Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes

Interferon regulatory factor 6 (IRF6) belongs to a family of nine transcription factors that share a highly conserved helix-turn-helix DNA-binding domain and a less conserved protein-binding domain. Most IRFs regulate the expression of interferon-alpha and -beta after viral infection(1), but the function of IRF6 is unknown. The gene encoding IRF6 is located in the critical region for the Van der Woude syndrome (VWS; OMIM 119300) locus at chromosome 1q32-q41 (refs 2,3). The disorder is an autosomal dominant form of cleft lip and palate with lip pits(4), and is the most common syndromic form of cleft lip or palate. Popliteal pterygium syndrome (PPS; OMIM 119500) is a disorder with a similar orofacial phenotype that also includes skin and genital anomalies(5). Phenotypic overlap(6) and linkage data(7) suggest that these two disorders are allelic. We found a nonsense mutation in IRF6 in the affected twin of a pair of monozygotic twins who were discordant for VWS. Subsequently, we identified mutations in IRF6 in 45 additional unrelated families affected with VWS and distinct mutations in 13 families affected with PPS. Expression analyses showed high levels of Irf6 mRNA along the medial edge of the fusing palate, tooth buds, hair follicles, genitalia and skin. Our observations demonstrate that haploinsufficiency of IRF6 disrupts orofacial development and are consistent with dominant-negative mutations disturbing development of the skin and genitalia.

The Tomato (Solanum Lycopersicum cv. Micro-Tom) Natural Genetic Variation Rg1 and the DELLA Mutant Procera Control the Competence Necessary to Form Adventitious Roots and Shoots

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Prevalence and nonrandom distribution of exonic mutations in interferon regulatory factor 6 in 307 families with Van der Woude syndrome and 37 families with popliteal pterygium syndrome

Purpose: Interferon regulatory factor 6 encodes a member of the IRF family of transcription factors. Mutations in interferon regulatory factor 6 cause Van der Woude and popliteal pterygium syndrome, two related orofacial clefting disorders. Here, we compared and contrasted the frequency and distribution of exonic Mutations in interferon regulatory factor 6 between two large geographically distinct collections of families with Van der Woude and between one collection of families with popliteal pterygium syndrome. Methods: We performed direct sequence analysis of interferon regulatory factor 6 exons oil samples from three collections, two with Van der Woude and one with popliteal pterygium syndrome. Results: We identified mutations in interferon regulatory factor 6 exons in 68% of families in both Van der Woude collections and in 97% of families with popliteal pterygium syndrome. In sum, 106 novel disease-causing variants were found. The distribution of mutations in the interferon regulatory factor 6 exons in each collection was not random; exons 3, 4, 7, and 9 accounted for 80%. In the Van der Woude collections, the mutations were evenly divided between protein truncation and missense, whereas most mutations identified in the popliteal pterygium syndrome collection were missense. Further, the missense mutations associated with popliteal pterygium syndrome were localized significantly to exon 4, at residues that are predicted to bind directly to DNA. Conclusion: The nonrandom distribution of mutations in the interferon regulatory factor 6 exons suggests a two-tier approach for efficient mutation screens for interferon regulatory factor 6. The type and distribution of mutations are consistent with the hypothesis that Van der Woude is caused by haploinsufficiency of interferon regulatory factor 6. Oil the other hand, the distribution of popliteal pterygium syndrome-associated mutations suggests a different, though not mutually exclusive, effect oil interferon regulatory factor 6 function. Genet Med 2009:11(4):241-247.

Genomic Strategy Identifies a Missense Mutation in WD-Repeat Domain 65 (WDR65) in an Individual With Van der Woude Syndrome

Genetic variation in the transcription factor interferon regulatory factor 6 (IRF6) causes and contributes risk for oral clefting disorders. We hypothesized that genes regulated by IRF6 are also involved in oral clefting disorders. We used five criteria to identify potential IRF6 target genes; differential gene expression in skin taken from wild-type and Irf6-deficient murine embryos, localization to the Van der Woude syndrome 2 (VWS2) locus at 1p36-1p32, overlapping expression with Irf6, presence of a conserved predicted-binding site in the promoter region, and a mutant murine phenotype that was similar to the Irf6 mutant mouse. Previously, we observed altered expression for 573 genes; 13 were located in the murine region syntenic to the VWS2 locus. Two of these genes, Wdr65 and Stratifin, met 4 of 5 criteria. Wdr65 was a novel gene that encoded a predicted protein of 1,250 amino acids with two WD domains. As potential targets for Irf6 regulation, we hypothesized that disease-causing mutations will be found in WDR65 and Stratifin in individuals with VWS or VWS-like syndromes. We identified a potentially etiologic missense mutation in WDR65 in a person with VWS who does not have an exonic mutation in IRF6. The expression and mutation data were consistent with the hypothesis that WDR65 was a novel gene involved in oral clefting. (C) 2011 Wiley-Liss, Inc.

Contribuição para o conhecimento da biologia de Cynoscion jamaicensis (Vaillant & Bocourt, 1883), na área entre Cabo de São Tomé (22º04's) e Torres (29º21'S), Brasil

Este trabalho baseia-se na análise de dados obtidos de 1891 exemplares de Cynoscion jamaicensis coletados durante quatro cruzeiros oceanográficos realizados por intermédio do N/Oc. Prof. W. Besnard, na área entre Cabo de Sao Tomé (22º04'S) e Torres (29º30'S), até a isóbata de 200 m, dentro do programa FAUNEC. A espécie distribui-se ao longo da plataforma continental, preferencialmente na região banhada pela agua costeira, com temperaturas entre 27ºC e 18ºC. Ocorrem concentrações de jovens e adultos, indiscriminadamente da distância da costa; os jovens ocorreram, em fevereiro-março, entre 22ºS e 27ºS e, nos demais períodos, entre 23º20'S e 27º30'S, enquanto os adultos distribulram-se, em fevereiro-março e maio, entre 26ºS e 27º30'S e, em setembro e novembro, entre 23ºS e 29º30'S. A desova ocorre entre as latitudes 24º30'S e 26º30'S, durante o fim do inverno-primavera (setembro-novembro). Concordando com o ciclo reprodutivo, o fator de condição mostrou variações cíclicas, com valor mais baixo durante setembro, período de desova. O pico de recrutamento verificou-se em maio, quando ocorreram indivíduos com comprimento total entre 70 e 90 mm, provenientes da desova do ano anterior, que ainda nao completaram um ano de idade. 0 comprimento médio de início da primeira maturação sexual é de 154 mm, sendo que aos 200 mm todos os indivíduos estão aptos para a reprodução. A relação peso total/comprimento total apresentou diferenças estatisticamente significativas entre sexos, com α = 3,25 para machos e 3,10 para fêmeas.

Emerging infectious diseases in cetaceans worldwide and the possible role of environmental stressors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

BCS superconductivity in the van Hove scenario in s and d waves

The effect of including a van Hove singularity in the density of state of a renormalized BCS equation in s and d waves and its appropriateness in describing some properties of high-Tc cuprates in the weak-coupling region are studied in two space dimensions. The specific heat and knight shift as a function of temperature exhibit scaling below the critical temperature in d wave. We also study the jump in the specific heat at the critical temperature Tc in s and d waves, which can have values significantly higher than the standard BCS values and which increases with Tc, as experimentally observed in many d-wave high-Tc materials. The experimental results on the specific heat and knight shift of the Y-123 system are compared with the theoretical predictions.

Effective Fokker-Planck equation for birhythmic modified van der Pol oscillator

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Feeding associations between Guiana dolphins, Sotalia guianensis (Van Bénèden, 1864) and seabirds in the Lagamar estuary, Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Group size and composition of Guiana dolphins (Sotalia guianensis) (Van Bénèden, 1864) in the Paranaguá Estuarine Complex, Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Relationship between lower-lip fistulae and cleft lip and/or palate in Van der Woude syndrome

Objective: This study was conducted to evaluate the relationship between fistulae of the lower lip and cleft lip and/or palate in patients with Van der Woude syndrome.Methods: the medical records of 11,000 patients with cleft lip and/or palate registered at the Cleft Lip-Palate Research and Rehabilitation Hospital, University of São Paulo, Bauru were reviewed. of these patients, 133 (1.2%) presented with Van der Woude syndrome.Results: of the 133 patients, 88 (66.2%) exhibited full clefts, 22 (16.5%) only cleft lip, and 23 (17.3%) only cleft palate. The lower-lip fistulae observed in these 133 patients were bilateral symmetric in 66 (49.7%), bilateral asymmetric in 42 (31.6%), microform in 19 (14.3%), median in 5 (3.8%), and unilateral in 1 (0.7%).Conclusion: This population sample appears to exhibit the previously published tendency for bilateral, unilateral, or mixed-type congenital fistulae to be associated with cleft lip with or without cleft palate, while so-called microforms or conic elevations are almost exclusively associated with cleft palate.

Reinterpretation of Malvinoconularia cahuanotensis (Braniša and Vaněk) from the Devonian Altiplano and Western Andean Cordillera, Bolivia, South America

The holotype of Malvinoconularia cahuanotensis (Braniša and Vaněk) (Devonian, Bolivia), the type species of the monospecific genus Malvinoconularia Babcock et al., is redescribed and refigured. M. cahuanotensis exhibits several gross morphological features that together are uniquely shared with Reticulaconularia baini (Babcock and Feldmann). In both taxa, the transverse ribs are nodose, the inter-spaces bear longitudinal ridges (bars or crests) that are collinear (line up) across the transverse ribs, and the longitudinal centerline (midline) of the faces is marked by a subdued ridge. Additionally, the two species may also be similar in the anatomy and external ornament of the corner sulcus. The slightly undulose geometry of the transverse ribs of M. cahuanotensis also is exhibited by certain specimens of Reticulaconularia; however, whether this feature is primary or taphonomic in origin is unclear at present. Together, these similarities suggest that the genus Malvinoconularia probably is a junior synonym of the genus Reticulaconularia. © Asociación Paleontológica Argentina.

One-dimensional Fermi accelerator model with moving wall described by a nonlinear van der Pol oscillator

A modification of the one-dimensional Fermi accelerator model is considered in this work. The dynamics of a classical particle of mass m, confined to bounce elastically between two rigid walls where one is described by a nonlinear van der Pol type oscillator while the other one is fixed, working as a reinjection mechanism of the particle for a next collision, is carefully made by the use of a two-dimensional nonlinear mapping. Two cases are considered: (i) the situation where the particle has mass negligible as compared to the mass of the moving wall and does not affect the motion of it; and (ii) the case where collisions of the particle do affect the movement of the moving wall. For case (i) the phase space is of mixed type leading us to observe a scaling of the average velocity as a function of the parameter (χ) controlling the nonlinearity of the moving wall. For large χ, a diffusion on the velocity is observed leading to the conclusion that Fermi acceleration is taking place. On the other hand, for case (ii), the motion of the moving wall is affected by collisions with the particle. However, due to the properties of the van der Pol oscillator, the moving wall relaxes again to a limit cycle. Such kind of motion absorbs part of the energy of the particle leading to a suppression of the unlimited energy gain as observed in case (i). The phase space shows a set of attractors of different periods whose basin of attraction has a complicated organization. © 2013 American Physical Society.

Application of a bounded upwinding scheme to complex fluid dynamics problems

This paper is concerned with an overview of upwinding schemes, and further nonlinear applications of a recently introduced high resolution upwind differencing scheme, namely the ADBQUICKEST [V.G. Ferreira, F.A. Kurokawa, R.A.B. Queiroz, M.K. Kaibara, C.M. Oishi, J.A.Cuminato, A.F. Castelo, M.F. Tomé, S. McKee, assessment of a high-order finite difference upwind scheme for the simulation of convection-diffusion problems, International Journal for Numerical Methods in Fluids 60 (2009) 1-26]. The ADBQUICKEST scheme is a new TVD version of the QUICKEST [B.P. Leonard, A stable and accurate convective modeling procedure based on quadratic upstream interpolation, Computer Methods in Applied Mechanics and Engineering 19 (1979) 59-98] for solving nonlinear balance laws. The scheme is based on the concept of NV and TVD formalisms and satisfies a convective boundedness criterion. The accuracy of the scheme is compared with other popularly used convective upwinding schemes (see, for example, Roe (1985) [19], Van Leer (1974) [18] and Arora & Roe (1997) [17]) for solving nonlinear conservation laws (for example, Buckley-Leverett, shallow water and Euler equations). The ADBQUICKEST scheme is then used to solve six types of fluid flow problems of increasing complexity: namely, 2D aerosol filtration by fibrous filters; axisymmetric flow in a tubular membrane; 2D two-phase flow in a fluidized bed; 2D compressible Orszag-Tang MHD vortex; axisymmetric jet onto a flat surface at low Reynolds number and full 3D incompressible flows involving moving free surfaces. The numerical simulations indicate that this convective upwinding scheme is a good generic alternative for solving complex fluid dynamics problems. © 2012.

Biological notes on the parasitism of apoica flavissima Van der Vecht (Hymenoptera: Vespidae) by Seminota marginata (Westwood) (Hymenoptera: Trigonalidae): Are social paper wasps primary or secundary hosts of trigonalidae?

Hosts of Trigonalidae include larvae of social paper wasps, which have been considered secondary hosts, supposedly following predation of the primary host (usually caterpillars) by adult wasps. This study provides observations on biological aspects of the parasitism of Apoica flavissima Van der Vecht by Seminota marginata (Westwood), and suggests that social wasps may be both primary and secondary hosts, whereas they extract and chew vegetable fiber.