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Article: Cellular effects of leishmanial tubulin inhibitors on L. donovani.

Havens, C G / Bryant, N / Asher, L / Lamoreaux, L / Perfetto, S / Brendle, J J / Werbovetz, K A

2000 Volume 110, Issue 2, Page(s) 223–236

Abstract: ... These drugs affected the assembly of purified leishmanial tubulin and inhibited the growth of L. donovani ... Flow cytometric analysis of L. donovani promastigotes treated with these three drugs indicated a dramatic shift ... antileishmanial and anti-tubulin activity, on L. donovani. Treatment of parasites with WR85915 did not produce ...

Abstract	To aid our investigation of tubulin as an antileishmanial drug target, the effects of the mammalian antimicrotubule agents ansamitocin P3, taxol, and hemiasterlin on Leishmania donovani promastigotes were described. These drugs affected the assembly of purified leishmanial tubulin and inhibited the growth of L. donovani promastigotes at micromolar concentrations. When promastigotes were treated with these agents, mitotic partitioning of nuclear DNA and cytokinesis were usually inhibited. The spatial orientation of kinetoplasts was often disturbed, suggesting a role for microtubules in the segregation of these organelles during mitosis. Aberrant cell types produced in drug-treated cultures included parasites with one nucleus and two geometrically distinct kinetoplasts, parasites with multiple kinetoplasts, and cytoplasts containing a kinetoplast but no nucleus. A subset of unique cell types, parasites containing two nuclei, a spindle fiber, and two geometrically distinct kinetoplasts, were observed in hemiasterlin-treated cultures. Flow cytometric analysis of L. donovani promastigotes treated with these three drugs indicated a dramatic shift toward the G2 + M phase of the cell cycle, with some cells containing four times the amount of DNA present in G1. These results were used to evaluate the cellular effects of WR85915, an aromatic thiocyanate with in vitro antileishmanial and anti-tubulin activity, on L. donovani. Treatment of parasites with WR85915 did not produce the unusual cell types described above and did not cause the accumulation of parasites in G2 + M, suggesting that WR85915 acts on target(s) in Leishmania in addition to tubulin. These studies validate tubulin as a suitable antileishmanial drug target and provide criteria to assess the cellular mechanism of action of new candidate antileishmanial agents.
MeSH term(s)	Animals ; Antiprotozoal Agents/pharmacology ; Cell Cycle/drug effects ; DNA, Protozoan/analysis ; Flow Cytometry ; Leishmania donovani/drug effects ; Leishmania donovani/growth & development ; Leishmania donovani/ultrastructure ; Maytansine/analogs & derivatives ; Maytansine/pharmacology ; Microscopy, Electron ; Microscopy, Fluorescence ; Oligopeptides/pharmacology ; Oxadiazoles/pharmacology ; Paclitaxel/pharmacology ; Tubulin/metabolism
Chemical Substances	Antiprotozoal Agents ; DNA, Protozoan ; Oligopeptides ; Oxadiazoles ; Tubulin ; WR 85915 ; hemiasterlin A ; Maytansine (14083FR882) ; ansamitocins (69279-90-9) ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2000-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	756166-0
ISSN	1872-9428 ; 0166-6851
ISSN (online)	1872-9428
ISSN	0166-6851
DOI	10.1016/s0166-6851(00)00272-3
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Article ; Online: The Cyclin-dependent kinase 1: more than a cell cycle regulator.

Massacci, Giorgia / Perfetto, Livia / Sacco, Francesca

British journal of cancer

2023 Volume 129, Issue 11, Page(s) 1707–1716

Abstract: The Cyclin-dependent kinase 1, as a serine/threonine protein kinase, is more than a cell cycle regulator as it was originally identified. During the last decade, it has been shown to carry out versatile functions during the last decade. From cell cycle ... ...

Abstract	The Cyclin-dependent kinase 1, as a serine/threonine protein kinase, is more than a cell cycle regulator as it was originally identified. During the last decade, it has been shown to carry out versatile functions during the last decade. From cell cycle control to gene expression regulation and apoptosis, CDK1 is intimately involved in many cellular events that are vital for cell survival. Here, we provide a comprehensive catalogue of the CDK1 upstream regulators and substrates, describing how this kinase is implicated in the control of key 'cell cycle-unrelated' biological processes. Finally, we describe how deregulation of CDK1 expression and activation has been closely associated with cancer progression and drug resistance.
MeSH term(s)	Humans ; CDC2 Protein Kinase/genetics ; CDC2 Protein Kinase/metabolism ; Protein Serine-Threonine Kinases/genetics ; Genes, cdc ; Cell Cycle ; Cell Division
Chemical Substances	CDC2 Protein Kinase (EC 2.7.11.22) ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2023-10-28
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-023-02468-8
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Article ; Online: Experimental Results of Partial Discharge Localization in Bounded Domains.

Perfetto, Luca / D'Antona, Gabriele

Sensors (Basel, Switzerland)

2021 Volume 21, Issue 3

Abstract: This work presents a novel diagnostic method to localize Partial Discharges (PDs) inside Medium Voltage (MV) and High Voltage (HV) equipment. The method is well suited for that equipment presenting a bounded domain with fixed Boundary Conditions (BCs) ... ...

Abstract	This work presents a novel diagnostic method to localize Partial Discharges (PDs) inside Medium Voltage (MV) and High Voltage (HV) equipment. The method is well suited for that equipment presenting a bounded domain with fixed Boundary Conditions (BCs) such as Oil-Filled Power Transformers (OFPTs), Air Insulated Switchgears (AISs), Gas Insulated Switchgears (GISs) or Gas Insulated Transmission Lines (GILs). It is based on Electromagnetic (EM) measurements which are used to reconstruct the EM field produced by the PD and localize the PD itself. The reconstruction and localization tasks are based on the eigenfunctions series expansion method which intrinsically accounts for the physical information of the propagation phenomenon. This fact makes the proposed diagnostic method very robust and accurate even in real and complex scenarios. The promising experimental results, obtained in two different test cases, confirmed the ability and powerfulness of the proposed PD localization method.
Language	English
Publishing date	2021-01-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s21030935
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Article: UVA irradiation induces L-isoaspartyl formation in melanoma cell proteins.

D'Angelo, S / Ingrosso, D / Perfetto, B / Baroni, A / Zappia, M / Lobianco, L L / Tufano, M A / Galletti, P

Free radical biology & medicine

2001 Volume 31, Issue 1, Page(s) 1–9

Abstract: ... to UVA rays have been chosen as a model for monitoring the occurrence of L-isoaspartyl sites. A dramatic ... increase of these abnormal residues, specifically recognized and methylated by the enzyme L-isoaspartate(D ...

Abstract	It has been reported that UVA effects are partly mediated by production of reactive oxygen species. Moreover, oxidative stress increases protein damage, involving the occurrence of isoaspartyl residues, a product of protein deamidation/isomerization reactions. This work was undertaken in order to study the effects of UVA irradiation, mediated by oxidation, on sensitive protein targets. Melanoma cells exposed to UVA rays have been chosen as a model for monitoring the occurrence of L-isoaspartyl sites. A dramatic increase of these abnormal residues, specifically recognized and methylated by the enzyme L-isoaspartate(D-aspartate) O-methyltransferase (PCMT; EC 2.1.1.77), can be detected after exposure of M14 cells to raising doses of UVA. The effect of UVA on NO and TBARS accumulation, as well as on DNA fragmentation, has also been investigated. NO formation parallels the increase in isoaspartyl formation, while lipid peroxidation occurs only at the highest UVA doses. No DNA fragmentation has been detected under the employed experimental conditions. These results, as a whole, indicate that protein damages are one of the early events on UVA-induced cell injury. The endogenous activity of PCMT remains remarkably stable under UVA treatment, suggesting that this enzyme might play a crucial role in the repair and/or disposal of damaged proteins in UVA-irradiated cells.
MeSH term(s)	Animals ; Aspartic Acid/biosynthesis ; DNA Damage/radiation effects ; DNA Fragmentation ; DNA, Neoplasm/radiation effects ; Humans ; Melanoma/metabolism ; Melanoma/radiotherapy ; Neoplasm Proteins/metabolism ; Neoplasm Proteins/radiation effects ; Nitric Oxide/metabolism ; Protein D-Aspartate-L-Isoaspartate Methyltransferase ; Protein Methyltransferases/metabolism ; Rats ; Reactive Oxygen Species ; Tumor Cells, Cultured/radiation effects ; Ultraviolet Rays
Chemical Substances	DNA, Neoplasm ; Neoplasm Proteins ; Reactive Oxygen Species ; Aspartic Acid (30KYC7MIAI) ; Nitric Oxide (31C4KY9ESH) ; Protein Methyltransferases (EC 2.1.1.-) ; Protein D-Aspartate-L-Isoaspartate Methyltransferase (EC 2.1.1.77)
Language	English
Publishing date	2001-05-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/s0891-5849(01)00518-4
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Zs.A 2109: Show issues

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Article ; Online: Caregiver's psychological well-being and quality of relationship with cardiac amyloidosis patients.

Ponti, Lucia / Cappelli, Francesco / Perfetto, Federico / Maver, Perla / Smorti, Martina

Psychology, health & medicine

2023 Volume 29, Issue 1, Page(s) 66–78

Abstract: Caregivers' psychological well-being is linked to the quality of care provided for familiar with chronic illness. Despite caregivers of cardiac patients present an impaired psychological well-being, less investigated is the psychological well-being of ... ...

Abstract	Caregivers' psychological well-being is linked to the quality of care provided for familiar with chronic illness. Despite caregivers of cardiac patients present an impaired psychological well-being, less investigated is the psychological well-being of caregivers of individuals with a rare disease such as the Transthyretin Cardiac Amyloidosis (ATTR-CA). Specifically, given that no study explored the well-being of the caregiver and the caregiver-patient relationship, this study aimed to analyze the prevalence of anxiety and depression in ATTR-CA caregivers and if these disorders were associated with patient's and caregiver's characteristics. Fifty-eight dyad caregiver-ATTR-CA patients completed the Hospital Anxiety and Depression Scale and the Network of Relationships Inventory. Moreover, ATTR-CA patients completed the Kansas City Cardiomyopathy Questionnaire, while caregivers completed the Multidimensional Scale of Social Support. Results showed that anxious caregivers (44%) reported higher conflict with patients. They had ATTR-CA relatives with a worse perception of cardiac symptoms and higher anxiety and depression. Depressed caregivers (39%) reported higher conflict with ATTR-CA relatives and lower perceived social support. Caregiver reported a high prevalence of anxiety and depression associated with worse personal relational well-being and to patient's psycho-physical condition. The care of ATTR-CA patient should consider the caregiver well-being.
MeSH term(s)	Humans ; Caregivers/psychology ; Psychological Well-Being ; Anxiety/epidemiology ; Prevalence ; Amyloidosis
Language	English
Publishing date	2023-12-29
Publishing country	England
Document type	Journal Article
ZDB-ID	1477841-5
ISSN	1465-3966 ; 1354-8506
ISSN (online)	1465-3966
ISSN	1354-8506
DOI	10.1080/13548506.2023.2280463
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Article: Assembling Disease Networks From Causal Interaction Resources.

Cesareni, Gianni / Sacco, Francesca / Perfetto, Livia

Frontiers in genetics

2021 Volume 12, Page(s) 694468

Abstract: The development of high-throughput high-content technologies and the increased ease in their application in clinical settings has raised the expectation of an important impact of these technologies on diagnosis and personalized therapy. Patient genomic ... ...

Abstract	The development of high-throughput high-content technologies and the increased ease in their application in clinical settings has raised the expectation of an important impact of these technologies on diagnosis and personalized therapy. Patient genomic and expression profiles yield lists of genes that are mutated or whose expression is modulated in specific disease conditions. The challenge remains of extracting from these lists functional information that may help to shed light on the mechanisms that are perturbed in the disease, thus setting a rational framework that may help clinical decisions. Network approaches are playing an increasing role in the organization and interpretation of patients' data. Biological networks are generated by connecting genes or gene products according to experimental evidence that demonstrates their interactions. Till recently most approaches have relied on networks based on physical interactions between proteins. Such networks miss an important piece of information as they lack details on the functional consequences of the interactions. Over the past few years, a number of resources have started collecting causal information of the type protein A activates/inactivates protein B, in a structured format. This information may be represented as signed directed graphs where physiological and pathological signaling can be conveniently inspected. In this review we will (i) present and compare these resources and discuss the different scope in comparison with pathway resources; (ii) compare resources that explicitly capture causality in terms of data content and proteome coverage (iii) review how causal-graphs can be used to extract disease-specific Boolean networks.
Language	English
Publishing date	2021-06-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2021.694468
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Article: A Resource to Infer Molecular Paths Linking Cancer Mutations to Perturbation of Cell Metabolism.

Iannuccelli, Marta / Lo Surdo, Prisca / Licata, Luana / Castagnoli, Luisa / Cesareni, Gianni / Perfetto, Livia

Frontiers in molecular biosciences

2022 Volume 9, Page(s) 893256

Abstract: Some inherited or somatically-acquired gene variants are observed significantly more frequently in the genome of cancer cells. Although many of these cannot be confidently classified as driver mutations, they may contribute to shaping a cell environment ... ...

Abstract	Some inherited or somatically-acquired gene variants are observed significantly more frequently in the genome of cancer cells. Although many of these cannot be confidently classified as driver mutations, they may contribute to shaping a cell environment that favours cancer onset and development. Understanding how these gene variants causally affect cancer phenotypes may help developing strategies for reverting the disease phenotype. Here we focus on variants of genes whose products have the potential to modulate metabolism to support uncontrolled cell growth. Over recent months our team of expert curators has undertaken an effort to annotate in the database SIGNOR 1) metabolic pathways that are deregulated in cancer and 2) interactions connecting oncogenes and tumour suppressors to metabolic enzymes. In addition, we refined a recently developed graph analysis tool that permits users to infer causal paths leading from any human gene to modulation of metabolic pathways. The tool grounds on a human signed and directed network that connects ∼8400 biological entities such as proteins and protein complexes via causal relationships. The network, which is based on more than 30,000 published causal links, can be downloaded from the SIGNOR website. In addition, as SIGNOR stores information on drugs or other chemicals targeting the activity of many of the genes in the network, the identification of likely functional paths offers a rational framework for exploring new therapeutic strategies that revert the disease phenotype.
Language	English
Publishing date	2022-05-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2022.893256
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Article ; Online: SIGNORApp: a Cytoscape 3 application to access SIGNOR data.

De Marinis, Ilaria / Lo Surdo, Prisca / Cesareni, Gianni / Perfetto, Livia

Bioinformatics (Oxford, England)

2021 Volume 38, Issue 6, Page(s) 1764–1766

Abstract: Summary: SIGNORApp is a Cytoscape 3 (3.8 and later) application that provides access to causal interactions annotated in the SIGNOR resource. The application builds networks that can be represented as weighted, signed, directed graphs, where nodes are ... ...

Abstract	Summary: SIGNORApp is a Cytoscape 3 (3.8 and later) application that provides access to causal interactions annotated in the SIGNOR resource. The application builds networks that can be represented as weighted, signed, directed graphs, where nodes are interacting biological entities and edges represent causal interactions captured by expert curators from experiments reported in peer reviewed journals. Users can query the SIGNOR dataset with (i) single or multiple entity name(s) or identifier(s) and optionally they may require to include in the output network their interacting partners, (ii) browse pathways that are annotated in the SIGNOR resource and (iii) extract the entire causal interactome. The app offers two visualizations modes: one only displaying entity interactions and a second emphasizing the post-translational modifications occurring as a consequence of the interaction. In addition, users can click on nodes and edges to access entity and interaction annotations. Causal information is available for three model organisms: Homo sapiens, Mus musculus and Rattus norvegicus. Availability and implementation: SIGNORApp has been developed for Cytoscape 3 (3.8 and later) in the Java programming language. The latest source code and the plugin can be found at: https://github.com/SIGNORcysAPP/signor-app and https://apps.cytoscape.org/apps/signorapp, respectively. Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	Mice ; Humans ; Animals ; Rats ; Software ; Protein Processing, Post-Translational
Language	English
Publishing date	2021-12-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btab865
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Article ; Online: Direct Synthesis of CF

Zheng, Yongxiang / Perfetto, Anna / Luise, Davide / Ciofini, Ilaria / Miesch, Laurence

Organic letters

2021 Volume 23, Issue 14, Page(s) 5528–5532

Abstract: The significance of molecules containing difluoromethyl groups is driven by their potential applications in pharmaceutical and agrochemical science. Methods for the incorporation of lightly fluorinated groups such as ... ...

Abstract	The significance of molecules containing difluoromethyl groups is driven by their potential applications in pharmaceutical and agrochemical science. Methods for the incorporation of lightly fluorinated groups such as CF
Language	English
Publishing date	2021-06-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1523-7052
ISSN (online)	1523-7052
DOI	10.1021/acs.orglett.1c01876
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Article ; Online: Measuring Health and Well-Being: We Need to Get it Right for Patients, With Patients.

Perfetto, Eleanor M / Burke, Laurie / Love, T Rosie / Schrandt, M Suz / Hobart, Jeremy

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research

2022 Volume 26, Issue 3, Page(s) 435–437

MeSH term(s)	Humans ; Patients ; Health Status ; Health Status Indicators
Language	English
Publishing date	2022-11-15
Publishing country	United States
Document type	Letter
ZDB-ID	1471745-1
ISSN	1524-4733 ; 1098-3015
ISSN (online)	1524-4733
ISSN	1098-3015
DOI	10.1016/j.jval.2022.11.005
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