Effect of caffeine in Fanconi anemia

Sabatier, Laure; Dutrillaux, Bernard

doi:10.1007/bf00366244

“…Instead, the dominant coalition has been preferring to impose unilateral decisions or to negotiate with coalitions belonging to other subsystems (agriculture, mining and military). This kind of behavior induces a reflection about the study of "dialogue of deaf " (Sabatier, 1988) that is still little discussed in ACF empirical cases.…”

Section: Policy Change: Theoretical Discussion About Recent Brazilianmentioning

confidence: 99%

“…The Advocacy Coalition Framework -ACF was presented as a framework capable of providing an alternative to traditional approaches to public policy analysis (Sabatier, 1988;Sabatier & Jenkins-Smith, 1993, 1999. Its aim was to shift the analysis of the policy process from a linear and procedural perspective to an approach anchored in change, its causes, and its effects .…”

Section: Acf Overviewmentioning

confidence: 99%

Large-scale environmental policy change: analysis of the Brazilian reality

Capelari

¹

,

Araújo

²

,

Calmon

³

et al. 2020

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The Brazilian presidential elections of 2018 brought large-scale changes in the Brazilian environmental policy subsystem. The purpose of this article is to analyze these changes through the lenses of the Advocacy Coalition Framework - ACF. First, we introduced some of the main characteristics of this subsystem, then we presented a hemerographic analysis to describe and analyze the effects of four recent shocks in this subsystem. Two of these shocks were external: (i) the election of a new political elite in power that brought a clear discourse of denial of the relevance of environmental policy and (ii) calamitous environmental events that occurred in Brazil in 2019. The other two shocks were internal: (i) the capture of key positions and resources by dominant coalition members and (ii) the rise of conflict and polarization among the coalitions in the subsystem. The results showed: (i) the rise of a hyper-adversarial environmental policy subsystem; (ii) a realignment between non-dominant coalitions in a cooperative direction; (iii) the imposition of clear barriers to negotiation; (iv) changes in the use of scientific information by more politicized discourses with a high degree of bias. The article contributes to the understanding of the processes of institutional change in environmental policy, especially in contexts of large-scale change generated by increasing electoral polarization and fierce political disputes. It also contributes to the analysis of the limits and possibilities of the ACF in the Brazilian environmental agenda.

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“…It is of interest to note that a hamster cell mutant sensitive to killing by a variety of agents has been found to be hypomutable in association with a defect in post-replication repair (50). The involvement of an alteration in post-replication repair in FA cells is suggested also by the effect of caffeine, a known inhibitor of this process in eukaryotic cells (51).…”

Section: Discussionmentioning

confidence: 99%

Hypomutability in Fanconi anemia cells is associated with increased deletion frequency at the HPRT locus.

Papadopoulo

¹

,

Guillouf

²

,

Mohrenweiser

³

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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Fanconi anemia (FA) is an inherited human disorder associated with a predisposition to cancer and characterized by anomalies in the processing ofDNA cross-links and certain monoadducts. We reported previously that the frequency of psoralen-photoinduced mutations at the HPRT locus is lower in FA cells than in normal cells. This hypomutability is shown here to be associated with an increased frequency of deletions in the HPRT gene when either a mixture ofcross-links and monoadducts or monoadducts alone are induced. Molecular analysis of mutants in the HPRT gene was carried out. In normal cells the majority of spontaneous and induced mutants are point mutations whereas in FA deletion mutations predominate. In that case a majority of mutants were found to lack individual exons or small clusters of exons whereas in normal cells large (complete or major gene loss) and small deletions are almost equally represented. Thus we propose that the FA defect lies in a mutagenic pathway that, in normal cells, involves bypassing lesions and subsequent gap flling by a recombinational process during replication.Cells possess various mechanisms to repair DNA lesions in order to maintain cell viability and the functional stability of DNA. Lesions unrepaired or repaired inaccurately lead to changes in the genetic information. These heritable changes range from base substitutions to large chromosomal rearrangements. Knowledge of the DNA lesions produced by a mutagen, coupled with an analysis of the molecular nature of the induced mutations, can give clues as to which lesions are biologically relevant and how these lesions are processed. In addition, the determination of mutagenic specificity in the presence or absence of a particular repair system can suggest mechanisms by which this system modulates the mutagenic process. Mutational changes are implicated in human health problems, including genetic diseases and cancer. Thus it is important to acquire information directly from human cells. Molecular techniques have made it possible to examine the molecular events underlying mutations at specific loci in mammalian cells (for reviews, see refs. 1 and 2). The following systems have been established for this purpose: shuttle vectors (for review, see ref. 3 and references therein), single integrated copies of a transfected bacterial gene (4), or analysis of mutations at endogenous loci (5-7). Among these systems, the last is the most laborious, but the advantage is that the chromosomal location, the structural conformation of DNA, and the topological constraints correspond to a natural situation. Among the various endogenous genes studied, the HPRT gene has several advantages: its large size (45 kilobases), its X chromosome location, and the availability of hybridization probes and of nucloeotide sequence data (8, 9). Moreover, large deletions or rearrangements can be detected since the HPRT locus is not close to essential genes (6, 10).Cells from patients with defects in DNA-damage processing provide opportunities to explore the m...

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“…In contrast, changes only occurring in secondary beliefs indicate less abrupt changes. In this sense, policy-oriented beliefs were formed from the criterion of susceptibility to change, which makes them important elements to identify and characterize the changes (Sabatier, 1988).…”

Section: Acf Overviewmentioning

confidence: 99%

Mudança de larga escala na política ambiental: análise da realidade brasileira

Capelari

¹

,

Araújo

²

,

Calmon

³

et al. 2020

View full text Add to dashboard Cite

The Brazilian presidential elections of 2018 brought large-scale changes in the Brazilian environmental policy subsystem. The purpose of this article is to analyze these changes through the lenses of the Advocacy Coalition Framework - ACF. First, we introduced some of the main characteristics of this subsystem, then we presented a hemerographic analysis to describe and analyze the effects of four recent shocks in this subsystem. Two of these shocks were external: (i) the election of a new political elite in power that brought a clear discourse of denial of the relevance of environmental policy and (ii) calamitous environmental events that occurred in Brazil in 2019. The other two shocks were internal: (i) the capture of key positions and resources by dominant coalition members and (ii) the rise of conflict and polarization among the coalitions in the subsystem. The results showed: (i) the rise of a hyper-adversarial environmental policy subsystem; (ii) a realignment between non-dominant coalitions in a cooperative direction; (iii) the imposition of clear barriers to negotiation; (iv) changes in the use of scientific information by more politicized discourses with a high degree of bias. The article contributes to the understanding of the processes of institutional change in environmental policy, especially in contexts of large-scale change generated by increasing electoral polarization and fierce political disputes. It also contributes to the analysis of the limits and possibilities of the ACF in the Brazilian environmental agenda.

show abstract

Effect of caffeine in Fanconi anemia

Cited by 29 publications

References 13 publications

Large-scale environmental policy change: analysis of the Brazilian reality

Large-scale environmental policy change: analysis of the Brazilian reality

Hypomutability in Fanconi anemia cells is associated with increased deletion frequency at the HPRT locus.

Mudança de larga escala na política ambiental: análise da realidade brasileira

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