Carcinogenicity of a Single Administration of N-Nitrosomethylurea: a Comparison Between New-born and 5-Week-Old Mice and Rats

N-Nitrosomethylurea (NMUrea) was given as a single intraperitoneal injection either to newborn or to 5-week-old (C57BL * C3Hf)F1 mice and Wistar rats. Newborn mice were more susceptible than 5-week-old mice to the development of lymphosarcomas, lung adenomas and hepatomas, whereas newborn rats were more susceptible than their weaned counterparts to the development of renal anaplastic tumours. Other tumours occured with the same frequency in newborn and mature animals. Tumours of the forestomach in mice were more frequenty found in animals treated at 5 weeks than in those treated at birth. Since NMUrea persists for only a very short time and breaks down spontaneously it seems that the paucity of enzymes related to immaturity in newborns is not a major factor in determining the different susceptibility of newborn animals to NMUrea carcinogenicity

Preference Theory and Low Fertility: A Comparative Perspective

The discussion on the causes of the most recent fertility decline in Europe, and in particular on the emergence of lowest low fertility, emphasises the relevance of cultural factors in addition to economic ones. Being part of such a cultural framework, the heterogeneity of preferences concerning the "career vs. family" dichotomy has been systematised in the "Preference Theory" approach developed by Catherine Hakim. So far, however, this heterogeneity in preferences has been underinvestigated in a comparative framework. This paper makes use of new comparative data from the 2004/05 Round of the European Social Survey to test the links between individual-level preferences and both fertility outcomes and intentions in a variety of social settings. Results confirm a link between work-family lifestyle preferences and realised fertility in a variety of European countries, while they do not support the relevance of lifestyle preferences for fertility intentions.Preference Theory, low and lowest low fertility, Europe, European Social Survey, welfare regime.

Attitudes, norms and perceived behavioural control: explaining fertility intentions in Bulgaria

In this article, we study fertility decision-making through timing parity-progression intentions. The theoretical framework builds on Ajzen's social-psychological "Theory of Planned Behavior": intentions are seen as directly dependent on three components: attitudes, norms and perceived behavioural control. We study the case of Bulgaria, a "lowest-low" fertility country. In 2002, a sample survey containing a specially designed module was conducted. This module included an implementation of our framework, with a special attention to the links between normative pressure and the social network of respondents. Results show that the three components are broadly predictive of fertility intentions. More specifically, attitudes are more relevant than norms for higher parities. Socio-economic, ideational, psychological and social capital-based factors are relevant background determinants.Dans cet article, nous étudions les décisions en matière de fécondité à l'aide des intentions d'agrandissement avec référence temporelle. Le cadre conceptuel est celui de la théorie psychosociologique du comportement prévu d'Ajzen, selon laquelle les intentions dépendent de façon directe de trois éléments: les attitudes, les normes et le contrôle perçu du comportement. L'étude concerne la Bulgarie, un pays dont la fécondité est des plus basses. En 2002, une enquête par sondage comportant un module de questions construit à cette fin a été menée. Ce module comprenait les éléments pour mettre en œuvre notre cadre conceptuel, en accordant une attention particulière aux liens entre la pression normative et le réseau social des enquêtés. Les résultats montrent que les trois éléments de la théorie sont des facteurs de prédiction des intentions de fécondité. Plus spécifiquement, les attitudes sont plus pertinentes que les normes pour le passage au deuxième enfant. Les facteurs socio-économiques, idéationnels, psychologiques et ceux basés sur le capital social sont pertinents comme déterminants de contexte

Preference theory and low fertility: a comparative perspective

The discussion on the causes of the most recent fertility decline in Europe, and in particular on the emergence of lowest-low fertility, emphasizes the relevance of cultural factors in addition to economic ones. As part of such a cultural framework, the heterogeneity of preferences concerning the "career vs. family" dichotomy has been systematized in the "Preference Theory" approach developed by Catherine Hakim. This heterogeneity in preferences, however, has so far been underinvestigated in a comparative framework. This paper makes use of comparative data from the 2004/2005 Round of the European Social Survey to test the links between individual-level preferences and both fertility outcomes and fertility intentions, in a variety of societal settings. Results confirm an association between work–family lifestyle preferences and realized fertility in a variety of European countries, while they do not show a relationship between lifestyle preferences and fertility intentions. Results further support the existence of heterogeneous patterns of association between lifestyle preferences and fertility choices among welfare regimes.Le débat portant sur les causes de la baisse la plus récente de la fécondité en Europe, et en particulier sur l’émergence des fécondités les plus basses met l’accent sur le rôle des facteurs culturels, par-delà les facteurs économiques. Dans le cadre de ces facteurs culturels, l’hétérogénéité des préférences en matière de dilemme "carrière ou famille" a été formalisé par Catherine Hakim sous la forme de la "théorie des préférences". Cette hétérogénéité des préférences a toutefois été peu explorée dans une perspective comparative. Cet article exploite les données comparatives de la vague 2004/2005 de l’Enquête Sociale Européenne pour tester les liens entre les préférences individuelles, d’une part, et la fécondité réelle et souhaitée, d’autre part, dans des contextes sociaux très divers. Les résultats confirment une association entre les préférences en matière de mode de vie par rapport au travail et à la famille et la fécondité réelle dans toute une série de pays européens, mais ne mettent pas en évidence de lien entre les préférences en matière de mode de vie et la fécondité souhaitée. De plus, les résultats confirment l’existence de schémas hétérogènes d’association entre les préférences en matière de modes de vie et les choix de fécondité dans les différents régimes d’Etat-providence

A Wnt1 regulated Frizzled-1/β-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection.

BACKGROUND: Dopamine-synthesizing (dopaminergic, DA) neurons in the ventral midbrain (VM) constitute a pivotal neuronal population controlling motor behaviors, cognitive and affective brain functions, which generation critically relies on the activation of Wingless-type MMTV integration site (Wnt)/β-catenin pathway in their progenitors. In Parkinson's disease, DA cell bodies within the substantia nigra pars compacta (SNpc) progressively degenerate, with causes and mechanisms poorly understood. Emerging evidence suggests that Wnt signaling via Frizzled (Fzd) receptors may play a role in different degenerative states, but little is known about Wnt signaling in the adult midbrain. Using in vitro and in vivo model systems of DA degeneration, along with functional studies in both intact and SN lesioned mice, we herein highlight an intrinsic Wnt1/Fzd-1/β-catenin tone critically contributing to the survival and protection of adult midbrain DA neurons. RESULTS: In vitro experiments identifie Fzd-1 receptor expression at a mRNA and protein levels in dopamine transporter (DAT) expressing neurons, and demonstrate the ability of exogenous Wnt1 to exert robust neuroprotective effects against Caspase-3 activation, the loss of tyrosine hydroxylase-positive (TH+) neurons and [3H] dopamine uptake induced by different DA-specific insults, including serum and growth factor deprivation, 6-hydroxydopamine and MPTP/MPP+. Co-culture of DA neurons with midbrain astrocytes phenocopies Wnt1 neuroprotective effects, whereas RNA interference-mediated knockdown of Wnt1 in midbrain astrocytes markedly reduces astrocyte-induced TH+ neuroprotection. Likewise, silencing β-catenin mRNA or knocking down Fzd-1 receptor expression in mesencephalic neurons counteract astrocyte-induced TH+ neuroprotection. In vivo experiments document Fzd-1 co-localization with TH+ neurons within the intact SNpc and blockade of Fzd/β-catenin signaling by unilateral infusion of a Fzd/β-catenin antagonist within the SN induces reactive astrocytosis and acutely inhibits TH+ neuron survival in ipsilateral SNpc, an effect efficiently prevented by pharmacological activation of β-catenin signaling within the SNpc. CONCLUSION: These results defining a novel Wnt1/Fzd-1/β-catenin astrocyte-DA autoprotective loop provide a new mechanistic inside into the regulation of pro-survival processes, with potentially relevant consequences for drug design or drug action in Parkinson's disease.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Differential regulation of iron regulatory element-binding protein(s) in cell extracts of activated lymphocytes versus monocytes-macrophages.

The intracellular iron level exerts a negative feedback on transferrin receptor (TfR) expression in cells requiring iron for their proliferation, in contrast to the positive feedback observed in monocytes-macrophages. It has been suggested recently that modulation of TfR and ferritin synthesis by iron is mediated through a cytoplasmic protein(s) (iron regulatory element-binding protein(s) (IRE-BP)), which interacts with ferritin and TfR mRNA at the level of hairpin structures (IRE), thus leading to inhibition of transferrin mRNA degradation and repression of ferritin mRNA translation. In the present study we have evaluated in parallel the level of TfR expression, ferritin, and IRE-BP in cultures of: (i) circulating human lymphocytes stimulated to proliferate by phytohemagglutinin (PHA) and (ii) circulating human monocytes maturing in vitro to macrophages. The cells were grown in either standard or iron-supplemented culture. TfR and ferritin expression was evaluated at both the protein and mRNA level. IRE-BP activity was measured by gel retardation assay in the absence or presence of beta-mercaptoethanol (spontaneous or total IRE-BP activity, respectively). Spontaneous IRE-BP activity, already present at low level in quiescent T lymphocytes, shows a gradual and marked increase in PHA-stimulated T cells from day 1 of culture onward. This increase is directly and strictly correlated with the initiation and gradual rise of TfR expression, which is in turn associated with a decrease of ferritin content. Both the rise of TfR and spontaneous IRE-BP activity are completely inhibited in iron-supplemented T cell cultures. In contrast, the total IRE-BP level is similar in both quiescent and PHA-stimulated lymphocytes, grown in cultures supplemented or not with iron salts. Monocytes maturing in vitro to macrophages show a sharp increase of spontaneous and, to a lesser extent, total IRE-BP; the addition of iron moderately stimulates the spontaneous IRE-BP activity but not the total one. Here again, the rise of spontaneous IRE-BP from very low to high activity is strictly related to the parallel increase of TfR expression and, suprisingly, also with a very pronounced rise of ferritin expression observed at both the mRNA and protein level. It is noteworthy the effect of beta-mercaptoethanol is cell specific, i.e. the ratio of total versus spontaneous IRE-BP activity is different in activated lymphocytes and maturing monocytes.(ABSTRACT TRUNCATED AT 400 WORDS

Antibodies from multiple sclerosis patients preferentially recognize hyperglucosylated adhesin of non-typeable Haemophilus influenzae

In autoimmune diseases, there have been proposals that exogenous "molecular triggers", i.e., specific this should be 'non-self antigens' accompanying infectious agents, might disrupt control of the adaptive immune system resulting in serious pathologies. The etiology of the multiple sclerosis (MS) remains unclear. However, epidemiologic data suggest that exposure to infectious agents may be associated with increased MS risk and progression may be linked to exogenous, bacterially-derived, antigenic molecules, mimicking mammalian cell surface glycoconjugates triggering autoimmune responses. Previously, antibodies specific to a gluco-asparagine (N-Glc) glycopeptide, CSF114(N-Glc), were identified in sera of an MS patient subpopulation. Since the human glycoproteome repertoire lacks this uniquely modified amino acid, we turned our attention to bacteria, i.e., Haemophilus influenzae, expressing cell-surface adhesins including N-Glc, to establish a connection between H. influenzae infection and MS. We exploited the biosynthetic machinery from the opportunistic pathogen H. influenzae (and the homologous enzymes from A. pleuropneumoniae) to produce a unique set of defined glucosylated adhesin proteins. Interestingly we revealed that a hyperglucosylated protein domain, based on the cell-surface adhesin HMW1A, is preferentially recognized by antibodies from sera of an MS patient subpopulation. In conclusion the hyperglucosylated adhesin is the first example of an N-glucosylated native antigen that can be considered a relevant candidate for triggering pathogenic antibodies in MS