Crude Extracts of Caenorhabditis elegans Suppress Airway Inflammation in a Murine Model of Allergic Asthma

Epidemiological studies suggest an inverse relationship between helminth infections and allergic disease, and several helminth-derived products have been shown to suppress allergic responses in animals. This study was undertaken to evaluate the effect of a crude extract of Caenorhabditis elegans on allergic airway inflammation in a murine model of asthma. Allergic airway inflammation was induced in BALB/c mice by sensitization with ovalbumin. The effect of the C. elegans crude extract on the development of asthma and on established asthma was evaluated by analyzing airway hyperresponsiveness, serum antibody titers, lung histology and cell counts and cytokine levels in the bronchoalveolar lavage fluid. The role of IFN-γ in the suppression of asthma by the C. elegans crude extract was investigated in IFN-γ knockout and wild-type mice. When mice were sensitized with ovalbumin together with the crude extract of C. elegans, cellular infiltration into the lung was dramatically reduced in comparison with the ovalbumin-treated group. Treatment of mice with the C. elegans crude extract significantly decreased methacholine-induced airway hyperresponsiveness and the total cell counts and levels of IL-4, IL-5 and IL-13 in the bronchoalveolar lavage fluid but increased the levels of IFN-γ and IL-12. Sensitization with the C. elegans crude extract significantly diminished the IgE and IgG1 responses but provoked elevated IgG2a levels. However, the suppressive effect of the C. elegans crude extract was abolished in IFN-γ knockout mice, and the Th2 responses in these mice were as strong as those in wild-type mice sensitized with ovalbumin. The crude extract of C. elegans also suppressed the airway inflammation associated with established asthma. This study provides new insights into immune modulation by the C. elegans crude extract, which suppressed airway inflammation in mice not only during the development of asthma but also after its establishment by skewing allergen-induced Th2 responses to Th1 responses

Multiple Classifier Fusion using k-Nearest Localized Templates

Abstract. This paper presents a method for combining classifiers that uses knearest localized templates. The localized templates are estimated from a training set using C-means clustering algorithm, and matched to the decision profile of a new incoming sample by a similarity measure. The sample is assigned to the class which is most frequently represented among the k most similar templates. The appropriate value of k is determined according to the characteristics of the given data set. Experimental results on real and artificial data sets show that the proposed method performs better than the conventional fusion methods

An Antioxidant Defense System in Radiation-Resistant Bacterium <em>Deinococcus geothermalis</em> against Oxidative Stress

A radiation-resistant bacterium, Deinococcus geothermalis has various stress response mechanisms, including antioxidation. Features that maintain vitality at high radiation doses include the following: enzymatic scavengers of ROS such as catalase, SOD, and peroxidase; strain-specific DNA repair systems such as Deinococcal unique proteins; non-enzymatic responses such as manganese complexes, carotenoids, and DNA-binding proteins. This chapter summarizes the primary response mechanism by redox balance centered on the cystine transporter. It also reviews action characteristics of DNA-binding protein Dps and a putative LysR family protein, and effects on loss of function of the carotenoid biosynthesis genes by transposition of insertion sequences. Environmental adaptation and molecular evolution of radiation-resistant bacterium are also considered to explain the potentials of molecular behavior induced by oxidative stress

Effect of Adenotonsillectomy on Attention in Korean Children With Sleep-Disordered Breathing

Objectives Pediatric sleep-disordered breathing (SDB) is a common debilitating disorder that can adversely affect the attention and academic performance of school-age children. Unfortunately, only a few studies have examined the effect of SDB treatment on attention in pediatric populations. Therefore, the aim of this study was to prospectively investigate the effect of SDB treatment on attention in children. Methods This study consecutively enrolled SDB children with adenotonsillar hypertrophy. All subjects underwent standard-of-care treatment (adenotonsillectomy or close observation) and were evaluated using a computerized comprehensive attention test at the initial visit. Comprehensive attention tests consisted of both sustained and divided attention tasks. Each completed task was assigned an attention score, which was based on the number of omission or commission errors. The comprehension attention test was repeated 1 year later. Results A total of 171 children who underwent adenotonsillectomy and 32 children who did not undergo adenotonsillectomy were included in this study. At baseline, there was no significant difference according to the score of all type comprehension attention tests between children in the adenotonsillectomy group and in the observation group. One year after treatment, children in the adenotonsillectomy group had significantly improved scores in all attention tasks. Children in the observation group had only significant improvement in omission errors on sustained attention tasks. Meanwhile, the attention score based on commission errors of divided attention tasks was significantly worse than at baseline for those. Conclusion Our study showed that adenotonsillectomy may be helpful in improving attention in children with SDB

Prediction of Quantitative Traits Using Common Genetic Variants: Application to Body Mass Index

With the success of the genome-wide association studies (GWASs), many candidate loci for complex human diseases have been reported in the GWAS catalog. Recently, many disease prediction models based on penalized regression or statistical learning methods were proposed using candidate causal variants from significant single-nucleotide polymorphisms of GWASs. However, there have been only a few systematic studies comparing existing methods. In this study, we first constructed risk prediction models, such as stepwise linear regression (SLR), least absolute shrinkage and selection operator (LASSO), and Elastic-Net (EN), using a GWAS chip and GWAS catalog. We then compared the prediction accuracy by calculating the mean square error (MSE) value on data from the Korea Association Resource (KARE) with body mass index. Our results show that SLR provides a smaller MSE value than the other methods, while the numbers of selected variables in each model were similar

Vestibular dysfunction in lateral semicircular canal dysplasia

IntroductionLateral semicircular canal (LSCC) dysplasia is the most common inner ear malformation. The severity of dysplasia can appear in various spectrums, from a short and broad LSCC with normal or small-sized central bony island (CBI) to a single fluid-filled cavity confluent with the vestibule without CBI. However, reports on the association between LSCC dysplasia and the loss of vestibular function are still lacking. In this study, the results of vestibular function tests [caloric test and video-head impulse test (vHIT)] in patients with LSCC dysplasia were analyzed and compared between groups with and without CBI.MethodsThis study retrospectively enrolled 17 patients (23 ears) who had LSCC dysplasia following computed tomography or magnetic resonance imaging and underwent vestibular function tests.ResultsLSCC dysplasia was observed unilaterally in 11 patients and bilaterally in six patients. Nine of 23 ears had CBIs, and 14 ears had no CBI. Three of 17 patients experienced dizziness. Abnormal caloric tests were detected in 11 of the 16 patients who underwent the caloric tests (69%); in contrast, 11 of 12 patients who underwent the vHIT (92%) had normal LSCC vestibulo-ocular reflex (VOR) gain on vHIT. A significant correlation was found between the maximum slow-phase velocity of the caloric test and LSCC VOR gain of the vHIT (correlation coefficient 0.792, p = 0.004). The CBI-absent group showed significantly lower SPV and LSCC VOR gains than the CBI-present group (p = 0.001 and 0.004, respectively).DiscussionLSCC dysplasia impairs VOR function, especially in the absence of CBI

Homeobox gene Dlx-2 is implicated in metabolic stress-induced necrosis

<p>Abstract</p> <p>Background</p> <p>In contrast to tumor-suppressive apoptosis and autophagic cell death, necrosis promotes tumor progression by releasing the pro-inflammatory and tumor-promoting cytokine high mobility group box 1 (HMGB1), and its presence in tumor patients is associated with poor prognosis. Thus, necrosis has important clinical implications in tumor development; however, its molecular mechanism remains poorly understood.</p> <p>Results</p> <p>In the present study, we show that Distal-less 2 (Dlx-2), a homeobox gene of the Dlx family that is involved in embryonic development, is induced in cancer cell lines dependently of reactive oxygen species (ROS) in response to glucose deprivation (GD), one of the metabolic stresses occurring in solid tumors. Increased Dlx-2 expression was also detected in the inner regions, which experience metabolic stress, of human tumors and of a multicellular tumor spheroid, an <it>in vitro </it>model of solid tumors. Dlx-2 short hairpin RNA (shRNA) inhibited metabolic stress-induced increase in propidium iodide-positive cell population and HMGB1 and lactate dehydrogenase (LDH) release, indicating the important role(s) of Dlx-2 in metabolic stress-induced necrosis. Dlx-2 shRNA appeared to exert its anti-necrotic effects by preventing metabolic stress-induced increases in mitochondrial ROS, which are responsible for triggering necrosis.</p> <p>Conclusions</p> <p>These results suggest that Dlx-2 may be involved in tumor progression via the regulation of metabolic stress-induced necrosis.</p

Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A

Hepatitis C virus (HCV) utilizes autophagy to promote its propagation. Here we show the autophagy-mediated suppression of HCV replication via the endoplasmic reticulum (ER) protein SCOTIN. SCOTIN overexpression inhibits HCV replication and infectious virion production in cells infected with cell culture-derived HCV. HCV nonstructural 5A (NS5A) protein, which is a critical factor for HCV RNA replication, interacts with the IFN-beta-inducible protein SCOTIN, which transports NS5A to autophagosomes for degradation. Furthermore, the suppressive effect of SCOTIN on HCV replication is impaired in both ATG7-silenced cells and cells treated with autophagy or lysosomal inhibitors. SCOTIN does not affect the overall flow of autophagy; however, it is a substrate for autophagic degradation. The physical association between the transmembrane/proline-rich domain (TMPRD) of SCOTIN and Domain-II of NS5A is essential for autophagosomal trafficking and NS5A degradation. Altogether, our findings suggest that IFN-beta-induced SCOTIN recruits the HCV NS5A protein to autophagosomes for degradation, thereby restricting HCV replication.1110Ysciescopu