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Subjects affected by Duchenne muscular dystrophy (DMD) develop severe malocclusions with the progression of the disease, due to changes in orofacial musculature and function, including tongue hypertrophy. We aimed to evaluate the benefits of maintaining mandibular interarch width with the help of a simple fixed orthodontic appliance. Three adolescent DMD boys were selected consecutively to receive a passive rigid mandibular lingual arch, and followed for 4–5 years. An untreated age-matched control group was chosen and followed for a similar period. Study casts were obtained at baseline and after follow-up. Outcomes measured were overjet, overbite, maxillary and mandibular intermolar widths, mandibular arch depth, molar relationships, and the presence of lateral crossbites and anterior or lateral openbites. Changes in measurements obtained between the two time points were compared in each age-matched pair. There was a clinically important increase in the mandibular intermolar width in the non-treated children ranging from 2.5 mm to 9 mm, but not in those treated. Malocclusions generally deteriorated in untreated children while they remained stable in treated children. The use of a rigid mandibular lingual arch in boys with DMD can help slow down the rapid deterioration of the developing malocclusions that accompanies the progression of the disease.

Aim The aim of this study was to describe the longitudinal changes in facial morphology, dental arch alterations and oral functional capacities that occur in growing patients with Duchenne muscular dystrophy (DMD) in order to identify the effects of the progression of the disease. Subjects and methods Twelve DMD patients (6.5-17.5 years of age) and 12 matched controls were screened on two different occasions (T1 and T2), 2 years apart. Dental casts, lateral cephalometric radiographs, maximal posterior bite force and labial force were measured to determine changes in their functional capacities and dentofacial morphology. Furthermore, the thickness and echogenicity of the masseter muscle were measured during clenching. Statistical evaluation Unpaired t-tests were performed to evaluate the differences between the DMD patients and their healthy matched controls; paired t-tests were used to assess the changes that occurred within each group between T1 and T2. Results Between T1 and T2 the following changes were observed: widening of the lower dental arch for the DMD patients of 2.6mm (±0.9mm) compared to a slight reduction of -0.1mm (±0.8mm) for the control group (P = 0.001). We found a statistically significant reduction of the sagittal skeletal intermaxillary relationship (ANB-angle) of 2.0° (±2.0°) in the DMD group (P = 0.012). In T1 and T2, the maximal posterior bite force and the labial force were lower for the DMD patients compared to the control group (P = 0.001), who showed an increase during this period. Conclusion The results indicate that DMD influences the facial morphology, dental arch dimensions and oral functional capacities. The longitudinal perspective of this study revealed that the worsening of most of the measured parameters is associated with the progression of the disease. Besides the expected deterioration of the functional measurements, we found in all patients, a marked transverse increase of the posterior part of the dental arches, more in the lower than in the upper, resulting in posterior crossbites, as well as a tendency towards a skeletal Class III relationship.

International audience; Integrative and conjugative elements (ICEs) are mobile genetic elements encoding their own excision from a replicon of their bacterial host, transfer by conjugation to a recipient bacterium and reintegration for maintenance. The conjugation, recombination and regulation modules of ICEs of the ICESt3 family are grouped together in a region called the ICE 'core region'. In addition to this core region, elements belonging to this family carry a highly variable region including cargo genes that could be involved in bacterial adaptation or in the maintenance of the element. Although ICEs are a major class of mobile elements through bacterial genomes, the functionality of an element encoding only its excision, transfer, integration and regulation has never been demonstrated experimentally. We engineered MiniICESt3, an artificial ICE derived from ICESt3, devoid of its cargo genes and thus only harbouring the core region. The functionality of this minimal element was assessed. MiniICESt3 was found to be able to excise at a rate of 3.1 %, transfer with a frequency of 1.0 x 10(-5) transconjugants per donor cell and stably maintain by site-specific integration into the 3' end of the fda gene, the same as ICESt3. Furthermore, MiniICESt3 was found in similar to 10 copies per chromosome, this multicopy state likely contributing to its stability for >100 generations even in the absence of selection. Therefore, although ICEs were primarily assumed to only replicate along with the chromosome, our results uncovered extrachromosomal rolling-circle replicating plasmid-like forms of MiniICESt3.

Genomic islands, flanked by attachment sites, devoid of conjugation and recombination modules and related to the integrative and conjugative element (ICE) ICESt3, were previously found in Streptococcus thermophilus. Here, we show that ICESt3 transfers to a recipient harbouring a similar engineered genomic island, CIMEL3catR3, and integrates by site-specific recombination into its attachment sites, leading to their accretion. The resulting composite island can excise, showing that ICESt3 mobilizes CIMEL3catR3 in cis. ICESt3, CIMEL3catR3 and the whole composite element can transfer from the strain harbouring the composite structure. The ICESt3 transfer to a recipient bearing CIMEL3catR3 can also lead to retromobilization, i.e. its capture by the donor. This is the first demonstration of specific conjugative mobilization of a genomic island in cis and the first report of ICE-mediated retromobilization. CIMEL3catR3 would be the prototype of a novel class of non-autonomous mobile elements (CIMEs: CIs mobilizable elements), which hijack the recombination and conjugation machinery of related ICEs to excise, transfer and integrate. Few genome analyses have shown that CIMEs could be widespread and have revealed internal repeats that could result from accretions in numerous genomic islands, suggesting that accretion and cis mobilization have a key role in evolution of genomic islands.

The integrative and conjugative elements (ICEs) excise by site-specific recombination between attL and attR flanking sites, self-transfer the resulting circular form and integrate into the genome of the recipient cell. Two putative ICEs, ICESt1 and ICESt3, are integrated in the same locus in 2 strains of Streptococcusthermophilus. ICESt1 is a composite element harbouring an internal recombination site, attL’. The recombination between attL’ and attR leads to the excision of a shorter putative ICE, ICESt2. ICESt1/ICESt2 and ICESt3 carry related regulation modules sharing the open reading frame arp1 that encodes a protein related to the cI repressor of the phage λ. The repressors belonging to this family autoproteolyse in the presence of damaged DNA. Treatments with mitomycin C induce an increase in the excision of ICESt1, ICESt2 and ICESt3. Furthermore, the arp1 deletion leads to a 1,000-fold increase in the excision of ICESt1 and ICESt2 and to a decrease in the excision induction by mitomycin C. Thus, all together, these results suggest that the autocleavage of the arp1 repressor is involved in derepression of the S. thermophilus putative ICE excision by mitomycin C.

Wnt and Notch signaling have long been established as strongly oncogenic in the mouse mammary gland. Aberrant expression of several Wnts and other components of this pathway in human breast carcinomas has been reported, but evidence for a causative role in the human disease has been missing. Here we report that increased Wnt signaling, as achieved by ectopic expression of Wnt-1, triggers the DNA damage response (DDR) and an ensuing cascade of events resulting in tumorigenic conversion of primary human mammary epithelial cells. Wnt-1-transformed cells have high telomerase activity and compromised p53 and Rb function, grow as spheres in suspension, and in mice form tumors that closely resemble medullary carcinomas of the breast. Notch signaling is up-regulated through a mechanism involving increased expression of the Notch ligands Dll1, Dll3, and Dll4 and is required for expression of the tumorigenic phenotype. Increased Notch signaling in primary human mammary epithelial cells is sufficient to reproduce some aspects of Wnt-induced transformation. The relevance of these findings for human breast cancer is supported by the fact that expression of Wnt-1 and Wnt-4 and of established Wnt target genes, such as Axin-2 and Lef-1, as well as the Notch ligands, such as Dll3 and Dll4, is up-regulated in human breast carcinomas.

The aim of this article is to critically assess the content and rationale of the French 2003 law on private patronage and foundations. More specifically, it investigates the extent to which this law can truly encourage companies to become more involved in arts support. Before reviewing and explaining the major aspects of the reform and the advantages it is meant to bring to corporate donors, a short historical account is offered to demonstrate that even though the involvement of the private sector in the support of the arts has been on the agenda of various Ministers of Culture over the last forty years, the development of adequate and effective measures to encourage such an involvement has been difficult and erratic and, above all, has been met with little success. The third part of the article questions the relevance of a law largely based on tax reductions to support the arts in France and wonders whose interests it will really serve.

The phylogenetic relationships between 26 Streptococcus thermophilus strains were investigated by hybridization of 15 DNA probes. They indicate that IP6757 and NST2280 strains are genetically very closely related. They are included in a group of eight closely related strains which contain identical eps loci, apart from IP6757 which possesses a different one. The IP6757 and NST2280 eps loci contain identical epsA–epsD region whereas the remainder of the loci are completely different in size and sequence. The IP6757 genes are conserved in only one of the 26 S. thermophilus strains tested, LMG18311. The IP6757 eps locus could result from sequence replacement and the new sequence may have been acquired by putative horizontal transfer. Hybridization data and sequence comparison of IP6757 and NST2280 eps loci with those of other S. thermophilus strains show that eps loci are highly variable and could quickly evolve by sequence replacement.

At a time when observers of French cultural policy are almost unanimously calling for major reforms of the Ministry of Culture's role and structure as well as a redefinition of its missions, it is worth reflecting on the part that corporate patrons might play if public-private cultural partnerships were truly to be considered. Could businesses, for example, participate in the Ministry's ultimate mission of cultural democratisation? Using examples of companies located in the northern city of Lille, this article looks at the ways some of them have decided, in association with cultural organisations, to offer arts classes to their staff. Although limited in scope, these projects have been relatively successful. However, to what extent could and should such schemes be extended to other companies? A discussion of the material and ethical issues raised by these companies' contribution to cultural democratisation is offered in order to answer this question.

Laboratory incubation experiments were carried out to estimate the risk of enhanced carbofuran biodegradation in soil following previous treatments with various carbamate compounds. Two soils with different sensitivities to the enhanced degradation phenomenon were used. In the Montardon soil, prior treatments with 15 N -methylcarbamates led to an enhanced rate of [ 14 C-carbonyl]carbofuran degradation and an increase in the number of carbofuran-degrading microorganisms; prior treatment with formetanate and pirimicarb had no enhancing effect. In the Dijon soil, prior treatment with six N -methylcarbamates, chlorpropham or aldicarb had no apparent effect on the subsequent rate of carbofuran degradation and carbofuran-degrading microorganisms were not detected in any of the prior treated samples. Chloroform fumigation of previously untreated and carbofuran treated soil showed that carbofuran degradation in the Montardon soil was mainly due to biological activity, whereas abiotic activity represented a third of the total degradation in Dijon soil. Treatment of both soils with cycloheximide and chloramphenicol led to a decrease in the rate of carbofuran degradation, but streptomycin had a limited effect on the degradation rate. Further studies are needed to characterize the carbofuran-degrading microorganisms which are present in soil after prior treatments with various N -methylcarbamate pesticides.

International audience; The Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://AtlasGeneticsOncology.org) is a peer-reviewed internet journal/encyclopaedia/database focused on genes implicated in cancer, cytogenetics and clinical entities in cancer and cancer-prone hereditary diseases. The main goal of the Atlas is to provide review articles that describe complementary topics, namely, genes, genetic abnormalities, histopathology, clinical diagnoses and a large iconography. This description, which was historically based on karyotypic abnormalities and in situ hybridization (fluorescence in situ hybridization) techniques, now benefits from comparative genomic hybridization and massive sequencing, uncovering a tremendous amount of genetic rearrangements. As the Atlas combines different types of information (genes, genetic abnormalities, histopathology, clinical diagnoses and external links), its content is currently unique. The Atlas is a cognitive tool for fundamental and clinical research and has developed into an encyclopaedic work. In clinical practice, it contributes to the cytogenetic diagnosis and may guide treatment decision making, particularly regarding rare diseases (because they are numerous and are frequently encountered). Readers as well as the authors of the Atlas are researchers and/or clinicians.

Genomic islands, flanked by attachment sites, devoid of conjugation and recombination modules and related to the integrative and conjugative element (ICE) ICESt3, were previously found in Streptococcus thermophilus. Here, we show that ICESt3 transfers to a recipient harbouring a similar engineered genomic island, CIMEL₃catR₃, and integrates by site-specific recombination into its attachment sites, leading to their accretion. The resulting composite island can excise, showing that ICESt3 mobilizes CIMEL₃catR₃, in cis. ICESt3, CIMEL₃catR₃, and the whole composite element can transfer from the strain harbouring the composite structure. The ICESt3 transfer to a recipient bearing CIMEL₃catR₃, can also lead to retromobilization, i.e. its capture by the donor. This is the first demonstration of specific conjugative mobilization of a genomic island in cis and the first report of ICE-mediated retromobilization. CIMEL₃catR₃, would be the prototype of a novel class of non-autonomous mobile elements (CIMEs: CIs mobilizable elements), which hijack the recombination and conjugation machinery of related ICEs to excise, transfer and integrate. Few genome analyses have shown that CIMEs could be widespread and have revealed internal repeats that could result from accretions in numerous genomic islands, suggesting that accretion and cis mobilization have a key role in evolution of genomic islands.

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International audience

Background Two closely related ICEs, ICESt1 and ICESt3, have been identified in the lactic acid bacterium Streptococcus thermophilus. While their conjugation and recombination modules are almost identical (95% nucleotide identity) and their regulation modules related, previous work has demonstrated that transconjugants carrying ICESt3 were generated at rate exceeding by a 1000 factor that of ICESt1. Results The functional regulation of ICESt1 and ICESt3 transcription, excision and replication were investigated under different conditions (exponential growth or stationary phase, DNA damage by exposition to mitomycin C). Analysis revealed an identical transcriptional organization of their recombination and conjugation modules (long unique transcript) whereas the transcriptional organization of their regulation modules were found to be different (two operons in ICESt1 but only one in ICESt3) and to depend on the conditions (promoter specific of stationary phase in ICESt3). For both elements, stationary phase and DNA damage lead to the rise of transcript levels of the conjugation-recombination and regulation modules. Whatever the growth culture conditions, excision of ICESt1 was found to be lower than that of ICESt3, which is consistent with weaker transfer frequencies. Furthermore, for both elements, excision increases in stationary phase (8.9-fold for ICESt1 and 1.31-fold for ICESt3) and is strongly enhanced by DNA damage (38-fold for ICESt1 and 18-fold for ICESt3). Although ICEs are generally not described as replicative elements, the copy number of ICESt3 exhibited a sharp increase (9.6-fold) after mitomycin C exposure of its harboring strain CNRZ385. This result was not observed when ICESt3 was introduced in a strain deriving ICESt1 host strain CNRZ368, deleted for this element. This finding suggests an impact of the host cell on ICE behavior. Conclusions All together, these results suggest a novel mechanism of regulation shared by ICESt1, ICESt3 and closely related ICEs, which we identified by analysis of recently sequenced genomes of firmicutes. This is the first report of a partial shutdown of the activity of an ICE executed by a strain belonging to its primary host species. The sharp increase of ICESt3 copy number suggests an induction of replication; such conditional intracellular replication may be common among ICEs.

P>During the rearing process of gilthead sea bream (Sparus aurata), abnormal development of the opercular bone is particularly common (Aquaculture 156, 1997, 165). In order to alleviate its occurrence in rearing facilities, it's crucial to identify the very first physical signs of deviation in normal skeletal development. Nano-CT-scanning was tested for its applicability to quantify deviations in bone mineralization levels. Seven opercles were dissected from larvi of 65 days post hatching, randomly sampled at the commercial sea bream hatchery Maricoltura di Rosignano Solvay (Livorno, Italy). The samples were nano-CT-scanned and computationally reconstructed. Mineralization intensity was colorcoded using Amira software, resulting in a detailed visualization of opercular morphology and mineralization patterns. In conclusion, nano-CT-scanning promises to be a good tool to both describe morphology and detect mineralization levels in the early onset of deformities.

International audience

Integrative and conjugative elements (ICEs), also called conjugative transposons, are genomic islands that excise, self-transfer by conjugation, and integrate in the genome of the recipient bacterium. The current investigation shows the intraspecies conjugative transfer of the first described ICEs in Streptococcus thermophilus , ICE St1 and ICE St3 . Mitomycin C, a DNA-damaging agent, derepresses ICE St3 conjugative transfer almost 25-fold. The ICE St3 host range was determined using various members of the Firmicutes as recipients. Whereas numerous ICE St3 transconjugants of Streptococcus pyogenes and Enterococcus faecalis were recovered, only one transconjugant of Lactococcus lactis was obtained. The newly incoming ICEs, except the one from L. lactis , are site-specifically integrated into the 3′ end of the fda gene and are still able to excise in these transconjugants. Furthermore, ICE St3 was retransferred from E. faecalis to S. thermophilus . Recombinant plasmids carrying different parts of the ICE St1 recombination module were used to show that the integrase gene is required for the site-specific integration and excision of the ICEs, whereas the excisionase gene is required for the site-specific excision only.

Duchenne muscular dystrophy (DMD) affects orofacial function. Our aim was to evaluate certain characteristics of orofacial function in DMD and relate possible deteriorations to the age of the patients and to the diminished internal structure quality of the masseter muscle. Bite force and finger force were measured in 16 DMD patients (6-20 years old) and 16 age matched controls. The thickness and internal structure quality of the masseter muscle were evaluated ultrasonographically. We found reduced mouth opening but no signs of masticatory muscle tenderness. Bite force values were lower for DMD patients. Masseter thickness showed no significant differences between the two groups, but poorer internal muscle structure quality characterised the elder, non-walking DMD patients explaining their low bite force values. In conclusion, the masseter muscle follows the general progress of the disease. Orofacial function in DMD patients is becoming ever more important as their life expectancy increases.

SUMMARY Occlusal traits and craniofacial morphology were studied in growing patients with Duchenne muscular dystrophy (DMD). Sixteen patients from 6 to 20 years of age were examined and compared with 16 healthy male individuals matched according to age. The dental arches and occlusal traits of both groups were analysed on dental casts and compared with the norms of healthy individuals from the literature. Lateral cephalograms of the patients were compared with normal individuals by using scored values based on standard deviations in order to compensate for heterogeneity in the age of the subjects. Statistical analysis was undertaken for continuous variables with a paired Student’s t -test and non-continuous variables with a chi-square test. Linear regressions were used to evaluate the infl uence of age. A high prevalence of malocclusions was found, including posterior crossbites, anterior and lateral open bites, a tendency towards mesio-occlusion due to a skeletal Class III malocclusion, and dental compensations of the Class III relationship by retrusion of the lower incisors. Both upper and lower arches were widened posteriorly. The lower arches were even wider than the upper arches, resulting in frequent posterior crossbites. No signifi cant skeletal vertical deviations were observed in this group of DMD patients, except for the maxillary plane angle (NL/NSL) that was larger than normal, while the anterior upper face height (NSp) was smaller. However, no difference was found in lower face height. The posterior enlargement of the dental arches and the dentoalveolar development towards an Angle Class III relationship were signifi cantly related to age and found more frequently among the older subjects.

The integrative and conjugative elements (ICEs) excise by site-specific recombination between attL and attR flanking sites, self-transfer the resulting circular form and integrate into the genome of the recipient cell. Two putative ICEs, ICESt1 and ICESt3, are integrated in the same locus in 2 strains of Streptococcusthermophilus. ICESt1 is a composite element harbouring an internal recombination site, attL'. The recombination between attL' and attR leads to the excision of a shorter putative ICE, ICESt2. ICESt1/ICESt2 and ICESt3 carry related regulation modules sharing the open reading frame arp1 that encodes a protein related to the cI repressor of the phage lambda. The repressors belonging to this family autoproteolyse in the presence of damaged DNA. Treatments with mitomycin C induce an increase in the excision of ICESt1, ICESt2 and ICESt3. Furthermore, the arp1 deletion leads to a 1,000-fold increase in the excision of ICESt1 and ICESt2 and to a decrease in the excision induction by mitomycin C. Thus, all together, these results suggest that the autocleavage of the arp1 repressor is involved in derepression of the S. thermophilus putative ICE excision by mitomycin C.

A DNA-damaging agent, mitomycin C, derepresses the site-specific excision of two integrative and potentially conjugative elements from Streptococcus thermophilus , ICE St1 and ICE St3 . The regulation pathway involves a repressor related to phage lambda cI repressor. It could also involve a putative regulator related to another type of phage repressors, the “cI-like” repressors.

International audience; In Streptococcus thermophilus, the eps clusters involved in exopolysaccharide (EPS) biosynthesis are very polymorphic, nevertheless they all contain a highly conserved sequence corresponding to that of orf14.9. This open reading frame (ORF) is transcribed in a reverse direction with respect to eps genes. Amino acid sequence analysis showed a possible transmembrane location of the putative Orf14.9 protein but did not permit a proposed function. Insertional mutants of orf14.9 were obtained in strains NST2280 and A054 of S. thermophilus. EPS yields of these mutants are similar to those of their respective wild strains, suggesting that orf14.9 does not modify the quantity of produced EPS. Growth parameter determination for wild strains and their respective mutants showed that orf14.9 is involved in the cell growth of S. thermophilus; Les clusters eps de Streptococcus thermophilus, impliqués dans la biosynthèse des exopolysaccharides (EPS), présentent une variabilité génétique importante. Néanmoins, tous se caractérisent par la présence d'une séquence hautement conservée, orf14.9. Cette ORF est orientée en sens inverse par rapport aux ORF opéroniques du cluster eps et est transcrite. Les analyses de séquence suggèrent que la protéine potentielle Orf14.9 est transmembranaire mais de fonction inconnue. Des mutants insertionnels d'orf14.9 ont été réalisés chez S. thermophilus NST2280 et A054. Chez ces mutants, le taux d'EPS produit ne présente pas de différence statistiquement significative avec le taux d'EPS produit par leurs souches sauvages respectives. Chez ces mutants, l'absence de l'orf14.9 fonctionnelle ne modifie donc pas la quantité d'EPS produit. La détermination des paramètres de la croissance pour les souches sauvages et leurs mutants respectifs montre qu'orf14.9 est impliquée dans la croissance cellulaire de S. thermophilus

International audience; The sequence analysis of the eps locus of Streptococcus thermophilus IP6756 shows that it is very different from all other eps loci studied in S. thermophilus: it is smaller and displays only a few open reading frames (ORFs) compared with other eps loci. Moreover, none of the identified ORF encodes glycosyltransferases, which are required for exopolysaccharides (EPS) production, whereas IP6756 is an EPS-producing strain. The functional study of this locus shows that it is organized in an operon and that its polar interruption does not lead to any modification in EPS yield. These results indicate that the eps locus of S. thermophilus IP6756 is not involved in EPS production and describe for the first time that EPS production is under the control of gene(s) encoded elsewhere in the genome in S. thermophilus.

The nucleotide sequence of two ORFs and five copies of three insertion sequences (IS) types belonging to the eps locus of Streptococcus thermophilusCNRZ368 involved in exopolysac- charide synthesis are almost identical to ISs and ORFs sequences from Lactococcus lactis. Further- more, sequence comparison of eps loci of three S. thermophilusstrains and hybridization of probes isolated from the S. thermophilus CNRZ368 eps locus with DNA of 17 S. thermophilus strains revealed a very high polymorphism. A small constant region is detected in all the strains whereas a large region is extremely variable. The 17 tested strains could be arranged in six groups according to the presence or absence of a hybridization signal with the different probes tested. A phylogenetic anal- ysis indicated that the ropy NST2280 strain and the non-ropy IP6757 strain are very closely related strains but possess different eps loci. The eps locus of IP6757 could result from sequence replacement in an IP6757 ancestor. Sequence comparison of different eps loci of S. thermophilussuggests that the high polymorphism of these loci largely results from sequence replacement following horizontal transfers. exopolysaccharide / horizontal transfer / Lactococcus lactis / polymorphism / Streptococcus thermophilus