CDKL5 expression is modulated during neuronal development and its subcellular distribution is tightly regulated by the C-terminal tail

Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in patients with Rett syndrome (RTT), West syndrome, and X-linked infantile spasms, sharing the common feature of mental retardation and early seizures. CDKL5 is a rather uncharacterized kinase, but its involvement in RTT seems to be explained by the fact that it works upstream of MeCP2, the main cause of Rett syndrome. To understand the role of this kinase for nervous system functions and to address if molecular mechanisms are involved in regulating its distribution and activity, we studied the ontogeny of CDKL5 expression in developing mouse brains by immunostaining and Western blotting. The expression profile of CDKL5 was compared with that of MeCP2. The two proteins share a general expression profile in the adult mouse brain, but CDKL5 levels appear to be highly modulated at the regional level. Its expression is strongly induced in early postnatal stages, and in the adult brain CDKL5 is present in mature neurons, but not in astroglia. Interestingly, the presence of CDKL5 in the cell nucleus varies at the regional level of the adult brain and is developmentally regulated. CDKL5 shuttles between the cytoplasm and the nucleus and the C-terminal tail is involved in localizing the protein to the cytoplasm in a mechanism depending on active nuclear export. Accordingly, Rett derivatives containing disease-causing truncations of the C terminus are constitutively nuclear, suggesting that they might act as gain of function mutations in this cellular compartment

Functional consequences of mutations in CDKL5, an X-linked gene involved in infantile spasms and mental retardation

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in patients with Rett syndrome, West syndrome, and X-linked infantile spasms sharing the common features of generally intractable early seizures and mental retardation. Disease-causing mutations are distributed in both the catalytic domain and in the large COOH terminus. In this report, we examine the functional consequences of some Rett mutations of CDKL5 together with some synthetically designed derivatives useful to underline the functional domains of the protein. The mutated CDKL5 derivatives have been subjected to in vitro kinase assays and analyzed for phosphorylation of the TEY (Thr-Glu-Tyr) motif within the activation loop, their subcellular localization, and the capacity of CDKL5 to interact with itself. Whereas wild-type CDKL5 autophosphorylates and mediates the phosphorylation of the methyl-CpG-binding protein 2 (MeCP2) in vitro, Rett-mutated proteins show both impaired and increased catalytic activity suggesting that a tight regulation of CDKL5 is required for correct brain functions. Furthermore, we show that CDKL5 can self-associate and mediate the phosphorylation of its own TEY (Thr-Glu-Tyr) motif. Eventually, we show that the COOH terminus regulates CDKL5 properties; in particular, it negatively influences the catalytic activity and is required for its proper sub-nuclear localization. We propose a model in which CDKL5 phosphorylation is required for its entrance into the nucleus whereas a portion of the COOH-terminal domain is responsible for a stable residency in this cellular compartment probably through protein-protein interactions

Draft Genome Sequence of Beneficial Rice Rhizosphere Isolate Pseudomonas aeruginosa PUPa3.

Published onlinePseudomonas aeruginosa PUPa3 is a rhizosphere-colonizing and plant growth-promoting strain isolated from the rhizosphere of rice. This strain has, however, been shown to be pathogenic in two nonmammalian infection models. Here we report the draft genome sequence of P. aeruginosa PUPa3.G.U. and M.K. were funded by the Ministry of Education, Science and Technological Development, Republic of Serbia (grant no. 173019). G.U. is also the beneficiary of FEMS Research Fellowship 2014-1. The laboratory of V.V. was financed by ICGEB core funding

A model to explain angular distributions of J/ψJ/\psi and ψ(2S)\psi(2S) decays into ΛΛ‾\Lambda\overline{\Lambda} and Σ0Σ‾0\Sigma^0\overline{\Sigma}^0

BESIII data show a particular angular distribution for the decay of the $J/\psi$ and $\psi(2S)$ mesons into the hyperons $\Lambda\overline{\Lambda}$ and $\Sigma^0\overline{\Sigma}^0$. More in details the angular distribution of the decay $\psi(2S) \to \Sigma^0\overline{\Sigma}^0$ exhibits an opposite trend with respect to that of the other three channels: $J/\psi \to \Lambda\overline{\Lambda}$, $J/\psi \to \Sigma^0\overline{\Sigma}^0$ and $\psi(2S) \to \Lambda\overline{\Lambda}$. We define a model to explain the origin of this phenomenon.Comment: 6 pages, 7 figures, to be published in Chinese Physics

A Cylindrical GEM Inner Tracker for the BESIII experiment at IHEP

The Beijing Electron Spectrometer III (BESIII) is a multipurpose detector that collects data provided by the collision in the Beijing Electron Positron Collider II (BEPCII), hosted at the Institute of High Energy Physics of Beijing. Since the beginning of its operation, BESIII has collected the world largest sample of J/{\psi} and {\psi}(2s). Due to the increase of the luminosity up to its nominal value of 10^33 cm-2 s-1 and aging effect, the MDC decreases its efficiency in the first layers up to 35% with respect to the value in 2014. Since BESIII has to take data up to 2022 with the chance to continue up to 2027, the Italian collaboration proposed to replace the inner part of the MDC with three independent layers of Cylindrical triple-GEM (CGEM). The CGEM-IT project will deploy several new features and innovation with respect the other current GEM based detector: the {\mu}TPC and analog readout, with time and charge measurements will allow to reach the 130 {\mu}m spatial resolution in 1 T magnetic field requested by the BESIII collaboration. In this proceeding, an update of the status of the project will be presented, with a particular focus on the results with planar and cylindrical prototypes with test beams data. These results are beyond the state of the art for GEM technology in magnetic field

Gas Analysis and Monitoring Systems for the RPC Detector of CMS at LHC

The Resistive Plate Chambers (RPC) detector of the CMS experiment at the LHC proton collider (CERN, Switzerland) will employ an online gas analysis and monitoring system of the freon-based gas mixture used. We give an overview of the CMS RPC gas system, describe the project parameters and first results on gas-chromatograph analysis. Finally, we report on preliminary results for a set of monitor RPC.Comment: 9 pages, 8 figures. Presented by Stefano Bianco (Laboratori Nazionali di Frascati dell'INFN) at the IEEE NSS, San Diego (USA), October 200

Caracterização de órgãos de galinha envolvidos na imunidade à infecção por Eimeria tenella

Projeto/Plano de Ação: 16.00.30004.0