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.

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.

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

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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.

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.

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.

Ciclos limites e a equação de van der Pol

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Aplicações da equação de Van Der Waals no estudo de colisões entre átomos e moléculas

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Weyl-van der Waerden spinor technique for spin-3/2 fermions

We use the Weyl-van der Waerden spinor technique to construct helicity wave functions for massless and massive spin-3/2 fermions. We apply our formalism to evaluate helicity amplitudes taking into account some phenomenological couplings involving these particles.

Review of The Biology of Freshwater Wetlands: Biology of Habitats by Arnold G. van der Valko

Wetland ecology is a relatively new field that developed from an initial interest in a few direct benefits that wetlands provide to society. Consequently, much early scientific work was stimulated by economic returns from specific wetland services, such as production of peat and provision of habitat for economically valuable wildlife (e.g., waterfowl and furbearers). Over time, societal interest in wetlands broadened, and these unique habitats are now valued for many additional services, including some that bear non market value. Common examples include carbon sequestration, flood reduction, water purification, and aesthetics. The increased recognition of the importance of wetlands has generated a diversity of job opportunities in wetland ecology and management. Despite the increased knowledge base and enhanced job market, I am not aware of any institutions that offer specialty degrees in this new discipline. Indeed, relatively few institutions offer specific wetland ecology classes, with Arnold G. van der Valk and a few of his peers at other universities being notable exceptions.

Encapsulation of small magnetic clusters in fullerene cages: A density functional theory investigation within van der Waals corrections

The encapsulation of magnetic transition-metal (TM) clusters inside carbon cages (fullerenes, nanotubes) has been of great interest due to the wide range of applications, which spread from medical sensors in magnetic resonance imaging to photonic crystals. Several theoretical studies have been reported; however, our atomistic understanding of the physical properties of encapsulated magnetic TM 3d clusters is far from satisfactory. In this work, we will report general trends, derived from density functional theory within the generalized gradient approximation proposed by Perdew, Burke, and Ernzerhof (PBE), for the encapsulation properties of the TMm@C-n (TM = Fe, Co, Ni; m = 2-6, n = 60,70,80,90) systems. Furthermore, to understand the role of the van der Waals corrections to the physical properties, we employed the empirical Grimme's correction (PBE + D2). We found that both PBE and PBE + D2 functionals yield almost the same geometric parameters, magnetic and electronic properties, however, PBE + D2 strongly enhances the encapsulation energy. We found that the center of mass of the TMm clusters is displaced towards the inside C-n surfaces, except for large TMm clusters (m = 5 and 6). For few cases, e. g., Co-4 and Fe-4, the encapsulation changes the putative lowest-energy structure compared to the isolated TMm clusters. We identified few physical parameters that play an important role in the sign and magnitude of the encapsulation energy, namely, cluster size, fullerene equatorial diameter, shape, curvature of the inside C-n surface, number of TM atoms that bind directly to the inside C-n surface, and the van der Waals correction. The total magnetic moment of encapsulated TMm clusters decreases compared with the isolated TMm clusters, which is expected due to the hybridization of the d-p states, and strongly depends on the size and shape of the fullerene cages.

Ethanol and Water Adsorption on Close-Packed 3d, 4d, and 5d Transition-Metal Surfaces: A Density Functional Theory Investigation with van der Waals Correction

Nowadays, there is a great interest in the economic success of direct ethanol fuel cells; however, our atomistic understanding of the designing of stable and low-cost catalysts for the steam reforming of ethanol is still far from satisfactory, in particular due to the large number of undesirable intermediates. In this study, we will report a first-principles investigation of the adsorption properties of ethanol and water at low coverage on close-packed transition-metal (TM) surfaces, namely, Fe(110), Co(0001), Ni(111), Cu(111), Ru(0001), Rh(111), Pd(111), Ag(111), Os(0001), Ir(111), Pt(111), and Au(111), employing density functional theory (DFT) calculations. We employed the generalized gradient approximation with the formulation proposed by Perdew, Burke, and Erzenholf (PBE) to the exchange correlation functional and the empirical correction proposed by S. Grimme (DFT+D3) for the van der Waals correction. We found that both adsorbates binds preferentially near or on the on top sites of the TM surfaces through the 0 atoms. The PBE adsorption energies of ethanol and water decreases almost linearly with the increased occupation of the 4d and 5d d-band, while there is a deviation for the 3d systems. The van der Waals correction affects the linear behavior and increases the adsorption energy for both adsorbates, which is expected as the van der Waals energy due to the correlation effects is strongly underestimated by DFT-PBE for weak interacting systems. The geometric parameters for water/TM are not affected by the van der Waals correction, i.e., both DFT and DFT+D3 yield an almost parallel orientation for water on the TM surfaces; however, DFT+D3 changes drastically the ethanol orientation. For example, DFT yields an almost perpendicular orientation of the C-C bond to the TM surface, while the C-C bond is almost parallel to the surface using DFT +D3 for all systems, except for ethanol/Fe(110). Thus, the van der Waals correction decreases the distance of the C atoms to the TM surfaces, which might contribute to break the C-C bond. The work function decreases upon the adsorption of ethanol and water, and both follow the same trends, however, with different magnitude (larger for ethanol/TM) due to the weak binding of water to the surface. The electron density increases mainly in the region between the topmost layer and the adsorbates, which explains the reduction of the substrate work function.