Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease

Background/Aims: We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji). Methods: A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. Results: For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. Conclusions: The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients

A Case of Neurosarcoidosis-Induced Syndrome of Inappropriate Secretion of Antidiuretic Hormone Diagnosed with Neuroendoscopy

We treated a patient with neurosarcoidosis, which caused the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), in whom diagnosis was performed using neuroendoscopy. The patient was a 56-year-old female who was hospitalized for hyponatremia and diagnosed with SIADH based on a detailed examination. During the course, she developed impaired consciousness due to acute hydrocephalus, which improved after ventricular drainage. Head magnetic resonance imaging (MRI) confirmed nodular lesions at the floor of the third ventricle and the cerebral aqueduct. Neuroendoscopic biopsy led to the diagnosis of neurosarcoidosis. Her hyponatremia improved after steroid therapy. Neurosarcoidosis can cause SIADH, and complication of hydrocephalus may lead to a poor prognosis. Neuroendoscopy appears to be effective for the diagnosis of neurosarcoidosis with hydrocephalus and helps in deciding the treatment modality

Temperature–amplitude coupling for stable biological rhythms at different temperatures

<div><p>Most biological processes accelerate with temperature, for example cell division. In contrast, the circadian rhythm period is robust to temperature fluctuation, termed temperature compensation. Temperature compensation is peculiar because a system-level property (i.e., the circadian period) is stable under varying temperature while individual components of the system (i.e., biochemical reactions) are usually temperature-sensitive. To understand the mechanism for period stability, we measured the time series of circadian clock transcripts in cultured C6 glioma cells. The amplitudes of <i>Cry1</i> and <i>Dbp</i> circadian expression increased significantly with temperature. In contrast, other clock transcripts demonstrated no significant change in amplitude. To understand these experimental results, we analyzed mathematical models with different network topologies. It was found that the geometric mean amplitude of gene expression must increase to maintain a stable period with increasing temperatures and reaction speeds for all models studied. To investigate the generality of this temperature–amplitude coupling mechanism for period stability, we revisited data on the yeast metabolic cycle (YMC) period, which is also stable under temperature variation. We confirmed that the YMC amplitude increased at higher temperatures, suggesting temperature-amplitude coupling as a common mechanism shared by circadian and 4 h-metabolic rhythms.</p></div

MAGI-1 Is Required for Rap1 Activation upon Cell-Cell Contact and for Enhancement of Vascular Endothelial Cadherin-mediated Cell Adhesion

Rap1 is a small GTPase that regulates adherens junction maturation. It remains elusive how Rap1 is activated upon cell-cell contact. We demonstrate for the first time that Rap1 is activated upon homophilic engagement of vascular endothelial cadherin (VE-cadherin) at the cell-cell contacts in living cells and that MAGI-1 is required for VE-cadherin-dependent Rap1 activation. We found that MAGI-1 localized to cell-cell contacts presumably by associating with β-catenin and that MAGI-1 bound to a guanine nucleotide exchange factor for Rap1, PDZ-GEF1. Depletion of MAGI-1 suppressed the cell-cell contact-induced Rap1 activation and the VE-cadherin-mediated cell-cell adhesion after Ca(2+) switch. In addition, relocation of vinculin from cell-extracellular matrix contacts to cell-cell contacts after the Ca(2+) switch was inhibited in MAGI-1-depleted cells. Furthermore, inactivation of Rap1 by overexpression of Rap1GAPII impaired the VE-cadherin-dependent cell adhesion. Collectively, MAGI-1 is important for VE-cadherin-dependent Rap1 activation upon cell-cell contact. In addition, once activated, Rap1 upon cell-cell contacts positively regulate the adherens junction formation by relocating vinculin that supports VE-cadherin-based cell adhesion

Menthol-enhanced cytotoxicity of cigarette smoke demonstrated in two bioassay models

Background Cigarette smoke is harmful to human health at both cellular and genetic levels. Recently, a unique bioassay for smoke cytotoxicity using air pollution-sensitive plant cells (tobacco) has been proposed. Methods Model plant cells (tobacco Bel-W3 cells) and human cells (alveolar epithelial A549 cells) suspended in fresh culture media were exposed to cigarette smoke sampled after lighting the tip of cigarettes (with vs. without menthol capsules) which were attached to a glass pipe connected to the cell-containing plastic tubes. Control cultures were also assessed. Results After exposing tobacco plant cells to cigarette smoke, cell death occurred in a dose-dependent manner. Cell death was significantly enhanced by mentholated smoke, while menthol alone was shown to be inert suggesting that menthol synergistically contributes to the enhancement of cell death, initiated by smoke-associated compounds. The enhanced toxicity of mentholated smoke was confirmed in human alveolar epithelial A549 cells. Conclusions Cigarette smoke cytotoxicity leading to cell death assessed in plant and human model cells was enhanced by menthol. Further research into these findings is encouraged

Sensitivities of period and amplitude to temperature in a detailed mammalian circadian model [30].

<p>(A-D) Temperature-dependent time series of oscillatory variables for the model proposed by Kim and Forger (2012). We used the original parameter set described [<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005501#pcbi.1005501.ref030" target="_blank">30</a>] and randomly increased the reaction rate parameters. Here we show examples of calculated time series for <i>Bmal1</i>, <i>Per2</i>, <i>Cry1</i>, and <i>Reverb</i> mRNAs at high (red) and low temperature (blue). Parameter values are listed in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005501#pcbi.1005501.s001" target="_blank">S1 Text</a>. (E) Distribution of geometric mean of all relative amplitudes (180 variables) as a function of relative period for 2,495 parameter sets as reaction rates are increased. We randomly increased parameter values from 1.1- to 1.9-fold and generated a total of 10,000 parameter sets. The average parameter increase was ~1.5-fold. Of these sets, oscillations are sustained for 2,495. For each set, we plot the distribution of period change. (F) Variation in the parameter sets yielding relatively stable period (ratio of the new period to the original period >0.8). We assume that the parameter for “volume ratio between cytosol and nucleus (<i>Nf</i>)” is not sensitive to temperature and so was fixed. Ordinary differential equations were solved numerically using the Euler method with Δ<i>t</i> = 0.001.</p