180 research outputs found
Emerging Roles of Neuronal Ca2+ Sensor-1 in Cardiac and Neuronal Tissues: A Mini Review
The EF-hand calcium (Ca2+)-binding protein, neuronal Ca2+ sensor-1 (NCS-1/frequenin), is predominantly expressed in neuronal tissues and plays a crucial role in neuronal functions, including synaptic transmission and plasticity. NCS-1 has diverse functional roles, as elucidated in the past 15 years, which include the regulation of phosphatidylinositol 4-kinase IIIβ (PI-4K-β) and several ion channels such as voltage-gated K+ and Ca2+ channels, the D2 dopamine receptors, and inositol 1,4,5-trisphosphate receptors (InsP3Rs). Functional analyses demonstrated that NCS-1 enhances exocytosis and neuronal survival after injury, as well as promotes learning and memory in mice. NCS-1 is also expressed in the heart including the Purkinje fibers (PFs) of the conduction system. NCS-1 interacts with KV4 K+ channels together with dipeptidyl peptidase-like protein-6 (DPP-6), and this macromolecule then composes the transient outward current in PFs and contributes to the repolarization of PF action potential, thus being responsible for idiopathic arrhythmia. Moreover, NCS-1 expression was reported to be significantly high at the immature stage and at hypertrophy in adults. That report demonstrated that NCS-1 positively regulates cardiac contraction in immature hearts by increasing intracellular Ca2+ signals through interaction with InsP3Rs. With the related signals, NCS-1 activates nuclear Ca2+ signals, which would be a mechanism underlying hormone-induced cardiac hypertrophy. Furthermore, NCS-1 contributes to stress tolerance in cardiomyocytes by activating mitochondrial detoxification pathways, with a key role in Ca2+-dependent pathways. In this review, we will discuss recent findings supporting the functional significance of NCS-1 in the brain and heart and will address possible underlying molecular mechanisms
Distribution of β2-adrenergic receptor mRNA expression along the hamster nephron segments
AbstractDistribution of β2-adrenergic receptor mRNA expression along the microdissected hamster nephron segments was examined by the reverse transcription-polymerase chain reaction (RT-PCR) technique. Conventional RT-PCR using a set of primers on separate exons could not be applied for the detection of β2-adrenergic receptor mRNA because of its intronless nature. We used the ‘rapid amplification of cDNA ends’ protocol [(1985) Proc. Natl. Acad. Sci. USA 85, 8998-9002] as a maneuver for RT-PCR of an intronless gene. Using this method, we successfully located hamster β2-adrenergic receptor mRNA only in glomeruli and early proximal convoluted tubule along the nephron segments tested
Interpretation Structure Modeler for FOL
Import 05/08/2014Obsahem této diplomové práce je analýza a návrh systému pro podporu výuky předmětu Matematická logika. Vytvářený systém se bude týkat problematiky 3D vizualizace úlohy na hledání modelu množiny formulí v predikátové logice prvního řádu a modelování důležitých vlastností relací. Nástroj bude také obsahovat nápovědu pro vytvoření modelu množiny. V první části práce, je čtenář seznámen s teoretickými základy z dané oblasti, na které plynule navazuje specifikace požadavků na nový systém. Dále je text práce zaměřen především na analýzu a návrh jednotlivých částí systému, která je doplněna o třídní a sekvenční diagramy UML.The goal of this thesis is to Provide design and analysis of a new system, which could then be used as a teaching tool in subject called Mathematical Logic. The new system will consist of two main parts. The first part will be dealing with the problem of 3D visualization of formula set models. The second part will include an environment for modeling important properties of relations. Our system will also include an aid for creating formula set models. In the first part of the thesis we focus on theoretical background and requirement specification for the new system. Following parts ot the thesis are mainly focused on analysis and design of individual system parts, accompanied with class and sequence UML diagrams.460 - Katedra informatikydobř
Phamacogenomics of Clozapine-Induced Agranulocytosis
Background: Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine.
Methods: To examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects.
Results: We identified a significant association in the human leukocyte antigen (HLA) region (rs1800625, p = 3.46 × 10−9, odds ratio [OR] = 3.8); therefore, subsequent HLA typing was performed. We detected a significant association of HLA-B*59:01 with CIAG (p = 3.81 × 10−8, OR = 10.7) and confirmed this association by comparing with an independent clozapine-tolerant control group (n = 380, p = 2.97 × 10−5, OR = 6.3). As we observed that the OR of CIA (OR: 9.3~15.8) was approximately double that in CIG (OR: 4.4~7.4), we hypothesized that the CIG subjects were a mixed population of those who potentially would develop CIA and those who would not develop CIA (non-CIA). This hypothesis allowed the proportion of the CIG who were non-CIA to be calculated, enabling us to estimate the positive predictive value of the nonrisk allele on non-CIA in CIG subjects. Assuming this model, we estimated that 1) ~50% of CIG subjects would be non-CIA; and 2) ~60% of the CIG subjects without the risk allele would be non-CIA and therefore not expected to develop CIA.
Conclusions: Our results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated
Adjunctive benzodiazepine treatment of hospitalized schizophrenia patients in Asia from 2001 to 2008
10.1017/S146114571000163XThe International Journal of Neuropsychopharmacology146735-74
An Improved Measurement of Mixing-induced CP Violation in the Neutral B Meson System
We present an improved measurement of the standard model CP violation
parameter sin2phi_1 (also known as sin2beta) based on a sample of 85 times 10^6
B Bbar pairs collected at the Upsilon(4S) resonance with the Belle detector at
the KEKB asymmetric-energy e+e- collider. One neutral B meson is reconstructed
in a J/psi K_S, psi(2S) K_S, chi_{c1} K_S, eta_c K_S, J/psi K^{*0}, or J/psi
K_L CP-eigenstate decay channel and the flavor of accompanying B meson is
identified from itsdecay products. From the asymmetry in the distribution of
the time intervals between the two B meson decay points, we obtain sin2phi_1 =
0.719 +/- 0.074(stat) +/- 0.035(syst). We also report measurements of CP
violation parameters for the related B^0 -> J/psi pi^0 decay mode and the
penguin-dominated processes B^0 -> eta' K_S, phi K_S and K^+K^- K_S.Comment: 11 pages, 4 figures, 4 tables, contributed to ICHEP200
De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity
Here we report de novo non-synonymous single-nucleotide variants (SNVs) by conducting whole exome sequencing of 18 trios consisting of Japanese patients with sporadic schizophrenia and their parents. Among nine SNVs, we explored the functional impact of the de novo mutation in TBL1XR1 [c.30 C > G (p.Phe10Leu)], a gene previously found to be associated with autism spectrum disorder and epilepsy. Protein structural analysis revealed that Phe10Leu mutation may decrease the structural stability of the TBL1XR1 protein. We demonstrate that Phe10Leu mutation alters the interaction of TBL1XR1 with N-CoR and β-catenin, which play critical roles in regulation of Wnt-mediated transcriptional activity. Consistently, TBL1XR1-mediated activation of Wnt signaling was up-regulated by Phe10Leu mutation. These results suggest that a de novo TBL1XR1 point mutation could alter Wnt/β-catenin signaling activity. Further studies are required to clarify the involvement of TBL1XR1 mutations in neuropsychiatric conditions. © The Author(s) 2017
De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity
Here we report de novo non-synonymous single-nucleotide variants (SNVs) by conducting whole exome sequencing of 18 trios consisting of Japanese patients with sporadic schizophrenia and their parents. Among nine SNVs, we explored the functional impact of the de novo mutation in TBL1XR1 [c.30C>G (p.Phe10Leu)], a gene previously found to be associated with autism spectrum disorder and epilepsy. Protein structural analysis revealed that Phe10Leu mutation may decrease the structural stability of the TBL1XR1 protein. We demonstrate that Phe10Leu mutation alters the interaction of TBL1XR1 with N-CoR and β-catenin, which play critical roles in regulation of Wnt-mediated transcriptional activity. Consistently, TBL1XR1-mediated activation of Wnt signaling was up-regulated by Phe10Leu mutation. These results suggest that a de novo TBL1XR1 point mutation could alter Wnt/β-catenin signaling activity. Further studies are required to clarify the involvement of TBL1XR1 mutations in neuropsychiatric conditions
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