Novel Genetic Determinants of Dental Maturation in Children.

Dental occlusion requires harmonious development of teeth, jaws, and other elements of the craniofacial complex, which are regulated by environmental and genetic factors. We performed the first genome-wide association study (GWAS) on dental development (DD) using the Demirjian radiographic method. Radiographic assessments from participants of the Generation R Study (primary study population, N1 = 2,793; mean age of 9.8 y) were correlated with ~30 million genetic variants while adjusting for age, sex, and genomic principal components (proxy for population stratification). Variants associated with DD at genome-wide significant level (P < 5 × 10-8) mapped to 16q12.2 (IRX5) (lead variant rs3922616, B = 0.16; P = 2.2 × 10-8). We used Fisher's combined probability tests weighted by sample size to perform a meta-analysis (N = 14,805) combining radiographic DD at a mean age of 9.8 y from Generation R with data from a previous GWAS (N2 = 12,012) on number of teeth (NT) in infants used as proxy of DD at a mean age of 9.8 y (including the ALSPAC and NFBC1966). This GWAS meta-analysis revealed 3 novel loci mapping to 7p15.3 (IGF2BP3: P = 3.2 × 10-8), 14q13.3 (PAX9: P = 1.9 × 10-8), and 16q12.2 (IRX5: P = 1.2 × 10-9) and validated 8 previously reported NT loci. A polygenic allele score constructed from these 11 loci was associated with radiographic DD in an independent Generation R set of children (N = 703; B = 0.05, P = 0.004). Furthermore, profiling of the identified genes across an atlas of murine and human stem cells observed expression in the cells involved in the formation of bone and/or dental tissues (>0.3 frequency per kilobase of transcript per million mapped reads), likely reflecting functional specialization. Our findings provide biological insight into the polygenic architecture of the pediatric dental maturation process.

Associations of adult genetic risk scores for adiposity with childhood abdominal, liver and pericardial fat assessed by magnetic resonance imaging.

BACKGROUND: Genome-wide association studies (GWASs) identified single-nucleotide polymorphisms (SNPs) involved in adult fat distribution. Whether these SNPs also affect abdominal and organ-specific fat accumulation in children is unknown. METHODS: In a population-based prospective cohort study among 1995 children (median age: 9.8 years, 95% range 9.4-10.8), we tested the associations of six genetic risk scores based on previously identified SNPs for childhood body mass index (BMI), adult BMI, liver fat, waist-hip ratio, pericardial fat mass, visceral and subcutaneous adipose tissue ratio (VAT/SAT ratio) and four individual SAT- and VAT-associated SNPs for association with SAT (N=1746), VAT (N=1742), VAT/SAT ratio (N=1738), liver fat fraction (N=1950) and pericardial fat mass (N=1803) measured by magnetic resonance imaging. RESULTS: Per additional risk allele in the childhood BMI genetic risk score, SAT increased 0.020 s.d. scores (SDS) (95% confidence interval (CI): 0.009 to 0.031, P-value: 3.28 × 10-4) and VAT increased 0.021 SDS (95% CI: 0.009 to 0.032, P-value: 4.68 × 10-4). The adult BMI risk score was positively associated with SAT (0.022 SDS increase, CI: 0.015 to 0.029, P-value: 1.33 × 10-9) and VAT (0.017 SDS increase, CI: 0.010 to 0.025, P-value: 7.00 × 10-6) and negatively with VAT/SAT ratio (-0.012 SDS decrease, CI: -0.019 to -0.006, P-value: 2.88 × 10-4). The liver fat risk score was associated with liver fat fraction (0.121 SDS, CI: 0.086 to 0.157, P-value: 2.65 × 10-11). Rs7185735 (SAT) was associated with SAT (0.151 SDS, CI: 0.087 to 0.214, P-value: 3.00 × 10-6) and VAT/SAT ratio (-0.126 SDS, CI: -0.186 to -0.065, P-value: 4.70 × 10-5). After stratification by sex the associations of the adult BMI risk score with SAT and VAT and of the liver fat risk score with liver fat fraction remained in both sexes. Associations of the childhood BMI risk score with SAT, and the adult BMI risk score with VAT/SAT ratio, were present among boys only, whereas the association of the pericardial fat risk score with pericardial fat was present among girls only. CONCLUSION: Genetic variants associated with BMI, body fat distribution, liver and pericardial fat already affect body fat distribution in childhood.

A combined theoretical and experimental investigation on the influence of the bromine substitution pattern on the photophysics of conjugated organic chromophores.

A large series of structurally related two-photon photosensitizers with heavy atom substitution were synthesized and evaluated through a combined spectroscopic (steady-state and time resolved), photophysical and computational study. Our aim was to identify some relevant parameters related to their excited state dynamics including photo-induced singlet oxygen generation. Although these dynamics result from the interplay of many factors, we show that the triplet excited state generation kinetics can generally be correlated with the calculated values of both the spin-orbit coupling and the energy gap between S1 and T1 states, which themselves mostly depend on the positioning of the heavy atoms along the π-conjugated structure rather than their number.

A Fluorescent Polymer Probe with High Selectivity toward Vascular Endothelial Cells for and beyond Noninvasive Two-Photon Intravital Imaging of Brain Vasculature.

A chromophore-engineering strategy that relies on the introduction of a ground-state distortion in a quadrupolar chromophore was used to obtain a quasi-quadrupolar chromophore with red emission and large two-photon absorption (2PA) cross-section in polar solvents. This molecule was functionalized with water-solubilizing polymer chains. It constitutes not only a remarkable contrast agent for intravital two-photon microscopy of the functional cerebral vasculature in a minimally invasive configuration but presents intriguing endothelial staining ability that makes it a valuable probe for premortem histological staining.

Adult adiposity susceptibility loci, early growth and general and abdominal fatness in childhood: the Generation R Study.

BACKGROUND: Genome-wide association studies in adults have identified genetic loci associated with adiposity measures. Little is known about the effects of these loci on growth and body fat distribution from early childhood onwards. METHODS: In a population-based prospective cohort study among 4144 children, we examined the associations of weighted risk scores combining 29 known genetic markers of adult body mass index (BMI) and 14 known genetic markers of adult waist-hip ratio (WHR) with peak weight velocity, peak height velocity, age at adiposity peak and BMI at adiposity peak in early infancy and additionally with BMI, total fat mass, android/gynoid fat ratio and preperitoneal fat area at the median age of 6.0 years (95% range 5.7, 7.8). RESULTS: A higher adult BMI genetic risk score was associated with a higher age at adiposity peak in infancy and a higher BMI, total fat mass, android/gynoid fat ratio and preperitoneal fat area in childhood (P=0.05, 1.5 × 10(-24), 3.6 × 10(-18), 4.0 × 10(-11) and 1.3 × 10(-5), respectively), with the strongest association for childhood BMI with a 0.04 higher s.d. score BMI (95% confidence interval 0.03, 0.05) per additional risk allele. A higher adult WHR genetic risk score was not associated with infant growth measures or childhood BMI and total fat mass, but was associated with childhood android/gynoid fat ratio and preperitoneal fat area (P<0.05). CONCLUSION: Genetic variants associated with BMI and WHR in adults influence growth patterns and general and abdominal fat development from early childhood onwards.

Photophysical, amplified spontaneous emission and charge transport properties of oligofluorene derivatives in thin films.

We investigate the photophysical and amplified spontaneous emission properties of a series of monodisperse solution-processable oligofluorenes functionalized with hexyl chains at the C9 position of each fluorene unit. Thin films of these oligofluorenes are then used in organic field-effect transistors and their charge transport properties are examined. We have particularly focused our attention on the influence of oligofluorene length on the absorption and steady-state fluorescence spectra, on the HOMO/LUMO energy levels, on the photoluminescence lifetime and quantum yield as well as on the amplified spontaneous emission properties and the charge carrier mobilities. Differential scanning calorimetry and X-ray diffraction measurements demonstrate that, among all oligofluorene derivatives used in this study, only the structure and morphology of the pentafluorene film is significantly modified by a thermal treatment above the glass transition temperature, resulting in a 9 nm blue-shift of the fluorescence spectrum without significant changes in the photoluminescence quantum yield and in the amplified spontaneous emission threshold. In parallel, hole field-effect mobility is significantly increased from 8.6 × 10(-7) to 3.8 × 10(-5) cm(2) V(-1) s(-1) upon thermal treatment, due to an increase of crystallinity. This study provides useful insights into the morphological control of oligofluorene thin films and how it affects their photophysical and charge transport properties. Moreover, we provide evidence that, because of the low threshold, the tunability of the amplified spontaneous emission and the photostability of the films, these oligofluorenes are promising candidates for organic solid-state laser applications.

[Prenatal screening of cytomegalovirus in France: an increasing frequency practices of screening from 2000 to 2003 despite no recommendation in favor]. / Dépistage prénatal du cytomégalovirus en France: une augmentation des pratiques de prescription de 2000 à 2003 malgré l'absence de recommandation favorable.

BACKGROUND: Screening cytomegalovirus infection in pregnant women is still controversial in 2004 in France. In this context, we evaluated the interest of such a screening in 2004 in France. This paper was designed to describe trends in CMV prenatal screening practices in 2000-2003 in France. METHODS: This retrospective study, describes the prescription of CMV screening in HIV-negative pregnant women giving birth in the private care sector, according to their occupational category and geographical area. Data were provided by the "Caisse d'Assurance-maladie des Travailleurs Indépendants" (independent workers health insurance fund). RESULTS: The study included 34.347 women, delivering in 2001-2004 (beginning of pregnancy in 2000-2003). The number of pregnant women screened for CMV increased significantly between 2000 (5.8%, 301/5.177), 2001 (11.1%, 1.130/10.139) and 2002 (22.1%, 2.701/12.223), (p<0.001), then was stable in 2003 (22.0%, 1.496/6.808). The percentage of women screened for CMV, at least once during pregnancy, doubled between 2001 and 2002 (p<0.001) in each occupational category and geographical area. It was significantly different between occupational categories (p<0.01), with a higher percentage of women in the self-employed and commercial agent occupational categories than in the craftsman category. There was also a significant difference between geographical areas (p<0.001), with a higher rate in Paris. CONCLUSION: This study providing baseline information on CMV practices showed: 1- a significant increase in the frequency of CMV screening among pregnant women over the period 2000-2002 with a stabilization in 2003; 2- a similar trend observed in each occupation category and geographical area but with a markedly higher frequency of screening practices in the Paris area and among self-employed women. A study measuring the effect of the 2004 ANAES recommendation suggesting not to screen for CMV during pregnancy should be conducted.

Topology of slightly polydisperse real foams.

The topology of slightly polydisperse, (meta-)stable, real foams was investigated by means of optical tomography associated with a numerical reconstruction procedure. The values of the mean numbers of faces per bubble and edges per face were very close to Matzke's data (1946). The real foams were essentially disordered and possessed a noncentered symmetry, and ideal structures also could not be observed. The disorder was quantified by the second moment of the edge per face and face per bubble distributions, and also by a statistical correlation coefficient between the numbers of edges of adjacent faces. It was found that the edge distributions of the internal bubbles, and not of the external ones, were significantly anticorrelated even during foam aging, which provided a measure of the disorder in the foam. No obvious relationship could be deduced between the isoperimetric quotient and the face combination in an individual bubble. Eventually, it was shown that the physical boundaries of the foam sample had no influence on the foam topology beyond a single bubble layer.