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  1. Artikel ; 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.
    Schlagwörter cell proliferation ; genes ; neoplasm progression ; neoplasms ; neurons ; transcription (genetics)
    Sprache Englisch
    Erscheinungsverlauf 2022-1129
    Erscheinungsort Multidisciplinary Digital Publishing Institute
    Dokumenttyp Artikel ; Online
    ZDB-ID 2527218-4
    ISSN 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes13122240
    Datenquelle NAL Katalog (AGRICOLA)

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

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

    Genes

    2022  Band 13, Heft 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 ... ...

    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.
    Sprache Englisch
    Erscheinungsdatum 2022-11-29
    Erscheinungsland Switzerland
    Dokumenttyp 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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  3. Buch ; 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
    Schlagwörter Computer Science - Robotics ; I.2.9
    Thema/Rubrik (Code) 629
    Erscheinungsdatum 2023-05-25
    Erscheinungsland us
    Dokumenttyp Buch ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; 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  Band 24, Heft 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-Begriff(e) 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
    Chemische Substanzen 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)
    Sprache Englisch
    Erscheinungsdatum 2023-03-12
    Erscheinungsland Switzerland
    Dokumenttyp 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
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; 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  Band 192, Seite(n) 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-Begriff(e) Humans ; Animals ; Endangered Species ; Sharks ; Fisheries ; Seafood ; Mediterranean Sea
    Sprache Englisch
    Erscheinungsdatum 2023-10-14
    Erscheinungsland England
    Dokumenttyp 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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  6. Artikel ; 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  Band 37, Heft 4, Seite(n) 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-Begriff(e) Male ; Humans ; Female ; Mitral Valve Insufficiency/diagnostic imaging ; Echocardiography, Doppler, Color/methods ; Echocardiography, Three-Dimensional/methods ; ROC Curve ; Heart Failure ; Severity of Illness Index
    Sprache Englisch
    Erscheinungsdatum 2024-01-18
    Erscheinungsland United States
    Dokumenttyp 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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  7. Artikel ; 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  Band 181, Seite(n) 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-Begriff(e) Animals ; Seawater ; Carbon Dioxide/toxicity ; Anemone ; Hydrogen-Ion Concentration ; Ocean Acidification ; Perciformes ; Fishes/physiology
    Chemische Substanzen Carbon Dioxide (142M471B3J)
    Sprache Englisch
    Erscheinungsdatum 2022-09-26
    Erscheinungsland England
    Dokumenttyp 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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  8. Artikel ; 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  Band 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.
    Schlagwörter Neuroblastoma ; MYCN ; RB ; E2F ; palbociclib ; ribociclib ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2023-03-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  9. Artikel ; 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  Band 13, Heft 1, Seite(n) 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-Begriff(e) Animals ; Conservation of Natural Resources ; Elasmobranchii ; Fisheries ; Humans
    Sprache Englisch
    Erscheinungsdatum 2022-08-09
    Erscheinungsland England
    Dokumenttyp 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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  10. Artikel ; 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  Band 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.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2022-08-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
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