24 results on '"Nicolis S"'
Search Results
2. Sox2 is dispensable for primary melanoma and metastasis formation
- Author
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Schaefer, S M, Segalada, C, Cheng, P F, Bonalli, M, Parfejevs, V, Levesque, M P, Dummer, R, Nicolis, S K, and Sommer, L
- Abstract
Tumor initiation and metastasis formation in many cancers have been associated with emergence of a gene expression program normally active in embryonic or organ-specific stem cells. In particular, the stem cell transcription factor Sox2 is not only expressed in a variety of tumors, but is also required for their formation. Melanoma, the most aggressive skin tumor, derives from melanocytes that during development originate from neural crest stem cells. While neural crest stem cells do not express Sox2, expression of this transcription factor has been reported in melanoma. However, the role of Sox2 in melanoma is controversial. To study the requirement of Sox2 for melanoma formation, we therefore performed CRISPR-Cas9-mediated gene inactivation in human melanoma cells. In addition, we conditionally inactivated Sox2in a genetically engineered mouse model, in which melanoma spontaneously develops in the context of an intact stroma and immune system. Surprisingly, in both models, loss of Sox2 did neither affect melanoma initiation, nor growth, nor metastasis formation. The lack of a tumorigenic role of Sox2 in melanoma might reflect a distinct stem cell program active in neural crest stem cells and during melanoma formation.
- Published
- 2017
- Full Text
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3. Sox2 is not required for melanomagenesis, melanoma growth and melanoma metastasis in vivo
- Author
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Cesarini, V, Guida, E, Todaro, F, Di Agostino, S, Tassinari, V, Nicolis, S, Favaro, R, Caporali, S, Lacal, P M, Botti, E, Costanzo, A, Rossi, P, Jannini, E A, and Dolci, S
- Abstract
Melanoma is a dangerous form of skin cancer derived from the malignant transformation of melanocytes. The transcription factor SOX2 is not expressed in melanocytes, however, it has been shown to be differentially expressed between benign nevi and malignant melanomas and to be essential for melanoma stem cell maintenance and expansion in vitroand in xenograft models. By using a mouse model in which BRafV600Emutation cooperates with Ptenloss to induce the development of metastatic melanoma, we investigated if Sox2 is required during the process of melanomagenesis, melanoma growth and metastasis and in the acquisition of resistance to BRAF inhibitors (BRAFi) treatments. We found that deletion of Sox2specifically in Ptennull and BRafV600E-expressing melanocytes did not prevent tumor formation and did not modify the temporal kinetics of melanoma occurrence compared to Sox2 wtmice. In addition, tumor growth was similar between Sox2 wtand Sox2 deleted (del)melanomas. By querying publicly available databases, we did not find statistically significant differences in SOX2 expression levels between benign nevi and melanomas, and analysis on two melanoma patient cohorts confirmed that Sox2 levels did not significantly change between primary and metastatic melanomas. Melanoma cell lines derived from both Sox2genotypes showed a similar sensitivity to vemurafenib treatment and the same ability to develop vemurafenib resistance in long-term cultures. Development of vemurafenib resistance was not dependent on SOX2 expression also in human melanoma cell lines in vitro. Our findings exclude an oncogenic function for Sox2 during melanoma development and do not support a role for this transcription factor in the acquisition of resistance to BRAFi treatments.
- Published
- 2017
- Full Text
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4. The Selfish to Egalitarian Transition in Young Children: Developmental Processes versus Cooperative Interactions.
- Author
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Nicolis, H. and Nicolis, S. C.
- Subjects
SOCIAL groups ,MANNERS & customs ,HISTRIONIC personality disorder ,MATHEMATICAL models ,SELFISHNESS - Abstract
There is evidence that a tendency to share resources equitably among members of a social group emerges in middle childhood. It is regarded by many investigators as a central and unique feature of human social life. In this work the relative roles of developmental processes and collective effects generated by interindividual interactions on the selfish to egalitarian transition observed in middle childhood are analyzed. Using mathematical modeling, conditions are identified under which the transition becomes sharp and gives rise to hysteretic behavior. [ABSTRACT FROM AUTHOR]
- Published
- 2010
5. Catalytic Activity of Myoglobin Immobilized on Zirconium Phosphonates
- Author
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Bellezza, F., Cipiciani, A., Costantino, U., and Nicolis, S.
- Abstract
The adsorption and catalytic activity of myoglobin (Mb) on zirconium phosphonates (α-zirconium benzenephosphonate (α-ZrBP), α-zirconium carboxyethanephosphonate (α-ZrCEP), and a novel layered zirconium fluoride aminooctyl-N,N-bis(methylphosphonate) (ZrC8)) were investigated. The maximum adsorption was reached after 16 h of contact and was greater on hydrophobic supports such as α-ZrBP and ZrC8 compared to hydrophilic supports such as α-ZrCEP. The equilibrium adsorption isotherms fitted the Langmuir equation, suggesting the presence of a monolayer of protein molecules on the support surfaces. The catalytic activities of free Mb and of the obtained biocomposites were studied in terms of the oxidation of two aromatic substrates, o-phenylenediamine and 2-methoxyphenol (guaiacol), by hydrogen peroxide. The oxidation catalyzed by immobilized myoglobin followed the Michaelis−Menten kinetics, similar to oxidation by free Mb. The kinetic parameters, k
cat and KM , were significantly affected by the adsorption process. Mb/α-ZrCEP was the most efficient biocatalyst obtained, probably because of the hydrophilic nature of the support. The effect of immobilization on the stability of Mb toward inactivation by hydrogen peroxide was also investigated, and an increased resistance was found. The biocomposites obtained can be stored at 4 °C for months without a significant loss of catalytic activity.- Published
- 2004
6. Multi-layer structure in the strongly coupled 5D abelian Higgs model
- Author
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Dimopoulos, P., Farakos, K., and Nicolis, S.
- Abstract
Abstract.: We explore the phase diagram of the five-dimensional anisotropic Abelian Higgs model by Monte Carlo simulations. In particular, we study the transition between the confining phase and the four-dimensional layered Higgs phase. We find that, in a certain region of the lattice parameter space, this transition can be first order, and that each layer moves into the Higgs phase independently of the others (decoupling of layers). As the Higgs couplings vary, we find, using mean field techniques, that this transition may probably become second order.
- Published
- 2002
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7. Sox2 regulatory sequences direct expression of a (beta)-geo transgene to telencephalic neural stem cells and precursors of the mouse embryo, revealing regionalization of gene expression in CNS stem cells.
- Author
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Zappone, M V, Galli, R, Catena, R, Meani, N, De Biasi, S, Mattei, E, Tiveron, C, Vescovi, A L, Lovell-Badge, R, Ottolenghi, S, and Nicolis, S K
- Abstract
Sox2 is one of the earliest known transcription factors expressed in the developing neural tube. Although it is expressed throughout the early neuroepithelium, we show that its later expression must depend on the activity of more than one regionally restricted enhancer element. Thus, by using transgenic assays and by homologous recombination-mediated deletion, we identify a region upstream of Sox2 (-5.7 to -3.3 kb) which can not only drive expression of a (beta)-geo transgene to the developing dorsal telencephalon, but which is required to do so in the context of the endogenous gene. The critical enhancer can be further delimited to an 800 bp fragment of DNA surrounding a nuclease hypersensitive site within this region, as this is sufficient to confer telencephalic expression to a 3.3 kb fragment including the Sox2 promoter, which is otherwise inactive in the CNS. Expression of the 5.7 kb Sox2(beta)-geo transgene localizes to the neural plate and later to the telencephalic ventricular zone. We show, by in vitro clonogenic assays, that transgene-expressing (and thus G418-resistant) ventricular zone cells include cells displaying functional properties of stem cells, i.e. self-renewal and multipotentiality. We further show that the majority of telencephalic stem cells express the transgene, and this expression is largely maintained over two months in culture (more than 40 cell divisions) in the absence of G418 selective pressure. In contrast, stem cells grown in parallel from the spinal cord never express the transgene, and die in G418. Expression of endogenous telencephalic genes was similarly observed in long-term cultures derived from the dorsal telencephalon, but not in spinal cord-derived cultures. Thus, neural stem cells of the midgestation embryo are endowed with region-specific gene expression (at least with respect to some networks of transcription factors, such as that driving telencephalic expression of the Sox2 transgene), which can be inherited through multiple divisions outside the embryonic environment.
- Published
- 2000
8. Immortalization of multipotent growth‐factor dependent hemopoietic progenitors from mice transgenic for GATA‐1 driven SV40 tsA58 gene.
- Author
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Cairns, L.A., Crotta, S., Minuzzo, M., Moroni, E., Granucci, F., Nicolis, S., Schiró, R., Pozzi, L., Giglioni, B., and Ricciardi‐Castagnoli, P.
- Abstract
The transcription factor GATA‐1 is required for the normal development of erythroid cells. GATA‐1 is also expressed in other hemopoietic cells, suggesting that it might be initially activated in a multipotent progenitor. To immortalize GATA‐1‐expressing progenitors, we generated mice transgenic for a thermosensitive SV40 T gene, driven by the GATA‐1 promoter‐enhancer. Immortalized marrow cells grow in culture at 32 degrees C but not at 38 degrees C, and are dependent on erythropoietin (Epo) or interleukin 3 (IL‐3). Epo dependent cells express hemoglobin, high levels of GATA‐1, GATA‐2 and NF‐E2 p45 mRNAs, and are positive for stem cell antigen 2 (Sca‐2) and the early myeloid marker ER‐MP12. IL‐3 dependent cells can be derived from Epo dependent lines, and are hemoglobin‐, Sca‐2‐ and ER‐MP12‐negative, have low GATA‐1 and NF‐E2 p45 mRNA levels, and express myeloid markers Mac‐1, F4/80 and Gr‐1. Brief treatment of Epo dependent cells with myeloid growth factors (plus Epo) leads to the induction of Mac‐1, F4/80 and Gr‐1, concomitant with the disappearance from most cells of Sca‐2, ER‐MP12 and GATA‐1 driven T antigen nuclear expression. Thus, the immortalized Epo dependent cells have the property of a progenitor capable of differentiation towards either the erythroid or myeloid lineages. These cells initiate transcription of a proportion of GATA‐1 RNA molecules at an upstream promoter, previously known to be expressed only in testis cells.
- Published
- 1994
- Full Text
- View/download PDF
9. Transcriptional and posttranscriptional regulation of the expression of the erythropoietin receptor gene in human erythropoietin-responsive cell lines
- Author
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Migliaccio, AR, Jiang, Y, Migliaccio, G, Nicolis, S, Crotta, S, Ronchi, A, Ottolenghi, S, and Adamson, JW
- Abstract
With erythroid differentiation, committed progenitor cells acquire the ability to respond to erythropoietin (Epo). Epo interacts with target cells through the Epo receptor (Epo-R), whose expression is tightly regulated in a lineage-specific fashion. Epo-R expression is presumed to be progressively activated or repressed as cells progress along the erythroid or the myeloid pathway, respectively. Little is known of the mechanisms that underlie the erythroid-specific expression of the Epo-R gene. GATA-1, the major known transcription factor involved in Epo-R gene regulation, is not erythroid-specific. We have studied the regulation of the expression of the Epo-R gene in two related human Epo- responsive cell lines, UT-7 and UT-7 Epo. These lines express Epo-R at high levels because of amplification of the endogenous gene, which is apparently not rearranged. Treatment for 6 to 24 hours with the tumor promoter, phorbol myristate acetate (PMA), or 24 hours of growth factor starvation (Epo or granulocyte/macrophage colony-stimulating factor [GM- CSF]) decreased or increased the levels of Epo-R mRNA, respectively. In the case of growth factor starvation, the increase (approximately equal to threefold) in the level of Epo-R mRNA correlated directly with an increase in the rate of Epo-R gene transcription as measured by run-off assay. Both increases were observed as early as 3 hours after the growth factor was withdrawn and were reversible; levels of mRNA and transcription rates returned to baseline 3 hours after the cells were reexposed to growth factors. The changes in Epo-R expression after growth factor starvation were coordinated with changes in the level of expression of GATA-1 that were detected both at the mRNA and at the gene transcription level under these conditions (suggesting that GATA-1 was responsible for this upregulation). During PMA treatment, after a transient increase in Epo-R mRNA at 1 hour, a progressive decline in the level of Epo-R mRNA was observed; the level of Epo-R mRNA decreased by 50%, and fell below the level of detection by 6 and 24 hours, respectively. This decrement was explained in part by a fourfold reduction in the rate of gene transcription as well as a reduction (measured as levels of Epo-R mRNA in the presence of actinomycin D) in mRNA stability. The changes in transcription rate occurred in the absence of changes in the level of GATA-1 binding activity.(ABSTRACT TRUNCATED AT 400 WORDS)
- Published
- 1993
- Full Text
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10. Neural potentials as stimuli for attractor neural networks
- Author
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Amit, Daniel J, Parisi, G, and Nicolis, S
- Abstract
The retrieval properties of attractor neural networks are studied, subject to a modification of the representation of the stimulus input. In the present study the stimulus imposes an initial state on the network and then remains as a persistent potential input (local field) of weakened amplitude, but containing the same number of errors as the initial, strong input. The dynamics of this network is analysed assuming three different types of error distributions in the persistent stimulus, i.e. Gaussian, discrete and hidden units. It is found that, below saturation of the free network, the persistent stimulus does not damage the retrieval properties of the free network up to rather high values of the field amplitude. Even above saturation, for all loading levels, the network corrects errors if the field amplitude is not too low. The system is studied by solving mean-field equations for its attractors. The solutions are then compared with simulations.The results lead to the conclusion that the memory loading level at which the network stops acting as an effective associative memory is determined, biologically, by the size of a plausible stimulus input and by the level of errors that can be biologically tolerated.In order to extend the study to a potential sequence of error-correcting oversaturated networks we introduce random synaptic dilution. It is intended to prevent much correlation between the error bits in the dynamics of the two coupled networks. This compound system is studied by simulations. Finally, we discuss a potential theoretical project in which the dynamics of the coupled networks can be studied analytically.
- Published
- 1990
- Full Text
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11. Chiral defect fermions and the layered phase
- Author
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Korthals-Altes, C.P., Nicolis, S., and Prades, J.
- Abstract
Chiral defect fermions on the lattice in 4 + 1 dimensions are analyzed using mean field theory. The fermion propagator has a localized chiral model in weak coupling but loses it when the coupling in the unphysical fifth direction becomes too large. A layered phase à la Fu-Nielsen appears where the theory is vector-like in every layer.
- Published
- 1993
- Full Text
- View/download PDF
12. DNA Sequences Regulating Human Globin Gene Transcription in Nondeletional Hereditary Persistence of Fetal Hemoglobin
- Author
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Ottolenghi, S., Mantovani, R., Nicolis, S., Ronchi, A., and Giglioni, B.
- Abstract
Strong genetic evidence supports the idea that point mutations in the promoter of γ-globin genes overexpressed in adult age [hereditary persistence of fetal hemoglobin (HPFH)] are responsible for the observed phenotype. DNA binding sites for ubiquitous and/or erythroid specific nuclear proteins correlate in location with the positions of point mutations responsible for HPFH. The analysis of the effects of one of these mutations (-175 T°C) on in vitro binding of nuclear proteins and on the activity of the mutated promoter in transfection assays indicates that altered binding of the erythroid-specific protein NFE-1 may be responsible for increased activity of the mutated promoter. Other HPFH mutations close to the distal CCAAT box (-117 G→A and 13 nucleotide deletions, -114 to -102) have complex effects on in vitro binding of nuclear proteins; their only common effect is the loss of binding of the erythroid-specific factor NFE3. If mechanisms generating the HPFH phenotype are homogeneous, NFE3 might be a negatively acting factor; alternatively, heterogeneous mechanisms might operate and HPFH might additionally be related to loss of binding to the distal CCAAT box region of either NFE1 (-117 HPFH) or of the ubiquitous CCAAT displacement protein-CDP (13 nucleotides deletion).
- Published
- 1989
- Full Text
- View/download PDF
13. Transcriptional and Posttranscriptional Regulation of the Expression of the Erythropoietin Receptor Gene in Human Erythropoietin-Responsive Cell Lines
- Author
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Migliaccio, A.R., Jiang, Y., Migliaccio, G., Nicolis, S, Crotta, S., Ronchi, A., Ottolenghi, S., and Adamson, J.W.
- Abstract
With erythroid differentiation, committed progenitor cells acquire the ability to respond to erythropoietin (Epo). Epo interacts with target cells through the Epo receptor (EpoR), whose expression is tightly regulated in a lineage-specific fashion. Epo-R expression is presumed to be progressively activated or repressed as cells progress along the erythroid or the myeloid pathway, respectively. Little is known of the mechanisms that underlie the erythroid-specific expression of the Epo-R gene. GATA-1, the major known transcription factor involved in Epo-R gene regulation, is not erythroid-specific. We have studied the regulation of the expression of the Epo-R gene in two related human Epo-responsive cell lines, UT-7 and UT-7 Epo. These lines express Epo-R at high levels because of amplification of the endogenous gene, which is apparently not rearranged. Treatment for 6 to 24 hours with the tumor promoter, phorbol myristate acetate (PMA), or 24 hours of growth factor starvation (Epo or granulocyte/macrophage colony-stimulating factor [GM-CSF]) decreased or increased the levels of Epo-R mRNA, respectively. In the case of growth factor starvation, the increase (≅threefold) in the level of Epo-R mRNA correlated directly with an increase in the rate of Epo-R gene transcription as measured by run-off assay. Both increases were observed as early as 3 hours after the growth factor was withdrawn and were reversible; levels of mRNA and transcription rates returned to baseline 3 hours after the cells were reexposed to growth factors. The changes in Epo-R expression after growth factor starvation were coordinated with changes in the level of expression of GATA-1 that were detected both at the mRNA and at the gene transcription level under these conditions (suggesting that GATA-1 was responsible for this upregulation). During PMA treatment, after a transient increase in Epo-R mRNA at 1 hour, a progressive decline in the level of Epo-R mRNA was observed; the level of Epo-R mRNA decreased by 50%, and fell below the level of detection by 6 and 24 hours, respectively. This decrement was explained in part by a fourfold reduction in the rate of gene transcription as well as a reduction (measured as levels of Epo-R mRNA in the presence of actinomycin D) in mRNA stability. The changes in transcription rate occurred in the absence of changes in the level of GATA-1 binding activity. The decrement in Epo-R mRNA stability (from 2.5 hours to 30 minutes) was observed after 2 hours of incubation with PMA, and was dependent on de novo gene activation. These results indicate that multiple levels of Epo-R gene regulation exist, not all of them GATA-1 dependent. In particular, a GATA-1-independent mechanism appears to be involved in the repression of Epo-R gene expression during PMA treatment. This mechanism could be important in myeloid-specific suppression of Epo-R gene expression.
- Published
- 1993
- Full Text
- View/download PDF
14. Response to erythropoietin in erythroid subclones of the factor-dependent cell line 32D is determined by translocation of the erythropoietin receptor to the cell surface.
- Author
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Migliaccio, A R, Migliaccio, G, D'Andrea, A, Baiocchi, M, Crotta, S, Nicolis, S, Ottolenghi, S, and Adamson, J W
- Abstract
Regulation of the expression of the erythropoietin (Epo) receptor (EpoR) gene is under the control of transcriptional regulatory factor GATA-1. GATA-1 is expressed widely among the nonerythroid, factor-dependent subclones of the interleukin 3-dependent mouse cell line 32D. Consequently, to determine whether GATA-1 and EpoR gene expression are linked even in nonerythroid cells, we have studied the correlation of GATA-1 expression with expression and function of EpoR in these cell lines. EpoR mRNA (by RNase protection analysis) and EpoR protein (by specific antibody immunoprecipitation of metabolically labeled EpoR protein) were detectable not only in 32D and 32D Epo (an Epo-dependent subclone) but also in 32D GM, a subclone dependent for growth on granulocyte/macrophage colony-stimulating factor. EpoR mRNA also was detectable by PCR in 32D G, a subclone dependent for growth on granulocyte colony-stimulating factor. However, only 32D Epo cells bound 125I-labeled Epo and expressed EpoR protein on the cell surface, as determined by immunoprecipitation of surface-labeled proteins. These results indicate that, in these factor-dependent cell lines, the major regulatory step determining the erythroid-specific response to Epo is the efficiency of EpoR protein translocation to the cell surface. Mechanisms that could affect lineage-specific translocation are the presence of a chaperone protein, erythroid-specific editing of EpoR mRNA, or altered processing of the EpoR protein to the cell surface. In this model, lineage-restricted responses to growth factors such as Epo are determined not by expression of the genes for growth factor receptors but, rather, by appropriate processing of the receptor protein.
- Published
- 1991
- Full Text
- View/download PDF
15. Immortalization of multipotent growth‐factor dependent hemopoietic progenitors from mice transgenic for GATA‐1 driven SV40 tsA58 gene.
- Author
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Cairns, L.A., Crotta, S., Minuzzo, M., Moroni, E., Granucci, F., Nicolis, S., Schiró, R., Pozzi, L., Giglioni, B., and Ricciardi‐Castagnoli, P.
- Abstract
The transcription factor GATA‐1 is required for the normal development of erythroid cells. GATA‐1 is also expressed in other hemopoietic cells, suggesting that it might be initially activated in a multipotent progenitor. To immortalize GATA‐1‐expressing progenitors, we generated mice transgenic for a thermosensitive SV40 T gene, driven by the GATA‐1 promoter‐enhancer. Immortalized marrow cells grow in culture at 32 degrees C but not at 38 degrees C, and are dependent on erythropoietin (Epo) or interleukin 3 (IL‐3). Epo dependent cells express hemoglobin, high levels of GATA‐1, GATA‐2 and NF‐E2 p45 mRNAs, and are positive for stem cell antigen 2 (Sca‐2) and the early myeloid marker ER‐MP12. IL‐3 dependent cells can be derived from Epo dependent lines, and are hemoglobin‐, Sca‐2‐ and ER‐MP12‐negative, have low GATA‐1 and NF‐E2 p45 mRNA levels, and express myeloid markers Mac‐1, F4/80 and Gr‐1. Brief treatment of Epo dependent cells with myeloid growth factors (plus Epo) leads to the induction of Mac‐1, F4/80 and Gr‐1, concomitant with the disappearance from most cells of Sca‐2, ER‐MP12 and GATA‐1 driven T antigen nuclear expression. Thus, the immortalized Epo dependent cells have the property of a progenitor capable of differentiation towards either the erythroid or myeloid lineages. These cells initiate transcription of a proportion of GATA‐1 RNA molecules at an upstream promoter, previously known to be expressed only in testis cells.
- Published
- 1994
- Full Text
- View/download PDF
16. A cis-acting DNA signal for encapsidation of simian virus 40
- Author
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Oppenheim, A, Sandalon, Z, Peleg, A, Shaul, O, Nicolis, S, and Ottolenghi, S
- Abstract
Encapsidation of simian virus 40 is a complex biological process involving DNA-protein and protein-protein interactions in the formation of a unique three-dimensional structure around the viral minichromosome. A pseudoviral system developed in our laboratory, in which the viral early and late gene products are supplied in trans (by helpers), was used to analyze the encapsidation process independent of viral gene expression. With this experimental system we have discovered a requirement for a specific DNA signal for encapsidation, ses (for simian virus 40 encapsidation signal).ses is present within a 200-bp DNA fragment, which includes, in addition to the viral origin of replication (ori), six GGGCGG repeats (GC boxes) and 26 bp of the enhancer element. Deletion of the GC boxes and the enhancer sequences almost abolished encapsidation, while DNA replication was only moderately decreased. The ability to encapsidate was not regained by reinserting a DNA fragment carrying ses in the sesdeleted plasmid 2 kbp away from the ori, suggesting that for encapsidation the two DNA elements have to be close to each other. These findings afford novel strategies for the investigation of viral encapsidation.
- Published
- 1992
- Full Text
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17. Gauge theories with a layered phase
- Author
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Nicolis, S.
- Abstract
The mean field theory of gauge theories with anisotropic couplings shows that they possess a layered phase, in addition to the usual confining and Coulomb phases. We find that the layered to Coulomb phase transition is second order in the absence, as well as in the presence of fermions. This is supported by Monte Carlo simulations and leads to the possibility of defining sensible models with domain wall fermions.
- Published
- 1995
- Full Text
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18. Mapping the gene encoding the human erythroid transcriptional factor NFE1-GF1 to Xp11.23
- Author
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Caiulo, A., Nicolis, S., Bianchi, P., Zuffardi, O., Bardoni, B., Maraschio, P., Ottolenghi, S., Camerino, G., and Giglioni, B.
- Abstract
The X-linked NFE1 gene encodes an erythroid factor involved in globin gene transcription. Using a human cDNA clone encoding this factor, we show, by in situ hybridization and by analysis of human-rodent hybrid cell lines, that this gene is located in Xp11.23. In the absence of polymorphisms in the NFE1 gene, these results allow the study of the possible relationships between NFE1 mutations and X-linked hereditary persistence of fetal hemoglobin by linkage analysis with RFLP markers of the region. A female patient, hemizygous for the NFE1 locus, shows essentially normal hematological parameters.
- Published
- 1991
- Full Text
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19. Sardinian Gγ-HPFH: A T → C Substitution in a Conserved “Octamer” Sequence in the Gγ-Globin Promoter
- Author
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Ottolenghi, S., Nicolis, S., Taramelli, R., Malgaretti, N., Mantovani, R., Comi, P., Giglioni, B., Longinotti, M., Dore, F., Oggiano, L., Pistidda, P., Serra, A., Camaschella, C., and Saglio, G.
- Abstract
A survey of hemoglobinopathies in Northern Sardinia allowed the identification of two subjects heterozygous for a new type of Gγhereditary persistence of fetal hemoglobin (HPFH). The Gγ-globin gene from the HPFH chromosome shows the presence of a T → C substitution 175 nucleotides upstream of the CAP site, adding a new example of single-point mutations occurring in the promoter region of the γ -globin genes and linked to HPFH phenotypes. In this case the mutation affects the 3’ end nucleotide of a conserved octamer sequence known to be present in other regulatory elements of several genes.
- Published
- 1988
- Full Text
- View/download PDF
20. Sardinian G gamma-HPFH: a T----C substitution in a conserved "octamer" sequence in the G gamma-globin promoter
- Author
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Ottolenghi, S, Nicolis, S, Taramelli, R, Malgaretti, N, Mantovani, R, Comi, P, Giglioni, B, Longinotti, M, Dore, F, and Oggiano, L
- Abstract
A survey of hemoglobinopathies in Northern Sardinia allowed the identification of two subjects heterozygous for a new type of G gamma hereditary persistence of fetal hemoglobin (HPFH). The G gamma-globin gene from the HPFH chromosome shows the presence of a T----C substitution 175 nucleotides upstream of the CAP site, adding a new example of single-point mutations occurring in the promoter region of the gamma-globin genes and linked to HPFH phenotypes. In this case the mutation affects the 3' end nucleotide of a conserved octamer sequence known to be present in other regulatory elements of several genes.
- Published
- 1988
- Full Text
- View/download PDF
21. The effects of HPFH mutations in the human {gamma}-globin promoter on binding of ubiquitous and erythroid specific nuclear factors
- Author
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Mantovani, R., Malgaretti, N., Nicolis, S., Ronchi, A., Giglioni, B., and Ottolenghi, S.
- Abstract
Genetic evldence Indicates that single point mutations in the γ-globin promoter may be the cause of high expression of the mutated gene in the adult period (Hereditary Persistence of Fetal Hemoglobin, HPFH). Here we show that one of these mutations characterized by a T > C substitution at position 175 in a conserved octamer (ATGCAAAT) sequence, abollshes the ability of a ubiquitous octamer binding nuclear protein to bind a γ-globln promoter fragment containing the mutated sequence: however, the ability of two erythroid specific proteins to bind the same fragment is increased three to five fold. DMS Interference and binding experiments with mutated fragments indicate that the ubiquitous protein recognizes the octamer sequence, while the erythrold specific proteins B2, B3 recognize flanking nucieotldes. Competition experiments indicate that protein B2 corresponds to an erythrold-specific protein known to bind to a consensus GATAG sequence present at several locations In α β and γ-globin genes. Although the distal CCAAT box region oil the γ-globin gene shows a related sequence, an oligonucleotide Including this sequence does not show any ability to bind the above mentioned erythroid protein; Instead, It binds a different erythrold specific protein, in addition to a ubiquitous protein. The -117 G > A mutation also known to cause HPFH, and mapping two nucleotides upstream from the CCAAT box, greatly decreases the binding of the erythrold-specific, but not that oil the ubiquitous protein, to the CCAAT box region fragment.
- Published
- 1988
- Full Text
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22. Gauge theories with a layered phase
- Author
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NICOLIS, S
- Published
- 1995
- Full Text
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23. The erythroid transcription factor NFE1 is expressed in progenitor myeloid cells
- Author
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Ottolenghi, S, Nicolis, S., Crotta, S., Ronchi, A., Migliaccio, G., Ruzzi, L., Migliaccio, A.R., and Adamson, J.
- Published
- 1990
- Full Text
- View/download PDF
24. Gauge theories with a layered phase
- Author
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Hulsebos, A., Korthals-Altes, C. P., and Nicolis, S.
- Published
- 1995
- Full Text
- View/download PDF
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