Littérature scientifique sur le sujet « BCR promoter »
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Articles de revues sur le sujet "BCR promoter"
1
Shah, N. P., O. N. Witte et C. T. Denny. « Characterization of the BCR promoter in Philadelphia chromosome-positive and -negative cell lines ». Molecular and Cellular Biology 11, no 4 (avril 1991) : 1854–60. http://dx.doi.org/10.1128/mcb.11.4.1854-1860.1991.
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The t(9;22) Philadelphia chromosome translocation fuses 5' regulatory and coding sequences of the BCR gene to the c-ABL proto-oncogene. This results in the formation of hybrid BCR-ABL mRNAs and proteins. The shift in ABL transcriptional control to the BCR promoter may play a role in cellular transformation mediated by this rearrangement. We have functionally localized the BCR promoter to a region 1 kb 5' of BCR exon 1 coding sequences by using a chloramphenicol acetyltransferase reporter gene assay. Nucleotide sequence analysis of this region revealed many consensus binding sequences for transcription factor SP1 as well as two potential CCAAT box binding factor sites and one putative helix-loop-helix transcription factor binding site. No TATA-like or "initiator" element sequences were found. Because of low steady-state levels of BCR mRNA and the high GC content (78%) of the promoter region, definitive mapping of transcription start sites required artificial amplification of BCR promoter-directed transcripts. Overexpression from the BCR promoter in a COS cell system was effective in demonstrating multiple transcription initiation sites. In order to assess the effects of chromosomal translocation on the transcriptional control of the BCR gene, we determined S1 nuclease protection patterns of poly(A)+ RNA from tumor cell lines. No differences were observed in the locations and levels of BCR transcription initiation sites between those lines that harbored the t(9;22) translocation and those that did not. This demonstrates that BCR promoter function remains intact in spite of genomic rearrangement. The BCR promoter is structurally similar to the ABL promoters. Together, this suggests that the structural fusion of BCR-ABL and not its transcriptional deregulation is primarily responsible for the transforming effect of the t(9;22) translocation.
2
Shah, N. P., O. N. Witte et C. T. Denny. « Characterization of the BCR promoter in Philadelphia chromosome-positive and -negative cell lines. » Molecular and Cellular Biology 11, no 4 (avril 1991) : 1854–60. http://dx.doi.org/10.1128/mcb.11.4.1854.
Texte intégralRésumé :
The t(9;22) Philadelphia chromosome translocation fuses 5' regulatory and coding sequences of the BCR gene to the c-ABL proto-oncogene. This results in the formation of hybrid BCR-ABL mRNAs and proteins. The shift in ABL transcriptional control to the BCR promoter may play a role in cellular transformation mediated by this rearrangement. We have functionally localized the BCR promoter to a region 1 kb 5' of BCR exon 1 coding sequences by using a chloramphenicol acetyltransferase reporter gene assay. Nucleotide sequence analysis of this region revealed many consensus binding sequences for transcription factor SP1 as well as two potential CCAAT box binding factor sites and one putative helix-loop-helix transcription factor binding site. No TATA-like or "initiator" element sequences were found. Because of low steady-state levels of BCR mRNA and the high GC content (78%) of the promoter region, definitive mapping of transcription start sites required artificial amplification of BCR promoter-directed transcripts. Overexpression from the BCR promoter in a COS cell system was effective in demonstrating multiple transcription initiation sites. In order to assess the effects of chromosomal translocation on the transcriptional control of the BCR gene, we determined S1 nuclease protection patterns of poly(A)+ RNA from tumor cell lines. No differences were observed in the locations and levels of BCR transcription initiation sites between those lines that harbored the t(9;22) translocation and those that did not. This demonstrates that BCR promoter function remains intact in spite of genomic rearrangement. The BCR promoter is structurally similar to the ABL promoters. Together, this suggests that the structural fusion of BCR-ABL and not its transcriptional deregulation is primarily responsible for the transforming effect of the t(9;22) translocation.
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Makri, Maria, Chikashi Yoshida, Akihiko Muto, Kazuhiko Igarashi et Junia V. Melo. « Transcriptional Regulation of the Bach2 B-Cell Differentiation and Apoptotic Factor by the Bcr-Abl Oncoprotein. » Blood 106, no 11 (16 novembre 2005) : 2991. http://dx.doi.org/10.1182/blood.v106.11.2991.2991.
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Abstract Transformation by the Bcr-Abl oncoprotein of CML is mediated by the activation of a variety of signalling pathways, leading to transcriptional regulation of genes conferring the malignant phenotype of increased proliferation, altered adhesion and inhibition of apoptosis. We previously reported that expression of the BACH2 gene is downregulated by Bcr-Abl. Bach2 is a B-lymphoid specific transcription factor, which regulates somatic hypermutation and class switch recombination of Ig genes. It is also a pro-apoptotic factor, coupling oxidative stress to transcription repression. It is possible that in an environment of increased genomic instability, Bcr-Abl transformed cells may repress pro-apoptotic signals by suppressing BACH2 transcription. To determine the direct association between Bcr-Abl and decreased BACH2 transcription, we infected human B-lymphoid cells with a retroviral vector expressing both p210Bcr-Abl and eGFP genes. Infected cells were treated with imatinib, an Abl tyrosine kinase inhibitor, prior to quantification of BACH2 transcripts by Real Time RT/PCR. Ectopic expression of BCR-ABL significantly decreased BACH2 mRNA levels, and this effect was completely abolished by imatinib. To investigate whether this regulation was exerted at the transcriptional level, we identified the BACH2 transcription initiation site (TIS), and then cloned and characterised a 3.9 Kb genomic DNA fragment including the BACH2 promoter region. By generating luciferase reporter constructs of various lengths of the BACH2 promoter we found that a region of 725 bp upstream the TIS conferred maximum promoter activity in human B-lymphoid cells. The effect of Bcr-Abl on promoter activity was demonstrated by co-transfection of the reporter and p210Bcr-Abl constructs. BACH2-promoter activity was reduced up to 60% in the presence of Bcr-Abl. Furthermore, when co-transfected cells were incubated with different concentrations of imatinib, the Bcr-Abl-mediated promoter repression was abrogated in a dose dependent manner, confirming the dependence of the effect on the tyrosine kinase activity of the oncoprotein. In support of these data, no effect on promoter activity was seen when the BACH2 promoter was co-transfected with a kinase-dead BCR-ABL construct. Moreover, treatment with imatinib of the BCR-ABL+ cell line BV173 transfected with the reporter induced a nearly 2-fold upregulation in its activity. Bioinformatics inspection of the promoter sequence revealed potential sites for the Pax5 B-cell differentiation factor and the Foxo3a transcription factor, a regulator of pro-apoptotic genes. In co-transfection experiments of either factor with the BACH2 promoter, both demonstrated a significant inducing effect on its activity. Gel shift and chromatin immunoprecipitation showed direct binding of Pax5 within the BACH2 promoter in vitro and in vivo. Moreover, Western analysis showed elevated Pax5 levels in BCR-ABL+ cell lines after imatinib treatment, indicating that inhibition of Bach2 expression by Bcr-Abl is mediated at least in part by Pax5. As to Foxo3a, it has been reported to be constitutively phosphorylated and inactivated in BCR-ABL+ cells, processes which prevent its translocation to the cell nucleus. Altogether, our data suggest that Bcr-Abl transcriptional repression of Bach2 via Pax5 could lead to a differentiation arrest in transformed B-cells, and that Foxo3a may induce imatinib-mediated apoptosis through up-regulation of the Bach2 apoptotic function.
4
Burgess, Gem S., Elizabeth A. Williamson, Larry D. Cripe, Sara Litz-Jackson, Jay A. Bhatt, Kurt Stanley, Mark J. Stewart, Andrew S. Kraft, Harikrishna Nakshatri et H. Scott Boswell. « Regulation of the c-jun Gene in p210 BCR-ABL Transformed Cells Corresponds With Activity of JNK, the c-jun N-Terminal Kinase ». Blood 92, no 7 (1 octobre 1998) : 2450–60. http://dx.doi.org/10.1182/blood.v92.7.2450.
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Abstract Activity of the c-jun N-terminal kinase (JNK) has been shown in hematopoietic cells transformed by p210 BCR-ABL. However, analysis has not been reported for hematopoietic cells on the consequences of this activity for c-jun promoter regulation within its distinctive proximal 8-base consensus CRE-like element, an element linked to JNK-mediated increase in c-jun transcription. In the present study, regulation of the proximal c-jun promoter was studied in murine myeloid cells transformed by p210 BCR-ABL. Promoter regulation in p210 BCR-ABL transformed cells was compared with regulation of the promoter in nontransformed interleukin-3 (IL-3)–dependent parental cells. The composition of nuclear AP-1 proteins contained within cells with p210 BCR-ABL, and their binding to the c-jun promoter proximal CRE-like element, was compared with the composition and binding of AP-1 proteins in IL-3–treated parental cells without p210 BCR-ABL. The present analysis found fivefold increased c-jun transcription occurring in p210 BCR-ABL transformed murine myeloid cells possessing a corresponding magnitude of increased kinase activity of JNK, compared with IL-3–stimulated parental cells. Augmented JNK activity was accompanied by increased nuclear abundance of c-jun and c-fos proteins that bound specifically to the proximal c-jun promoter CRE element. Also, representative human leukemic cell lines expressing p210 BCR-ABL and possessing abundant kinase activity of JNK, when compared with parental cells that were deficient in JNK activity, had increased c-jun and c-fosproteins. Finally, to show the relevance of these observations in model systems, we studied blast cells from patients with Philadelphia chromosome–positive acute leukemic transformation, and observed comparable activities of JNK catalysis and c-jun/AP-1 protein relative to the cell lines that possessed p210 BCR-ABL and JNK activity. These studies provide a basis for investigating the set of downstream genes which augmented c-jun/AP-1 activity enlists in the process of transformation by p210 BCR-ABL.
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Burgess, Gem S., Elizabeth A. Williamson, Larry D. Cripe, Sara Litz-Jackson, Jay A. Bhatt, Kurt Stanley, Mark J. Stewart, Andrew S. Kraft, Harikrishna Nakshatri et H. Scott Boswell. « Regulation of the c-jun Gene in p210 BCR-ABL Transformed Cells Corresponds With Activity of JNK, the c-jun N-Terminal Kinase ». Blood 92, no 7 (1 octobre 1998) : 2450–60. http://dx.doi.org/10.1182/blood.v92.7.2450.2450_2450_2460.
Texte intégralRésumé :
Activity of the c-jun N-terminal kinase (JNK) has been shown in hematopoietic cells transformed by p210 BCR-ABL. However, analysis has not been reported for hematopoietic cells on the consequences of this activity for c-jun promoter regulation within its distinctive proximal 8-base consensus CRE-like element, an element linked to JNK-mediated increase in c-jun transcription. In the present study, regulation of the proximal c-jun promoter was studied in murine myeloid cells transformed by p210 BCR-ABL. Promoter regulation in p210 BCR-ABL transformed cells was compared with regulation of the promoter in nontransformed interleukin-3 (IL-3)–dependent parental cells. The composition of nuclear AP-1 proteins contained within cells with p210 BCR-ABL, and their binding to the c-jun promoter proximal CRE-like element, was compared with the composition and binding of AP-1 proteins in IL-3–treated parental cells without p210 BCR-ABL. The present analysis found fivefold increased c-jun transcription occurring in p210 BCR-ABL transformed murine myeloid cells possessing a corresponding magnitude of increased kinase activity of JNK, compared with IL-3–stimulated parental cells. Augmented JNK activity was accompanied by increased nuclear abundance of c-jun and c-fos proteins that bound specifically to the proximal c-jun promoter CRE element. Also, representative human leukemic cell lines expressing p210 BCR-ABL and possessing abundant kinase activity of JNK, when compared with parental cells that were deficient in JNK activity, had increased c-jun and c-fosproteins. Finally, to show the relevance of these observations in model systems, we studied blast cells from patients with Philadelphia chromosome–positive acute leukemic transformation, and observed comparable activities of JNK catalysis and c-jun/AP-1 protein relative to the cell lines that possessed p210 BCR-ABL and JNK activity. These studies provide a basis for investigating the set of downstream genes which augmented c-jun/AP-1 activity enlists in the process of transformation by p210 BCR-ABL.
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Zhu, Qin-Shi, Nora Heisterkamp et John Groffen. « Unique organization of the human BCR gene promoter ». Nucleic Acids Research 18, no 23 (1990) : 7119–25. http://dx.doi.org/10.1093/nar/18.23.7119.
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Wong, Wei. « PTEN as a tumor promoter ». Science Signaling 9, no 423 (12 avril 2016) : ec84-ec84. http://dx.doi.org/10.1126/scisignal.aaf8449.
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PTEN is generally considered to be a tumor suppressor because it limits the activity of the PI3K-Akt pathway, which usually promotes cell survival. However, in pre-B cells transformed with BCR-ABL1 or NRASG12D, oncogenes common to acute lymphoblastic leukemia (ALL), Shojaee et al. found that deletion of Pten resulted in cell death, and mice transplanted with the transformed pre-B cells in which Pten was also deleted did not develop leukemia. Pten deletion in transformed pre-B cells resulted in increased phosphorylation of Akt, which is activated downstream of the pre-B cell receptor through the tyrosine kinase Syk. Pharmacological inhibition of Akt or Syk reduced cell death caused by Pten deletion; it also prevented the cell death of autoreactive B cells, which are eliminated through negative selection because the pre-BCR binds to self-antigen. Pten deletion did not affect the abundance of the tumor suppressor p53 or the survival of BCR-ABL1–transformed chronic myeloid leukemia (CML) cells. In contrast, Pten deletion in BCR-ABL1–transformed pre-B ALL cells triggered the phosphorylation of p53 and its accumulation, effects that required Akt activity. Overexpression of the myeloid transcription factor C/EBP-α converts cells of the B cell lineage to the myeloid lineage, and Pten deletion increased glycolysis to a greater extent in pre-B ALL cells than in myeloid-reprogrammed cells, as indicated by increased glucose consumption and lactate production and depletion of ATP. Analysis of a genetic database of human cancers indicated that PTEN deletions or point mutations were not detected in pre-B ALL patient samples, and PTEN abundance was increased in pre-B ALL patient samples compared to that in patient samples of other types of lymphomas and leukemias. PTEN knockdown reduced cell viability in four different patient-derived pre-B ALL cell lines, and pharmacological inhibition of PTEN increased AKT signaling; the phosphorylation and accumulation of p53; and glycolytic metabolism in human pre-B ALL cells. Thus, PTEN may be a potential therapeutic target for the treatment of pre-B ALL (see also Fortin et al.). S. Shojaee, L. N. Chan, M. Buchner, V. Cazzaniga, K. N. Cosgun, H. Geng, Y. H. Qiu, M. Dühren-von Minden, T. Ernst, A. Hochhaus, G. Cazzaniga, A. Melnick, S. M. Kornblau, T. G. Graeber, H. Wu, H. Jumaa, M. Müschen, PTEN opposes negative selection and enables oncogenic transformation of pre-B cells. Nat. Med. 22,379–387 (2016). [PubMed] J. Fortin, C. Bassi, T. W. Mak, PTEN enables the development of pre-B acute lymphoblastic leukemia. Nat. Med. 22, 339–340 (2016). [PubMed]
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Gary-Gouy, Hélène, Julie Harriague, Georges Bismuth, Cornelia Platzer, Christian Schmitt et Ali H. Dalloul. « Human CD5 promotes B-cell survival through stimulation of autocrine IL-10 production ». Blood 100, no 13 (15 décembre 2002) : 4537–43. http://dx.doi.org/10.1182/blood-2002-05-1525.
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CD5 is a negative regulator of B-cell receptor (BCR) signaling that is up-regulated after BCR stimulation and likely contributes to B-cell tolerance in vivo. However, CD5 is constitutively expressed on the B-1 subset of B cells. Contrary to CD5− B-2 B cells, B-1 B cells are long-lived because of autocrine interleukin-10 (IL-10) production through unknown mechanisms. We demonstrate herein a direct relationship between CD5 expression and IL-10 production. Human peripheral blood CD5+ B cells produce more IL-10 than CD5− B cells after BCR activation. Introducing CD5 into CD5− B cells induces the production of IL-10 by activating its promoter and the synthesis of its mRNA. The cytoplasmic domain of CD5 is sufficient for this process. CD5 also protects normal human B cells from apoptosis after BCR stimulation while reducing the BCR-induced Ca2+ response. We conclude that CD5 supports the survival of B cells by stimulating IL-10 production and by concurrently exerting negative feedback on BCR-induced signaling events that can promote cell death.
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Binné, Ulrich K., Wolfgang Amon et Paul J. Farrell. « Promoter Sequences Required for Reactivation of Epstein-Barr Virus from Latency ». Journal of Virology 76, no 20 (15 octobre 2002) : 10282–89. http://dx.doi.org/10.1128/jvi.76.20.10282-10289.2002.
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ABSTRACT A luciferase reporter system with stably transfected oriP plasmids in Akata Burkitt's lymphoma cells provides a quantitative assay for the BZLF1 Zp promoter in response to B-cell receptor (BCR) activation by cross-linking with anti-immunoglobulin. In this system, detailed kinetic studies of promoter activity are possible. Previously reported promoter elements upstream of −221 from the transcription start and the ZIIR sequence had little effect on the Zp promoter, but the ZI and ZIIIA elements were essential for early activation. The ZIIIB element mediates autoactivation. Mutation of the ZV repressor sequence greatly increased the induction of the promoter but did not make it constitutively active. Zp transcription in response to BCR cross-linking declined after a few hours; this decline was reduced and delayed by acyclovir or phosphonoacetic acid, indicating that viral DNA replication or a late viral gene can play a role in the switch off of the Zp promoter. Late expression of the LMP1 protein may account for this.
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Casolari, Debora A., Jun Ishiko, Michelle Perugini, Richard J. D'Andrea et Junia V. Melo. « BCR-ABL-Induced Downregulation of GADD45G in Chronic Myeloid Leukemia ». Blood 120, no 21 (16 novembre 2012) : 3731. http://dx.doi.org/10.1182/blood.v120.21.3731.3731.
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Abstract Abstract 3731 Chronic myeloid leukemia (CML) is characterized by the presence of the BCR-ABL oncogene which encodes an activated tyrosine kinase. Despite the success of tyrosine kinase inhibitors (TKI), such as imatinib (IM), in CML treatment, a considerable percentage (12–50%) of patients develops resistance to TKIs. This can result in progression to blast crisis (BC), at which stage durable response to any TKI therapy is minimal. It is still unclear how additional genetic lesions, believed to play a major role in the transformation to BC, are generated, but it is likely that the BCR-ABL induction of DNA damage and low-fidelity DNA repair, added to inhibition of apoptosis contributes to this process. The Growth Arrest and DNA Damage 45 (GADD45A, B and G) proteins are tumor suppressors which coordinate cell cycle arrest, DNA repair and apoptosis in response to genotoxic and oncogenic stress. Failure to activate GADD45 expression, e.g. due to the presence of leukemic oncogenes or its promoter methylation, is associated with an attenuated DNA-damage response and impaired drug response. A microarray study showed that GADD45G is in the top 10% of genes downregulated in CML patients in BC compared to those in chronic phase (CP). Given the critical role of GADD45 proteins as key regulators of the cellular stress response, our hypothesis is that GADD45G reduced expression in CML-BC is mediated by BCR-ABL and contributes to the accumulation of mutations seen in BC. Therefore the aims of this work are to determine the mechanism of GADD45G downregulation by BCR-ABL and its functional effects on CML cells. We have confirmed the reduced GADD45G levels in CD34+ cells from BC patients versus CP and normal controls using quantitative RT-PCR. Furthermore, ectopic expression of BCR-ABL in a myeloid cell line resulted in decreased expression of GADD45G and, conversely, BCR-ABL inhibition with IM in several CML cell lines resulted in induction of GADD45G expression. These results confirm GADD45G as a down-modulated target of BCR-ABL. To determine the effect of GADD45G expression on CML cells, a CML cell line was transduced with GADD45G and showed significantly reduced proliferation, G1 cell cycle arrest and decrease in cell viability due to increased apoptosis. Once the GADD45G tumor suppressor effect in CML was confirmed, we investigated the mechanism by which BCR-ABL inhibits its expression. Silencing of GADD45G expression in solid tumors can occur by promoter methylation; therefore, we analyzed the GADD45G promoter methylation status in the presence or absence of BCR-ABL. Bisulfite genomic sequencing of BCR-ABL-positive and –negative hematopoietic cell lines and on peripheral blood mononuclear cells from CML-CP and BC patients, as well as of normal controls, showed no correlation between the presence of BCR-ABL and promoter methylation. Another mechanism possibly employed by BCR-ABL to regulate GADD45G expression is interference with transcription factor (TF) binding to the promoter. Bioinformatics analysis revealed, among several other TF binding sites, the presence of two highly conserved RUNX1/AML1 binding sites on the promoter. The TF RUNX1 is a key controller of hematopoiesis and heterodimerises with CBF-β to regulate gene expression. RUNX1 mutations in AML result in lower GADD45A expression and increase in DNA damage. In CML, RUNX1 was reported as mutated in >30% of patients in BC, and was suggested to cooperate with Bcr-Abl in the induction of AML in mice. It has also been shown to be a target of inhibitory phosphorylation by SRC kinases, which display increased activity in CML-BC. We therefore co-transfected a CML cell line with a GADD45G promoter luciferase reporter and both RUNX1 and CBF-β constructs. This resulted in a 10-fold increase in luciferase activity, indicating that RUNX1 is involved in the regulation of GADD45G expression in CML cells. Overall, our results suggest that GADD45G has a tumor suppressor role in CML and that its down-regulation by BCR-ABL could, therefore, contribute to the accumulation of DNA damage and progression to BC. In addition, our data identify RUNX1 as an inducer of GADD45G expression and, together with data from the literature, suggest that RUNX1 mutations or protein inactivation in CML could result in the observed reduced GADD45G expression. We are currently investigating this possibility. Disclosures: No relevant conflicts of interest to declare.
Thèses sur le sujet "BCR promoter"
1
Marusyk, Andriy. « Decreased cellular fitness as a tumor promoter / ». Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2006.
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Thesis (Ph.D. in Molecular Biology) -- University of Colorado at Denver and Health Sciences Center, 2006.Typescript. Includes bibliographical references (leaves 124-145). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;
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SHARMA, NITESH DEVINARAYAN. « CHARACTERIZATION OF SOME MOLECULAR MECHANISMS ASSOCIATED TO CML PROGRESSION ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2015. http://hdl.handle.net/10281/63684.
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La Leucemia Mieloide Cronica(CML) è caratterizzata dalla presenza del gene di fusione BCRABL, prodotto dalla traslocazione tra i cromosomi 9 e 22. Se non trattata questa patologia progredisce entro 3 anni da una forma cronica(CP) a una forma acuta, la crisi blastica(BC). I meccanismi molecolari alla base della progressione della malattia non sono ancora completamente chiariti. Per raggiungere questo scopo ho quindi utilizzato un duplice approccio: 1)Grazie alla disponibilità di campioni CP/BC derivanti dagli stessi pazienti progrediti in BC dopo terapia standard, abbiamo sequenziato l’intero esoma(Whole Exome Sequencing-WES) e analizzato i dati utilizzando il campione CP come controllo. In questo modo l’analisi ha permesso di evidenziare solamente le alterazioni genetiche acquisite dopo progressione in BC. Ho quindi individuato la presenza di 2 mutazioni ricorrenti a carico dei geni RUNX1 e UBE2A, con quest’ultimo associato per la prima volta all’evoluzione in leucemia acuta e trovato mutato in circa l’11per cento dei campioni BC. Analisi successive invitro e invivo permetteranno di chiarire in particolare il ruolo delle mutazioni a carico di UBE2A nella progressione di CML. 2)Il secondo approccio si basa sullo studio del promotore del gene BCR. Dopo la traslocazione il gene di fusione BCRABL è sotto il controllo del promotore di BCR. Attualmente i meccanismi di regolazione di questo promotore sono poco chiari. Nel nostro laboratorio è stata precedentemente identificata una deregolazione trascrizonale di entrambi i geni BCR e BCRABL durante la progressione in BC. Ho quindi messo a punto un’analisi insilico per identificare i fattori di trascrizione che possano avere un ruolo nella regolazione del promotore BCR. Utilizzando tecniche di immunoprecipitazione di cromatina ho confermato in-vitro il legame dei fattori di trascrizione MYC e MAX a siti di legame specifici sul promotore di BCR(PBS1-4). Ho quindi osservato come l’overespressione di MYC e MAX sia in grado di indurre un aumento dell’espressione di BCR e di BCRABL, e che questo aumento risulta più evidente quando entrambi i fattori di trascrizione sono overespressi. Il silenziamento specifico di MYC nelle stesse linee cellulari ha dimostrato ulteriormente l’effetto regolatorio su entrambi i promotori. Per confermare questi risultati ho messo a punto un saggio di luciferasi inserendo il promotore di BCR nel plasmide pGL3. Cellule silenziate o meno per il gene MYC sono state poi trasfettate con i plasmidi di interesse. I risultati di questi esperimenti dimostrano l’importanza di MYC nella regolazione del promotore BCR. Ho inoltre osservato come il silenziamento di MYC in cellule BCRABL+ induca anche una alterazione del potenziale proliferativo e un aumento del tasso apoptotico. Questi dati descrivono quindi per la prima volta un meccanismo di regolazione del promotore BCR basato sul legame specifico di MYC e MAX e indicano una diretta associazione tra i livelli di espressione di MYC e quelli di BCRABL, entrambi upregolati durante l’evoluzione della malattia. E’ quindi suggerito un meccanismo molecolare alla base dell’aumento dell’espressione di BCRABL e dell’evoluzione in BC.Chronic Myeloid Leukemia (CML) is caused by the BCR/ABL fusion gene. If untreated CML progresses within 3 years from a mild and easy to control form, called chronic phase (CP), into an aggressive and deadly acute leukemia called blast crisis (BC). Despite the aggressiveness of BC and the poor overall survival of BC patients, little is known about the molecular mechanisms responsible for the progression of the disease. Therefore to gain insight into the molecular lesions responsible for BC, I used a two prong approach. First, I performed whole-exome SEQ analysis of paired CP/BC CML samples from patients that underwent progression to BC after standard therapy. By comparing exome-sequences of 11 paired CP (used as a control) and BC samples we found a total of 38 single nucleotide mutations occurring in BC and that were absent in the corresponding CP sample. By using this approach we found recurrent somatic single nucleotide mutations in RUNX1 and UBE2A in 2 out of 11 BC samples. UBE2A is here associated with CML progression for the first time. In addition, Copy Number Alteration analysis of 9 matched BC/CP exomes reveals the presence of large chromosomal alterations acquired during BC transformation, among which the bulky alteration of chromosome 7 in 3/9 BC samples. In conclusion, despite some heterogeneity in the genetic alterations identified in BC samples, we were able to find 2 recurrently mutated genes associated with blastic transformation RUNX1 and UBE2A, with the last one never been detected in CML samples. Ongoing analysis on additional BC/CP samples and in vitro experiments will help to clarify the role of UBE2A mutations in CML progression. The second approach involves the study of the BCR promoter. After the oncogenic translocation, the BCRABL gene is transcriptionally controlled by the BCR promoter. In spite of all the research performed in the field, little is known in the regulation of BCR promoter. We thus need to understand what are the transcription factors or the mechanisms that regulate BCRABL expression. By in-silico analysis and in-vitro Chromatin Immunoprecipitation experiments we found that COUP-TF1, CTCF, MYC and MAX proteins bind at BCR promoter at specific sites. As many studies have indicated the involvement of MYC in CML progression, we here focused the study on MYC and its co-factor MAX for our further analysis. In the present study we demonstrate that MYC_MAX heterocomplex binds to the BCR promoter at four different loci, leading to upregulation of BCR and BCRABL at both transcriptional and protein level. In contrast, silencing of MYC expression in various BCRABL positive cell lines causes significant downregulation of BCR and BCRABL, which consequently leads to decreased proliferation and induction of apoptosis. Taken together all these results demonstrate that MYC_MAX heterocomplex regulates BCR promoter basal activity and can contribute to BCRABL overexpression and blast aggressiveness of CML advanced phase.
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Elango, Rajula. « Break-induced replication repair pathway promotes mutagenesis and genomic instability in Saccharomyces cerevisiae ». Diss., University of Iowa, 2017. https://ir.uiowa.edu/etd/5933.
Texte intégralRésumé :
DNA double strand breaks can occur from various sources and the timely and accurate repair of these breaks is critical to maintain the genomic integrity of the cell. Break-induced replication (BIR) is a repair pathway that has been shown to repair DSBs where only one end of the break can locate homology, similar to ends seen at collapsed replication forks or eroded telomeres. BIR progresses by an unusual bubble-like intermediate. The asynchrony between the synthesis of leading and lagging strand synthesis during BIR leads to the accumulation of long single-stranded DNA (ssDNA) behind the bubble. This mechanism leads to the conservative inheritance of newly synthesized DNA. BIR repair can lead to increased mutations, loss of heterozygosity and gross chromosomal rearrangements. In this thesis I investigated the deleterious effects of the ssDNA formed during BIR. Using yeast, Saccharomyces cerevisiae, I showed that the regulation of Rad51 that binds ssDNA during BIR is important to prevent the accumulation of toxic joint intermediates. Here, I demonstrate that a known Rad51-interacting protein, Srs2, plays two key roles in counteracting the accumulation of lethal recombination intermediates. First, Srs2 dislodges Rad51 from long ssDNA formed during DSB repair and therefore prevents promiscuous strand invasions that generate lethal joint molecules. Second, Srs2 helicase dismantles toxic intermediates that have already formed. We also demonstrate that the structure-specific endonucleases, Mus81 and Yen1, can resolve toxic joint molecules formed in the absence of Srs2, thus promoting cell survival.
The other goal of this thesis was to study the effects of ssDNA accumulated during BIR in the formation of base-substitution mutagenesis. I test whether this ssDNA is mutagenic by analyzing BIR with and without the presence of DNA damaging agents, including methyl methanesulfonate (MMS) and APOBEC3A. I observed a hypermutagenic effect of BIR with respect to base- substitutions in both cases. Importantly, BIR synergizes with ssDNA damaging agents to produce mutation clusters similar to those previously observed in cancer. I also report the critical role translesion polymerase Polζ plays in the formation of base-substitutions resulting from BIR. Finally, I have discovered a completely novel, UNG1-dependent mechanism of supposed error-free bypasses of APOBEC-induced DNA lesions during BIR that promotes chromosomal rearrangements.
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Li, Frank. « Analysis of the Effects of BCL-2 Promoter G-Quadruplex Formation on Protein Expression ». Thesis, The University of Arizona, 2012. http://hdl.handle.net/10150/244406.
Texte intégralRésumé :
Bcl-2 is an anti-apoptotic protein that has been implicated in a number of human diseases, including some cancers. Within the P1 promoter region, which is involved in 80-90% of bcl-2 transcriptional control, a G-rich region (Pu39) can form various monomeric G-quadruplex folding structures, each with four of the six runs of multiple guanines present. The midG4 and 5'5G4 structures have been found to be the most stable and are the potential targets of comparative studies on transcriptional effects. Plasmids containing a luciferase reporter gene under the control of this bcl-2 P1 promoter region, along with mutants to alter or eliminate G-quadruplex formation, were constructed in order to study the ability of Pu39 to control transcription. Initial luciferase assay results in HeLa and HEK293 cells suggest that mutants designed to isolate certain G-quadruplex structures caused an overall decrease in protein expression while mutants designed to knock out major folding structures caused an increase in protein expression. DNA mutant constructs in conjunction with quadruplex-specific, quadruplex-interacting drugs appear to consistently decrease protein activity, supporting the idea that the G-quadruplex has an inhibitory effect on transcription.
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DUGRAY, AYMERIC. « Controle de l'hematopoiese maligne a l'aide de retrovirus a promoteurs inductibles : modele de leucemogenese par bcr-abl ». Paris 7, 2001. http://www.theses.fr/2001PA077133.
Texte intégralRésumé :
Les phenomenes moleculaires qui sont responsables de la progression du clone leucemique ph1 vers la phase blastique au cours de la leucemie myeloide chronique sont indetermines. Ce travail a consiste a modeliser un des aspects phenotypiques de cette progression qui consiste en l'augmentation de l'expression de bcr-abl. Dans ce but, nous avons genere un modele de leucemogenese a l'aide d'un systeme retroviral a promoteur inductible gouvernant l'expression du gene bcr-abl. Ce retrovirus inductible a permis la transduction de la lignee hematopoietique ba/f3 avec obtention de clones uniques dans lesquels l'expression de bcr-abl peut etre modulee par l'ajout de tetracycline dans le milieu. La fonctionnalite du systeme inductible a pu etre testee avec succes dans les experiences de transformation et/ou de tumorigenicite in vivo. Les outils inductibles generes, ainsi que les modeles in vitro disponibles dans le laboratoire, nous ont par la suite permis de demontrer la responsabilite directe de bcr-abl dans la degradation proteasome-dependante de dna-pkcs, proteine de reparation majeure des cassures double-brin. Cet evenement moleculaire pourrait etre un phenomene clef responsable de l'instabilite genetique favorisant ainsi la progression du clone ph1 vers la crise blastique. Enfin, ce modele inductible nous a permis de realiser une etude plus large des effets de l'expression de bcr-abl grace a l'utilisation de la methode de puces a adn. Nous avons ainsi mis en evidence l'induction de l'expression de plusieurs genes, notamment valosin-containing protein, (vcp) et de cis1/socs1, intervenant respectivement dans la reparation de l'adn et dans la regulation negative de la voie jak/stat. La relevance de ces anomalies d'expression a ete testee dans des modeles de leucemies in vitro ainsi que dans les cellules primaires de patients atteints de lmc. La demonstration de leur role dans la leucemogenese induite par bcr-abl necessitera des experiences futures de surexpression ou d'inhibition.
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Rodríguez, José M. « Bcl-2 related ovarian killer, Bok, is cell cycle regulated and sensitizes to stress-induced apoptosis ». Scholar Commons, 2007. http://scholarcommons.usf.edu/etd/2342.
Texte intégralRésumé :
Bok/Mtd (Bcl-2-related ovarian killer/Matador) is considered a pro-apoptotic member of the Bcl-2 family. Though identified in 1997, little is known about its biological role. We have previously demonstrated that Bok mRNA is upregulated following E2F1 over-expression. In the current work, we demonstrate that Bok RNA is low in quiescent cells and rises upon serum stimulation. To determine the mechanism underlying this regulation, we cloned and characterized the mouse Bok promoter. We find that the mouse promoter contains a conserved E2F binding site (-43 to -49) and that a Bok promoter-driven luciferase reporter is activated by serum stimulation dependent on this site. Chromatin immunoprecipitation assays demonstrate that endogenous E2F1 and E2F3 associate with the Bok promoter in vivo. Surprisingly, we find that H1299 cells can stably express high levels of exogenous Bok. However, these cells are highly sensitive to chemotherapeutic drug treatment. Taken together these results demonstrate that Bok represents a cell cycle-regulated pro-apoptotic member of the Bcl-2 family, which may predispose growing cells to chemotherapeutic treatment.
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Checkett, Jane Melinda. « Development of a micro-scale microtransfection technique exploiting reporter gene systems to analyse bcl-2 family promoter activity ». Thesis, Keele University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325826.
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Ogunnowo-Bada, Emmanuel Oluwatobi. « The role of brain glucokinase and Bcl-2-associated death promoter in the control of blood glucose homeostasis ». Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648754.
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Abomoelak, Bassam. « Développement et immunogénicité de souches recombinantes de BCG produisant des antigènes bactériens chimériques ». Lille 1, 1997. http://www.theses.fr/1997LIL10220.
Texte intégralRésumé :
Deux souches recombinantes de bcg exprimant une fusion protéique entre s1, la sous-unité enzymatique de la toxine pertussique et le tetc, le fragment cc de la toxine tétanique ont été développées sous deux promoteurs différents (85a, hsp60). L'immunisation des souris avec la première souche n'a pas induit de réponse immunitaire, tandis que l'immunisation des souris avec la deuxième souche a induit une réponse immunitaire humorale et cellulaire. Une autre souche recombinante de bcg capable d'exprimer une fusion protéique entre s1, tetc et le fragment b de la toxine diphtérique a été développée.
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Tollin, Craig Jeffrey. « The characterization of Clostridium beijerinckii NRRL B592 cells transformed with plasmids containing the butanol-production genes under the control of constitutive promoters ». Diss., Virginia Tech, 2012. http://hdl.handle.net/10919/77235.
Texte intégralRésumé :
Clostridium beijerinckii is a spore-forming, obligate anaerobe that is capable of producing butanol, acetone and isopropanol. These industrial chemicals are traditionally known as solvents. The regulation of solventogenic fermentation is linked to the onset of sporulation, so that by the time the organism begins to produce solvents, it is also entering into spore formation and metabolic slowdown. The goal of this research project was to study the effect of placing the solvent-production genes from C. beijerinckii under the control of constitutive promoters from other genes, in an attempt to allow an earlier start of butanol production during the growth phase than is the case with the wild-type cells.
The aldehyde dehydrogenase from C. beijerinckii NRRL B593 (ald) and alcohol dehydrogenase from C. beijerinckii NRRL B592 (adhA) were placed under the control of the promoter from the acid-producing operon (the BCS operon) in one vector, and under the control of the promoter from the ferredoxin gene in another. In both cases, aldehyde dehydrogenase activity was produced earlier in the growth phase in transformed cells, but alcohol dehydrogenase activity was not.
The adhA gene from C. beijerinckii NRRL B592 was paired with the adhB gene from the same organism in a third vector, both under the control of the promoter from the BCS operon. In cells transformed with this vector, alcohol dehydrogenase activity was observed earlier in the growth phase than it was in wild-type NRRL B592 cells.Ph. D.
Livres sur le sujet "BCR promoter"
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American Bar Association. Commission on Opportunities for Minorities in the Profession., dir. American Bar Association's Goal IX : To promote full and equal participation in the legal profession by minorities, women and persons with disabilities. [Chicago, Ill. ? : American Bar Association, Commission on Opportunities for Minorites in the Profession, 1999.
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Chupilkin, Yuriy, Yuriy Lyahov, Sergey Voroncov et Sergey Nazarov. Law enforcement agencies of the Russian Federation. ru : INFRA-M Academic Publishing LLC., 2022. http://dx.doi.org/10.12737/1867896.
Texte intégralRésumé :
The textbook meets the requirements of the state educational standard for the discipline "Law Enforcement agencies", contains information about state bodies engaged in law enforcement activities, as well as non-governmental organizations designed to promote it, reflects changes in legislation on the judicial system, the bar, the notary, the prosecutor's office, bodies of inquiry and preliminary investigation, justice, internal affairs and the federal security Service.
For students and teachers of educational institutions of secondary professional education of a legal profile, as well as a wide range of readers interested in the protection of life, health, human and civil rights and freedoms, property, security and law and order from criminal encroachments.
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Chupilkin, Yuriy, Sergey Voroncov, Yuriy Lyahov et Sergey Nazarov. Law enforcement agencies of the Russian Federation. ru : INFRA-M Academic Publishing LLC., 2022. http://dx.doi.org/10.12737/1867575.
Texte intégralRésumé :
The textbook meets the requirements of the state educational standard for the discipline "Law Enforcement agencies", contains information about state bodies engaged in law enforcement activities, as well as non-governmental organizations designed to promote it, reflects changes in legislation on the judicial system, the bar, the notary, the prosecutor's office, bodies of inquiry and preliminary investigation, justice, internal affairs and the federal security Service.
For students of higher educational institutions, graduate students, teachers, law enforcement officers, employees of private detective and security services, as well as a wide range of readers interested in the protection of life, health, human and civil rights and freedoms, property, security and law enforcement from criminal encroachments.
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Dalbeth, Nicola. Basic calcium phosphate crystal deposition. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199668847.003.0053.
Texte intégralRésumé :
Basic calcium phosphate (BCP) crystals deposit within periarticular and articular sites, leading to a variety of clinical presentations. The most well-recognized clinical syndromes associated with BCP crystal deposition are calcific tendinitis and BCP crystal-associated destructive arthritis such as Milwaukee shoulder syndrome. There is emerging evidence that BCP crystals also play a role in osteoarthritis pathogenesis. Within the joint, tissue responses to BCP crystals include induction of pro-catabolic and inflammatory pathways. Clinical management of BCP crystal-associated arthropathies is limited by the lack of reliable and feasible methods to detect crystals, and the current unavailability of systemic therapies that promote BCP crystal dissolution.
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Harlow, Ralph Volney. Samuel Adams, Promoter of the American Revolution : A Study in Psychology and Politics (Bcl One, United States History Ser). Reprint Services Corp, 1991.
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Peters, Joris, Nadja Pöllath et Benjamin S. Arbuckle. The emergence of livestock husbandry in Early Neolithic Anatolia. Sous la direction de Umberto Albarella, Mauro Rizzetto, Hannah Russ, Kim Vickers et Sarah Viner-Daniels. Oxford University Press, 2017. http://dx.doi.org/10.1093/oxfordhb/9780199686476.013.18.
Texte intégralRésumé :
Analysis of spatio-temporal variation in patterns of animal exploitation helps our understanding of the transition from hunting to husbandry of Ovis, Capra, Sus, and Bos in Pre-Pottery Neolithic Anatolia (c.9500–7000 bce). Despite interaction with humans since the final Pleistocene, domestication of Sus in southeastern Anatolia is only evidenced after 8500 bce. This timing coincides with efforts to exert cultural control over Ovis, Capra, and Bos. Applying a broad methodological spectrum, it is shown that in southeastern Anatolia, the Neolithic ‘package’ was in place at the end of the ninth millennium bce, whereas in contemporaneous central Anatolia, livestock husbandry only included sheep and goat. Initially, animal management practices may have focused on a single species, but after 8000 bce, herding strategies comprised at least two species, likely a risk-reducing strategy. Conceivably, large-scale social gatherings, e.g. at Göbekli Tepe, promoted the spread of practices associated with ungulate management and domestication.
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Nabil, Farah, Daniela Fusco, Cristina Muñoz et Guillermo Z. Martínez-Pérez. Guia prático para o especialista em ética para a avaliação da pesquisa pré-clínica a partir de uma perspetiva do sexo e do género : Um guia do projeto "Building capacities in gender mainstreaming for ethics committees members from Senegal to West Wfrica" (BCA-WA-ETHICS). Universidad de Zaragoza, 2021. http://dx.doi.org/10.26754/uz.2021_csa2018erc-2314.
Texte intégralRésumé :
Este guia é um produto do Secretariado para a Integração de Género da BCA-WA-ETHICS O Secretariado para a Integração de Género é um centro de assistência virtual a serviço de todos os comités nacionais de ética (CNE) e comités de revisão institucional apoiados pelos CNE na África Ocidental. Seu objetivo é promover que todos os CNE desenvolvam ou aprimorem seus próprios regulamentos, diretrizes e procedimentos operacionais padrão para: Considerar a representação dos sexos na composição das CNE. Estabelecer procedimentos de recrutamento, orçamento, aquisições e administração sensíveis ao género. Incorporar uma perspetiva de género na avaliação do protocolo de estudo da CNE. Apoiar a integração de uma perspetiva de género na pesquisa em saúde e ciências sociais. Promover abordagens de sexo e género na recolha e análise de dados. Desenvolver programas educativos e de desenvolvimento profissional sensíveis ao género. Desenvolver e facilitar programas de formação sobre igualdade de género. Projetar e implementar planos de igualdade de género
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Nabil, Farah. Harmonização da integração do género na ética da pesquisa em saúde : para una communidade de pratica na Africa Ocidental. Universidad de Zaragoza, 2021. http://dx.doi.org/10.26754/uz.2021_csa2018erc-2314.2.
Texte intégralRésumé :
Este roteiro é um produto do Secretariado para a Integração de Género da BCA-WA-ETHICS O Secretariado para a Integração de Género é um centro de assistência virtual a serviço de todos os comités nacionais de ética (CNE) e comités de revisão institucional apoiados pelos CNE na África Ocidental. Seu objetivo é promover que todos os CNE desenvolvam ou aprimorem seus próprios regulamentos, diretrizes e procedimentos operacionais padrão para: Considerar a representação dos sexos na composição das CNE. Estabelecer procedimentos de recrutamento, orçamento, aquisições e administração sensíveis ao género. Incorporar uma perspetiva de género na avaliação do protocolo de estudo da CNE. Apoiar a integração de uma perspetiva de género na pesquisa em saúde e ciências sociais. Promover abordagens de sexo e género na recolha e análise de dados. Desenvolver programas educativos e de desenvolvimento profissional sensíveis ao género. Desenvolver e facilitar programas de formação sobre igualdade de género. Projetar e implementar planos de igualdade de género.
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Mark, McNeill, et Ryan Margaret Clare. Part VI Discovery and Document Production, 17 Meeting the Requirements of Article 3(3) of the IBA Rules : Recommendations for Successful Requests for Document Production. Oxford University Press, 2016. http://dx.doi.org/10.1093/law/9780198783206.003.0018.
Texte intégralRésumé :
The International Bar Association (IBA) Rules on the Taking of Evidence, first issued in 1999, were designed as a tool for parties and for arbitrators to promote ‘an efficient, economical, and fair process for the taking of evidence in international arbitration’. Article 3 of these Rules, concerning the taking and presentation of documentary evidence, is arguably the central provision given the important role played by documentary evidence in international arbitral proceedings compared to other means of evidence. However, disputing parties often debate the practical application and interpretation of Article 3-particularly relating to Article 3.3, which sets forth the positive requirements that a party must meet when submitting a request to produce documents that are in the control of an opposing party (a ‘Request to Produce’). This chapter explores the most debated criteria of Article 3.3 in order to identify the characteristics of a well-drafted Request to Produce. Meeting the Article 3.3 requirements will assist a party in advancing its case by obtaining the production of vital and specific documents in an adversary’s possession. It will also promote an efficient and cost-effective process of taking evidence in international arbitration.
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Formisano, Ronald P. Populist Currents in the 2008 Presidential Campaign. University of Illinois Press, 2017. http://dx.doi.org/10.5406/illinois/9780252036606.003.0009.
Texte intégralRésumé :
This chapter highlights the populist strains in the 2008 campaigns and connects them to the nation's long history of politics “for the people.” When “Joe the Plumber” heckled Obama in Toledo, when Clinton hoisted a brew at a bar in Indiana, when Palin proudly introduced herself to the nation as a “hockey mom,” they were participating in a tradition of populist electoral appeals that can be traced back to the Whig Party's “Log Cabin and Hard Cider” campaign of 1840. Though populist campaigning took a digital turn in 2008 with the emergence of campaigning via interactive digital communications technologies, this chapter concludes that, as in the past, the populist rhetoric of the 2008 campaigns often had very little to do with policies that promoted the greatest good for the greatest number.
Chapitres de livres sur le sujet "BCR promoter"
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Fulford, Bill. « The Realpolitik of Values-Based Practice : An Introduction to Part VI, Reflections ». Dans International Perspectives in Values-Based Mental Health Practice, 367–77. Cham : Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-47852-0_43.
Texte intégralRésumé :
AbstractThe three chapters in this Part reflect on their authors’ respective experiences of the challenges presented by the realpolitik of implementing projects in values-based practice. The challenges reflect the ‘3 Rs’ of values-based practice by which (as described in our concluding chapter 47, “Co-writing Values: What We Did and Why We Did It”) we have been guided in developing this book: Raising awareness, chapter 44, “Reflections on the Impact of Mental Health Ward Staff Training in Race Equality and Values-Based Practice”, a project combining race equality training and values-based practice for ward staff; Recognition, chapter 45, “Connecting Patients, Practitioners and Regulators in Supporting Positive Experiences and Processes of Shared Decision-Making in Osteopathy: A Case Study in Co-production”, a project in positive practice bringing together regulators, clinicians and patients; and Respect, chapter 46, “Beyond the Colour Bar: Sharing Narratives in Order to Promote a Clearer Understanding of Mental Health Issues Across Cultural and Racial Boundaries”, a project aimed at getting beyond the colour bar between white and black in mental health diagnosis. The chapter concludes with a note on the significance of the resources available from a culturally enriched form of values-based mental health practice for meeting the challenges of implementation.
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King, Colin, Simon Clarke, Steven Gillard et Bill Fulford. « Beyond the Color Bar : Sharing Narratives in Order to Promote a Clearer Understanding of Mental Health Issues Across Cultural and Racial Boundaries ». Dans International Perspectives in Values-Based Mental Health Practice, 403–9. Cham : Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-47852-0_46.
Texte intégralRésumé :
AbstractThis chapter describes through the narratives of those involved the contrasting experiences of one black and three white men who have worked together over a number of years on a series of academic and training projects. The shared aim of the group is to reach better understanding of each other’s perspectives (to get ‘beyond the colour bar’) thus gaining insights that could contribute to reducing the black-white inequalities that continue within mental health service provision. The extent of the differences between group members revealed by their respective narratives might suggest that they have failed in their shared aim. Held together however as they are by the premise of mutual respect underpinning values-based practice, the differences between them point instead to the importance of ‘whiteness’ as an implicit cultural frame driving racial inequalities in mental health. Challenging this frame and thus delivering more equal treatment will involve overcoming the challenge of pluralism at the heart of values-based practice.
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Cheng, Haifeng, Pei Xin, Jie Liu, Fengfeng Gu, Qi Shen et Lu Han. « Morphological Evolution and Driving Factors of Tidal Flats in the Yangtze Estuary (China) During 1998–2019 ». Dans Lecture Notes in Civil Engineering, 1152–67. Singapore : Springer Nature Singapore, 2023. http://dx.doi.org/10.1007/978-981-19-6138-0_101.
Texte intégralRésumé :
AbstractThis paper studies the morphological evolution and driving factors of the tidal flats in the Yangtze Estuary (YE), based on the bathymetric data over the last 20 years (1998–2019) and a three-dimensional numerical model (SWEM3D). The results show that: In the past two decades, the combined action of fluvial sediment decline and estuarine engineering has changed the morphological evolution trend of tidal flats in the YE. The fluvial sediment decline caused the decrease of suspended sediment concentration successively from the inner estuary to the mouth bar area (the outer estuary), which led to the erosion and steepening of the tidal flats in the YE, and the erosion of tidal flats in the inner estuary was earlier and more obvious than that in the mouth bar area. The estuarine engineering is the main controlling factor of the distribution and trend change of erosion-deposition in the adjacent tidal flat. The waterway regulation projects promoted the deposition of tidal flats within its sheltered area, while the reclamation and reservoir projects intensified the erosion of the lower tidal flats nearby. As for the remaining non-human-intervention tidal flats, those adjacent to the mainstream of ebb current in the inner estuary were significantly eroded, while those on the north side of the channel were slowly deposited due to the weaker hydrodynamics. In the future, the fluvial sediment supply may keep decreasing and maintain a lower level under the continued influence of anthropogenic activities in the Yangtze River basin, the unprotected tidal flats in the YE will face a risk of further erosion. It is necessary to take appropriate protection measures to improve the ecological service function of the tidal flats in the YE.
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Dettler, Jamie M., et Edwin A. Lewis. « Biophysical Studies of the Structure, Stability, and Ligand Binding Properties of G-Quadruplex DNA : Thoughts and Comparisons of the K-ras, c-MYC, and Bcl-2 Oncogene Promoter Sequence Quadruplexes ». Dans ACS Symposium Series, 33–50. Washington, DC : American Chemical Society, 2011. http://dx.doi.org/10.1021/bk-2011-1082.ch003.
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Herring, Jonathan. « 14. Gender, race, and diversity in the legal profession ». Dans Legal Ethics. Oxford University Press, 2017. http://dx.doi.org/10.1093/he/9780198788928.003.0014.
Texte intégralRésumé :
This chapter examines the issue of diversity in the legal profession. It first explains the meaning of diversity and the reasons why it should be promoted. It reviews the current status of the profession in terms of diversity. It considers diversity rules in the Equality Act 2010, Solicitors Regulation Authority (SRA) Handbook, and the Bar Standards Board (BSB) Handbook. Barriers to diversity and steps to promote diversity are also discussed.
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Lacaze, Xavier, Philippe Palanque, Eric Barboni et David Navarre. « Design Rationale for Increasing Profitability of Interactive Systems Development ». Dans Encyclopedia of Human Computer Interaction, 154–59. IGI Global, 2006. http://dx.doi.org/10.4018/978-1-59140-562-7.ch024.
Texte intégralRésumé :
User-centred development (Norman & Draper, 1986; Vredenburg, Isensee, & Righi, 2001) processes advocate the use of participatory design activities, end-user evaluations, and brainstorming in the early phases of development. Such approaches work in opposition of some software-engineering techniques that promote iterative development processes such as in agile processes (Beck, 1999) in order to produce software as quickly and as cheaply as possible. One way of justifying the profitability of development processes promoted in the field of human-computer interaction (HCI) is to not only take into account development costs, but also to take into account costs of use, that is, costs related to employment, training, and usage errors. Gain, in terms of performance (for instance, by providing default values in the various fields of a computer form) or in reducing the impact of errors (by providing undo facilities, for instance), can only be evaluated if the actual use of the system is integrated in the computation of the development costs. These considerations are represented in Figure 1. The upper bar of Figure 1 shows that development costs (grey part and black part) are higher than the development costs of RAD (rapid application development), represented in the lower bar (grey part). The black part of the upper bar shows the additional costs directly attributed to user-centred design. User-
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Salkind, Micah E. « Remediating the Underground ». Dans Do You Remember House ?, 85–118. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780190698416.003.0004.
Texte intégralRésumé :
The third chapter of Do You Remember House? traces the routes by which mostly straight, Black, and middle-class teenagers accessed and adapted the social and sonic templates developed by house music’s queer of color progenitors. Using close readings of radio “hot mixes” and oral history interviews with DJs, promoters, and dancers involved in the city’s all-ages “juice bar” scene, this chapter also suggests that house music radio was made by an emergent cohort of middle-class, Black, radio entrepreneurs who remediated Chicago musical repertoires for increasingly heterogeneous listening publics. The term remediation (Bolter & Grusin, 1999) helps account for the ways that the WBMX and WGCI hot mix shows incorporated and transformed the aesthetic priorities of teen juice bars, gay discotheques, and Black appeal radio programs to promote house music as a shared, if often contested, soundscape in greater Chicagoland.
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Kemmerer, Lisa. « Hunting Hype ». Dans Eating Earth. Oxford University Press, 2014. http://dx.doi.org/10.1093/oso/9780199391844.003.0008.
Texte intégralRésumé :
When faced with the ecological horrors of animal agriculture, some look to hunting as an escape—as the environmentally friendly way to put meat on the table. This chapter explores the environmental effects of hunting, exposing a handful of myths that help to make this sport appear to be environmentally friendly, animal friendly, socially acceptable—even morally exemplary. As noted, this book is written specifically for those who have a choice as to what they eat. This book is not a criticism of those who truly have few dietary options (for example, due to affordability or lack of availability). . . .For millennia men dreamed of acquiring absolute mastery over nature, of converting the cosmos into one immense hunting ground. . . . . . .—HORKHEIMER AND ADORNO 2 4 8 . . . In the United States, wildlife conservation was established by hunters for hunters because of hunters. In the late 19th century, Theodore Roosevelt complained that commercial hunters had decimated wildlife—that a comparatively small population of “market” hunters profited while the nation was stripped of hunter-target species (S. Fox 123). To address these concerns, he founded the Boone and Crockett Club (BCC) in 1897, with the following mission: “[T] o promote the conservation and management of wildlife, especially big game, and its habitat, to preserve and encourage hunting and to maintain the highest ethical standards of fair chase and sportsmanship in North America” (“About the B & C Club”). “Conservation” is a utilitarian, human-centered term promoting the protection of wildlife and wilderness for human use. Accordingly, the BCC promoted laws protecting “every citizen’s freedom to hunt and fish,” and established wildlife as “owned by the people and managed in trust for the people by government agencies” (“About the B & C Club”). As a result of the BCC, the U.S. government was placed in charge of managing wildlife on behalf of hunters.
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Geyer, Holly L., Deepti Radia, Nicholas Sarlis et Ruben A. Mesa. « Assessment of disease burden in patients with myeloproliferative neoplasms ». Dans Oxford Specialist Handbook : Myeloproliferative Neoplasms, 267–85. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198744214.003.0017.
Texte intégralRésumé :
The BCR-ABL-negative myeloproliferative neoplasms (MPN) collectively represent a diverse assortment of clonal myeloid malignancies with variability in both genotypic and phenotypic presentation. MPN subtypes including essential thrombocythaemia (ET), polycythaemia vera (PV), myelofibrosis (MF), systemic mast cell disorders have been best studied in terms of symptom profiles and heterogeneously incur disease burdens that impact treatment options, overall quality of life, and survival. Recent treatment strategies have aimed to incorporate disease burden assessment into the selection of therapeutic interventions. Patient-reported outcome (PRO) tools have been developed to objectively assess the MPN disease burden in both clinical and trial formats. Their development supports recent FDA efforts to promote PROs in supporting labelling claims for novel targeted agents. This chapter discusses the spectrum of symptoms inherent to MPN disorders, available risk scoring tools and PRO options, and the emerging role of patient outcomes as trial endpoints.
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Milata, V., S. Rádl et S. Voltrová. « Titanium(IV) Chloride Promoted Formation of Enol Ethers ». Dans X-Ene-X (X=F, Cl, Br, I, O, S, Se, Te, N, P), Ene-Hal, and Ene-O Compounds, 1. Georg Thieme Verlag KG, 2008. http://dx.doi.org/10.1055/sos-sd-032-00690.
Texte intégralActes de conférences sur le sujet "BCR promoter"
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Tupone, Maria Grazia, Daniela Trisciuoglio, Marianna Desideri, Marta Di Martile, Chiara Gabellini, Simonetta Buglioni, Laura De Salvo, Gabriele Alessandrini, Simona D'Aguanno et Donatella Del Bufalo. « Abstract 933 : Bcl-xL overexpression promotes tumor aggressiveness ». Dans Proceedings : AACR Annual Meeting 2017 ; April 1-5, 2017 ; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-933.
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Hirano, Isao, Satoki Nakamura, Tomonari Takemura, Daisuke Yokota, Taka-aki Ono, Kaori Shinjo, Kazuyuki Shigeno, Shin-ya Fujisawa et Kazunori Ohnishi. « Abstract 5053 : Depletion of PHLPP1 and 2 by Bcr-Abl promotes CML cell proliferation ». Dans Proceedings : AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010 ; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-5053.
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Yokota, Daisuke, Satoki Nakamura, Tomonari Takemura, Isao Hirano, Takaaki Ono, Kazuyuki Shigeno, Shinya Fujisawa, Kaori Takeshita, Kiyoshi Misawa et Kazunori Ohnishi. « Abstract 5060 : Downregulation of THAP11 by Bcr-Abl promotes CML cell proliferation through c-Myc expression ». Dans Proceedings : AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010 ; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-5060.
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Zhang, Tiantian, Sha Li, Joseph Na, Soyoung Chi, George Zhang et Yi-Chieh Nancy Du. « Abstract 1123 : Bcl-xL promotes metastasis via a novel nuclear function ». Dans Proceedings : AACR Annual Meeting 2019 ; March 29-April 3, 2019 ; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-1123.
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Zhang, Tiantian, Sha Li, Joseph Na, Soyoung Chi, George Zhang et Yi-Chieh Nancy Du. « Abstract 1123 : Bcl-xL promotes metastasis via a novel nuclear function ». Dans Proceedings : AACR Annual Meeting 2019 ; March 29-April 3, 2019 ; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-1123.
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Scott, Iain, Dharendra Thapa, Paramesha Bugga, Bellina Mushala, Janet Manning, Michael Stoner, Brenda McMahon et al. « BS3 GCN5L1 promotes diastolic dysfunction by inhibiting cardiac pyruvate oxidation ». Dans British Cardiovascular Society Annual Conference, ‘100 years of Cardiology’, 6–8 June 2022. BMJ Publishing Group Ltd and British Cardiovascular Society, 2022. http://dx.doi.org/10.1136/heartjnl-2022-bcs.183.
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Tomonari, Takemura, Satoki Nakamura, Daisuke Yokota, Isao Hirano, Takaaki Ono, Kazuyuki Shigeno, Shinya Fujisawa, Naoyuki Miura et Kazunori Ohnishi. « Abstract 5161 : Activation of Raf-1 through the depletion of RKIP by Bcr-Abl promotes CML cell proliferation ». Dans Proceedings : AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010 ; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-5161.
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Abelniece, Zane, Helle-Mai Piirsoo, Hugo Mandar et Aile Tamm. « CHARACTERIZATION AND ACTIVITY OF COBALT BASED SBA-15 SUPPORTED CATALYSTS FOR CARBON DIOXIDE HYDROGENATION ». Dans 22nd SGEM International Multidisciplinary Scientific GeoConference 2022. STEF92 Technology, 2022. http://dx.doi.org/10.5593/sgem2022/4.1/s17.02.
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Utilization of renewable energy sources is future solution for providing the word energy demand and to solve the problems of climate changes. Carbon dioxide is greenhouse gas and major contributor to the global warming. Hydrogenation process of carbon dioxide with renewable hydrogen will not only mitigate the problem of global warming but will also produce valuable products and renewable energy. The hydrogenation of carbon dioxide to value-added chemicals and fuels is a promising route, providing products such as carbon monoxide, methanol, hydrocarbons, and higher alcohols. Among these, the synthesis of higher alcohols from carbon dioxide hydrogenation is a challenging task. The literature showed that Co3O4 catalysts with ordered mesoporous structure could promote the growth of carbon chains for higher hydrocarbon and alcohol production. In our study the cobalt based catalysts Co3O4 on SBA-15 support (mesoporous silica) - Co3O4/SBA-15, K/Co3O4/SBA-15 and Pt/Co3O4/SBA-15 - have been prepared and characterized using XRD analysis, N2 adsorption-desorption analysis and SEM-EDX analysis. The results showed that on the contrary from addition of Pt promoter, addition of K promoter decreased the surface area and pore volume, that could be explained with metal oxide dispersion into the pores and on the external surface of the support. CO2 hydrogenation in a fixed-bed tubular micro-activity reactor at 20 bar 250 �C with H2 to CO2 molar ratio 4 to 1 was studied using these catalysts.
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Pal, Rekha, et Stephanie Greene. « Abstract 3082 : miRNA-10b promotes medulloblastoma proliferation and survival via Bcl-2. » Dans Proceedings : AACR 104th Annual Meeting 2013 ; Apr 6-10, 2013 ; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-3082.
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Jones, Sarah, Amelia Drysdale, Fahmina Khanom, Sadiyah Kalsoom, Anuoluwapo Opadiran et Ryan Riley. « BS12 Investigating optimal platelet prepartions to promote angiogenesis and wound healing ». Dans British Cardiovascular Society Annual Conference ‘Digital Health Revolution’ 3–5 June 2019. BMJ Publishing Group Ltd and British Cardiovascular Society, 2019. http://dx.doi.org/10.1136/heartjnl-2019-bcs.175.
Texte intégralRapports d'organisations sur le sujet "BCR promoter"
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Barash, Itamar, J. Mina Bissell, Alexander Faerman et Moshe Shani. Modification of Milk Composition via Transgenesis : The Role of the Extracellular Matrix in Regulating Transgene Expression. United States Department of Agriculture, juillet 1995. http://dx.doi.org/10.32747/1995.7570558.bard.
Texte intégralRésumé :
Altering milk composition via transgenesis depends on three main factors. (1) The availability of an efficient regulatory sequences for targeting transgene(s) to the mammary gland; (2) a reliable in vitro model to test the expression of transgenes prior to their introduction to the animal genome; and (3) better understanding of the major factors which determine the rate of gene expression and protein synthesis. The current studies provide the necessary means and knowledge to alter milk protein composition via transgenesis. The following specific goals were achieved: a: Identifying regulatory regions in the b-lactoglobulin (BLG) gene and the cross-talk between elements which enabled us to construct an efficient vector for the expression of desirable cDNA's in the mammary gland. b: The establishment of a sheep mammary cell line that serves as a model for the analysis of endogenous and exogenous milk protein synthesis in the mammary gland of livestock. c: An accurate comparison of the potency of the 5' regulatory sequences from the BLG and whey acidic protein (WAP) promoters in directing the expression of human serum albumin (HSA) to the mammary gland in vitro and in vivo. In this study we have also shown that sequences within the coding region may determine a specific pattern of expression for the transgene, distinct from that of the native milk protein genes. d: Characterizing the dominant role of ECM in transgene expression in mammary epithelial cells. e: Further characterization of the BCE-1 enhancer element in the promoter of the b-casein gene as a binding site for the c/EBP-b and Stat5. Identifying its interaction with chromatin and its up regulation by inhibitors of histone deacetylation. f: Identifying a mechanism of translational control as a mediator for the synergistic effect of insulin and prolactin on protein synthesis in the mammary gland.
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Macdonald, Keir. The Impact of Business Environment Reforms on Poverty, Gender and Inclusion. Institute of Development Studies (IDS), janvier 2021. http://dx.doi.org/10.19088/k4d.2021.006.
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This rapid review synthesises the literature from academic, policy, and knowledge institution sources on how business environment reforms in middle-income countries impacts on poverty, gender and inclusion. Although, there is limited evidence on the direct impact of business environment reforms on poverty, gender, and inclusion, this review illustrates that there is evidence of indirect effects of such reforms. Business environment reform (BER) targets inadequate business regulations and institutions, in order to remove constraints to business investment and expansion, enabling growth and job creation, as well as new opportunities for international business to contribute to and benefit from this growth. However, there is a lack of detailed knowledge of the impact of BER on gender and inclusion (G&I) outcomes, in terms of the potential to remove institutional barriers which exclude formerly marginalised groups from business opportunities, in ways that promote equal access to resources, opportunities, benefits, and services. The literature shows how the business environment affects women in business, and how women’s experiences of a given business environment can be different from those of men. This is the result of disparities in how they are treated under the law, but also based on structural and sociocultural factors which influence how men and women behave in a given business environment and the barriers they face.
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Douglas, Thomas, Matthew Sturm, Joel Blum, Christopher Polashenski, Svetlana Stuefer, Christopher Hiemstra, Alexandra Steffen, Simon Filhol et Romain Prevost. A pulse of mercury and major ions in snowmelt runoff from a small Arctic Alaska watershed. Engineer Research and Development Center (U.S.), juillet 2021. http://dx.doi.org/10.21079/11681/41203.
Texte intégralRésumé :
Atmospheric mercury (Hg) is deposited to Polar Regions during springtime atmospheric mercury depletion events (AMDEs) that require halogens and snow or ice surfaces. The fate of this Hg during and following snowmelt is largely unknown. We measured Hg, major ions, and stable water isotopes from the snowpack through the entire spring melt runoff period for two years. Our small (2.5 ha) watershed is near Barrow (now Utqiaġvik), Alaska. We measured discharge, made 10 000 snow depths, and collected over 100 samples of snow and meltwater for chemical analysis in 2008 and 2009 from the watershed snowpack and ephemeral stream channel. Our results suggest AMDE Hg complexed with Cl⁻ or Br⁻ may be less likely to be photochemically reduced and re-emitted to the atmosphere prior to snowmelt, and we estimate that roughly 25% of the Hg in snowmelt is attributable to AMDEs. Projected Arctic warming, with more open sea ice leads providing halogen sources that promote AMDEs, may provide enhanced Hg deposition, reduced Hg emission and, ultimately, an increase in snowpack and snowmelt runoff Hg concentrations.
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Theory of change : Bet You Can Help. Addiction Recovery Agency, Beacon Counselling Trust, juin 2021. http://dx.doi.org/10.33684/2021.004.
Texte intégralRésumé :
Gambling-related harms are a significant public health issue in Great Britain. These harms are often underrecognized and most people who experience harms go without support. Under the leadership of Addiction recovery Agency (Ara) and Beacon Counselling Trust (BCT), the Bet You Can Help (BYCH) programme is filling the need for place-based education and training to identify and address gambling related harms. The BYCH programme is a community first aid model for safer gambling that promotes the early identification of people who are at risk of gambling related harms. Offered as a Level 2 Qualification through the Royal Society of Public Health, this programme aims to reduce harms and prevent lives being lost from gambling related harms in Great Britain. This theory of change considers the inputs, activities, outputs, and outcomes necessary to achieve these goals. It can be used by organizations, groups, and individuals in any sector impacted by gambling related harms in Great Britain.