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  1. Article ; Online: Pediatrician and parental evaluation of child neurodevelopment at 2 years of age.

    Segre, Giulia / Clavenna, Antonio / Roberti, Elisa / Scarpellini, Francesca / Cartabia, Massimo / Pandolfini, Chiara / Tessarollo, Valeria / Costantino, Ilaria / Bonati, Maurizio

    BMC pediatrics

    2024  Volume 24, Issue 1, Page(s) 137

    Abstract: Background: The early identification of infants with a risk for neurodevelopmental disorders in the first few years of life is essential for better developmental outcomes. Screenings should be carried out by combining the family pediatricians' and ... ...

    Abstract Background: The early identification of infants with a risk for neurodevelopmental disorders in the first few years of life is essential for better developmental outcomes. Screenings should be carried out by combining the family pediatricians' and parents' perspectives, the two fundamental sources of information on children's health. The present study has three aims: (a) to test the feasibility of parent-report instruments to detect warning signs in their children's development; (b) to ascertain whether there is an agreement between the family pediatricians' (FP) clinical judgments of warning signs and the parental perceptions; (c) to determine whether there is a link between parents' distress and child development.
    Methods: Within the NASCITA birth cohort, in addition to the family pediatrician's clinical evaluation with routine tools, the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) was completed by parents to assess the child's language, social skills, behavior, and sensory areas. Parents were also asked to complete the Parenting Stress Index, Short Form (PSI-SF) to verify the magnitude of stress in the parent-child system. Univariate and multivariate analyses were performed to evaluate the association between child and parental characteristics and the presence of warning signs.
    Results: The follow-up assessment was completed for 435 infants: 69 (15.8%) presented warning signs: 43 in the pediatrician's assessment and 36 in the M-CHAT-R (10 in both). A total of 16 children (14 with warning signs) received a diagnosis after a specialist evaluation. Being male (OR 2.46, 95%CI: 1.23-4.91) and having sleep disorders (OR 2.43, 95% CI 1.17-5.04) was associated with a greater likelihood of warning signs in the multivariate analysis, while reading aloud was a protective factor (not exposed versus exposed (OR = 3.14; 95% CI 1.60-6.17). For 73 children (18.4%), at least one parent tested positive for PSI-SF. An increased prevalence of parental distress was observed in children with warning signs (OR 2.36, 95% CI 1.27-4.37).
    Conclusions: Integrating physician and parental perspectives during well-child visits and in clinical practice appears feasible and can improve the identification of children at risk of developmental disorders.
    MeSH term(s) Infant ; Humans ; Male ; Female ; Parents ; Child Development ; Autistic Disorder ; Neurodevelopmental Disorders/diagnosis ; Neurodevelopmental Disorders/etiology ; Pediatricians
    Language English
    Publishing date 2024-02-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041342-7
    ISSN 1471-2431 ; 1471-2431
    ISSN (online) 1471-2431
    ISSN 1471-2431
    DOI 10.1186/s12887-024-04616-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Regulating the regulators: the post-translational code of class I HDAC1 and HDAC2.

    Segré, Chiara V / Chiocca, Susanna

    Journal of biomedicine & biotechnology

    2010  Volume 2011, Page(s) 690848

    Abstract: Class I histone deacetylases (HDACs) are cellular enzymes expressed in many tissues and play crucial roles in differentiation, proliferation, and cancer. HDAC1 and HDAC2 in particular are highly homologous proteins that show redundant or specific roles ... ...

    Abstract Class I histone deacetylases (HDACs) are cellular enzymes expressed in many tissues and play crucial roles in differentiation, proliferation, and cancer. HDAC1 and HDAC2 in particular are highly homologous proteins that show redundant or specific roles in different cell types or in response to different stimuli and signaling pathways. The molecular details of this dual regulation are largely unknown. HDAC1 and HDAC2 are not only protein modifiers, but are in turn regulated by post-translational modifications (PTMs): phosphorylation, acetylation, ubiquitination, SUMOylation, nitrosylation, and carbonylation. Some of these PTMs occur and crosstalk specifically on HDAC1 or HDAC2, creating a rational "code" for a differential, context-related regulation. The global comprehension of this PTM code is central for dissecting the role of single HDAC1 and HDAC2 in physiology and pathology.
    MeSH term(s) Animals ; Histone Deacetylase 1/metabolism ; Histone Deacetylase 2/metabolism ; Humans ; Mice ; Protein Processing, Post-Translational ; Signal Transduction
    Chemical Substances Histone Deacetylase 1 (EC 3.5.1.98) ; Histone Deacetylase 2 (EC 3.5.1.98)
    Language English
    Publishing date 2010-12-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2052552-7
    ISSN 1110-7251 ; 1110-7243
    ISSN (online) 1110-7251
    ISSN 1110-7243
    DOI 10.1155/2011/690848
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Viral manipulation of cellular protein conjugation pathways: The SUMO lesson.

    Mattoscio, Domenico / Segré, Chiara V / Chiocca, Susanna

    World journal of virology

    2013  Volume 2, Issue 2, Page(s) 79–90

    Abstract: Small ubiquitin-like modifier (SUMO)ylation is a key post-translational modification mechanism that controls the function of a plethora of proteins and biological processes. Given its central regulatory role, it is not surprising that it is widely ... ...

    Abstract Small ubiquitin-like modifier (SUMO)ylation is a key post-translational modification mechanism that controls the function of a plethora of proteins and biological processes. Given its central regulatory role, it is not surprising that it is widely exploited by viruses. A number of viral proteins are known to modify and/or be modified by the SUMOylation system to exert their function, to create a cellular environment more favorable for virus survival and propagation, and to prevent host antiviral responses. Since the SUMO pathway is a multi-step cascade, viral proteins engage with it at many levels, to advance and favor each stage of a typical infection cycle: replication, viral assembly and immune evasion. Here we review the current knowledge on the interplay between the host SUMO system and viral lifecycle.
    Language English
    Publishing date 2013-07-01
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2829019-7
    ISSN 2220-3249
    ISSN 2220-3249
    DOI 10.5501/wjv.v2.i2.79
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Regulating the Regulators

    Chiara V. Segré / Susanna Chiocca

    Journal of Biomedicine and Biotechnology, Vol

    The Post-Translational Code of Class I HDAC1 and HDAC2

    2011  Volume 2011

    Abstract: Class I histone deacetylases (HDACs) are cellular enzymes expressed in many tissues and play crucial roles in differentiation, proliferation, and cancer. HDAC1 and HDAC2 in particular are highly homologous proteins that show redundant or specific roles ... ...

    Abstract Class I histone deacetylases (HDACs) are cellular enzymes expressed in many tissues and play crucial roles in differentiation, proliferation, and cancer. HDAC1 and HDAC2 in particular are highly homologous proteins that show redundant or specific roles in different cell types or in response to different stimuli and signaling pathways. The molecular details of this dual regulation are largely unknown. HDAC1 and HDAC2 are not only protein modifiers, but are in turn regulated by post-translational modifications (PTMs): phosphorylation, acetylation, ubiquitination, SUMOylation, nitrosylation, and carbonylation. Some of these PTMs occur and crosstalk specifically on HDAC1 or HDAC2, creating a rational “code” for a differential, context-related regulation. The global comprehension of this PTM code is central for dissecting the role of single HDAC1 and HDAC2 in physiology and pathology.
    Keywords Biotechnology ; TP248.13-248.65 ; Chemical technology ; TP1-1185 ; Technology ; T ; DOAJ:Biotechnology ; DOAJ:Life Sciences ; DOAJ:Biology and Life Sciences
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: Inhibition of the SUMO pathway by Gam1.

    Pozzebon, Mariaelena / Segré, Chiara V / Chiocca, Susanna

    Methods in molecular biology (Clifton, N.J.)

    2009  Volume 497, Page(s) 285–301

    Abstract: We have previously demonstrated that Gam1, an avian adenoviral protein inhibits sumoylation. By counteracting the SUMO pathway, Gam1 has a significant impact on virus-infected cells, but in isolation the inhibitory effects of the Gam1 protein can be ... ...

    Abstract We have previously demonstrated that Gam1, an avian adenoviral protein inhibits sumoylation. By counteracting the SUMO pathway, Gam1 has a significant impact on virus-infected cells, but in isolation the inhibitory effects of the Gam1 protein can be exploited to intentionally manipulate the SUMO system in vivo or in vitro. Here we discuss in detail the techniques we use to inhibit the SUMO pathway using the Gam1 protein.
    MeSH term(s) Animals ; Cells, Cultured ; Clinical Laboratory Techniques ; Humans ; Protein Processing, Post-Translational/drug effects ; Recombinant Proteins/isolation & purification ; Recombinant Proteins/pharmacology ; SUMO-1 Protein/antagonists & inhibitors ; SUMO-1 Protein/metabolism ; Signal Transduction/drug effects ; Viral Proteins/isolation & purification ; Viral Proteins/pharmacology
    Chemical Substances CELO protein, adenovirus ; Recombinant Proteins ; SUMO-1 Protein ; Viral Proteins
    Language English
    Publishing date 2009
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ISSN 1064-3745
    ISSN 1064-3745
    DOI 10.1007/978-1-59745-566-4_19
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Dynamic phosphorylation of Histone Deacetylase 1 by Aurora kinases during mitosis regulates zebrafish embryos development.

    Loponte, Sara / Segré, Chiara V / Senese, Silvia / Miccolo, Claudia / Santaguida, Stefano / Deflorian, Gianluca / Citro, Simona / Mattoscio, Domenico / Pisati, Federica / Moser, Mirjam A / Visintin, Rosella / Seiser, Christian / Chiocca, Susanna

    Scientific reports

    2016  Volume 6, Page(s) 30213

    Abstract: Histone deacetylases (HDACs) catalyze the removal of acetyl molecules from histone and non-histone substrates playing important roles in chromatin remodeling and control of gene expression. Class I HDAC1 is a critical regulator of cell cycle progression, ...

    Abstract Histone deacetylases (HDACs) catalyze the removal of acetyl molecules from histone and non-histone substrates playing important roles in chromatin remodeling and control of gene expression. Class I HDAC1 is a critical regulator of cell cycle progression, cellular proliferation and differentiation during development; it is also regulated by many post-translational modifications (PTMs). Herein we characterize a new mitosis-specific phosphorylation of HDAC1 driven by Aurora kinases A and B. We show that this phosphorylation affects HDAC1 enzymatic activity and it is critical for the maintenance of a proper proliferative and developmental plan in a complex organism. Notably, we find that Aurora-dependent phosphorylation of HDAC1 regulates histone acetylation by modulating the expression of genes directly involved in the developing zebrafish central nervous system. Our data represent a step towards the comprehension of HDAC1 regulation by its PTM code, with important implications in unravelling its roles both in physiology and pathology.
    Language English
    Publishing date 2016-07-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep30213
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: A monoclonal antibody specific for prophase phosphorylation of histone deacetylase 1: a readout for early mitotic cells.

    Segré, Chiara V / Senese, Silvia / Loponte, Sara / Santaguida, Stefano / Soffientini, Paolo / Grigorean, Gabriela / Cinquanta, Mario / Ossolengo, Giuseppe / Seiser, Christian / Chiocca, Susanna

    mAbs

    2016  Volume 8, Issue 1, Page(s) 37–42

    Abstract: Histone deacetylases (HDACs) are modification enzymes that regulate a plethora of biological processes. HDAC1, a crucial epigenetic modifier, is deregulated in cancer and subjected to a variety of post-translational modifications. Here, we describe the ... ...

    Abstract Histone deacetylases (HDACs) are modification enzymes that regulate a plethora of biological processes. HDAC1, a crucial epigenetic modifier, is deregulated in cancer and subjected to a variety of post-translational modifications. Here, we describe the generation of a new monoclonal antibody that specifically recognizes a novel highly dynamic prophase phosphorylation of serine 406-HDAC1, providing a powerful tool for detecting early mitotic cells.
    MeSH term(s) Animals ; Antibodies, Monoclonal, Murine-Derived/chemistry ; Histone Deacetylase 1/chemistry ; Histone Deacetylase 1/metabolism ; Humans ; Mice ; Phosphoproteins/chemistry ; Phosphoproteins/metabolism ; Phosphorylation ; Prophase
    Chemical Substances Antibodies, Monoclonal, Murine-Derived ; Phosphoproteins ; HDAC1 protein, human (EC 3.5.1.98) ; Histone Deacetylase 1 (EC 3.5.1.98)
    Language English
    Publishing date 2016
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1942-0870
    ISSN (online) 1942-0870
    DOI 10.1080/19420862.2015.1098795
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Adolescents' Health Awareness and Understanding of Cancer and Tumor Prevention: When and Why an Adolescent Decides to Consult a Physician.

    Magni, Chiara / Segrè, Chiara / Finzi, Cosimo / Veneroni, Laura / Clerici, Carlo Alfredo / Massimino, Maura / Casanova, Michela / Martinella, Vera / Chiaravalli, Stefano / Ricci, Angelo / Biondi, Andrea / Ferrari, Andrea

    Pediatric blood & cancer

    2016  Volume 63, Issue 8, Page(s) 1357–1361

    Abstract: Background: A feature often seen in adolescent patients with cancer is a lengthy symptom interval, especially in comparison with children. It has been suggested that inadequate awareness of cancer risk among adolescents may play an important role in ... ...

    Abstract Background: A feature often seen in adolescent patients with cancer is a lengthy symptom interval, especially in comparison with children. It has been suggested that inadequate awareness of cancer risk among adolescents may play an important role in this study.
    Methods: The Società Italiana Adolescenti con Malattie Onco-ematologiche and the Fondazione Umberto Veronesi conducted a survey to investigate health awareness among healthy adolescents and their understanding of cancer and its signs and symptoms by commissioning a specialized agency (AstraRicerche). A questionnaire was administered to 500 Italian adolescents from the age group of 15 to 19 years using the computer-aided web interviewing method.
    Results: Approximately 80% of the adolescents interviewed claimed to be well informed about their own health, 85% said they were aware that some lifestyle habits could influence their health, and 80% reported that they know that cancer can develop in adolescence too. It was also noted that, while some adolescents were worried about a given symptom, 22% of them reportedly preferred a wait-and-see approach (either to avoid alarming their parents, or they hoped that the symptom would be temporary).
    Conclusions: This study showed that a majority of adolescents are concerned about their own health, but sometimes prefer not to report their symptoms to anyone. Hence, it is important to develop information campaigns tailored to raise awareness among this age group and help them interpret their symptoms.
    MeSH term(s) Adolescent ; Delayed Diagnosis ; Health Knowledge, Attitudes, Practice ; Health Promotion ; Humans ; Neoplasms/diagnosis ; Neoplasms/prevention & control ; Physician-Patient Relations ; Surveys and Questionnaires
    Language English
    Publishing date 2016
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2131448-2
    ISSN 1545-5017 ; 1545-5009
    ISSN (online) 1545-5017
    ISSN 1545-5009
    DOI 10.1002/pbc.25985
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The human cytomegalovirus DNA polymerase processivity factor UL44 is modified by SUMO in a DNA-dependent manner.

    Sinigalia, Elisa / Alvisi, Gualtiero / Segré, Chiara V / Mercorelli, Beatrice / Muratore, Giulia / Winkler, Michael / Hsiao, He-Hsuan / Urlaub, Henning / Ripalti, Alessandro / Chiocca, Susanna / Palù, Giorgio / Loregian, Arianna

    PloS one

    2012  Volume 7, Issue 11, Page(s) e49630

    Abstract: During the replication of human cytomegalovirus (HCMV) genome, the viral DNA polymerase subunit UL44 plays a key role, as by binding both DNA and the polymerase catalytic subunit it confers processivity to the holoenzyme. However, several lines of ... ...

    Abstract During the replication of human cytomegalovirus (HCMV) genome, the viral DNA polymerase subunit UL44 plays a key role, as by binding both DNA and the polymerase catalytic subunit it confers processivity to the holoenzyme. However, several lines of evidence suggest that UL44 might have additional roles during virus life cycle. To shed light on this, we searched for cellular partners of UL44 by yeast two-hybrid screenings. Intriguingly, we discovered the interaction of UL44 with Ubc9, an enzyme involved in the covalent conjugation of SUMO (Small Ubiquitin-related MOdifier) to cellular and viral proteins. We found that UL44 can be extensively sumoylated not only in a cell-free system and in transfected cells, but also in HCMV-infected cells, in which about 50% of the protein resulted to be modified at late times post-infection, when viral genome replication is accomplished. Mass spectrometry studies revealed that UL44 possesses multiple SUMO target sites, located throughout the protein. Remarkably, we observed that binding of UL44 to DNA greatly stimulates its sumoylation both in vitro and in vivo. In addition, we showed that overexpression of SUMO alters the intranuclear distribution of UL44 in HCMV-infected cells, and enhances both virus production and DNA replication, arguing for an important role for sumoylation in HCMV life cycle and UL44 function(s). These data report for the first time the sumoylation of a viral processivity factor and show that there is a functional interplay between the HCMV UL44 protein and the cellular sumoylation system.
    MeSH term(s) Amino Acid Sequence ; Animals ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cell Line ; Cell Nucleus/metabolism ; Cytomegalovirus/genetics ; Cytomegalovirus/metabolism ; DNA/metabolism ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Gene Expression ; Humans ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Transport ; Small Ubiquitin-Related Modifier Proteins/genetics ; Small Ubiquitin-Related Modifier Proteins/metabolism ; Sumoylation ; Ubiquitin-Conjugating Enzymes/genetics ; Ubiquitin-Conjugating Enzymes/metabolism ; Viral Proteins/chemistry ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Virus Replication
    Chemical Substances Carrier Proteins ; DNA-Binding Proteins ; ICP36 protein, Cytomegalovirus ; Small Ubiquitin-Related Modifier Proteins ; Viral Proteins ; DNA (9007-49-2) ; Ubiquitin-Conjugating Enzymes (EC 2.3.2.23) ; ubiquitin-conjugating enzyme UBC9 (EC 6.3.2.-)
    Keywords covid19
    Language English
    Publishing date 2012-11-15
    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.0049630
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: The human cytomegalovirus DNA polymerase processivity factor UL44 is modified by SUMO in a DNA-dependent manner.

    Elisa Sinigalia / Gualtiero Alvisi / Chiara V Segré / Beatrice Mercorelli / Giulia Muratore / Michael Winkler / He-Hsuan Hsiao / Henning Urlaub / Alessandro Ripalti / Susanna Chiocca / Giorgio Palù / Arianna Loregian

    PLoS ONE, Vol 7, Iss 11, p e

    2012  Volume 49630

    Abstract: During the replication of human cytomegalovirus (HCMV) genome, the viral DNA polymerase subunit UL44 plays a key role, as by binding both DNA and the polymerase catalytic subunit it confers processivity to the holoenzyme. However, several lines of ... ...

    Abstract During the replication of human cytomegalovirus (HCMV) genome, the viral DNA polymerase subunit UL44 plays a key role, as by binding both DNA and the polymerase catalytic subunit it confers processivity to the holoenzyme. However, several lines of evidence suggest that UL44 might have additional roles during virus life cycle. To shed light on this, we searched for cellular partners of UL44 by yeast two-hybrid screenings. Intriguingly, we discovered the interaction of UL44 with Ubc9, an enzyme involved in the covalent conjugation of SUMO (Small Ubiquitin-related MOdifier) to cellular and viral proteins. We found that UL44 can be extensively sumoylated not only in a cell-free system and in transfected cells, but also in HCMV-infected cells, in which about 50% of the protein resulted to be modified at late times post-infection, when viral genome replication is accomplished. Mass spectrometry studies revealed that UL44 possesses multiple SUMO target sites, located throughout the protein. Remarkably, we observed that binding of UL44 to DNA greatly stimulates its sumoylation both in vitro and in vivo. In addition, we showed that overexpression of SUMO alters the intranuclear distribution of UL44 in HCMV-infected cells, and enhances both virus production and DNA replication, arguing for an important role for sumoylation in HCMV life cycle and UL44 function(s). These data report for the first time the sumoylation of a viral processivity factor and show that there is a functional interplay between the HCMV UL44 protein and the cellular sumoylation system.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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