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31.
Smuc Michael Mayr Eva Lammarsch Tim Aigner Wolfgang Miksch Silvia G rtner Johannes 《Computer Graphics and Applications, IEEE》2009,29(3):29-38
For evaluating visual-analytics tools, many studies confine to scoring user insights into data. For participatory design of those tools, we propose a three-level methodology to make more out of users' insights. The Relational Insight Organizer (RIO) helps to understand how insights emerge and build on one each other. 相似文献
32.
Aigner W Miksch S Müller W Schumann H Tominski C 《IEEE transactions on visualization and computer graphics》2008,14(1):47-60
Providing appropriate methods to facilitate the analysis of time-oriented data is a key issue in many application domains. In this paper, we focus on the unique role of the parameter time in the context of visually driven data analysis. We will discuss three major aspects - visualization, analysis, and the user. It will be illustrated that it is necessary to consider the characteristics of time when generating visual representations. For that purpose we take a look at different types of time and present visual examples. Integrating visual and analytical methods has become an increasingly important issue. Therefore, we present our experiences in temporal data abstraction, principal component analysis, and clustering of larger volumes of time-oriented data. The third main aspect we discuss is supporting user-centered visual analysis. We describe event-based visualization as a promising means to adapt the visualization pipeline to needs and tasks of users. 相似文献
33.
Costanzi S Vincenzetti S Cristalli G Vita A 《Journal of molecular graphics & modelling》2006,25(1):10-16
Cytidine deaminase (CDA) is a cytosolic metalloprotein whose functional unit can be either a homotetramer (T-CDA) or a homodimer (D-CDA), depending on the species. In 1994, the first crystal structure of the dimeric Escherichia coli CDA has been published. However, a crystal structure of a tetrameric CDA was not determined until 2002. Prior to the disclosure of the experimentally elucidated structure of a tetrameric CDA, we derived a homology model of the human T-CDA employing the crystal structure of the dimeric E. coli CDA as a template. The comparison of our theoretical model with the crystal structure of the human T-CDA, subsequently published in 2004, validates our prediction: not only of the structural features of the monomer and the details of the binding site, but also the multimeric arrangement of the subunits were determined with high accuracy in our model. By means of a phylogenetic analysis conducted on CDAs from various organisms, we demonstrate that the E. coli CDA is one of the furthest known homologues of the human enzyme. Nonetheless, despite the evolutionary distance and, more importantly, the different multimeric arrangement of their functional units, the E. coli CDA proved to have all the necessary information to accurately infer the structure of its human homologue. 相似文献
34.
Marina Martello Vincenza Solli Rosalinda Termini Ajsi Kanapari Daniel Remondini Enrica Borsi Andrea Poletti Silvia Armuzzi Barbara Taurisano Ilaria Vigliotta Gaia Mazzocchetti Elena Zamagni Alessandra Merlotti Paola Tacchetti Lucia Pantani Serena Rocchi Ilaria Rizzello Katia Mancuso Michele Cavo Carolina Terragna 《International journal of molecular sciences》2022,23(20)
DNA microarrays and RNA-based sequencing approaches are considered important discovery tools in clinical medicine. However, cross-platform reproducibility studies undertaken so far have highlighted that microarrays are not able to accurately measure gene expression, particularly when they are expressed at low levels. Here, we consider the employment of a digital PCR assay (ddPCR) to validate a gene signature previously identified by gene expression profile. This signature included ten Hedgehog (HH) pathways’ genes able to stratify multiple myeloma (MM) patients according to their self-renewal status. Results show that the designed assay is able to validate gene expression data, both in a retrospective as well as in a prospective cohort. In addition, the plasma cells’ differentiation status determined by ddPCR was further confirmed by other techniques, such as flow cytometry, allowing the identification of patients with immature plasma cells’ phenotype (i.e., expressing CD19+/CD81+ markers) upregulating HH genes, as compared to others, whose plasma cells lose the expression of these markers and were more differentiated. To our knowledge, this is the first technical report of gene expression data validation by ddPCR instead of classical qPCR. This approach permitted the identification of a Maturation Index through the integration of molecular and phenotypic data, able to possibly define upfront the differentiation status of MM patients that would be clinically relevant in the future. 相似文献
35.
Tomas Selicky Matus Jurcik Barbora Mikolaskova Alexandra Pitelova Nina Mayerova Miroslava Kretova Michaela Osadska Jan Jurcik Roman Holic Lenka Kohutova Jana Bellova Zsigmond Benko Juraj Gregan Silvia Bagelova Polakova Peter Barath Lubos Cipak Ingrid Cipakova 《International journal of molecular sciences》2022,23(21)
36.
Sebastian Andone Lnrd Farczdi Silvia Imre Rodica Blaa 《International journal of molecular sciences》2022,23(18)
Stroke is the primary cause of death and disability worldwide, with ischemic stroke up to 80% of the total cases. Lipid profile was established as a major risk factor for stroke, but recent studies show a paradoxical relationship between serum values and the outcome of stroke patients. Our study aims to analyze the impact of the classic extended lipid profile, including fatty acids as potential neuroprotective biomarkers for the outcome of ischemic stroke patients. We included 298 patients and collected clinical, paraclinical, and outcome parameters. We used a method consisting of high-performance liquid chromatography coupled with mass spectrometry to quantify serum fatty acids. We observed a negative correlation between National Institutes of Health Stroke Scale (NIHSS) at admission and total cholesterol (p = 0.040; r = −0.120), respectively triglycerides (p = 0.041; r = −0.122). The eicosapentaenoic to arachidonic acid ratio has a negative correlation, while the docosahexaenoic to eicosapentaenoic acid ratio positively correlates with all the prognostic parameters, showing a potential neuroprotective role for eicosapentaenoic acid in preventing severe ischemic stroke. The impact of the lipid profile paradox and the dependency relationship with the fatty acids represent a significant predictive factor for the functional and disability prognostic of ischemic stroke patients. 相似文献
37.
Ines Maestro Laura R. de la Ballina Gracia Porras Silvia Corrochano Eva De Lago Anne Simonsen Patricia Boya Ana Martinez 《International journal of molecular sciences》2022,23(20)
Mitophagy is the selective degradation of mitochondria by autophagy. It promotes the turnover of mitochondria and prevents the accumulation of dysfunctional mitochondria, which can lead to cellular degeneration. Mitophagy is known to be altered in several pathological conditions, especially in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We recently demonstrated an increase in autophagy flux in lymphoblasts from ALS patients bearing a mutation in SOD1. Thus, the identification of mitophagy inhibitors may be a therapeutic option to recover mitochondrial homeostasis. Here, using a phenotypic mitophagy assay, we identified a new mitophagy inhibitor, the small molecule named IGS2.7 from the MBC library. Interestingly, the treatment of different cellular and in vivo models of ALS with mutations on SOD1 and TARDBP with this inhibitor restores autophagy to control levels. These results point mitophagy inhibitors, especially IGS2.7, to a new therapeutic approach for familial ALS patients. 相似文献
38.
Silvia Pomella Antonella Porrazzo Matteo Cassandri Simona Camero Silvia Codenotti Luisa Milazzo Francesca Vulcano Giovanni Barillari Giovanni Cenci Cinzia Marchese Alessandro Fanzani Francesca Megiorni Rossella Rota Francesco Marampon 《International journal of molecular sciences》2022,23(21)
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and adolescence that includes FP-RMS, harboring the fusion oncoprotein PAX3/7-FOXO1 and FN-RMS, often mutant in the RAS pathway. Risk stratifications of RMS patients determine different prognostic groups and related therapeutic treatment. Current multimodal therapeutic strategies involve surgery, chemotherapy (CHT) and radiotherapy (RT), but despite the deeper knowledge of response mechanisms underpinning CHT treatment and the technological improvements that characterize RT, local failures and recurrence frequently occur. This review sums up the RMS classification and the management of RMS patients, with special attention to RT treatment and possible radiosensitizing strategies for RMS tumors. Indeed, RMS radioresistance is a clinical problem and further studies aimed at dissecting radioresistant molecular mechanisms are needed to identify specific targets to hit, thus improving RT-induced cytotoxicity. 相似文献
39.
Shelley Waters Silvia Lee Ibnu Ariyanto Shay Leary Kylie Munyard Silvana Gaudieri Ashley Irish Richard J. N. Allcock Patricia Price 《International journal of molecular sciences》2022,23(21)
Around 80% of adults worldwide carry human cytomegaloviris (HCMV). The HCMV gene UL18 is a homolog of HLA class I genes and encodes a protein with high affinity for the NK and T-cell cytotoxicity inhibitor LIR-1. UL18 was deep sequenced from blood, saliva or urine from Indonesian people with HIV (PWH) (n = 28), Australian renal transplant recipients (RTR) (n = 21), healthy adults (n = 7) and neonates (n = 4). 95% of samples contained more than one variant of HCMV UL18, as defined by carriage of nonsynonymous variations. When aligned with immunological markers of the host’s burden of HCMV, the S318N variation associated with high levels of antibody reactive with HCMV lysate in PWH over 12 months on antiretroviral therapy. The A107T variation associated with HCMV antibody levels and inflammatory biomarkers in PWH at early timepoints. Variants D32G, D248N, V250A and E252D aligned with elevated HCMV antibody levels in RTR, while M191K, E196Q and F165L were associated with HCMV-reactive T-cells and proportions of Vδ2− γδ T-cells—populations linked with high burdens of HCMV. We conclude that UL18 is a highly variable gene, where variation may alter the persistent burden of HCMV and/or the host response to that burden. 相似文献
40.
Sara Perego Valentina Alari Gianluca Pietra Andrea Lamperti Alessandro Vimercati Nicole Camporeale Maria Garzo Francesca Cogliati Donatella Milani Aglaia Vignoli Angela Peron Lidia Larizza Tommaso Pizzorusso Silvia Russo 《International journal of molecular sciences》2022,23(22)
Rett syndrome caused by MECP2 variants is characterized by a heterogenous clinical spectrum accounted for in 60% of cases by hot-spot variants. Focusing on the most frequent variants, we generated in vitro iPSC-neurons from the blood of RTT girls with p.Arg133Cys and p.Arg255*, associated to mild and severe phenotype, respectively, and of an RTT male harboring the close to p.Arg255*, p.Gly252Argfs*7 variant. Truncated MeCP2 proteins were revealed by Western blot and immunofluorescence analysis. We compared the mutant versus control neurons at 42 days for morphological parameters and at 120 days for electrophysiology recordings, including girls’ isogenic clones. A precocious reduced morphological complexity was evident in neurons with truncating variants, while in p.Arg133Cys neurons any significant differences were observed in comparison with the isogenic wild-type clones. Reduced nuclear size and branch number show up as the most robust biomarkers. Patch clamp recordings on mature neurons allowed the assessment of cell biophysical properties, V-gated currents, and spiking pattern in the mutant and control cells. Immature spiking, altered cell capacitance, and membrane resistance of RTT neurons, were particularly pronounced in the Arg255* and Gly252Argfs*7 mutants. The overall results indicate that the specific markers of in vitro cellular phenotype mirror the clinical severity and may be amenable to drug testing for translational purposes. 相似文献