Identification and characterization of neurofibromatosis type 1 (NF1) gene mutations

La neurofibromatose 1 (NF 1) affecte un individu sur 3000 et se caractérise par l'extrême variabilité des symptôme cliniques. Le gène de NF/, situé sur le chromosome l 7q 11.2, contient 350 kb et 60 exons. Le taux de mutation est de 1 x 104/gamète/génération. Environ 50% des mutations sont d'origine familiale et 50% sporadique. Nous avons identifié et caractérisé une mutation qui cause l'exclusion des exons 11 et l 2a, six délétions et un polymorphisme HinclI et aussi déterminé le déséquilibre de liaison dans la population québécoise. Une mutation originale a été identifiée grâce au test de tronquation des protéines; elle serait la cause de l'exclusion d'exons. Le séquençage de la région génomique entre les introns 1 Oc et 12a a permis d'identifier le changement d'un G en A en position 2056+ l dans le site d' épissage 5' de l 'exon 12a. Ceci engendre l'excision des deux exons l l et 12a sans changement du cadre de lecture et sans que la quantité des ARN messagers en soit affectée. Des essais d'épissage in vivo et in vitro nous ont permis de démontrer pour la première fois que le mutation naturelle supprime la définition des exons. Nos résultats montrent aussi que la séquence encodée par les exons 11 et l 2a est essentielle pour l'activité de la neurofibromine. L 'haplotypage de 19 familles a permis de détecter la perte d'hétérozygosité (LOH) grâce aux 4 microsatellites et aux RFLPs RsaI et EcoRI. Six délétions (2 familles:76 l 0 et 74 73, et 4 patients: 178, 184, 236 et 23 7) ont été identifiées et caractérisées par la LOH et des buvardages de type Southern. La délétion dans la famille 7610 est d'origine maternelle et seul restent les exons l-4b. La délétion dans la famille 7473 est aussi d'origine maternelle et les exons de là 5 sont délétés, la délétion s'arrêtant quelque part avant l' intron 26. Avec le patient 1 78 la délétion commence entre les exons 23-2 et 27b pour se terminer après la région 3' de NFJ. La délétion dans le patient 184 commence au 5' du gène et se termine entre les exons 27b-29. La délétion dans le patient 236 commence entre les exons 14-18 et se termine après l'extrémité 3' de NFJ. Avec le patient 237, la délétion commence entre les exons 38-45 et se termine après la région 3' du gène. Ces délétions sont distribuées au hasard dans le gène NF 1.Abstract: Neurofibromatosis type 1 (NF1) afflicts 1 in 3,000 individuals and is characterized with variable clinical presentations. The NF1 gene spans 350 kb on chromosome 17q11.2 with 60 exons. The gene exhibits high mutation rate of 1 × 104/gamete/generation and approximately 50% are sporadic new mutations. In this study, a splice site mutation and 6 gross deletions have been identified and characterized. Also, a HincII polymorphism was detected and the linkage disequilibrium was investigated. Using a protein truncation assay, we have identified a exon skipping mutation. The mutation, which consists of a G to A transition at position +1 (2056+1) of the 5' splice site of exon 12a, is associated with the loss of both exons 11 and 12a in the NF1 mRNA. The mutation inactivates the 5' splice site of exon 12a, prevents exon definition and leads to the skipping of both exons 11 and 12a. These results document the first example of a natural mutation that inactivates exon definition, and suggest that the 11-12a region of NF1 plays an important role in the activity of neurofibromin. Six gross deletions (families 7610 and 7473, patients 178, 184, 236 and 236) have been identified. The breakpoint of the deletion is located between exons 5 and 26. The deletions are unique and different from those reported previously. The deletions are not associated with unusual clinical features. The HincII polymorphism is located between exons 1 and 4a as defined by probe GE2-400 bp. Three alleles are detected: A1 (3.1 and 3.3 kb), A2 (2.4 and 4.0 kb), A3 (1.3 and 5.1 kb). The detected heterozygote forms are A1-A2, or A1-A3 and the homozygote forms A1-A1 or A2-A2. Analysis haplotypes of the 19 NF1 families indicates that the four intragenic polymorphic microsatellites are strongly linked with the NF1 disease. However, no linkage disequilibrium and founder effect was observed in this Québec population collection. In conclusion, the study shows that the analysis of NF1 gene mutation is complex. No particular founder mutation has been observed in the Québec population."--Résumé abrégé par UM

Antecedents driving the different levels of behavioral engagement in online travel communities

With the rapid development of online travel communities, understanding the determinants of users ’ engagement with the online travel communities is critically important for researchers and practitioners. The purpose of this study is to understand which environmental cues drive the engagement behaviors. Specifically, by using a rich data set from a large travel knowledge sharing website and seemingly unrelated regression model, we investigate and compare the antecedents leading to two different behavioral engagements including liking and social interaction. We find that information-, source-, and social interaction-level cues are associated with these behavioral engagements. The results also demonstrate the differential effectiveness of these cues between these two engagement behaviors. Our empirical findings provide theoretical and practical implication for online travel community operators to build a vibrant and successful online travel community

On a heuristic point of view concerning the optical activity

Motivated by a recent finding that Fresnel's phenomenological description of the optical activity in the chiral medium is not self-consistent, we conduct a thorough investigation into the nature of the polarization of a plane light wave. We demonstrate that the polarization of light is the reflection of one of its quantum-mechanical properties, called the quasi-spin. Unexpectedly, the quasi-spin is not an observable with respect to the laboratory coordinate system. Instead, it is with respect to the momentum-dependent local coordinate system. The representative operators for the quasi-spin are the Pauli matrices. The wavefunction is the Jones vector. In order to completely determine a state of polarization, two different kinds of degrees of freedom are needed. One is the degrees of freedom to characterize the state of quasi-spin. They are the Stokes parameters, the expectation values of the Pauli matrices in the state described by the Jones vector. The other is the degrees of freedom to specify the local coordinate system, including the propagation direction and an angle of rotation about it. Accordingly, there are two independent mechanisms to change the state of polarization. One is to change the state of quasi-spin in a fixed local coordinate system. This is the traditional mechanism that can be expressed as an SU(2) rotation of the Jones vector. The other is to change the local coordinate system with the state of quasi-spin remaining fixed in it. At last, we show that it is the newly-identified mechanism that accounts for the optical activity.Comment: 24 page

A SiO J = 5 - 4 Survey Toward Massive Star Formation Regions

We performed a survey in the SiO $J=5\rightarrow4$ line toward a sample of 199 Galactic massive star-forming regions at different evolutionary stages with the SMT 10 m and CSO 10.4 m telescopes. The sample consists of 44 infrared dark clouds (IRDCs), 86 protostellar candidates, and 69 young \HII\ regions. We detected SiO $J=5\rightarrow4$ line emission in 102 sources, with a detection rate of 57\%, 37\%, and 65\% for IRDCs, protostellar candidates, and young \HII\ regions, respectively. We find both broad line with Full Widths at Zero Power (FWZP) $>$ 20 \kms and narrow line emissons of SiO in objects at various evolutionary stages, likely associated with high-velocity shocks and low-velocity shocks, respectively. The SiO luminosities do not show apparent differences among various evolutionary stages in our sample. We find no correlation between the SiO abundance and the luminosity-to-mass ratio, indicating that the SiO abundance does not vary significantly in regions at different evolutionary stages of star formation.Comment: 25 pages, 9 figures, 5 tables, accepted for publication in Ap

Stokes parameters alone cannot completely characterize the polarization of plane light waves

It was generally assumed that the Stokes parameters are complete characterization for the state of polarization of a plane light wave so that their counterparts in quantum optics, called the Stokes operators, represent the polarization of photons. Here we show, through analyzing the properties of polarized plane waves in an optically active medium, that the Stokes parameters are not able to completely characterize the state of polarization of a plane wave. The key point is that only when a plane wave is expanded in terms of the orthogonal base modes, which are physically meaningful, can the two expansion coefficients make up the Jones vector. Taking this into consideration, we demonstrate that the Stokes parameters of any elliptically polarized wave in an isotropic chiral medium, determined solely by its Jones vector, are transmitted unchanged. They are not able to reflect the rotation of its polarization ellipse along with the propagation. The relationship of the Stokes parameters with the polarization of light needs further investigation.Comment: 13 page

Millimeter Spectral Line Mapping Observations Toward Four Massive Star Forming HII Regions

We present spectral line mapping observations toward four massive star-forming regions (Cepheus A, DR21S, S76E and G34.26+0.15), with the IRAM 30 meter telescope at 2 mm and 3 mm bands. Totally 396 spectral lines from 51 molecules, one helium recombination line, ten hydrogen recombination lines, and 16 unidentified lines were detected in these four sources. An emission line of nitrosyl cyanide (ONCN, 14$_{0,14}$-13$_{0,13}$) was detected in G34.26+0.15, as first detection in massive star-forming regions. We found that the $c$-C$_{3}$H$_{2}$ and NH$_{2}$D show enhancement in shocked regions as suggested by evidences of SiO and/or SO emission. Column density and rotational temperature of CH$_{3}$CN were estimated with the rotational diagram method for all four sources. Isotope abundance ratios of $^{12}$C/$^{13}$C were derived using HC$_{3}$N and its $^{13}$C isotopologue, which were around 40 in all four massive star-forming regions and slightly lower than the local interstellar value ($\sim$65). $^{14}$N/$^{15}$N and $^{16}$O/$^{18}$O abundance ratios in these sources were also derived using double isotopic method, which were slightly lower than that in local interstellar medium. Except for Cep A, $^{33}$S/$^{34}$S ratio in the other three targets were derived, which were similar to that in the local interstellar medium. The column density ratios of N(DCN)/N(HCN) and N(DCO$^{+}$)/N(HCO$^{+}$) in these sources were more than two orders of magnitude higher than the elemental [D]/[H] ratio, which is 1.5$\times$10$^{-5}$. Our results show the later stage sources, G34.26+0.15 in particular, present more molecular species than earlier stage ones. Evidence of shock activity is seen in all stages studied.Comment: 32 pages, 11 figures, 8 tables, accepted for publication in MNRA

Photosynthetic characteristics and nitrogen distribution of large-spike wheat in Northwest China

AbstractThe leaf photosynthesis and nitrogen (N) translocation in three large-spike lines and control cultivar (Xi'nong 979) of winter wheat (Triticum aestivum L.) were studied in 2010–2011 and 2011–2012. The objectives of this study were to investigate the differences in the physiological characteristics of large-spike lines and control cultivar and identify the limiting factors that play a role in improving the yield of breeding materials. The average yield, grain number per spike, kernel weight per spike, and 1000-kernel weight of the large-spike lines were 16.0, 26.8, 42.6, and 15.4%, respectively, significantly higher than those of control. The average photosynthetic rates (Pn) were not significant between the large-spike lines and control cultivar during the active growth period. The average PSII maximum energy conversion efficiency (Fv/Fm), PSII actual quantum efficiency (ΦPS??), photochemical quenching coefficient (qP), PSII reaction center activity (Fv‘/Fv‘) and water-use efficiency (WUE) of the large-spike lines were 1.0, 5.1, 3.6, 0.8, and 43.4%, respectively, higher than those of the control during the active growth stages. The N distribution proportions in different tissues were ranked in the order of grains<culms+sheathes<ra-chis+glumes<flag leaves<penultimate leaves<remain leaves. This study suggested that utilization of the large-spike wheat might be a promising approach to obtain higher grain yield in Northwest China

Recovery of peripheral refractive errors and ocular shape in rhesus monkeys (Macaca mulatta) with experimentally induced myopia

AbstractThis study aimed to investigate the changes in ocular shape and relative peripheral refraction during the recovery from myopia produced by form deprivation (FD) and hyperopic defocus. FD was imposed in six monkeys by securing a diffuser lens over one eye; hyperopic defocus was produced in another six monkeys by fitting one eye with −3D spectacle. When unrestricted vision was re-established, the treated eyes recovered from the vision-induced central and peripheral refractive errors. The recovery of peripheral refractive errors was associated with corresponding changes in the shape of the posterior globe. The results suggest that vision can actively regulate ocular shape and the development of central and peripheral refractions in infant primates