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Article: High clonality of

Turco, Silvia / Russo, Simone / Pietrucci, Daniele / Filippi, Anita / Milanesi, Marco / Luzzago, Camilla / Garbarino, Chiara / Palladini, Giorgia / Chillemi, Giovanni / Ricchi, Matteo

Frontiers in veterinary science

2024 Volume 11, Page(s) 1301667

Abstract: Mycobacterium ... ...

Abstract	Mycobacterium avium
Language	English
Publishing date	2024-02-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2024.1301667
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Article ; Online: New Insights into the Effect of Residue Mutations on the Rotavirus VP1 Function Using Molecular Dynamic Simulations.

Abid, Nabil / Pietrucci, Daniele / Salemi, Marco / Chillemi, Giovanni

Journal of chemical information and modeling

2020 Volume 60, Issue 10, Page(s) 5011–5025

Abstract: Rotavirus group A remains a major cause of diarrhea in infants and young children worldwide. The permanent emergence of new genotypes puts the potential effectiveness of vaccines under serious questions. Thirteen VP1 structures with mutations mapping to ... ...

Abstract	Rotavirus group A remains a major cause of diarrhea in infants and young children worldwide. The permanent emergence of new genotypes puts the potential effectiveness of vaccines under serious questions. Thirteen VP1 structures with mutations mapping to the RNA entry site were analyzed using molecular dynamics simulations, and the results were combined with the experimental findings reported previously. The results revealed structural fluctuations in the protein-protein recognition sites and in the bottleneck of the RNA entry site that may affect the interaction of different proteins and delay the initiation of the viral replication, respectively. Altogether, the structural analysis of VP1 in the region crucial for the initiation of the viral replication, mainly the bottleneck site, may boost efforts to develop antivirals, as they might complement the available vaccines.
MeSH term(s)	Genotype ; Molecular Dynamics Simulation ; Mutation ; Rotavirus/genetics ; Viral Core Proteins/genetics ; Virus Replication
Chemical Substances	VP1 protein, Rotavirus ; Viral Core Proteins
Language	English
Publishing date	2020-08-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	190019-5
ISSN	1549-960X ; 0095-2338
ISSN (online)	1549-960X
ISSN	0095-2338
DOI	10.1021/acs.jcim.0c00475
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Article: Dissecting the Gene Expression Networks Associated with Variations in the Major Components of the Fatty Acid

Zappaterra, Martina / Gioiosa, Silvia / Chillemi, Giovanni / Zambonelli, Paolo / Davoli, Roberta

Animals : an open access journal from MDPI

2021 Volume 11, Issue 3

Abstract: To date, high-throughput technology such as RNA-sequencing has been successfully applied in livestock sciences to investigate molecular networks involved in complex traits, such as meat quality. Pork quality depends on several organoleptic, technological, ...

Abstract	To date, high-throughput technology such as RNA-sequencing has been successfully applied in livestock sciences to investigate molecular networks involved in complex traits, such as meat quality. Pork quality depends on several organoleptic, technological, and nutritional characteristics, and it is also influenced by the fatty acid (FA) composition of intramuscular fat (IMF). To explore the molecular networks associated with different IMF FA compositions, the
Language	English
Publishing date	2021-02-27
Publishing country	Switzerland
Document type	Journal Article
ISSN	2076-2615
ISSN	2076-2615
DOI	10.3390/ani11030628
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Article: Dissecting the Gene Expression Networks Associated with Variations in the Major Components of the Fatty Acid Semimembranosus Muscle Profile in Large White Heavy Pigs

Zappaterra, Martina / Gioiosa, Silvia / Chillemi, Giovanni / Zambonelli, Paolo / Davoli, Roberta

Animals. 2021 Feb. 27, v. 11, no. 3

2021

Abstract	To date, high-throughput technology such as RNA-sequencing has been successfully applied in livestock sciences to investigate molecular networks involved in complex traits, such as meat quality. Pork quality depends on several organoleptic, technological, and nutritional characteristics, and it is also influenced by the fatty acid (FA) composition of intramuscular fat (IMF). To explore the molecular networks associated with different IMF FA compositions, the Semimembranosus muscle (SM) from two groups of Italian Large White (ILW) heavy pigs divergent for SM IMF content was investigated using transcriptome analysis. After alignment and normalization, the obtained gene counts were used to perform the Weighted Correlation Network Analysis (WGCNA package in R environment). Palmitic and palmitoleic contents showed association with the same gene modules, comprising genes significantly enriched in autophagy, mitochondrial fusion, and mitochondrial activity. Among the key genes related to these FAs, we found TEAD4, a gene regulating mitochondrial activity that seems to be a promising candidate for further studies. On the other hand, the genes comprised in the modules associated with the IMF contents of oleic, n-6, and n-3 polyunsaturated FAs (PUFAs) were significantly enriched in Mitogen-Activated Protein Kinase (MAPK) signaling, in agreement with previous studies suggesting that several MAPK players may have a primary role in regulating lipid deposition. These results give an insight into the molecular cascade associated with different IMF FA composition in ILW heavy pigs. Further studies are needed to validate the results and confirm whether some of the identified key genes may be effective candidates for pork quality.
Keywords	Large White ; autophagy ; gene expression ; genes ; intramuscular fat ; mitochondria ; mitogen-activated protein kinase ; polyunsaturated fatty acids ; pork quality ; semimembranosus muscle ; sequence analysis ; transcriptomics
Language	English
Dates of publication	2021-0227
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ISSN	2076-2615
DOI	10.3390/ani11030628
Database	NAL-Catalogue (AGRICOLA)

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Article: Coding-Gene Coevolution Analysis of Rotavirus Proteins: A Bioinformatics and Statistical Approach

Abid, Nabil / Chillemi, Giovanni / Salemi, Marco

Genes. 2019 Dec. 24, v. 11, no. 1

2019

Abstract: Rotavirus remains a major cause of diarrhea in infants and young children worldwide. The permanent emergence of new genotypes puts the potential effectiveness of vaccines under serious question. The distribution of unusual genotypes subject to viral ... ...

Abstract	Rotavirus remains a major cause of diarrhea in infants and young children worldwide. The permanent emergence of new genotypes puts the potential effectiveness of vaccines under serious question. The distribution of unusual genotypes subject to viral fitness is influenced by interactions among viral proteins. The present work aimed at analyzing the genetic constellation and the coevolution of rotavirus coding genes for the available rotavirus genotypes. Seventy-two full genome sequences of different genetic constellations were analyzed using a genetic algorithm. The results revealed an extensive genome-wide covariance network among the 12 viral proteins. Altogether, the emergence of new genotypes represents a challenge to the outcome and success of vaccination and the coevolutionary analysis of rotavirus proteins may boost efforts to better understand the interaction networks of proteins during viral replication/transcription.
Keywords	Rotavirus ; algorithms ; bioinformatics ; children ; coevolution ; covariance ; diarrhea ; genes ; genotype ; infants ; nucleotide sequences ; transcription (genetics) ; vaccination ; vaccines ; viral proteins ; virus replication
Language	English
Dates of publication	2019-1224
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes11010028
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Article: HECT-Type E3 Ubiquitin Ligases in Cancer

Bernassola, Francesca / Chillemi, Giovanni / Melino, Gerry

Trends in biochemical sciences. 2019 Dec., v. 44, no. 12

2019

Abstract: Ubiquitination, a post-translational modification that involves a covalent attachment of ubiquitin to a protein substrate, is essential for cellular homeostatic maintenance. At the end of a three-enzyme cascade, E3 ubiquitin ligases (E3s) recruit ... ...

Abstract	Ubiquitination, a post-translational modification that involves a covalent attachment of ubiquitin to a protein substrate, is essential for cellular homeostatic maintenance. At the end of a three-enzyme cascade, E3 ubiquitin ligases (E3s) recruit substrates and promote or directly catalyze ubiquitin transfer to targets. These enzymes largely determine the specificity of the ubiquitination reaction. Genetic alteration, abnormal expression, or dysfunction of E3s account for the occurrence and progression of human cancers. Indeed, excessive degradation of relevant tumor-suppressor molecules and impaired disposal of oncogenic proteins have been linked to tumorigenesis. This review focuses on the emerging roles of HECT-type E3s in tumorigenesis, and emphasizes how perturbations of these enzymes contribute to cancer pathogenesis.
Keywords	carcinogenesis ; humans ; neoplasms ; ubiquitin ; ubiquitination ; ubiquitin-protein ligase
Language	English
Dates of publication	2019-12
Size	p. 1057-1075.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	194220-7
ISSN	0968-0004 ; 0376-5067
ISSN	0968-0004 ; 0376-5067
DOI	10.1016/j.tibs.2019.08.004
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Coding-Gene Coevolution Analysis of Rotavirus Proteins: A Bioinformatics and Statistical Approach.

Abid, Nabil / Chillemi, Giovanni / Salemi, Marco

Genes

2019 Volume 11, Issue 1

Abstract	Rotavirus remains a major cause of diarrhea in infants and young children worldwide. The permanent emergence of new genotypes puts the potential effectiveness of vaccines under serious question. The distribution of unusual genotypes subject to viral fitness is influenced by interactions among viral proteins. The present work aimed at analyzing the genetic constellation and the coevolution of rotavirus coding genes for the available rotavirus genotypes. Seventy-two full genome sequences of different genetic constellations were analyzed using a genetic algorithm. The results revealed an extensive genome-wide covariance network among the 12 viral proteins. Altogether, the emergence of new genotypes represents a challenge to the outcome and success of vaccination and the coevolutionary analysis of rotavirus proteins may boost efforts to better understand the interaction networks of proteins during viral replication/transcription.
MeSH term(s)	Computational Biology/methods ; Evolution, Molecular ; Genotype ; Phylogeny ; Rotavirus/genetics ; Rotavirus/metabolism ; Rotavirus/physiology ; Viral Proteins/genetics ; Virus Replication
Chemical Substances	Viral Proteins
Language	English
Publishing date	2019-12-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes11010028
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Article ; Online: Smyd2 conformational changes in response to p53 binding: role of the C-terminal domain.

Chandramouli, Balasubramanian / Melino, Gerry / Chillemi, Giovanni

Molecular oncology

2019 Volume 13, Issue 6, Page(s) 1450–1461

Abstract: Smyd2 lysine methyltransferase regulates monomethylation of histone and nonhistone lysine residues using S-adenosylmethionine cofactor as the methyl donor. The nonhistone interactors include several tumorigenic targets, including p53. Understanding this ... ...

Abstract	Smyd2 lysine methyltransferase regulates monomethylation of histone and nonhistone lysine residues using S-adenosylmethionine cofactor as the methyl donor. The nonhistone interactors include several tumorigenic targets, including p53. Understanding this interaction would allow the structural principles that underpin Smyd2-mediated p53 methylation to be elucidated. Here, we performed μ-second molecular dynamics (MD) simulations on binary Smyd2-cofactor and ternary Smyd2-cofactor-p53 peptide complexes. We considered both unmethylated and monomethylated p53 peptides (at Lys370 and Lys372). The results indicate that (a) the degree of conformational freedom of the C-terminal domain of Smyd2 is restricted by the presence of the p53 peptide substrate, (b) the Smyd2 C-terminal domain shows distinct dynamic properties when interacting with unmethylated and methylated p53 peptides, and (c) Lys372 methylation confines the p53 peptide conformation, with detectable influence on Lys370 accessibility to the cofactor. These MD results are therefore of relevance for studying the biology of p53 in cancer progression.
MeSH term(s)	Binding Sites ; Histone-Lysine N-Methyltransferase/chemistry ; Histone-Lysine N-Methyltransferase/genetics ; Histone-Lysine N-Methyltransferase/metabolism ; Humans ; Lysine/metabolism ; Molecular Dynamics Simulation ; Protein Binding ; Protein Domains ; Substrate Specificity ; Tumor Suppressor Protein p53/chemistry ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Tumor Suppressor Protein p53 ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43) ; SMYD2 protein, human (EC 2.1.1.43) ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2019-05-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2415106-3
ISSN	1878-0261 ; 1574-7891
ISSN (online)	1878-0261
ISSN	1574-7891
DOI	10.1002/1878-0261.12502
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Article: HECT-Type E3 Ubiquitin Ligases in Cancer.

Bernassola, Francesca / Chillemi, Giovanni / Melino, Gerry

Trends in biochemical sciences

2019 Volume 44, Issue 12, Page(s) 1057–1075

Abstract	Ubiquitination, a post-translational modification that involves a covalent attachment of ubiquitin to a protein substrate, is essential for cellular homeostatic maintenance. At the end of a three-enzyme cascade, E3 ubiquitin ligases (E3s) recruit substrates and promote or directly catalyze ubiquitin transfer to targets. These enzymes largely determine the specificity of the ubiquitination reaction. Genetic alteration, abnormal expression, or dysfunction of E3s account for the occurrence and progression of human cancers. Indeed, excessive degradation of relevant tumor-suppressor molecules and impaired disposal of oncogenic proteins have been linked to tumorigenesis. This review focuses on the emerging roles of HECT-type E3s in tumorigenesis, and emphasizes how perturbations of these enzymes contribute to cancer pathogenesis.
MeSH term(s)	Animals ; Carcinogenesis/genetics ; Carcinogenesis/metabolism ; Humans ; Neoplasms/enzymology ; Neoplasms/genetics ; Proteolysis ; Ubiquitin/genetics ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
Chemical Substances	Ubiquitin ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2019-10-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	194216-5
ISSN	1362-4326 ; 0968-0004 ; 0376-5067
ISSN (online)	1362-4326
ISSN	0968-0004 ; 0376-5067
DOI	10.1016/j.tibs.2019.08.004
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Article ; Online: Muscle transcriptome analysis identifies genes involved in ciliogenesis and the molecular cascade associated with intramuscular fat content in Large White heavy pigs.

Zappaterra, Martina / Gioiosa, Silvia / Chillemi, Giovanni / Zambonelli, Paolo / Davoli, Roberta

PloS one

2020 Volume 15, Issue 5, Page(s) e0233372

Abstract: Intramuscular fat content (IMF) is a complex trait influencing the technological and sensorial features of meat products and determining pork quality. Thus, we aimed at analyzing through RNA-sequencing the Semimembranosus muscle transcriptome of Italian ... ...

Abstract	Intramuscular fat content (IMF) is a complex trait influencing the technological and sensorial features of meat products and determining pork quality. Thus, we aimed at analyzing through RNA-sequencing the Semimembranosus muscle transcriptome of Italian Large White pigs to study the gene networks associated with IMF deposition. Two groups of samples were used; each one was composed of six unrelated pigs with extreme and divergent IMF content (0.67 ± 0.09% in low IMF vs. 6.81 ± 1.17% in high IMF groups) that were chosen from 950 purebred individuals. Paired-end RNA sequences were aligned to Sus scrofa genome assembly 11.1 and gene counts were analyzed using WGCNA and DeSeq2 packages in R environment. Interestingly, among the 58 differentially expressed genes (DEGs), several were related to primary cilia organelles (such as Lebercilin 5 gene), in addition to the genes involved in the regulation of cell differentiation, in the control of RNA-processing, and G-protein and ERK signaling pathways. Together with cilia-related genes, we also found in high IMF pigs an over-expression of the Fibroblast Growth Factor 2 (FGF2) gene, which in other animal species was found to be a regulator of ciliogenesis. Four WGCNA gene modules resulted significantly associated with IMF deposition: grey60 (P = 0.003), darkturquoise (P = 0.022), skyblue1 (P = 0.022), and lavenderblush3 (P = 0.030). The genes in the significant modules confirmed the results obtained for the DEGs, and the analysis with "cytoHubba" indicated genes controlling RNA splicing and cell differentiation as hub genes. Among the complex molecular processes affecting muscle fat depots, genes involved in primary cilia may have an important role, and the transcriptional reprogramming observed in high IMF pigs may be related to an FGF-related molecular cascade and to ciliogenesis, which in the literature have been associated with fibro-adipogenic precursor differentiation.
MeSH term(s)	Adipose Tissue/growth & development ; Animals ; Body Composition ; Cell Differentiation/genetics ; Cilia/genetics ; Fibroblast Growth Factor 2/genetics ; Food Quality ; Gene Expression Profiling ; Gene Regulatory Networks ; Muscle, Skeletal/cytology ; Pork Meat ; RNA Splicing/genetics ; Swine
Chemical Substances	Fibroblast Growth Factor 2 (103107-01-3)
Language	English
Publishing date	2020-05-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0233372
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