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Article ; Online: Single-Cell Sequencing Identifies Master Regulators Affected by Panobinostat in Neuroblastoma Cells

Milazzo, Giorgio / Perini, Giovanni / Giorgi, Federico M.

Genes (Basel). 2022 Nov. 29, v. 13, no. 12

2022

Abstract: The molecular mechanisms and gene regulatory networks sustaining cell proliferation in neuroblastoma (NBL) cells are still not fully understood. In this tumor context, it has been proposed that anti-proliferative drugs, such as the pan-HDAC inhibitor ... ...

Abstract	The molecular mechanisms and gene regulatory networks sustaining cell proliferation in neuroblastoma (NBL) cells are still not fully understood. In this tumor context, it has been proposed that anti-proliferative drugs, such as the pan-HDAC inhibitor panobinostat, could be tested to mitigate tumor progression. Here, we set out to investigate the effects of panobinostat treatment at the unprecedented resolution offered by single-cell sequencing. We identified a global senescence signature paired with reduction in proliferation in treated Kelly cells and more isolated transcriptional responses compatible with early neuronal differentiation. Using master regulator analysis, we identified BAZ1A, HCFC1, MAZ, and ZNF146 as the transcriptional regulators most significantly repressed by panobinostat. Experimental silencing of these transcription factors (TFs) confirmed their role in sustaining NBL cell proliferation in vitro.
Keywords	cell proliferation ; genes ; neoplasm progression ; neoplasms ; neurons ; transcription (genetics)
Language	English
Dates of publication	2022-1129
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13122240
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Single-Cell Sequencing Identifies Master Regulators Affected by Panobinostat in Neuroblastoma Cells.

Milazzo, Giorgio / Perini, Giovanni / Giorgi, Federico M

Genes

2022 Volume 13, Issue 12

Abstract	The molecular mechanisms and gene regulatory networks sustaining cell proliferation in neuroblastoma (NBL) cells are still not fully understood. In this tumor context, it has been proposed that anti-proliferative drugs, such as the pan-HDAC inhibitor panobinostat, could be tested to mitigate tumor progression. Here, we set out to investigate the effects of panobinostat treatment at the unprecedented resolution offered by single-cell sequencing. We identified a global senescence signature paired with reduction in proliferation in treated Kelly cells and more isolated transcriptional responses compatible with early neuronal differentiation. Using master regulator analysis, we identified BAZ1A, HCFC1, MAZ, and ZNF146 as the transcriptional regulators most significantly repressed by panobinostat. Experimental silencing of these transcription factors (TFs) confirmed their role in sustaining NBL cell proliferation in vitro.
Language	English
Publishing date	2022-11-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13122240
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Book ; Online: Modeling and Control of a Novel Variable Stiffness Three DoFs Wrist

Milazzo, Giuseppe / Catalano, Manuel Giuseppe / Bicchi, Antonio / Grioli, Giorgio

2023

Abstract: This study introduces an innovative design for a Variable Stiffness 3 Degrees of Freedom actuated wrist capable of actively and continuously adjusting its overall stiffness by modulating the active length of non-linear elastic elements. This modulation ... ...

Abstract	This study introduces an innovative design for a Variable Stiffness 3 Degrees of Freedom actuated wrist capable of actively and continuously adjusting its overall stiffness by modulating the active length of non-linear elastic elements. This modulation is akin to human muscular cocontraction and is achieved using only four motors. The mechanical configuration employed results in a compact and lightweight device with anthropomorphic characteristics, making it potentially suitable for applications such as prosthetics and humanoid robotics. This design aims to enhance performance in dynamic tasks, improve task adaptability, and ensure safety during interactions with both people and objects. The paper details the first hardware implementation of the proposed design, providing insights into the theoretical model, mechanical and electronic components, as well as the control architecture. System performance is assessed using a motion capture system. The results demonstrate that the prototype offers a broad range of motion ($[55, -45]${\deg} for flexion/extension, $\pm48${\deg} for radial/ulnar deviation, and $\pm180${\deg} for pronation/supination) while having the capability to triple its stiffness. Furthermore, following proper calibration, the wrist posture can be reconstructed through multivariate linear regression using rotational encoders and the forward kinematic model. This reconstruction achieves an average Root Mean Square Error of 6.6{\deg}, with an $R^2$ value of 0.93. Comment: 15 pages + appendix (3 pages), 18 figures, submitted to IJRR
Keywords	Computer Science - Robotics ; I.2.9
Subject code	629
Publishing date	2023-05-25
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: MYCN

De Rosa, Piergiuseppe / Severi, Federica / Zadran, Suleman Khan / Russo, Marco / Aloisi, Sara / Rigamonti, Alberto / Capranico, Giovanni / Milazzo, Giorgio / Perini, Giovanni

International journal of molecular sciences

2023 Volume 24, Issue 6

Abstract: Neuroblastoma (NB) is one of the primary causes of death for pediatric malignancies. Given the high heterogeneity in NB's mutation landscape, optimizing individualized therapies is still challenging. In the context of genomic alterations, ...

Abstract	Neuroblastoma (NB) is one of the primary causes of death for pediatric malignancies. Given the high heterogeneity in NB's mutation landscape, optimizing individualized therapies is still challenging. In the context of genomic alterations,
MeSH term(s)	Child ; Humans ; Cell Cycle/genetics ; Cell Line, Tumor ; Cell Proliferation ; Cyclin-Dependent Kinase 4/genetics ; Cyclin-Dependent Kinase 4/metabolism ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; N-Myc Proto-Oncogene Protein/genetics ; N-Myc Proto-Oncogene Protein/metabolism ; Neuroblastoma/drug therapy ; Neuroblastoma/genetics ; Neuroblastoma/metabolism ; Retinoblastoma Binding Proteins/genetics ; Retinoblastoma Binding Proteins/metabolism ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	CDK4 protein, human (EC 2.7.11.22) ; Cyclin-Dependent Kinase 4 (EC 2.7.11.22) ; MYCN protein, human ; N-Myc Proto-Oncogene Protein ; RB1 protein, human ; Retinoblastoma Binding Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; CDK6 protein, human (EC 2.7.11.22)
Language	English
Publishing date	2023-03-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24065408
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Article ; Online: Multiple interannual records of young-of-the-year identify an important area for the protection of the shortfin mako, Isurus oxyrinchus.

Cattano, Carlo / Gambardella, Chiara / Grancagnolo, Desiree / Principato, Elena / Aglieri, Giorgio / Turco, Gabriele / Quattrocchi, Federico / Milazzo, Marco

Marine environmental research

2023 Volume 192, Page(s) 106217

Abstract: The shortfin mako (Isurus oxyrinchus) is the second most fishery-exploited pelagic shark in the Mediterranean Sea, thus its conservation status is a cause for concern. Despite the species has been listed in fishery and trade regulations to hinder its ... ...

Abstract	The shortfin mako (Isurus oxyrinchus) is the second most fishery-exploited pelagic shark in the Mediterranean Sea, thus its conservation status is a cause for concern. Despite the species has been listed in fishery and trade regulations to hinder its population decline, the lack of knowledge on its distribution patterns and habitats essential for its persistence still hampers the implementation of sound conservation actions. Combining data from local expert knowledge, opportunistic catch records, and Baited Remote Underwater Videos, we show evidence of the interannual presence of young-of-the-year (YOY) I. oxyrinchus in the Pelagie Archipelago (Central Mediterranean Sea). A total of twenty-one individuals ranging 71-92.5 cm FL were incidentally caught (on average 2.3 YOY/1000 hooks) or documented on BRUVS in July and August over three consecutive years. These data coupled with questionnaires administered to longline fishers identify one specific area used by YOY in the summer months. Our study presents the most abundant record of YOY shortfin makos in the Mediterranean Sea within such a restricted time and limited area providing important information for improving the protection of this critically endangered species.
MeSH term(s)	Humans ; Animals ; Endangered Species ; Sharks ; Fisheries ; Seafood ; Mediterranean Sea
Language	English
Publishing date	2023-10-14
Publishing country	England
Document type	Journal Article
ZDB-ID	1502505-6
ISSN	1879-0291 ; 0141-1136
ISSN (online)	1879-0291
ISSN	0141-1136
DOI	10.1016/j.marenvres.2023.106217
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Article ; Online: Clinical Impact of the Volumetric Quantification of Ventricular Secondary Mitral Regurgitation by Three-Dimensional Echocardiography.

Tomaselli, Michele / Badano, Luigi P / Oliverio, Giorgio / Curti, Emanuele / Pece, Cinzia / Springhetti, Paolo / Milazzo, Salvatore / Clement, Alexandra / Penso, Marco / Gavazzoni, Mara / Hădăreanu, Diana R / Mihaila, Sorina Baldea / Pugliesi, Giordano M / Delcea, Caterina / Muraru, Denisa

Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography

2024 Volume 37, Issue 4, Page(s) 408–419

Abstract: Background: The assessment of ventricular secondary mitral regurgitation (v-SMR) severity through effective regurgitant orifice area (EROA) and regurgitant volume (RegVol) calculations using the proximal isovelocity surface area (PISA) method and the ... ...

Abstract	Background: The assessment of ventricular secondary mitral regurgitation (v-SMR) severity through effective regurgitant orifice area (EROA) and regurgitant volume (RegVol) calculations using the proximal isovelocity surface area (PISA) method and the two-dimensional echocardiography volumetric method (2DEVM) is prone to underestimation. Accordingly, we sought to investigate the accuracy of the three-dimensional echocardiography volumetric method (3DEVM) and its association with outcomes in v-SMR patients. Methods: We included 229 patients (70 ± 13 years, 74% men) with v-SMR. We compared EROA and RegVol calculated by the 3DEVM, 2DEVM, and PISA methods. The end point was a composite of heart failure hospitalization and death for any cause. Results: After a mean follow-up of 20 ±11 months, 98 patients (43%) reached the end point. Regurgitant volume and EROA calculated by 3DEVM were larger than those calculated by 2DEVM and PISA. Using receiver operating characteristic curve analysis, both EROA (area under the curve, 0.75; 95% CI, 0.68-0.81; P = .008) and RegVol (AUC, 0.75; 95% CI, 0.68-0.82; P = .02) measured by 3DEVM showed the highest association with the outcome at 2 years compared to PISA and 2DEVM (P < .05 for all). Kaplan-Meier analysis demonstrated a significantly higher rate of events in patients with EROA ≥ 0.3 cm Conclusions: Effective regurgitant orifice area and RegVol calculated by 3DEVM were independently associated with the end point, improving the risk stratification of patients with v-SMR compared to the 2DEVM and PISA methods.
MeSH term(s)	Male ; Humans ; Female ; Mitral Valve Insufficiency/diagnostic imaging ; Echocardiography, Doppler, Color/methods ; Echocardiography, Three-Dimensional/methods ; ROC Curve ; Heart Failure ; Severity of Illness Index
Language	English
Publishing date	2024-01-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	1035622-8
ISSN	1097-6795 ; 0894-7317
ISSN (online)	1097-6795
ISSN	0894-7317
DOI	10.1016/j.echo.2024.01.004
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Zs.A 2638: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Limited behavioural effects of ocean acidification on a Mediterranean anemone goby (Gobius incognitus) chronically exposed to elevated CO

Spatafora, Davide / Cattano, Carlo / Aglieri, Giorgio / Quattrocchi, Federico / Turco, Gabriele / Quartararo, Giulia / Dudemaine, Jeanne / Calosi, Piero / Milazzo, Marco

Marine environmental research

2022 Volume 181, Page(s) 105758

Abstract: An in situ reciprocal transplant experiment was carried around a volcanic ... ...

Abstract	An in situ reciprocal transplant experiment was carried around a volcanic CO
MeSH term(s)	Animals ; Seawater ; Carbon Dioxide/toxicity ; Anemone ; Hydrogen-Ion Concentration ; Ocean Acidification ; Perciformes ; Fishes/physiology
Chemical Substances	Carbon Dioxide (142M471B3J)
Language	English
Publishing date	2022-09-26
Publishing country	England
Document type	Journal Article
ZDB-ID	1502505-6
ISSN	1879-0291 ; 0141-1136
ISSN (online)	1879-0291
ISSN	0141-1136
DOI	10.1016/j.marenvres.2022.105758
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Article ; Online: MYCN Amplification, along with Wild-Type RB1 Expression, Enhances CDK4/6 Inhibitors’ Efficacy in Neuroblastoma Cells

Piergiuseppe De Rosa / Federica Severi / Suleman Khan Zadran / Marco Russo / Sara Aloisi / Alberto Rigamonti / Giovanni Capranico / Giorgio Milazzo / Giovanni Perini

International Journal of Molecular Sciences, Vol 24, Iss 5408, p

2023 Volume 5408

Abstract: Neuroblastoma (NB) is one of the primary causes of death for pediatric malignancies. Given the high heterogeneity in NB’s mutation landscape, optimizing individualized therapies is still challenging. In the context of genomic alterations, MYCN ... ...

Abstract	Neuroblastoma (NB) is one of the primary causes of death for pediatric malignancies. Given the high heterogeneity in NB’s mutation landscape, optimizing individualized therapies is still challenging. In the context of genomic alterations, MYCN amplification is the most correlated event with poor outcomes. MYCN is involved in the regulation of several cellular mechanisms, including cell cycle. Thus, studying the influence of MYCN overexpression in the G1/S transition checkpoint of the cell cycle may unveil novel druggable targets for the development of personalized therapeutical approaches. Here, we show that high expression of E2F3 and MYCN correlate with poor prognosis in NB despite the RB1 mRNA levels. Moreover, we demonstrate through luciferase reporter assays that MYCN bypasses RB function by incrementing E2F3-responsive promoter activity. We showed that MYCN overexpression leads to RB inactivation by inducing RB hyperphosphorylation during the G1 phase through cell cycle synchronization experiments. Moreover, we generated two MYCN -amplified NB cell lines conditionally knockdown (cKD) for the RB1 gene through a CRISPRi approach. Indeed, RB KD did not affect cell proliferation, whereas cell proliferation was strongly influenced when a non-phosphorylatable RB mutant was expressed. This finding revealed the dispensable role of RB in regulating MYCN -amplified NB’s cell cycle. The described genetic interaction between MYCN and RB1 provides the rationale for using cyclin/CDK complexes inhibitors in NBs carrying MYCN amplification and relatively high levels of RB1 expression.
Keywords	Neuroblastoma ; MYCN ; RB ; E2F ; palbociclib ; ribociclib ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Small-scale fisheries catch more threatened elasmobranchs inside partially protected areas than in unprotected areas.

Di Lorenzo, Manfredi / Calò, Antonio / Di Franco, Antonio / Milisenda, Giacomo / Aglieri, Giorgio / Cattano, Carlo / Milazzo, Marco / Guidetti, Paolo

Nature communications

2022 Volume 13, Issue 1, Page(s) 4381

Abstract: Elasmobranchs are heavily impacted by fishing. Catch statistics are grossly underestimated due to missing data from various fishery sectors such as small-scale fisheries. Marine Protected Areas are proposed as a tool to protect elasmobranchs and counter ... ...

Abstract	Elasmobranchs are heavily impacted by fishing. Catch statistics are grossly underestimated due to missing data from various fishery sectors such as small-scale fisheries. Marine Protected Areas are proposed as a tool to protect elasmobranchs and counter their ongoing depletion. We assess elasmobranchs caught in 1,256 fishing operations with fixed nets carried out in partially protected areas within Marine Protected Areas and unprotected areas beyond Marine Protected Areas borders at 11 locations in 6 Mediterranean countries. Twenty-four elasmobranch species were recorded, more than one-third belonging to the IUCN threatened categories (Vulnerable, Endangered, or Critically Endangered). Catches per unit of effort of threatened and data deficient species were higher (with more immature individuals being caught) in partially protected areas than in unprotected areas. Our study suggests that despite partially protected areas having the potential to deliver ecological benefits for threatened elasmobranchs, poor small-scale fisheries management inside Marine Protected Areas could hinder them from achieving this important conservation objective.
MeSH term(s)	Animals ; Conservation of Natural Resources ; Elasmobranchii ; Fisheries ; Humans
Language	English
Publishing date	2022-08-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-32035-3
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Article ; Online: Small-scale fisheries catch more threatened elasmobranchs inside partially protected areas than in unprotected areas

Manfredi Di Lorenzo / Antonio Calò / Antonio Di Franco / Giacomo Milisenda / Giorgio Aglieri / Carlo Cattano / Marco Milazzo / Paolo Guidetti

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 11

Abstract: Marine protected areas are proposed to protect elasmobranchs (sharks, skates, and rays) but the fishing impact from small-scale fisheries in these areas is unknown. From 1256 fishing operations carried out in partially protected and unprotected areas in ... ...

Abstract	Marine protected areas are proposed to protect elasmobranchs (sharks, skates, and rays) but the fishing impact from small-scale fisheries in these areas is unknown. From 1256 fishing operations carried out in partially protected and unprotected areas in six Mediterranean countries, this study shows that catches were higher in partially protected areas than in unprotected areas, indicating poor small-scale fisheries management as a threat for these species.
Keywords	Science ; Q
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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