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861.
Dario Antonelli Elena Baralis Giulia Bruno Silvia Chiusano Naeem A. Mahoto Caterina Petrigni 《Flexible Services and Manufacturing Journal》2012,24(4):379-399
Colon cancer is a pathology that benefits largely from an early cure. There are screening guidelines well assessed and overall accepted in several world nations. The question is if they are actually applied in the healthcare practice. The difficulty in the analysis of the application of diagnostic pathways is in the necessity to do a sort of time travel in the past: to chose a group of patients that have the same diagnosis, say colon cancer, and to be able to trace the pathways that led to the diagnosis. By exploiting the ability of data mining techniques to extract sequences from large masses of raw data, it has been possible to reconstruct the actual diagnostic services accessed with larger frequency by the patients and even the sequence of accessed services. The results show that there is a large majority of patients that followed pathways differing from the standard guidelines. The study describes how the database was built, the techniques adopted to extract and group together the data and concludes with an analysis of the diagnostic pathways. 相似文献
862.
Diego Forni Rachele Cagliani Claudia Tresoldi Uberto Pozzoli Luca De Gioia Giulia Filippi Stefania Riva Giorgia Menozzi Marta Colleoni Mara Biasin Sergio Lo Caputo Francesco Mazzotta Giacomo P. Comi Nereo Bresolin Mario Clerici Manuela Sironi 《PLoS genetics》2014,10(3)
The antigenic repertoire presented by MHC molecules is generated by the antigen processing and presentation (APP) pathway. We analyzed the evolutionary history of 45 genes involved in APP at the inter- and intra-species level. Results showed that 11 genes evolved adaptively in mammals. Several positively selected sites involve positions of fundamental importance to the protein function (e.g. the TAP1 peptide-binding domains, the sugar binding interface of langerin, and the CD1D trafficking signal region). In CYBB, all selected sites cluster in two loops protruding into the endosomal lumen; analysis of missense mutations responsible for chronic granulomatous disease (CGD) showed the action of different selective forces on the very same gene region, as most CGD substitutions involve aminoacid positions that are conserved in all mammals. As for ERAP2, different computational methods indicated that positive selection has driven the recurrent appearance of protein-destabilizing variants during mammalian evolution. Application of a population-genetics phylogenetics approach showed that purifying selection represented a major force acting on some APP components (e.g. immunoproteasome subunits and chaperones) and allowed identification of positive selection events in the human lineage.We also investigated the evolutionary history of APP genes in human populations by developing a new approach that uses several different tests to identify the selection target, and that integrates low-coverage whole-genome sequencing data with Sanger sequencing. This analysis revealed that 9 APP genes underwent local adaptation in human populations. Most positive selection targets are located within noncoding regions with regulatory function in myeloid cells or act as expression quantitative trait loci. Conversely, balancing selection targeted nonsynonymous variants in TAP1 and CD207 (langerin). Finally, we suggest that selected variants in PSMB10 and CD207 contribute to human phenotypes. Thus, we used evolutionary information to generate experimentally-testable hypotheses and to provide a list of sites to prioritize in follow-up analyses. 相似文献
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865.
Giulia M. Stella Simona Inghilleri Ymera Pignochino Michele Zorzetto Tiberio Oggionni Patrizia Morbini Maurizio Luisetti 《Translational oncology》2014,7(5):650-655
Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. The most recent hypotheses on IPF pathogenesis suggest a central role of epithelial cell damage, followed by a dysregulated molecular cross talk between epithelial cells and fibroblasts. Thus, IPF progression has often been assimilated to that of cancer, and several signaling patterns appear to be disrupted in both diseases. Here, we analyze the expression in an IPF series of a panel of molecules, which are known to play a role in tumorigenic process. Our findings, although preliminary, reveal that IPF landscape is enriched in neoplastic potential expressed in a context of complex genomic polyclonality and cellular heterogeneity. These results provide a rationale for further investigations aimed to exploit—in a similar fashion to cancer—targeted therapies for a “precision medicine” approach to IPF. 相似文献
866.
Giovanna Gambarotta Giulia Ronchi Olivier Friard Pantaleo Galletta Isabelle Perroteau Stefano Geuna 《PloS one》2014,9(8)
Injury to the peripheral nerve induces dramatic changes in terms of cellular composition that are reflected on RNA quality and quantity, making messenger RNA expression analysis very complex. Several commonly used housekeeping genes are regulated following peripheral nerve injury and are thus not suitable for quantitative real-time PCR normalization; moreover, the presence of pseudogenes in some of them impairs their use. To deal with this problem, we have developed a new method to identify new stable housekeeping genes based on publicly available microarray data on normal and injured nerves. Four new candidate stable genes were identified and validated by quantitative real-time PCR analysis on nerves during the different phases after nerve injury: nerve degeneration, regeneration and remyelination. The stability measure of these genes was calculated with both NormFinder and geNorm algorithms and compared with six commonly used housekeeping genes. This procedure allowed us to identify two new and highly stable genes that can be employed for normalizing injured peripheral nerve data: ANKRD27 and RICTOR. Besides providing a tool for peripheral nerve research, our study also describes a simple and cheap procedure that can be used to identify suitable housekeeping genes in other tissues and organs. 相似文献
867.
868.
The ability to rapidly and accurately predict the effects of mutations on the physicochemical properties of proteins holds tremendous importance in the rational design of modified proteins for various types of industrial, environmental or pharmaceutical applications, as well as in elucidating the genetic background of complex diseases. In many cases, the absence of an experimentally resolved structure represents a major obstacle, since most currently available predictive software crucially depend on it. We investigate here the relevance of combining coarse-grained structure-based stability predictions with a simple comparative modeling procedure. Strikingly, our results show that the use of average to high quality structural models leads to virtually no loss in predictive power compared to the use of experimental structures. Even in the case of low quality models, the decrease in performance is quite limited and this combined approach remains markedly superior to other methods based exclusively on the analysis of sequence features. 相似文献
869.
Brancucci A Prete G Meraglia E di Domenico A Lugli V Penolazzi B Tommasi L 《PloS one》2012,7(3):e34367
The present study investigates hemispheric asymmetries in the neural adaptation processes occurring during alternating auditory stimulation. Stimuli were two monaural pure tones having a frequency of 400 or 800 Hz and a duration of 500 ms. Electroencephalogram (EEG) was recorded from 14 volunteers during the presentation of the following stimulus sequences, lasting 12 s each: 1) evoked potentials (EP condition, control), 2) alternation of frequency and ear (FE condition), 3) alternation of frequency (F condition), and 4) alternation of ear (E condition). Main results showed that in the central area of the left hemisphere (around C3 site) the N100 response underwent adaptation in all patterns of alternation, whereas in the same area of the right hemisphere the tones presented at the right ear in the FE produced no adaptation. Moreover, the responses to right-ear stimuli showed a difference between hemispheres in the E condition, which produced less adaptation in the left hemisphere. These effects are discussed in terms of lateral symmetry as a product of hemispheric, pathway and ear asymmetries. 相似文献
870.
A proper phytogeographic affiliation of Antarctic lichen species has become feasible using molecular phylogeographic methods. Caloplaca citrina is a heterogeneous taxon including several species which occurs in polar regions and is common in Antarctica. Collections of C. citrina from the Antarctic were revised using morphological, anatomical and molecular characters (ITS). They were found to belong to two species: Caloplaca darbishirei (C.W. Dodge & G.E. Baker) Cretz. and C. soropelta (E.S. Hansen, Poelt & S?chting) S?chting. The molecular phylogeny showed them to be sister species, but well separated. Morphological and chemical characters, ecology and distribution of the species are discussed. C. darbishirei is the most common species in the Antarctic, and it is so far known only from Antarctica and Southern South America. C. soropelta, reported here as new to South America, is a bipolar species with all close relatives in the Southern Hemisphere; it is therefore most likely that the species colonized the Arctic from the south. C. citrina s. str. is not confirmed to occur in Antarctica. The study emphasizes the suitability of genotyping for understanding the taxonomy and phylogeography of bipolar lichens. 相似文献