Pratiques discursives et savoir social : l’exemple de la Commission royale sur les nouvelles techniques de reproduction

Les commissions royales d’enquête ont été traditionnellement considérées comme des institutions visant à produire des consensus à propos des politiques gouvernementales. Notre article refuse cet argument et s’appuie sur une interprétation plus dynamique du rôle des commissions. La rapidité des changements technologiques et sociaux, tout comme le désir d’une plus grande participation des citoyens à des décisions de plus en plus complexes, indiquent le besoin de lieux où puissent se conjuguer savoir spécialisé et démocratie. Cet article soutient que les commissions royales d’enquête peuvent constituer un tel lieu. Nous défendons cette thèse en analysant la Commission royale sur les nouvelles techniques de reproduction. Nous soutenons que tout en accueillant des formes de savoir très diversifiées, celles-ci n’ont pas toutes été prises en compte, en définitive, à la suite de querelles politiques et idéologiques.Royal commissions have traditionally been dismissed as legitimizing mechanisms aimed at achieving consensus on government policy. This article rejects this argument and calls for a more dynamic interpretation of royal commissions. The increased complexity of policy-making due the rapidity of technological and social change, along with the growing demand for participatory politics, stresses the need for both democratic practices and expert knowledge in policy analysis. This article suggests that royal commissions have the capacity to engage in discursive policy analysis by providing a forum for both expert and nonexpert forms of knowledge in the policy process. These arguments are made in relation to the Royal Commission on New Reproductive Technologies. The article contends that while the Commission generated and accommodated alternative forms of knowledge on the issue of reproductive technologies, its discursive capacity was ultimately constrained by internal political and ideological battles

Capital Expenditure Financing in Italian Municipalities: An Analytic Approach

The economic literature finds a strong link between infrastructure endowment and economic growth. In recent years, the Italian infrastructure backwardness has become a central theme in the national political, economic and social debate. By definition, infrastructure investment implies the allocation of financial resources at present to obtain future advantages. The temporal gap brings up questions related to the financing mechanism, which is one of the most interesting themes of the debate.Traditionally, within the Italian system of derived finance and according to the inter-generational equity principle, Italian Municipalities (IMs) have financed investment expenditures by resorting to borrowing, for a minimum amount with the banking system, and for the most part with the Cassa Depositi e Prestiti S.p.A. (CDP). Unfortunately, this financing method has imposed heavy burdens on future budgets, in terms of refund of interest and capital. Moreover, in 2001, the reform of the Constitution (especially the part regarding Local Authorities (Las), Title V, Part II) has strengthened the political, administrative, and financial autonomy of LAs

Potent and Stable Attenuation of Live-HIV-1 by Gain of a Proteolysis-resistant Inhibitor of NF-κB (IκB-αS32/36A) and the Implications for Vaccine Development *

Live-attenuated human immunodeficiency viruses (HIVs) are candidates for Acquired Immunodeficiency Syndrome (AIDS) vaccine. Based on the simian immunodeficiency virus (SIV) model for AIDS, loss-of-function (e.g. deletion of accessory genes such as nef) has been forwarded as a primary approach for creating enfeebled, but replication-competent, HIV-1/SIV. Regrettably, recent evidence suggests that loss-of-function alone is not always sufficient to prevent the emergence of virulent mutants. New strategies that attenuate via mechanisms distinct from loss-of-function are needed for enhancing the safety phenotype of viral genome. Here, we propose gain-of-function to be used simultaneously with loss-of-function as a novel approach for attenuating HIV-1. We have constructed an HIV-1 genome carrying the cDNA of a proteolysis-resistant nuclear factor-kappaB inhibitor (IkappaB-alphaS32/36A) in the nef region. HIV-1 expressing IkappaB-alphaS32/36A down-regulates viral expression and is highly attenuated in both Jurkat and peripheral blood mononuclear cells. We provide formal proof that the phenotypic and attenuating characteristics of IkappaB-alphaS32/36A permit its stable maintenance in a live, replicating HIV-1 despite 180 days of forced ex vivo passaging in tissue culture. As compared with other open-reading frames embedded into HIV/SIV genome, this degree of stability is unprecedented. Thus, IkappaB-alphaS32/36A offers proof-of-principle that artifactually gained functions, when used to attenuate the replication of live HIV-1, can be stable. These findings illustrate gain-of-function as a feasible strategy for developing safer live-attenuated HIVs to be tested as candidates for AIDS vaccine

Towards a comprehensive view of 8-oxo-7,8-dihydro-2'-deoxyguanosine: Highlighting the intertwined roles of DNA damage and epigenetics in genomic instability

8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a major product of DNA oxidation, is a pre-mutagenic lesion which is prone to mispair, if left unrepaired, with 2'-deoxyadenosine during DNA replication. While unrepaired or incompletely repaired 8-oxodG has classically been associated with genome instability and cancer, it has recently been reported to have a role in the epigenetic regulation of gene expression. Despite the growing collection of genome-wide 8-oxodG mapping studies that have been used to provide new insight on the functional nature of 8-oxodG within the genome, a comprehensive view that brings together the epigenetic and the mutagenic nature of the 8-oxodG is still lacking. To help address this gap, this review aims to provide (i) a description of the state-of-the-art knowledge on both the mutagenic and epigenetic roles of 8-oxodG; (ii) putative molecular models through which the 8-oxodG can cause genome instability; (iii) a possible molecular model on how 8-oxodG, acting as an epigenetic signal, could cause the translocations and deletions which are associated with cancer

Inhibition of HIV-1 replication in primary human monocytes by the IκB-αS32/36A repressor of NF-κB

BACKGROUND: The identification of the molecular mechanisms of human immunodeficiency virus type 1, HIV-1, transcriptional regulation is required to develop novel inhibitors of viral replication. NF-κB transacting factors strongly enhance the HIV/SIV expression in both epithelial and lymphoid cells. Controversial results have been reported on the requirement of NF-κB factors in distinct cell reservoirs, such as CD4-positive T lymphocytes and monocytes. We have previously shown that IκB-αS32/36A, a proteolysis-resistant inhibitor of NF-κB, potently inhibits the growth of HIV-1 and SIVmac239 in cell cultures and in the SIV macaque model of AIDS. To further extend these observations, we have generated NL(AD8)IκB-αS32/36A, a macrophage-tropic HIV-1 recombinant strain endowed to express IκB-αS32/36A. RESULTS: In this work, we show that infection with NL(AD8)IκB-αS32/36A down-regulated the NF-κB DNA binding activity in cells. NL(AD8)IκB-αS32/36A was also highly attenuated for replication in cultures of human primary monocytes. CONCLUSIONS: These results point to a major requirement of NF-κB activation for the optimal replication of HIV-1 in monocytes and suggest that agents which interfere with NF-κB activity could counteract HIV-1 infection of monocytes-macrophages in vivo

Blood and skin-derived Sezary cells: differences in proliferation-index, activation of PI3K/AKT/mTORC1 pathway and its prognostic relevance

Sézary syndrome (SS) is a rare and aggressive variant of Cutaneous T-Cell Lymphoma characterized by neoplastic distribution mainly involving blood, skin, and lymph-node. Although a role of the skin microenvironment in SS pathogenesis has long been hypothesized, its function in vivo is poorly characterized. To deepen this aspect, here we compared skin to blood-derived SS cells concurrently obtained from SS patients highlighting a greater proliferation-index and a PI3K/AKT/mTORC1 pathway activation level, particularly of mTOR protein, in skin-derived-SS cells. We proved that SDF-1 and CCL21 chemokines, both overexpressed in SS tissues, induce mTORC1 signaling activation, cell proliferation and Ki67 up-regulation in a SS-derived cell line and primary-SS cells. In a cohort of 43 SS cases, we observed recurrent copy number variations (CNV) of members belonging to this cascade, namely: loss of LKB1 (48%), PTEN (39%) and PDCD4 (35%) and gains of P70S6K (30%). These alterations represent druggable targets unraveling new therapeutic treatments as metformin here evaluated in vitro. Moreover, CNV of PTEN, PDCD4, and P70S6K, evaluated individually or in combination, are associated with reduced survival of SS patients. These data shed light on effects in vivo of skin-SS cells interaction underlying the prognostic and therapeutic relevance of mTORC1 pathway in SS

Electrical release of dopamine and levodopa mediated by amphiphilic \u3b2-cyclodextrins immobilized on polycrystalline gold

Vesicles of cationic amphiphilic \u3b2-cyclodextrins have been immobilized on polycrystalline gold by exploiting the chemical affinity between their amino groups and Au atoms. The presence of cyclodextrins has been widely investigated by means of AFM, XPS, kelvin probe and electrochemical measurements. This multi-functional coating confers distinct electrochemical features such as pH-dependent behavior and partial/total blocking properties towards electro-active species. The host-guest properties of \u3b2-cyclodextrins have been successfully exploited in order to trap drugs, like dopamine and levodopa. The further release of these drugs was successfully achieved by providing specific electrical stimuli. This proof-of-concept led us to fabricate an electronic device (i.e. an organic transistor) capable of dispensing both dopamine and levodopa in aqueous solution

Fragmentation of biomass-templated CaO-based pellets

The use of biomass templating materials with a cheap production method as an enhanced sorbent for CO2 uptake has been proposed recently. However, the attrition and fragmentation behaviour of this type of material, which is a vital parameter for calcium looping sorbents, has not yet been investigated in detail. In this work the fragmentation behaviour of biomass-templated sorbents is investigated. Three types of materials were prepared using a mechanical pelletiser: 1. lime and cement (LC); 2. lime and flour (LF); and 3. lime, cement and flour (LCF). These samples were heat treated in a pressurised heated strip reactor (PHSR) and in a bubbling fluidised bed (BFB) and changes in particle size distribution were measured to assess fragmentation. Results indicated that the addition of biomass enhances the propensity to undergo fragmentation. Upon heat treatment in the PHSR the particle size of LC was not modified significantly; on the contrary the mean particle diameter of LF decreased from 520 μm to 116 μm and that of LCF from 524 μm to 290 μm. Fragmentation tests in the BFB confirmed the trend: 67% of the particles of LF fragmented, against 53% of LCF and 18% of LC samples. The addition of cement to the LF samples partially counteracts this performance degradation with respect to attrition. However, calcium aluminate pellets (LC) showed the lowest rate of fragmentation amongst all of the samples tested