the proliferation rates of Huh7 cells at 10,000 cells well(-1) seeding density. However, a significant anti-proliferative effect was observed at 1250 cells well(-1) density at each time point throughout 72 h. Furthermore, significant inhibitory effects on A7r5 proliferation were observed at both 5000 and 2500 cells well(-1) for 72 h. Conclusions: Data suggest that the effects of transient silencing on cell proliferation differ depending on the initial cell seeding density. While high seeding densities mask the significant changes in proliferation, the inhibitory effects of silencing become apparent at lower seeding densities as the entry into log phase is delayed. Using the optimal initial seeding density is crucial when studying the effects of transient gene silencing. In addition, the results suggest that TRPC1 may contribute to proliferation and phenotypic switching of vascular smooth muscle cells.Scientific and Technological Research Council of Turkey (TUBITAK Research Project)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [108S072]; Novartis (Turkey)Novartis; Research Infrastructure Project, The State Planning Organization of Turkey (DPT) [2009K120640]This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK Research Project, 108S072) and Novartis (Turkey) to MT. The xCELLigence system was purchased within the Research Infrastructure Project, The State Planning Organization of Turkey (DPT, 2009K120640)

Role of S100 proteins in health and disease

The S100 family of proteins contains 25 known members that share a high degree of sequence and structural similarity. However, only a limited number of family members have been characterized in depth, and the roles of other members are likely undervalued. Their importance should not be underestimated however, as S100 family members function to regulate a diverse array of cellular processes including proliferation, differentiation, inflammation, migration and/or invasion, apoptosis, Ca2+ homeostasis, and energy metabolism. Here we detail S100 target protein interactions that underpin the mechanistic basis to their function, and discuss potential intervention strategies targeting S100 proteins in both preclinical and clinical situations