Tissue Characterization of Coronary Plaque by Using Fractal Analysis-based Features of IVUS RF-signal

We propose a precise tissue characterization method of coronary plaque by using fractal analysis-based features which are obtained from radiofrequency (RF) signal employing intravascular ultrasound (IVUS) method. The IVUS method is used for the diagnosis of the acute coronary syndromes (ACS). In the proposed method, the fact that the RF signal reflects the complexity of the structure of tissue is used. The effectiveness of the proposed method is verified through a series of experiments by using IVUS RF signals obtained from a rabbit and a human patient

Time-dependent and site-dependent morphological changes in rupture-prone arteries : ovariectomized rat intracranial aneurysm model

OBJECTIVE The pathogenesis of intracranial aneurysm rupture remains unclear. Because it is difficult to study the time course of human aneurysms and most unruptured aneurysms are stable, animal models are used to investigate the characteristics of intracranial aneurysms. The authors have newly established a rat intracranial aneurysm rupture model that features site-specific ruptured and unruptured aneurysms. In the present study the authors examined the time course of changes in the vascular morphology to clarify the mechanisms leading to rupture. METHODS Ten-week-old female Sprague-Dawley rats were subjected to hemodynamic changes, hypertension, and ovariectomy. Morphological changes in rupture-prone intracranial arteries were examined under a scanning electron microscope and the association with vascular degradation molecules was investigated. RESULTS At 2–6 weeks after aneurysm induction, morphological changes and rupture were mainly observed at the posterior cerebral artery; at 7–12 weeks they were seen at the anterior Willis circle including the anterior communicating artery. No aneurysms at the anterior cerebral artery–olfactory artery bifurcation ruptured, suggesting that the inception of morphological changes is site dependent. On week 6, the messenger RNA level of matrix metalloproteinase–9, interleukin-1β, and the ratio of matrix metalloproteinase–9 to the tissue inhibitor of metalloproteinase–2 was significantly higher at the posterior cerebral artery, but not at the anterior communicating artery, of rats with aneurysms than in sham-operated rats. These findings suggest that aneurysm rupture is attributable to significant morphological changes and an increase in degradation molecules. CONCLUSIONS Time-dependent and site-dependent morphological changes and the level of degradation molecules may be indicative of the vulnerability of aneurysms to rupture

偏光分解顕微鏡を用いたアルコール性肝線維症の線維化の量的・質的評価系の開発

Liver fibrosis is assessed mainly by conventional staining or second harmonic generation (SHG) microscopy, which can only provide collagen content in fibrotic area. We propose to use polarization-resolved SHG (PR-SHG) microscopy to quantify liver fibrosis in terms of collagen fiber orientation and crystallization. Liver samples obtained from autopsy cases with fibrosis stage of F0–F4 were evaluated with an SHG microscope, and 12 consecutive PR-SHG images were acquired while changing the polarization azimuth angle of the irradiated laser from 0° to 165° in 15° increments using polarizer. The fiber orientation angle (φ) and degree (ρ) of collagen were estimated from the images. The SHG-positive area increased as the fibrosis stage progressed, which was well consistent with Sirius Red staining. The value of φ was random regardless of fibrosis stage. The mean value of ρ (ρ-mean), which represents collagen fiber crystallinity, varied more as fibrosis progressed to stage F3, and converged to a significantly higher value in F4 than in other stages. Spatial dispersion of ρ (ρ-entropy) also showed increased variation in the stage F3 and decreased variation in the stage F4. It was shown that PR-SHG could provide new information on the properties of collagen fibers in human liver fibrosis

Sources of uncertainty in estimating stream solute export from headwater catchments at three sites

Uncertainty in the estimation of hydrologic export of solutes has never been fully evaluated at the scale of a small-watershed ecosystem. We used data from the Gomadansan Experimental Forest, Japan, Hubbard Brook Experimental Forest, USA, and Coweeta Hydrologic Laboratory, USA, to evaluate many sources of uncertainty, including the precision and accuracy of measurements, selection of models, and spatial and temporal variation. Uncertainty in the analysis of stream chemistry samples was generally small but could be large in relative terms for solutes near detection limits, as is common for ammonium and phosphate in forested catchments. Instantaneous flow deviated from the theoretical curve relating height to discharge by up to 10% at Hubbard Brook, but the resulting corrections to the theoretical curve generally amounted to \u3c0.5% of annual flows. Calibrations were limited to low flows; uncertainties at high flows were not evaluated because of the difficulties in performing calibrations during events. However, high flows likely contribute more uncertainty to annual flows because of the greater volume of water that is exported during these events. Uncertainty in catchment area was as much as 5%, based on a comparison of digital elevation maps with ground surveys. Three different interpolation methods are used at the three sites to combine periodic chemistry samples with streamflow to calculate fluxes. The three methods differed by \u3c5% in annual export calculations for calcium, but up to 12% for nitrate exports, when applied to a stream at Hubbard Brook for 1997–2008; nitrate has higher weekly variation at this site. Natural variation was larger than most other sources of uncertainty. Specifically, coefficients of variation across streams or across years, within site, for runoff and weighted annual concentrations of calcium, magnesium, potassium, sodium, sulphate, chloride, and silicate ranged from 5 to 50% and were even higher for nitrate. Uncertainty analysis can be used to guide efforts to improve confidence in estimated stream fluxes and also to optimize design of monitoring programmes

Tumour resistance in induced pluripotent stem cells derived from naked mole-rats

The naked mole-rat (NMR, Heterocephalus glaber), which is the longest-lived rodent species, exhibits extraordinary resistance to cancer. Here we report that NMR somatic cells exhibit a unique tumour-suppressor response to reprogramming induction. In this study, we generate NMR-induced pluripotent stem cells (NMR-iPSCs) and find that NMR-iPSCs do not exhibit teratoma-forming tumorigenicity due to the species-specific activation of tumour-suppressor alternative reading frame (ARF) and a disruption mutation of the oncogene ES cell-expressed Ras (ERAS). The forced expression of Arf in mouse iPSCs markedly reduces tumorigenicity. Furthermore, we identify an NMR-specific tumour-suppression phenotype—ARF suppression-induced senescence (ASIS)—that may protect iPSCs and somatic cells from ARF suppression and, as a consequence, tumorigenicity. Thus, NMR-specific ARF regulation and the disruption of ERAS regulate tumour resistance in NMR-iPSCs. Our findings obtained from studies of NMR-iPSCs provide new insight into the mechanisms of tumorigenicity in iPSCs and cancer resistance in the NMR

Synaptic activity prompts γ-secretase–mediated cleavage of EphA4 and dendritic spine formation

Alzheimer's disease is an age-dependent neurodegenerative disorder that is characterized by a progressive decline in cognitive function. γ-secretase dysfunction is evident in many cases of early onset familial Alzheimer's disease. However, the mechanism by which γ-secretase dysfunction results in memory loss and neurodegeneration is not fully understood. Here, we demonstrate that γ-secretase is localized at synapses and regulates spine formation. We identify EphA4, one of the Ephrin receptor family members, as a substrate of γ-secretase, and find that EphA4 processing is enhanced by synaptic activity. Moreover, overexpression of EphA4 intracellular domain increases the number of dendritic spines by activating the Rac signaling pathway. These findings reveal a function for EphA4-mediated intracellular signaling in the morphogenesis of dendritic spines and suggest that the processing of EphA4 by γ-secretase affects the pathogenesis of Alzheimer's disease

The differential role of L-selectin and ICAM-1 in Th1-type and Th2-type contact hypersensitivity.

Sensitization and challenge using DNFB induce contact hypersensitivity (CHS) with predominant type 1 helper (Th1) cell infiltration, whereas those using FITC generate CHS with Th2 cell infiltration. CHS results from inflammatory cell infiltration, a process that is highly regulated by the expression of multiple adhesion molecules. We attempted to determine the role of L-selectin and ICAM-1 in Th1- and Th2-type CHS induced by DNFB or FITC in mice lacking either L-selectin, ICAM-1, or both. Th1-type CHS induced by DNFB was inhibited by L-selectin and/or ICAM-1 deficiency, which was associated with reduced IFN-gamma expression. Similarly, Th2-type CHS induced by FITC was inhibited by L-selectin deficiency. However, Th2-type CHS was increased by ICAM-1 deficiency and accompanied by increased Th2 cytokine expression. Infiltration of in vitro-generated Th1 cells into the FITC-challenged skin decreased in ICAM-1-deficient mice, whereas in vitro-generated Th2 cell infiltration increased, suggesting that ICAM-1 mediates Th1 cell migration and that in the absence of ICAM-1, Th1 cell recruitment decreased, whereas relative Th2 cell migration increased. These results suggest that ICAM-1 mediates Th1 cell recruitment irrespective of DNFB or FITC and that L-selectin recruits Th1 cells in Th1-type CHS, whereas it recruits Th2 cells in Th2-type CHS