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971.
Marica Garziera Ettore Bidoli Erika Cecchin Enrico Mini Stefania Nobili Sara Lonardi Angela Buonadonna Domenico Errante Nicoletta Pella Mario D’Andrea Francesco De Marchi Antonino De Paoli Chiara Zanusso Elena De Mattia Renato Tassi Giuseppe Toffoli 《PloS one》2015,10(12)
An important hallmark of CRC is the evasion of immune surveillance. HLA-G is a negative regulator of host’s immune response. Overexpression of HLA-G protein in primary tumour CRC tissues has already been associated to worse prognosis; however a definition of the role of immunogenetic host background is still lacking. Germline polymorphisms in the 3’UTR region of HLA-G influence the magnitude of the protein by modulating HLA-G mRNA stability. Soluble HLA-G has been associated to 3’UTR +2960 Ins/Ins and +3035 C/T (lower levels) and +3187 G/G (high levels) genotypes. HLA-G 3’UTR SNPs have never been explored in CRC outcome. The purpose of this study was to investigate if common HLA-G 3’UTR polymorphisms have an impact on DFS and OS of 253 stage II-III CRC patients, after primary surgery and ADJ-CT based on FL. The 3’UTR was sequenced and SNPs were analyzed for their association with survival by Kaplan-Meier and multivariate Cox models; results underwent internal validation using a resampling method (bootstrap analysis). In a multivariate analysis, we estimated an association with improved DFS in Ins allele (Ins/Del +Ins/Ins) carriers (HR 0.60, 95% CI 0.38–0.93, P = 0.023) and in patients with +3035 C/T genotype (HR 0.51, 95% CI 0.26–0.99, P = 0.045). The +3187 G/G mutated carriers (G/G vs A/A+A/G) were associated to a worst prognosis in both DFS (HR 2.46, 95% CI 1.19–5.05, P = 0.015) and OS (HR 2.71, 95% CI 1.16–6.63, P = 0.022). Our study shows a prognostic and independent role of 3 HLA-G 3’UTR SNPs, +2960 14-bp INDEL, +3035 C>T, and +3187 A>G. 相似文献
972.
Enke Baldini Chiara Tuccilli Natalie Prinzi Salvatore Sorrenti Laura Falvo Corrado De Vito Antonio Catania Francesco Tartaglia Renzo Mocini Carmela Coccaro Stefania Alessandrini Susi Barollo Caterina Mian Alessandro Antonelli Enrico De Antoni Massimino D’Armiento Salvatore Ulisse 《PloS one》2015,10(3)
A number of reports indicated that Aurora-A or Aurora-B overexpression represented a negative prognostic factor in several human malignancies. In thyroid cancer tissues a deregulated expression of Aurora kinases has been also demonstrated, butno information regarding its possible prognostic role in differentiated thyroid cancer is available. Here, weevaluated Aurora-A and Aurora-B mRNA expression and its prognostic relevance in a series of 87 papillary thyroid cancers (PTC), with a median follow-up of 63 months. The analysis of Aurora-A and Aurora-B mRNA levels in PTC tissues, compared to normal matched tissues, revealed that their expression was either up- or down-regulatedin the majority of cancer tissues. In particular, Aurora-A and Aurora-B mRNA levels were altered, respectively, in 55 (63.2%) and 79 (90.8%) out of the 87 PTC analyzed.A significant positive correlation between Aurora-A and Aurora-B mRNAswas observed (p=0.001). The expression of both Aurora genes was not affected by the BRAFV600E mutation. Univariate, multivariate and Kaplan-Mayer analyses documented the lack of association between Aurora-A or Aurora-B expression and clinicopathological parameterssuch as gender, age, tumor size, histology, TNM stage, lymph node metastasis and BRAF status as well asdisease recurrences or disease-free interval. Only Aurora-B mRNA was significantly higher in T(3-4) tissues, with respect to T(1-2) PTC tissues. The data reported here demonstrate that the expression of Aurora kinases is deregulated in the majority of PTC tissues, likely contributing to PTC progression. However, differently from other human solid cancers, detection of Aurora-A or Aurora-B mRNAs is not a prognostic biomarker inPTC patients. 相似文献
973.
Alexander B. Taylor Livia Pica-Mattoccia Chiara M. Polcaro Enrica Donati Xiaohang Cao Annalisa Basso Alessandra Guidi Anastasia R. Rugel Stephen P. Holloway Timothy J. C. Anderson P. John Hart Donato Cioli Philip T. LoVerde 《PLoS neglected tropical diseases》2015,9(10)
Background
For over two decades, a racemic mixture of oxamniquine (OXA) was administered to patients infected by Schistosoma mansoni, but whether one or both enantiomers exert antischistosomal activity was unknown. Recently, a ~30 kDa S. m ansoni sulfotransferase (SmSULT) was identified as the target of OXA action.Methodology/Principal Findings
Here, we separate the OXA enantiomers using chromatographic methods and assign their optical activities as dextrorotary [(+)-OXA] or levorotary [(-)-OXA]. Crystal structures of the parasite enzyme in complex with optically pure (+)-OXA and (-)-OXA) reveal their absolute configurations as S- and R-, respectively. When tested in vitro, S-OXA demonstrated the bulk of schistosomicidal activity, while R-OXA had antischistosomal effects when present at relatively high concentrations. Crystal structures R-OXA•SmSULT and S-OXA•SmSULT complexes reveal similarities in the modes of OXA binding, but only the S-OXA enantiomer is observed in the structure of the enzyme exposed to racemic OXA.Conclusions/Significance
Together the data suggest the higher schistosomicidal activity of S-OXA is correlated with its ability to outcompete R-OXA binding the sulfotransferase active site. These findings have important implications for the design, syntheses, and dosing of new OXA-based antischistosomal compounds. 相似文献974.
Giuseppina Andreotti Maria Chiara Monti Valentina Citro Maria Vittoria Cubellis 《PloS one》2015,10(10)
The most frequent disorder of glycosylation is due to mutations in the gene encoding phosphomannomutase2 (PMM2-CDG). For this disease, which is autosomal and recessive, there is no cure at present. Most patients are composite heterozygous and carry one allele encoding an inactive mutant, R141H, and one encoding a hypomorphic mutant. Phosphomannomutase2 is a dimer. We reproduced composite heterozygosity in vitro by mixing R141H either with the wild type protein or the most common hypomorphic mutant F119L and compared the quaternary structure, the activity and the stability of the heterodimeric enzymes. We demonstrated that the activity of R141H/F119L heterodimers in vitro, which reproduces the protein found in patients, has the same activity of wild type/R141H, which reproduces the protein found in healthy carriers. On the other hand the stability of R141H/F119L appears to be reduced both in vitro and in vivo. These findings suggest that a therapy designed to enhance protein stability such as those based on pharmacological chaperones or modulation of proteostasis could be beneficial for PMM2-CDG patients carrying R141H/F119L genotype as well as for other genotypes where protein stability rather than specific activity is affected by mutations. 相似文献
975.
976.
Maria Cristina Colombo Chiara Giverso Elena Faggiano Carlo Boffano Francesco Acerbi Pasquale Ciarletta 《PloS one》2015,10(7)
Glioblastoma multiforme (GBM) is the most aggressive and malignant among brain tumors. In addition to uncontrolled proliferation and genetic instability, GBM is characterized by a diffuse infiltration, developing long protrusions that penetrate deeply along the fibers of the white matter. These features, combined with the underestimation of the invading GBM area by available imaging techniques, make a definitive treatment of GBM particularly difficult. A multidisciplinary approach combining mathematical, clinical and radiological data has the potential to foster our understanding of GBM evolution in every single patient throughout his/her oncological history, in order to target therapeutic weapons in a patient-specific manner. In this work, we propose a continuous mechanical model and we perform numerical simulations of GBM invasion combining the main mechano-biological characteristics of GBM with the micro-structural information extracted from radiological images, i.e. by elaborating patient-specific Diffusion Tensor Imaging (DTI) data. The numerical simulations highlight the influence of the different biological parameters on tumor progression and they demonstrate the fundamental importance of including anisotropic and heterogeneous patient-specific DTI data in order to obtain a more accurate prediction of GBM evolution. The results of the proposed mathematical model have the potential to provide a relevant benefit for clinicians involved in the treatment of this particularly aggressive disease and, more importantly, they might drive progress towards improving tumor control and patient’s prognosis. 相似文献
977.
Mauro Prato Chiara Magnetto Jithin Jose Amina Khadjavi Federica Cavallo Elena Quaglino Alice Panariti Ilaria Rivolta Emilio Benintende Gianfranco Varetto Monica Argenziano Adriano Troia Roberta Cavalli Caterina Guiot 《PloS one》2015,10(3)
Perfluoropentane (PFP)-based oxygen-loaded nanobubbles (OLNBs) were previously proposed as adjuvant therapeutic tools for pathologies of different etiology sharing hypoxia as a common feature, including cancer, infection, and autoimmunity. Here we introduce a new platform of oxygen nanocarriers, based on 2H,3H-decafluoropentane (DFP) as core fluorocarbon. These new nanocarriers have been named oxygen-loaded nanodroplets (OLNDs) since DFP is liquid at body temperature, unlike gaseous PFP. Dextran-shelled OLNDs, available either in liquid or gel formulations, display spherical morphology, ~600 nm diameters, anionic charge, good oxygen carrying capacity, and no toxic effects on human keratinocytes after cell internalization. In vitro OLNDs result more effective in releasing oxygen to hypoxic environments than former OLNBs, as demonstrated by analysis through oxymetry. In vivo, OLNDs effectively enhance oxy-hemoglobin levels, as emerged from investigation by photoacoustic imaging. Interestingly, ultrasound (US) treatment further improves transdermal oxygen release from OLNDs. Taken together, these data suggest that US-activated, DFP-based OLNDs might be innovative, suitable and cost-effective devices to topically treat hypoxia-associated pathologies of the cutaneous tissues. 相似文献
978.
While the role of selective attention in filtering out irrelevant information has been extensively studied, its characteristics and neural underpinnings when multiple environmental stimuli have to be processed in parallel are much less known. Building upon a dual-task paradigm that induced spatial awareness deficits for contralesional hemispace in right hemisphere-damaged patients, we investigated the electrophysiological correlates of multimodal load during spatial monitoring in healthy participants. The position of appearance of briefly presented, lateralized targets had to be reported either in isolation (single task) or together with a concurrent task, visual or auditory, which recruited additional attentional resources (dual-task). This top-down manipulation of attentional load, without any change of the sensory stimulation, modulated the amplitude of the first positive ERP response (P1) and shifted its neural generators, with a suppression of the signal in the early visual areas during both visual and auditory dual tasks. Furthermore, later N2 contralateral components elicited by left targets were particularly influenced by the concurrent visual task and were related to increased activation of the supramarginal gyrus. These results suggest that the right hemisphere is particularly affected by load manipulations, and confirm its crucial role in subtending automatic orienting of spatial attention and in monitoring both hemispaces. 相似文献
979.
Julie K. K. Vishram Anders Borglykke Anne H. Andreasen J?rgen Jeppesen Hans Ibsen Torben J?rgensen Luigi Palmieri Simona Giampaoli Chiara Donfrancesco Frank Kee Giuseppe Mancia Giancarlo Cesana Kari Kuulasmaa Veikko Salomaa Susana Sans Jean Ferrieres Jean Dallongeville Stefan S?derberg Dominique Arveiler Aline Wagner Hugh Tunstall-Pedoe Wojciech Drygas Michael H. Olsen MORGAM Project 《PloS one》2015,10(5)
980.
Paul D. Taylor Chiara Lombardi Silvia Cocito 《Biological reviews of the Cambridge Philosophical Society》2015,90(4):1118-1150
Many animal phyla have the physiological ability to produce biomineralized skeletons with functional roles that have been shaped by natural selection for more than 500 million years. Among these are bryozoans, a moderately diverse phylum of aquatic invertebrates with a rich fossil record and importance today as bioconstructors in some shallow‐water marine habitats. Biomineralizational patterns and, especially, processes are poorly understood in bryozoans but are conventionally believed to be similar to those of the related lophotrochozoan phyla Brachiopoda and Mollusca. However, bryozoan skeletons are more intricate than those of these two phyla. Calcareous skeletons have been acquired independently in two bryozoan clades – Stenolaemata in the Ordovician and Cheilostomata in the Jurassic – providing an evolutionary replicate. This review aims to highlight the importance of biomineralization in bryozoans and focuses on their skeletal ultrastructures, mineralogy and chemistry, the roles of organic components, the evolutionary history of bimineralization in bryozoans with respect to changes in seawater chemistry, and the impact of contemporary global changes, especially ocean acidification, on bryozoan skeletons. Bryozoan skeletons are constructed from three different wall types (exterior, interior and compound) differing in the presence/absence and location of organic cuticular layers. Skeletal ultrastructures can be classified into wall‐parallel (i.e. laminated) and wall‐perpendicular (i.e. prismatic) fabrics, the latter apparently found in only one of the two biomineralizing clades (Cheilostomata), which is also the only clade to biomineralize aragonite. A plethora of ultrastructural fabrics can be recognized and most occur in combination with other fabrics to constitute a fabric suite. The proportion of aragonitic and bimineralic bryozoans, as well as the Mg content of bryozoan skeletons, show a latitudinal increase into the warmer waters of the tropics. Responses of bryozoan mineralogy and skeletal thickness to oscillations between calcite and aragonite seas through geological time are equivocal. Field and laboratory studies of living bryozoans have shown that predicted future changes in pH (ocean acidification) combined with global warming are likely to have detrimental effects on calcification, growth rate and production of polymorphic zooids for defence and reproduction, although some species exhibit reasonable levels of resilience. Some key questions about bryozoan biomineralization that need to be addressed are identified. 相似文献