@article{pmid34205480,

title = {NGS-Based Analysis of Atypical Deep Penetrating Nevi},

author = {Antonella Manca and Maria Cristina Sini and Anna Maria Cesinaro and Francesca Portelli and Carmelo Urso and Maria Lentini and Roberta Cardia and Llucia Alos and Martin Cook and Sara Simi and Panagiotis Paliogiannis and Vincenzo De Giorgi and Antonio Cossu and Giuseppe Palmieri and Daniela Massi},

doi = {10.3390/cancers13123066},

issn = {2072-6694},

year  = {2021},

date = {2021-05-04},

journal = {Cancers (Basel)},

volume = {13},

number = {12},

abstract = {Deep penetrating nevi (DPNs) are rare melanocytic neoplasms consisting of pigmented spindled or epithelioid melanocytes with a distinctive wedge-shaped configuration showing activation of the WNT pathway, with unusual cyto-architectural features. It is unclear whether they show a distinct genomic profile associated with a diverse metastatic potential. We describe herein a cohort of 21 atypical DPNs analyzed by next-generation sequencing using the Ion AmpliSeq™ Comprehensive Cancer Panel. We found that β-catenin exon 3 was mutated in 95% and MAP kinase pathway genes in 71% of the cases. Less frequent mutations were observed in HRAS (19%) and MAP2K1 (24%). Isocitrate dehydrogenases 1 (IDH1) mutations, including R132C, V178I, and S278L, were identified in 38% of cases and co-existed with BRAF/HRAS mutations. The only case with progressive nodal disease carried alterations in the β-catenin pathway and mutations in IDH1 and NRAS (codon 61). By a comprehensive mutation analysis, we found low genetic heterogeneity and a lack of significant associations between specific gene mutations and histopathological features, despite atypical features. Whether the acquisition of an NRAS or IDH1 mutation in an atypical DPN may represent a molecular evolution implying a pathway to melanoma progression should be confirmed in a larger series.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Anticancer activity of two novel hydroxylated biphenyl compounds toward malignant melanoma cells.},

author = {Marina Pisano and Maria Antonietta Dettori and Davide Fabbri and Giovanna Delogu and Giuseppe Palmieri and Carla Rozzo. },

url = {https://irgb.cnr.it/wp-content/uploads/2024/05/Pisano-et-al-2021-reprint.pdf},

doi = {10.3390/ijms22115636},

issn = {1422-0067},

year  = {2021},

date = {2021-03-26},

urldate = {2021-03-26},

journal = {International Journal of Molecular Sciences},

volume = {22},

number = {5636},

pages = {1-18},

abstract = {Melanoma, the deadliest form of skin cancer, is still one of the most difficult cancers to treat despite recent advances in targeted and immune therapies. About 50% of advanced melanoma do not benefit of such therapies, and novel treatments are requested. Curcumin and its analogs have shown good anticancer properties and are being considered for use in combination with or sequence to recent therapies to improve patient outcomes. Our group previously published the synthesis and anticancer activity characterization of a novel curcumin-related compound against melanoma and neuroblastoma cells (D6). Here, two hydroxylated biphenyl compounds—namely, compounds 11 and 12—were selected among a small collection of previously screened C2-symmetric hydroxylated biphenyls structurally related to D6 and curcumin, showing the best antitumor potentiality against melanoma cells (IC50 values of 1.7 uM 0.5 uM for 11 and 2.0 uM 0.7 uM for 12) and no toxicity of normal fibroblasts up to 32 uM. Their antiproliferative activity was deeply characterized on five melanoma cell lines by performing dose-response and clonal growth inhibition assays, which revealed longlasting and irreversible effects for both compounds. Apoptosis induction was ascertained by the annexin V and TUNEL assays, whereas Western blotting showed caspase activation and PARP cleavage. A cell cycle analysis, following cell treatments with either compound 11 or 12, highlighted an arrest in the G2/M transition. Taking all this evidence together, 11 and 12 were shown to be good candidates as lead compounds to develop new anticancer drugs against malignant melanoma.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33125761,

title = {Pathobiologic Mechanisms of Neurodegeneration in Osteopetrosis Đerived From Structural and Functional Analysis of 14 ClC-7 Mutants},

author = {E Di Zanni and E Palagano and L Lagostena and D Strina and A Rehman and M Abinun and L De Somer and B Martire and J Brown and A Kariminejad and S Balasubramaniam and G Baynam and F Gurrieri and M A Pisanti and I De Maggio and M R Abboud and R Chiesa and C P Burren and A Villa and C Sobacchi and A Picollo},

year  = {2021},

date = {2021-03-01},

journal = {J Bone Miner Res},

volume = {36},

number = {3},

pages = {531--545},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33475257,

title = {Modeling, optimization, and comparable efficacy of Ŧ cell and hematopoietic stem cell gene editing for treating hyper-IgM syndrome},

author = {V Vavassori and E Mercuri and G E Marcovecchio and M C Castiello and G Schiroli and L Albano and C Margulies and F Buquicchio and E Fontana and S Beretta and I Merelli and A Cappelleri and P M Rancoita and V Lougaris and A Plebani and M Kanariou and A Lankester and F Ferrua and E Scanziani and C Cotta-Ramusino and A Villa and L Naldini and P Genovese},

year  = {2021},

date = {2021-03-01},

journal = {EMBO Mol Med},

volume = {13},

number = {3},

pages = {e13545},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33670365,

title = {Integrated Genomics Identifies miR-181/ŦFAM Pathway as a Critical Đriver of Đrug Resistance in Melanoma},

author = {A Barbato and A Iuliano and M Volpe and R DÁlterio and S Brillante and F Massa and R De Cegli and S Carrella and M Salati and A Russo and G Russo and S Riccardo and D Cacchiarelli and M Capone and G Madonna and P A Ascierto and B Franco and A Indrieri and P Carotenuto},

year  = {2021},

date = {2021-02-01},

journal = {Int J Mol Sci},

volume = {22},

number = {4},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ferrando2021-ga,

title = {Active human and porcine serum induce competence for genetic  transformation in the emerging zoonotic pathogen Streptococcus  suis},

author = {Maria Laura Ferrando and Alex Gussak and Saskia Mentink and Marcela Fernandez Gutierrez and Peter Baarlen and Jerry Mark Wells},

year  = {2021},

date = {2021-02-01},

urldate = {2021-02-01},

journal = {Pathogens},

volume = {10},

number = {2},

pages = {156},

publisher = {MDPI AG},

abstract = {The acquisition of novel genetic traits through natural 

 competence is a strategy used by bacteria in microbe-rich 

 environments where microbial competition, antibiotics, and host 

 immune defenses threaten their survival. Here, we show that 

 virulent strains of Streptococcus suis, an important zoonotic 

 agent and porcine pathogen, become competent for genetic 

 transformation with plasmid or linear DNA when cultured in 

 active porcine and human serum. Competence was not induced in 

 active fetal bovine serum, which contains less complement 

 factors and immunoglobulins than adult serum and was strongly 

 reduced in heat-treated or low-molecular weight fractions of 

 active porcine serum. Late competence genes, encoding the uptake 

 machinery for environmental DNA, were upregulated in the active 

 serum. Competence development was independent of the early 

 competence regulatory switch involving XIP and ComR, as well as 

 sigma factor ComX, suggesting the presence of an alternative 

 stress-induced pathway for regulation of the late competence 

 genes required for DNA uptake.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Angius2021-bx,

title = {Portrait of cancer stem cells on colorectal cancer: Molecular 

 biomarkers, signaling pathways and miRNAome},

author = {Andrea Ängius and Antonio Mario Scanu and Caterina Arru and Maria Rosaria Muroni and Vincenzo Rallo and Giulia Deiana and Maria Chiara Ninniri and Ciriaco Carru and Alberto Porcu and Giovanna Pira and Paolo Uva and Paolo Cossu-Rocca and Maria Rosaria" De Miglio},

year  = {2021},

date = {2021-02-01},

journal = {Int. J. Mol. Sci.},

volume = {22},

number = {4},

pages = {1603},

publisher = {MDPI AG},

abstract = {Colorectal cancer (CRC) is a leading cause of cancer death 

 worldwide, and about 20% is metastatic at diagnosis and 

 untreatable. Increasing evidence suggests that the heterogeneous 

 nature of CRC is related to colorectal cancer stem cells 

 (CCSCs), a small cells population with stemness behaviors and 

 responsible for tumor progression, recurrence, and therapy 

 resistance. Growing knowledge of stem cells (SCs) biology has 

 rapidly improved uncovering the molecular mechanisms and 

 possible crosstalk/feedback loops between signaling pathways 

 that directly influence intestinal homeostasis and 

 tumorigenesis. The generation of CCSCs is probably connected to 

 genetic changes in members of signaling pathways, which control 

 self-renewal and pluripotency in SCs and then establish function 

 and phenotype of CCSCs. Particularly, various deregulated 

 CCSC-related miRNAs have been reported to modulate stemness 

 features, controlling CCSCs functions such as regulation of cell 

 cycle genes expression, epithelial-mesenchymal transition, 

 metastasization, and drug-resistance mechanisms. Primarily, 

 CCSC-related miRNAs work by regulating mainly signal pathways 

 known to be involved in CCSCs biology. This review intends to 

 summarize the epigenetic findings linked to miRNAome in the 

 maintenance and regulation of CCSCs, including their 

 relationships with different signaling pathways, which should 

 help to identify specific diagnostic, prognostic, and predictive 

 biomarkers for CRC, but also develop innovative CCSCs-targeted 

 therapies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32091431,

title = {KIT and PDGFRa mutational patterns in Sardinian patients with gastrointestinal stromal tumors},

author = {Grazia Palomba and Panagiotis Paliogiannis and Maria C Sini and Maria Colombino and Milena Casula and Antonella Manca and Marina Pisano and Giovanni Sotgiu and Valentina Doneddu and Giuseppe Palmieri and Antonio Cossu},

doi = {10.1097/CEJ.0000000000000581},

issn = {1473-5709},

year  = {2021},

date = {2021-01-30},

journal = {Eur J Cancer Prev},

volume = {30},

number = {1},

pages = {53--58},

abstract = {Gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignancy of the gastrointestinal tract. We provide in the present article the molecular characterization of a series of primary GISTs in a cohort of Sardinian patients (Italy), with the aim to describe the patterns of KIT and PDGFRa mutations and the corresponding clinical features. Ninety-nine Sardinian patients with histologically-proven diagnosis of GIST were included in the study. Medical records and pathology reports were used to assess the demographic and clinical features of the patients and the disease at the time of the diagnosis. Formalin-fixed, paraffin-embedded tissue samples were retrieved for each case, and mutation analysis of the KIT and PDGFRa genes was performed. KIT and PDGFRa mutations were detected in 81.8% and 5% of the cases, respectively. The most common KIT mutation was W557_K558del in exon 11, while D842V in exon 18 was the most common PDGFRa genetic alteration; V561D was the only PDGFRa mutation found in exon 12. The global "wild-type" cases, with no mutations in either the KIT or PDGFRa genes, were 13 (13.1%). The mean survival of those patients was approximately 46.9 (±43.9) months. Globally, 86.9% of Sardinian patients with GIST had a KIT or PDGFRa mutation; the former were more frequent in comparison with other Italian cohorts, while PDGFRa mutations were rare. No statistical differences in survival between mutated and wild-type cases, and between KIT and PDGFRa mutated cases were detected in our study.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33274847,

title = {Synthesis of Hydroxylated Biphenyls Derivatives Bearing an α,β-Unsaturated Ketone as Lead Structure for the Development of New Drug Candidates Against Malignant Melanoma},

author = {Maria Antonietta Dettori and Davide Fabbri and Marina Pisano and Carla Rozzo and Giovanna Delogu },

url = {https://irgb.cnr.it/wp-content/uploads/2024/05/reprint-1.pdf},

doi = {doi.org/10.1002/cmdc.202000709},

year  = {2021},

date = {2021-01-21},

urldate = {2021-01-21},

journal = {ChemMedChem},

volume = {16},

pages = {1022-1033},

abstract = {A small collection of C 2 -symmetry hydroxylated biphenyls derivatives featured with a α,β-unsaturated ketone as lead structure was prepared and the capability of such compounds to act as antiproliferative agents against four human malignant melanoma cell lines was assayed. The prodrug approach was applied in order to improve delivery of compounds into the cell by modulation of the phenolic-OH protective group. The hydroxylated biphenyl structure bearing an α,β-unsaturated ketone and a phenolic- O -prenylated chain would facilitated the delivery of the molecule and interactions with the biological targets. Four compounds showed antiproliferative activity resulting in IC 50 value in the range 1.2 - 2.8 µM..},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33216968,

title = {Induction of therapeutic levels of HbF in genome-edited primary β0 39-thalassaemia haematopoietic stem and progenitor cells},

author = {M Mingoia and C A Caria and L Ye and I Asunis and M F Marongiu and L Manunza and M C Sollaino and J Wang and A Cabriolu and R Kurita and Y Nakamura and F Cucca and Y W Kan and M G Marini and P Moi},

year  = {2021},

date = {2021-01-01},

journal = {Br J Haematol},

volume = {192},

number = {2},

pages = {395--404},

abstract = {Hereditary persistence of fetal haemoglobin (HPFH) is the major modifier of the clinical severity of β-thalassaemia. The homozygous mutation c.-196 C>T in the Aγ-globin (HBG1) promoter, which causes Sardinian δβ0 -thalassaemia, is able to completely rescue the β-major thalassaemia phenotype caused by the β0 39-thalassaemia mutation, ensuring high levels of fetal haemoglobin synthesis during adulthood. Here, we describe a CRISPR/Cas9 genome-editing approach, combined with the non-homologous end joining (NHEJ) pathway repair, aimed at reproducing the effects of this naturally occurring HPFH mutation in both HBG promoters. After selecting the most efficient guide RNA in K562 cells, we edited the HBG promoters in human umbilical cord blood-derived erythroid progenitor 2 cells (HUDEP-2) and in haematopoietic stem and progenitor cells (HSPCs) from β0 -thalassaemia patients to assess the therapeutic potential of HbF induction. Our results indicate that small deletions targeting the -196-promoter region restore high levels of fetal haemoglobin (HbF) synthesis in all cell types tested. In pools of HSPCs derived from homozygous β0 39-thalassaemia patients, a 20% editing determined a parallel 20% increase of HbF compared to unedited pools. These results suggest that editing the region of HBG promoters around the -196 position has the potential to induce therapeutic levels of HbF in patients with most types of β-thalassaemia irrespective of the β-globin gene (HBB) mutations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33208929,

title = {Macrophage expression and prognostic significance of the long pentraxin PŦX3 in COVIĐ-19},

author = {E Brunetta and M Folci and B Bottazzi and M De Santis and G Gritti and A Protti and S N Mapelli and S Bonovas and D Piovani and R Leone and I My and V Zanon and G Spata and M Bacci and D Supino and S Carnevale and M Sironi and S Davoudian and C Peano and F Landi and F Di Marco and F Raimondi and A Gianatti and C Angelini and A Rambaldi and C Garlanda and M Ciccarelli and M Cecconi and A Mantovani},

year  = {2021},

date = {2021-01-01},

journal = {Nat Immunol},

volume = {22},

number = {1},

pages = {19--24},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33494335,

title = {Gut Microbiota Functional Đysbiosis Relates to Individual Điet in Subclinical Carotid Atherosclerosis},

author = {A Baragetti and M Severgnini and E Olmastroni and C C Dioguardi and E Mattavelli and A Angius and L Rotta and J Cibella and G Caredda and C Consolandi and L Grigore and F Pellegatta and F Giavarini and D Caruso and G D Norata and A L Catapano and C Peano},

year  = {2021},

date = {2021-01-01},

journal = {Nutrients},

volume = {13},

number = {2},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32387109,

title = {Efficacy and safety of anti-CD45-saporin as conditioning agent for RAG deficiency},

author = {M C Castiello and M Bosticardo and N Sacchetti and E Calzoni and E Fontana and Y Yamazaki and E Draghici and C Corsino and I Bortolomai and L Sereni and H H Yu and P Uva and R Palchaudhuri and D T Scadden and A Villa and L D Notarangelo},

year  = {2021},

date = {2021-01-01},

journal = {J Allergy Clin Immunol},

volume = {147},

number = {1},

pages = {309--320},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31949009,

title = {Expanded circulating hematopoietic stem/progenitor cells as novel cell source for the treatment of ŦCIRG1 osteopetrosis},

author = {V Capo and S Penna and I Merelli and M Barcella and S Scala and L Basso-Ricci and E Draghici and E Palagano and E Zonari and G Desantis and P Uva and R Cusano and L Sergi Sergi and L Crisafulli and D Moshous and P Stepensky and K Drabko and Z Kaya and E Unal and A Gezdirici and G Menna and M Serafini and A Aiuti and S L Locatelli and C Carlo-Stella and A S Schulz and F Ficara and C Sobacchi and B Gentner and A Villa},

year  = {2021},

date = {2021-01-01},

journal = {Haematologica},

volume = {106},

number = {1},

pages = {74--86},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33125266,

title = {Comprehensive Investigation of Circulating Biomarkers and Ŧheir Causal Role in Atherosclerosis-Related Risk Factors and Clinical Events},

author = {D. Zanetti and S. Gustafsson and T. L. Assimes and E. Ingelsson},

year  = {2020},

date = {2020-12-01},

journal = {Circ Genom Precis Med},

volume = {13},

number = {6},

pages = {e002996},

abstract = {Circulating biomarkers have been previously associated with atherosclerosis-related risk factors, but the nature of these associations is incompletely understood. 933 participants of the UK Biobank. ). Our results suggest that it is unlikely that CRP (C-reactive protein) and vitamin D play causal roles of any meaningful magnitude in development of cardiometabolic disease. We confirmed and extended known associations and reported several novel causal associations providing important insights about the cause of these diseases, which can help accelerate new prevention strategies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33216977,

title = {A Sardinian founder mutation in glycoprotein Ib platelet subunit beta(GP1BB) that impacts thrombocytopenia},

author = { F. Busonero and M. Steri and V. Orrù and G. Sole and S. Olla and M. Marongiu and A. Maschio and C. Sidore and S. Lai and A. Mulas and M. Zoledziewska and M. Floris and M. Pala and P. Forabosco and I. Asunis and M. Pitzalis and F. Deidda and M. Masala and C. A. Caria and S. Barella and G. R. Abecasis and D. Schlessinger and S. Sanna and E. Fiorillo and F. Cucca},

year  = {2020},

date = {2020-11-01},

journal = {Br J Haematol},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33171872,

title = {Modulatory Role of microRNAs in Triple Negative Breast Cancer with Basal-Like Phenotype},

author = { },

year  = {2020},

date = {2020-11-01},

journal = {Cancers (Basel)},

volume = {12},

number = {11},

abstract = {Development of new research, classification, and therapeutic options are urgently required due to the fact that TNBC is a heterogeneous malignancy. The expression of high molecular weight cytokeratins identifies a biologically and clinically distinct subgroup of TNBCs with a basal-like phenotype, representing about 75% of TNBCs, while the remaining 25% includes all other intrinsic subtypes. The triple negative phenotype in basal-like breast cancer (BLBC) makes it unresponsive to endocrine therapy, i.e., tamoxifen, aromatase inhibitors, and/or anti-HER2-targeted therapies; for this reason, only chemotherapy can be considered an approach available for systemic treatment even if it shows poor prognosis. Therefore, treatment for these subgroups of patients is a strong challenge for oncologists due to disease heterogeneity and the absence of unambiguous molecular targets. Dysregulation of the cellular miRNAome has been related to huge cellular process deregulations underlying human malignancy. Consequently, epigenetics is a field of great promise in cancer research. Increasing evidence suggests that specific miRNA clusters/signatures might be of clinical utility in TNBCs with basal-like phenotype. The epigenetic mechanisms behind tumorigenesis enable progress in the treatment, diagnosis, and prevention of cancer. This review intends to summarize the epigenetic findings related to miRNAome in TNBCs with basal-like phenotype.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32785653,

title = {Macrophage morphology correlates with single-cell diversity and prognosis in colorectal liver metastasis},

author = {M Donadon and G Torzilli and N Cortese and C Soldani and L Di Tommaso and B Franceschini and R Carriero and M Barbagallo and A Rigamonti and A Anselmo and F S Colombo and G Maggi and A Lleo and J Cibella and C Peano and P Kunderfranco and M Roncalli and A Mantovani and F Marchesi},

year  = {2020},

date = {2020-11-01},

journal = {J Exp Med},

volume = {217},

number = {11},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32311393,

title = {Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome},

author = {R Rigoni and E Fontana and K Dobbs and V Marrella and V Taverniti and V Maina and A Facoetti and G DÁmico and W Al-Herz and M E Cruz-Munoz and C Schuetz and A R Gennery and E K Garabedian and S Giliani and D Draper and G Dbaibo and R S Geha and I Meyts and T Tousseyn and B Neven and D Moshous and A Fischer and A Schulz and A Finocchi and D B Kuhns and D L Fink and M S Lionakis and M Swamydas and S Guglielmetti and J Alejo and I A Myles and S Pittaluga and L D Notarangelo and A Villa and B Cassani},

year  = {2020},

date = {2020-11-01},

journal = {J Allergy Clin Immunol},

volume = {146},

number = {5},

pages = {1165--1179},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2020-xo,

title = {Complex genetic signatures in immune cells underlie autoimmunity 

 and inform therapy},

author = {Valeria Örr`u and Maristella Steri and Carlo Sidore and Michele Marongiu and Valentina Serra and Stefania Olla and Gabriella Sole and Sandra Lai and Mariano Dei and Antonella Mulas and Francesca Virdis and Maria Grazia Piras and Monia Lobina and Mara Marongiu and Maristella Pitzalis and Francesca Deidda and Annalisa Loizedda and Stefano Onano and Magdalena Zoledziewska and Stephen Sawcer and Marcella Devoto and Myriam Gorospe and Gonc calo R Abecasis and Matteo Floris and Mauro Pala and David Schlessinger and Edoardo Fiorillo and Francesco" Cucca},

year  = {2020},

date = {2020-10-01},

journal = {Nat. Genet.},

volume = {52},

number = {10},

pages = {1036--1045},

publisher = {Springer Science and Business Media LLC},

abstract = {We report on the influence of ~22 million variants on 731 immune 

 cell traits in a cohort of 3,757 Sardinians. We detected 122 

 significant (P < 1.28 $times$ 10-11) independent association 

 signals for 459 cell traits at 70 loci (53 of them novel) 

 identifying several molecules and mechanisms involved in cell 

 regulation. Furthermore, 53 signals at 36 loci overlapped with 

 previously reported disease-associated signals, predominantly 

 for autoimmune disorders, highlighting intermediate phenotypes 

 in pathogenesis. Collectively, our findings illustrate complex 

 genetic regulation of immune cells with highly selective effects 

 on autoimmune disease risk at the cell-subtype level. These 

 results identify drug-targetable pathways informing the design 

 of more specific treatments for autoimmune diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2020-ku,

title = {Complex genetic signatures in immune cells underlie autoimmunity 

 and inform therapy},

author = {Valeria Örr`u and Maristella Steri and Carlo Sidore and Michele Marongiu and Valentina Serra and Stefania Olla and Gabriella Sole and Sandra Lai and Mariano Dei and Antonella Mulas and Francesca Virdis and Maria Grazia Piras and Monia Lobina and Mara Marongiu and Maristella Pitzalis and Francesca Deidda and Annalisa Loizedda and Stefano Onano and Magdalena Zoledziewska and Stephen Sawcer and Marcella Devoto and Myriam Gorospe and Gonc calo R Abecasis and Matteo Floris and Mauro Pala and David Schlessinger and Edoardo Fiorillo and Francesco" Cucca},

year  = {2020},

date = {2020-10-01},

journal = {Nat. Genet.},

volume = {52},

number = {10},

pages = {1036--1045},

publisher = {Springer Science and Business Media LLC},

abstract = {We report on the influence of ~22 million variants on 731 immune 

 cell traits in a cohort of 3,757 Sardinians. We detected 122 

 significant (P < 1.28 $times$ 10-11) independent association 

 signals for 459 cell traits at 70 loci (53 of them novel) 

 identifying several molecules and mechanisms involved in cell 

 regulation. Furthermore, 53 signals at 36 loci overlapped with 

 previously reported disease-associated signals, predominantly 

 for autoimmune disorders, highlighting intermediate phenotypes 

 in pathogenesis. Collectively, our findings illustrate complex 

 genetic regulation of immune cells with highly selective effects 

 on autoimmune disease risk at the cell-subtype level. These 

 results identify drug-targetable pathways informing the design 

 of more specific treatments for autoimmune diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2020-mz,

title = {Complex genetic signatures in immune cells underlie autoimmunity 

 and inform therapy},

author = {Valeria Örr`u and Maristella Steri and Carlo Sidore and Michele Marongiu and Valentina Serra and Stefania Olla and Gabriella Sole and Sandra Lai and Mariano Dei and Antonella Mulas and Francesca Virdis and Maria Grazia Piras and Monia Lobina and Mara Marongiu and Maristella Pitzalis and Francesca Deidda and Annalisa Loizedda and Stefano Onano and Magdalena Zoledziewska and Stephen Sawcer and Marcella Devoto and Myriam Gorospe and Gonc calo R Abecasis and Matteo Floris and Mauro Pala and David Schlessinger and Edoardo Fiorillo and Francesco" Cucca},

year  = {2020},

date = {2020-10-01},

journal = {Nat. Genet.},

volume = {52},

number = {10},

pages = {1036--1045},

publisher = {Springer Science and Business Media LLC},

abstract = {We report on the influence of ~22 million variants on 731 immune 

 cell traits in a cohort of 3,757 Sardinians. We detected 122 

 significant (P < 1.28 $times$ 10-11) independent association 

 signals for 459 cell traits at 70 loci (53 of them novel) 

 identifying several molecules and mechanisms involved in cell 

 regulation. Furthermore, 53 signals at 36 loci overlapped with 

 previously reported disease-associated signals, predominantly 

 for autoimmune disorders, highlighting intermediate phenotypes 

 in pathogenesis. Collectively, our findings illustrate complex 

 genetic regulation of immune cells with highly selective effects 

 on autoimmune disease risk at the cell-subtype level. These 

 results identify drug-targetable pathways informing the design 

 of more specific treatments for autoimmune diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2020-va,

title = {Complex genetic signatures in immune cells underlie autoimmunity  and inform therapy},

author = {Valeria Örr`u and Maristella Steri and Carlo Sidore and Michele Marongiu and Valentina Serra and Stefania Olla and Gabriella Sole and Sandra Lai and Mariano Dei and Antonella Mulas and Francesca Virdis and Maria Grazia Piras and Monia Lobina and Mara Marongiu and Maristella Pitzalis and Francesca Deidda and Annalisa Loizedda and Stefano Onano and Magdalena Zoledziewska and Stephen Sawcer and Marcella Devoto and Myriam Gorospe and Gonc calo R Abecasis and Matteo Floris and Mauro Pala and David Schlessinger and Edoardo Fiorillo and Francesco" Cucca},

url = {https://www.nature.com/articles/s41588-020-0684-4},

year  = {2020},

date = {2020-10-01},

urldate = {2020-10-01},

journal = {Nat. Genet.},

volume = {52},

number = {10},

pages = {1036--1045},

publisher = {Springer Science and Business Media LLC},

abstract = {We report on the influence of ~22 million variants on 731 immune 

 cell traits in a cohort of 3,757 Sardinians. We detected 122 

 significant (P < 1.28 $times$ 10-11) independent association 

 signals for 459 cell traits at 70 loci (53 of them novel) 

 identifying several molecules and mechanisms involved in cell 

 regulation. Furthermore, 53 signals at 36 loci overlapped with 

 previously reported disease-associated signals, predominantly 

 for autoimmune disorders, highlighting intermediate phenotypes 

 in pathogenesis. Collectively, our findings illustrate complex 

 genetic regulation of immune cells with highly selective effects 

 on autoimmune disease risk at the cell-subtype level. These 

 results identify drug-targetable pathways informing the design 

 of more specific treatments for autoimmune diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2020-vab,

title = {Complex genetic signatures in immune cells underlie autoimmunity  and inform therapy},

author = {Valeria Örr`u and Maristella Steri and Carlo Sidore and Michele Marongiu and Valentina Serra and Stefania Olla and Gabriella Sole and Sandra Lai and Mariano Dei and Antonella Mulas and Francesca Virdis and Maria Grazia Piras and Monia Lobina and Mara Marongiu and Maristella Pitzalis and Francesca Deidda and Annalisa Loizedda and Stefano Onano and Magdalena Zoledziewska and Stephen Sawcer and Marcella Devoto and Myriam Gorospe and Gonc calo R Abecasis and Matteo Floris and Mauro Pala and David Schlessinger and Edoardo Fiorillo and Francesco" Cucca},

doi = {10.1038/s41588-020-0684-4},

year  = {2020},

date = {2020-10-01},

urldate = {2020-10-01},

journal = {Nat. Genet.},

volume = {52},

number = {10},

pages = {1036--1045},

publisher = {Springer Science and Business Media LLC},

abstract = {We report on the influence of ~22 million variants on 731 immune 

 cell traits in a cohort of 3,757 Sardinians. We detected 122 

 significant (P < 1.28 $times$ 10-11) independent association 

 signals for 459 cell traits at 70 loci (53 of them novel) 

 identifying several molecules and mechanisms involved in cell 

 regulation. Furthermore, 53 signals at 36 loci overlapped with 

 previously reported disease-associated signals, predominantly 

 for autoimmune disorders, highlighting intermediate phenotypes 

 in pathogenesis. Collectively, our findings illustrate complex 

 genetic regulation of immune cells with highly selective effects 

 on autoimmune disease risk at the cell-subtype level. These 

 results identify drug-targetable pathways informing the design 

 of more specific treatments for autoimmune diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2020-vac,

title = {Complex genetic signatures in immune cells underlie autoimmunity 

 and inform therapy},

author = {Valeria Örr`u and Maristella Steri and Carlo Sidore and Michele Marongiu and Valentina Serra and Stefania Olla and Gabriella Sole and Sandra Lai and Mariano Dei and Antonella Mulas and Francesca Virdis and Maria Grazia Piras and Monia Lobina and Mara Marongiu and Maristella Pitzalis and Francesca Deidda and Annalisa Loizedda and Stefano Onano and Magdalena Zoledziewska and Stephen Sawcer and Marcella Devoto and Myriam Gorospe and Gonc calo R Abecasis and Matteo Floris and Mauro Pala and David Schlessinger and Edoardo Fiorillo and Francesco" Cucca},

year  = {2020},

date = {2020-10-01},

journal = {Nat. Genet.},

volume = {52},

number = {10},

pages = {1036--1045},

publisher = {Springer Science and Business Media LLC},

abstract = {We report on the influence of ~22 million variants on 731 immune 

 cell traits in a cohort of 3,757 Sardinians. We detected 122 

 significant (P < 1.28 $times$ 10-11) independent association 

 signals for 459 cell traits at 70 loci (53 of them novel) 

 identifying several molecules and mechanisms involved in cell 

 regulation. Furthermore, 53 signals at 36 loci overlapped with 

 previously reported disease-associated signals, predominantly 

 for autoimmune disorders, highlighting intermediate phenotypes 

 in pathogenesis. Collectively, our findings illustrate complex 

 genetic regulation of immune cells with highly selective effects 

 on autoimmune disease risk at the cell-subtype level. These 

 results identify drug-targetable pathways informing the design 

 of more specific treatments for autoimmune diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2020-vad,

title = {Complex genetic signatures in immune cells underlie autoimmunity 

 and inform therapy},

author = {Valeria Örr`u and Maristella Steri and Carlo Sidore and Michele Marongiu and Valentina Serra and Stefania Olla and Gabriella Sole and Sandra Lai and Mariano Dei and Antonella Mulas and Francesca Virdis and Maria Grazia Piras and Monia Lobina and Mara Marongiu and Maristella Pitzalis and Francesca Deidda and Annalisa Loizedda and Stefano Onano and Magdalena Zoledziewska and Stephen Sawcer and Marcella Devoto and Myriam Gorospe and Gonc calo R Abecasis and Matteo Floris and Mauro Pala and David Schlessinger and Edoardo Fiorillo and Francesco" Cucca},

year  = {2020},

date = {2020-10-01},

journal = {Nat. Genet.},

volume = {52},

number = {10},

pages = {1036--1045},

publisher = {Springer Science and Business Media LLC},

abstract = {We report on the influence of ~22 million variants on 731 immune 

 cell traits in a cohort of 3,757 Sardinians. We detected 122 

 significant (P < 1.28 $times$ 10-11) independent association 

 signals for 459 cell traits at 70 loci (53 of them novel) 

 identifying several molecules and mechanisms involved in cell 

 regulation. Furthermore, 53 signals at 36 loci overlapped with 

 previously reported disease-associated signals, predominantly 

 for autoimmune disorders, highlighting intermediate phenotypes 

 in pathogenesis. Collectively, our findings illustrate complex 

 genetic regulation of immune cells with highly selective effects 

 on autoimmune disease risk at the cell-subtype level. These 

 results identify drug-targetable pathways informing the design 

 of more specific treatments for autoimmune diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2020-ce,

title = {Complex genetic signatures in immune cells underlie autoimmunity  and inform therapy},

author = {Valeria Örr`u and Maristella Steri and Carlo Sidore and Michele Marongiu and Valentina Serra and Stefania Olla and Gabriella Sole and Sandra Lai and Mariano Dei and Antonella Mulas and Francesca Virdis and Maria Grazia Piras and Monia Lobina and Mara Marongiu and Maristella Pitzalis and Francesca Deidda and Annalisa Loizedda and Stefano Onano and Magdalena Zoledziewska and Stephen Sawcer and Marcella Devoto and Myriam Gorospe and Gonc calo R Abecasis and Matteo Floris and Mauro Pala and David Schlessinger and Edoardo Fiorillo and Francesco" Cucca},

doi = {10.1038/s41588-020-0684-4},

year  = {2020},

date = {2020-10-01},

urldate = {2020-10-01},

journal = {Nat. Genet.},

volume = {52},

number = {10},

pages = {1036--1045},

publisher = {Springer Science and Business Media LLC},

abstract = {We report on the influence of ~22 million variants on 731 immune 

 cell traits in a cohort of 3,757 Sardinians. We detected 122 

 significant (P < 1.28 $times$ 10-11) independent association 

 signals for 459 cell traits at 70 loci (53 of them novel) 

 identifying several molecules and mechanisms involved in cell 

 regulation. Furthermore, 53 signals at 36 loci overlapped with 

 previously reported disease-associated signals, predominantly 

 for autoimmune disorders, highlighting intermediate phenotypes 

 in pathogenesis. Collectively, our findings illustrate complex 

 genetic regulation of immune cells with highly selective effects 

 on autoimmune disease risk at the cell-subtype level. These 

 results identify drug-targetable pathways informing the design 

 of more specific treatments for autoimmune diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2020-uk,

title = {Complex genetic signatures in immune cells underlie autoimmunity  and inform therapy},

author = {Valeria Örr`u and Maristella Steri and Carlo Sidore and Michele Marongiu and Valentina Serra and Stefania Olla and Gabriella Sole and Sandra Lai and Mariano Dei and Antonella Mulas and Francesca Virdis and Maria Grazia Piras and Monia Lobina and Mara Marongiu and Maristella Pitzalis and Francesca Deidda and Annalisa Loizedda and Stefano Onano and Magdalena Zoledziewska and Stephen Sawcer and Marcella Devoto and Myriam Gorospe and Gonc calo R Abecasis and Matteo Floris and Mauro Pala and David Schlessinger and Edoardo Fiorillo and Francesco" Cucca},

doi = {10.1038/s41588-020-0684-4},

year  = {2020},

date = {2020-10-01},

urldate = {2020-10-01},

journal = {Nat. Genet.},

volume = {52},

number = {10},

pages = {1036--1045},

publisher = {Springer Science and Business Media LLC},

abstract = {We report on the influence of ~22 million variants on 731 immune 

 cell traits in a cohort of 3,757 Sardinians. We detected 122 

 significant (P < 1.28 $times$ 10-11) independent association 

 signals for 459 cell traits at 70 loci (53 of them novel) 

 identifying several molecules and mechanisms involved in cell 

 regulation. Furthermore, 53 signals at 36 loci overlapped with 

 previously reported disease-associated signals, predominantly 

 for autoimmune disorders, highlighting intermediate phenotypes 

 in pathogenesis. Collectively, our findings illustrate complex 

 genetic regulation of immune cells with highly selective effects 

 on autoimmune disease risk at the cell-subtype level. These 

 results identify drug-targetable pathways informing the design 

 of more specific treatments for autoimmune diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33201769,

title = {Paracrine effect of human adipose-derived stem cells on lymphatic endothelial cells},

author = {C Marcozzi and A Frattini and M Borgese and F Rossi and L Barone and E Solari and R Valli and R Gornati},

year  = {2020},

date = {2020-09-01},

journal = {Regen Med},

volume = {15},

number = {9},

pages = {2085--2098},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32978159,

title = {GAĐĐ34 is a modulator of autophagy during starvation},

author = {G Gambardella and L Staiano and M N Moretti and R De Cegli and L Fagnocchi and G Di Tullio and S Polletti and C Braccia and A Armirotti and A Zippo and A Ballabio and M A De Matteis and D di Bernardo},

year  = {2020},

date = {2020-09-01},

journal = {Sci Adv},

volume = {6},

number = {39},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32751423,

title = {Comparison of BRAF Mutation Screening Strategies in a Large Real-Life Series of Advanced Melanoma Patients},

author = {Colombino, M. and Rozzo, C. and Paliogiannis, P. and Casula, M. and Manca, A. and Doneddu, V. and Fedeli, M. A. and Sini, M. C. and Palomba, G. and Pisano, M. and Ascierto, P. A. and Caracò, C. and Lissia, A. and Cossu, A. and Palmieri, G.},

year  = {2020},

date = {2020-07-01},

urldate = {2020-07-01},

journal = {J Clin Med},

volume = {9},

number = {8},

abstract = {Malignant melanoma (MM) is one of the deadliest skin cancers. BRAF mutation status plays a predominant role in the management of MM patients. The aim of this study was to compare BRAF mutational testing performed by conventional nucleotide sequencing approaches with either real-time polymerase chain reaction (rtPCR) or next-generation sequencing (NGS) assays in a real-life, hospital-based series of advanced MM patients. Consecutive patients with AJCC (American Joint Committee on Cancer) stage IIIC and IV MM from Sardinia, Italy, who were referred for molecular testing, were enrolled into the study. Initial screening was performed to assess the mutational status of the BRAF and NRAS genes, using the conventional methodologies recognized by the nationwide guidelines, at the time of the molecular classification, required by clinicians: at the beginning, Sanger-based sequencing (SS) and, after, pyrosequencing. The present study was then focused on BRAF mutation detecting approaches only. BRAF wild-type cases with available tissue and adequate DNA were further tested with rtPCR (Idyllaâ„¢) and NGS assays. Globally, 319 patients were included in the study; pathogenic BRAF mutations were found in 144 (45.1%) cases examined with initial screening. The rtPCR detected 11 (16.2%) and 3 (4.8%) additional BRAF mutations after SS and pyrosequencing, respectively. NGS detected one additional BRAF-mutated case (2.1%) among 48 wild-type cases previously tested with pyrosequencing and rtPCR. Our study evidenced that rtPCR and NGS were able to detect additional BRAF mutant cases in comparison with conventional sequencing methods; therefore, we argue for the preferential utilization of the aforementioned assays (NGS and rtPCR) in clinical practice, to eradicate false-negative cases and improve the accuracy of BRAF detection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31938717,

title = {Generation of an immunodeficient mouse model of tcirg1-deficient autosomal recessive osteopetrosis},

author = {E Palagano and S Muggeo and L Crisafulli and I L Tourkova and D Strina and S Mantero and E Fontana and S L Locatelli and M Monari and E Morenghi and C Carlo-Stella and J B Barnett and H C Blair and P Vezzoni and A Villa and C Sobacchi and F Ficara},

year  = {2020},

date = {2020-06-01},

journal = {Bone Rep},

volume = {12},

pages = {100242},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32099849,

title = {Chromosome Ŧransplantation: A Possible Approach to Ŧreat Ħuman X-linked Đisorders},

author = {M Paulis and L Susani and A Castelli and T Suzuki and T Hara and L Straniero and S Duga and D Strina and S Mantero and E Caldana and L S Sergi and A Villa and P Vezzoni},

year  = {2020},

date = {2020-06-01},

journal = {Mol Ther Methods Clin Dev},

volume = {17},

pages = {369--377},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31302897,

title = {Arterial stiffness and multiple organ damage: a longitudinal study in population},

author = { A. Scuteri and C. H. Morrell and D. A. Fegatelli and E. Fiorillo and A. Delitala and M. Orru' and M. Marongiu and D. Schlessinger and F. Cucca},

year  = {2020},

date = {2020-05-01},

volume = {32},

number = {5},

pages = {781--788},

abstract = {Previous cross-sectional observation identified arterial aging, indexed as pulse-wave velocity (PWV), as a key determinant of the simultaneous multiple organ damage (heart, carotid artery, and kidney). The aim of the present cohort study is to investigate trajectories of repeated measures of PWV and traditional CV risk factors in subjects who eventually presented clinical evidence of multiple organ damage in the SardiNIA study. Organ damage was measured in the heart (left ventricular hypertrophy, LVH), the common carotid artery (intima-media thickness > 0.9 mm and/or plaque), and the kidney (eGFR < 60 ml/min/1.73 m2) of 2130 men and women of a broad age range participating the SardiNIA study. SHATS was defined as the simultaneous occurrence of all the three-organ damages. Trajectory in traditional CV risk factors and PWV was analyzed retrospectively (four observations over 9 years) according to the number of organ damage (from 0 to 3). Compared to subjects with no organ damage, after controlling for traditional CV risk factors, each 1 m/s increase in baseline PWV was accompanied by a 93% higher odds of developing SHATS; and each 1 cm/s (0.01 m/s) annual increase in PWV by a 31% greater odds of developing SHATS. Arterial stiffness, a proxy of arterial aging that can be measured clinically as PWV, is an integrated predictive marker of multiple age-associated organ damage recognized as clinical diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31605138,

title = {Neural crest-derived tumor neuroblastoma and melanoma share 1p13.2 as susceptibility locus that shows a long-range interaction with the SLC16A1 gene},

author = {M. Ävitabile and M. Succoio and A. Testori and A. Cardinale and Z. Vaksman and V. A. Lasorsa and S. Cantalupo and M. Esposito and F. Cimmino and A. Montella and D. Formicola and J. Koster and V. Andreotti and P. Ghiorzo and M. F. Romano and S. Staibano and M. Scalvenzi and F. Ayala and H. Hakonarson and M. V. Corrias and M. Devoto and M. H. Law and M. M. Iles and K. Brown and S. Diskin and N. Zambrano and A. Iolascon and M. Capasso},

year  = {2020},

date = {2020-05-01},

urldate = {2020-05-01},

journal = {Carcinogenesis},

volume = {41},

number = {3},

pages = {284--295},

abstract = {10-4 demonstrated enrichment of biological processes such as cell migration, cell cycle, metabolism and immune response, which are essential of human NCC development, underlying both tumors. In vitro and in silico analyses indicated that the rs2153977-T protective allele, located in an NB and CMM enhancer, decreased expression of SLC16A1 via long-range loop formation and altered a T-box protein binding site. Upon depletion of SLC16A1, we observed a decrease of cellular proliferation and invasion in both NB and CMM cell lines, suggesting its role as oncogene. This is the largest study to date examining pleiotropy across two NC cell-derived tumors identifying 1p13.2 as common susceptibility locus for NB and CMM risk. We demonstrate that combining genome-wide association studies results across cancers with same origins can identify new loci common to neuroblastoma and melanoma arising from tissues which originate from neural crest cells. Our results also show 1p13.2 confer risk to neuroblastoma and melanoma by regulating SLC16A1.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32325986,

title = {Study of the Effects Induced by Ball Milling Treatment on Different Types of Hydrocolloids in a Corn Starch-Rice Flour System},

author = {Luca Nuvoli and Paola Conte and Sebastiano Garroni and Valeria Farina and Antonio Piga and Costantino Fadda},

doi = {10.3390/foods9040517},

issn = {2304-8158},

year  = {2020},

date = {2020-04-15},

journal = {Foods},

volume = {9},

number = {4},

abstract = {The effects of ball milling treatment on both the structure and properties of guar gum (GG), tara gum (TG), and methylcellulose (MC) were analyzed prior to assessing their potential interactions with starch components when they are used alone or in blends in a corn starch-rice flour system. X-ray diffraction profiles showed that the ball milling caused a reduction in the crystallin domain and, in turn, a diminished viscosity of the GG aqueous solutions. Despite an increase in its viscosity properties, effects on TG were minimal, while the milled MC exhibited reduced crystallinity, but similar viscosity. When both milled and un-milled hydrocolloids were individually added to the starch-flour system, the pasting properties of the resulting mixtures seemed to be affected by the type of hydrocolloid added rather than the structural changes induced by the treatment. All hydrocolloids increased the peak viscosity of the binary blends (especially pure GG), but only milled and un-milled MC showed values of setback and final viscosity similar to those of the individual starch. Ball milling seemed to be more effective when two combined hydrocolloids (milled GG and MC) were simultaneously used. No significant differences were observed in the viscoelastic properties of the blends, except for un-milled GG/starch, milled TG/starch, and milled MC/milled TG/starch gels.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32197476,

title = {Ŧhe Pervasive Role of the miR-181 Family in Đevelopment, Neurodegeneration, and Cancer},

author = {A Indrieri and S Carrella and P Carotenuto and S Banfi and B Franco},

year  = {2020},

date = {2020-03-01},

journal = {Int J Mol Sci},

volume = {21},

number = {6},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32008434,

title = {Urinary Albumin, Sodium, and Potassium and Cardiovascular Outcomes in the UK Biobank: Observational and Mendelian Randomization Analyses},

author = {D. Zanetti and H. Bergman and S. Burgess and T. L. Assimes and V. Bhalla and E. Ingelsson},

year  = {2020},

date = {2020-03-01},

journal = {Hypertension},

volume = {75},

number = {3},

pages = {714--722},

abstract = {=0.02). Our comprehensive study of urinary biomarkers performed using state-of-the-art analyses of causality mirror and extend findings from randomized interventional trials which have established UNa/UK as a risk factor for hypertension. In addition, we detect a causal feedback loop between albumin and hypertension, and our finding of a bidirectional causal association between albumin and T2D reflects the well-known nephropathy in T2D.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31949199,

title = {Landscape of transcriptome variations uncovering known and novel driver events in colorectal carcinoma},

author = {G Pira and P Uva and A M Scanu and P C Rocca and L Murgia and E Uleri and C Piu and A Porcu and C Carru and A Manca and I Persico and M R Muroni and F Sanges and C Serra and A Dolei and A Angius and M R De Miglio},

year  = {2020},

date = {2020-01-01},

journal = {Sci Rep},

volume = {10},

number = {1},

pages = {432},

abstract = {We focused on an integrated view of genomic changes in Colorectal cancer (CRC) and distant normal colon tissue (NTC) to test the effectiveness of expression profiling on identification of molecular targets. We performed transcriptome on 16 primary coupled CRC and NTC tissues. We identified pathways and networks related to pathophysiology of CRC and selected potential therapeutic targets. CRC cells have multiple ways to reprogram its transcriptome: a functional enrichment analysis in 285 genes, 25% mutated, showed that they control the major cellular processes known to promote tumorigenesis. Among the genes showing alternative splicing, cell cycle related genes were upregulated (CCND1, CDC25B, MCM2, MCM3), while genes involved in fatty acid metabolism (ACAAA2, ACADS, ACAT1, ACOX, CPT1A, HMGCS2) were downregulated. Overall 148 genes showed differential splicing identifying 17 new isoforms. Most of them are involved in the pathogenesis of CRC, although the functions of these variants remain unknown. We identified 2 in-frame fusion events, KRT19-KRT18 and EEF1A1-HSP90AB1, encoding for chemical proteins in two CRC patients. We draw a functional interactome map involving integrated multiple genomic features in CRC. Finally, we underline that two functional cell programs are prevalently deregulated and absolutely crucial to determinate and sustain CRC phenotype.},

note = {[PubMed Central:hrefhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965099PMC6965099] [DOI:hrefhttps://dx.doi.org/10.1038/s41598-019-57311-z10.1038/s41598-019-57311-z] [PubMed:hrefhttps://www.ncbi.nlm.nih.gov/pubmed/2548054825480548]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33004804,

title = {Mendelian randomization while jointly modeling cis genetics identifies causal relationships between gene expression and lipids},

author = {A van der Graaf and A Claringbould and A Rimbert and H J Westra and Y Li and C Wijmenga and S Sanna and B T Heijmans and P A C ' Hoen and J B J van Meurs and R Jansen and L Franke},

year  = {2020},

date = {2020-01-01},

journal = {Nat Commun},

volume = {11},

number = {1},

pages = {4930},

abstract = {Inference of causality between gene expression and complex traits using Mendelian randomization (MR) is confounded by pleiotropy and linkage disequilibrium (LD) of gene-expression quantitative trait loci (eQTL). Here, we propose an MR method, MR-link, that accounts for unobserved pleiotropy and LD by leveraging information from individual-level data, even when only one eQTL variant is present. In simulations, MR-link shows false-positive rates close to expectation (median 0.05) and high power (up to 0.89), outperforming all other tested MR methods and coloc. Application of MR-link to low-density lipoprotein cholesterol (LDL-C) measurements in 12,449 individuals with expression and protein QTL summary statistics from blood and liver identifies 25 genes causally linked to LDL-C. These include the known SORT1 and ApoE genes as well as PVRL2, located in the APOE locus, for which a causal role in liver was not known. Our results showcase the strength of MR-link for transcriptome-wide causal inferences.},

note = {[PubMed Central:hrefhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530717PMC7530717] [DOI:hrefhttps://dx.doi.org/10.1038/s41467-020-18716-x10.1038/s41467-020-18716-x] [PubMed:hrefhttps://www.ncbi.nlm.nih.gov/pubmed/2346866323468663]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32929287,

title = {Complex genetic signatures in immune cells underlie autoimmunity and inform therapy},

author = {V Orrù and M Steri and C Sidore and M Marongiu and V Serra and S Olla and G Sole and S Lai and M Dei and A Mulas and F Virdis and MG Piras and M Lobina and M Marongiu and M Pitzalis and F Deidda and A Loizedda and S Onano and M Zoledziewska and S Sawcer and M Devoto and M Gorospe and GR Abecasis and M Floris and M Pala and D Schlessinger and E Fiorillo and F Cucca},

doi = {10.1038/s41588-020-0684-4},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Nat Genet},

volume = {52},

number = {10},

pages = {1036--1045},

abstract = {We report on the influence of ~22 million variants on 731 immune cell traits in a cohort of 3,757 Sardinians. We detected 122 significant (P < 1.28 × 10-11) independent association signals for 459 cell traits at 70 loci (53 of them novel) identifying several molecules and mechanisms involved in cell regulation. Furthermore, 53 signals at 36 loci overlapped with previously reported disease-associated signals, predominantly for autoimmune disorders, highlighting intermediate phenotypes in pathogenesis. Collectively, our findings illustrate complex genetic regulation of immune cells with highly selective effects on autoimmune disease risk at the cell-subtype level. These results identify drug-targetable pathways informing the design of more specific treatments for autoimmune diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30678613,

title = {Oxidative Status in Multiple Sclerosis and Off-Targets of Antioxidants: The Case of Edaravone},

author = {Cristina Agresti and Rosella Mechelli and Stefania Olla and Caterina Veroni and Cecilia Eleuteri and Giovanni Ristori and Marco Salvetti},

year  = {2020},

date = {2020-01-01},

journal = {Curr Med Chem},

volume = {27},

number = {13},

pages = {2095--2105},

abstract = {MS is a chronic inflammatory disease of the CNS leading to demyelination and neurodegeneration, with a complex and still to be clarified aetiology. Several data, coming from patients' samples and from animal models, show that Oxidative Status (OS) plays an important role in MS pathogenesis. Overproduction of reactive oxidative species by macrophages/microglia can bring about cellular injury and ensuing cell death by oxidizing cardinal cellular components. Oxidized molecules are present in active MS lesions and are associated with neurodegeneration. We undertook a structured search of bibliographic databases for peer-reviewed research literature focusing on OS in MS. The contents of the selected papers were described in the context of a conceptual framework. A special emphasis was given to the results of our study in the field. The results of our three recent studies were put in the context and discussed taking into account the literature on the topic. Oxidative damage underpinned an imbalance shared by MS and neurodegenerative diseases such as Alzheimer and Parkinson diseases. In people with clinically isolated syndrome (an early phase of MS) oxidative stress proved to contribute to disease pathophysiology and to provide biomarkers that may help predict disease evolution. A drug screening platform based on multiple assays to test the remyelinating potential of library of approved compounds showed two anti-oxidants, edaravone and 5-methyl-7- methoxyisoflavone, as active drugs. Moreover, an analysis of 'structure activity relationship' showed off-targets sites of these compounds that accounted for their remyelinating activity, irrespective of their antioxidant action. Overall, edaravone emerges as a candidate to treat complex disease such as MS, where inflammation, oxidative stress and neurodegeneration contribute to disease progression, together or individually, in different phases and disease types. Furthermore, approaches based on drug repositioning seem to maintain the promise of helping discover novel treatment for complex diseases, where molecular targets are largely unknown.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30678613b,

title = {Oxidative Status in Multiple Sclerosis and Off-Targets of Antioxidants: The Case of Edaravone},

author = {Agresti, C. and Mechelli, R. and Olla, S. and Veroni, C. and Eleuteri, C. and Ristori, G. and Salvetti, M.},

year  = {2020},

date = {2020-01-01},

journal = {Curr Med Chem},

volume = {27},

number = {13},

pages = {2095--2105},

abstract = {MS is a chronic inflammatory disease of the CNS leading to demyelination and neurodegeneration, with a complex and still to be clarified aetiology. Several data, coming from patients' samples and from animal models, show that Oxidative Status (OS) plays an important role in MS pathogenesis. Overproduction of reactive oxidative species by macrophages/microglia can bring about cellular injury and ensuing cell death by oxidizing cardinal cellular components. Oxidized molecules are present in active MS lesions and are associated with neurodegeneration. We undertook a structured search of bibliographic databases for peer-reviewed research literature focusing on OS in MS. The contents of the selected papers were described in the context of a conceptual framework. A special emphasis was given to the results of our study in the field. The results of our three recent studies were put in the context and discussed taking into account the literature on the topic. Oxidative damage underpinned an imbalance shared by MS and neurodegenerative diseases such as Alzheimer and Parkinson diseases. In people with clinically isolated syndrome (an early phase of MS) oxidative stress proved to contribute to disease pathophysiology and to provide biomarkers that may help predict disease evolution. A drug screening platform based on multiple assays to test the remyelinating potential of library of approved compounds showed two anti-oxidants, edaravone and 5-methyl-7- methoxyisoflavone, as active drugs. Moreover, an analysis of 'structure activity relationship' showed off-targets sites of these compounds that accounted for their remyelinating activity, irrespective of their antioxidant action. Overall, edaravone emerges as a candidate to treat complex disease such as MS, where inflammation, oxidative stress and neurodegeneration contribute to disease progression, together or individually, in different phases and disease types. Furthermore, approaches based on drug repositioning seem to maintain the promise of helping discover novel treatment for complex diseases, where molecular targets are largely unknown.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31497877,

title = {Crisponi/cold-induced sweating syndrome: Differential diagnosis, pathogenesis and treatment concepts},

author = {Buers, I. and Persico, I. and Schöning, L. and Nitschke, Y. and Di Rocco, M. and Loi, A. and Sahi, P. K. and Utine, G. E. and Bayraktar-Tanyeri, B. and Zampino, G. and Crisponi, G. and Rutsch, F. and Crisponi, L.},

year  = {2020},

date = {2020-01-01},

journal = {Clin Genet},

volume = {97},

number = {1},

pages = {209--221},

abstract = {Crisponi/cold-induced sweating syndrome (CS/CISS) is an autosomal recessive disease characterized by hyperthermia, camptodactyly, feeding and respiratory difficulties often leading to sudden death in the neonatal period. The affected individuals who survived the first critical years of life, develop cold-induced sweating and scoliosis in early childhood. The disease is caused by variants in the CRLF1 or in the CLCF1 gene. Both proteins form a heterodimeric complex that acts on cells expressing the ciliary neurotrophic factor receptor (CNTFR). CS/CISS belongs to the family of "CNTFR-related disorders" showing a similar clinical phenotype. Recently, variants in other genes, including KLHL7, NALCN, MAGEL2 and SCN2A, previously linked to other diseases, have been associated with a CS/CISS-like phenotype. Therefore, retinitis pigmentosa and Bohring-Optiz syndrome-like (KLHL7), Congenital contractures of the limbs and face, hypotonia, and developmental delay syndrome (NALCN), Chitayat-Hall/Schaaf-Yang syndrome (MAGEL2), and early infantile epileptic encephalopathy-11 syndrome (SCN2A) all share an overlapping phenotype with CS/CISS, especially in the neonatal period. This review aims to summarize the existing literature on CS/CISS, focusing on the current state of differential diagnosis, pathogenesis and treatment concepts in order to achieve an accurate and rapid diagnosis. This will improve patient management and enable specific treatments for the affected individuals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32528964,

title = {Delta-Globin Gene Expression Is Enhanced in vivo by Interferon Type I},

author = {Manchinu, M. F. and Simbula, M. and Caria, C. A. and Musu, E. and Perseu, L. and Porcu, S. and Steri, M. and Poddie, D. and Frau, J. and Cocco, E. and Manunza, L. and Barella, S. and Ristaldi, M. S.},

year  = {2020},

date = {2020-01-01},

journal = {Front Med (Lausanne)},

volume = {7},

pages = {163},

abstract = {Beta hemoglobinopathies are widely spread monogenic lethal diseases. Delta-globin gene activation has been proposed as a possible approach for curing these pathologies. The therapeutic potential of delta-globin, the non-alpha component of Hemoglobin A2 (α2δ2; HbA2), has been demonstrated in a mouse model of beta thalassemia, while its anti-sickling effect, comparable to that of gamma globin, was established some time ago. Here we show that the delta-globin mRNA level is considerably increased in a Deoxyribonuclease II-alpha knockout mouse model in which type 1 interferon (interferon beta, IFNb) is activated. IFNb activation in the fetal liver improves the delta-globin mRNA level, while the beta-globin mRNA level is significantly reduced. In addition, we show that HbA2 is significantly increased in patients with multiple sclerosis under type 1 interferon treatment. Our results represent a proof of principle that delta-globin expression can be enhanced through the use of molecules. This observation is potentially interesting in view of a pharmacological approach able to increase the HbA2 level.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33123155,

title = {Evolutionarily Selected Overexpression of the Cytokine BAFF Enhances Mucosal Immune Response Against P. falciparum},

author = { V. Lodde and M. Floris and I. Beerman and R. Munk and R. Guha and M. Steri and V. Orrù and K. Abdelmohsen and P. D. Crompton and M. Gorospe and M. L. Idda and F. Cucca},

year  = {2020},

date = {2020-01-01},

journal = {Front Immunol},

volume = {11},

pages = {575103},

abstract = {We have previously shown that a variant of the TNFSF13B gene that we called BAFF-var increases the production of the cytokine BAFF, upregulating humoral immunity and increasing the risk for certain autoimmune diseases. In addition, genetic population signatures revealed that BAFF-var was evolutionarily advantageous, most likely by increasing resistance to malaria infection, which is a prime candidate for selective pressure. To evaluate whether the increased soluble BAFF (sBAFF) production confers protection, we experimentally assessed the role of BAFF-var in response to malaria antigens. Lysates of erythrocytes infected with Plasmodium falciparum (iRBCs) or left uninfected (uRBCs, control) were used to treat peripheral blood mononuclear cells (PBMCs) with distinct BAFF genotypes. The PBMCs purified from BAFF-var donors and treated with iRBCs showed different levels of specific cells, immunoglobulins, and cytokines as compared with BAFF-WT. In particular, a relevant differential effect on mucosal immunity B subpopulations have been observed. These findings point to specific immune cells and molecules through which the evolutionary selected BAFF-var may have improved fitness during P. falciparum infection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32690655,

title = {Human Hepatitis B Viral Infection Outcomes Are Linked to Naturally Occurring Variants of HLA-DOA That Have Altered Function},

author = {A. M. Graves and F. Virdis and E. Morrison and M. Álvaro-Benito and A. A. Khan and C. Freund and T. V. Golovkina and L. K. Denzin},

year  = {2020},

date = {2020-01-01},

journal = {J Immunol},

volume = {205},

number = {4},

pages = {923--935},

abstract = {HLA molecules of the MHC class II (MHCII) bind and present pathogen-derived peptides for CD4 T cell activation. Peptide loading of MHCII in the endosomes of cells is controlled by the interplay of the nonclassical MHCII molecules, HLA-DM (DM) and HLA-DO (DO). DM catalyzes peptide loading, whereas DO, an MHCII substrate mimic, prevents DM from interacting with MHCII, resulting in an altered MHCII-peptide repertoire and increased MHCII-CLIP. Although the two genes encoding DO (DOA and DOB) are considered nonpolymorphic, there are rare natural variants. Our previous work identified DOB variants that altered DO function. In this study, we show that natural variation in the DOA gene also impacts DO function. Using the 1000 Genomes Project database, we show that ∼98% of individuals express the canonical DOA*0101 allele, and the remaining individuals mostly express DOA*0102, which we found was a gain-of-function allele. Analysis of 25 natural occurring DOα variants, which included the common alleles, identified three null variants and one variant with reduced and nine with increased ability to modulate DM activity. Unexpectedly, several of the variants produced reduced DO protein levels yet efficiently inhibited DM activity. Finally, analysis of associated single-nucleotide polymorphisms genetically linked the DOA*0102 common allele, a gain-of-function variant, with human hepatitis B viral persistence. In contrast, we found that the DOα F114L null allele was linked with viral clearance. Collectively, these studies show that natural variation occurring in the human DOA gene impacts DO function and can be linked to specific outcomes of viral infections.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32719615,

title = {Ŧhe Broad Spectrum of LMNA Cardiac Điseases: From Molecular Mechanisms to Clinical Phenotype},

author = {S Crasto and I My and E Di Pasquale},

year  = {2020},

date = {2020-01-01},

journal = {Front Physiol},

volume = {11},

pages = {761},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32094358,

title = {Genetic history from the Middle Neolithic to present on the Mediterranean island of Sardinia},

author = { J. H. Marcus and C. Posth and H. Ringbauer and L. Lai and R. Skeates and C. Sidore and J. Beckett and A. Furtwängler and A. Olivieri and C. W. K. Chiang and H. Al-Asadi and K. Dey and T. A. Joseph and C. C. Liu and C. Der Sarkissian and R. Radzevičiūtė and M. Michel and M. G. Gradoli and P. Marongiu and S. Rubino and V. Mazzarello and D. Rovina and A. La Fragola and R. M. Serra and P. Bandiera and R. Bianucci and E. Pompianu and C. Murgia and M. Guirguis and R. P. Orquin and N. Tuross and P. van Dommelen and W. Haak and D. Reich and D. Schlessinger and F. Cucca and J. Krause and J. Novembre},

year  = {2020},

date = {2020-01-01},

journal = {Nat Commun},

volume = {11},

number = {1},

pages = {939},

abstract = {The island of Sardinia has been of particular interest to geneticists for decades. The current model for Sardinia's genetic history describes the island as harboring a founder population that was established largely from the Neolithic peoples of southern Europe and remained isolated from later Bronze Age expansions on the mainland. To evaluate this model, we generate genome-wide ancient DNA data for 70 individuals from 21 Sardinian archaeological sites spanning the Middle Neolithic through the Medieval period. The earliest individuals show a strong affinity to western Mediterranean Neolithic populations, followed by an extended period of genetic continuity on the island through the Nuragic period (second millennium BCE). Beginning with individuals from Phoenician/Punic sites (first millennium BCE), we observe spatially-varying signals of admixture with sources principally from the eastern and northern Mediterranean. Overall, our analysis sheds light on the genetic history of Sardinia, revealing how relationships to mainland populations shifted over time.},

note = {[PubMed Central:hrefhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039977PMC7039977] [DOI:hrefhttps://dx.doi.org/10.1038/s41467-020-14523-610.1038/s41467-020-14523-6] [PubMed:hrefhttps://www.ncbi.nlm.nih.gov/pubmed/3128189731281897]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33488405,

title = {Peptide-Based Ŧargeting of the L-Ŧype Calcium Channel Corrects the Loss-of-Function Phenotype of Ŧwo Novel Mutations of the CACNA1 Gene Associated With Brugada Syndrome},

author = {V Di Mauro and P Ceriotti and F Lodola and N Salvarani and J Modica and M L Bang and A Mazzanti and C Napolitano and S G Priori and D Catalucci},

year  = {2020},

date = {2020-01-01},

journal = {Front Physiol},

volume = {11},

pages = {616819},

keywords = {},

pubstate = {published},

tppubtype = {article}

}