Search

Old age in Walter Pater's works is the time when the individual has the opportunity to think thoroughly upon life and culture. The feeling of growing old may first engender melancholy and bitterness as one considers all those lost days of youth. However, Pater's characters generally take the opportunity to start again and fulfill their quest of wisdom. Old people are more sympathetic with the sorrows of humankind. Looking back upon their own past, they remember their childhood and their first experiences and reflect on their own identity, on the human condition and on culture. Ageing is also an essential element in the arts, especially in architecture as buildings mature and ripen in the course of years and centuries. Old worn stones, old aesthetic forms are for future generations witnesses of immemorial times, allowing Pater's nineteenth-century arts critic to spiritually restore the past and contribute to the development of culture thoughout the ages.

Hosting the Olympic Games in 2012 was a wonderful opportunity for Britain to advertise for its position as a hub in the global leisure economy. The Games Opening Ceremony, which was watched by millions of viewers nationwide and billions worldwide, whether on television or via digital applications, presented a great opportunity for the mediatisation of British culture in ways appealing to domestic and global consumers. A film director, producer, screenwriter and theatre director with international recognition, Danny Boyle was well-positioned to create a show that both conformed to Olympic ethos and presented evolving images of British cultural and technological contributions down to the digital age. Moreover Danny Boyle’s simulations in the show can be interpreted as investigations into consumerism, especially in the leisure industry. While Danny Boyle featured the network of signs surrounding consumers – from emblematic tourist hotspots to British musical and cinematographic hits –, he also suggested personal and collective re-appropriations of products to counter the commodification of goods. Thus he chose to present products crafted by human labour as symbols – rather than fetishes – for human values such as solidarity, social rights and the promotion of ethnic diversity. The use of digital technology in the show was effective to spread those values, presented as part of British nation-building, across cultural borders. Though sometimes viewed as an implied criticism of the Conservative government’s policies, the Opening Ceremony was generally praised by the British press, which was responsive to the collective symbols Danny Boyle chose to present of British culture.

Orthotopic liver transplantation is limited by the shortage of liver donors, leading to elderly patients being enrolled as donors with increasing frequency. Alternative strategies such as cell therapy are therefore needed. Because transplanted hepatocytes do not proliferate into a recipient liver, repopulation strategies have been developed. We have previously published a proof of concept that hepatocytes harboring a survival selective advantage can efficiently repopulate a mouse liver. We develop here an alternative approach by conferring a selective proliferative advantage on transplanted hepatocytes over resident ones. FoxM1B is a transcription factor that, when over-expressed into hepatocytes, accelerates the cell cycle and maintains the hepatocyte in vivo proliferative capacity of aged livers. We now demonstrate that transplanted hepatocytes over-expressing FoxM1B repopulate the liver of mice subjected to continuous injury far more efficiently than control hepatocytes. We show that old hepatocytes that over-express FoxM1B retain their cell division capacity and repopulate liver as well as young ones, in contrast with old non-modified hepatocytes, which lose their proliferative capacity. In conclusion, our results point to the potential use of FoxM1B expression in hepatocyte-based therapy protocols in diseases where host hepatocytes are chronically injured, especially if donor hepatocytes come from old livers.

Background Apoptosis has been shown to contribute to myocardial reperfusion injury. It has been suggested that, in reducing the apoptotic component within the ischemic area at risk, Bcl-2 overexpression could lead to a ventricular function improvement. Methods Transgenic mice overexpressing the anti-apoptotic human Bcl-2 cDNA in heart were subjected to a 1-h left coronary artery occlusion followed by a 24-h reperfusion. At the end of the experiment, left ventricular function was assessed by two-dimensional echocardiography. After sacrifice, the area at risk (AR) and the infarct area (IA) were determined by Evans blue and triphenyltetrazolium chloride staining, respectively. The extent of apoptosis was assessed by the TUNEL method. Non-transgenic littermates served as controls. Results Baseline AR was not different between Bcl-2 transgenic mice and their wild-type littermates. In contrast, left ventricular ejection fraction was significantly improved in the transgenic mice line (61.25±4.0%) compared to non-transgenic littermates (43.2±5.0%, p

International audience; GH is a pleiotropic hormone that plays a major role in proliferation, differentiation, and metabolism via its specific receptor. It has been previously suggested that GH signaling pathways are required for normal liver regeneration but the molecular mechanisms involved have yet to be determined. The aim of this study was to identify the mechanisms by which GH controls liver regeneration. We performed two thirds partial hepatectomies in GH receptor (GHR)-deficient mice and wild-type littermates and showed a blunted progression in the G(1)/S transition phase of the mutant hepatocytes. This impaired liver regeneration was not corrected by reestablishing IGF-1 expression. Although the initial response to partial hepatectomy at the priming phase appeared to be similar between mutant and wild-type mice, cell cycle progression was significantly blunted in mutant mice. The main defect in GHR-deficient mice was the deficiency of the epidermal growth factor receptor activation during the process of liver regeneration. Finally, among the pathways activated downstream of GHR during G(1) phase progression, namely Erk1/2, Akt, and signal transducer and activator of transcription 3, we only found a reduced Erk1/2 phosphorylation in mutant mice. In conclusion, our results demonstrate that GH signaling plays a major role in liver regeneration and strongly suggest that it acts through the activation of both epidermal growth factor receptor and Erk1/2 pathways.

The pattern of expression of two distal transcripts initiated in the 62nd intron of the dystrophin gene was investigated under different circumstances: (i) during the development of different rat tissues these transcripts and Dp 71, a protein encoded by one of them, increased with brain development and decreased with muscle development; (ii) in cultured glial and neuronal cells, the distal promoter was coactivated with tissue-specific upstream promoters, the muscle-type promoter in glial cells and the brain-type promoter in neuronal cells, which suggests that activity of the upstream promoter does not interfere with activity of the distal promoter; (iii) in lymphoblasts of DMD patients with various deletions of the dystrophin gene, the most distal of which included the 56th intron, the production of the distal transcript was not perturbed.

Muscle dystrophin mRNAs from Duchenne (DMD) and Becker (BMD) patients with internal deletion of the DMD gene were quantitated and sequenced. In all cases (eight DMD and three BMD), truncated mature transcripts were found, and their amount was correlated to the clinical phenotype and to the reading frame. We focused on four cases that were apparently not in agreement with the reading frame rule. In two DMD cases, slightly reduced amounts of in-frame truncated mRNA are present but no dystrophin is detected, suggesting impaired translation and/or instability of the protein. In two BMD patients with out-of-frame deletions, the presence of minor in-frame alternatively spliced mRNA species is congruent with the observed truncated dystrophin and the mild phenotype.

Stable gene transfer into hepatocytes has been proposed to compensate for genetic deficiencies that affect liver function, or to deliver diffusible factors into the circulation. This strategy can be achieved using retroviral vectors; however, cell division must occur. We describe a simple and reproductive method that enables the induction of hepatocyte replication in a controlled fashion, thus allowing an efficient in vivo retroviral liver transduction that is applicable to mouse models of human genetic disorders. The approach is based on liver susceptibility to apoptosis via the Fas/CD95 pathway. We show that, 4 days following a single Fas agonist antibody (JO2) injection, hepatocyte replication occurs, the intensity of which is correlated with the level of the induced hepatic cytolysis. This treatment enables in vivo liver transduction, and its efficiency also correlates with the level of hepatic cytolysis. When recombinant retroviral vectors were infused intravenously during the period of hepatocyte replication, 15.4% +/- 1.7% of the hepatocytes were transduced, reaching up to 32.5%.

In the course of a systematic survey of DMD and BMD patients with intronic probes and with cDNA probes covering three-fourths of the coding sequence, 45 molecular deletions within the DMD gene were investigated. Forty-two percent of the breakpoints were located in the intronic sequence containing probe P20, whereas the other deletions were widespread around the more proximal part of the gene. Most of the BMD deletions were in the P20 region. Pulsed field gel electrophoresis was used to determine the size of some deletions and allowed us to estimate the physical distance between the intronic probes JBir and P20. The reading frame was checked in 11 cases with proximal deletions and found to be disrupted in 6 of 7 DMD patients, in 1 intermediate case, and, unexpectedly, in 3 BMD patients.

Lambert-Gorges Martine. Les avatars d'une commanderie santiaguiste au temps des Habsbourg: Almendralejo. In: Mélanges de la Casa de Velázquez, tome 19, 1983. pp. 169-196.

Saignes Thierry, Heredia Herrera Antonia, Muro Romero Fernando, Lambert-Gorges Martine, Milhou Alain, Vila Vilar Enriqueta, Lavalle Bernard, Serrera Ramón María, Acosta Antonio, Gonzales Pujana Laura, del Pino Diaz Fermín, Helmer Marie. Iglesia y politica en Hispanoamerica (Siglos XVI-XVIII) : un acercamiento. Mesa redonda 30-31 de marzo de 1981. In: Mélanges de la Casa de Velázquez, tome 18-2, 1982. pp. 111-128.

Lambert-Gorges Martine. Le bréviaire du bon enquêteur, ou trois siècles d'information sur les candidats à l'habit des ordres militaires. In: Mélanges de la Casa de Velázquez, tome 18-1, 1982. pp. 165-198.

The single X chromosome of a girl with Turner syndrome (45,X) and typical Duchenne muscular dystrophy was investigated at the chromosomal and DNA levels. No visible abnormality of the residual X chromosome was found upon high-resolution R-banding. The DNA was analysed by Southern blotting and hybridization with seven cloned probes mapping in the Xp21 region where the Duchenne locus is thought to be located. A molecular deletion was detected with probes pERT 87.1, pERT 87.8, and pERT 87.15. The other probes (754, C7, 99.6, and RC8) gave a normal signal. The DNA alleles seen in the two parents indicated that the deletion found in the propositus had occurred de novo on a maternal X chromosome.

We report a case of a boy with Duchenne muscular dystrophy (DMD) associated with GK deficiency (GK), congenital adrenal hypoplasia (AHC), and mental retardation. Cytogenetic analysis of prometaphasic chromosomes revealed an interstitial chromosome deletion at Xp21.2 possibly extending to Xp21.1 or Xp21.3. His phenotypically normal mother was heterozygous for this deletion. DNA probe analysis on Southern blots showed that the deletion affected the following probe sites: 754, pERT 84, 21A, XJ2.3, pERT 87, JBir, and J66-H1, whereas L1, C7, and CX5.4 probes gave a normal signal. Pulse field gel electrophoresis after SfiI digestion did not show abnormal fragments with L1. These data are consistent with a deletion of about 4 megabases and indicate that the GK and AHC loci are proximal to L1 and distal to J66-H1.

SPECIFIC AIMSStable liver gene transfer is generally limited by the low efficiency of commonly used vectors. One way to circumvent this difficulty is to confer a selective advantage on transduced hepatocytes, allowing them to progressively repopulate the liver. The aim of this study was to investigate the possibility to repopulate a normal liver to a desired level with in vivo retrovirally engineered hepatocytes.PRINCIPAL FINDINGS1. A retroviral vector encoding Bcl-2 can repopulate the liver up to 85% after 10 wkWe have previously shown that transplanted transgenic hepatocytes expressing Bcl-2 could repopulate a normal mouse liver submitted to repeated Fas apoptotic challenges.We constructed two retroviral plasmids containing either the green fluorescent protein reporter gene alone (MFG-GFP) or a bicistronic cassette including human Bcl-2 cDNA and the GFP reporter gene (MFG-BIG) separated by an internal ribosomal entry site. To compare our liver repopulation approach with direct retroviral transduction, o...

International audience