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51.
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
52.
Theanne Schiros Gregor Kladnik Deborah Prezzi Andrea Ferretti Giorgia Olivieri Albano Cossaro Luca Floreano Alberto Verdini Christine Schenck Marshall Cox Alon A. Gorodetsky Kyle Plunkett Dean Delongchamp Colin Nuckolls Alberto Morgante Dean Cvetko Ioannis Kymissis 《Liver Transplantation》2013,3(7):894-902
While the demonstrated power conversion efficiency of organic photovoltaics (OPVs) now exceeds 10%, new design rules are required to tailor interfaces at the molecular level for optimal exciton dissociation and charge transport in higher efficiency devices. We show that molecular shape‐complementarity between donors and acceptors can drive performance in OPV devices. Using core hole clock (CHC) X‐ray spectroscopy and density functional theory (DFT), we compare the electronic coupling, assembly, and charge transfer rates at the interface between C60 acceptors and flat‐ or contorted‐hexabenzocorone (HBC) donors. The HBC donors have similar optoelectronic properties but differ in molecular contortion and shape matching to the fullerene acceptors. We show that shape‐complementarity drives self‐assembly of an intermixed morphology with a donor/acceptor (D/A) ball‐and‐socket interface, which enables faster electron transfer from HBC to C60. The supramolecular assembly and faster electron transfer rates in the shape complementary heterojunction lead to a larger active volume and enhanced exciton dissociation rate. This work provides fundamental mechanistic insights on the improved efficiency of organic photovoltaic devices that incorporate these concave/convex D/A materials. 相似文献
53.
The coalescent with recombination is a fundamental model to describe the genealogical history of DNA sequence samples from recombining organisms. Considering recombination as a process which acts along genomes and which creates sequence segments with shared ancestry, we study the influence of single recombination events upon tree characteristics of the coalescent. We focus on properties such as tree height and tree balance and quantify analytically the changes in these quantities incurred by recombination in terms of probability distributions. We find that changes in tree topology are often relatively mild under conditions of neutral evolution, while changes in tree height are on average quite large. Our results add to a quantitative understanding of the spatial coalescent and provide the neutral reference to which the impact by other evolutionary scenarios, for instance tree distortion by selective sweeps, can be compared. 相似文献
54.
Marilena Carbone Theodora Zlateva Luca Quaroni 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
The pH of a biological system is a crucial determinant of the structures and reactivity of its components and cellular homeostasis of H+ is critical for cell viability. Control and monitoring of cellular acidity are highly desirable for the purpose of studying biochemical processes in vivo.Methods
The effect of photolysis of a caged strong acid, the ester 1-(2-nitrophenyl)-ethylhexadecyl sulfonate (HDNS) is used to cause a controlled drop in pH in single cells. An isolated cell is selected under the IR microscope, irradiated with near-UV light and monitored by FTIR.Results
We demonstrate the use of FTIR spectromicroscopy to monitor light-induced acidification of the cellular medium by measuring the increased concentration of CO2 and corresponding decrease of HCO3− in the cell and in the surrounding medium.Conclusions
We have demonstrated a method to control and accurately monitor the changes in pH of a cellular system by coupling a caged proton-releasing agent with FTIR spectromicroscopy detection. The overall implementation of photolysis and spectroscopic detection in a microscope optical configuration ensures single cell selectivity in both acidification and monitoring. We show the viability of monitoring of pH changes by FTIR spectromicroscopy with sensitivity comparable to that of glass electrodes, better than the existing methods for determining cell pH.General significance
Reporting the effect of small variations of cellular acidity provides a major improvement in the understanding of the interplay between molecular properties as assessed in vitro and cell physiology. 相似文献55.
Olga De Castro Antonietta Di Maio José Armando Lozada García Danilo Piacenti Mario Vázquez-Torres Paolo De Luca 《Annals of botany》2013,112(3):589-602
Background and Aims
Recent research on the history of Platanus reveals that hybridization phenomena occurred in the central American species. This study has two goals: to help resolve the evolutive puzzle of central American Platanus, and to test the potential of real-time polymerase chain reaction (PCR) for detecting ancient hybridization.Methods
Sequencing of a uniparental plastid DNA marker [psbA-trnH(GUG) intergenic spacer] and qualitative and quantitative single nucleotide polymorphism (SNP) genotyping of biparental nuclear ribosomal DNA (nrDNA) markers [LEAFY intron 2 (LFY-i2) and internal transcribed spacer 2 (ITS2)] were used.Key Results
Based on the SNP genotyping results, several Platanus accessions show the presence of hybridization/introgression, including some accessions of P. rzedowskii and of P. mexicana var. interior and one of P. mexicana var. mexicana from Oaxaca (= P. oaxacana). Based on haplotype analyses of the psbA-trnH spacer, five haplotypes were detected. The most common of these is present in taxa belonging to P. orientalis, P. racemosa sensu lato, some accessions of P. occidentalis sensu stricto (s.s.) from Texas, P. occidentalis var. palmeri, P. mexicana s.s. and P. rzedowskii. This is highly relevant to genetic relationships with the haplotypes present in P. occidentalis s.s. and P. mexicana var. interior.Conclusions
Hybridization and introgression events between lineages ancestral to modern central and eastern North American Platanus species occurred. Plastid haplotypes and qualitative and quantitative SNP genotyping provide information critical for understanding the complex history of Mexican Platanus. Compared with the usual molecular techniques of sub-cloning, sequencing and genotyping, real-time PCR assay is a quick and sensitive technique for analysing complex evolutionary patterns. 相似文献56.
Paolo Bianco Roger Barker Oliver Brüstle Elena Cattaneo Hans Clevers George Q Daley Michele De Luca Lawrence Goldstein Olle Lindvall Christine Mummery Clara Sattler de Sousa e Brito Austin Smith 《The EMBO journal》2013,32(11):1489-1495
At the time of writing, the Italian Parliament is debating a new law that would make it legal to practice an unproven stem cell treatment in public hospitals. The treatment, offered by a private non‐medical organization, may not be safe, lacks a rationale, and violates current national laws and European regulations. This case raises multiple concerns, most prominently the urgent need to protect patients who are severely ill, exposed to significant risks, and vulnerable to exploitation. The scientific community must consider the context—social, financial, medical, legal—in which stem cell science is currently situated and the need for stringent regulation. Additional concerns are emerging. These emanate from the novel climate, created within science itself, and stem cell science in particular, by the currently prevailing model of ‘translational medicine’. Only rigorous science and rigorous regulation can ensure translation of science into effective therapies rather than into ineffective market products, and mark, at the same time, the sharp distinction between the striving for new therapies and the deceit of patients. 相似文献
57.
Sébastien Besseau Franziska Kellner Arnaud Lanoue Antje M.K. Thamm Vonny Salim Bernd Schneider Fernando Geu-Flores René H?fer Grégory Guirimand Anthony Guihur Audrey Oudin Ga?lle Glevarec Emilien Foureau Nicolas Papon Marc Clastre Nathalie Giglioli-Guivarc’h Benoit St-Pierre Danièle Werck-Reichhart Vincent Burlat Vincenzo De Luca Sarah E. O’Connor Vincent Courdavault 《Plant physiology》2013,163(4):1792-1803
58.
Annamaria Spina Luca Sorvillo Francesca Di Maiolo Antonietta Esposito Raffaella D'Auria Davide Di Gesto Emilio Chiosi Silvio Naviglio 《Journal of cellular physiology》2013,228(1):198-206
Osteosarcoma is the most common malignant primary bone tumor in children and adolescents. The clinical outcome for osteosarcoma remains discouraging despite aggressive surgery and intensive radiotherapy and chemotherapy regimens. Thus, novel therapeutic approaches are needed. Previously, we have shown that inorganic phosphate (Pi) inhibits proliferation and aggressiveness of human osteosarcoma U2OS cells identifying adenylate cyclase, beta3 integrin, Rap1, ERK1/2 as proteins whose expression and function are relevantly affected in response to Pi. In this study, we investigated whether Pi could affect chemosensitivity of osteosarcoma cells and the underlying molecular mechanisms. Here, we report that Pi inhibits proliferation of p53‐wild type U2OS cells (and not of p53‐null Saos and p53‐mutant MG63 cells) by slowing‐down cell cycle progression, without apoptosis occurrence. Interestingly, we found that Pi strongly enhances doxorubicin‐induced cytotoxicity in U2OS, and not in Saos and MG63 cells, by apoptosis induction, as revealed by a marked increase of sub‐G1 population, Bcl‐2 downregulation, caspase‐3 activation, and PARP cleavage. Remarkably, Pi/doxorubicin combination‐induced cytotoxicity was accompanied by an increase of p53 protein levels and of p53 target genes mdm2, p21 and Bax, and was significantly reduced by the p53 inhibitor pifithrine‐alpha. Moreover, the doxorubicin‐induced cytotoxicity was associated with ERK1/2 pathway inhibition in response to Pi. Altogether, our data enforce the evidence of Pi as a novel signaling molecule capable of inhibiting ERK pathway and inducing sensitization to doxorubicin of osteosarcoma cells by p53‐dependent apoptosis, implying that targeting Pi levels might represent a rational strategy for improving osteosarcoma therapy. J. Cell. Physiol. 228: 198–206, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
59.
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
60.
Theresa K. Hodges Kate L. Laskowski Giuseppe L. Squadrito Maria De Luca Jeff Leips 《Evolution; international journal of organic evolution》2013,67(3):749-760
Populations of Drosophila melanogaster face significant mortality risks from parasitoid wasps that use species‐specific strategies to locate and survive in hosts. We tested the hypothesis that parasitoids with different strategies select for alternative host defense characteristics and in doing so contribute to the maintenance of fitness variation and produce trade‐offs among traits. We characterized defense traits of Drosophila when exposed to parasitoids with different host searching behaviors (Aphaereta sp. and Leptopilina boulardi). We used host larvae with different natural alleles of the gene Dopa decarboxylase (Ddc), a gene controlling the production of dopamine and known to influence the immune response against parasitoids. Previous population genetic analyses indicate that our focal alleles are maintained by balancing selection. Genotypes exhibited a trade‐off between the immune response against Aphaereta sp. and the ability to avoid parasitism by L. boulardi. We also identified a trade‐off between the ability to avoid parasitism by L. boulardi and larval competitive ability as indicated by differences in foraging and feeding behavior. Genotypes differed in dopamine levels potentially explaining variation in these traits. Our results highlight the potential role of parasitoid biodiversity on host fitness variation and implicate Ddc as an antagonistic pleiotropic locus influencing larval fitness traits. 相似文献