Abnormal pontine activation in pathological laughing as shown by functional magnetic resonance imaging

To explore the aetiology of pathological laughing, a 65-year-old woman with pathological laughing was examined by 3-T functional magnetic resonance imaging (fMRI) before and after treatment with drugs. Here, we report that the patient consistently showed exaggerated pontine activation during the performance of three tasks before treatment, whereas abnormal pontine activation was no longer found after successful treatment with the selective serotonin reuptake inhibitor, paroxetine. Our findings in this first fMRI study of pathological laughing suggest that serotonergic replacement decreases the aberrant activity in a circuit that involves the pons

両大戦間期における陸上貨物輸送の変容 : 近畿地方の大都市を中心として

立命館大学博士(文学)thesi

「生きられる空間」の複相性をめぐって : 文学テクストに見る出来事の表象と記憶の問題

2007-03-31departmental bulletin pape

Writing Lives

Writing Lives, a collection of short stories, featuring Lawrence Hoba, Tendai Huchu, Tendai Machingaidze, Nevanji Madanhire, Daniel Mandishona, Christopher Mlalazi, Blessing Musariri, Chiedza Musengezi, Sekai Nzenza, Fungisayi Sasa and Emmanuel Sigauke. Writing Lives is the seventh of Weaver's anthologies of short stories following Writing Still, Writing Now, Laughing Now, Women Writing Zimbabwe, Mazambuko and Writing Free. As with the other anthologies, this vibrant collection reflects the lives and experiences of Zimbabweans as filtered through the lens of each author's perceptions. Writing Lives gives us stories that will make us laugh and bring tears to our eyes as it provides a focus on the past, the present and even the future

Summary of identified <i>NKX2-5</i> sequence variations in patients with CHD.

<p>(<b>A</b>) their location along the gene; (<b>B, C</b>) patients and parents positive for the mutation.</p

The Gcn2 Regulator Yih1 Interacts with the Cyclin Dependent Kinase Cdc28 and Promotes Cell Cycle Progression through G2/M in Budding Yeast

<div><p>The <i>Saccharomyces cerevisiae</i> protein Yih1, when overexpressed, inhibits the eIF2 alpha kinase Gcn2 by competing for Gcn1 binding. However, deletion of <i>YIH1</i> has no detectable effect on Gcn2 activity, suggesting that Yih1 is not a general inhibitor of Gcn2, and has no phenotypic defect identified so far. Thus, its physiological role is largely unknown. Here, we show that Yih1 is involved in the cell cycle. Yeast lacking Yih1 displays morphological patterns and DNA content indicative of a delay in the G2/M phases of the cell cycle, and this phenotype is independent of Gcn1 and Gcn2. Accordingly, the levels of phosphorylated eIF2α, which show a cell cycle-dependent fluctuation, are not altered in cells devoid of Yih1. We present several lines of evidence indicating that Yih1 is in a complex with Cdc28. Yih1 pulls down endogenous Cdc28 <i>in vivo</i> and this interaction is enhanced when Cdc28 is active, suggesting that Yih1 modulates the function of Cdc28 in specific stages of the cell cycle. We also demonstrate, by Bimolecular Fluorescence Complementation, that endogenous Yih1 and Cdc28 interact with each other, confirming Yih1 as a <i>bona fide</i> Cdc28 binding partner. Amino acid substitutions within helix H2 of the RWD domain of Yih1 enhance Yih1-Cdc28 association. Overexpression of this mutant, but not of wild type Yih1, leads to a phenotype similar to that of <i>YIH1</i> deletion, supporting the view that Yih1 is involved through Cdc28 in the regulation of the cell cycle. We further show that IMPACT, the mammalian homologue of Yih1, interacts with CDK1, the mammalian counterpart of Cdc28, indicating that the involvement with the cell cycle is conserved. Together, these data provide insights into the cellular function of Yih1/IMPACT, and provide the basis for future studies on the role of this protein in the cell cycle.</p></div

<i>yih1Δ</i> cells remain longer in the G2/M phases.

<p><b>(A)</b> Exponentially growing wild type (MSY-WT2) and <i>yih1Δ</i> (MSY-Y2) cells were synchronized in G1 with α-factor and released into fresh YPD media. Samples were collected at the indicated time intervals and cells were fixed. The DNA was stained with DAPI. The percentage of budded cells (mean ± S.E. of three independent experiments) was determined. <b>(B)</b> Cells were synchronized in metaphase with nocodazole and released into fresh YPD media. Samples were taken and stained as in A. The percentage of small-budded cells (mean ± S.E. of three independent experiments) was determined. For each time point given in the graphs, more than 300 cells were analyzed.</p

Transactivation potential of the p.A119E and p.A119S <i>NKX2-5</i> mutations.

<p>Presented in <b>A-C</b> is the average fold of luciferase reporter induction, relative to the activity measured at the lower galactose concentration in the absence of NKX2-5 proteins. Error bars correspond to the standard deviation of at least three biological repeats. Results were obtained with a reporter strain where the luciferase gene is controlled by a minimal promoter containing two repeats of the NK-RE derived from the ECE target gene (<b>A</b>), two repeats of the low-affinity NK-RE derived from the ANF target gene (<b>B</b>) or 14 repeats of the ANF NK-RE (<b>C</b>). The different NKX2-5 mutants and the galactose concentrations used to modulate expression are indicated. With the ECE reporter, the activity of p.A119E and p.A119S is significantly, albeit modestly reduced compared to wild type NKX2-5 (*  =  wt NKX2-5 compared to each mutant alleles; p<0.05; t-test). The haplotype found in patient #58LM [c.356A (p.A119E) + c. 543A (p.Q181) + c.63G (rs2277923)] further reduced transactivation (?  =  A119E mutant alone compared to patient #58LM haplotype; p<0.05; t-test). The reference (wild type) <i>NKX2-5</i> NM_004387.2 used here as control has the haplotype [c.356C + c. 543G + c.63A]. (<b>C</b>) The p.A119E mutation alone was tested with the highly responsive ANF-14 reporter strain using 4 different levels of protein induction obtained using the indicated concentrations of galactose in the medium. The complete panel of alleles was examined at high expression levels. (<b>D</b>) The impact of the HAND1 p.R84L mutation was examined using D-box and E-box reporter strain in co-expression experiments with E47–see text for details- The average relative light units normalized for the optical density of the cultures (OD_600nm) and the standard deviations of 4 replicates are presented.</p