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Journal Articles
2022
11.
Falconieri A; Minervini G; Quaglia F; Sartori G; Tosatto S C E
Characterization of the pVHL Interactome in Human Testis Using High-Throughput Library Screening Journal Article
In: Cancers, vol. 14, no. 4, 2022, (Cited by: 1; Open Access).
Abstract | Altmetric | Dimensions | PlumX | Links:
@article{SCOPUS_ID:85124955220,
title = {Characterization of the pVHL Interactome in Human Testis Using High-Throughput Library Screening},
author = {Antonella Falconieri and Giovanni Minervini and Federica Quaglia and Geppo Sartori and Silvio C. E. Tosatto},
url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85124955220&origin=inward},
doi = {10.3390/cancers14041009},
year = {2022},
date = {2022-01-01},
journal = {Cancers},
volume = {14},
number = {4},
publisher = {MDPI},
abstract = {© 2022 by the authors. Licensee MDPI, Basel, Switzerland.Functional impairment of the von Hippel–Lindau tumor suppressor (pVHL) is causative of a familiar increased risk of developing cancer. As an E3 substrate recognition particle, pVHL marks the hypoxia inducible factor 1α (HIF-1α) for degradation in normoxic conditions, thus acting as a key regulator of both acute and chronic cell adaptation to hypoxia. The male mice model carrying VHL gene conditional knockout presents significant abnormalities in testis development paired with defects in spermatogenesis and infertility, indicating that pVHL exerts testis-specific roles. Here we aimed to explore whether pVHL could have a similar role in humans by performing a testis-tissue library screening complemented with in-depth bioinformatics analysis. We identified 55 novel pVHL binding proteins directly involved in spermatogenesis, cell differentiation and reproductive metabolism. In addition, computational investigation of these new interactors identified multiple pVHL-specific binding motifs and demonstrated that somatic mutations described in human cancers reside in these binding regions. Collectively, these findings suggest that, in addition to its role in cancer formation, pVHL may also be pivotal in normal gonadal development in humans.},
note = {Cited by: 1; Open Access},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.Functional impairment of the von Hippel–Lindau tumor suppressor (pVHL) is causative of a familiar increased risk of developing cancer. As an E3 substrate recognition particle, pVHL marks the hypoxia inducible factor 1α (HIF-1α) for degradation in normoxic conditions, thus acting as a key regulator of both acute and chronic cell adaptation to hypoxia. The male mice model carrying VHL gene conditional knockout presents significant abnormalities in testis development paired with defects in spermatogenesis and infertility, indicating that pVHL exerts testis-specific roles. Here we aimed to explore whether pVHL could have a similar role in humans by performing a testis-tissue library screening complemented with in-depth bioinformatics analysis. We identified 55 novel pVHL binding proteins directly involved in spermatogenesis, cell differentiation and reproductive metabolism. In addition, computational investigation of these new interactors identified multiple pVHL-specific binding motifs and demonstrated that somatic mutations described in human cancers reside in these binding regions. Collectively, these findings suggest that, in addition to its role in cancer formation, pVHL may also be pivotal in normal gonadal development in humans.
12.
Fusto A; Cassandrini D; Fiorillo C; Codemo V; Astrea G; D’Amico A; Maggi L; Magri F; Pane M; Tasca G; Sabbatini D; Bello L; Battini R; Bernasconi P; Fattori F; Bertini E S; Comi G; Messina S; Mongini T; Moroni I; Panicucci C; Berardinelli A; Donati A; Nigro V; Pini A; Giannotta M; Dosi C; Ricci E; Mercuri E; Minervini G; Tosatto S; Santorelli F; Bruno C; Pegoraro E
Expanding the clinical-pathological and genetic spectrum of RYR1-related congenital myopathies with cores and minicores: an Italian population study Journal Article
In: Acta Neuropathologica Communications, vol. 10, no. 1, 2022, (Cited by: 9; Open Access).
Abstract | Altmetric | Dimensions | PlumX | Links:
@article{SCOPUS_ID:85128316270,
title = {Expanding the clinical-pathological and genetic spectrum of RYR1-related congenital myopathies with cores and minicores: an Italian population study},
author = {Aurora Fusto and Denise Cassandrini and Chiara Fiorillo and Valentina Codemo and Guja Astrea and Adele D’Amico and Lorenzo Maggi and Francesca Magri and Marika Pane and Giorgio Tasca and Daniele Sabbatini and Luca Bello and Roberta Battini and Pia Bernasconi and Fabiana Fattori and Enrico Silvio Bertini and Giacomo Comi and Sonia Messina and Tiziana Mongini and Isabella Moroni and Chiara Panicucci and Angela Berardinelli and Alice Donati and Vincenzo Nigro and Antonella Pini and Melania Giannotta and Claudia Dosi and Enzo Ricci and Eugenio Mercuri and Giovanni Minervini and Silvio Tosatto and Filippo Santorelli and Claudio Bruno and Elena Pegoraro},
url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85128316270&origin=inward},
doi = {10.1186/s40478-022-01357-0},
year = {2022},
date = {2022-01-01},
journal = {Acta Neuropathologica Communications},
volume = {10},
number = {1},
publisher = {BioMed Central Ltd},
abstract = {© 2022, The Author(s).Mutations in the RYR1 gene, encoding ryanodine receptor 1 (RyR1), are a well-known cause of Central Core Disease (CCD) and Multi-minicore Disease (MmD). We screened a cohort of 153 patients carrying an histopathological diagnosis of core myopathy (cores and minicores) for RYR1 mutation. At least one RYR1 mutation was identified in 69 of them and these patients were further studied. Clinical and histopathological features were collected. Clinical phenotype was highly heterogeneous ranging from asymptomatic or paucisymptomatic hyperCKemia to severe muscle weakness and skeletal deformity with loss of ambulation. Sixty-eight RYR1 mutations, generally missense, were identified, of which 16 were novel. The combined analysis of the clinical presentation, disease progression and the structural bioinformatic analyses of RYR1 allowed to associate some phenotypes to mutations in specific domains. In addition, this study highlighted the structural bioinformatics potential in the prediction of the pathogenicity of RYR1 mutations. Further improvement in the comprehension of genotype–phenotype relationship of core myopathies can be expected in the next future: the actual lack of the human RyR1 crystal structure paired with the presence of large intrinsically disordered regions in RyR1, and the frequent presence of more than one RYR1 mutation in core myopathy patients, require designing novel investigation strategies to completely address RyR1 mutation effect.},
note = {Cited by: 9; Open Access},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
© 2022, The Author(s).Mutations in the RYR1 gene, encoding ryanodine receptor 1 (RyR1), are a well-known cause of Central Core Disease (CCD) and Multi-minicore Disease (MmD). We screened a cohort of 153 patients carrying an histopathological diagnosis of core myopathy (cores and minicores) for RYR1 mutation. At least one RYR1 mutation was identified in 69 of them and these patients were further studied. Clinical and histopathological features were collected. Clinical phenotype was highly heterogeneous ranging from asymptomatic or paucisymptomatic hyperCKemia to severe muscle weakness and skeletal deformity with loss of ambulation. Sixty-eight RYR1 mutations, generally missense, were identified, of which 16 were novel. The combined analysis of the clinical presentation, disease progression and the structural bioinformatic analyses of RYR1 allowed to associate some phenotypes to mutations in specific domains. In addition, this study highlighted the structural bioinformatics potential in the prediction of the pathogenicity of RYR1 mutations. Further improvement in the comprehension of genotype–phenotype relationship of core myopathies can be expected in the next future: the actual lack of the human RyR1 crystal structure paired with the presence of large intrinsically disordered regions in RyR1, and the frequent presence of more than one RYR1 mutation in core myopathy patients, require designing novel investigation strategies to completely address RyR1 mutation effect.
13.
Quaglia F; Salladini E; Carraro M; Minervini G; Tosatto S C E; Mercier P L
SARS-CoV-2 variants preferentially emerge at intrinsically disordered protein sites helping immune evasion Journal Article
In: FEBS Journal, vol. 289, no. 14, pp. 4240-4250, 2022, (Cited by: 27; Open Access).
Abstract | Altmetric | Dimensions | PlumX | Links:
@article{SCOPUS_ID:85124603120,
title = {SARS-CoV-2 variants preferentially emerge at intrinsically disordered protein sites helping immune evasion},
author = {Federica Quaglia and Edoardo Salladini and Marco Carraro and Giovanni Minervini and Silvio C. E. Tosatto and Philippe Le Mercier},
url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85124603120&origin=inward},
doi = {10.1111/febs.16379},
year = {2022},
date = {2022-01-01},
journal = {FEBS Journal},
volume = {289},
number = {14},
pages = {4240-4250},
publisher = {John Wiley and Sons Inc},
abstract = {© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.The SARS-CoV-2 pandemic is maintained by the emergence of successive variants, highlighting the flexibility of the protein sequences of the virus. We show that experimentally determined intrinsically disordered regions (IDRs) are abundant in the SARS-CoV-2 viral proteins, making up to 28% of disorder content for the S1 subunit of spike and up to 51% for the nucleoprotein, with the vast majority of mutations occurring in the 13 major variants mapped to these IDRs. Strikingly, antigenic sites are enriched in IDRs, in the receptor-binding domain (RBD) and in the N-terminal domain (NTD), suggesting a key role of structural flexibility in the antigenicity of the SARS-CoV-2 protein surface. Mutations occurring in the S1 subunit and nucleoprotein (N) IDRs are critical for immune evasion and antibody escape, suggesting potential additional implications for vaccines and monoclonal therapeutic strategies. Overall, this suggests the presence of variable regions on S1 and N protein surfaces, which confer sequence and antigenic flexibility to the virus without altering its protein functions.},
note = {Cited by: 27; Open Access},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.The SARS-CoV-2 pandemic is maintained by the emergence of successive variants, highlighting the flexibility of the protein sequences of the virus. We show that experimentally determined intrinsically disordered regions (IDRs) are abundant in the SARS-CoV-2 viral proteins, making up to 28% of disorder content for the S1 subunit of spike and up to 51% for the nucleoprotein, with the vast majority of mutations occurring in the 13 major variants mapped to these IDRs. Strikingly, antigenic sites are enriched in IDRs, in the receptor-binding domain (RBD) and in the N-terminal domain (NTD), suggesting a key role of structural flexibility in the antigenicity of the SARS-CoV-2 protein surface. Mutations occurring in the S1 subunit and nucleoprotein (N) IDRs are critical for immune evasion and antibody escape, suggesting potential additional implications for vaccines and monoclonal therapeutic strategies. Overall, this suggests the presence of variable regions on S1 and N protein surfaces, which confer sequence and antigenic flexibility to the virus without altering its protein functions.
14.
Catoni C; Poggiana C; Facchinetti A; Pigozzo J; Piccin L; Chiarion-Sileni V; Rosato A; Minervini G; Scaini M C
Investigating the Retained Inhibitory Effect of Cobimetinib against p.P124L Mutated MEK1: A Combined Liquid Biopsy and in Silico Approach Journal Article
In: Cancers, vol. 14, no. 17, 2022, (Cited by: 5; Open Access).
Abstract | Altmetric | Dimensions | PlumX | Links:
@article{SCOPUS_ID:85137888553,
title = {Investigating the Retained Inhibitory Effect of Cobimetinib against p.P124L Mutated MEK1: A Combined Liquid Biopsy and in Silico Approach},
author = {Cristina Catoni and Cristina Poggiana and Antonella Facchinetti and Jacopo Pigozzo and Luisa Piccin and Vanna Chiarion-Sileni and Antonio Rosato and Giovanni Minervini and Maria Chiara Scaini},
url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85137888553&origin=inward},
doi = {10.3390/cancers14174153},
year = {2022},
date = {2022-01-01},
journal = {Cancers},
volume = {14},
number = {17},
publisher = {MDPI},
abstract = {© 2022 by the authors.The systemic treatment of metastatic melanoma has radically changed, due to an improvement in the understanding of its genetic landscape and the advent of targeted therapy. However, the response to BRAF/MEK inhibitors is transitory, and big efforts were made to identify the mechanisms underlying the resistance. We exploited a combined approach, encompassing liquid biopsy analysis and molecular dynamics simulation, for tracking tumor evolution, and in parallel defining the best treatment option. The samples at different time points were collected from a BRAF-mutant melanoma patient who developed an early resistance to dabrafenib/trametinib. The analysis of the circulating tumor DNA (ctDNA) identified the MEK1 p.P124L mutation that confers resistance to trametinib. With an in silico modeling, we identified cobimetinib as an alternative MEK inhibitor, and consequently suggested a therapy switch to vemurafenib/cobimetinib. The patient response was followed by ctDNA tracking and circulating melanoma cell (CMC) count. The cobimetinib administration led to an important reduction in the BRAF p.V600E and MEK1 p.P124L allele fractions and in the CMC number, features suggestive of a putative response. In summary, this study emphasizes the usefulness of a liquid biopsy-based approach combined with in silico simulation, to track real-time tumor evolution while assessing the best treatment option.},
note = {Cited by: 5; Open Access},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
© 2022 by the authors.The systemic treatment of metastatic melanoma has radically changed, due to an improvement in the understanding of its genetic landscape and the advent of targeted therapy. However, the response to BRAF/MEK inhibitors is transitory, and big efforts were made to identify the mechanisms underlying the resistance. We exploited a combined approach, encompassing liquid biopsy analysis and molecular dynamics simulation, for tracking tumor evolution, and in parallel defining the best treatment option. The samples at different time points were collected from a BRAF-mutant melanoma patient who developed an early resistance to dabrafenib/trametinib. The analysis of the circulating tumor DNA (ctDNA) identified the MEK1 p.P124L mutation that confers resistance to trametinib. With an in silico modeling, we identified cobimetinib as an alternative MEK inhibitor, and consequently suggested a therapy switch to vemurafenib/cobimetinib. The patient response was followed by ctDNA tracking and circulating melanoma cell (CMC) count. The cobimetinib administration led to an important reduction in the BRAF p.V600E and MEK1 p.P124L allele fractions and in the CMC number, features suggestive of a putative response. In summary, this study emphasizes the usefulness of a liquid biopsy-based approach combined with in silico simulation, to track real-time tumor evolution while assessing the best treatment option.
15.
Quaglia F; Meszáros B; Salladini E; Hatos A; Pancsa R; Chemes L B; Pajkos M; Lazar T; Peña-Díaz S; Santos J; Ács V; Farahi N; Fichó E; Aspromonte M C; Bassot C; Chasapi A; Davey N E; Davidović R; Dobson L; Elofsson A; Erdos G; Gaudet P; Giglio M; Glavina J; Iserte J; Iglesias V; Kálmán Z; Lambrughi M; Leonardi E; Longhi S; Macedo-Ribeiro S; Maiani E; Marchetti J; Marino-Buslje C; Meszáros A; Monzon A M; Minervini G; Nadendla S; Nilsson J F; Novotný M; Ouzounis C A; Palopoli N; Papaleo E; Pereira P J B; Pozzati G; Promponas V J; Pujols J; Rocha A C S; Salas M; Sawicki L R; Schad E; Shenoy A; Szaniszló T; Tsirigos K D; Veljkovic N; Parisi G; Ventura S; Dosztányi Z; Tompa P; Tosatto S C E; Piovesan D
DisProt in 2022: Improved quality and accessibility of protein intrinsic disorder annotation Journal Article
In: Nucleic Acids Research, vol. 50, no. D1, pp. D480-D487, 2022, (Cited by: 123; Open Access).
Abstract | Altmetric | Dimensions | PlumX | Links:
@article{SCOPUS_ID:85125157608,
title = {DisProt in 2022: Improved quality and accessibility of protein intrinsic disorder annotation},
author = {Federica Quaglia and Bálint Meszáros and Edoardo Salladini and András Hatos and Rita Pancsa and Lucía B. Chemes and Mátyás Pajkos and Tamas Lazar and Samuel Peña-Díaz and Jaime Santos and Veronika Ács and Nazanin Farahi and Erzsebet Fichó and Maria Cristina Aspromonte and Claudio Bassot and Anastasia Chasapi and Norman E. Davey and Radoslav Davidović and Laszlo Dobson and Arne Elofsson and Gábor Erdos and Pascale Gaudet and Michelle Giglio and Juliana Glavina and Javier Iserte and Valentín Iglesias and Zsófia Kálmán and Matteo Lambrughi and Emanuela Leonardi and Sonia Longhi and Sandra Macedo-Ribeiro and Emiliano Maiani and Julia Marchetti and Cristina Marino-Buslje and Attila Meszáros and Alexander Miguel Monzon and Giovanni Minervini and Suvarna Nadendla and Juliet F. Nilsson and Marian Novotný and Christos A. Ouzounis and Nicolás Palopoli and Elena Papaleo and Pedro Jose Barbosa Pereira and Gabriele Pozzati and Vasilis J. Promponas and Jordi Pujols and Alma Carolina Sanchez Rocha and Martin Salas and Luciana Rodriguez Sawicki and Eva Schad and Aditi Shenoy and Tamás Szaniszló and Konstantinos D. Tsirigos and Nevena Veljkovic and Gustavo Parisi and Salvador Ventura and Zsuzsanna Dosztányi and Peter Tompa and Silvio C. E. Tosatto and Damiano Piovesan},
url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85125157608&origin=inward},
doi = {10.1093/nar/gkab1082},
year = {2022},
date = {2022-01-01},
journal = {Nucleic Acids Research},
volume = {50},
number = {D1},
pages = {D480-D487},
publisher = {Oxford University Press},
abstract = {© 2022 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.The Database of Intrinsically Disordered Proteins (DisProt, URL: https://disprot.org) is the major repository of manually curated annotations of intrinsically disordered proteins and regions from the literature. We report here recent updates of DisProt version 9, including a restyled web interface, refactored Intrinsically Disordered Proteins Ontology (IDPO), improvements in the curation process and significant content growth of around 30%. Higher quality and consistency of annotations is provided by a newly implemented reviewing process and training of curators. The increased curation capacity is fostered by the integration of DisProt with APICURON, a dedicated resource for the proper attribution and recognition of biocuration efforts. Better interoperability is provided through the adoption of the Minimum Information About Disorder (MIADE) standard, an active collaboration with the Gene Ontology (GO) and Evidence and Conclusion Ontology (ECO) consortia and the support of the ELIXIR infrastructure.},
note = {Cited by: 123; Open Access},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
© 2022 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.The Database of Intrinsically Disordered Proteins (DisProt, URL: https://disprot.org) is the major repository of manually curated annotations of intrinsically disordered proteins and regions from the literature. We report here recent updates of DisProt version 9, including a restyled web interface, refactored Intrinsically Disordered Proteins Ontology (IDPO), improvements in the curation process and significant content growth of around 30%. Higher quality and consistency of annotations is provided by a newly implemented reviewing process and training of curators. The increased curation capacity is fostered by the integration of DisProt with APICURON, a dedicated resource for the proper attribution and recognition of biocuration efforts. Better interoperability is provided through the adoption of the Minimum Information About Disorder (MIADE) standard, an active collaboration with the Gene Ontology (GO) and Evidence and Conclusion Ontology (ECO) consortia and the support of the ELIXIR infrastructure.
16.
Leonardi E; Savojardo C; Minervini G
Molecular Effects of Mutations in Human Genetic Diseases Journal Article
In: International Journal of Molecular Sciences, vol. 23, no. 12, 2022, (Cited by: 0; Open Access).
Altmetric | Dimensions | PlumX | Links:
@article{SCOPUS_ID:85131521999,
title = {Molecular Effects of Mutations in Human Genetic Diseases},
author = {Emanuela Leonardi and Castrense Savojardo and Giovanni Minervini},
url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85131521999&origin=inward},
doi = {10.3390/ijms23126408},
year = {2022},
date = {2022-01-01},
journal = {International Journal of Molecular Sciences},
volume = {23},
number = {12},
publisher = {MDPI},
note = {Cited by: 0; Open Access},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2021
17.
Laquatra C; Sanchez-Martin C; Dinarello A; Cannino G; Minervini G; Moroni E; Schiavone M; Tosatto S; Argenton F; Colombo G; Bernardi P; Masgras I; Rasola A
HIF1α-dependent induction of the mitochondrial chaperone TRAP1 regulates bioenergetic adaptations to hypoxia Journal Article
In: Cell Death and Disease, vol. 12, no. 5, 2021, (Cited by: 24; Open Access).
Abstract | Altmetric | Dimensions | PlumX | Links:
@article{SCOPUS_ID:85105148823,
title = {HIF1α-dependent induction of the mitochondrial chaperone TRAP1 regulates bioenergetic adaptations to hypoxia},
author = {Claudio Laquatra and Carlos Sanchez-Martin and Alberto Dinarello and Giuseppe Cannino and Giovanni Minervini and Elisabetta Moroni and Marco Schiavone and Silvio Tosatto and Francesco Argenton and Giorgio Colombo and Paolo Bernardi and Ionica Masgras and Andrea Rasola},
url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85105148823&origin=inward},
doi = {10.1038/s41419-021-03716-6},
year = {2021},
date = {2021-01-01},
journal = {Cell Death and Disease},
volume = {12},
number = {5},
publisher = {Springer Nature},
abstract = {© 2021, The Author(s).The mitochondrial paralog of the Hsp90 chaperone family TRAP1 is often induced in tumors, but the mechanisms controlling its expression, as well as its physiological functions remain poorly understood. Here, we find that TRAP1 is highly expressed in the early stages of Zebrafish development, and its ablation delays embryogenesis while increasing mitochondrial respiration of fish larvae. TRAP1 expression is enhanced by hypoxic conditions both in developing embryos and in cancer models of Zebrafish and mammals. The TRAP1 promoter contains evolutionary conserved hypoxic responsive elements, and HIF1α stabilization increases TRAP1 levels. TRAP1 inhibition by selective compounds or by genetic knock-out maintains a high level of respiration in Zebrafish embryos after exposure to hypoxia. Our data identify TRAP1 as a primary regulator of mitochondrial bioenergetics in highly proliferating cells following reduction in oxygen tension and HIF1α stabilization.},
note = {Cited by: 24; Open Access},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
© 2021, The Author(s).The mitochondrial paralog of the Hsp90 chaperone family TRAP1 is often induced in tumors, but the mechanisms controlling its expression, as well as its physiological functions remain poorly understood. Here, we find that TRAP1 is highly expressed in the early stages of Zebrafish development, and its ablation delays embryogenesis while increasing mitochondrial respiration of fish larvae. TRAP1 expression is enhanced by hypoxic conditions both in developing embryos and in cancer models of Zebrafish and mammals. The TRAP1 promoter contains evolutionary conserved hypoxic responsive elements, and HIF1α stabilization increases TRAP1 levels. TRAP1 inhibition by selective compounds or by genetic knock-out maintains a high level of respiration in Zebrafish embryos after exposure to hypoxia. Our data identify TRAP1 as a primary regulator of mitochondrial bioenergetics in highly proliferating cells following reduction in oxygen tension and HIF1α stabilization.
18.
Dassie F; Lorusso R; Benavides-Varela S; Milan G; Favaretto F; Callus E; Cagnin S; Reggiani F; Minervini G; Tosatto S; Vettor R; Semenza C; Maffei P
Neurocognitive assessment and DNA sequencing expand the phenotype and genotype spectrum of Alström syndrome Journal Article
In: American Journal of Medical Genetics, Part A, vol. 185, no. 3, pp. 732-742, 2021, (Cited by: 6).
Abstract | Altmetric | Dimensions | PlumX | Links:
@article{SCOPUS_ID:85099072292,
title = {Neurocognitive assessment and DNA sequencing expand the phenotype and genotype spectrum of Alström syndrome},
author = {Francesca Dassie and Riccardina Lorusso and Silvia Benavides-Varela and Gabriella Milan and Francesca Favaretto and Edward Callus and Stefano Cagnin and Francesco Reggiani and Giovanni Minervini and Silvio Tosatto and Roberto Vettor and Carlo Semenza and Pietro Maffei},
url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85099072292&origin=inward},
doi = {10.1002/ajmg.a.62029},
year = {2021},
date = {2021-01-01},
journal = {American Journal of Medical Genetics, Part A},
volume = {185},
number = {3},
pages = {732-742},
publisher = {John Wiley and Sons Inc},
abstract = {© 2021 Wiley Periodicals LLCAlström syndrome (OMIM#203800) is an ultra-rare autosomal recessive monogenic disease presenting pathogenic variants in ALMS1 (chromosome 2p13). It is characterized by early onset of blindness, hearing loss and systemic comorbidities, with delayed development without cognitive impairment. We aimed to investigate the cognitive functions and describe new pathogenic variants in Alström syndrome patients. Nineteen patients (13 adults, 6 children) underwent a thorough clinical, genetic, laboratory, instrumental, and neurocognitive assessment. Six new pathogenic variants in ALMS1 including the first described in exon 6 were identified. Four patients displayed a “mild phenotype” characterized by slow disease onset or absence of complications, including childhood obesity and association with at least one pathogenic variant in exon 5 or 6. At neurocognitive testing, a significant proportion of patients had deficits in three neurocognitive domains: similarities, phonological memory, and apraxia. In particular, 53% of patients showed difficulties in the auditory working memory test. We found ideomotor and buccofacial apraxia in 74% of patients. “Mild phenotype” patients performed better on auditory working memory and ideomotor apraxia test than “typical phenotype” ones (91.9 + 16.3% vs. 41.7 + 34.5% of correct answers},
note = {Cited by: 6},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
© 2021 Wiley Periodicals LLCAlström syndrome (OMIM#203800) is an ultra-rare autosomal recessive monogenic disease presenting pathogenic variants in ALMS1 (chromosome 2p13). It is characterized by early onset of blindness, hearing loss and systemic comorbidities, with delayed development without cognitive impairment. We aimed to investigate the cognitive functions and describe new pathogenic variants in Alström syndrome patients. Nineteen patients (13 adults, 6 children) underwent a thorough clinical, genetic, laboratory, instrumental, and neurocognitive assessment. Six new pathogenic variants in ALMS1 including the first described in exon 6 were identified. Four patients displayed a “mild phenotype” characterized by slow disease onset or absence of complications, including childhood obesity and association with at least one pathogenic variant in exon 5 or 6. At neurocognitive testing, a significant proportion of patients had deficits in three neurocognitive domains: similarities, phonological memory, and apraxia. In particular, 53% of patients showed difficulties in the auditory working memory test. We found ideomotor and buccofacial apraxia in 74% of patients. “Mild phenotype” patients performed better on auditory working memory and ideomotor apraxia test than “typical phenotype” ones (91.9 + 16.3% vs. 41.7 + 34.5% of correct answers
19.
Necci M; Piovesan D; Hoque M T; Walsh I; Iqbal S; Vendruscolo M; Sormanni P; Wang C; Raimondi D; Sharma R; Zhou Y; Litfin T; Galzitskaya O V; Lobanov M Yu; Vranken W; Wallner B; Mirabello C; Malhis N; Dosztányi Z; Erdős G; Mészáros B; Gao J; Wang K; Hu G; Wu Z; Sharma A; Hanson J; Paliwal K; Callebaut I; Bitard-Feildel T; Orlando G; Peng Z; Xu J; Wang S; Jones D T; Cozzetto D; Meng F; Yan J; Gsponer J; Cheng J; Wu T; Kurgan L; Promponas V J; Tamana S; Marino-Buslje C; Martínez-Pérez E; Chasapi A; Ouzounis C; Dunker A K; Kajava A V; Leclercq J Y; Aykac-Fas B; Lambrughi M; Maiani E; Papaleo E; Chemes L B; Álvarez L; González-Foutel N S; Iglesias V; Pujols J; Ventura S; Palopoli N; Benítez G I; Parisi G; Bassot C; Elofsson A; Govindarajan S; Lamb J; Salvatore M; Hatos A; Monzon A M; Bevilacqua M; Mičetić I; Minervini G; Paladin L; Quaglia F; Leonardi E; Davey N; Horvath T; Kovacs O P; Murvai N; Pancsa R; Schad E; Szabo B; Tantos A; Macedo-Ribeiro S; Manso J A; Pereira P J B; Davidović R; Veljkovic N; Hajdu-Soltész B; Pajkos M; Szaniszló T; Guharoy M; Lazar T; Macossay-Castillo M; Tompa P; Tosatto S C E
Critical assessment of protein intrinsic disorder prediction Journal Article
In: Nature Methods, vol. 18, no. 5, pp. 472-481, 2021, (Cited by: 221; Open Access).
Abstract | Altmetric | Dimensions | PlumX | Links:
@article{SCOPUS_ID:85104988931,
title = {Critical assessment of protein intrinsic disorder prediction},
author = {Marco Necci and Damiano Piovesan and Md Tamjidul Hoque and Ian Walsh and Sumaiya Iqbal and Michele Vendruscolo and Pietro Sormanni and Chen Wang and Daniele Raimondi and Ronesh Sharma and Yaoqi Zhou and Thomas Litfin and Oxana Valerianovna Galzitskaya and Michail Yu. Lobanov and Wim Vranken and Björn Wallner and Claudio Mirabello and Nawar Malhis and Zsuzsanna Dosztányi and Gábor Erdős and Bálint Mészáros and Jianzhao Gao and Kui Wang and Gang Hu and Zhonghua Wu and Alok Sharma and Jack Hanson and Kuldip Paliwal and Isabelle Callebaut and Tristan Bitard-Feildel and Gabriele Orlando and Zhenling Peng and Jinbo Xu and Sheng Wang and David T. Jones and Domenico Cozzetto and Fanchi Meng and Jing Yan and Jörg Gsponer and Jianlin Cheng and Tianqi Wu and Lukasz Kurgan and Vasilis J. Promponas and Stella Tamana and Cristina Marino-Buslje and Elizabeth Martínez-Pérez and Anastasia Chasapi and Christos Ouzounis and A. Keith Dunker and Andrey V. Kajava and Jeremy Y. Leclercq and Burcu Aykac-Fas and Matteo Lambrughi and Emiliano Maiani and Elena Papaleo and Lucia Beatriz Chemes and Lucía Álvarez and Nicolás S. González-Foutel and Valentin Iglesias and Jordi Pujols and Salvador Ventura and Nicolás Palopoli and Guillermo Ignacio Benítez and Gustavo Parisi and Claudio Bassot and Arne Elofsson and Sudha Govindarajan and John Lamb and Marco Salvatore and András Hatos and Alexander Miguel Monzon and Martina Bevilacqua and Ivan Mičetić and Giovanni Minervini and Lisanna Paladin and Federica Quaglia and Emanuela Leonardi and Norman Davey and Tamas Horvath and Orsolya Panna Kovacs and Nikoletta Murvai and Rita Pancsa and Eva Schad and Beata Szabo and Agnes Tantos and Sandra Macedo-Ribeiro and Jose Antonio Manso and Pedro José Barbosa Pereira and Radoslav Davidović and Nevena Veljkovic and Borbála Hajdu-Soltész and Mátyás Pajkos and Tamás Szaniszló and Mainak Guharoy and Tamas Lazar and Mauricio Macossay-Castillo and Peter Tompa and Silvio C. E. Tosatto},
url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85104988931&origin=inward},
doi = {10.1038/s41592-021-01117-3},
year = {2021},
date = {2021-01-01},
journal = {Nature Methods},
volume = {18},
number = {5},
pages = {472-481},
publisher = {Nature Research},
abstract = {© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.Intrinsically disordered proteins, defying the traditional protein structure–function paradigm, are a challenge to study experimentally. Because a large part of our knowledge rests on computational predictions, it is crucial that their accuracy is high. The Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment was established as a community-based blind test to determine the state of the art in prediction of intrinsically disordered regions and the subset of residues involved in binding. A total of 43 methods were evaluated on a dataset of 646 proteins from DisProt. The best methods use deep learning techniques and notably outperform physicochemical methods. The top disorder predictor has Fmax = 0.483 on the full dataset and Fmax = 0.792 following filtering out of bona fide structured regions. Disordered binding regions remain hard to predict, with Fmax = 0.231. Interestingly, computing times among methods can vary by up to four orders of magnitude.},
note = {Cited by: 221; Open Access},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.Intrinsically disordered proteins, defying the traditional protein structure–function paradigm, are a challenge to study experimentally. Because a large part of our knowledge rests on computational predictions, it is crucial that their accuracy is high. The Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment was established as a community-based blind test to determine the state of the art in prediction of intrinsically disordered regions and the subset of residues involved in binding. A total of 43 methods were evaluated on a dataset of 646 proteins from DisProt. The best methods use deep learning techniques and notably outperform physicochemical methods. The top disorder predictor has Fmax = 0.483 on the full dataset and Fmax = 0.792 following filtering out of bona fide structured regions. Disordered binding regions remain hard to predict, with Fmax = 0.231. Interestingly, computing times among methods can vary by up to four orders of magnitude.
20.
Galber C; Minervini G; Cannino G; Boldrin F; Petronilli V; Tosatto S; Lippe G; Giorgio V
The f subunit of human ATP synthase is essential for normal mitochondrial morphology and permeability transition Journal Article
In: Cell Reports, vol. 35, no. 6, 2021, (Cited by: 31; Open Access).
Abstract | Altmetric | Dimensions | PlumX | Links:
@article{SCOPUS_ID:85105603447,
title = {The f subunit of human ATP synthase is essential for normal mitochondrial morphology and permeability transition},
author = {Chiara Galber and Giovanni Minervini and Giuseppe Cannino and Francesco Boldrin and Valeria Petronilli and Silvio Tosatto and Giovanna Lippe and Valentina Giorgio},
url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85105603447&origin=inward},
doi = {10.1016/j.celrep.2021.109111},
year = {2021},
date = {2021-01-01},
journal = {Cell Reports},
volume = {35},
number = {6},
publisher = {Elsevier B.V.},
abstract = {© 2021 The AuthorsThe f subunit is localized at the base of the ATP synthase peripheral stalk. Its function in the human enzyme is poorly characterized. Because full disruption of its ATP5J2 gene with the CRISPR-Cas9 strategy in the HAP1 human model has been shown to cause alterations in the amounts of other ATP synthase subunits, here we investigated the role of the f subunit in HeLa cells by regulating its levels through RNA interference. We confirm the role of the f subunit in ATP synthase dimer stability and observe that its downregulation per se does not alter the amounts of the other enzyme subunits or ATP synthase synthetic/hydrolytic activity. We show that downregulation of the f subunit causes abnormal crista organization and decreases permeability transition pore (PTP) size, whereas its re-expression in f subunit knockdown cells rescues mitochondrial morphology and PTP-dependent swelling.},
note = {Cited by: 31; Open Access},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
© 2021 The AuthorsThe f subunit is localized at the base of the ATP synthase peripheral stalk. Its function in the human enzyme is poorly characterized. Because full disruption of its ATP5J2 gene with the CRISPR-Cas9 strategy in the HAP1 human model has been shown to cause alterations in the amounts of other ATP synthase subunits, here we investigated the role of the f subunit in HeLa cells by regulating its levels through RNA interference. We confirm the role of the f subunit in ATP synthase dimer stability and observe that its downregulation per se does not alter the amounts of the other enzyme subunits or ATP synthase synthetic/hydrolytic activity. We show that downregulation of the f subunit causes abnormal crista organization and decreases permeability transition pore (PTP) size, whereas its re-expression in f subunit knockdown cells rescues mitochondrial morphology and PTP-dependent swelling.
