@article{%a1.%Y_129,

title = {Thermostable Lactonases Inhibit Pseudomonas aeruginosa Biofilm: Effect In Vitro and in Drosophila melanogaster Model of Chronic Infection},

author = {Porzio E and Andrenacci D and Manco G},

url = {https://www.mdpi.com/1422-0067/24/23/17028},

doi = {10.3390/ijms242317028},

year  = {2023},

date = {2023-08-18},

journal = {International journal of molecular sciences},

volume = {24},

issue = {23},

pages = {17028},

abstract = {Pseudomonas aeruginosa is one of the six antimicrobial-resistant pathogens known as "ESKAPE" that represent a global threat to human health and are considered priority targets for the development of novel antimicrobials and alternative therapeutics. The virulence of P. aeruginosa is regulated by a four-chemicals communication system termed quorum sensing (QS), and one main class of QS signals is termed acylhomoserine lactones (acyl-HSLs), which includes 3-Oxo-dodecanoil homoserine lactone (3-Oxo-C12-HSL), which regulates the expression of genes implicated in virulence and biofilm formation. Lactonases, like Paraoxonase 2 (PON2) from humans and the phosphotriesterase-like lactonases (PLLs) from thermostable microorganisms, are able to hydrolyze acyl-HSLs. In this work, we explored in vitro and in an animal model the effect of some lactonases on the production of Pseudomonas virulence factors. This study presents a model of chronic infection in which bacteria were administered by feeding, and Drosophila adults were treated with enzymes and the antibiotic tobramycin, alone or in combination. In vitro, we observed significant effects of lactonases on biofilm formation as well as effects on bacterial motility and the expression of virulence factors. The treatment in vivo by feeding with the lactonase SacPox allowed us to significantly increase the biocidal effect of tobramycin in chronic infection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y__504,

title = {Interleukin-6 neutralization ameliorates symptoms in prematurely aged mice.},

author = {Squarzoni S and Schena E and Sabatelli P and Mattioli E and Capanni C and Cenni V and D'Apice MR and Andrenacci D and Sarli G and Pellegrino V and Festa A and Baruffaldi F and

Storci G and Bonafè M and Barboni C and Sanapo M and Zaghini A and Lattanzi G},

url = {https://onlinelibrary.wiley.com/doi/10.1111/acel.13285},

doi = {10.1111/acel.13285},

year  = {2021},

date = {2021-03-09},

urldate = {2021-03-09},

journal = {Aging Cell},

volume = {20},

number = {1},

pages = {e13285},

abstract = {Hutchinson-Gilford progeria syndrome (HGPS) causes premature aging in children, with adipose tissue, skin and bone deterioration, and cardiovascular impairment. In HGPS cells and mouse models, high levels of interleukin-6, an inflammatory cytokine linked to aging processes, have been detected. Here, we show that inhibition of interleukin-6 activity by tocilizumab, a neutralizing antibody raised against interleukin-6 receptors, counteracts progeroid features in both HGPS fibroblasts and LmnaG609G / G609G progeroid mice. Tocilizumab treatment limits the accumulation of progerin, the toxic protein produced in HGPS cells, rescues nuclear envelope and chromatin abnormalities, and attenuates the hyperactivated DNA damage response. In vivo administration of tocilizumab reduces aortic lesions and adipose tissue dystrophy, delays the onset of lipodystrophy and kyphosis, avoids motor impairment, and preserves a good quality of life in progeroid mice. This work identifies tocilizumab as a valuable tool in HGPS therapy and, speculatively, in the treatment of a variety of aging-related disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Yb_71,

title = {Retrotransposons Down- and Up-Regulation in Aging Somatic Tissue},

author = {Giordani G and Cavaliere V and Gargiulo G and Lattanzi G and Andrenacci D},

url = {https://www.mdpi.com/2073-4409/11/1/79},

doi = {10.3390/cells11010079},

year  = {2021},

date = {2021-12-30},

journal = {Cells},

volume = {11},

number = {1},

pages = {79},

abstract = {The transposon theory of aging hypothesizes the activation of transposable elements (TEs) in somatic tissues with age, leading to a shortening of the lifespan. It is thought that TE activation in aging produces an increase in DNA double-strand breaks, contributing to genome instability and promoting the activation of inflammatory responses. To investigate how TE regulation changes in somatic tissues during aging, we analyzed the expression of some TEs, as well as a source of small RNAs that specifically silence the analyzed TEs; the Drosophila cluster named flamenco. We found significant variations in the expression levels of all the analyzed TEs during aging, with a trend toward reduction in middle-aged adults and reactivation in older individuals that suggests dynamic regulation during the lifespan.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_434,

title = {Silencing of Euchromatic Transposable Elements as a Consequence of Nuclear Lamina Dysfunction.},

author = {Cavaliere V and Lattanzi G and Andrenacci D},

url = {https://www.mdpi.com/2073-4409/9/3/625},

doi = {10.3390/cells9030625},

year  = {2020},

date = {2020-01-01},

journal = {Cells},

volume = {9},

number = {3},

pages = {e625},

abstract = {Transposable elements (TEs) are mobile genomic sequences that are normally repressed to avoid proliferation and genome instability. Gene silencing mechanisms repress TEs by RNA degradation or heterochromatin formation. Heterochromatin maintenance is therefore important to keep TEs silent. Loss of heterochromatic domains has been linked to lamin mutations, which have also been associated with derepression of TEs. In fact, lamins are structural components of the nuclear lamina (NL), which is considered a pivotal structure in the maintenance of heterochromatin domains at the nuclear periphery in a silent state. Here, we show that a lethal phenotype associated with Lamin loss-of-function mutations is influenced by Drosophila gypsy retrotransposons located in euchromatic regions, suggesting that NL dysfunction has also effects on active TEs located in euchromatic loci. In fact, expression analysis of different long terminal repeat (LTR) retrotransposons and of one non-LTR retrotransposon located near active genes shows that Lamin inactivation determines the silencing of euchromatic TEs. Furthermore, we show that the silencing effect on euchromatic TEs spreads to the neighboring genomic regions, with a repressive effect on nearby genes. We propose that NL dysfunction may have opposed regulatory effects on TEs that depend on their localization in active or repressed regions of the genome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_423,

title = {Tendon Extracellular Matrix Remodeling and Defective Cell Polarization in the Presence of Collagen VI Mutations.},

author = {Antoniel M and Traina F and Merlini L and Andrenacci D and Tigani D and Santi S and Cenni V and Sabatelli P and Faldini C and Squarzoni S},

url = {https://www.mdpi.com/2073-4409/9/2/409},

doi = {10.3390/cells9020409},

year  = {2020},

date = {2020-01-01},

journal = {Cells},

volume = {9},

number = {2},

pages = {e409},

abstract = {Mutations in collagen VI genes cause two major clinical myopathies, Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), and the rarer myosclerosis myopathy. In addition to congenital muscle weakness, patients affected by collagen VI-related myopathies show axial and proximal joint contractures, and distal joint hypermobility, which suggest the involvement of tendon function. To gain further insight into the role of collagen VI in human tendon structure and function, we performed ultrastructural, biochemical, and RT-PCR analysis on tendon biopsies and on cell cultures derived from two patients affected with BM and UCMD. In vitro studies revealed striking alterations in the collagen VI network, associated with disruption of the collagen VI-NG2 (Collagen VI-neural/glial antigen 2) axis and defects in cell polarization and migration. The organization of extracellular matrix (ECM) components, as regards collagens I and XII, was also affected, along with an increase in the active form of metalloproteinase 2 (MMP2). In agreement with the in vitro alterations, tendon biopsies from collagen VI-related myopathy patients displayed striking changes in collagen fibril morphology and cell death. These data point to a critical role of collagen VI in tendon matrix organization and cell behavior. The remodeling of the tendon matrix may contribute to the muscle dysfunction observed in BM and UCMD patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_478,

title = {The Impact of Drosophila Awd/NME1/2 Levels on Notch and Wg Signaling Pathways. },

author = {Serafini G and Giordani G and Grillini L and Andrenacci D and Gargiulo G and Cavaliere V},

url = {https://www.mdpi.com/1422-0067/21/19/7257},

doi = {10.3390/ijms21197257},

year  = {2020},

date = {2020-01-01},

journal = {International journal of molecular sciences},

volume = {21},

number = {19},

pages = {7257},

abstract = {Awd, the Drosophila homologue of NME1/2 metastasis suppressors, plays key roles in many signaling pathways. Mosaic analysis of the null awdJ2A4 allele showed that loss of awd gene function blocks Notch signaling and the expression of its target genes including the Wingless (Wg/Wnt1) morphogen. We also showed that RNA interference (RNAi)-mediated awd silencing (awdi) in larval wing disc leads to chromosomal instability (CIN) and to Jun amino-terminal kinases (JNK)-mediated cell death. Here we show that this cell death is independent of p53 activity. Based on our previous finding showing that forced survival of awdi-CIN cells leads to aneuploidy without the hyperproliferative effect, we investigated the Wg expression in awdi wing disc cells. Interestingly, the Wg protein is expressed in its correct dorso-ventral domain but shows an altered cellular distribution which impairs its signaling. Further, we show that RNAi-mediated knock down of awd in wing discs does not affect Notch signaling. Thus, our analysis of the hypomorphic phenotype arising from awd downregulation uncovers a dose-dependent effect of Awd in Notch and Wg signaling.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_90,

title = {The role of transposable elements activity in aging and their possible involvement in laminopathic diseases.},

author = {Andrenacci D and Cavaliere V and Lattanzi G},

url = {https://www.sciencedirect.com/science/article/pii/S1568163719301837?via%3Dihub},

doi = {10.1016/j.arr.2019.100995},

year  = {2020},

date = {2020-01-08},

journal = {Ageing research reviews},

volume = {57},

pages = {100995},

abstract = {Eukaryotic genomes contain a large number of transposable elements, part of which are still active and able to transpose in the host genome. Mobile element activation is repressed to avoid deleterious effects, such as gene mutations or chromosome rearrangements. Control of transposable elements includes a variety of mechanisms comprising silencing pathways, which are based on the production of small non-coding RNAs. Silencing can occur either through transposable element RNA degradation or through the targeting of DNA sequences by heterochromatin formation and consequent transcriptional inhibition. Since the important role of the heterochromatin silencing, the gradual loss of heterochromatin marks in constitutive heterochromatin regions during the aging process promotes derepression of transposable elements, which is considered a cause of the progressive increase in genomic instability and of the activation of inflammatory responses. This review provides an overview of the effects of heterochromatin loss on the activity of transposable elements during the aging process and the possible impact on genome function. In this context, we discuss the possible role of the nuclear lamina, a major player in heterochromatin dynamics, in the regulation of transposable element activity and potential implications in laminopathic diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%_48,

title = {Altered adipocyte differentiation and unbalanced autophagy in type 2 Familial Partial Lipodystrophy: an in vitro and in vivo study of adipose tissue browning.},

author = {Pellegrini C and Columbaro M and Schena E and Prencipe S and Andrenacci D and Iozzo P and Angela Guzzardi M and Capanni C and Mattioli E and Loi M and Araujo-Vilar D and Squarzoni S and Cinti S and Morselli P and Giorgetti A and Zanotti L and Gambineri A and Lattanzi G},

url = {https://www.nature.com/articles/s12276-019-0289-0},

doi = {10.1038/s12276-019-0289-0},

year  = {2019},

date = {2019-03-04},

urldate = {2019-03-04},

journal = {Experimental & molecular medicine.},

volume = {51},

number = {8},

pages = {89},

abstract = {Type-2 Familial Partial Lipodystrophy is caused by LMNA mutations. Patients gradually lose subcutaneous fat from the limbs, while they accumulate adipose tissue in the face and neck. Several studies have demonstrated that autophagy is involved in the regulation of adipocyte differentiation and the maintenance of the balance between white and brown adipose tissue. We identified deregulation of autophagy in laminopathic preadipocytes before induction of differentiation. Moreover, in differentiating white adipocyte precursors, we observed impairment of large lipid droplet formation, altered regulation of adipose tissue genes, and expression of the brown adipose tissue marker UCP1. Conversely, in lipodystrophic brown adipocyte precursors induced to differentiate, we noticed activation of autophagy, formation of enlarged lipid droplets typical of white adipocytes, and dysregulation of brown adipose tissue genes. In agreement with these in vitro results indicating conversion of FPLD2 brown preadipocytes toward the white lineage, adipose tissue from FPLD2 patient neck, an area of brown adipogenesis, showed a white phenotype reminiscent of its brown origin. Moreover, in vivo morpho-functional evaluation of fat depots in the neck area of three FPLD2 patients by PET/CT analysis with cold stimulation showed the absence of brown adipose tissue activity. These findings highlight a new pathogenetic mechanism leading to improper fat distribution in lamin A-linked lipodystrophies and show that both impaired white adipocyte turnover and failure of adipose tissue browning contribute to disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%_43,

title = {Comparative Expression Profiling of Wild Type Drosophila Malpighian Tubules and von Hippel-Lindau Haploinsufficient Mutant.},

author = {Ignesti M and Andrenacci D and Fischer B and Cavaliere V and Gargiulo G},

url = {https://www.frontiersin.org/articles/10.3389/fphys.2019.00619/full#h6},

doi = {10.3389/fphys.2019.00619},

year  = {2019},

date = {2019-02-21},

journal = {Frontiers in physiology},

volume = {10},

pages = {619},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_74,

title = {Statins and Histone Deacetylase Inhibitors Affect Lamin A/C - Histone Deacetylase 2 Interaction in Human Cells.},

author = {Mattioli E and Andrenacci D and Mai A and Valente S and Robijns J and De Vos WH and Capanni C and Lattanzi G},

url = {https://www.frontiersin.org/articles/10.3389/fcell.2019.00006/full},

doi = {10.3389/fcell.2019.00006},

year  = {2019},

date = {2019-03-08},

urldate = {2019-03-08},

journal = {Frontiers in cell and developmental biology},

volume = {7},

pages = {6},

abstract = {We recently identified lamin A/C as a docking molecule for human histone deacetylase 2 (HDAC2) and showed involvement of HDAC2-lamin A/C complexes in the DNA damage response. We further showed that lamin A/C-HDAC2 interaction is altered in Hutchinson-Gilford Progeria syndrome and other progeroid laminopathies. Here, we show that both inhibitors of lamin A maturation and small molecules inhibiting HDAC activity affect lamin A/C interaction with HDAC2. While statins, which inhibit prelamin A processing, reduce protein interaction, HDAC inhibitors strengthen protein binding. Moreover, treatment with HDAC inhibitors restored the enfeebled lamin A/C-HDAC2 interaction observed in HGPS cells. Based on these results, we propose that prelamin A levels as well as HDAC2 activation status might influence the extent of HDAC2 recruitment to the lamin A/C-containing platform and contribute to modulate HDAC2 activity. Our study links prelamin A processing to HDAC2 regulation and provides new insights into the effect of statins and histone deacetylase inhibitors on lamin A/C functionality in normal and progeroid cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_159,

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

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

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

doi = {10.1111/acel.12824},

year  = {2018},

date = {2018-02-14},

journal = {Aging cell},

volume = {17},

number = {5},

pages = {e1282},

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

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_285,

title = {Production of Small Noncoding RNAs from the flamenco Locus Is Regulated by the gypsy Retrotransposon of Drosophila melanogaster.},

author = {Guida V and Cernilogar FM and Filograna A and De Gregorio R and Ishizu H and Siomi MC and Schotta G and Bellenchi GC and Andrenacci D},

url = {http://www.genetics.org/content/204/2/631.long},

doi = {10.1534/genetics.116.187922},

year  = {2016},

date = {2016-10-12},

journal = {Genetics},

volume = {204},

number = {2},

pages = {631-644},

abstract = {Protective mechanisms based on RNA silencing directed against the propagation of transposable elements are highly conserved in eukaryotes. The control of transposable elements is mediated by small noncoding RNAs, which derive from transposon-rich heterochromatic regions that function as small RNA-generating loci. These clusters are transcribed and the precursor transcripts are processed to generate Piwi-interacting RNAs (piRNAs) and endogenous small interfering RNAs (endo-siRNAs), which silence transposable elements in gonads and somatic tissues. The flamenco locus is a Drosophila melanogaster small RNA cluster that controls gypsy and other transposable elements, and has played an important role in understanding how small noncoding RNAs repress transposable elements. In this study, we describe a cosuppression mechanism triggered by new euchromatic gypsy insertions in genetic backgrounds carrying flamenco alleles defective in gypsy suppression. We found that the silencing of gypsy is accompanied by the silencing of other transposons regulated by flamenco, and of specific flamenco sequences from which small RNAs against gypsy originate. This cosuppression mechanism seems to depend on a post-transcriptional regulation that involves both endo-siRNA and piRNA pathways and is associated with the occurrence of developmental defects. In conclusion, we propose that new gypsy euchromatic insertions trigger a post-transcriptional silencing of gypsy sense and antisense sequences, which modifies the flamenco activity. This cosuppression mechanism interferes with some developmental processes, presumably by influencing the expression of specific genes. Copyright 2016 by the Genetics Society of America.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}