@article{%a1:%Y_116,

title = {Ripples on the surface. Surnames and genes in Sicily and Southern Italy.},

author = {Boattini A and Sarno S and Fiorani O and Lisa A and Luiselli D and Pettener D},

url = {http://www.tandfonline.com/doi/abs/10.1080/03014460.2017.1411525?journalCode=iahb20},

doi = {10.1080/03014460.2017.1411525},

year  = {2018},

date = {2018-02-14},

journal = {Annals of Human Biology},

volume = {45},

number = {1},

pages = {57-65},

abstract = {Southern Italy and Sicily played a key role in the peopling history of the Mediterranean. While genetic research showed the remarkable homogeneity of these regions, surname-based studies instead suggested low population mobility, hence potential structuring. AIM: In order to better understand these different patterns, this study (1) thoroughly analysed the surname structure of Sicily and Southern Italy and (2) tested its relationships with a wide set of molecular markers. SUBJECTS AND METHODS: Surname data were collected from 1213 municipalities and compared to uniparental and autosomal genetic markers typed in about 300 individuals from 8-10 populations. Surname analyses were performed using different multivariate methods, while comparisons with genetic data relied on correlation tests. RESULTS: Surnames were clearly structured according to regional geographic patterns, which likely emerged because of recent isolation-by-distance-like population dynamics. In general, genetic markers, hinting at a pervasive homogeneity, did not correlate with surname distribution. However, long autosomal haplotypes (>5 cM) that compared to genotypic (SNPs) data identify more "recent" relatedness, showing a clear association with surname patterns. CONCLUSION: The apparent contradiction between surname structure and genetic homogeneity was resolved by figuring surnames as recent "ripples" deposited on a vast and ancient homogeneous genetic "surface".},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_117,

title = {Cells Escape an Operational Mitotic Checkpoint through a Stochastic Process.},

author = {Bonaiuti P and Chiroli E and Gross F and Corno A and Vernieri C and Stefl M and Cosentino Lagomarsino M and Knop M and Ciliberto A},

url = {https://www.sciencedirect.com/science/article/pii/S0960982217315130?via%3Dihub},

doi = {10.1016/j.cub.2017.11.031},

year  = {2018},

date = {2018-02-14},

journal = {Current Biology},

volume = {28},

number = {1},

pages = {28-37},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_119,

title = {Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription.},

author = {Brambati A and Zardoni L and Achar YJ and Piccini D and Galanti L and Colosio A and Foiani M and Liberi G},

url = {https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkx945/4559489},

doi = {doi.org/10.1093/nar/gkx945},

year  = {2018},

date = {2018-02-14},

journal = {Nucleic Acids Research},

volume = {46},

number = {3},

pages = {12271239},

abstract = {The yeast RNA/DNA helicase Sen1, Senataxin in human, preserves the integrity of replication forks encountering transcription by removing RNA-DNA hybrids. Here we show that, in sen1 mutants, when a replication fork clashes head-on with transcription is arrested and, as a consequence, the progression of the sister fork moving in the opposite direction within the same replicon is also impaired. Therefore, sister forks remain coupled when one of the two forks is arrested by transcription, a fate different from that experienced by forks encountering Double Strand Breaks. We also show that dormant origins of replication are activated to ensure DNA synthesis in the proximity to the forks arrested by transcription. Dormant origin firing is not inhibited by the replication checkpoint, rather dormant origins are fired if they cannot be timely inactivated by passive replication. In sen1 mutants, the Mre11 and Mrc1-Ctf4 complexes protect the forks arrested by transcription from processing mediated by the Exo1 nuclease. Thus, a harmless head-on replication-transcription clash resolution requires the fine-tuning of origin firing and coordination among Sen1, Exo1, Mre11 and Mrc1-Ctf4 complexes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_154,

title = {Cell cycle and apoptosis regulator 2 at the interface between DNA damage response and cell physiology},

author = {Magni M and Buscemi G and Zannini L},

url = {https://www.sciencedirect.com/science/article/pii/S1383574218300073?via%3Dihub},

doi = {10.1016/j.mrrev.2018.03.004},

year  = {2018},

date = {2018-02-14},

journal = {Mutation research - Reviews in Mutation Research},

volume = {776},

pages = {1-9},

abstract = {Cell cycle and apoptosis regulator 2 (CCAR2 or DBC1) is a human protein recently emerged as a novel and important player of the DNA damage response (DDR). Indeed, upon genotoxic stress, CCAR2, phosphorylated by the apical DDR kinases ATM and ATR, increases its binding to the NAD+-dependent histone deacetylase SIRT1 and inhibits SIRT1 activity. This event promotes the acetylation and activation of p53, a SIRT1 target, and the subsequent induction of p53 dependent apoptosis. In addition, CCAR2 influences DNA repair pathway choice and promotes the chromatin relaxation necessary for the repair of heterochromatic DNA lesions. However, besides DDR, CCAR2 is involved in several other cellular functions. Indeed, through the interaction with transcription factors, nuclear receptors, epigenetic modifiers and RNA polymerase II, CCAR2 regulates transcription and transcript elongation. Moreover, promoting Rev-erbα protein stability and repressing BMAL1 and CLOCK expression, it was reported to modulate the circadian rhythm. Through SIRT1 inhibition, CCAR2 is also involved in metabolism control and, suppressing RelB and p65 activities in the NFkB pathway, it restricts B cell proliferation and immunoglobulin production. Notably, CCAR2 expression is deregulated in several tumors and, compared to the non-neoplastic counterpart, it may be up- or down-regulated. Since its up-regulation in cancer patients is usually associated with poor prognosis and its depletion reduces cancer cell growth in vitro, CCAR2 was suggested to act as a tumor promoter. However, there is also evidence that CCAR2 functions as a tumor suppressor and therefore its role in cancer formation and progression is still unclear. In this review we discuss CCAR2 functions in the DDR and its multiple biological activities in unstressed cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_159,

title = {Altered modulation of lamin A/C-HDAC2 interaction and p21 expression during oxidative stress response in HGPS.},

author = {Mattioli E and Andrenacci D and Garofalo C and Prencipe S and Scotlandi K and Remondini D and Gentilini D and {Di Blasio AM} and Valente S and Scarano E and Cicchilitti L and Piaggio G and Mai A and Lattanzi G},

url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/acel.12824},

doi = {10.1111/acel.12824},

year  = {2018},

date = {2018-02-14},

journal = {Aging cell},

volume = {17},

number = {5},

pages = {e1282},

abstract = {Defects in stress response are main determinants of cellular senescence and organism aging. In fibroblasts from patients affected by Hutchinson-Gilford progeria, a severe LMNA-linked syndrome associated with bone resorption, cardiovascular disorders, and premature aging, we found altered modulation of CDKN1A, encoding p21, upon oxidative stress induction, and accumulation of senescence markers during stress recovery. In this context, we unraveled a dynamic interaction of lamin A/C with HDAC2, an histone deacetylase that regulates CDKN1A expression. In control skin fibroblasts, lamin A/C is part of a protein complex including HDAC2 and its histone substrates; protein interaction is reduced at the onset of DNA damage response and recovered after completion of DNA repair. This interplay parallels modulation of p21 expression and global histone acetylation, and it is disrupted by LMNAmutations leading to progeroid phenotypes. In fact, HGPS cells show impaired lamin A/C-HDAC2 interplay and accumulation of p21 upon stress recovery. Collectively, these results link altered physical interaction between lamin A/C and HDAC2 to cellular and organism aging. The lamin A/C-HDAC2 complex may be a novel therapeutic target to slow down progression of progeria symptoms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_171,

title = {Age-Related Epigenetic Derangement upon Reprogramming and Differentiation of Cells from the Elderly.},

author = {Ravaioli F and Bacalini MG and Franceschi C and Garagnani P},

url = {https://www.mdpi.com/2073-4425/9/1/39},

doi = {10.3390/genes9010039},

year  = {2018},

date = {2018-02-14},

urldate = {2018-02-14},

journal = {Genes},

volume = {9},

number = {1},

pages = {pii: E39},

abstract = {Aging is a complex multi-layered phenomenon. The study of aging in humans is based on the use of biological material from hard-to-gather tissues and highly specific cohorts. The introduction of cell reprogramming techniques posed promising features for medical practice and basic research. Recently, a growing number of studies have been describing the generation of induced pluripotent stem cells (iPSCs) from old or centenarian biologic material. Nonetheless, Reprogramming techniques determine a profound remodelling on cell epigenetic architecture whose extent is still largely debated. Given that cell epigenetic profile changes with age, the study of cell-fate manipulation approaches on cells deriving from old donors or centenarians may provide new insights not only on regenerative features and physiology of these cells, but also on reprogramming-associated and age-related epigenetic derangement.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_111,

title = {Elevated TGF beta2 serum levels in Emery-Dreifuss muscular dystrophy: implications for myocyte and tenocyte differentiation and fibrogenic processes.},

author = {Bernasconi P and Carboni N and Ricci G and Siciliano G and Politano L and Maggi L and Mongini T and Vercelli L and Rodolico C and Biagini E and Boriani G and Ruggiero L and Santoro L and Schena E and Prencipe S and Evangelisti C and Pegoraro E and Morandi L and Columbaro M and Lanzuolo C and Sabatelli P and Cavalcante P and Cappelletti C and Bonne G and Muchir A and Lattanzi G},

url = {https://www.tandfonline.com/doi/abs/10.1080/19491034.2018.1467722},

doi = {10.1080/19491034.2018.1467722},

year  = {2018},

date = {2018-02-13},

journal = {Nucleus},

volume = {25},

number = {1},

pages = {24},

abstract = {Among rare diseases caused by mutations in LMNA gene, Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B are characterized by muscle weakness and wasting, joint contractures, cardiomyopathy with conduction system disorders. Circulating biomarkers for these pathologies have not been identified. Here, we analyzed the secretome of a cohort of patients affected by these muscular laminopathies in the attempt to identify a common signature. Multiplex cytokine assay showed that transforming growth factor beta 2 (TGF beta2) and interleukin 17 serum levels are consistently elevated in the vast majority of examined patients, while interleukin 6 and basic fibroblast growth factor are altered in subgroups of patients. Levels of TGF beta2 are also increased in fibroblast and myoblast cultures established from patient biopsies as well as in serum from mice bearing the H222P Lmna mutation causing Emery-Dreifuss muscular dystrophy in humans. Both patient serum and fibroblast conditioned media activated a TGF beta2-dependent fibrogenic program in normal human myoblasts and tenocytes and inhibited myoblast differentiation. Consistent with these results, a TGF beta2 neutralizing antibody avoided fibrogenic marker activation and myogenesis impairment. Cell intrinsic TGF beta2-dependent mechanisms were also determined in laminopathic cells, where TGF beta2 activated AKT/mTOR phosphorylation. These data show that TGF beta2 contributes to the pathogenesis of Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B and can be considered a potential biomarker of those diseases. Further, the evidence of TGF beta2 pathogenetic effects in tenocytes provides the first mechanistic insight into occurrence of joint contractures in muscular laminopathies},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_128,

title = {Autofluorescence based optical biopsy: an effective diagnostic tool in hepatology.},

author = {Croce AC and Ferrigno A and Bottiroli G and Vairetti M},

url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/liv.13753},

doi = {10.1111/liv.13753},

year  = {2018},

date = {2018-02-07},

journal = {Liver International},

volume = {38},

number = {7},

pages = {1160-1174},

abstract = {Autofluorescence emission of liver tissue depends on the presence of endogenous biomolecules able to fluoresce under suitable light excitation. Overall autofluorescence emission contains much information of diagnostic value, because it is the sum of individual autofluorescence contributions from fluorophores involved in metabolism, for example NAD(P)H, flavins, lipofuscins, retinoids, porphyrins, bilirubin and lipids, or in structural architecture, for example fibrous proteins, in close relationship with normal, altered or diseased conditions of the liver. Since the 1950s, hepatocytes and liver have been historical models to study NAD(P)H and flavins as in situ, real time autofluorescence biomarkers of energy metabolism and redox state. Later investigations designed to monitor organ responses to ischemia/reperfusion, were able to predict the risk of dysfunction in surgery and transplantation, or support the development of procedures to ameliorate the liver outcome. Subsequently, fluorescent fatty acids, lipofuscin‐like lipopigments and collagen were characterized as optical biomarkers of liver steatosis, oxidative stress damage, fibrosis and disease progression. Currently, serum AF is being investigated to improve non invasive optical diagnosis of liver disease. Validation of endogenous fluorophores and in situ discrimination of cancerous from non‐cancerous tissue belong to the few studies on liver in human subjects. These reports, along with other optical techniques and the huge work performed on animal models suggest many optically based applications in hepatology. Optical diagnosis is currently offering beneficial outcomes in clinical fields ranging from the respiratory and gastrointestinal tracts, to dermatology and ophthalmology. Accordingly, this review aims to promote an effective bench to bedside transfer in hepatology. This article is protected by copyright. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_124,

title = {Mapping of the Human Placenta: Experimental Evidence of Amniotic Epithelial Cell Heterogeneity.},

author = {Centurione L and Passaretta F and Centurione MA and Munari S and Vertua E and Silini A and Liberati M and Parolini O and Pietro RD},

url = {http://journals.sagepub.com/doi/abs/10.1177/0963689717725078?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&},

doi = {10.1177/0963689717725078},

year  = {2018},

date = {2018-01-31},

journal = {Cell transplantation},

volume = {27},

number = {1},

pages = {12-22},

abstract = {The human placenta is an important source of stem cells that can be easily collected without ethical concerns since it is usually discarded after childbirth. In this study, we analyzed the amniotic membrane (AM) from the human placenta with the aim of mapping different regions with respect to their morpho-functional features and regenerative potential. AMs were obtained from 24 healthy women, undergoing a caesarean section, and mapped into 4 different regions according to their position in relation to the umbilical cord: the central, intermediate, peripheral, and reflected areas. We carried out a multiparametric analysis focusing our attention on amniotic epithelial cells (AECs). Our results revealed that AECs, isolated from the different areas, are a heterogeneous cell population with different pluripotency and proliferation marker expression (octamer-binding transcription factor 4 [OCT-4], tyrosine-protein kinase KIT [c-KIT], sex determining region Y-box 2 [SOX-2], alpha-fetoprotein, cyclic AMP response element binding [CREB] protein, and phosphorylated active form of CREB [p-CREB]), proliferative ability, and osteogenic potential. Our investigation discloses interesting findings that could be useful for increasing the efficiency of AM isolation and application for therapeutic purposes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_136,

title = {Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update.},

author = {Evangelisti C and Chiarini F and McCubrey JA and Martelli AM},

url = {https://www.mdpi.com/1422-0067/19/7/1878},

doi = {10.3390/ijms19071878},

year  = {2018},

date = {2018-01-26},

journal = {International journal of molecular sciences},

volume = {19},

number = {7},

pages = {pii: E1878},

abstract = {T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood malignancy that arises from the clonal expansion of transformed T-cell precursors. Although T-ALL prognosis has significantly improved due to the development of intensive chemotherapeutic protocols, primary drug-resistant and relapsed patients still display a dismal outcome. In addition, lifelong irreversible late effects from conventional therapy are a growing problem for leukemia survivors. Therefore, novel targeted therapies are required to improve the prognosis of high-risk patients. The mechanistic target of rapamycin (mTOR) is the kinase subunit of two structurally and functionally distinct multiprotein complexes, which are referred to as mTOR complex 1 (mTORC1) and mTORC2. These two complexes regulate a variety of physiological cellular processes including protein, lipid, and nucleotide synthesis, as well as autophagy in response to external cues. However, mTOR activity is frequently deregulated in cancer, where it plays a key oncogenetic role driving tumor cell proliferation, survival, metabolic transformation, and metastatic potential. Promising preclinical studies using mTOR inhibitors have demonstrated efficacy in many human cancer types, including T-ALL. Here, we highlight our current knowledge of mTOR signaling and inhibitors in T-ALL, with an emphasis on emerging evidence of the superior efficacy of combinations consisting of mTOR inhibitors and either traditional or targeted therapeutics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_121,

title = {Therapeutic targeting of CK2 in acute and chronic leukemias.},

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

url = {https://www.nature.com/articles/leu2017301},

doi = {10.1038/leu.2017.301},

year  = {2018},

date = {2018-01-11},

journal = {Leukemia},

volume = {32},

number = {1},

pages = {1-10},

abstract = {CK2 is a ubiquitously expressed, constitutively active Ser/Thr protein kinase, which is considered the most pleiotropic protein kinase in the human kinome. Such a pleiotropy explains the involvement of CK2 in many cellular events. However, its predominant roles are stimulation of cell growth and prevention of apoptosis. High levels of CK2 messenger RNA and protein are associated with CK2 pathological functions in human cancers. Over the last decade, basic and translational studies have provided evidence of CK2 as a pivotal molecule driving the growth of different blood malignancies. CK2 overexpression has been demonstrated in nearly all the types of hematological cancers, including acute and chronic leukemias, where CK2 is a key regulator of signaling networks critical for cell proliferation, survival and drug resistance. The findings that emerged from these studies suggest that CK2 could be a valuable therapeutic target in leukemias and supported the initiation of clinical trials using CK2 antagonists. In this review, we summarize the recent advances on the understanding of the signaling pathways involved in CK2 inhibition-mediated effects with a particular emphasis on the combinatorial use of CK2 inhibitors as novel therapeutic strategies for treating both acute and chronic leukemia patients.Leukemia advance online publication, 24 October 2017},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_232,

title = {MiRNA-210: A Current Overview.},

author = {Bavelloni A and Ramazzotti G and Poli A and Piazzi M and Focaccia E and Blalock WL and Faenza I},

url = {http://ar.iiarjournals.org/content/37/12/6511.long},

year  = {2017},

date = {2017-12-18},

urldate = {2017-12-18},

journal = {Anticancer Research},

volume = {37},

number = {12},

pages = {6511-6521},

abstract = {microRNAs (miRNAs) are a group of highly conserved small non-coding RNAs that were found to enhance mRNA degradation or inhibit post-transcriptional translation. Accumulating evidence indicates that miRNAs contribute to tumorigenesis and cancer metastasis. microRNA-210 has been largely studied in the past several years and has been identified as a major miRNA induced under hypoxia. A variety of miR-210 targets have been identified pointing to its role, not only in mitochondrial metabolism, but also in angiogenesis, the DNA damage response, cell proliferation, and apoptosis. Based on earlier research findings, this review aims to provide a current overview on the involvement of miRNA-210 in biological processes and diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_238,

title = {Relation between circulating oxidized-LDL and metabolic syndrome in children with obesity: the role of hypertriglyceridemic waist phenotype.},

author = {Calcaterra V and De Giuseppe R and Biino G and Mantelli M and Marchini S and Bendotti G and Madè A and Avanzini MA and Montalbano C and Cossellu G and Larizza D and Cena H},

url = {https://www.degruyter.com/view/j/jpem.ahead-of-print/jpem-2017-0239/jpem-2017-0239.xml},

doi = {doi.org/10.1515/jpem-2017-0239},

year  = {2017},

date = {2017-11-27},

journal = {Journal of pediatric endocrinology and metabolism},

volume = {30},

number = {12},

pages = {1257-1263},

abstract = {BACKGROUND: The association between oxidative stress (OS) and metabolic syndrome (MetS) has been reported in adults. We analyzed the relation between circulating oxidized low-density lipoproteins (Ox-LDL) and MetS in pediatric ages in order to define whether plasma Ox-LDL levels are correlated to obesity and whether oxidative damage, using serum Ox-LDL levels as a proxy, are associated with MetS. METHODS: We enrolled 178 children (11.8±2.6 years). On the basis of a body mass index (BMI) threshold, the subjects were classified as: normal weight BMI <75th percentile; overweight BMI 75-97th percentile; obese BMI >97th percentile. Patients were classified as having MetS if they met three or more of the following criteria for age and sex: BMI >97th percentile, triglyceride levels >95th percentile, high-density lipoprotein (HDL) cholesterol level <5th percentile, systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) >95th percentile and impaired glucose tolerance. RESULTS: Obese children showed increased MetS prevalence (p=0.001) and higher Ox-LDL levels compared to normal- and overweight subjects (p<0.05), with a limited relation between Ox-LDL and MetS (p=0.06). Waist-to-height ratio (W/HtR) (p=0.02), triglycerides (TG) (p=0.001) and LDL-cholesterol (p<0.001) resulted independent predictors of increased plasma Ox-LDL levels. CONCLUSIONS: Oxidative damage was correlated with a hypertriglyceridemic waist phenotype and can be a precocious marker of MetS and cardiometabolic risk in obese children.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_224,

title = {Living on the Edge: DNA Polymerase Lambda between Genome Stability and Mutagenesis.},

author = {van Loon B and Hubscher U and Maga G},

url = {http://pubs.acs.org/doi/abs/10.1021/acs.chemrestox.7b00152},

doi = {10.1021/acs.chemrestox.7b00152},

year  = {2017},

date = {2017-11-20},

journal = {Chemical research in toxicology},

volume = {30},

number = {11},

pages = {1936-1941},

abstract = {In human cells, only four DNA polymerases (pols) are necessary and sufficient for the duplication of the genetic information. However, more than a dozen DNA pols are required to maintain its integrity. Such a high degree of specialization makes DNA repair pols able to cope with specific lesions or repair pathways. On the other hand, the same DNA pols can have partially overlapping roles, which could result in possible conflicts of functions, if the DNA pols are not properly regulated. DNA pol λ is a typical example of such an enzyme. It is a multifunctional enzyme, endowed with special structural and biochemical properties, which make it capable of participating in different DNA repair pathways such as base excision repair, nonhomologous end joining, and translesion synthesis. However, when mutated or deregulated, DNA pol λ can also be a source of genetic instability. Its multiple roles in DNA damage tolerance and its ability in promoting tumor progression make it also a possible target for novel anticancer approaches.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_218,

title = {Human White Adipocytes Convert Into "Rainbow" Adipocytes In Vitro.},

author = {Maurizi G and Poloni A and Mattiucci D and Santi S and Maurizi A and Izzi V and Giuliani A and Mancini S and Zingaretti MC and Perugini J and Severi I and Falconi M and Vivarelli M and Rippo MR and Corvera S and Giordano A and Leoni P and Cinti S},

url = {http://onlinelibrary.wiley.com/doi/10.1002/jcp.25743/abstract},

doi = {10.1002/jcp.25743.},

year  = {2017},

date = {2017-10-28},

journal = {Journal of cellular physiology},

volume = {232},

number = {10},

pages = {2887-2899},

abstract = {White adipocytes are plastic cells able to reversibly transdifferentiate into brown adipocytes and into epithelial glandular cells under physiologic stimuli in vivo. These plastic properties could be used in future for regenerative medicine, but are incompletely explored in their details. Here, we focused on plastic properties of human mature adipocytes (MA) combining gene expression profile through microarray analysis with morphologic data obtained by electron and time lapse microscopy. Primary MA showed the classic morphology and gene expression profile of functional mature adipocytes. Notably, despite their committed status, MA expressed high levels of reprogramming genes. MA from ceiling cultures underwent transdifferentiation toward fibroblast-like cells with a well-differentiated morphology and maintaining stem cell gene signatures. The main morphologic aspect of the transdifferentiation process was the secretion of large lipid droplets and the development of organelles necessary for exocrine secretion further supported the liposecretion process. Of note, electron microscope findings suggesting liposecretion phenomena were found also in explants of human fat and rarely in vivo in fat biopsies from obese patients. In conclusion, both MA and post-liposecretion adipocytes show a well-differentiated phenotype with stem cell properties in line with the extraordinary plasticity of adipocytes in vivo. J. Cell. Physiol. 232: 2887-2899, 2017. 2016 Wiley Periodicals, Inc.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_207,

title = {Transcription and DNA Damage: Holding Hands or Crossing Swords? First dual AK/GSK-3beta inhibitors endowed with antioxidant properties as multifunctional, potential neuroprotective agents.},

author = {D'Alessandro G and {d'Adda di Fagagna F}},

url = {http://www.sciencedirect.com/science/article/pii/S0022283616304715?via%3Dihub},

doi = {10.1016/j.jmb.2016.11.002},

year  = {2017},

date = {2017-10-27},

journal = {Journal of Molecular Biology},

volume = {429},

number = {21},

pages = {3215-3229},

abstract = {Transcription has classically been considered a potential threat to genome integrity. Collision between transcription and DNA replication machinery, and retention of DNA:RNA hybrids, may result in genome instability. On the other hand, it has been proposed that active genes repair faster and preferentially via homologous recombination. Moreover, while canonical transcription is inhibited in the proximity of DNA double-strand breaks, a growing body of evidence supports active non-canonical transcription at DNA damage sites. Small non-coding RNAs accumulate at DNA double-strand break sites in mammals and other organisms, and are involved in DNA damage signaling and repair. Furthermore, RNA binding proteins are recruited to DNA damage sites and participate in the DNA damage response. Here, we discuss the impact of transcription on genome stability, the role of RNA binding proteins at DNA damage sites, and the function of small non-coding RNAs generated upon damage in the signaling and repair of DNA lesions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_408,

title = {Telomerase abrogates aneuploidy-induced telomere replication stress, senescence and cell depletion.},

author = {Meena JK and Cerutti A and Beichler C and Morita Y and Bruhn C and Kumar M and Kraus JM and Speicher MR and Wang ZQ and Kestler HA and {d'Adda di Fagagna F} and Günes C and Rudolph KL},

url = {https://www.embopress.org/doi/full/10.15252/embj.201490070},

doi = {10.15252/embj.201490070},

year  = {2017},

date = {2017-10-13},

journal = {Embo Journal},

volume = {34},

number = {10},

pages = {1371-1384},

abstract = {The causal role of aneuploidy in cancer initiation remains under debate since mutations of euploidy-controlling genes reduce cell fitness but aneuploidy strongly associates with human cancers. Telomerase activation allows immortal growth by stabilizing telomere length, but its role in aneuploidy survival has not been characterized. Here, we analyze the response of primary human cells and murine hematopoietic stem cells (HSCs) to aneuploidy induction and the role of telomeres and the telomerase in this process. The study shows that aneuploidy induces replication stress at telomeres leading to telomeric DNA damage and p53 activation. This results in p53/Rb-dependent, premature senescence of human fibroblast, and in the depletion of hematopoietic cells in telomerase-deficient mice. Endogenous telomerase expression in HSCs and enforced expression of telomerase in human fibroblasts are sufficient to abrogate aneuploidy-induced replication stress at telomeres and the consequent induction of premature senescence and hematopoietic cell depletion. Together, these results identify telomerase as an aneuploidy survival factor in mammalian cells based on its capacity to alleviate telomere replication stress in response to aneuploidy induction. 2015 The Authors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_187,

title = {Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.},

author = {Joshi PK and Pirastu N and Kentistou KA and Fischer K and Hofer E and {et al} and Biino G and {et al} and Hayward C and Chasman D and Martin NG and Sattar N and Campbell H and Esko T and Kutalik Z and Wilson JF},

url = {https://www.nature.com/articles/s41467-017-00934-5},

doi = {10.1038/s41467-017-00934-5},

year  = {2017},

date = {2017-10-13},

journal = {Nature Communications},

volume = {8},

number = {1},

pages = {910},

abstract = {Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_215,

title = {Glycogen Synthase Kinase-3beta Inhibition Links Mitochondrial Dysfunction, Extracellular Matrix Remodelling and Terminal Differentiation in Chondrocytes.},

author = {Guidotti S and Minguzzi M and Platano D and Santi S and Trisolino G and Filardo G and Mariani E and Borzì RM},

url = {www.nature.com/articles/s41598-017-12129-5},

doi = {10.1038/s41598-017-12129-5},

year  = {2017},

date = {2017-09-21},

journal = {Scientific reports},

volume = {7},

number = {1},

pages = {12059},

abstract = {Following inflammatory stimuli, GSK3 inhibition functions as a hub with pleiotropic effects leading to cartilage degradation. However, little is known about the effects triggered by its direct inhibition as well as the effects on mitochondrial pathology, that contributes to osteoarthritis pathogenesis. To this aim we assessed the molecular mechanisms triggered by GSK3β inactivating stimuli on 3-D (micromass) cultures of human articular chondrocytes. Stimuli were delivered either at micromass seeding (long term) or after maturation (short term) to explore "late" effects on terminal differentiation or "early" mitochondrial effects, respectively. GSK3β inhibition significantly enhanced mitochondrial oxidative stress and damage and endochondral ossification based on increased nuclear translocation of Runx-2 and β-catenin, calcium deposition, cell death and enhanced remodelling of the extracellular matrix as demonstrated by the increased collagenolytic activity of supernatants, despite unmodified (MMP-1) or even reduced (MMP-13) collagenase gene/protein expression. Molecular dissection of the underlying mechanisms showed that GSK3β inhibition achieved with pharmacological/silencing strategies impacted on the control of collagenolytic activity, via both decreased inhibition (reduced TIMP-3) and increased activation (increased MMP-10 and MMP-14). To conclude, the inhibition of GSK3β enhances terminal differentiation via concerted effects on ECM and therefore its activity represents a tool to keep articular cartilage homeostasis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_189,

title = {Phosphorylation regulates human pol-eta stability and damage bypass throughout the cell cycle.},

author = {Bertoletti F and Cea V and Liang CC and Lanati T and Maffia A and Avarello MDM and Cipolla L and Lehmann AR and Cohn MA and Sabbioneda S},

url = {https://academic.oup.com/nar/article/45/16/9441/4002723},

doi = {10.1093/nar/gkx619},

year  = {2017},

date = {2017-09-19},

journal = {Nucleic Acids Research},

volume = {45},

number = {16},

pages = {9441-9454},

abstract = {DNA translesion synthesis (TLS) is a crucial damage tolerance pathway that oversees the completion of DNA replication in the presence of DNA damage. TLS polymerases are capable of bypassing a distorted template but they are generally considered inaccurate and they need to be tightly regulated. We have previously shown that pol-eta is phosphorylated on Serine 601 after DNA damage and we have demonstrated that this modification is important for efficient damage bypass. Here we report that pol-eta is also phosphorylated by CDK2, in the absence of damage, in a cell cycle-dependent manner and we identify serine 687 as an important residue targeted by the kinase. We discover that phosphorylation on serine 687 regulates the stability of the polymerase during the cell cycle, allowing it to accumulate in late S and G2 when productive TLS is critical for cell survival. Furthermore, we show that alongside the phosphorylation of S601, the phosphorylation of S687 and S510, S512 and/or S514 are important for damage bypass and cell survival after UV irradiation. Taken together our results provide new insights into how cells can, at different times, modulate DNA TLS for improved cell survival.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_194,

title = {Recent Advancements in DNA Damage-Transcription Crosstalk and High-Resolution Mapping of DNA Breaks.},

author = {Vitelli V and Galbiati A and Iannelli F and Pessina F and Sharma S and {d'Adda di Fagagna F}},

url = {http://www.annualreviews.org/doi/full/10.1146/annurev-genom-091416-035314?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&},

doi = {10.1146/annurev-genom-091416-035314},

year  = {2017},

date = {2017-08-31},

journal = {Annual review of genomics and human genetics},

volume = {18},

pages = {87-113},

abstract = {"Until recently, DNA damage arising from physiological DNA metabolism was considered a detrimental by-product for cells. However, an increasing amount of evidence has shown that DNA damage could have a positive role in transcription activation. In particular, DNA damage has been detected in transcriptional elements following different stimuli. These physiological DNA breaks are thought to be instrumental for the correct expression of genomic loci through different mechanisms. In this regard, although a plethora of methods are available to precisely map transcribed regions and transcription start sites, commonly used techniques for mapping DNA breaks lack sufficient resolution and sensitivity to draw a robust correlation between DNA damage generation and transcription. Recently, however, several methods have been developed to map DNA damage at single-nucleotide resolution, thus providing a new set of tools to correlate DNA damage and transcription. Here, we review how DNA damage can positively regulate transcription initiation, the current techniques for mapping DNA breaks at high resolution, and how these techniques can benefit future studies of DNA damage and transcription.

"},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_200,

title = {Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome.},

author = {Guastafierro T and Bacalini MG and Marcoccia A and Gentilini D and Pisoni S and Di Blasio AM and Corsi A and Franceschi C and Raimondo D and Spanò A and Garagnani P and Bondanini F},

url = {https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-017-0389-4},

doi = {10.1186/s13148-017-0389-4},

year  = {2017},

date = {2017-08-30},

journal = {Clinical epigenetics},

volume = {9},

pages = {92},

abstract = {BACKGROUND: Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidentified. RESULTS: To address whether epigenetic changes can be associated with Werner syndrome phenotype, we analysed genome-wide DNA methylation profile using the Infinium MethylationEPIC BeadChip in the whole blood from three patients affected by Werner syndrome compared with three age- and sex-matched healthy controls. Hypermethylated probes were enriched in glycosphingolipid biosynthesis, FoxO signalling and insulin signalling pathways, while hypomethylated probes were enriched in PI3K-Akt signalling and focal adhesion pathways. Twenty-two out of 47 of the differentially methylated genes belonging to the enriched pathways resulted differentially expressed in a publicly available dataset on Werner syndrome fibroblasts. Interestingly, differentially methylated regions identified CERS1 and CERS3, two members of the ceramide synthase family. Moreover, we found differentially methylated probes within ITGA9 and ADAM12 genes, whose methylation is altered in systemic sclerosis, and within the PRDM8 gene, whose methylation is affected in dyskeratosis congenita and Down syndrome. CONCLUSIONS: DNA methylation changes in the peripheral blood from Werner syndrome patients provide new insight in the pathogenesis of the disease, highlighting in some cases a functional correlation of gene expression and methylation status.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_192,

title = {ESCO1/2's roles in chromosome structure and interphase chromatin organization.},

author = {Kawasumi R and Abe T and Arakawa H and Garre M and Hirota K and Branzei D},

url = {http://genesdev.cshlp.org/content/31/21/2136.long},

doi = {10.1101/gad.306084.117},

year  = {2017},

date = {2017-08-10},

journal = {Genes and development},

volume = {31},

number = {21},

pages = {2136-2150},

abstract = {ESCO1/2 acetyltransferases mediating SMC3 acetylation and sister chromatid cohesion (SCC) are differentially required for genome integrity and development. Here we established chicken DT40 cell lines with mutations in ESCO1/2, SMC3 acetylation, and the cohesin remover WAPL. Both ESCO1 and ESCO2 promoted SCC, while ESCO2 was additionally and specifically required for proliferation and centromere integrity. ESCO1 overexpression fully suppressed the slow proliferation and centromeric separation phenotypes of esco2 cells but only partly suppressed its chromosome arm SCC defects. Concomitant inactivation of ESCO1 and ESCO2 caused lethality owing to compromised mitotic chromosome segregation. Neither wapl nor acetyl-mimicking smc3-QQ mutations rescued esco1 esco2 lethality. Notably, esco1 esco2 wapl conditional mutants showed very severe proliferation defects associated with catastrophic mitoses and also abnormal interphase chromatin organization patterns. The results indicate that cohesion establishment by vertebrate ESCO1/2 is linked to interphase chromatin architecture formation, a newly identified function of cohesin acetyltransferases that is both fundamentally and medically relevant.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_201,

title = {The cohesin complex prevents Myc-induced replication stress.},

author = {Rohban S and Cerutti A and Morelli MJ and {d'Adda di Fagagna F} and Campaner S},

url = {https://www.nature.com/articles/cddis2017345},

doi = {10.1038/cddis.2017.345},

year  = {2017},

date = {2017-07-27},

journal = {Cell Death and Disease},

volume = {8},

pages = {e2956},

abstract = {The cohesin complex is mutated in cancer and in a number of rare syndromes collectively known as Cohesinopathies. In the latter case, cohesin deficiencies have been linked to transcriptional alterations affecting Myc and its target genes. Here, we set out to understand to what extent the role of cohesins in controlling cell cycle is dependent on Myc expression and activity. Inactivation of the cohesin complex by silencing the RAD21 subunit led to cell cycle arrest due to both transcriptional impairment of Myc target genes and alterations of replication forks, which were fewer and preferentially unidirectional. Ectopic activation of Myc in RAD21 depleted cells rescued Myc-dependent transcription and promoted S-phase entry but failed to sustain S-phase progression due to a strong replicative stress response, which was associated to a robust DNA damage response, DNA damage checkpoint activation and synthetic lethality. Thus, the cohesin complex is dispensable for Myc-dependent transcription but essential to prevent Myc-induced replicative stress. This suggests the presence of a feed-forward regulatory loop where cohesins by regulating Myc level control S-phase entry and prevent replicative stress.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_183,

title = {WoPPER: Web server for Position Related data analysis of gene Expression in Prokaryotes.},

author = {Puccio S and Grillo G and Licciulli F and Severgnini M and Liuni S and Bicciato S and De Bellis G and Ferrari F and Peano C},

url = {https://academic.oup.com/nar/article/45/W1/W109/3782601},

doi = {10.1093/nar/gkx329},

year  = {2017},

date = {2017-07-13},

journal = {Nucleic Acids Research},

volume = {45},

number = {W1},

pages = {W109-W115},

abstract = {The structural and conformational organization of chromosomes is crucial for gene expression regulation in eukaryotes and prokaryotes as well. Up to date, gene expression data generated using either microarray or RNA-sequencing are available for many bacterial genomes. However, differential gene expression is usually investigated with methods considering each gene independently, thus not taking into account the physical localization of genes along a bacterial chromosome. Here, we present WoPPER, a web tool integrating gene expression and genomic annotations to identify differentially expressed chromosomal regions in bacteria. RNA-sequencing or microarray-based gene expression data are provided as input, along with gene annotations. The user can select genomic annotations from an internal database including 2780 bacterial strains, or provide custom genomic annotations. The analysis produces as output the lists of positionally related genes showing a coordinated trend of differential expression. Graphical representations, including a circular plot of the analyzed chromosome, allow intuitive browsing of the results. The analysis procedure is based on our previously published R-package PREDA. The release of this tool is timely and relevant for the scientific community, as WoPPER will fill an existing gap in prokaryotic gene expression data analysis and visualization tools. WoPPER is open to all users and can be reached at the following URL: https://WoPPER.ba.itb.cnr.it.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_221,

title = {MCM5: a new actor in the link between DNA replication and Meier-Gorlin syndrome.},

author = {Vetro A and Savasta S and Russo Raucci A and Cerqua C and Sartori G and Limongelli I and Forlino A and Maruelli S and Perucca P and Vergani D and Mazzini G and Mattevi A and Stivala LA and Salviati L and Zuffardi O},

url = {http://www.nature.com/ejhg/journal/vaop/ncurrent/full/ejhg20175a.html},

doi = {10.1038/ejhg.2017.5},

year  = {2017},

date = {2017-05-18},

journal = {European journal of human genetics},

volume = {25},

number = {5},

pages = {646-650},

abstract = {Meier-Gorlin syndrome (MGORS) is a rare disorder characterized by primordial dwarfism, microtia, and patellar aplasia/hypoplasia. Recessive mutations in ORC1, ORC4, ORC6, CDT1, CDC6, and CDC45, encoding members of the pre-replication (pre-RC) and pre-initiation (pre-IC) complexes, and heterozygous mutations in GMNN, a regulator of cell-cycle progression and DNA replication, have already been associated with this condition. We performed whole-exome sequencing (WES) in a patient with a clinical diagnosis of MGORS and identified biallelic variants in MCM5. This gene encodes a subunit of the replicative helicase complex, which represents a component of the pre-RC. Both variants, a missense substitution within a conserved domain critical for the helicase activity, and a single base deletion causing a frameshift and a premature stop codon, were predicted to be detrimental for the MCM5 function. Although variants of MCM5 have never been reported in specific human diseases, defect of this gene in zebrafish causes a phenotype of growth restriction overlapping the one associated with orc1 depletion. Complementation experiments in yeast showed that the plasmid carrying the missense variant was unable to rescue the lethal phenotype caused by mcm5 deletion. Moreover cell-cycle progression was delayed in patient's cells, as already shown for mutations in the ORC1 gene. Altogether our findings support the role of MCM5 as a novel gene involved in MGORS, further emphasizing that this condition is caused by impaired DNA replication.European Journal of Human Genetics advance online publication, 15 February 2017; doi:10.1038/ejhg.2017.5.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_212,

title = {Regulation of Cancer Cell Responsiveness to Ionizing Radiation Treatment by Cyclic AMP Response Element Binding Nuclear Transcription Factor.},

author = {D'Auria F and Centurione L and Centurione MA and Angelini A and Di Pietro R},

url = {https://www.frontiersin.org/articles/10.3389/fonc.2017.00076/full},

doi = {10.3389/fonc.2017.00076},

year  = {2017},

date = {2017-05-10},

journal = {Frontiers in oncology},

volume = {7},

number = {1},

pages = {76},

abstract = {Cyclic AMP response element binding (CREB) protein is a member of the CREB/activating transcription factor (ATF) family of transcription factors that play an important role in the cell response to different environmental stimuli leading to proliferation, differentiation, apoptosis, and survival. A number of studies highlight the involvement of CREB in the resistance to ionizing radiation (IR) therapy, demonstrating a relationship between IR-induced CREB family members' activation and cell survival. Consistent with these observations, we have recently demonstrated that CREB and ATF-1 are expressed in leukemia cell lines and that low-dose radiation treatment can trigger CREB activation, leading to survival of erythro-leukemia cells (K562). On the other hand, a number of evidences highlight a proapoptotic role of CREB following IR treatment of cancer cells. Since the development of multiple mechanisms of resistance is one key problem of most malignancies, including those of hematological origin, it is highly desirable to identify biological markers of responsiveness/unresponsiveness useful to follow-up the individual response and to adjust anticancer treatments. Taking into account all these considerations, this mini-review will be focused on the involvement of CREB/ATF family members in response to IR therapy, to deepen our knowledge of this topic, and to pave the way to translation into a therapeutic context.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_205,

title = {Inhibitors of GLUT/SLC2A Enhance the Action of BCNU and Temozolomide against High-Grade Gliomas.},

author = {Azzalin A and Nato G and Parmigiani E and Garello F and Buffo A and Magrassi L},

url = {http://www.neoplasia.com/article/S1476-5586(16)30347-5/fulltext},

doi = {10.1016/j.neo.2017.02.009},

year  = {2017},

date = {2017-04-27},

journal = {Neoplasia},

volume = {19},

number = {4},

pages = {364-373},

abstract = {Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2) superfamily, phlorizin (PHZ), in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma. PHZ was inactive on the same cells. Similar results were obtained when cells were grown in adherence or as 3D multicellular tumor spheroids. RTV treatment but not IDV treatment induced AMP-activated protein kinase (AMPKα) phosphorylation that paralleled the decrease in glycolytic activity and cell growth. IDV, but not RTV, induced an increase in GLUT1/SLC2A1 whose activity could compensate for the inhibition of GLUT4/SLC2A4 by IDV. RTV and IDV pass poorly the blood brain barrier and are unlikely to reach sufficient liquoral concentrations in vivo to inhibit glioblastoma growth as single agents. Isobologram analysis of the association of RTV or IDV and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 4-methyl-5-oxo-2,3,4,6,8-pentazabicyclo[4.3.0]nona-2,7,9-triene-9-carboxamide (TMZ) indicated synergy only with RTV on inhibition of glioblastoma cells. Finally, we tested in vivo the combination of RTV and BCNU on established GL261 tumors. This drug combination increased the overall survival and allowed a five-fold reduction in the dose of BCNU.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_204,

title = {PI3K isoform inhibition associated with anti Bcr-Abl drugs shows in vitro increased anti-leukemic activity in Philadelphia chromosome-positive B-acute lymphoblastic leukemia cell lines.},

author = {Ultimo S and Simioni C and Martelli AM and Zauli G and Evangelisti C and Celeghini C and McCubrey JA and Marisi G and Ulivi P and Capitani S and Neri LM},

url = {http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=15542&pubmed-linkout=1},

doi = {10.18632/oncotarget.15542},

year  = {2017},

date = {2017-04-04},

journal = {Oncotarget},

volume = {8},

number = {14},

pages = {23213-23227},

abstract = {B-acute lymphoblastic leukemia (B-ALL) is a malignant disorder characterized by the abnormal proliferation of B-cell progenitors. Philadelphia chromosome-positive (Ph+) B-ALL is a subtype that expresses the Bcr-Abl fusion protein which represents a negative prognostic factor. Constitutive activation of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) network is a common feature of B-ALL, influencing cell growth and survival. In the present study, we aimed to investigate the efficacy of PI3K isoform inhibition in B-ALL cell lines harboring the Bcr-Abl fusion protein.We studied the effects of anti Bcr-Abl drugs Imatinib, Nilotinib and GZD824 associated with PI3K isoform inhibitors. We used a panel of six compounds which specifically target PI3K isoforms including the pan-PI3K inhibitor ZSTK474, p110alpha BYL719 inhibitor and the dual p110gamma/p110delta inhibitor IPI145. The effects of single drugs and of several drug combinations were analyzed to assess cytotoxicity by MTS assays, apoptosis and autophagy by flow cytometry and Western blot, as well as the phosphorylation status of the pathway.ZSTK474, BYL719 and IPI145 administered in combination with imatinib, nilotinib and GZD824 for 48 h, decreased cell viability, induced apoptosis and autophagy in a marked synergistic manner.These findings suggest that selected PI3K isoform inhibitors used in combination with anti Bcr-Abl drugs may be an attractive novel therapeutic intervention in Ph+ B-ALL.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_208,

title = {First dual AK/GSK-3beta inhibitors endowed with antioxidant properties as multifunctional, potential neuroprotective agents.},

author = {Brogi S and Ramunno A and Savi L and Chemi G and Alfano G and Pecorelli A and Pambianchi E and Galatello P and Compagnoni G and Focher F and Biamonti G and Valacchi G and Butini S and Gemma S and Campiani G and Brindisi M},

url = {http://www.sciencedirect.com/science/article/pii/S0223523417304634?via%3Dihub},

doi = {10.1016/j.ejmech.2017.06.017},

year  = {2017},

date = {2017-03-24},

journal = {European journal of medicinal chemistry},

volume = {138},

pages = {438-457},

abstract = {The manuscript deals with the design, synthesis and biological evaluation of novel benzoxazinone-based and indole-based compounds as multifunctional neuroprotective agents. These compounds inhibit human adenosine kinase (hAK) and human glycogen synthase kinase 3 beta (hGSK-3β) enzymes. Computational analysis based on a molecular docking approach underlined the potential structural requirements for simultaneously targeting both proteins' allosteric sites. In silico hints drove the synthesis of appropriately decorated benzoxazinones and indoles (5a-s, and 6a-c) and biochemical analysis revealed their behavior as allosteric inhibitors of hGSK-3beta. For both our hit 4 and the best compounds of the series (5c,l and 6b) the potential antioxidant profile was assessed in human neuroblastoma cell lines (IMR 32, undifferentiated and neuronal differentiated), by evaluating the protective effect of selected compounds against H2O2 cytotoxicity and reactive oxygen species (ROS) production. Results showed a strong efficacy of the tested compounds, even at the lower doses, in counteracting the induced oxidative stress (50 μM of H2O2) and in preventing ROS formation. In addition, the tested compounds did not show any cytotoxic effect determined by the LDH release, at the concentration range analyzed (from 0.1 to 50 μM). This study allowed the identification of compound 5l, as the first dual hAK/hGSK-3β inhibitor reported to date. Compound 5l, which behaves as an effective antioxidant, holds promise for the development of new series of potential therapeutic agents for the treatment of neurodegenerative diseases characterized by an innovative pharmacological profile.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_223,

title = {Letter to the editor: Comments on Wette et al. (2017): "Characterization of muscle ankyrin repeat proteins in human skeletal muscle".},

author = {Cenni V},

url = {http://ajpcell.physiology.org/content/313/4/C469.long},

doi = {10.1152/ajpcell.00151.2017},

year  = {2017},

date = {2017-03-23},

journal = {American journal of physiology. Cell physiology},

volume = {313},

number = {4},

pages = {C469-C470},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_239,

title = {Patterns of calcium signaling: A link between chronic emotions and cancer.},

author = {Pregnolato M and Damiani G and Pereira A Jr},

url = {https://content.iospress.com/articles/journal-of-integrative-neuroscience/jin066},

doi = {10.3233/JIN-170066},

year  = {2017},

date = {2017-03-23},

journal = {Journal of integrative neuroscience},

volume = {16},

number = {s1},

pages = {s43-s-63},

abstract = {Intra and inter-cellular calcium signaling is present in all types of cells and body tissues. In the human brain, calcium currents and waves are related to mental activities, including emotions. We present a theoretical interpretation of these phenomena suggesting their involvement in chronic emotional patterns and in the pathology of cancer. Recent developments on biophysics, translational biology and psychoneuroendocrinoimmunology (PNEI) can support explanatory hypotheses about the link between emotional stresses and the origin and development of different types of tumor cells. Chronic stresses may cause perturbations of rhythms of the PNEI system, excessive activation of HPA axis and abnormal activation of calcium signals in somatic tissues, with deleterious effects on different parts of the body. The increasing of calcium signaling inside cells may lead to a deregulation of different pathways and epigenetic systems that promote the production of genomic mutations in a second phase. In particular, the hyperactivation of the transcription nuclear factor kappaB (NF-κB), if is not counterbalanced by the following activation of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or Nrf2), increases the production of oxidative catabolites, as the advanced glycation end products (AGE), which play a key role in the progression of different types of cancer and other degenerative diseases. Cortisol binding to glucocorticoid receptor (GR) reduces the activity of both NF-κB and Nrf2 inside the cells but inhibits the cellular immunity and the anabolic processes of tissue regeneration. The tissue atrophy and the defective anti-ageing mechanisms promotes the tumoral cells growth and their escape from the immune-surveillance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_190,

title = {Ribonucleotide incorporation by human DNA polymerase eta impacts translesion synthesis and RNase H2 activity.},

author = {Mentegari E and Crespan E and Bavagnoli L and Kissova M and Bertoletti F and Sabbioneda S and Imhof R and Sturla SJ and Nilforoushan A and Hubscher U and van Loon B and Maga G},

url = {https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkw1275},

doi = {doi.org/10.1093/nar/gkw1275},

year  = {2017},

date = {2017-03-16},

journal = {Nucleic Acids Research},

volume = {45},

number = {5},

pages = {2600-2614},

abstract = {Ribonucleotides (rNs) incorporated in the genome by DNA polymerases (Pols) are removed by RNase H2. Cytidine and guanosine preferentially accumulate over the other rNs. Here we show that human Pol η can incorporate cytidine monophosphate (rCMP) opposite guanine, 8-oxo-7,8-dihydroguanine, 8-methyl-2'-deoxyguanosine and a cisplatin intrastrand guanine crosslink (cis-PtGG), while it cannot bypass a 3-methylcytidine or an abasic site with rNs as substrates. Pol eta is also capable of synthesizing polyribonucleotide chains, and its activity is enhanced by its auxiliary factor DNA Pol delta interacting protein 2 (PolDIP2). Human RNase H2 removes cytidine and guanosine less efficiently than the other rNs and incorporation of rCMP opposite DNA lesions further reduces the efficiency of RNase H2. Experiments with XP-V cell extracts indicate Pol eta as the major basis of rCMP incorporation opposite cis-PtGG. These results suggest that translesion synthesis by Pol eta can contribute to the accumulation of rCMP in the genome, particularly opposite modified guanines.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_228,

title = {The contribution of surgical brain mapping to the understanding of the anatomo-functional basis of syntax: A critical review.},

author = {Zanin E and Riva M and Bambini V and Cappa SF and Magrassi L and Moro A},

url = {https://link.springer.com/article/10.1007%2Fs10072-017-3016-4},

doi = {10.1007/s10072-017-3016-4},

year  = {2017},

date = {2017-03-15},

journal = {Neurological Sciences},

volume = {38},

number = {9},

pages = {1579-1589},

abstract = {A wide range of studies on language assessment during awake brain surgery is nowadays available. Yet, a consensus on a standardized protocol for intraoperative language mapping is still lacking. More specifically, very limited information is offered about intraoperative assessment of a crucial component of language such as syntax. This review aims at critically analyzing the intraoperative studies investigating the cerebral basis of syntactic processing. A comprehensive query was performed on the literature, returning a total of 18 studies. These papers were analyzed according to two complementary criteria, based on the distinction between morphosyntax and syntax. The first criterion focused on the tasks and stimuli employed intraoperatively. Studies were divided into three different groups: group 1 included those studies that overtly aimed at investigating morphosyntactic processes; group 2 included studies that did not explicitly focus on syntax, yet employed stimuli requiring morphosyntactic processing; and group 3 included studies reporting some generic form of syntactic deficit, although not further investigated. The second criterion focused on the syntactic structures of the sentences assessed intraoperatively, analyzing the canonicity of sentence structure (i.e., canonical versus non-canonical word order). The global picture emerging from our analysis indicates that what was investigated in the intraoperative literature is morphosyntactic processing, rather than pure syntax. The study of the neurobiology of syntax during awake surgery seems thus to be still at an early stage, in need of systematic, linguistically grounded investigations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_236,

title = {Mast cell in innate immunity mediated by proinflammatory and antiinflammatory IL-1 family members.},

author = {Robuffo I and Toniato E and Tettamanti L and Mastrangelo F and Ronconi G and Frydas I and Caraffa A and Kritas SK and Conti P},

url = {https://www.biolifesas.org/biolife/category/journals/journal-of-biological-regulators-and-homeostatic-agents/},

year  = {2017},

date = {2017-03-15},

journal = {Journal of biological regulators and homeostatic agents},

volume = {31},

number = {4},

pages = {837-842},

abstract = {Innate immunity consists of physical and chemical barriers which provide the early defense against infections. Innate immunity orchestrates the defense of the host with cellular and biochemical proteins. Mast cells (MCs) are involved in innate and adaptive immunity and are the first line of defense which generates multiple inflammatory cytokines/chemokines in response to numerous antigens. MC-activated antigen receptor Fc-RI provokes a number of important biochemical pathways with secretion of numerous vasoactive, chemoattractant and inflammatory compounds which participate in allergic and inflammatory diseases. MCs can also be activated by Th1 cytokines and generate pre-formed and de novo inflammatory mediators, including TNF. IL-37 is an anti-inflammatory cytokine which binds IL-18R-alpha chain and reduces the production of inflammatory IL-1 family members. IL-37 down-regulates innate immunity by inhibiting macrophage response and its accumulation and reduces the cytokines that mediate inflammatory diseases. Here, we discuss the relationship between MCs, innate immunity, and pro-inflammatory and anti-inflammatory cytokines.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_222,

title = {The Incorporation of Ribonucleotides Induces Structural and Conformational Changes in DNA.},

author = {Meroni A and Mentegari E and Crespan E and Muzi-Falconi M and Lazzaro F and Podestà A},

url = {https://www.ncbi.nlm.nih.gov/pubmed/28978432},

doi = {10.1016/j.bpj.2017.07.013},

year  = {2017},

date = {2017-03-08},

journal = {Biophysical journal},

volume = {113},

number = {7},

pages = {1373-1382},

abstract = {Ribonucleotide incorporation is the most common error occurring during DNA replication. Cells have hence developed mechanisms to remove ribonucleotides from the genome and restore its integrity. Indeed, the persistence of ribonucleotides into DNA leads to severe consequences, such as genome instability and replication stress. Thus, it becomes important to understand the effects of ribonucleotides incorporation, starting from their impact on DNA structure and conformation. Here we present a systematic study of the effects of ribonucleotide incorporation into DNA molecules. We have developed, to our knowledge, a new method to efficiently synthesize long DNA molecules (hundreds of basepairs) containing ribonucleotides, which is based on a modified protocol for the polymerase chain reaction. By means of atomic force microscopy, we could therefore investigate the changes, upon ribonucleotide incorporation, of the structural and conformational properties of numerous DNA populations at the single-molecule level. Specifically, we characterized the scaling of the contour length with the number of basepairs and the scaling of the end-to-end distance with the curvilinear distance, the bending angle distribution, and the persistence length. Our results revealed that ribonucleotides affect DNA structure and conformation on scales that go well beyond the typical dimension of the single ribonucleotide. In particular, the presence of ribonucleotides induces a systematic shortening of the molecules, together with a decrease of the persistence length. Such structural changes are also likely to occur in vivo, where they could directly affect the downstream DNA transactions, as well as interfere with protein binding and recognition.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_231,

title = {Cell Cycle Arrest and Apoptosis Induced by Kinamycin F in Human Osteosarcoma Cells.},

author = {Bavelloni A and Focaccia E and Piazzi M and Errani C and Blalock WL and Faenza I},

url = {http://ar.iiarjournals.org/content/37/8/4103.long},

year  = {2017},

date = {2017-03-07},

journal = {Anticancer Research},

volume = {37},

number = {8},

pages = {4103-4109},

abstract = {Background/Aim: Kinamycin F is a bacterial metabolite which contains an unusual and potentially reactive diazo group that is known for its ability to inhibit cell growth. In this study, the potential anti-tumor activity of kinamycin F was investigated in three human osteosarcoma cell lines, MG-63, U-2 OS and HOS as an antitumor agent with a potentially novel target. Materials and Methods: Proliferation and cell viability were measured in three human osteosarcoma cell lines by commercially available kits. We also evaluated the effects of the drug on cell cycle progression using the Muse™ Cell Analyzer. Caspase-3 activity was determined by a fluorometric EnzChek assay kit. Finally, following treatment with kinamycin F the protein levels of cyclin D3, cyclin A and cdK-2 were examined. Results: Kinamycin F induced a concentration-dependent cell death in all the three cell lines. Flow cytometry revealed that kinamycin F treatment at 1 μM concentration significantly increased the cell population in the G2/M-phase (60-65%). Kinamycin F activated caspase 3 in all the three cell lines, clearly demonstrating that the growth inhibitory effect of kinamycin F can be attributed to apoptosis induction. Finally, kinamycin F suppressed osteosarcoma cell proliferation affecting cyclin A and D3 expression. Conclusion: Understanding the mechanism by which kinamycin F exerts its ability to inhibit cell growth may be a step forward in the development of new therapeutic strategies for the treatment of OS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_202,

title = {Emery-Dreifuss Muscular Dystrophy-Associated Mutant Forms of Lamin A Recruit the Stress Responsive Protein Ankrd2 into the Nucleus, Affecting the Cellular Response to Oxidative Stress.},

author = {Angori S and Capanni C and Faulkner G and Bean C and Boriani G and Lattanzi G and Cenni V},

url = {https://www.karger.com/Article/FullText/477309},

doi = {10.1159/000477309},

year  = {2017},

date = {2017-03-07},

urldate = {2017-03-07},

journal = {Cellular Physiology and Biochemistry},

volume = {42},

pages = {169-184},

abstract = {Ankrd2 is a stress responsive protein mainly expressed in muscle cells. Upon the application of oxidative stress, Ankrd2 translocates into the nucleus where it regulates the activity of genes involved in cellular response to stress. Emery-Dreifuss Muscular Dystrophy 2 (EDMD2) is a muscular disorder caused by mutations of the gene encoding lamin A, LMNA. As well as many phenotypic abnormalities, EDMD2 muscle cells also feature a permanent basal stress state, the underlying molecular mechanisms of which are currently unclear. METHODS: Experiments were performed in EDMD2-lamin A overexpressing cell lines and EDMD2-affected human myotubes. Oxidative stress was produced by H2O2 treatment. Co-immunoprecipitation, cellular subfractionation and immunofluorescence analysis were used to validate the relation between Ankrd2 and forms of lamin A; cellular sensibility to stress was monitored by the analysis of Reactive Oxygen Species (ROS) release and cell viability. RESULTS: Our data demonstrate that oxidative stress induces the formation of a complex between Ankrd2 and lamin A. However, EDMD2-lamin A mutants were able to bind and mislocalize Ankrd2 in the nucleus even under basal conditions. Nonetheless, cells co-expressing Ankrd2 and EDMD2-lamin A mutants were more sensitive to oxidative stress than the Ankrd2-wild type lamin A counterpart. CONCLUSIONS: For the first time, we present evidence that in muscle fibers from patients affected by EDMD2, Ankrd2 has an unusual nuclear localization. By introducing a plausible mechanism ruling this accumulation, our data hint at a novel function of Ankrd2 in the pathogenesis of EDMD2-affected cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_216,

title = {Transcriptional and post-transcriptional regulation of the ionizing radiation response by ATM and p53.},

author = {Venkata Narayanan I and Paulsen MT and Bedi K and Berg N and Ljungman EA and Francia S and Veloso A and Magnuson B and {d'Adda di Fagagna F} and Wilson TE and Ljungman M},

url = {www.nature.com/articles/srep43598},

doi = {10.1038/srep43598},

year  = {2017},

date = {2017-03-01},

journal = {Scientific reports},

volume = {7},

number = {1},

pages = {43598},

abstract = {In response to ionizing radiation (IR), cells activate a DNA damage response (DDR) pathway to re-program gene expression. Previous studies using total cellular RNA analyses have shown that the stress kinase ATM and the transcription factor p53 are integral components required for induction of IR-induced gene expression. These studies did not distinguish between changes in RNA synthesis and RNA turnover and did not address the role of enhancer elements in DDR-mediated transcriptional regulation. To determine the contribution of synthesis and degradation of RNA and monitor the activity of enhancer elements following exposure to IR, we used the recently developed Bru-seq, BruChase-seq and BruUV-seq techniques. Our results show that ATM and p53 regulate both RNA synthesis and stability as well as enhancer element activity following exposure to IR. Importantly, many genes in the p53-signaling pathway were coordinately up-regulated by both increased synthesis and RNA stability while down-regulated genes were suppressed either by reduced synthesis or stability. Our study is the first of its kind that independently assessed the effects of ionizing radiation on transcription and post-transcriptional regulation in normal human cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_322,

title = {Damage-induced lncRNAs control the DNA damage response through interaction with DDRNAs at individual double-strand breaks.},

author = {Michelini F and Pitchiaya S and Vitelli V and Sharma S and Gioia U and Pessina F and Cabrini M and Wang Y and Capozzo I and Iannelli F and Matti V and Francia S and Shivashankar GV and Walter NG and {d'Adda di Fagagna F}},

url = {https://www.nature.com/articles/ncb3643},

doi = {10.1038/ncb3643},

year  = {2017},

date = {2017-02-28},

journal = {Nature cell biology},

volume = {19},

number = {2},

pages = {1400-1410},

abstract = {The DNA damage response (DDR) preserves genomic integrity. Small non-coding RNAs termed DDRNAs are generated at DNA double-strand breaks (DSBs) and are critical for DDR activation. Here we show that active DDRNAs specifically localize to their damaged homologous genomic sites in a transcription-dependent manner. Following DNA damage, RNA polymerase II (RNAPII) binds to the MRE11-RAD50-NBS1 complex, is recruited to DSBs and synthesizes damage-induced long non-coding RNAs (dilncRNAs) from and towards DNA ends. DilncRNAs act both as DDRNA precursors and by recruiting DDRNAs through RNA-RNA pairing. Together, dilncRNAs and DDRNAs fuel DDR focus formation and associate with 53BP1. Accordingly, inhibition of RNAPII prevents DDRNA recruitment, DDR activation and DNA repair. Antisense oligonucleotides matching dilncRNAs and DDRNAs impair site-specific DDR focus formation and DNA repair. We propose that DDR signalling sites, in addition to sharing a common pool of proteins, individually host a unique set of site-specific RNAs necessary for DDR activation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}