@article{%a1:%Y_366,

title = {Height-reducing variants and selection for short stature in Sardinia.},

author = {Zoledziewska M and Sidore C and Chiang CW and Sanna S and Mulas A and Steri M and Busonero F and Marcus JH and Marongiu M and Maschio A and Del Vecchyo DO and Floris M and Meloni A and Delitala A and Concas MP and Murgia F and Biino G and Vaccargiu S and Nagaraja R and Lohmueller KE and UK10K Consortium and Timpson NJ and Soranzo N and Tachmazidou I and Dedoussis G and Zeggini E and Understanding Society Scientific Group and Uzzau S and Jones C and Lyons R and Angius A and Abecasis GR and Novembre J and Schlessinger D and Cucca F},

url = {https://www.nature.com/articles/ng.3403},

doi = {10.1038/ng.3403},

year  = {2015},

date = {2015-11-25},

journal = {Nature Genetics},

volume = {47},

number = {11},

pages = {1352-1356},

abstract = {We report sequencing-based whole-genome association analyses to evaluate the impact of rare and founder variants on stature in 6,307 individuals on the island of Sardinia. We identify two variants with large effects. One variant, which introduces a stop codon in the GHR gene, is relatively frequent in Sardinia (0.87% versus <0.01% elsewhere) and in the homozygous state causes Laron syndrome involving short stature. We find that this variant reduces height in heterozygotes by an average of 4.2 cm (-0.64 s.d.). The other variant, in the imprinted KCNQ1 gene (minor allele frequency (MAF) = 7.7% in Sardinia versus <1% elsewhere) reduces height by an average of 1.83 cm (-0.31 s.d.) when maternally inherited. Additionally, polygenic scores indicate that known height-decreasing alleles are at systematically higher frequencies in Sardinians than would be expected by genetic drift. The findings are consistent with selection for shorter stature in Sardinia and a suggestive human example of the proposed 'island effect' reducing the size of large mammals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_370,

title = {Homology Model-Based Virtual Screening for the Identification of Human Helicase DDX3 Inhibitors.},

author = {Fazi R and Tintori C and Brai A and Botta L and Selvaraj M and Garbelli A and Maga G and Botta M},

url = {https://pubs.acs.org/doi/10.1021/acs.jcim.5b00419},

doi = {10.1021/acs.jcim.5b00419},

year  = {2015},

date = {2015-11-23},

journal = {Journal of Chemical Information and Modeling},

volume = {55},

number = {11},

pages = {2443-2454},

abstract = {Targeting cellular cofactors instead of viral enzymes represents a new strategy to combat infectious diseases, which should help to overcome the problem of viral resistance. Recently, it has been revealed that the cellular ATPase/RNA helicase X-linked DEAD-box polypeptide 3 (DDX3) is an essential host factor for the replication of several viruses such as HIV, HCV, JEV, Dengue, and West Nile. Accordingly, a drug targeting DDX3 could theoretically inhibit all viruses that are dependent on this host factor. Herein, for the first time, a model of hDDX3 in its closed conformation, which binds the viral RNA was developed by using the homology module of Prime through the Maestro interface of Schrodinger. Next, a structure-based virtual screening protocol was applied to identify DDX3 small molecule inhibitors targeting the RNA binding pocket. As a result, an impressive hit rate of 40% was obtained with the identification of 10 active compounds out of the 25 tested small molecules. The best poses of the active ligands highlighted the crucial residues to be targeted for the inhibition of the helicase activity of DDX3. The obtained results confirm the reliability of the constructed DDX3/RNA model and the proposed computational strategy for investigating novel DDX3 inhibitors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_416,

title = {Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.},

author = {Kato N and Loh M and {et al}},

url = {https://www.nature.com/articles/ng.3405},

doi = {10.1038/ng.3405},

year  = {2015},

date = {2015-11-11},

journal = {Nature Genetics},

volume = {47},

number = {11},

abstract = {We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_375,

title = {Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes.},

author = {Cesarini E and Mozzetta C and Marullo F and Gregoretti F and Gargiulo A and Columbaro M and Cortesi A and Antonelli L and Di Pelino S and Squarzoni S and Palacios D and Zippo A and Bodega B and Oliva G and Lanzuolo C},

url = {https://rupress.org/jcb/article-lookup/doi/10.1083/jcb.201504035},

doi = {10.1083/jcb.201504035},

year  = {2015},

date = {2015-11-09},

journal = {Journal of Cell Biology},

volume = {211},

number = {3},

pages = {533-551},

abstract = {Beyond its role in providing structure to the nuclear envelope, lamin A/C is involved in transcriptional regulation. However, its cross talk with epigenetic factors-and how this cross talk influences physiological processes-is still unexplored. Key epigenetic regulators of development and differentiation are the Polycomb group (PcG) of proteins, organized in the nucleus as microscopically visible foci. Here, we show that lamin A/C is evolutionarily required for correct PcG protein nuclear compartmentalization. Confocal microscopy supported by new algorithms for image analysis reveals that lamin A/C knock-down leads to PcG protein foci disassembly and PcG protein dispersion. This causes detachment from chromatin and defects in PcG protein-mediated higher-order structures, thereby leading to impaired PcG protein repressive functions. Using myogenic differentiation as a model, we found that reduced levels of lamin A/C at the onset of differentiation led to an anticipation of the myogenic program because of an alteration of PcG protein-mediated transcriptional repression. Collectively, our results indicate that lamin A/C can modulate transcription through the regulation of PcG protein epigenetic factors. 2015 Cesarini et al.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_414,

title = {The novel influenza A virus protein PA-X and its naturally deleted variant show different enzymatic properties in comparison to the viral endonuclease PA.},

author = {Bavagnoli L and Cucuzza S and Campanini G and Rovida F and Paolucci S and Baldanti F and Maga G},

url = {https://academic.oup.com/nar/article/43/19/9405/2528196},

doi = {10.1093/nar/gkv926},

year  = {2015},

date = {2015-10-15},

journal = {Nucleic Acids Research},

volume = {43},

number = {19},

pages = {9405-9417},

abstract = {The PA protein of Influenza A virus (IAV) encoded by segment 3 acts as a specialized RNA endonuclease in the transcription of the viral genome. The same genomic segment encodes for a second shorter protein, termed PA-X, with the first 191 N-terminal aminoacids (aa) identical to PA, but with a completely different C-ter domain of 61 aa, due to a ribosomal frameshifting. In addition, it has been shown that several IAV isolates encode for a naturally truncated PA-X variant, PAXΔC20, missing the last 20 aa. The biochemical properties of PA-X and PAXΔC20 have been poorly investigated so far. Here, we have carried out an enzymatic characterization of PA-X and its naturally deleted form, in comparison with PA from the human IAV strain A/WSN/33 (H1N1). Our results showed, to the best of our knowledge for the first time, that PA-X possesses an endonucleolytic activity. Both PA and PA-X preferentially cut single stranded RNA regions, but with some differences. In addition, we showed that PAXΔC20 has severely reduced nuclease activity. These results point to a previously undetected role of the last C-ter 20 aa for the catalytic activity of PA-X and support distinct roles for these proteins in the viral life cycle. The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_411,

title = {The alternative splicing factor Nova2 regulates vascular development and lumen formation.},

author = {Giampietro C and Deflorian G and Gallo S and {Di Matteo A} and Pradella D and Bonomi S and Belloni E and Nyqvist D and Quaranta V and Confalonieri S and Bertalot G and Orsenigo F and Pisati F and Ferrero E and Biamonti G and Fredrickx E and Taveggia C and Wyatt CD and Irimia M and Di Fiore PP and Blencowe BJ and Dejana E and Ghigna C},

url = {https://www.nature.com/articles/ncomms9479},

doi = {10.1038/ncomms9479},

year  = {2015},

date = {2015-10-08},

urldate = {2015-10-08},

journal = {Nature communications},

volume = {6},

pages = {8479},

abstract = {Vascular lumen formation is a fundamental step during angiogenesis; yet, the molecular mechanisms underlying this process are poorly understood. Recent studies have shown that neural and vascular systems share common anatomical, functional and molecular similarities. Here we show that the organization of endothelial lumen is controlled at the post-transcriptional level by the alternative splicing (AS) regulator Nova2, which was previously considered to be neural cell-specific. Nova2 is expressed during angiogenesis and its depletion disrupts vascular lumen formation in vivo. Similarly, Nova2 depletion in cultured endothelial cells (ECs) impairs the apical distribution and the downstream signalling of the Par polarity complex, resulting in altered EC polarity, a process required for vascular lumen formation. These defects are linked to AS changes of Nova2 target exons affecting the Par complex and its regulators. Collectively, our results reveal that Nova2 functions as an AS regulator in angiogenesis and is a novel member of the 'angioneurins' family.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_364,

title = {Genome-wide association analysis on normal hearing function identifies PCDH20 and SLC28A3 as candidates for hearing function and loss.},

author = {Vuckovic D and Dawson S and Scheffer DI and Rantanen T and Morgan A and Di Stazio M and Vozzi D and Nutile T and Concas MP and Biino G and Nolan L and Bahl A and Loukola A and Viljanen A and Davis A and Ciullo M and Corey DP and Pirastu M and Gasparini P and Girotto G},

url = {https://academic.oup.com/hmg/article/24/19/5655/584102},

doi = {10.1093/hmg/ddv279},

year  = {2015},

date = {2015-10-01},

journal = {Human Molecular Genetics },

volume = {24},

number = {19},

pages = {5655-5664},

abstract = {Hearing loss and individual differences in normal hearing both have a substantial genetic basis. Although many new genes contributing to deafness have been identified, very little is known about genes/variants modulating the normal range of hearing ability. To fill this gap, we performed a two-stage meta-analysis on hearing thresholds (tested at 0.25, 0.5, 1, 2, 4, 8 kHz) and on pure-tone averages (low-, medium- and high-frequency thresholds grouped) in several isolated populations from Italy and Central Asia (total N = 2636). Here, we detected two genome-wide significant loci close to PCDH20 and SLC28A3 (top hits: rs78043697, P = 4.71E-10 and rs7032430, P = 2.39E-09, respectively). For both loci, we sought replication in two independent cohorts: B58C from the UK (N = 5892) and FITSA from Finland (N = 270). Both loci were successfully replicated at a nominal level of significance (P < 0.05). In order to confirm our quantitative findings, we carried out RT-PCR and reported RNA-Seq data, which showed that both genes are expressed in mouse inner ear, especially in hair cells, further suggesting them as good candidates for modulatory genes in the auditory system. Sequencing data revealed no functional variants in the coding region of PCDH20 or SLC28A3, suggesting that variation in regulatory sequences may affect expression. Overall, these results contribute to a better understanding of the complex mechanisms underlying human hearing function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_391,

title = {Personalized reference intervals for platelet count reduce the number of subjects with unexplained thrombocytopenia.},

author = {Zaninetti C and Biino G and Noris P and Melazzini F and Civaschi E and Balduini CL},

url = {http://www.haematologica.org/content/100/9/e338.long},

doi = {10.3324/haematol.2015.127597},

year  = {2015},

date = {2015-09-26},

journal = {Haematologica},

volume = {100},

number = {9},

pages = {e338-340},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_317,

title = {Peri-Synaptic Glia Recycles Brain-Derived Neurotrophic Factor for LTP Stabilization and Memory Retention.},

author = {Vignoli B and Battistini G and Melani R and Blum R and Santi S and Berardi N and Canossa M},

url = {http://www.sciencedirect.com/science/article/pii/S0896627316306328},

doi = {10.1016/j.neuron.2016.09.031},

year  = {2015},

date = {2015-09-17},

journal = {Neuron},

volume = {92},

number = {4},

pages = {873-887},

abstract = {Glial cells respond to neuronal activation and release neuroactive molecules (termed "gliotransmitters") that can affect synaptic activity and modulate plasticity. In this study, we used molecular genetic tools, ultra-structural microscopy, and electrophysiology to assess the role of brain-derived neurotrophic factor (BDNF) on cortical gliotransmission in vivo. We find that glial cells recycle BDNF that was previously secreted by neurons as pro-neurotrophin following long-term potentiation (LTP)-inducing electrical stimulation. Upon BDNF glial recycling, we observed tight, temporal, highly localized TrkB phosphorylation on adjacent neurons, a process required to sustain LTP. Engagement of BDNF recycling by astrocytes represents a novel mechanism by which cortical synapses can expand BDNF action and provide synaptic changes that are relevant for the acquisition of new memories. Accordingly, mice deficient in BDNF glial recycling fail to recognize familiar from novel objects, indicating a physiological requirement for this process in memory consolidation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_380,

title = {Methods for genetic optimization of biocatalysts for biofuel production from dairy waste through synthetic biology.},

author = {Pasotti L and Zucca S and Casanova M and Politi N and Massaiu I and Mazzini G and Micoli G and Calvio C and Cusella De Angelis MG and Magni P},

url = {https://ieeexplore.ieee.org/document/7318521},

doi = {10.1109/EMBC.2015.7318521},

year  = {2015},

date = {2015-08-26},

journal = {Conference proceedings : Annual International Conference of the IEEE Engineering in Medicine and Biology Society.},

volume = {2015},

pages = {953-956},

abstract = {Whey is an abundant by-product of cheese production process and it is considered a special waste due to its high nutritional load and hypertrophic potential. Technologies for whey valorization are available. They can convert such waste into high-value products, like whey proteins. However, the remaining liquid (called permeate) is still considered as a polluting waste due to its high lactose concentration. The alcoholic fermentation of lactose into ethanol will simultaneously achieve two important goals: safe disposal of a pollutant waste and green energy production. This methodology paper illustrates the workflow carried out to design and realize an optimized microorganism that can efficiently perform the lactose-to-ethanol conversion, engineered via synthetic biology experimental and computational approaches.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_376,

title = {Liposome-induced exfoliation of graphite to few-layer graphene dispersion with antibacterial activity.},

author = {Zappacosta R and {Di Giulio M} and Ettorre V and Bosco D and Hadad C and Siani G and Di Bartolomeo S and Cataldi A and Cellini L and Fontana A},

url = {https://pubs.rsc.org/en/content/articlelanding/2015/tb/c5tb00798d#!divAbstract},

doi = {10.1039/c5tb00798d},

year  = {2015},

date = {2015-08-21},

journal = {Journal of Materials Chemistry B},

volume = {3},

number = {31},

pages = {6520-6527},

abstract = {Few-layer graphene aqueous dispersions are obtained by exploiting liposomes as effective exfoliating agents for graphite. Raman measurements evidence the presence of non-oxidized double layer graphene as well as amphiphilic phospholipid molecules organized in bilayers in the samples. TEM analyses confirmed that the obtained homogeneous graphene nanosheets are embedded in the liposomal bilayer. The as-prepared graphene aqueous dispersion is stable for days and demonstrates significant antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) strains, with a reduction in the growth of S. aureus and E. coli as high as 60 and 78%, respectively.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_403,

title = {Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae.},

author = {Manfrini N and Clerici M and Wery M and Colombo CV and Descrimes M and Morillon A and {d'Adda di Fagagna F} and Longhese MP},

url = {https://elifesciences.org/articles/08942},

doi = {10.7554/eLife.08942.},

year  = {2015},

date = {2015-07-31},

journal = {Elife},

volume = {4},

abstract = {Emerging evidence indicate that the mammalian checkpoint kinase ATM induces transcriptional silencing in cis to DNA double-strand breaks (DSBs) through a poorly understood mechanism. Here we show that in Saccharomyces cerevisiae a single DSB causes transcriptional inhibition of proximal genes independently of Tel1/ATM and Mec1/ATR. Since the DSB ends undergo nucleolytic degradation (resection) of their 5′-ending strands, we investigated the contribution of resection in this DSB-induced transcriptional inhibition. We discovered that resection-defective mutants fail to stop transcription around a DSB, and the extent of this failure correlates with the severity of the resection defect. Furthermore, Rad9 and generation of γH2A reduce this DSB-induced transcriptional inhibition by counteracting DSB resection. Therefore, the conversion of the DSB ends from double-stranded to single-stranded DNA, which is necessary to initiate DSB repair by homologous recombination, is responsible for loss of transcription around a DSB in S. cerevisiae.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_390,

title = {Osteogenic differentiation of human MSCs: Specific occupancy of the mitochondrial DNA by NFATc1 transcription factor.},

author = {Lambertini E and Penolazzi L and Morganti C and Lisignoli G and Zini N and Angelozzi M and Bonora M and Ferroni L and Pinton P and Zavan B and Piva R},

url = {https://www.sciencedirect.com/science/article/pii/S1357272515001120?via%3Dihub},

doi = {10.1016/j.biocel.2015.04.011},

year  = {2015},

date = {2015-07-29},

journal = {International Journal of Biochemistry & Cell Biology},

volume = {64},

pages = {212-219},

abstract = {A substantial body of evidence indicates that mitochondrial morphology and function change during osteogenic differentiation. However, molecular mechanisms linking mitochondrial dynamics with the regulation of osteoblast functions are poorly understood. Amongst the molecules that influence the decision of human mesenchymal stem cells (hMSCs) to become osteoblasts are Slug and NFATc1 transcription factors (TFs). These molecules also interfere with different mitochondria-dependent pathways in response to a variety of cellular demands. The present study investigated the recruitment of Slug and NFATc1 at the D-loop regulatory region of mitochondrial DNA (mtDNA) in osteogenic differentiated hMSCs with the aim of exploring whether Slug and NFATc1 also act as mitoTFs in the mitochondrial pool of nuclear TFs. The results demonstrate that NFATc1, but not Slug, is localized in the mitochondria. Using chromatin immunoprecipitation assay, we found that NFATc1 is recruited at mtDNA, but this occurs only when the calcification process is at its highest in osteo-induced MSC and the maximum level of differentiation is reached. Occupancy of the mtDNA by NFATc1 is associated with a decreased expression of crucial mitochondrial genes such as Cytochrome B and NADH dehydrogenase 1. This suggests that NFATc1 acts as a negative regulator of mtDNA transcription during the calcification process and interruption of aerobic energy demand. The finding of NFATc1 participation in osteogenic differentiation through its direct involvement in the regulatory machinery of mitochondria suggests a new role for this TF and adds information on communication between mitochondrial and nuclear genomes. Copyright © 2015 Elsevier Ltd. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_371,

title = {Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species.},

author = {Baglio SR and Rooijers K and Koppers-Lalic D and Verweij FJ and Perez Lanzon M and Zini N and Naaijkens B and Perut F and Niessen HW and Baldini N and Pegtel DM},

url = {https://stemcellres.biomedcentral.com/articles/10.1186/s13287-015-0116-z},

doi = {10.1186/s13287-015-0116-z},

year  = {2015},

date = {2015-07-01},

journal = {Stem Cell Research & Therapy},

volume = {6},

pages = {127},

abstract = {INTRODUCTION: Administration of mesenchymal stem cells (MSCs) represents a promising treatment option for patients suffering from immunological and degenerative disorders. Accumulating evidence indicates that the healing effects of MSCs are mainly related to unique paracrine properties, opening opportunities for secretome-based therapies. Apart from soluble factors, MSCs release functional small RNAs via extracellular vesicles (EVs) that seem to convey essential features of MSCs. Here we set out to characterize the full small RNAome of MSC-produced exosomes. METHODS: We set up a protocol for isolating exosomes released by early passage adipose- (ASC) and bone marrow-MSCs (BMSC) and characterized them via electron microscopy, protein analysis and small RNA-sequencing. We developed a bioinformatics pipeline to define the exosome-enclosed RNA species and performed the first complete small RNA characterization of BMSCs and ASCs and their corresponding exosomes in biological replicates. RESULTS: Our analysis revealed that primary ASCs and BMSCs have highly similar small RNA expression profiles dominated by miRNAs and snoRNAs (together 64-71 %), of which 150-200 miRNAs are present at physiological levels. In contrast, the miRNA pool in MSC exosomes is only 2-5 % of the total small RNAome and is dominated by a minor subset of miRNAs. Nevertheless, the miRNAs in exosomes do not merely reflect the cellular content and a defined set of miRNAs are overrepresented in exosomes compared to the cell of origin. Moreover, multiple highly expressed miRNAs are precluded from exosomal sorting, consistent with the notion that these miRNAs are involved in functional repression of RNA targets. While ASC and BMSC exosomes are similar in RNA class distribution and composition, we observed striking differences in the sorting of evolutionary conserved tRNA species that seems associated with the differentiation status of MSCs, as defined by Sox2, POU5F1A/B and Nanog expression. CONCLUSIONS: We demonstrate that primary MSCs release small RNAs via exosomes, which are increasingly implicated in intercellular communications. tRNAs species, and in particular tRNA halves, are preferentially released and their specific sorting into exosomes is related to MSC tissue origin and stemness. These findings may help to understand how MSCs impact neighboring or distant cells with possible consequences for their therapeutic usage.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_378,

title = {Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression.},

author = {Nahta R and Al-Mulla F and Al-Temaimi R and Amedei A and Andrade-Vieira R and Bay S and G Brown D and Calaf GM and Castellino RC and Cohen-Solal KA and Colacci A and Cruickshanks N and Dent P and Di Fiore R and Forte S and Goldberg GS and Hamid RA and Krishnan H and Laird DW and Lasfar A and Marignani PA and Memeo L and Mondello C and Naus CC and Ponce-Cusi R and Raju J and Roy D and Roy R and P Ryan E and Salem HK and Scovassi AI and Singh N and Vaccari M and Vento R and Vondracek J and Wade M and Woodrick J and Bisson WH},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S2/310663},

doi = {10.1093/carcin/bgv028},

year  = {2015},

date = {2015-06-30},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S2-18},

abstract = {As part of the Halifax Project, this review brings attention to the potential effects of environmental chemicals on important molecular and cellular regulators of the cancer hallmark of evading growth suppression. Specifically, we review the mechanisms by which cancer cells escape the growth-inhibitory signals of p53, retinoblastoma protein, transforming growth factor-beta, gap junctions and contact inhibition. We discuss the effects of selected environmental chemicals on these mechanisms of growth inhibition and cross-reference the effects of these chemicals in other classical cancer hallmarks. The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_397,

title = {Probing the factor structure of metabolic syndrome in Sardinian genetic isolates.},

author = {Graziano F and Grassi M and Sacco S and Concas MP and Vaccargiu S and Pirastu M and Biino G},

url = {https://www.sciencedirect.com/science/article/pii/S0939475315000472?via%3Dihub},

doi = {10.1016/j.numecd.2015.02.004},

year  = {2015},

date = {2015-06-26},

journal = {Nutrition, Metabolism, and Cardiovascular Diseases : Nmcd. Letter To Editor},

volume = {25},

pages = {548-555},

abstract = {BACKGROUND AND AIMS: Owing to the multiplicity of the key components of metabolic syndrome (MetS), its diagnosis is very complex. The lack of a unique definition is responsible for the prevalence variability observed among studies; therefore, a definition based on continuous variables was recommended. The aim of this study was to compare competing models of the MetS factor structure for selecting the one that explains the best clustering pattern and to propose an algorithm for computing MetS as a continuous variable. METHODS AND RESULTS: Data were from isolated Sardinian populations (n = 8102). Confirmatory factor analysis (CFA) and two-group CFA by gender were performed to evaluate the sex-specific factor structure of MetS. After selecting the best model, an algorithm was obtained using factor loadings/residual variances. The quality of the MetS score was evaluated by the receiver operating characteristics curve and the area under the curve. Cross-validation was performed to validate the score and to determine the best cut point. The best fit model was a bifactor one with a general factor (MetS) and three specific factors (f1: obesity/adiposity trait; f2: hypertension/blood pressure trait; and f3: lipid trait). Gender-specific algorithms were implemented to obtain MetS scores showing a good diagnostic performance (0.80 specificity and 0.80 sensitivity for the cut point). Furthermore, cross-validation confirmed these results. CONCLUSION: These analyses suggested that the bifactor model was the most representative one. In addition, they provided a score and a cut point that are both clinically accessible and interpretable measures for MetS diagnosis and likely useful for evaluating the association with adverse cardiovascular disease and diabetes and for investigating the MetS genetic component.Copyright © 2015 Elsevier B.V. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_369,

title = {hnRNP L inhibits CD44 V10 exon splicing through interacting with its upstream intron},

author = {Loh TJ and Cho S and Moon H and Jang HN and Williams DR and Jung DW and Kim IC and Ghigna C and Biamonti G and Zheng X and Shen H},

url = {https://www.sciencedirect.com/science/article/pii/S1874939915000413?via%3Dihub},

doi = {10.1016/j.bbagrm.2015.01.004},

year  = {2015},

date = {2015-06-25},

journal = {Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms},

volume = {1849},

number = {6},

pages = {743-750},

abstract = {CD44 is a complex cell adhesion molecule that mediates communication and adhesion between adjacent cells as well as between cells and the extracellular matrix. CD44 pre-mRNA produces various mRNA isoforms through alternative splicing of 20 exons, among which exons 1-5 (C1-C5) and 16-20 (C6-C10) are constant exons, whereas exons 6-15 (V1-V10) are variant exons. CD44 V10 exon has important roles in breast tumor progression and Hodgkin lymphoma. Here we show that increased expression of hnRNP L inhibits V10 exon splicing of CD44 pre-mRNA, whereas reduced expression of hnRNP L promotes V10 exon splicing. In addition, hnRNP L also promotes V10 splicing of endogenous CD44 pre-mRNA. Through mutation analysis, we demonstrate that the effects of hnRNP L on V10 splicing are abolished when the CA-rich sequence on the upstream intron of V10 exon is disrupted. However, hnRNP L effects are stronger if more CA-repeats are provided. Furthermore, we show that hnRNP L directly contacts the CA-rich sequence. Importantly, we provide evidences that hnRNP L inhibits U2AF65 binding on the upstream Py tract of V10 exon. Our results reveal that hnRNP L is a new regulator for CD44 V10 exon splicing. Copyright  2015 Elsevier B.V. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_413,

title = {The impact of low-dose carcinogens and environmental disruptors on tissue invasion and metastasis.},

author = {Ochieng J and Nangami GN and Ogunkua O and Miousse IR and Koturbash I and Odero-Marah V and McCawley L and Nangia-Makker P and Ahmed N and Luqmani Y and Chen Z and Papagerakis S and Wolf GT and Dong C and Zhou BP and Brown DG and Colacci A and Hamid RA and Mondello C and Raju J and Ryan EP and Woodrick J and Scovassi AI and Singh N and Vaccari M and Roy R and Forte S and Memeo L and Salem HK and Amedei A and Al-Temaimi R and Al-Mulla F and Bisson WH and Eltom SE},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S128/313982},

doi = {10.1093/carcin/bgv034},

year  = {2015},

date = {2015-06-19},

urldate = {2015-06-19},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S128-159},

abstract = {The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial-mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis. The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_415,

title = {The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling.},

author = {Engstrom W and Darbre P and Eriksson S and Gulliver L and Hultman T and Karamouzis MV and Klaunig JE and Mehta R and Moorwood K and Sanderson T and Sone H and Vadgama P and Wagemaker G and Ward A and Singh N and Al-Mulla F and Al-Temaimi R and Amedei A and Colacci AM and Vaccari M and Mondello C and Scovassi AI and Raju J and Hamid RA and Memeo L and Forte S and Roy R and Woodrick J and Salem HK and Ryan E and Brown DG and Bisson WH},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S38/311505},

doi = {10.1093/carcin/bgv030},

year  = {2015},

date = {2015-06-12},

urldate = {2015-06-12},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S38-60},

abstract = {The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_419,

title = {Studies on the ATP Binding Site of Fyn Kinase for the Identification of New Inhibitors and Their Evaluation as Potential Agents against Tauopathies and Tumors.},

author = {Tintori C and La Sala G and Vignaroli G and Botta L and Fallacara AL and Falchi F and Radi M and Zamperini C and Dreassi E and Dello Iacono L and Orioli D and Biamonti G and Garbelli M and Lossani A and Gasparrini F and Tuccinardi T and Laurenzana I and Angelucci A and Maga G and Schenone S and Brullo C and Musumeci F and Desogus A and Crespan E and Botta M},

url = {https://pubs.acs.org/doi/10.1021/acs.jmedchem.5b00140},

doi = {10.1021/acs.jmedchem.5b00140},

year  = {2015},

date = {2015-06-11},

journal = {Journal of Medicinal Chemistry},

volume = {58},

number = {11},

pages = {4590-4609},

abstract = {Fyn is a member of the Src-family of nonreceptor protein-tyrosine kinases. Its abnormal activity has been shown to be related to various human cancers as well as to severe pathologies, such as Alzheimer's and Parkinson's diseases. Herein, a structure-based drug design protocol was employed aimed at identifying novel Fyn inhibitors. Two hits from commercial sources (1, 2) were found active against Fyn with K(i) of about 2 μM, while derivative 4a, derived from our internal library, showed a K(i) of 0.9 μM. A hit-to-lead optimization effort was then initiated on derivative 4a to improve its potency. Slightly modifications rapidly determine an increase in the binding affinity, with the best inhibitors 4c and 4d having K(i)s of 70 and 95 nM, respectively. Both compounds were found able to inhibit the phosphorylation of the protein Tau in an Alzheimer's model cell line and showed antiproliferative activities against different cancer cell lines.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_383,

title = {MRJF4, a novel histone deacetylase inhibitor, induces p21 mediated autophagy in PC3 prostate cancer cells.},

author = {{Di Giacomo V} and {Di Valerio V} and Rapino M and Bosco D and Cacciatore I and Ciulla M and Marrazzo A and Fiorito J and Di Stefano A and Cataldi A},

url = {https://www.cellmolbiol.org/index.php/CMB/article/view/663},

year  = {2015},

date = {2015-06-08},

journal = {Cellular and Molecular Biology (Noisy-le-Grand, France) },

volume = {61},

number = {3},

abstract = {Autophagy is a cellular defense mechanism which occurs through degradation and recycling of cytoplasmic constituents and represents a caspase-independent alternative to cell death by apoptosis. It is generally accepted that the suppression of autophagy in many cancer cells is directly correlated to malignancy; hence, the control of autophagy genes could represent a target for cancer therapy. The inhibition of cell proliferation through autophagy activation could be an important mechanism for many anti-tumor drugs. Here we report the effects of a novel histone deacetylase inhibitor MRJF4 (racemic mixture) and of its two enantiomers [(+)-MRJF4 and (-)-MRJF4] on the morphological and molecular mechanisms causing death and migration of PC3 prostatic cancer cells. In particular, we investigated the occurrence of the autophagic process, both at morphological and molecular levels (LC3 expression), and its relationship with p21, a key molecule which regulates cell cycle and autophagy cell death. Moreover, pERK/Nf-kB driven intracellular signaling, the expression of MMP9 protein - a key component of cell migration - invasion, and metastasis were assayed. Our results showed that the anti-proliferative effects of MRJF4 due to autophagy occurrence, documented by LC3 increase and ultrastructural modifications, and the reduction of invasiveness seem to be mediated by the down-regulation of pERK/NF-kB signaling pathway, along with p21 up-regulation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_361,

title = {Expansion of CAG triplet repeats by human DNA polymerases λ and β in vitro, is regulated by flap endonuclease 1 and DNA ligase 1.},

author = {Crespan E and Hübscher U and Maga G},

url = {https://www.sciencedirect.com/science/article/pii/S1568786415000178?via%3Dihub},

doi = {10.1016/j.dnarep.2015.01.005},

year  = {2015},

date = {2015-05-29},

journal = {DNA Repair},

volume = {29},

pages = {101-111},

abstract = {Huntington's disease (HD) is a neurological genetic disorder caused by the expansion of the CAG trinucleotide repeats (TNR) in the N-terminal region of coding sequence of the Huntingtin's (HTT) gene. This results in the addition of a poly-glutamine tract within the Huntingtin protein, resulting in its pathological form. The mechanism by which TRN expansion takes place is not yet fully understood. We have recently shown that DNA polymerase (Pol) beta can promote the microhomology-mediated end joining andtriplet expansion of a substrate mimicking a double strand break in the TNR region of the HTT gene. Here we show that TNRexpansion is dependent on the structure of the DNA substrate, as well as on the two essential Pol beta co-factors: flap endonuclease1 (Fen1) and DNA ligase 1 (Lig1). We found that Fen1 significantly stimulated TNR expansion by Pol beta, but not by the related enzyme Pol lambda, and subsequent ligation of the DNA products by Lig1. Interestingly, the deletion of N-terminal domains of Pol lambda, resulted in an enzyme which displayed properties more similar to Pol beta, suggesting a possible evolutionary mechanism. These results may suggest a novel mechanism for somatic TNR expansion in HD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_384,

title = {Multi-Faceted Characterization of a Novel LuxR-Repressible Promoter Library for Escherichia coli.},

author = {Zucca S and Pasotti L and Politi N and Casanova M and Mazzini G and Cusella De Angelis MG and Magni P},

url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0126264},

doi = {10.1371/journal.pone.0126264},

year  = {2015},

date = {2015-05-26},

journal = {Plos One},

volume = {10},

number = {5},

pages = {e0126264},

abstract = {The genetic elements regulating the natural quorum sensing (QS) networks of several microorganisms are widely used in synthetic biology to control the behaviour of single cells and engineered bacterial populations via ad-hoc constructed synthetic circuits. A number of novel engineering-inspired biological functions have been implemented and model systems have also been constructed to improve the knowledge on natural QS systems. Synthetic QS-based parts, such as promoters, have been reported in literature, to provide biological components with functions that are not present in nature, like modified induction logic or activation/repression by additional molecules. In this work, a library of promoters that can be repressed by the LuxR protein in presence of the QS autoinducer N-3-oxohexanoyl-L-homoserine lactone (AHL) was reported for Escherichia coli, to expand the toolkit of genetic parts that can be used to engineer novel synthetic QS-based systems. The library was constructed via polymerase chain reaction with highly constrained degenerate oligonucleotides, designed according to the consensus -35 and -10 sequences of a previously reported constitutive promoter library of graded strength, to maximize the probability of obtaining functional clones. All the promoters have a lux box between the -35 and -10 regions, to implement a LuxR-repressible behaviour. Twelve unique library members of graded strength (about 100-fold activity range) were selected to form the final library and they were characterized in several genetic contexts, such as in different plasmids, via different reporter genes, in presence of a LuxR expression cassette in different positions and in response to different AHL concentrations. The new obtained regulatory parts and corresponding data can be exploited by synthetic biologists to implement an artificial AHL-dependent repression of transcription in genetic circuits. The target transcriptional activity can be selected among the available library members to meet the design specifications of the biological system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_389,

title = {Novel nano-composite biomimetic biomaterial allows chondrogenic and osteogenic differentiation of bone marrow concentrate derived cells.},

author = {Grigolo B and Cavallo C and Desando G and Manferdini C and Lisignoli G and Ferrari A and Zini N and Facchini A},

url = {https://link.springer.com/article/10.1007%2Fs10856-015-5500-9},

doi = {10.1007/s10856-015-5500-9},

year  = {2015},

date = {2015-04-30},

journal = {Journal of Materials Science. Materials in Medicine},

volume = {26},

number = {4},

pages = {173},

abstract = {In clinical orthopedics suitable materials that induce and restore biological functions together with the right mechanical properties are particularly needed for the regeneration of osteochondral lesions. For this purpose, the ideal scaffold should possess the right properties with respect to degradation, cell binding, cellular uptake, non-immunogenicity, mechanical strength, and flexibility. In addition, it should be easy to handle and serve as a template for chondrocyte and bone cells guiding both cartilage and bone formation. The aim of the present study was to estimate the chondrogenic and osteogenic capability of bone marrow concentrated derived cells seeded onto a novel nano-composite biomimetic material. These properties have been evaluated by means of histological, immunohistochemical and electron microscopy analyses. The data obtained demonstrated that freshly harvested cells obtained from bone marrow were able, once seeded onto the biomaterial, to differentiate either down the chondrogenic and osteogenic pathways as evaluated by the expression and production of specific matrix molecules. These findings support the use, for the repair of osteochondral lesions, of this new nano-composite biomimetic material together with bone marrow derived cells in a "one step" transplantation procedure.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_392,

title = {PI-PLCbeta1b affects Akt activation, cyclin E expression, and caspase cleavage, promoting cell survival in pro-B-lymphoblastic cells exposed to oxidative stress.},

author = {Piazzi M and Blalock WL and Bavelloni A and Faenza I and Raffini M and Tagliavini F and Manzoli L and Cocco L},

url = {https://www.fasebj.org/doi/full/10.1096/fj.14-259051?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&},

doi = {10.1096/fj.14-259051},

year  = {2015},

date = {2015-04-30},

journal = {FASEB Journal},

volume = {29},

number = {4},

pages = {1383-1394},

abstract = {The phosphoinositide-dependent signal transduction pathway has been implicated in the control of a variety of biologic processes, such as the regulation of cellular metabolism and homeostasis, cell proliferation and differentiation, and apoptosis. One of the key players in the regulation of inositol lipid signaling is the phospholipase Cbeta1 (PI-PLCbeta1), that hydrolyzes phosphatidylinositol 4,5-bisphosphate [PtIns(4,5)P2], giving rise to the second messengers inositol triphosphate and diacylglicerol. PI-PLCbeta1 has been associated with the regulation of several cellular functions, some of which have not yet been fully understood. In particular, it has been reported that PI-PLCbeta1 protects murine fibroblasts from oxidative stress-induced cell death. The mediators of oxidative stress, reactive oxygen species (ROS), have been shown to regulate major epigenetic processes, causing the silencing of tumor suppressors and enhancing the proliferation of leukemic cells underoxidative stress. Investigation of the interplay between ROS, PI-PLCbeta1, and their signaling mediators in leukemia might therefore reveal innovative targets of pharmacological therapy in the treatment for leukemia. In this work, we demonstrate that in pro-B-lymphoblastic cells (Ba/F3), treated with H2O2, PI-PLCbeta1b conferred resistance to cell death, promoting cellcycle progression and cell proliferation and influencing the expression of cyclin A and E. Interestingly, we found that,expression of PI-PLCbeta1b affects the activity of caspase-3, caspase-7, and of several protein kinases induced by oxidativestress. In particular, PI-PLCbeta1b expression completely abolished the phosphorylation of Erk1/2 MAP kinases, down-regulated phosphatase and tensin homolog (PTEN), and up-regulated the phosphorylation of Akt, thereby sustaining cellular proliferation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_401,

title = {Replication and transcription on a collision course: eukaryotic regulation mechanisms and implications for DNA stability.},

author = {Brambati A and Colosio A and Zardoni L and Galanti L and Liberi G},

url = {https://www.frontiersin.org/articles/10.3389/fgene.2015.00166/full},

doi = {10.3389/fgene.2015.00166},

year  = {2015},

date = {2015-04-28},

journal = {Frontiers in Genetics},

volume = {6},

pages = {166},

abstract = {DNA replication and transcription are vital cellular processes during which the genetic information is copied into complementary DNA and RNA molecules. Highly complex machineries required for DNA and RNA synthesis compete for the same DNA template, therefore being on a collision course. Unscheduled replication-transcription clashes alter the gene transcription program and generate replication stress, reducing fork speed. Molecular pathways and mechanisms that minimize the conflict between replication and transcription have been extensively characterized in prokaryotic cells and recently identified also in eukaryotes. A pathological outcome of replication-transcription collisions is the formation of stable RNA:DNA hybrids in molecular structures called R-loops. Growing evidence suggests that R-loop accumulation promotes both genetic and epigenetic instability, thus severely affecting genome functionality. In the present review, we summarize the current knowledge related to replication and transcription conflicts in eukaryotes, their consequences on genome stability and the pathways involved in their resolution. These findings are relevant to clarify the molecular basis of cancer and neurodegenerative diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_399,

title = {Prohibitin 2: At a communications crossroads.},

author = {Bavelloni A and Piazzi M and Raffini M and Faenza I and Blalock WL},

url = {https://iubmb.onlinelibrary.wiley.com/doi/full/10.1002/iub.1366},

doi = {10.1002/iub.1366},

year  = {2015},

date = {2015-04-24},

journal = {IUBMB Life},

volume = {67},

number = {4},

pages = {239-254},

abstract = {Prohibitins (PHBs) are a highly conserved class of proteins first discovered as inhibitors of cellular proliferation. Since then PHBs have been found to have a significant role in transcription, nuclear signaling, mitochondrial structural integrity, cell division, and cellular membrane metabolism, placing these proteins among the key regulators of pathologies such as cancer, neuromuscular degeneration, and other metabolic diseases. The human genome encodes two PHB proteins, prohibitin 1 (PHB1) and prohibitin 2 (PHB2), which function not only as a heterodimeric complex, but also independently. While many previous reviews have focused on the better characterized prohibitin, PHB1, this review focuses on PHB2 and new data concerning its cellular functions both in complex with PHB1 and independent of PHB1. 2015 International Union of Biochemistry and Molecular Biology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_393,

title = {PI3K pan-inhibition impairs more efficiently proliferation and survival of T-cell acute lymphoblastic leukemia cell lines when compared to isoform-selective PI3K inhibitors.},

author = {Lonetti A and Cappellini A and Spartà AM and Chiarini F and Buontempo F and Evangelisti C and Evangelisti C and Orsini E and McCubrey JA and Martelli AM},

url = {https://www.fasebj.org/doi/full/10.1096/fj.14-259051?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&},

year  = {2015},

date = {2015-04-15},

journal = {Oncotarget},

volume = {6},

number = {12},

pages = {10399-10414},

abstract = {Class I phosphatidylinositol 3-kinases (PI3Ks) are frequently activated in T-cell acute lymphoblastic leukemia (T-ALL), mainly due to the loss of PTEN function. Therefore, targeting PI3Ks is a promising innovative approach for T-ALL treatment, however at present no definitive evidence indicated which is the better therapeutic strategy between pan or selective isoform inhibition, as all the four catalytic subunits might participate in leukemogenesis. Here, we demonstrated that in both PTEN deleted and PTEN non deleted T-ALL cell lines, PI3K pan-inhibition exerted the highest cytotoxic effects when compared to both selective isoform inhibition or dual p110γ/δ inhibition. Intriguingly, the dual p110γ/δ inhibitor IPI-145 was effective in Loucy cells, which are representative of early T-precursor (ETP)-ALL, a T-ALL subtype associated with a poor outcome. PTEN gene deletion did not confer a peculiar reliance of T-ALL cells on PI3K activity for their proliferation/survival, as PTEN was inactivated in PTEN non deleted cells, due to posttranslational mechanisms. PI3K pan-inhibition suppressed Akt activation and induced caspase-independent apoptosis. We further demonstrated that in some T-ALL cell lines, autophagy could exert a protective role against PI3K inhibition. Our findings strongly support clinical application of class I PI3K pan-inhibitors in T-ALL treatment, with the possible exception of ETP-ALL cases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_360,

title = {Epicardial fat thickness: threshold values and lifestyle association in male adolescents.},

author = {Cena H and Fonte ML and Casali PM and Maffoni S and Roggi C and Biino G},

url = {https://onlinelibrary.wiley.com/doi/full/10.1111/ijpo.227},

doi = {10.1111/ijpo.227},

year  = {2015},

date = {2015-04-10},

journal = {Pediatric Obesity},

volume = {10},

number = {2},

pages = {105-111},

abstract = {BACKGROUND: Obese adolescents with high proportion of visceral fat are at higher risk of developing the metabolic syndrome. OBJECTIVES: The study aims to investigate if echocardiographic epicardial fat thickness (EF) could be predictive of visceral obesity (VO) early in life and to provide EF threshold values specific for male adolescents. Further aim was to investigate the association between EF, lifestyle and metabolic disease familiarity. METHODS: Anthropometric data were collected from 102 normal weight and overweight, healthy male adolescents (mean age: 14.91 +/-  1.98 years); bioelectrical impedance analysis and transthoracic echocardiogram were performed in the same sample. Each participant fulfilled a validated self-administered lifestyle questionnaire. RESULTS: We found higher EF values in sedentary adolescents (P < 0.05), in those who never eat fruit and vegetables (P < 0.05), and in those with overweight mothers (P < 0.05). The strongest independent predictor of EF was waist circumference (P < 0.0001). Using the waist to height ratio as a marker of VO, logistic regression analysis revealed that 1 mm EF gain is responsible for seven times higher VO risk (P < 0.0001). Receiver Operating Characteristic (ROC) analysis showed that the optimal cut-off for EF thickness associated to youth VO is 3.2 mm.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_381,

title = {Modulation of TGFbeta 2 levels by lamin A in U2-OS osteoblast-like cells: understanding the osteolytic process triggered by altered lamins.},

author = {Evangelisti C and Bernasconi P and Cavalcante P and Cappelletti C and D'Apice MR and Sbraccia P and Novelli G and Prencipe S and Lemma S and Baldini N and Avnet S and Squarzoni S and Martelli AM and Lattanzi G},

url = {http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=3232&pubmed-linkout=1},

year  = {2015},

date = {2015-04-10},

journal = {Oncotarget},

volume = {6},

number = {10},

pages = {7424-7437},

abstract = {Transforming growth factor beta (TGFbeta) plays an essential role in bone homeostasis and deregulation of TGFbeta occurs in bone pathologies. Patients affected by Mandibuloacral Dysplasia (MADA), a progeroid disease linked to LMNA mutations, suffer from an osteolytic process. Our previous work showed that MADA osteoblasts secrete excess amount of TGFbeta 2, which in turn elicits differentiation of human blood precursors into osteoclasts. Here, we sought to determine how altered lamin A affects TGFbeta signaling. Our results show that wild-type lamin A negatively modulates TGFbeta 2 levels in osteoblast-like U2-OS cells, while the R527H mutated prelamin A as well as farnesylated prelamin A do not, ultimately leading to increased secretion of TGFbeta 2. TGFbeta 2 in turn, triggers the Akt/mTOR pathway and upregulates osteoprotegerin and cathepsin K. TGFbeta 2 neutralization rescues Akt/mTOR activation and the downstream transcriptional effects, an effect also obtained by statins or RAD001 treatment. Our results unravel an unexpected role of lamin A in TGFbeta 2 regulation and indicate rapamycin analogs and neutralizing antibodies to TGFbeta 2 as new potential therapeutic tools for MADA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_400,

title = {Reference genes for gene expression analysis in proliferating and differentiating human keratinocytes.},

author = {Lanzafame M and Botta E and Teson M and Fortugno P and Zambruno G and Stefanini M and Orioli D},

url = {https://iubmb.onlinelibrary.wiley.com/doi/full/10.1002/iub.1366},

doi = {10.1002/iub.1366},

year  = {2015},

date = {2015-04-07},

journal = {Experimental Dermatology},

volume = {24},

number = {4},

abstract = {Abnormalities in keratinocyte growth and differentiation have a pathogenic significance in many skin disorders and result in gene expression alterations detectable by quantitative real-time RT-PCR (qRT-PCR). Relative quantification based on endogenous control (EC) genes is the commonly adopted approach, and the use of multiple reference genes from independent pathways is considered a best practice guideline, unless fully validated EC genes are available. The literature on optimal reference genes during in vitro calcium-induced differentiation of normal human epidermal keratinocytes (NHEK) is inconsistent. In many studies, the expression of target genes is compared to that of housekeeping genes whose expression, however, significantly varies during keratinocyte differentiation. Here, we report the results of our investigations on the expression stability of 15 candidate EC genes, including those commonly used as reference in expression analysis by qRT-PCR, during NHEK calcium-induced differentiation. We demonstrate that YWHAZ and UBC are extremely stable genes, and therefore, they represent optimal EC genes for expression studies in proliferating and calcium-induced differentiating NHEK. Furthermore, we demonstrate that YWHAZ/14-3-3-zeta is a suitable reference for quantitative comparison of both transcript and protein levels. 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_386,

title = {NF-kB mediated down-regulation of collagen synthesis upon HEMA (2-hydroxyethyl methacrylate) treatment of primary human gingival fibroblast/Streptococcus mutans co-cultured cells.},

author = {Grande R and Pacella S and Di Giulio M and Rapino M and Di Valerio V and Cellini L and Cataldi A},

url = {https://link.springer.com/article/10.1007%2Fs00784-014-1304-4},

doi = {10.1007/s00784-014-1304-4},

year  = {2015},

date = {2015-03-25},

journal = {Clinical Oral Investigations},

volume = {19},

number = {4},

abstract = {PURPOSE: In vitro studies have evidenced the cytotoxic effect of HEMA (2-hydroxyethyl methacrylate), the most common component of dental resin-based restorative material, which is released within the oral cavity, on eukaryotic cells such as gingival fibroblast and epithelial cells. However, since the presence of microorganisms within the oral cavity cannot be excluded and little is known about the interactions occurring between eukaryotic cells and the human oral microbiota, our attention has been addressed to investigate the effect of 3 mM HEMA on the molecular mechanisms driving the response of human gingival fibroblasts (HGFs) co-cultured with Streptococcus mutans. METHODOLOGY:HGF/S. mutans co-culture has been set up in our lab, and upon HEMA treatment, S.mutans and HGF cells' viability and adhesion along with type I collagen gene and pro-collagen I, Bax, Bcl2, nuclear factor kB (NF-kB), IkBα, pIkBα protein expression by PCR, Western blotting and ELISA assays have been investigated. RESULTS:HEMA treatment determines a significant decrease of type I collagen protein production, even in the presence of S. mutans, in parallel to a decrease of cell viability and adhesion, which seem to be regulated by NF-kB activation. In fact, when SN50, NF-kB-specific pharmacological inhibitor, is added to the culture, cell proliferation along with collagen synthesis is restored. CONCLUSION: The modulation exerted by S. mutans on the cytotoxic effect of HEMA suggests that within the oral cavity, the eukaryotic/prokaryotic cell interactions, maintaining the balance of the environment, allow HEMA to perform its adhesive and bonding function and that the use of a co-culture system, which simulates the oral cavity organization, improves the knowledge concerning the biocompatibility of this dental material.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_362,

title = {FSH and LH receptors are differentially expressed in cumulus cells surrounding developmentally competent and incompetent mouse fully grown antral oocytes.},

author = {Vigone G and Merico V and Redi CA and Mazzini G and Garagna S and Zuccotti M},

doi = {10.1071/RD13251},

year  = {2015},

date = {2015-03-19},

journal = {Reproduction, fertility and development},

volume = {27},

number = {3},

pages = {497-503},

abstract = {Cumulus cells (CCs) maintain strict functional relationships with the enclosed antral oocyte and are thought to reflect its developmental competence. Several studies have described a correlation between CC gene expression and oocyte quality. Herein, we tested whether CC-specific FSH and LH receptors (FSHR and LHR, respectively) are differentially expressed in CCs enclosing developmentally competent or incompetent oocytes. To this end, mouse fully grown cumulus-oocyte complexes were isolated and their CCs and oocytes analysed separately. Based on their chromatin organisation, oocytes were classified as those with a surrounded nucleolus (SN) or a non-surrounded nucleolus (NSN), the former being developmentally competent, whereas the latter arrest at the 2-cell stage. The CCs were then analysed to compare the pattern of expression of the Fshr and Lhr genes and their proteins. Quantitative reverse transcription-polymerase chain reaction analysis revealed that only Lhr is significantly differentially expressed. Immunofluorescence analysis revealed that both FSHR and LHR proteins are significantly upregulated in CCs surrounding oocytes arrested at the 2-cell stage, reflecting their developmental incompetence.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_387,

title = {Notch is a direct negative regulator of the DNA-damage response.},

author = {Vermezovic J and Adamowicz M and Santarpia L and Rustighi A and Forcato M and Lucano C and Massimiliano L and Costanzo V and Bicciato S and Del Sal G and {d'Adda di Fagagna F}},

url = {https://www.nature.com/articles/nsmb.3013},

doi = {10.1038/nsmb.3013},

year  = {2015},

date = {2015-03-14},

journal = {Nature Structural & Molecular Biology},

volume = {22},

number = {5},

pages = {417-424},

abstract = {The DNA-damage response (DDR) ensures genome stability and proper inheritance of genetic information, both of which are essential to survival. It is presently unclear to what extent other signaling pathways modulate DDR function. Here we show that Notch receptor binds and inactivates ATM kinase and that this mechanism is evolutionarily conserved in Caenorhabditis elegans, Xenopus laevis and humans. In C. elegans, the Notch pathway impairs DDR signaling in gonad germ cells. In mammalian cells, activation of human Notch1 leads to reduced ATM signaling in a manner independent of Notch1 transcriptional activity. Notch1 binds directly to the regulatory FATC domain of ATM and inhibits ATM kinase activity. Notch1 and ATM activation are inversely correlated in human breast cancers, and inactivation of ATM by Notch1 contributes to the survival of Notch1-driven leukemia cells upon DNA damage.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_379,

title = {Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?},

author = {Robey RB and Weisz J and Kuemmerle NB and Salzberg AC and Berg A and Brown DG and Kubik L and Palorini R and Al-Mulla F and Al-Temaimi R and Colacci A and Mondello C and Raju J and Woodrick J and Scovassi AI and Singh N and Vaccari M and Roy R and Forte S and Memeo L and Salem HK and Amedei A and Hamid RA and Williams GP and Lowe L and Meyer J and Martin FL and Bisson WH and Chiaradonna F and Ryan EP},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S203/316346},

doi = {10.1093/carcin/bgv037},

year  = {2015},

date = {2015-03-13},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S203-231},

abstract = {Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling need to establish common or complementary frameworks for further exploration that experimentally and conceptually consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise enabling the development and selection of cancer are suggested. Published by Oxford University Press 2015.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_418,

title = {Unconventional Knoevenagel-type indoles: Synthesis and cell-based studies for the identification of pro-apoptotic agents.},

author = {Spallarossa A and Caneva C and Caviglia M and Alfei S and Butini S and Campiani G and Gemma S and Brindisi M and Zisterer DM and Bright SA and Williams CD and Crespan E and Maga G and Sanna G and Delogu I and Collu G and Loddo R},

url = {https://www.sciencedirect.com/science/article/pii/S0223523415301938?via%3Dihub},

doi = {10.1016/j.ejmech.2015.08.009},

year  = {2015},

date = {2015-03-12},

urldate = {2017-03-03},

journal = {European Journal of Medicinal Chemistry},

volume = {102},

pages = {648-660},

abstract = {A new series of indole-based analogues were recently identified as potential anticancer agents. The Knoevenagel-type indoles herein presented were prepared via a one-pot condensation of iminium salts with active methylene reagents and were isolated as single geometric isomers. Biological evaluation in different cell-based assays revealed an antiproliferative activity for some analogues already in the nanomolar range against leukaemia, breast and renal cancer cell lines. To explain these effects, the most promising analogues of the series were engaged in further cell-based studies. Compounds 5e, l, p and 6a, b highlighted a pro-apoptotic potential being able to induce apoptosis in HL60, K562 and MCF-7 cell lines in a dose and time-dependent manner. The ability of these compounds to arrest cell cycle at the G2/M phase inspired the immunofluorescence studies which allowed us to identify tubulin as a potential target for compounds 5l and 6b. Copyright 2015 Elsevier Masson SAS. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_407,

title = {Sound representation in higher language areas during language generation.},

author = {Magrassi L and Aromataris G and Cabrini A and Annovazzi-Lodi V and Moro A},

url = {https://www.pnas.org/content/112/6/1868.long},

doi = {10.1073/pnas.1418162112},

year  = {2015},

date = {2015-03-11},

journal = {Proceedings of the National Academy of Sciences of the United States of America},

volume = {112},

number = {6},

pages = {1868-1873},

abstract = {How language is encoded by neural activity in the higher-level language areas of humans is still largely unknown. We investigated whether the electrophysiological activity of Broca’s area correlates with the sound of the utterances produced. During speech perception, the electric cortical activity of the auditory areas correlates with the sound envelope of the utterances. In our experiment, we compared the electrocorticogram recorded during awake neurosurgical operations in Broca’s area and in the dominant temporal lobe with the sound envelope of single words versus sentences read aloud or mentally by the patients. Our results indicate that the electrocorticogram correlates with the sound envelope of the utterances, starting before any sound is produced and even in the absence of speech, when the patient is reading mentally. No correlations were found when the electrocorticogram was recorded in the superior parietal gyrus, an area not directly involved in language generation, or in Broca’s area when the participants were executing a repetitive motor task, which did not include any linguistic content, with their dominant hand. The distribution of suprathreshold correlations across frequencies of cortical activities varied whether the sound envelope derived from words or sentences. Our results suggest the activity of language areas is organized by sound when language is generated before any utterance is produced or heard.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_395,

title = {Poly(ADP-ribosylation) and neurodegenerative disorders.},

author = {Basello DA and Scovassi AI},

url = {https://www.sciencedirect.com/science/article/pii/S156772491530012X?via%3Dihub},

doi = {10.1016/j.mito.2015.07.005},

year  = {2015},

date = {2015-03-06},

journal = {Mitochondrion},

volume = {24},

pages = {56-63},

abstract = {Impaired mitochondrial structure and function are common features of neurodegenerative disorders, ultimately characterized by the death of neural cells promoted by still unknown signals. Among the possible modulators of neurodegeneration, the activation of poly(ADP-ribosylation), a post-translational modification of proteins, has been considered, being the product of the reaction, poly(ADP-ribose), a signaling molecule for different cell death paradigms. The basic properties of poly(ADP-ribosylation) are here described, focusing on the mitochondrial events; cell death paradigms such as apoptosis, parthanatos, necroptosis and mitophagy are illustrated. Finally, the promising use of poly(ADP-ribosylation) inhibitors to rescue neurodegeneration is addressed. Copyright  2015 Elsevier B.V. and Mitochondria Research Society. Published by Elsevier B.V. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_412,

title = {The effect of environmental chemicals on the tumor microenvironment.},

author = {Casey SC and Vaccari M and Al-Mulla F and Al-Temaimi R and Amedei A and Barcellos-Hoff MH and Brown DG and Chapellier M and Christopher J and Curran C and Forte S and Hamid RA and Heneberg P and Koch DC and Krishnakumar PK and Laconi E and Maguer-Satta V and Marongiu F and Memeo L and Mondello C and Raju J and Roman J and Roy R and Ryan EP and Ryeom S and Salem HK and Scovassi AI and Singh N and Soucek L and Vermeulen L and Whitfield JR and Woodrick J and Colacci A and Bisson WH and Felsher DW},

url = {https://academic.oup.com/carcin/article/36/Suppl_1/S160/315417},

doi = {10.1093/carcin/bgv035},

year  = {2015},

date = {2015-03-06},

journal = {Carcinogenesis},

volume = {36},

number = {Suppl. 1},

pages = {S160-183},

abstract = {Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis. The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_396,

title = {Posttranscriptional Regulation and RNA Binding Proteins in Cancer Biology.},

author = {Ghigna C and Cartegni L and Jordan P and Paronetto MP},

url = {https://www.hindawi.com/journals/bmri/2015/897821/},

doi = {10.1155/2015/897821},

year  = {2015},

date = {2015-03-05},

journal = {Biomed Research International},

volume = {2015},

pages = {897821},

keywords = {},

pubstate = {published},

tppubtype = {article}

}