Distinct predictive performance of Rac1 and Cdc42 in cell migration.

We propose a new computation-based approach for elucidating how signaling molecules are decoded in cell migration. In this approach, we performed FRET time-lapse imaging of Rac1 and Cdc42, members of Rho GTPases which are responsible for cell motility, and quantitatively identified the response functions that describe the conversion from the molecular activities to the morphological changes. Based on the identified response functions, we clarified the profiles of how the morphology spatiotemporally changes in response to local and transient activation of Rac1 and Cdc42, and found that Rac1 and Cdc42 activation triggers laterally propagating membrane protrusion. The response functions were also endowed with property of differentiator, which is beneficial for maintaining sensitivity under adaptation to the mean level of input. Using the response function, we could predict the morphological change from molecular activity, and its predictive performance provides a new quantitative measure of how much the Rho GTPases participate in the cell migration. Interestingly, we discovered distinct predictive performance of Rac1 and Cdc42 depending on the migration modes, indicating that Rac1 and Cdc42 contribute to persistent and random migration, respectively. Thus, our proposed predictive approach enabled us to uncover the hidden information processing rules of Rho GTPases in the cell migration

A novel frameshift mutation in the fibrinogen γC terminal region, FGG c.1169_1170 del AT, leading to hypofibrinogenemia

ArticleTHROMBOSIS RESEARCH.159:82-85(2017)journal articl

Estimation of Newtonian noise from KAGRA cooling system

KAGRA is the first km-scale gravitational wave detector to be constructed underground and employ cryogenics to cool down its test masses. While the underground location provides a quiet site with low seismic noise, the cooling infrastructure is known to generate large mechanical vibrations due to cryocooler operation and structural resonances of the cryostat. As cooling system components are relatively heavy and in close proximity to the test masses, oscillation of gravity force induced by their vibration, so-called Newtonian noise, could contaminate the detector sensitivity. In this paper, we use the results from vibration analysis of the KAGRA cryostat to estimate cooling system Newtonian noise in the 1-100 Hz frequency band. Our calculations show that, while this noise does not limit the current detector sensitivity or inspiral range, it will be an issue in the future when KAGRA improves its sensitivity. We conclude that KAGRA may need to implement Wiener filters to subtract this noise in the future

Genetic analyses of novel compound heterozygous hypodysfibrinogenemia, Tsukuba I: FGG c.1129+62_65 del AATA and FGG c.1299+4 del A

Epub 2016 Nov 5Introduction: Wefound a novel hypodysfibrinogenemia designated Tsukuba I caused by compound heterozygous nucleotide deletionswith FGG c. 1129+ 62_ 65 del AATA and FGG c. 1299+ 4 del A on different alleles. The former was deep in intron 8 of FGG (IVS-8 deletion) and the latter in exon 9 of FGG (Ex-9 deletion), which is translated for the gamma'-chain, but not the.A-chain. AWestern blot analysis of plasma fibrinogen from our patient revealed an aberrant gamma-chain that migrated slightly faster than the normal B beta-chain. Materials andmethods: To clarify the complex genetic mechanismunderlying Tsukuba I's hypodysfibrinogenemia induced by nucleotide deletions in two regions, we generated two minigenes incorporating each deletion region, transfected them into Chinese Hamster Ovary (CHO) cells, and analyzed RT-PCR products. We also established CHO cells producing the recombinant variant fibrinogen,gamma' 409.A (Ex-9 deletion). Results and conclusions: Minigene I incorporating the IVS-8 deletion showed two products: a normal splicing product and the unspliced product. Minigene II incorporating the Ex-9 deletion only produced the unspliced product. The established gamma' 409.A-CHOcells secreted variant fibrinogenmore effectively than normal fibrinogen. Therefore, the aberrant splicing products derived from the IVS-8 deletion cause hypofibrinogenemia most likely due to nonsense-mediated mRNA decay and the partial production of normal.A-and gamma'-chains; moreover, the Ex-9 deletion causes hypodysfibrinogenemia due to the absence of normal.A-and gamma'-chain production (hypofibrinogenemia) and augmented aberrant.'-chain production (dysfibrinogenemia). (C) 2016 Elsevier Ltd. All rights reserved.ArticleTHROMBOSIS RESEARCH. 148:111-117 (2016)journal articl

Progressing subglottic and tracheobronchial stenosis in a patient with CHARGE syndrome diagnosed in adulthood

AbstractA 33-year-old woman was admitted for a pseudocroup-like cough and wheezing after general anesthesia. Several months ago, she had undergone cardiac re-operation and turbinectomy, both of which had involved difficult intubations. Bronchoscopy indicated a pin-hall-like subglottic stenosis; therefore, emergency tracheotomy was performed. Six years later, a computed tomography scan demonstrated progressive stenosis of the entire circumference of the trachea and main bronchi. She died at 40 years. Her autopsy revealed marked tracheobronchial stenosis. She had many medical histories that had gone undiagnosed and had been clinically ill with only heart defects. She did not have coloboma but had microphthalmos, atresia choanae, retarded growth development, and deafness; thus, we diagnosed CHARGE syndrome that refers to multiple congenital anomalies, including airway abnormalities, which can lead to secondary complications such as traumatic stenosis after intubation. Physicians should have knowledge of this rare disease and should pay special attention to potential airway problems

Do People Explicitly Make a Frame Choice Based on the Reference Point?

Previous studies have shown that when choosing one of two logically equivalent frames (e.g., “half full” or “half empty”), people tend to choose based on a reference point. For example, when the amount of water in a glass with 500 ml capacity was originally 0 ml (or 500 ml), and then increased (or decreased) to 250 ml, people tend to express the amount of water in the glass as “half full” (or “half empty”). In the present study, we examined whether participants explicitly made a frame choice based on the reference point. We conducted four behavioral experiments relating to frame choice tasks. Specifically, participants were presented with a story-based or prime-based reference point and then made a frame choice. Furthermore, participants provided their reasons for the choice. Our findings on frame choices and their reasons can be summarized as follows. First, when participants were presented with a story-based reference point, some of them reported that they made frame choices based on the reference point. Second, when a reference point was presented as a prime, participants’ frame choices were affected by this reference point. However, almost no participants reported that they made frame choices based on the reference point. These results indicate that the effect of reference points on frame choices is robust and that people do not always explicitly make frame choices based on the reference point