Differential pathotropism of non-immortalized and immortalized human neural stem cell lines in a focal demyelination model

Cell therapy is reaching the stage of phase I clinical trials for post-traumatic, post-ischemic, or neurodegenerative disorders, and the selection of the appropriate cell source is essential. In order to assess the capacity of different human neural stem cell lines (hNSC) to contribute to neural tissue regeneration and to reduce the local inflammation after an acute injury, we transplanted GMP-grade non-immortalized hNSCs and v-myc (v-IhNSC), c-myc T58A (T-IhNSC) immortalized cells into the corpus callosum of adult rats after 5 days from focal demyelination induced by lysophosphatidylcholine. At 15 days from transplantation, hNSC and T-IhNSC migrated to the lesioned area where they promoted endogenous remyelination and differentiated into mature oligodendrocytes, while the all three cell lines were able to integrate in the SVZ. Moreover, where demyelination was accompanied by an inflammatory reaction, a significant reduction of microglial cells’ activation was observed. This effect correlated with a differential migratory pattern of transplanted hNSC and IhNSC, significantly enhanced in the former, thus suggesting a specific NSC-mediated immunomodulatory effect on the local inflammation. We provide evidence that, in the subacute phase of a demyelination injury, different human immortalized and non-immortalized NSC lines, all sharing homing to the stem niche, display a differential pathotropism, both through cell-autonomous and non-cell autonomous effects. Overall, these findings promote IhNSC as an inexhaustible cell source for large-scale preclinical studies and non-immortalized GMP grade hNSC lines as an efficacious, safe, and reliable therapeutic tool for future clinical applications.     

硅上的智能适应系统

硅上的智能适应系统能够在微米／纳米尺度上和在恶劣及特殊的环境下工作，例如行星、发动机、人体和人造卫星等，所以，智能系统已经在许多工程中得到实际的应用。本书论述这种系统的关键技术和应用前景。     

A natural polymorphism alters odour and DEET sensitivity in an insect odorant receptor

Blood-feeding insects such as mosquitoes are efficient vectors of human infectious diseases because they are strongly attracted by body heat, carbon dioxide and odours produced by their vertebrate hosts. Insect repellents containing DEET (N,N-diethyl-meta-toluamide) are highly effective, but the mechanism by which this chemical wards off biting insects remains controversial despite decades of investigation. DEET seems to act both at close range as a contact chemorepellent, by affecting insect gustatory receptors, and at long range, by affecting the olfactory system. Two opposing mechanisms for the observed behavioural effects of DEET in the gas phase have been proposed: that DEET interferes with the olfactory system to block host odour recognition and that DEET actively repels insects by activating olfactory neurons that elicit avoidance behaviour. Here we show that DEET functions as a modulator of the odour-gated ion channel formed by the insect odorant receptor complex. The functional insect odorant receptor complex consists of a common co-receptor, ORCO (ref. 15) (formerly called OR83B; ref. 16), and one or more variable odorant receptor subunits that confer odour selectivity. DEET acts on this complex to potentiate or inhibit odour-evoked activity or to inhibit odour-evoked suppression of spontaneous activity. This modulation depends on the specific odorant receptor and the concentration and identity of the odour ligand. We identify a single amino-acid polymorphism in the second transmembrane domain of receptor OR59B in a Drosophila melanogaster strain from Brazil that renders OR59B insensitive to inhibition by the odour ligand and modulation by DEET. Our data indicate that natural variation can modify the sensitivity of an odour-specific insect odorant receptor to odour ligands and DEET. Furthermore, they support the hypothesis that DEET acts as a molecular 'confusant' that scrambles the insect odour code, and provide a compelling explanation for the broad-spectrum efficacy of DEET against multiple insect species.     

Genome-wide association study identifies susceptibility loci for IgA nephropathy

We carried out a genome-wide association study of IgA nephropathy, a major cause of kidney failure worldwide. We studied 1,194 cases and 902 controls of Chinese Han ancestry, with targeted follow up in Chinese and European cohorts comprising 1,950 cases and 1,920 controls. We identified three independent loci in the major histocompatibility complex, as well as a common deletion of CFHR1 and CFHR3 at chromosome 1q32 and a locus at chromosome 22q12 that each surpassed genome-wide significance (P values for association between 1.59 × 10?2? and 4.84 × 10?? and minor allele odds ratios of 0.63-0.80). These five loci explain 4-7% of the disease variance and up to a tenfold variation in interindividual risk. Many of the alleles that protect against IgA nephropathy impart increased risk for other autoimmune or infectious diseases, and IgA nephropathy risk allele frequencies closely parallel the variation in disease prevalence among Asian, European and African populations, suggesting complex selective pressures.     

Effect of anabolic androgens on granulation tissue production in the rabbit

Résumé Les auteurs ont contrôlé l'effet de trois stéroïdes anabolisants sur la production du tissu de granulation par la méthode de la plaie cutanée chez le lapin. L'administration isolée de ces stéroïdes n'a modifié ni la quantité, ni la morphologie du tissue de granulation. L'association avec corticostéroïde, la fluprédnisolone, a donné des résultats différents selon la dose employée: en dose élévée, les anabolisants ont potencié l'effet inhibiteur de la fluprédnisolone, en dose faible, par contre, il n'ont eu aucun effet.     

One-Mode Classification of a Three-Way Data Matrix

X is the automatic hierarchical classification of one mode (units or variables or occasions) of X on the basis of the other two. In this paper the case of OMC of units according to variables and occasions is discussed. OMC is the synthesis of a set of hierarchical classifications Delta obtained from X; e.g., the OMC of units is the consensus (synthesis) among the set of dendograms individually defined by clustering units on the basis of variables, separately for each given occasion of X. However, because Delta is often formed by a large number of classifications, it may be unrealistic that a single synthesis is representative of the entire set. In this case, subsets of similar (homegeneous) dendograms may be found in Delta so that a consensus representative of each subset may be identified. This paper proposes, PARtition and Least Squares Consensus cLassifications Analysis (PARLSCLA) of a set of r hierarchical classifications Delta. PARLSCLA identifies the best least-squares partition of Delta into m (1 <= m <= r) subsets of homogeneous dendograms and simultaneously detects the closest consensus classification (a median classification called Least Squares Consensus Dendogram (LSCD) for each subset. PARLSCLA is a generalization of the problem to find a least-squares consensus dendogram for Delta. PARLSCLA is formalized as a mixed-integer programming problem and solved with an iterative, two-step algorithm. The method proposed is applied to an empirical data set.     

An enhanced text categorization method based on improved text frequency approach and mutual information algorithm

Text categorization plays an important role in data mining. Feature selection is the most important process of text categorization. Focused on feature selection, we present an improved text frequency method for filtering of low frequency features to deal with the data preprocessing, propose an improved mutual information algorithm for feature selection, and develop an improved tf.idf method for characteristic weights evaluation. The proposed method is applied to the benchmark test set Reuters-21578 Top10 to examine its effectiveness. Numerical results show that the precision, the recall and the value of F1 of the proposed method are all superior to those of existing conventional methods.