Search results for "Negative regulator"

2018

Aging is a complicated pathophysiological process accompanied by a wide array of biological adaptations. The physiological deterioration correlates with the reduced regenerative capacity of tissues. The rejuvenation of tissue regeneration in aging organisms has also been observed after heterochronic parabiosis. With this model, it has been shown that exposure to young blood can rejuvenate the regenerative capacity of peripheral tissues and brain in aged animals. An endogenous compound called growth differentiation factor 11 (GDF11) is a circulating negative regulator of cardiac hypertrophy, suggesting that raising GDF11 levels could potentially treat or prevent cardiac diseases. The protein…

Modulating Neuronal Competition Dynamics in the Dentate Gyrus to Rejuvenate Aging Memory Circuits.

2015

The neural circuit mechanisms underlying the integration and functions of adult-born dentate granule cell (DGCs) are poorly understood. Adult-born DGCs are thought to compete with mature DGCs for inputs to integrate. Transient genetic overexpression of a negative regulator of dendritic spines, Kruppel-like factor 9 (Klf9), in mature DGCs enhanced integration of adult-born DGCs and increased NSC activation. Reversal of Klf9 overexpression in mature DGCs restored spines and activity and reset neuronal competition dynamics and NSC activation, leaving the DG modified by a functionally integrated, expanded cohort of age-matched adult-born DGCs. Spine elimination by inducible deletion of Rac1 in …

Excessive CpG 1668 stimulation triggers IL-10 production by cDC that inhibits IFN-alpha responses by pDC.

2008

Upon stimulation with a wide range of concentrations of CpG oligodeoxynucleotide 2216 (CpG 2216), plasmacytoid DC are induced to produce type I IFN (IFN-alpha/beta). In contrast, CpG 1668 shows a bell-shaped dose-response correlation, i.e. only intermediate but not high doses of CpG 1668 induce IFN-alpha/beta. Interestingly, high-dose CpG 1668 completely inhibited IFN-alpha responses induced by CpG 2216. Experiments using supernatant of high-dose CpG-1668-treated cells indicated that secreted inhibitor(s) mediated the IFN-alpha shut-off. Among modulating cytokines, IL-10 turned out to be one important negative regulator. In line with this, supernatants of IL-10-deficient DC cultures stimula…

Molecular dynamics studies on Mdm2 complexes: An analysis of the inhibitor influence

2012

p53 is a powerful anti-tumoral molecule frequently inactivated by mutations or deletions in cancer. However, half of all human tumors expresses wild-type p53, and its activation, by antagonizing its negative regulator Mdm2, might offer a new strategy for therapeutic protocol. In this work, we present a molecular dynamics study on Mdm2 structure bound to two different known inhibitors with the aim to investigate the structural transitions between apo-Mdm2 and Mdm2-inhibitor complexes. We tried to gain information about conformational changes binding a benzodiazepine derivative inhibitor with respect the known nutlin and the apo form. The conformational changes alter the size of the cleft and…

Dorsal/Ventral asymmetric expression of nodal in the early sea urchin embryo relies on specific suppression in dorsal cells by the Hbox12 homeodomain…

2014

Dorsal/Ventral (DV) polarization of the sea urchin embryo is directed by a Nodal-expressing signaling centre located on the ventral side. The initial breaking of the symmetry and positioning of the organizer are unclear. We show that, in Paracentrotus lividus embryos, the Hbox12 homeodomaincontaining repressor is expressed on the opposite side and precedes the onset of nodal transcription. Hbox12 misexpression provokes DV abnormalities, attenuating nodal and nodal-dependent gene transcription. Reciprocally, clonal hbox12 loss-of-function imposed by blastomere transplantation or gene transfer assays disrupts DV polarization and allows ectopic expression of nodal. Remarkably, the localized kn…