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21.
Thorsten Klampfl Jelena D. Milosevic Ana Puda Andreas Sch?negger Klaudia Bagienski Tiina Berg Ashot S. Harutyunyan Bettina Gisslinger Elisa Rumi Luca Malcovati Daniela Pietra Chiara Elena Matteo Giovanni Della Porta Lisa Pieri Paola Guglielmelli Christoph Bock Michael Doubek Dana Dvorakova Nada Suvajdzic Dragica Tomin Natasa Tosic Zdenek Racil Michael Steurer Sonja Pavlovic Alessandro M. Vannucchi Mario Cazzola Heinz Gisslinger Robert Kralovics 《PloS one》2013,8(10)
Exome sequencing of primary tumors identifies complex somatic mutation patterns. Assignment of relevance of individual somatic mutations is difficult and poses the next challenge for interpretation of next generation sequencing data. Here we present an approach how exome sequencing in combination with SNP microarray data may identify targets of chromosomal aberrations in myeloid malignancies. The rationale of this approach is that hotspots of chromosomal aberrations might also harbor point mutations in the target genes of deletions, gains or uniparental disomies (UPDs). Chromosome 11 is a frequent target of lesions in myeloid malignancies. Therefore, we studied chromosome 11 in a total of 813 samples from 773 individual patients with different myeloid malignancies by SNP microarrays and complemented the data with exome sequencing in selected cases exhibiting chromosome 11 defects. We found gains, losses and UPDs of chromosome 11 in 52 of the 813 samples (6.4%). Chromosome 11q UPDs frequently associated with mutations of CBL. In one patient the 11qUPD amplified somatic mutations in both CBL and the DNA repair gene DDB1. A duplication within MLL exon 3 was detected in another patient with 11qUPD. We identified several common deleted regions (CDR) on chromosome 11. One of the CDRs associated with de novo acute myeloid leukemia (P=0.013). One patient with a deletion at the LMO2 locus harbored an additional point mutation on the other allele indicating that LMO2 might be a tumor suppressor frequently targeted by 11p deletions. Our chromosome-centered analysis indicates that chromosome 11 contains a number of tumor suppressor genes and that the role of this chromosome in myeloid malignancies is more complex than previously recognized. 相似文献
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Rosa Anna Iorio Stefano Del Duca Elisabetta Calamelli Chiara Pula Magda Lodolini Fortuna Scamardella Andrea Pession Giampaolo Ricci 《PloS one》2013,8(1)
Allergy to citrus fruits is often associated with pollinosis and sensitization to other plants due to a phenomenon of cross-reactivity. The aims of the present study were to highlight the cross-reactivity among citrus and the major allergenic pollens/fruits, throughout clinical and molecular investigations, and to evaluate the sensitization frequency to citrus fruits in a population of children and adults with pollinosis. We found a relevant percentage of sensitisation (39%) to citrus fruits in the patients recruited and in all of them the IgE-mediated mechanism has been confirmed by the positive response to the prick-to-prick test. RT-PCR experiments showed the expression of Cit s 1, Cit s 3 and a profilin isoform, already described in apple, also in Citrus clementine pollen. Data of multiple sequence alignments demonstrated that Citrus allergens shared high percentage identity values with other clinically relevant species (i.e. Triticum aestivum, Malus domestica), confirming the possible cross-allergenicity citrus/grasses and citrus/apple. Finally, a novelty of the present work has been the expression of two phospholipaseA2 isoforms (PLA2 α and β) in Citrus as well as in Triticum pollens; being PLA2 able to generate pro-inflammatory factors, this enzyme could participate in the activation of the allergenic inflammatory cascade. 相似文献
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Silvia Rossi Valeria Studer Alessandro Moscatelli Caterina Motta Giancarlo Coghe Giuseppe Fenu Stacy Caillier Fabio Buttari Francesco Mori Francesca Barbieri Maura Castelli Valentina De Chiara Fabrizia Monteleone Raffaele Mancino Giorgio Bernardi Sergio E. Baranzini Maria G. Marrosu Jorge R. Oksenberg Diego Centonze 《PloS one》2013,8(6)
Synaptic transmission and plasticity mediated by NMDA receptors (NMDARs) could modulate the severity of multiple sclerosis (MS). Here the role of NMDARs in MS was first explored in 691 subjects carrying specific allelic variants of the NR1 subunit gene or of the NR2B subunit gene of this glutamate receptor. The analysis was replicated for significant SNPs in an independent sample of 1548 MS subjects. The C allele of rs4880213 was found to be associated with reduced NMDAR-mediated cortical excitability, and with increased probability of having more disability than the CT/TT MS subjects. MS severity was higher in the CC group among relapsing-remitting MS (RR-MS) patients, while primary progressive MS (PP-MS) subjects homozygous for the T allele had more pronounced clinical worsening. Mean time to first relapse, but not to an active MRI scan, was lower in the CC group of RR-MS patients, and the number of subjects with two or more clinical relapses in the first two years of the disease was higher in CC compared to CT/TT group. Furthermore, the percentage of relapses associated with residual disability was lower in subjects carrying the T allele. Lesion load at the MRI was conversely unaffected by the C or T allele of this SNP in RR-MS patients. Axonal and neuronal degeneration at the optical coherence tomography was more severe in the TT group of PP-MS patients, while reduced retinal nerve fiber thickness had less consequences on visual acuity in RR-MS patients bearing the T allele. Finally, the T allele was associated with preserved cognitive abilities at the Rao’s brief repeatable neuropsychological battery in RR-MS. Signaling through glutamate NMDARs enhances both compensatory synaptic plasticity and excitotoxic neurodegeneration, impacting in opposite ways on RR-MS and PP-MS pathophysiological mechanisms. 相似文献
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Oecologia - Fluctuations in the abundance of main prey species might shape animal communities, by inducing numerical responses and dietary shifts in predators. Whether numerical responses and... 相似文献
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Vito A. Baldassarro Chiara Mangano Luciana Giardino Bruno P. Imbimbo Tiziana Antonelli Laura Calzà Luca Ferraro 《Journal of neurochemistry》2013,124(5):613-620
CHF5074, a new microglial modulator, attenuates memory deficit in Alzheimer's disease transgenic mice. In this study, the effect of an acute or subacute CHF5074 treatment on in vivo novel object recognition test and on [3H]Acetylcholine (ACh) and GABA release in pre‐plaque (7‐month‐old) Tg2576 mice have been compared with those induced by the γ‐secretase inhibitor LY450139 (semagacestat). Vehicle‐treated Tg2576 mice displayed an impairment of recognition memory compared with wild‐type animals. This impairment was recovered in transgenic animals acutely treated with CHF5074 (30 mg/kg), while LY450139 (1, 3, 10 mg/kg) was ineffective. In frontal cortex synaptosomes from vehicle‐treated Tg2576 mice, K+‐evoked [3H]ACh release was lower than that measured in wild‐type mice. This reduction was absent in transgenic animals subacutely treated with CHF5074 (30 mg/kg daily for 8 days), while it was slightly, not significantly, amplified by LY450139 (3 mg/kg daily for 8 days). There were no differences between the groups on spontaneous [3H]ACh release as well as spontaneous and K+‐evoked GABA release. These results suggest that CHF5074 has beneficial effects on visual memory and cortical cholinergic dysfunctions in pre‐plaque Tg2576 mice. Together with previous findings, these data suggest that CHF5074 could be a possible candidate for early Alzheimer's disease therapeutic regimens. 相似文献
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Chiara Barbieri Mário Vicente Jorge Rocha Sununguko?W. Mpoloka Mark Stoneking Brigitte Pakendorf 《American journal of human genetics》2013,92(2):285-292
Among the deepest-rooting clades in the human mitochondrial DNA (mtDNA) phylogeny are the haplogroups defined as L0d and L0k, which are found primarily in southern Africa. These lineages are typically present at high frequency in the so-called Khoisan populations of hunter-gatherers and herders who speak non-Bantu languages, and the early divergence of these lineages led to the hypothesis of ancient genetic substructure in Africa. Here we update the phylogeny of the basal haplogroups L0d and L0k with 500 full mtDNA genome sequences from 45 southern African Khoisan and Bantu-speaking populations. We find previously unreported subhaplogroups and greatly extend the amount of variation and time-depth of most of the known subhaplogroups. Our major finding is the definition of two ancient sublineages of L0k (L0k1b and L0k2) that are present almost exclusively in Bantu-speaking populations from Zambia; the presence of such relic haplogroups in Bantu speakers is most probably due to contact with ancestral pre-Bantu populations that harbored different lineages than those found in extant Khoisan. We suggest that although these populations went extinct after the immigration of the Bantu-speaking populations, some traces of their haplogroup composition survived through incorporation into the gene pool of the immigrants. Our findings thus provide evidence for deep genetic substructure in southern Africa prior to the Bantu expansion that is not represented in extant Khoisan populations. 相似文献
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Chiara Fabris Wladimiro De Colle Giovanni Sparacino 《Biomedical signal processing and control》2013,8(6):920-926
The quantitative analysis of vocal disorders by nonlinear signal processing methods has been extensively used in the last two decades. In this work, two algorithms for nonlinear time-series analysis, Sample Entropy and cross-Sample Entropy, are used on electroglottogram (EGG) and microphone (MIC) signals recorded from 51 normal and 80 dysphonic subjects, to obtain summary measures of voice disorders through SampEn and cross-SampEn indices. Such parameters quantify, respectively, the degree of irregularity (in the sense of self-dissimilarity) within a time-series and of asynchrony (in the sense of cross-dissimilarity) between two distinct time-series. The aims of this work are: to determine if statistically significant differences in terms of signal irregularity quantified by SampEn occur between normal and pathological subjects, investigating whether or not such differences can be equally seen in EGG and MIC; to assess if cross-SampEn reveals different degrees of asynchrony between EGG and MIC signals in the two groups. Results show that SampEn in pathological subjects is higher than in normal subjects for both EGG and MIC time-series, with a statistically significant difference detectable from both signals (Pe < 10?4 for EGG and Pe < 10?7 for MIC). Cross-SampEn exhibits a statistically significant difference too, showing a higher degree of cross-dissimilarity between EGG and MIC time-series for pathological subjects (Pe < 10?4). In conclusion, SampEn and cross-SampEn well quantify the increase of complexity of both EGG and MIC signals and the decrease of their cross-similarity in presence of vocal disorders. Thanks to the complementarity of nonlinear indicators to the traditionally considered linear ones, SampEn and cross-SampEn appear as suitable candidates to enter the pool of approaches to investigate speech pathologies and to obtain potentially new insights on their nature. 相似文献