Supplementary Tables 1-2, Figures 1-8 from Opposite Effects of Notch-1 and Notch-2 on Mesotheliom... more Supplementary Tables 1-2, Figures 1-8 from Opposite Effects of Notch-1 and Notch-2 on Mesothelioma Cell Survival under Hypoxia Are Exerted through the Akt Pathway
Supplementary Legends 1-5 and Table 1 Legend from Oxygen Concentration Determines the Biological ... more Supplementary Legends 1-5 and Table 1 Legend from Oxygen Concentration Determines the Biological Effects of NOTCH-1 Signaling in Adenocarcinoma of the Lung
Supplementary Table 1 from Oxygen Concentration Determines the Biological Effects of NOTCH-1 Sign... more Supplementary Table 1 from Oxygen Concentration Determines the Biological Effects of NOTCH-1 Signaling in Adenocarcinoma of the Lung
DOAJ (DOAJ: Directory of Open Access Journals), Dec 28, 2014
In examining the fresco decorations of the Palazzo Sampieri-Talon in Bologna, the final collectiv... more In examining the fresco decorations of the Palazzo Sampieri-Talon in Bologna, the final collective work by Ludovico, Agostino and Annibale Carracci, with later additions by Guercino, the article concentrates on the yet unresolved reconstruction of its iconographic programme. The proposed interpretation is based on Claudian’s Alexandrine poem De raptu Proserpinae .
One of the earliest studies of nonclassical protein release was devoted to secretory transglutami... more One of the earliest studies of nonclassical protein release was devoted to secretory transglutaminase (TO), an enzyme that cross-links extracellular polypeptides and is released into the extracellular space by cells of the prostate. The majority of proteins that are destined to be secreted are usually translated with an NH2-terminal cleavable signal peptide sequence. This structure is rich in hydrophobic amino acid residues that enable the polypeptide to dock and insert into the lumen of the endoplasmic reticulum for its further transport to the Golgi apparatus and eventual secretion as an intravesicular polypeptide. However, there are groups of extracellular proteins that neither display a signal peptide sequence in their primary structure nor utilize the classical endoplasmic reticulum (ER)-Golgi pathway for their release. This chapter focuses on the mechanisms of stress-induced release of two signaling proteins belonging to this group, fibroblast growth factor 1 (FGF-1) and interleukin 1ɑ (IL-lɑ). However, before discussing the export of these polypeptides, the literature concerning the nonclassical release of other signal peptide-less proteins is briefly reviewed.
Angiogenesis is controlled by several regulatory mechanisms, including the Notch and fibroblast g... more Angiogenesis is controlled by several regulatory mechanisms, including the Notch and fibroblast growth factor (FGF) signaling pathways. FGF1, a prototype member of FGF family, lacks a signal peptide and is released through an endoplasmic reticulum–Golgi-independent mechanism. A soluble extracellular domain of the Notch ligand Jagged1 (sJ1) inhibits Notch signaling and induces FGF1 release. Thrombin, a key protease of the blood coagulation cascade and a potent inducer of angiogenesis, stimulates rapid FGF1 release through a mechanism dependent on the major thrombin receptor protease-activated receptor (PAR) 1. This study demonstrates that thrombin cleaves Jagged1 in its extracellular domain. The sJ1 form produced as a result of thrombin cleavage inhibits Notch-mediated CBF1/Suppressor of Hairless [(Su(H)]/Lag-1–dependent transcription and induces FGF1 expression and release. The overexpression of Jagged1 in PAR1 null cells results in a rapid thrombin-induced export of FGF1. These dat...
Non-classical protein release independent of the ER-Golgi pathway has been reported for an increa... more Non-classical protein release independent of the ER-Golgi pathway has been reported for an increasing number of proteins lacking an N-terminal signal sequence. The export of FGF1 and IL-1α, two pro-angiogenic polypeptides, provides two such examples. In both cases, export is based on the Cu2+-dependent formation of multiprotein complexes containing the S100A13 protein and might involve translocation of the protein across the membrane as a `molten globule'. FGF1 and IL-1α are involved in pathological processes such as restenosis and tumor formation. Inhibition of their export by Cu2+ chelators is thus an effective strategy for treatment of several diseases.
Notch signaling involves proteolytic cleavage of the transmembrane Notch receptor after binding t... more Notch signaling involves proteolytic cleavage of the transmembrane Notch receptor after binding to its transmembrane ligands, Delta or Jagged; and the resultant soluble intracellular domain of Notch stimulates a cascade of transcriptional events. The Delta1 ligand also undergoes proteolytic cleavage upon Notch binding, resulting in the production of a free intracellular domain. We demonstrate that the expression of the intracellular domain of Delta1 results in a non‐proliferating senescent‐like cell phenotype which is dependent on the expression of the cell cycle inhibitor, p21, and is abolished by co‐expression of constitutively active Notch1. These data suggest a new intracellular role for Delta1.
NOTCH signaling is an evolutionarily conserved signaling pathway that regulates cell fate during ... more NOTCH signaling is an evolutionarily conserved signaling pathway that regulates cell fate during development and postnatal life. It has been increasingly linked to carcinogenesis, although its role in cancer seems to be highly context and tissue specific. Although NOTCH signaling is required for lung development, little is known about its role in lung cancer. In this study, we show that NOTCH signaling, as measured by the γ-secretase cleavage product NIC-1, is active in both normal human and lung tumor samples; however, downstream NOTCH readouts (i.e., HES-1 and HES-5) are elevated in lung tumors. Levels of NOTCH signaling components in primary human lung cells reflect observations in tissue samples, yet lung tumor cell lines showed little NOTCH signaling. Because oxygen concentrations are important in normal lung physiology and lung tumors are hypoxic, the effect of low oxygen on these lung tumor cell lines was evaluated. We found that hypoxia dramatically elevates NOTCH signaling ...
Malignant mesothelioma (MM) is a cancer of the lining of the lungs, heart, and intestine and is k... more Malignant mesothelioma (MM) is a cancer of the lining of the lungs, heart, and intestine and is known to respond poorly to chemotherapy. Here we show that malignant mesothelial cells have an elevated Notch signaling pathway compared with normal human mesothelial cells. We studied the role of Notch in MM under normoxic and hypoxic conditions, the latter condition best recapitulating the MM microenvironment. Genetic and chemical modulation of the Notch pathway indicated that MM cells are dependent on Notch signaling. More specifically, this signaling was Notch-1 dependent as the result of its negative transcriptional regulation on phosphatase and tensin homologue (PTEN), which led to activation of the prosurvival phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. Our study also provides evidence that whereas Notch-1 is elevated in the malignant setting, Notch-2 is diminished. This differential expression of the two Notch isoforms benefits ...
Mélanges de l'École française de Rome. Moyen Âge, 2019
Il contributo traccia sinteticamente la fortuna del tema iconografico della donna intenta alla sc... more Il contributo traccia sinteticamente la fortuna del tema iconografico della donna intenta alla scrittura, a partire dagli archetipi legati alla cultura classica, fino a giungere alle immagini emblematiche del Medioevo (la monaca, la mistica, le donne virtuose del De cleres et nobles femmes, ma anche l’allegoria della Grammatica e la raffigurazione della scrittrice Christine de Pizan) e dell’Eta moderna (la Vergine come allieva di Anna o maestra di Gesu, il modello ideale della “donna di palazzo”, la compositrice e l’accademica, l’aristocratica o la borghese colte nell’atto di scrivere una lettera privata). Questo saggio non ha la pretesa di presentare una rassegna completa delle iconografie relative al rapporto fra donna e cultura scritta, ma di mostrare alcuni esempi emblematici, privilegiando per quanto possibile tre punti di osservazione: le testimonianze figurative in cui la figura femminile e colta nell’atto di scrivere, piu che di leggere; le immagini in cui il testo manoscritto e reso fruibile alla lettura, in modo da esplicitare i contenuti ritenuti idonei all’occhio femminile; le opere dipinte da mano di donna, interessanti in quanto esito di un’ottica interna rispetto alla genesi di una coscienza di se.
Una fotografia conservata presso la Fondazione Federico Zeri documenta un dipinto di Stefano Tore... more Una fotografia conservata presso la Fondazione Federico Zeri documenta un dipinto di Stefano Torelli con Cristo e la Samaritana , firmato e datato 1774, fino ad oggi noto solo nel frammento della figura di Gesu (mercato dell'antiquariato, 1992): il rinvenimento offre lo spunto per un approfondimento relativo alla tarda produzione del pittore bolognese, che ne rivela gli interessi volti alla cultura artistica della Francia di Luigi XV, rafforzatisi durante il lungo periodo di carriera trascorso alla corte di Caterina II di Russia. L'arrivo nel 1766 a San Pietroburgo di Etienne-Maurice Falconet risveglia l'attrazione di Torelli per la seduttiva art de plaire messa a punto a Parigi dal grande scultore, gia collaboratore a Sevres di Francois Boucher, il «pittore delle grazie».
Supplementary Tables 1-2, Figures 1-8 from Opposite Effects of Notch-1 and Notch-2 on Mesotheliom... more Supplementary Tables 1-2, Figures 1-8 from Opposite Effects of Notch-1 and Notch-2 on Mesothelioma Cell Survival under Hypoxia Are Exerted through the Akt Pathway
Supplementary Legends 1-5 and Table 1 Legend from Oxygen Concentration Determines the Biological ... more Supplementary Legends 1-5 and Table 1 Legend from Oxygen Concentration Determines the Biological Effects of NOTCH-1 Signaling in Adenocarcinoma of the Lung
Supplementary Table 1 from Oxygen Concentration Determines the Biological Effects of NOTCH-1 Sign... more Supplementary Table 1 from Oxygen Concentration Determines the Biological Effects of NOTCH-1 Signaling in Adenocarcinoma of the Lung
DOAJ (DOAJ: Directory of Open Access Journals), Dec 28, 2014
In examining the fresco decorations of the Palazzo Sampieri-Talon in Bologna, the final collectiv... more In examining the fresco decorations of the Palazzo Sampieri-Talon in Bologna, the final collective work by Ludovico, Agostino and Annibale Carracci, with later additions by Guercino, the article concentrates on the yet unresolved reconstruction of its iconographic programme. The proposed interpretation is based on Claudian’s Alexandrine poem De raptu Proserpinae .
One of the earliest studies of nonclassical protein release was devoted to secretory transglutami... more One of the earliest studies of nonclassical protein release was devoted to secretory transglutaminase (TO), an enzyme that cross-links extracellular polypeptides and is released into the extracellular space by cells of the prostate. The majority of proteins that are destined to be secreted are usually translated with an NH2-terminal cleavable signal peptide sequence. This structure is rich in hydrophobic amino acid residues that enable the polypeptide to dock and insert into the lumen of the endoplasmic reticulum for its further transport to the Golgi apparatus and eventual secretion as an intravesicular polypeptide. However, there are groups of extracellular proteins that neither display a signal peptide sequence in their primary structure nor utilize the classical endoplasmic reticulum (ER)-Golgi pathway for their release. This chapter focuses on the mechanisms of stress-induced release of two signaling proteins belonging to this group, fibroblast growth factor 1 (FGF-1) and interleukin 1ɑ (IL-lɑ). However, before discussing the export of these polypeptides, the literature concerning the nonclassical release of other signal peptide-less proteins is briefly reviewed.
Angiogenesis is controlled by several regulatory mechanisms, including the Notch and fibroblast g... more Angiogenesis is controlled by several regulatory mechanisms, including the Notch and fibroblast growth factor (FGF) signaling pathways. FGF1, a prototype member of FGF family, lacks a signal peptide and is released through an endoplasmic reticulum–Golgi-independent mechanism. A soluble extracellular domain of the Notch ligand Jagged1 (sJ1) inhibits Notch signaling and induces FGF1 release. Thrombin, a key protease of the blood coagulation cascade and a potent inducer of angiogenesis, stimulates rapid FGF1 release through a mechanism dependent on the major thrombin receptor protease-activated receptor (PAR) 1. This study demonstrates that thrombin cleaves Jagged1 in its extracellular domain. The sJ1 form produced as a result of thrombin cleavage inhibits Notch-mediated CBF1/Suppressor of Hairless [(Su(H)]/Lag-1–dependent transcription and induces FGF1 expression and release. The overexpression of Jagged1 in PAR1 null cells results in a rapid thrombin-induced export of FGF1. These dat...
Non-classical protein release independent of the ER-Golgi pathway has been reported for an increa... more Non-classical protein release independent of the ER-Golgi pathway has been reported for an increasing number of proteins lacking an N-terminal signal sequence. The export of FGF1 and IL-1α, two pro-angiogenic polypeptides, provides two such examples. In both cases, export is based on the Cu2+-dependent formation of multiprotein complexes containing the S100A13 protein and might involve translocation of the protein across the membrane as a `molten globule'. FGF1 and IL-1α are involved in pathological processes such as restenosis and tumor formation. Inhibition of their export by Cu2+ chelators is thus an effective strategy for treatment of several diseases.
Notch signaling involves proteolytic cleavage of the transmembrane Notch receptor after binding t... more Notch signaling involves proteolytic cleavage of the transmembrane Notch receptor after binding to its transmembrane ligands, Delta or Jagged; and the resultant soluble intracellular domain of Notch stimulates a cascade of transcriptional events. The Delta1 ligand also undergoes proteolytic cleavage upon Notch binding, resulting in the production of a free intracellular domain. We demonstrate that the expression of the intracellular domain of Delta1 results in a non‐proliferating senescent‐like cell phenotype which is dependent on the expression of the cell cycle inhibitor, p21, and is abolished by co‐expression of constitutively active Notch1. These data suggest a new intracellular role for Delta1.
NOTCH signaling is an evolutionarily conserved signaling pathway that regulates cell fate during ... more NOTCH signaling is an evolutionarily conserved signaling pathway that regulates cell fate during development and postnatal life. It has been increasingly linked to carcinogenesis, although its role in cancer seems to be highly context and tissue specific. Although NOTCH signaling is required for lung development, little is known about its role in lung cancer. In this study, we show that NOTCH signaling, as measured by the γ-secretase cleavage product NIC-1, is active in both normal human and lung tumor samples; however, downstream NOTCH readouts (i.e., HES-1 and HES-5) are elevated in lung tumors. Levels of NOTCH signaling components in primary human lung cells reflect observations in tissue samples, yet lung tumor cell lines showed little NOTCH signaling. Because oxygen concentrations are important in normal lung physiology and lung tumors are hypoxic, the effect of low oxygen on these lung tumor cell lines was evaluated. We found that hypoxia dramatically elevates NOTCH signaling ...
Malignant mesothelioma (MM) is a cancer of the lining of the lungs, heart, and intestine and is k... more Malignant mesothelioma (MM) is a cancer of the lining of the lungs, heart, and intestine and is known to respond poorly to chemotherapy. Here we show that malignant mesothelial cells have an elevated Notch signaling pathway compared with normal human mesothelial cells. We studied the role of Notch in MM under normoxic and hypoxic conditions, the latter condition best recapitulating the MM microenvironment. Genetic and chemical modulation of the Notch pathway indicated that MM cells are dependent on Notch signaling. More specifically, this signaling was Notch-1 dependent as the result of its negative transcriptional regulation on phosphatase and tensin homologue (PTEN), which led to activation of the prosurvival phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. Our study also provides evidence that whereas Notch-1 is elevated in the malignant setting, Notch-2 is diminished. This differential expression of the two Notch isoforms benefits ...
Mélanges de l'École française de Rome. Moyen Âge, 2019
Il contributo traccia sinteticamente la fortuna del tema iconografico della donna intenta alla sc... more Il contributo traccia sinteticamente la fortuna del tema iconografico della donna intenta alla scrittura, a partire dagli archetipi legati alla cultura classica, fino a giungere alle immagini emblematiche del Medioevo (la monaca, la mistica, le donne virtuose del De cleres et nobles femmes, ma anche l’allegoria della Grammatica e la raffigurazione della scrittrice Christine de Pizan) e dell’Eta moderna (la Vergine come allieva di Anna o maestra di Gesu, il modello ideale della “donna di palazzo”, la compositrice e l’accademica, l’aristocratica o la borghese colte nell’atto di scrivere una lettera privata). Questo saggio non ha la pretesa di presentare una rassegna completa delle iconografie relative al rapporto fra donna e cultura scritta, ma di mostrare alcuni esempi emblematici, privilegiando per quanto possibile tre punti di osservazione: le testimonianze figurative in cui la figura femminile e colta nell’atto di scrivere, piu che di leggere; le immagini in cui il testo manoscritto e reso fruibile alla lettura, in modo da esplicitare i contenuti ritenuti idonei all’occhio femminile; le opere dipinte da mano di donna, interessanti in quanto esito di un’ottica interna rispetto alla genesi di una coscienza di se.
Una fotografia conservata presso la Fondazione Federico Zeri documenta un dipinto di Stefano Tore... more Una fotografia conservata presso la Fondazione Federico Zeri documenta un dipinto di Stefano Torelli con Cristo e la Samaritana , firmato e datato 1774, fino ad oggi noto solo nel frammento della figura di Gesu (mercato dell'antiquariato, 1992): il rinvenimento offre lo spunto per un approfondimento relativo alla tarda produzione del pittore bolognese, che ne rivela gli interessi volti alla cultura artistica della Francia di Luigi XV, rafforzatisi durante il lungo periodo di carriera trascorso alla corte di Caterina II di Russia. L'arrivo nel 1766 a San Pietroburgo di Etienne-Maurice Falconet risveglia l'attrazione di Torelli per la seduttiva art de plaire messa a punto a Parigi dal grande scultore, gia collaboratore a Sevres di Francois Boucher, il «pittore delle grazie».
Caterina Vigri, la Santa di Bologna: Arte e mistica femminile nei chiostri BOLOGNA 13-14 Nov. 202... more Caterina Vigri, la Santa di Bologna: Arte e mistica femminile nei chiostri BOLOGNA 13-14 Nov. 2024. Convegno di Studi a cura di Irene Graziani e Francesco Vincenti
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