@article{%a1:%Y_315,

title = {Multimodal transfer of MDR by exosomes in human osteosarcoma},

author = {Torreggiani E and Roncuzzi L and Perut F and Zini N and Baldini N},

url = {https://www.spandidos-publications.com/ijo/49/1/189},

doi = {10.3892/ijo.2016.3509},

year  = {2016},

date = {2016-07-19},

journal = {International Journal of Oncology},

volume = {49},

number = {1},

pages = {189-196},

abstract = {Exosomes are extracellular vesicles released by both normal and tumour cells which are involved in a new intercellular communication pathway by delivering cargo (e.g., proteins, microRNAs, mRNAs) to recipient cells. Tumour-derived exosomes have been shown to play critical roles in different stages of tumour growth and progression. In this study, we investigated the potential role of exosomes to transfer the multidrug resistance (MDR) phenotype in human osteosarcoma cells. Exosomes were isolated by differential centrifugation of culture media from multidrug resistant human osteosarcoma MG-63DXR30 (Exo/DXR) and MG-63 parental cells (Exo/S). Exosome purity was examined by transmission electron microscopy and confirmed by immunoblot analysis for the expression of specific exosomal markers. Our data showed that exosomes derived from doxorubicin-resistant osteosarcoma cells could be taken up into secondary cells and induce a doxorubicin-resistant phenotype. The incubation of osteosarcoma cells with Exo/DXR decreased the sensitivity of parental cells to doxorubicin, while exposure with Exo/S was ineffective. In addition, we demonstrated that Exo/DXR expressed higher levels of MDR-1 mRNA and P-glycoprotein compared to Exo/S (p=0.03). Interestingly, both MDR-1 mRNA and P-gp increased in MG-63 cells after incubation with Exo/DXR, suggesting this as the main mechanism of exosome-mediated transfer of drug resistance. Our findings suggest that multidrug resistant osteosarcoma cells are able to spread their ability to resist the effects of doxorubicin treatment on sensitive cells by transferring exosomes carrying MDR-1 mRNA and its product P-glycoprotein.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_271,

title = {Assessing Cell Cycle Independent Function of the CDK Inhibitor p21(CDKN1A) in DNA Repair.},

author = {Dutto I and Tillhon M and Prosperi E},

url = {https://link.springer.com/protocol/10.1007%2F978-1-4939-2926-9_11},

doi = {10.1007/978-1-4939-2926-9_11},

year  = {2016},

date = {2016-06-09},

journal = {Methods in Molecular Biology - Cyclin-Dependent Kinase (CDK) Inhibitors},

volume = {1336},

pages = {123-139},

abstract = {The cyclin-dependent kinase (CDK) inhibitor p21(CDKN1A) is a small protein that is able to regulate many important cell functions, often independently of its activity of CDK inhibitor. In addition to cell cycle, this protein regulates cell transcription, apoptosis, cell motility, and DNA repair. In particular, p21 may participate in different DNA repair processes, like the nucleotide excision repair (NER), base excision repair (BER), and double-strand breaks (DSB) repair, because of its ability to interact with DNA repair proteins, such as proliferating cell nuclear antigen (PCNA), a master regulator of many DNA transactions. Although this role has been debated for a long time, the influence of p21 in DNA repair has been now established. However, it remain to be clarified how this role is coupled to proteasomal degradation that has been shown to occur after DNA damage. This chapter describes procedures to study p21 protein recruitment to localized DNA damage sites in the cell nucleus. In particular, we describe a technique based on local irrradiation with UV light through a polycarbonate filter with micropores; an in situ lysis procedure to detect chromatin-bound proteins by immunofluorescence; a cell fractionation procedure to study chromatin association of p21 by Western blot analysis, and p21 protein-protein interactions by an immunoprecipitation assay.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_303,

title = {Overexpression of parkin rescues the defective mitochondrial phenotype and the increased apoptosis of Cockayne Syndrome A cells},

author = {Pascucci B and D'Errico M and Romagnoli A and De Nuccio C and Savino M and Pietraforte D and Lanzafame M and Calcagnile AS and Fortini P and Baccarini S and Orioli D and Degan P and Visentin S and Stefanini M and Isidoro C and Fimia GM and Dogliotti E},

url = {http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=9913&pubmed-linkout=1},

doi = {10.18632/oncotarget.9913},

year  = {2016},

date = {2016-06-07},

journal = {Oncotarget},

volume = {8},

number = {61},

pages = {102852-102867},

abstract = {The ERCC8/CSA gene encodes a WD-40 repeat protein (CSA) that is part of a E3-ubiquitin ligase/COP9 signalosome complex. When mutated, CSA causes the Cockayne Syndrome group A (CS-A), a rare recessive progeroid disorder characterized by sun sensitivity and neurodevelopmental abnormalities. CS-A cells features include ROS hyperproduction, accumulation of oxidative genome damage, mitochondrial dysfunction and increased apoptosis that may contribute to the neurodegenerative process. In this study, we show that CSA localizes to mitochondria and specifically interacts with the mitochondrial fission protein dynamin-related protein (DRP1) that is hyperactivated when CSA is defective. Increased fission is not counterbalanced by increased mitophagy in CS-A cells thus leading to accumulation of fragmented mitochondria. However, when mitochondria are challenged with the mitochondrial toxin carbonyl cyanide m-chloro phenyl hydrazine, CS-A fibroblasts undergo mitophagy as efficiently as normal fibroblasts, suggesting that this process remains targetable to get rid of damaged mitochondria. Indeed, when basal mitophagy was potentiated by overexpressing Parkin in CSA deficient cells, a significant rescue of the dysfunctional mitochondrial phenotype was observed. Importantly, Parkin overexpression not only reactivates basal mitophagy, but plays also an anti-apoptotic role by significantly reducing the translocation of Bax at mitochondria in CS-A cells. These findings provide new mechanistic insights into the role of CSA in mitochondrial maintenance and might open new perspectives for therapeutic approaches.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_301,

title = {Ultrastructural regenerating features of nasal mucosa following microdebrider-assisted turbinoplasty are related to clinical recovery.},

author = {Neri G and Cazzato F and Mastronardi V and Pugliese M and Centurione MA and Di Pietro R and Centurione L},

url = {http://translational-medicine.biomedcentral.com/articles/10.1186/s12967-016-0931-8},

doi = {10.1186/s12967-016-0931-8.},

year  = {2016},

date = {2016-06-02},

journal = {Journal of Translational Medicine},

volume = {14},

number = {1},

pages = {164},

abstract = {turbinoplasty},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_297,

title = {Specific inductive potential of a novel nanocomposite biomimetic biomaterial for osteochondral tissue regeneration},

author = {Manferdini C and Cavallo C and Grigolo B and Fiorini M and Nicoletti A and Gabusi E and Zini N and Pressato D and Facchini A and Lisignoli G},

url = {http://onlinelibrary.wiley.com/doi/10.1002/term.1723/abstract;jsessionid=0358FE4D72F098C66724266255F4F49A.f02t04},

year  = {2016},

date = {2016-05-27},

journal = {Journal of Tissue Engineering and Regenerative Medicine},

volume = {10},

pages = {374-391},

abstract = {Osteochondral lesions require treatment to restore the biology and functionality of the joint. A novel nanostructured biomimetic gradient scaffold was developed to mimic the biochemical and biophysical properties of the different layers of native osteochondral structure. The present results show that the scaffold presents important physicochemical characteristics and can support the growth and differentiation of mesenchymal stromal cells (h-MSCs), which adhere and penetrate into the cartilaginous and bony layers. H-MSCs grown in chondrogenic or osteogenic medium decreased their proliferation during days 14-52 on both scaffold layers and in medium without inducing factors used as controls. Both chondrogenic and osteogenic differentiation of h-MSCs occurred from day 28 and were increased on day 52, but not in the control medium. Safranin O staining and collagen type II and proteoglycans immunostaining confirmed that chondrogenic differentiation was specifically induced only in the cartilaginous layer. Conversely, von Kossa staining, osteocalcin and osteopontin immunostaining confirmed that osteogenic differentiation occurred on both layers. This study shows the specific potential of each layer of the biomimetic scaffold to induce chondrogenic or osteogenic differentiation of h-MSCs. These processes depended mainly on the media used but not the biomaterial itself, suggesting that the local milieu is fundamental for guiding cell differentiation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_254,

title = {Human DDX3 protein is a valuable target to develop broad spectrum antiviral agents.},

author = {Brai A and Fazi R and Tintori C and Zamperini C and Bugli F and Sanguinetti M and Stigliano E and Este' J and Badia R and Franco S and Martinez MA and Martinez JP and Meyerhans A and Saladini F and Zazzi M and Garbelli A and Maga G and Botta M},

url = {http://www.pnas.org/content/113/19/5388.long},

doi = {10.1073/pnas.1522987113},

year  = {2016},

date = {2016-05-10},

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

volume = {113},

number = {9},

pages = {5388-5393},

abstract = {Targeting a host factor essential for the replication of different viruses but not for the cells offers a higher genetic barrier to the development of resistance, may simplify therapy regimens for coinfections, and facilitates management of emerging viral diseases. DEAD-box polypeptide 3 (DDX3) is a human host factor required for the replication of several DNA and RNA viruses, including some of the most challenging human pathogens currently circulating, such as HIV-1, Hepatitis C virus, Dengue virus, and West Nile virus. Herein, we showed for the first time, to our knowledge, that the inhibition of DDX3 by a small molecule could be successfully exploited for the development of a broad spectrum antiviral agent. In addition to the multiple antiviral activities, hit compound 16d retained full activity against drug-resistant HIV-1 strains in the absence of cellular toxicity. Pharmacokinetics and toxicity studies in rats confirmed a good safety profile and bioavailability of 16d. Thus, DDX3 is here validated as a valuable therapeutic target.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_284,

title = {External validation of the MetS score, a prediction tool for metabolic syndrome.},

author = {Graziano F and Grassi M and Bonati MT and Zanchetti A and Biino G},

url = {http://www.sciencedirect.com/science/article/pii/S093947531500263X},

doi = {10.1016/j.numecd.2015.12.014},

year  = {2016},

date = {2016-04-29},

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

volume = {26},

number = {4},

pages = {359-360},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_249,

title = {Experimental measurements and mathematical modeling of biological noise arising from transcriptional and translational regulation of basic synthetic gene circuits.},

author = {Bandiera L and Pasini A and Pasotti L and Zucca S and Mazzini G and Magni P and Giordano E and Furini S},

url = {http://www.sciencedirect.com/science/article/pii/S0022519316000941},

doi = {10.1016/j.jtbi.2016.02.004},

year  = {2016},

date = {2016-04-21},

journal = {Journal of Theoretical Biology},

volume = {395},

pages = {153-160},

abstract = {The small number of molecules, unevenly distributed within an isogenic cell population, makes gene expression a noisy process, and strategies have evolved to deal with this variability in protein concentration and to limit its impact on cellular behaviors. As translational efficiency has a major impact on biological noise, a possible strategy to control noise is to regulate gene expression processes at the post-transcriptional level. In this study, fluctuations in the concentration of a green fluorescent protein were compared, at the single cell level, upon transformation of an isogenic bacterial cell population with synthetic gene circuits implementing either a transcriptional or a post-transcriptional control of gene expression. Experimental measurements showed that protein variability is lower under post-transcriptional control, when the same average protein concentrations are compared. This effect is well reproduced by stochastic simulations, supporting the hypothesis that noise reduction is due to the control mechanism acting on the efficiency of translation. Similar strategies are likely to play a role in noise reduction in natural systems and to be useful for controlling noise in synthetic biology applications. Copyright 2016 Elsevier Ltd. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_319,

title = {A comprehensive strategy for the analysis of acoustic compressibility and optical deformability on single cells.},

author = {Yang T and Bragheri F and Nava G and Chiodi I and Mondello C and Osellame R and Berg-Sørensen K and Cristiani I and Minzioni P},

url = {http://www.nature.com/articles/srep23946},

doi = {10.1038/srep23946},

year  = {2016},

date = {2016-04-20},

journal = {Scientific Reports},

volume = {6},

pages = {23946},

abstract = {We realized an integrated microfluidic chip that allows measuring both optical deformability and acoustic compressibility on single cells, by optical stretching and acoustophoresis experiments respectively. Additionally, we propose a measurement protocol that allows evaluating the experimental apparatus parameters before performing the cell-characterization experiments, including a non-destructive method to characterize the optical force distribution inside the microchannel. The chip was used to study important cell-mechanics parameters in two human breast cancer cell lines, MCF7 and MDA-MB231. Results indicate that MDA-MB231 has both higher acoustic compressibility and higher optical deformability than MCF7, but statistical analysis shows that optical deformability and acoustic compressibility are not correlated parameters. This result suggests the possibility to use them to analyze the response of different cellular structures. We also demonstrate that it is possible to perform both measurements on a single cell, and that the order of the two experiments does not affect the retrieved values.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_289,

title = {Non‑invasive prostate cancer detection by measuring miRNA variants (isomiRs) in urine extracellular vesicles.},

author = {Koppers-Lalic D and Hackenberg M and Menezes R and Misovic B and Wachalska M and Geldof A and Zini N and Reijke T and Wurdinger T and Vis A and Moorselaar JV and Pegtel M and Bijnsdorp I},

url = {http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=8124&pubmed-linkout=1},

doi = {10.18632/oncotarget.8124},

year  = {2016},

date = {2016-04-19},

journal = {Oncotarget},

volume = {7},

number = {16},

pages = {22566-22578},

abstract = {In many cancer types, the expression and function of ~22 nucleotide-long microRNAs (miRNA) is deregulated. Mature miRNAs can be stably detected in extracellular vesicles (EVs) in biofluids, therefore they are considered to have great potential as biomarkers. In the present study, we investigated whether miRNAs have a distinct expression pattern in urine-EVs of prostate cancer (PCa) patients compared to control males. By next generation sequencing, we determined the miRNA expression in a discovery cohort of 4 control men and 9 PCa patients. miRNAs were validated by using a stemloop RT-PCR in an independent cohort of 74 patients (26 control and 48 PCa-patients). Whereas standard mapping protocols identified > 10 PCa associated miRNAs in urinary EVs, miR-21, miR-375 and miR-204 failed to robustly discriminate for disease in a validation study with RT-PCR-detection of mature miRNA sequences. In contrast, we observed that miRNA isoforms (isomiRs) with 3' end modifications were highly discriminatory between samples from control men and PCa patients. Highly differentially expressed isomiRs of miR-21, miR-204 and miR-375 were subsequently validated in an independent group of 74 patients. Receiver-operating characteristic analysis was performed to evaluate the diagnostic performance of three isomiRs, resulting in a 72.9% sensitivity with a high (88%) specificity and an area under the curve (AUC) of 0.866. In comparison, prostate specific antigen had an AUC of 0.707 and measuring the mature form of these miRNAs yielded a lower 70.8% sensitivity and 72% specificity (AUC 0.766). We propose that isomiRs may carry discriminatory information which is useful to generate stronger biomarkers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_290,

title = {GTF2E2 Mutations Destabilize the General Transcription Factor Complex TFIIE in Individuals with DNA Repair-Proficient Trichothiodystrophy.},

author = {Kuschal C and Botta E and Orioli D and Digiovanna JJ and Seneca S and Keymolen K and Tamura D and Heller E and Khan SG and Caligiuri G and Lanzafame M and Nardo T and Ricotti R and Peverali FA and Stephens R and Zhao Y and Lehmann AR and Baranello L and Levens D and Kraemer KH and Stefanini M},

url = {http://www.sciencedirect.com/science/article/pii/S0002929716000598},

doi = {10.1016/j.ajhg.2016.02.008},

year  = {2016},

date = {2016-04-16},

journal = {American Journal of Human Genetics},

volume = {98},

number = {4},

pages = {627-642},

abstract = {The general transcription factor IIE (TFIIE) is essential for transcription initiation by RNA polymerase II (RNA pol II) via direct interaction with the basal transcription/DNA repair factor IIH (TFIIH). TFIIH harbors mutations in two rare genetic disorders, the cancer-prone xeroderma pigmentosum (XP) and the cancer-free, multisystem developmental disorder trichothiodystrophy (TTD). The phenotypic complexity resulting from mutations affecting TFIIH has been attributed to the nucleotide excision repair (NER) defect as well as to impaired transcription. Here, we report two unrelated children showing clinical features typical of TTD who harbor different homozygous missense mutations in GTF2E2 (c.448G>C [p.Ala150Pro] and c.559G>T [p.Asp187Tyr]) encoding the beta subunit of transcription factor IIE (TFIIEbeta). Repair of ultraviolet-induced DNA damage was normal in the GTF2E2 mutated cells, indicating that TFIIE was not involved in NER. We found decreased protein levels of the two TFIIE subunits (TFIIEalpha and TFIIEbeta) as well as decreased phosphorylation of TFIIEalpha in cells from both children. Interestingly, decreased phosphorylation of TFIIEalpha was also seen in TTD cells with mutations in ERCC2, which encodes the XPD subunit of TFIIH, but not in XP cells with ERCC2 mutations. Our findings support the theory that TTD is caused by transcriptional impairments that are distinct from the NER disorder XP. Copyright  2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_279,

title = {Solution and Solid-State Analysis of Binding of 13-Substituted Berberine Analogues to Human Telomeric G-quadruplexes.},

author = {Ferraroni M and Bazzicalupi C and Papi F and Fiorillo G and Guamán-Ortiz LM and Nocentini A and Scovassi AI and Lombardi P and Gratteri P},

url = {http://onlinelibrary.wiley.com/doi/10.1002/asia.201600116/abstract;jsessionid=41A7EB754351C529E5530508A971084B.f04t01},

doi = {10.1002/asia.201600116},

year  = {2016},

date = {2016-04-05},

journal = {Chemistry, an Asian Journal},

volume = {11},

number = {7},

pages = {1107-1115},

abstract = {he interaction between 13-phenylalkyl and 13-diphenylalkyl berberine derivatives (NAX) and human telomeric DNA G4 structures has been investigated by both spectroscopic and crystallographic methods. NAX042 and NAX053 are the best compounds improving the performance of the natural precursor berberine. This finding is in agreement with the X-ray diffraction result for the NAX053-Tel12 adduct, showing the ligand which interacts via π-stacking, sandwiched at the interface of two symmetry-related quadruplex units, with its benzhydryl group contributing to the overall stability of the adduct by means of additional π-stacking interactions with the DNA residues. The berberine derivatives were also investigated for their cytotoxic activity towards a panel of human cancer cell lines. Compounds NAX042 and NAX053 affect the viability of cancer cell lines in a dose-dependent manner. 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_277,

title = {Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.},

author = {Fan Q and Verhoeven VJ and Wojciechowski R and Barathi VA and Hysi PG and Guggenheim JA and Höhn R and Vitart V and Khawaja AP and Yamashiro K and Hosseini SM and {et aò} and Biino G and Vaccargiu S and Fossarello M and Fleck B and Yazar S and Tideman JW and Tedja M and Deangelis MM and Morrison M and Farrer L and Zhou X and Chen W and Mizuki N and Meguro A and Makela KM},

url = {http://www.nature.com/ncomms/2016/160329/ncomms11008/full/ncomms11008.html},

doi = {10.1038/ncomms11008},

year  = {2016},

date = {2016-03-29},

journal = {Nature Communications},

volume = {7},

pages = {11008},

abstract = {Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_252,

title = {Snail levels control the migration mechanism of mesenchymal tumor cells.},

author = {Belgiovine C and Chiesa G and Chiodi I and Frapolli R and Bonezzi K and Taraboletti G and D'Incalci M and Mondello C},

url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907273/},

doi = {10.3892/ol.2016.4642},

year  = {2016},

date = {2016-03-16},

journal = {Oncology Letters},

volume = {12},

number = {1},

pages = {767-771},

abstract = {Cancer cells use two major types of movement: Mesenchymal, which is typical of cells of mesenchymal origin and depends on matrix metalloproteinase (MMP) activity, and amoeboid, which is characteristic of cells with a rounded shape and relies on the activity of Rho-associated kinase (ROCK). The present authors previously demonstrated that, during neoplastic transformation, telomerase-immortalized human fibroblasts (cen3tel cells) acquired a ROCK-dependent/MMP independent mechanism of invasion, mediated by the downregulation of the ROCK cellular inhibitor Round (Rnd)3/RhoE. In the present study, cen3tel transformation was also demonstrated to be paralleled by downregulation of Snail, a major determinant of the mesenchymal movement. To test whether Snail levels could determine the type of movement adopted by mesenchymal tumor cells, Snail was ectopically expressed in tumorigenic cells. It was observed that ectopic Snail did not increase the levels of typical mesenchymal markers, but induced cells to adopt an MMP-dependent mechanism of invasion. In cells expressing ectopic Snail, invasion became sensitive to the MMP inhibitor Ro 28-2653 and insensitive to the ROCK inhibitor Y27632, suggesting that, once induced by Snail, the mesenchymal movement prevails over the amoeboid one. Snail-expressing cells had a more aggressive behavior in vivo, and exhibited increased tumor growth rate and metastatic ability. These results confirm the high plasticity of cancer cells, which can adopt different types of movement in response to changes in the expression of specific genes. Furthermore, the present findings indicate that Rnd3 and Snail are possible regulators of the type of invasion mechanism adopted by mesenchymal tumor cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_261,

title = {Telomere and telomerase stability in human diseases and cancer.},

author = {Chiodi I and Mondello C},

year  = {2016},

date = {2016-03-11},

journal = {Frontiers In  Bioscience},

volume = {21},

pages = {203-224},

abstract = {Telomeres are the nucleoprotein structures at the end of linear eukaryotic chromosomes required for genome stability. Telomerase is the specialized enzyme deputed to their elongation. Maintenance of a proper telomere structure, an accurate regulation of telomerase biogenesis and activity, as well as a correct telomere-telomerase interaction and a faithful telomeric DNA replication are all processes that a cell has to precisely control to safeguard its functionality. Here, we review key factors that play a role in the development of these processes and their relationship with human health.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_262,

title = {The Regulation of DNA Damage Tolerance by Ubiquitin and Ubiquitin-Like Modifiers.},

author = {Cipolla L and Maffia A and Bertoletti F and Sabbioneda S},

url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904029/},

doi = {10.3389/fgene.2016.00105},

year  = {2016},

date = {2016-03-11},

journal = {Frontiers in Genetics},

volume = {7},

pages = {105},

abstract = {DNA replication is an extremely complex process that needs to be executed in a highly accurate manner in order to propagate the genome. This task requires the coordination of a number of enzymatic activities and it is fragile and prone to arrest after DNA damage. DNA damage tolerance provides a last line of defense that allows completion of DNA replication in the presence of an unrepaired template. One of such mechanisms is called post-replication repair (PRR) and it is used by the cells to bypass highly distorted templates caused by damaged bases. PRR is extremely important for the cellular life and performs the bypass of the damage both in an error-free and in an error-prone manner. In light of these two possible outcomes, PRR needs to be tightly controlled in order to prevent the accumulation of mutations leading ultimately to genome instability. Post-translational modifications of PRR proteins provide the framework for this regulation with ubiquitylation and SUMOylation playing a pivotal role in choosing which pathway to activate, thus controlling the different outcomes of damage bypass. The proliferating cell nuclear antigen (PCNA), the DNA clamp for replicative polymerases, plays a central role in the regulation of damage tolerance and its modification by ubiquitin, and SUMO controls both the error-free and error-prone branches of PRR. Furthermore, a significant number of polymerases are involved in the bypass of DNA damage possess domains that can bind post-translational modifications and they are themselves target for ubiquitylation. In this review, we will focus on how ubiquitin and ubiquitin-like modifications can regulate the DNA damage tolerance systems and how they control the recruitment of different proteins to the replication fork.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_308,

title = {Tendon Extracellular Matrix Alterations in Ullrich Congenital Muscular Dystrophy.},

author = {Sardone F and Traina F and Bondi A and Merlini L and Santi S and Maraldi NM and Faldini C and Sabatelli P},

url = {http://journal.frontiersin.org/article/10.3389/fnagi.2016.00131/full},

doi = {10.3389/fnagi.2016.00131},

year  = {2016},

date = {2016-03-10},

journal = {Frontiers in Aging Neuroscience},

volume = {8},

pages = {131},

abstract = {Collagen VI (COLVI) is a non-fibrillar collagen expressed in skeletal muscle and most connective tissues. Mutations in COLVI genes cause two major clinical forms, Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD). In addition to congenital muscle weakness, patients affected by COLVI myopathies show axial and proximal joint contractures and distal joint hypermobility, which suggest the involvement of the tendon function. We examined a peroneal tendon biopsy and tenocyte culture of a 15-year-old patient affected by UCMD with compound heterozygous COL6A2 mutations. In patient's tendon biopsy, we found striking morphological alterations of tendon fibrils, consisting in irregular profiles and reduced mean diameter. The organization of the pericellular matrix of tenocytes, the primary site of collagen fibril assembly, was severely affected, as determined by immunoelectron microscopy, which showed an abnormal accumulation of COLVI and altered distribution of collagen I (COLI) and fibronectin (FBN). In patient's tenocyte culture, COLVI web formation and cell surface association were severely impaired; large aggregates of COLVI, which matched with COLI labeling, were frequently detected in the extracellular matrix. In addition, metalloproteinase MMP-2, an extracellular matrix-regulating enzyme, was increased in the conditioned medium of patient's tenocytes, as determined by gelatin zymography and western blot. Altogether, these data indicate that COLVI deficiency may influence the organization of UCMD tendon matrix, resulting in dysfunctional fibrillogenesis. The alterations of tendon matrix may contribute to the complex pathogenesis of COLVI related myopathies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_321,

title = {The human tyrosine kinase Kit and its gatekeeper mutant T670I, show different kinetic properties: Implications for drug design.},

author = {Kissova M and Maga G and Crespan E},

url = {http://www.sciencedirect.com/science/article/pii/S0968089616305806},

doi = {10.1016/j.bmc.2016.07.059},

year  = {2016},

date = {2016-03-10},

journal = {Bioorganic & Medicinal Chemistry},

volume = {24},

number = {19},

pages = {4555-4532},

abstract = {The tyrosine kinase Kit, a receptor for Stem Cell Factor, is involved, among others, in processes associated to cell survival, proliferation and migration. Upon physiological conditions, the activity of Kit is tightly regulated. However, primary mutations that lead to its constitutive activation are the causal oncogenic driver of gastrointestinal stromal tumours (GISTs). GISTs are known to be refractory to conventional therapies but the introduction of Imatinib, a selective inhibitor of tyrosine kinases Abl and Kit, significantly ameliorated the treatment options of GISTs patients. However, the acquisition of secondary mutations renders Kit resistant towards all available drugs. Mutation involving gatekeeper residues (such as V654a and T670I) influence both the structure and the catalytic activity of the enzyme. Therefore, detailed knowledge of the enzymatic properties of the mutant forms, in comparison with the wild type enzyme, is an important pre-requisite for the rational development of specific inhibitors. In this paper we report a thorough kinetic analysis of the reaction catalyzed by the Kit kinase and its gatekeeper mutated form T670I. Our results revealed the different mechanisms of action of these two enzymes and may open a new avenue for the future design of specific Kit inhibitors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_283,

title = {Intolerant contact lens wearers exhibit ocular surface impairment despite 3 months wear discontinuation.},

author = {Giannaccare G and Blalock WL and Fresina M and Vagge A and Versura P},

url = {http://link.springer.com/article/10.1007%2Fs00417-016-3400-4},

doi = {10.1007/s00417-016-3400-4},

year  = {2016},

date = {2016-03-09},

journal = {Graefe's Archive for Clinical and Experimental Ophthalmology },

volume = {254},

number = {9},

pages = {1825-1831},

abstract = {Purpose: To evaluate ocular surface (OS) parameters recovery in intolerant contact lens (CL) wearers after a period of discontinuation. Methods: This is a retrospective analysis of data from 87 intolerant CL wearers who had discontinued their use for an average period of 12 weeks because of associated discomfort and failure to successfully refit. Data were collected from clinical charts. Data from 50 matched healthy volunteers served as controls. Clinical tests included subjective discomfort symptoms questionnaire (Ocular Surface Disease Index, OSDI), Schirmer test, break-up time (BUT), corneal esthesiometry and corneo-conjunctival staining. Laboratory tests included scraping and imprint cytology. Tear protein analysis included dosage of total tear protein (TP), lysozyme-C (LYS-C), lactoferrin (LACTO), zinc-α2-glycoprotein (ZAG-2), IgA heavy chain bands (Ig-A), and serum albumin (ALB). Data were correlated to wear parameters. Results: All values were significantly worse in intolerant CL wearers group (p always <0.001). In particular, lower values compared to controls were found for BUT, corneal esthesiometry, goblet cell density, LYS-C, LACTO, ZAG-2, and TP. On the contrary, higher values compared to controls were found for OSDI, staining, imprint cytology, scraping cytology, ALB, IgA-heavy chain. The IgA/LYS-C ratio calculated as an index of the increased activity of the IgA-producing cell was found significantly higher in the intolerant group and in correlation with discomfort symptoms. Conclusions: Ocular surface parameters were altered in intolerant CL wearers, even after a prolonged discontinuation period. Our data suggest that OS recovery necessary to successfully refit lenses may need a discontinuation time longer than 3 months.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_246,

title = {Manipulation of Intracellular pH in Cancer Cells by NHE1 Inhibitors.},

author = {Aredia F and Scovassi AI},

url = {http://www.eurekaselect.com/146253/article},

doi = {10.2174/0929866523666161013125536 },

year  = {2016},

date = {2016-03-08},

journal = {Protein and peptide letters},

volume = {23},

number = {12},

pages = {1123-1129},

abstract = {Cancer cells are characterized by a peculiar pH condition, being the extracellular compartment acidic and the intracellular one neutral or basic, i.e. the opposite of what happens in normal cells. The reversal of the pH contributes to cancer cell proliferation and drug resistance. Among the different enzymes regulating pH gradient, proton transporters Na+/H+ exchangers (NHEs) are considered as suitable targets for drugs that ultimately counteract cancer cell survival. This review will describe the properties of NHEs, focusing on the prototype NHE1 and on the effect of its inhibition on cancer cell metabolism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_253,

title = {Detection of mesenchymal stem cells senescence by prelamin A accumulation at the nuclear level.},

author = {Bellotti C and Capanni C and Lattanzi G and Donati D and Lucarelli E and Duchi S},

url = {http://springerplus.springeropen.com/articles/10.1186/s40064-016-3091-7},

doi = {10.1186/s40064-016-3091-7},

year  = {2016},

date = {2016-03-08},

urldate = {2016-03-08},

journal = {Springerplus},

volume = {5},

number = {1},

pages = {1427},

abstract = {Human mesenchymal stem cells (MSC), during in vitro expansion, undergo a progressive loss of proliferative potential that leads to the senescent state, associated with a reduction of their "medicinal" properties. This may hampers their efficacy in the treatment of injured tissues. Quality controls on MSC-based cell therapy products should include an assessment of the senescent state. However, a reliable and specific marker is still missing. From studies on lamin-associated disorders, has emerged the correlation between defective lamin A maturation and cellular senescence. FINDINGS: Primary cultured hMSC lines (n = 3), were analyzed by immunostaining at different life-span stages for the accumulation of prelamin A, along with other markers of cellular senescence. During culture, cells at the last stage of their life span displayed evident signs of senescence consistent with the positivity of SA-β-gal staining. We also observed a significant increase of prelamin A positive cells. Furthermore, we verified that the cells marked by prelamin A were also positive for p21(Waf1) while negative for Ki67. CONCLUSIONS: Overall data support that the detection of prelamin A identifies senescent MSC, providing an easy and reliable tool to be use alone or in combination with known senescence markers to screen MSC before their use in clinical applications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_293,

title = {Barrier-to-Autointegration Factor (BAF) involvement in prelamin A-related chromatin organization changes.},

author = {Loi M and Cenni V and Duchi S and Squarzoni S and {Lopez-Otin C} and Foisner R and Lattanzi G and Capanni C},

url = {http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=6697&pubmed-linkout=1},

doi = {10.18632/oncotarget.6697},

year  = {2016},

date = {2016-03-08},

urldate = {2016-03-08},

journal = {Oncotarget},

volume = {7},

number = {13},

pages = {15662-15677},

abstract = {Chromatin disorganization is one of the major alterations linked to prelamin A processing impairment. In this study we demonstrate that BAF is necessary to modulate prelamin A effects on chromatin structure. We show that when prelamin A and BAF cannot properly interact no prelamin A-dependent effects on chromatin occur; similar to what is observed in human Nestor Guillermo Progeria Syndrome cells harboring a BAF mutation, in HEK293 cells expressing a BAF mutant unable to bind prelamin A, or in siRNA mediated BAF-depleted HEK293 cells expressing prelamin A. BAF is necessary to induce histone trimethyl-H3K9 as well as HP1-alpha and LAP2-alpha nuclear relocalization in response to prelamin A accumulation. These findings are enforced by electron microscopy evaluations showing how the prelamin A-BAF interaction governs overall chromatin organization. Finally, we demonstrate that the LAP2-alpha nuclear localization defect observed in HGPS cells involves the progerin-BAF interaction, thus establishing a functional link between BAF and prelamin A pathological forms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_305,

title = {BMP-2 Induced Expression of PLCbeta1 That Is a Positive Regulator of Osteoblast Differentiation.},

author = {Ramazzotti G and Bavelloni A and Blalock WL and Piazzi M and Cocco L and Faenza I},

url = {http://onlinelibrary.wiley.com/doi/10.1002/jcp.25107/abstract;jsessionid=9619766386605F1FBD94DD07A67E9B42.f04t02},

year  = {2016},

date = {2016-03-07},

journal = {Journal of Cellular Physiology},

volume = {231},

number = {3},

pages = {623-629},

abstract = {"Bone morphogenetic protein 2 (BMP-2) is a critical growth factor that directs osteoblast differentiation and bone formation. Phosphoinositide-phospholipase Cbeta 1 (PLCbeta1) plays a crucial role in the initiation of the genetic program responsible for muscle differentiation. Differentiation of C2C12 mouse myoblasts in response to insulin stimulation is characterized by a marked increase in nuclear PLCbeta1. Here, the function of PLCbeta1 in the osteogenic differentiation was investigated. Briefly, in C2C12 cells treated with BMP-2 we assist to a remarkable increase in PLCbeta1 protein and mRNA expression. The data regarding the influence on differentiation demonstrated that PLCbeta1 promotes osteogenic differentiation by up-regulating alkaline phosphatase (ALP). Moreover, PLCbeta1 is present in the nuclear compartment of these cells and overexpression of a cytosolic-PLCbeta1mutant (cyt-PLCbeta1), which lacks a nuclear localization sequence, prevented the differentiation of C2C12 cells into osteocytes. Recent evidence indicates that miRNAs act as important post transcriptional regulators in a large number of processes, including osteoblast differentiation. Since miR-214 is a regulator of Osterix (Osx) which is an osteoblast-specific transcription factor that is needful for osteoblast differentiation and bone formation, we further investigated whether PLCbeta1 could be a potential target of miR-214 in the control of osteogenic differentiation by gain- and loss- of function experiment. The results indicated that inhibition of miR-214 in C2C12 cells significantly enhances the protein level of PLCbeta1 and promotes C2C12 BMP-2-induced osteogenesis by targeting PLCbeta1. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.



"},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_296,

title = {Osteogenic potential of dualblocks cultured with human periodontal ligament stem cells: in vitro and synchrotron microtomography study.},

author = {Manescu A and Giuliani A and Mohammadi S and Tromba G and Mazzoni S and Diomede F and Zini N and Piattelli A and Trubiani O},

url = {http://onlinelibrary.wiley.com/doi/10.1111/jre.12289/abstract},

doi = {10.1111/jre.12289},

year  = {2016},

date = {2016-02-29},

journal = {Journal of Periodontal Research},

volume = {51},

number = {1},

pages = {112-124},

abstract = {"BACKGROUND AND OBJECTIVE: In the present study, the early stages of in vitro bone formation in collagenated porcine scaffolds cultured with human periodontal ligament cells were investigated. The comparison between the osteogenic potential of this structure in basal and differentiating culture media was explored to predict the mechanism of its biological behavior as graft in human defect. Results were validated by synchrotron radiation X-Ray phase contrast computed microtomography (micro-CT). As the periodontal disease plays a key role in systemic and oral diseases, it is crucial to find advanced therapeutic clinical interventions to repair periodontal defects. This has been recently explored using cells and tissues developed in vitro that should ideally be immunologically, functionally, structurally and mechanically identical to the native tissue. MATERIAL AND METHODS:

In vitro cultures of human periodontal ligament cells, easily obtained by scraping of alveolar crestal and horizontal fibers of the periodontal ligament, were seeded on to collagenated porcine blocks constituted by natural cancellous and cortical bone. 3D images were obtained by synchrotron radiation micro-CT and processed with a phase-retrieval algorithm based on the transport of intensity equation. RESULTS: Starting from the second week of culture, newly formed mineralized bone was detected in all the scaffolds, both in basal and differentiating media. Bone mineralization was proved to occur preferentially in the trabecular portion and in differentiating media. CONCLUSION: The chosen method, supported by phase contrast micro-CT analysis, successfully and quantitatively monitored the early stages of bone formation and the rate of the bioscaffold resorption in basal and differentiating culture media. 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd."},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_302,

title = {Genome-wide association study identifies 74 loci associated with educational attainment.},

author = {Okbay A and Beauchamp JP and Fontana MA and Lee JJ and Pers TH and Rietveld CA and Turley P and Chen GB and Emilsson V and Meddens SF and Oskarsson S and Pickrell JK and Thom K and Timshel P and {et al} and Biino G and {et al} and Benjamin DJ},

url = {http://www.nature.com/nature/journal/v533/n7604/full/nature17671.html},

doi = {10.1038/nature17671},

year  = {2016},

date = {2016-02-29},

journal = {Nature},

volume = {533},

number = {7604},

pages = {539-542},

abstract = {Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_268,

title = {MCD diet-induced steatohepatitis is associated with alterations in asymmetric dimethylarginine (ADMA) and its transporters.},

author = {{Di Pasqua LG} and Berardo C and Rizzo V and Richelmi P and Croce AC and Vairetti M and Ferrigno A},

url = {http://link.springer.com/article/10.1007%2Fs11010-016-2758-2},

doi = {10.1007/s11010-016-2758-2},

year  = {2016},

date = {2016-02-27},

journal = {Molecular and Cellular Biochemistry},

volume = {419},

number = {1},

pages = {147-155},

abstract = {Using an experimental model of NASH induced by a methionine-choline-deficient (MCD) diet, we investigated whether changes occur in serum and tissue levels of asymmetric dimethylarginine (ADMA). Male Wistar rats underwent NASH induced by 8-week feeding with an MCD diet. Serum and hepatic biopsies at 2, 4 and 8 weeks were taken, and serum enzymes, ADMA and nitrate/nitrite (NOx), were evaluated. Hepatic biopsies were used for mRNA and protein expression analysis of dimethylarginine dimethylaminohydrolase-1 (DDAH-1) and protein methyltransferases (PRMT-1), enzymes involved in ADMA metabolism and synthesis, respectively, and ADMA transporters (CAT-1, CAT-2A and CAT-2B). Lipid peroxides (TBARS), glutathione, ATP/ADP and DDAH activity were quantified. An increase in serum AST and ALT was detected in MCD animals. A time-dependent decrease in serum and tissue ADMA and increase in mRNA expression of DDAH-1 and PRMT-1 as well as higher rates of mRNA expression of CAT-1 and lower rates of CAT-2A and CAT-2B were found after 8-week MCD diet. An increase in serum NOx and no changes in protein expression in DDAH-1 and CAT-1 and higher content in CAT-2 and PRMT-1 were found at 8 weeks. Hepatic DDAH activity decreased with a concomitant increase in oxidative stress, as demonstrated by high TBARS levels and low glutathione content. In conclusion, a decrease in serum and tissue ADMA levels in the MCD rats was found associated with a reduction in DDAH activity due to the marked oxidative stress observed. Changes in ADMA levels and its transporters are innovative factors in the onset and progression of hepatic alterations correlated with MCD diet-induced NASH.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_298,

title = {Genetic variants linked to education predict longevity.},

author = {Marioni RE and Ritchie SJ and Joshi PK and Hagenaars SP and Okbay A and Fischer K and Adams MJ and Hill WD and Davies G and {et al} nad and Biino G and {et al} and Benjamin DJ},

url = {http://www.pnas.org/content/early/2016/10/25/1605334113.long},

doi = {10.1073/pnas.1605334113},

year  = {2016},

date = {2016-02-27},

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

volume = {113},

number = {47},

pages = {13366-13371},

abstract = {Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland, n = ∼17,000; UK Biobank, n = ∼115,000; and the Estonian Biobank, n = ∼6,000) to test whether education-linked genetic variants can predict lifespan length. We did so by using cohort members' polygenic profile score for education to predict their parents' longevity. Across the three cohorts, meta-analysis showed that a 1 SD higher polygenic education score was associated with ∼2.7% lower mortality risk for both mothers (total ndeaths = 79,702) and ∼2.4% lower risk for fathers (total ndeaths = 97,630). On average, the parents of offspring in the upper third of the polygenic score distribution lived 0.55 y longer compared with those of offspring in the lower third. Overall, these results indicate that the genetic contributions to educational attainment are useful in the prediction of human longevity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_263,

title = {Impact of ribonucleotide incorporation by DNA polymerases beta and lambda on oxidative base excision repair.},

author = {Crespan E and Furrer A and Rösinger M and Bertoletti F and Mentegari E and Chiapparini G and Imhof R and Ziegler N and Sturla SJ and Hubscher U and van Loon B and Maga G},

url = {http://www.nature.com/ncomms/2016/160226/ncomms10805/full/ncomms10805.html},

doi = {10.1038/ncomms10805},

year  = {2016},

date = {2016-02-26},

journal = {Nature Communications},

volume = {7},

pages = {10805},

abstract = {Oxidative stress is a very frequent source of DNA damage. Many cellular DNA polymerases (Pols) can incorporate ribonucleotides (rNMPs) during DNA synthesis. However, whether oxidative stress-triggered DNA repair synthesis contributes to genomic rNMPs incorporation is so far not fully understood. Human specialized Pols beta and lamdda are the important enzymes involved in the oxidative stress tolerance, acting both in base excision repair and in translesion synthesis past the very frequent oxidative lesion 7,8-dihydro-8-oxoguanine (8-oxo-G). We found that Pol beta, to a greater extent than Pol lambda can incorporate rNMPs opposite normal bases or 8-oxo-G, and with a different fidelity. Further, the incorporation of rNMPs opposite 8-oxo-G delays repair by DNA glycosylases. Studies in Pol beta- and lambda-deficient cell extracts suggest that Pol beta levels can greatly affect rNMP incorporation opposite oxidative DNA lesions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_288,

title = {Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)},

author = {Klionsky DJ and Abdelmohsen K and Abe A and Scovassi AI and {et al}},

url = {http://www.tandfonline.com/doi/full/10.1080/15548627.2015.1100356},

doi = {10.1080/15548627.2015.1100356},

year  = {2016},

date = {2016-02-26},

journal = {Autophagy},

volume = {12},

number = {1},

pages = {222},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_250,

title = {Genome-wide analysis identifies 12 loci influencing human reproductive behavior.},

author = {Barban N and Jansen R and de Vlaming R and Vaez A and Mandemakers JJ and Tropf FC and Shen X and Wilson JF and Chasman DI and Nolte IM and {et al} and Biino G and {et al } and Koellinger PD and den Hoed M and Snieder H and Mills MC},

url = {http://www.nature.com/ng/journal/v48/n12/full/ng.3698.html},

doi = {10.1038/ng.3698},

year  = {2016},

date = {2016-02-25},

journal = {Nature Genetics},

volume = {48},

number = {12},

pages = {1462-1472},

abstract = {The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_266,

title = {Hydrogen peroxide-dependent oxidative stress induces SOD1 transcription gene is independent from Nrf2 transcription factor in a cellular model of neurodegeneration.},

author = {{Dell'Orco M} and Milani P and Arrigoni L and Pansarasa O and Sardone V and Maffioli E and Polveraccio F and Bordoni M and Diamanti L and Peverali FA and Tedeschi G and Cereda C},

url = {http://www.sciencedirect.com/science/article/pii/S1874939915002485},

doi = {10.1016/j.bbagrm.2015.11.009},

year  = {2016},

date = {2016-02-25},

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

volume = {1859},

number = {2},

pages = {315-323},

abstract = {BACKGROUND: It is still unclear whether oxidative stress (OS) is a disease consequence or is directly involved in the etiology of neurodegenerative disorders (NDs) onset and/or progression; however, many of these conditions are associated with increased levels of oxidation markers and damaged cell components. Previously we demonstrated the accumulation of reactive oxygen species (ROS) and increased SOD1 gene expression within H2O2 SH-SY5Y treated cells recapitulating pathological features of Amyotrophic Lateral Sclerosis (ALS). Since we observed a post-transcriptional regulation of SOD1 gene in this cellular model of ALS, we investigated the transcriptional regulation of SOD1 mRNA under oxidative stress (OS). RESULTS: In response to H2O2 treatment, PolII increased its association to SOD1 promoter. Electrophoretic mobility shift assays (EMSA) and mass spectrometry analyses on SOD1 promoter highlighted the formation of a transcriptional complex bound to the ARE sequences. WB analyses showed that in our in vitro model, H2O2 exposure increases Nrf2 nuclear fraction while IP experiments confirmed its phosphorylation and release from Keap1 inhibition. However, H2O2 treatment did not modify Nrf2 binding on SOD1 promoter, which seems to be regulated by different TFs. CONCLUSIONS: Although our data suggest that SOD1 is transcriptionally regulated in response to OS, Nrf2 does not appear to associate with SOD1 promoter in this model of ALS. Our results open new perspectives in the comprehension of two key antioxidant pathways involved in neurodegeneration. Copyright 2015. Published by Elsevier B.V.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_278,

title = {Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect.},

author = {Fassihi H and Sethi M and Fawcett H and Wing J and Chandler N and Mohammed S and Craythorne E and Morley AM and Lim R and Turner S and Henshaw T and Garrood I and Giunti P and Hedderly T and Abiona A and Naik H and Harrop G and McGibbon D and Jaspers NG and Botta E and Nardo T and Stefanini M and Young AR and Sarkany RP and Lehmann AR},

url = {http://www.pnas.org/content/113/9/E1236.long},

doi = {10.1073/pnas.1519444113},

year  = {2016},

date = {2016-02-25},

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

volume = {113},

number = {9},

pages = {1236-1245},

abstract = {Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by increased susceptibility to UV radiation (UVR)-induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Genetically, it is assigned to eight complementation groups (XP-A to -G and variant). For the last 5 y, the UK national multidisciplinary XP service has provided follow-up for 89 XP patients, representing most of the XP patients in the United Kingdom. Causative mutations, DNA repair levels, and more than 60 clinical variables relating to dermatology, ophthalmology, and neurology have been measured, using scoring systems to categorize disease severity. This deep phenotyping has revealed unanticipated heterogeneity of clinical features, between and within complementation groups. Skin cancer is most common in XP-C, XP-E, and XP-V patients, previously considered to be the milder groups based on cellular analyses. These patients have normal sunburn reactions and are therefore diagnosed later and are less likely to adhere to UVR protection. XP-C patients are specifically hypersensitive to ocular damage, and XP-F and XP-G patients appear to be much less susceptible to skin cancer than other XP groups. Within XP groups, different mutations confer susceptibility or resistance to neurological damage. Our findings on this large cohort of XP patients under long-term follow-up reveal that XP is more heterogeneous than has previously been appreciated. Our data now enable provision of personalized prognostic information and management advice for each XP patient, as well as providing new insights into the functions of the XP proteins.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_318,

title = {3D tumor spheroid models for in vitro therapeutic screening: a systematic approach to enhance the biological relevance of data obtained.},

author = {Zanoni M and Piccinini F and Arienti C and Zamagni A and Santi S and Polico R and Bevilacqua A and Tesei A},

url = {http://www.nature.com/articles/srep19103},

doi = {10.1038/srep19103},

year  = {2016},

date = {2016-02-25},

journal = {Scientific Reports},

volume = {6},

pages = {19103},

abstract = {The potential of a spheroid tumor model composed of cells in different proliferative and metabolic states for the development of new anticancer strategies has been amply demonstrated. However, there is little or no information in the literature on the problems of reproducibility of data originating from experiments using 3D models. Our analyses, carried out using a novel open source software capable of performing an automatic image analysis of 3D tumor colonies, showed that a number of morphology parameters affect the response of large spheroids to treatment. In particular, we found that both spheroid volume and shape may be a source of variability. We also compared some commercially available viability assays specifically designed for 3D models. In conclusion, our data indicate the need for a pre-selection of tumor spheroids of homogeneous volume and shape to reduce data variability to a minimum before use in a cytotoxicity test. In addition, we identified and validated a cytotoxicity test capable of providing meaningful data on the damage induced in large tumor spheroids of up to diameter in 650 μm by different kinds of treatments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_258,

title = {Autophagy activation in COL6 myopathic patients by a low-protein-diet pilot trial.},

author = {Castagnaro S and Pellegrini C and Pellegrini M and Chrisam M and Sabatelli P and Toni S and Grumati P and Ripamonti C and Pratelli L and Maraldi NM and Cocchi D and Righi V and Faldini C and Sandri M and Bonaldo P and Merlini L},

url = {http://www.tandfonline.com/doi/full/10.1080/15548627.2016.1231279},

doi = {10.1080/15548627.2016.1231279},

year  = {2016},

date = {2016-02-24},

journal = {Autophagy},

volume = {12},

number = {12},

pages = {2484-2495},

abstract = {A pilot clinical trial based on nutritional modulation was designed to assess the efficacy of a one-year low-protein diet in activating autophagy in skeletal muscle of patients affected by COL6/collagen VI-related myopathies. Ullrich congenital muscular dystrophy and Bethlem myopathy are rare inherited muscle disorders caused by mutations of COL6 genes and for which no cure is yet available. Studies in col6 null mice revealed that myofiber degeneration involves autophagy defects and that forced activation of autophagy results in the amelioration of muscle pathology. Seven adult patients affected by COL6 myopathies underwent a controlled low-protein diet for 12 mo and we evaluated the presence of autophagosomes and the mRNA and protein levels for BECN1/Beclin 1 and MAP1LC3B/LC3B in muscle biopsies and blood leukocytes. Safety measures were assessed, including muscle strength, motor and respiratory function, and metabolic parameters. After one y of low-protein diet, autophagic markers were increased in skeletal muscle and blood leukocytes of patients. The treatment was safe as shown by preservation of lean:fat percentage of body composition, muscle strength and function. Moreover, the decreased incidence of myofiber apoptosis indicated benefits in muscle homeostasis, and the metabolic changes pointed at improved mitochondrial function. These data provide evidence that a low-protein diet is able to activate autophagy and is safe and tolerable in patients with COL6 myopathies, pointing at autophagy activation as a potential target for therapeutic applications. In addition, our findings indicate that blood leukocytes are a promising noninvasive tool for monitoring autophagy activation in patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_259,

title = {Hyaluronan scaffold supports osteogenic differentiation of bone marrow concentrate cells.},

author = {Cavallo C and Desando G and Ferrari A and Zini N and Mariani E and Grigolo B},

url = {https://www.biolifesas.org/biolife/jbrha-2/},

year  = {2016},

date = {2016-02-20},

journal = {Journal of Biological Regulators and Homeostatic Agents},

volume = {30},

number = {2},

pages = {409-420},

abstract = {Osteochondral lesions are considered a challenge for orthopedic surgeons. Currently, the treatments available are often unsatisfactory and unable to stimulate tissue regeneration. Tissue engineering offers a new therapeutic strategy, taking into account the role exerted by cells, biomaterial and growth factors in restoring tissue damage. In this light, Mesenchymal Stem Cells (MSCs) have been indicated as a fascinating tool for regenerative medicine thanks to their ability to differentiate into bone, cartilage and adipose tissue. However, in vitro-cultivation of MSCs could be associated with some risks such as de-differentiation/reprogramming, infection and contaminations of the cells. To overcome these shortcomings, a new approach is represented by the use of Bone Marrow Concentrate (BMC), that could allow the delivery of cells surrounded by their microenvironment in injured tissue. For this purpose, cells require a tridimensional scaffold that can support their adhesion, proliferation and differentiation. This study is focused on the potentiality of BMC seeded onto a hyaluronan-based scaffold (Hyaff-11) to differentiate into osteogenic lineage. This process depends on the specific interaction between cells derived from bone marrow (surrounded by their niche) and scaffold, that create an environment able to support the regeneration of damaged tissue. The data obtained from the present study demonstrate that BMC grown onto Hyaff-11 are able to differentiate toward osteogenic sense, producing specific osteogenic genes and matrix proteins.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_291,

title = {Energy metabolism in osteoclast formation and activity.},

author = {Lemma S and Sboarina M and Porporato PE and Zini N and Sonveaux P and Di Pompo G and Baldini N and Avnet S},

url = {10.1016/j.biocel.2016.08.034},

doi = {10.1016/j.biocel.2016.08.034},

year  = {2016},

date = {2016-02-20},

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

volume = {79},

pages = {168-180},

abstract = {Osteoclastogenesis and osteolysis are energy-consuming processes supported by high metabolic activities. In human osteoclasts derived from the fusion of monocytic precursors, we found a substantial increase in the number of mitochondria with differentiation. In mature osteoclasts, mitochondria were also increased in size, rich of cristae and arranged in a complex tubular network. When compared with immature cells, fully differentiated osteoclasts showed higher levels of enzymes of the electron transport chain, a higher mitochondrial oxygen consumption rate and a lower glycolytic efficiency, as evaluated by extracellular flux analysis and by the quantification of metabolites in the culture supernatant. Thus, oxidative phosphorylation appeared the main bioenergetic source for osteoclast formation. Conversely, we found that bone resorption mainly relied on glycolysis. In fact, osteoclast fuelling with galactose, forcing cells to depend on Oxidative Phosphorylation by reducing the rate of glycolysis, significantly impaired Type I collagen degradation, whereas non-cytotoxic doses of rotenone, an inhibitor of the mitochondrial complex I, enhanced osteoclast activity. Furthermore, we found that the enzymes associated to the glycolytic pathway are localised close to the actin ring of polarised osteoclasts, where energy-demanding activities associated with bone degradation take place. In conclusion, we demonstrate that the energy required for osteoclast differentiation mainly derives from mitochondrial oxidative metabolism, whereas the peripheral cellular activities associated with bone matrix degradation are supported by glycolysis. A better understanding of human osteoclast energy metabolism holds the potential for future therapeutic interventions aimed to target osteoclast activity in different pathological conditions of bone.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_300,

title = {DNA and RNA metabolism meet at chromatin to control genome stability},

author = {Montecucco A and Biamonti G},

url = {http://journal.frontiersin.org/article/10.3389/fgene.2016.00067/full},

doi = {doi: 10.3389/fgene.2016.00067},

year  = {2016},

date = {2016-02-19},

journal = {Frontiers in Genetics},

volume = {7},

pages = {67},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_311,

title = {Exosomes: Extracellular vesicles transporting macromolecules},

author = {Scovassi AI},

url = {http://www.omicsgroup.org/journals/exosomes-extracellular-vesicles-transporting-macromolecules-2167-0501-1000e181.php?aid=70857},

doi = { 10.4172/2167-0501.1000e181},

year  = {2016},

date = {2016-02-19},

journal = {Biochemistry & Pharmacology: Open Access},

volume = {5},

pages = {e181},

abstract = {Extracellular vesicles (EVs), firstly identified in 1983 in the conditioned culture medium collected during the maturation of reticulocytes into erythrocytes, are released by the cells into the extracellular milieu. EVs are present in all human body fluids; their number and content are often modulated in pathological samples, thus making interesting their evaluation as possible disease biomarkers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_251,

title = {Effects of microwaves (900 MHz) on peroxidase systems: a comparison between lactoperoxidase and horseradish peroxidase.},

author = {Barteri M and De Carolis R and Marinelli F and Tomassetti G and Montemiglio LC},

url = {http://www.tandfonline.com/doi/abs/10.3109/15368378.2014.1002135?journalCode=iebm20},

doi = {10.3109/15368378.2014.1002135},

year  = {2016},

date = {2016-02-18},

journal = {Electromagnetic Biology and Medicine},

volume = {35},

number = {2},

pages = {126-133},

abstract = {This work shows the effects of exposure to an electromagnetic field at 900 MHz on the catalytic activity of the enzymes lactoperoxidase (LPO) and horseradish peroxidase (HRP). Experimental evidence that irradiation causes conformational changes of the active sites and influences the formation and stability of the intermediate free radicals is documented by measurements of enzyme kinetics, circular dichroism spectroscopy (CD) and cyclic voltammetry.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_280,

title = {DICER, DROSHA and DNA damage response RNAs are necessary for the secondary recruitment of DNA damage response factors.},

author = {Francia S and Cabrini M and Matti V and Oldani A and {d'Adda di Fagagna F}},

url = {http://jcs.biologists.org/content/129/7/1468.long},

doi = {10.1242/jcs.182188},

year  = {2016},

date = {2016-02-18},

journal = {Journal of Cell Science},

volume = {129},

pages = {1468-1476},

abstract = {The DNA damage response (DDR) plays a central role in preserving genome integrity. Recently, we reported that the endoribonucleases DICER and DROSHA contribute to DDR activation by generating small non-coding RNAs, termed DNA damage response RNA (DDRNA), carrying the sequence of the damaged locus. It is presently unclear whether DDRNAs act by promoting the primary recognition of DNA lesions or the secondary recruitment of DDR factors into cytologically detectable foci and consequent signal amplification. Here, we demonstrate that DICER and DROSHA are dispensable for primary recruitment of the DDR sensor NBS1 to DNA damage sites. Instead, the accumulation of the DDR mediators MDC1 and 53BP1 (also known as TP53BP1), markers of secondary recruitment, is reduced in DICER- or DROSHA-inactivated cells. In addition, NBS1 (also known as NBN) primary recruitment is resistant to RNA degradation, consistent with the notion that RNA is dispensable for primary recognition of DNA lesions. We propose that DICER, DROSHA and DDRNAs act in the response to DNA damage after primary recognition of DNA lesions and, together with γH2AX, are essential for enabling the secondary recruitment of DDR factors and fuel the amplification of DDR signaling. 2016. Published by The Company of Biologists Ltd.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}