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.

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.

Comparative electrical behavior at low and high current of SnO(2)- and ZnO-based varistors

The complete I-V characteristics of SnO(2)-based varistors, particularly of the Pianaro system SCNCr consisting in 98.9%SnO(2)+1%CoO+0.05%Nb(2)O(5)+0.05%Cr(2)O(3), all in mol%, have been seldom reported in the literature. A comparative study at low and high currents of the nonohmic behavior of SCNCr- and ZnO-based varistors (modified Matsuoka system) is proposed in this work. The SCNCr system showed higher nonlinearity coefficients in the whole range of measured current. The electrical breakdown field (E(b)) was twice as high for the SCNCr system (5400 V/cm) than for the ZnO varistor (2600 V/cm) due to a smaller average grain size of the former (4.5 mu m) with respect to the latter (8.5 mu m). Nevertheless, we consider that another important factor responsible for the high E(b) in the SCNCr system is the great number of electrically active interfaces (85%) as determined with electrostatic force microscopy (EFM). It was also established that the SCNCr system might be produced in disks of smaller dimensions than that of commercial ZnO-based product, with a 5.0 cm(-1) minimal area-volume (A/V) ratio. The SCNCr reached the saturation current in a short time because of the high resistivity of the grains, which is five times higher than that of the grains in ZnO-based varistors.

Preliminary Overview of the Economies of Latin America and the Caribbean 2008

Includes bibliography

Alianzas público-privadas y escalamiento industrial. El caso del Complejo de Alta Tecnología de Jalisco, México

Incluye Bibliografía

Myogenin, MyoD and IGF-I regulate muscle mass but not fiber-type conversion during resistance training in rats

The purpose of this study was to test the hypothesis that skeletal muscle adaptations induced by long-term resistance training (RT) are associated with increased myogenic regulatory factors (MRF) and insulin-like growth factor-I (IGF-I) mRNA expression in rats skeletal muscle. Male Wistar rats were divided into 4 groups: 8-week control (C8), 8-week trained (T8), 12-week control (C12) and 12-week trained (T12). Trained rats were submitted to a progressive RT program (4 sets of 10-12 repetitions at 65-75% of the 1RM, 3 day/week), using a squat-training apparatus with electric stimulation. Muscle hypertrophy was determined by measurement of muscle fiber cross-sectional area (CSA) of the muscle fibers, and myogenin, MyoD and IGF-I mRNA expression were measured by RT-qPCR. A hypertrophic stabilization occurred between 8 and 12 weeks of RT (control-relative % area increase, T8: 29% vs. T12: 35%; p>0.05) and was accompanied by the stabilization of myogenin (control-relative % increase, T8: 44.8% vs. T12: 37.7%, p>0.05) and MyoD (control-relative % increase, T8: 22.9% vs. T12: 22.3%, p>0.05) mRNA expression and the return of IGF-I mRNA levels to the baseline (control-relative % increase, T8: 30.1% vs. T12: 1.5%, p<0.05). Moreover, there were significant positive correlations between the muscle fiber CSA and mRNA expression for MyoD (r=0.85, p=0.0001), myogenin (r=0.87, p=0.0001), and IGF-I (r=0.88, p=0.0001). The significant (p<0.05) increase in myogenin, MyoD and IGF-I mRNA expression after 8 weeks was not associated with changes in the fiber-type frequency. In addition, there was a type IIX/D-to-IIA fiber conversion at 12 weeks, even with the stabilization of MyoD and myogenin expression and the return of IGF-I levels to baseline. These results indicate a possible interaction between MRFs and IGF-I in the control of muscle hypertrophy during long-term RT and suggest that these factors are involved more in the regulation of muscle mass than in fiber-type conversion. © Georg Thieme Verlag KG Stuttgart · New York.

La nueva pobreza urbana: dinámica global, regional y argentina en las últimas dos décadas

Incluye Bibliografía

Three-dimensional finite element analysis of stress distribution in retention screws of different crown-implant ratios

The retaining screw of the implant-supported dental prosthesis is the weakest point of the crown/implant system. Furthermore, crown height is another important factor that may increase the lever arm. Therefore, the aim of this study was to assess the stress distribution in implant prosthetic screws with different heights of the clinical crown of the prosthesis using the method of three-dimensional finite element analysis. Three models were created with implants (3.75 mm × 10 mm) and crowns (heights of 10, 12.5 and 15 mm). The results were visualised by means of von Mises stress maps that increased the crown heights. The screw structure exhibited higher levels of stresses in the oblique load. The oblique loading resulted in higher stress concentration when compared with the axial loading. It is concluded that the increase of the crown was damaging to the stress distribution on the screw, mainly in oblique loading. © 2013 Taylor & Francis.

Análise dos parâmetros clínicos periodontais e expressão genética de interferons alfa, gama e genes relacionados em indivíduos portadores de Síndrome de Down com doença periodontal

Pós-graduação em Ciências Odontológicas - FOAR

Viagem ao sono: relações de tradicionalidade e consumo na Praia do Sono - Parati (RJ)

Pós-graduação em Ciências Sociais - FFC

Estudo histomorfométrico do processo de reparo de incisivos de ratos diabéticos submetidos à luxação extrusiva

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação da gestão de áreas contaminadas de uma unidade industrial, localizada no município de Cubatão, São Paulo

Pós-graduação em Geociências e Meio Ambiente - IGCE

A importância da observação da estrutura textual durante a catalogação de assunto de livros científicos em bibliotecas universitárias: uma análise realizada a partir da técnica de Protocolo Verbal

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

Desenvolvimento vegetativo de quatro espécies de grama irrigadas com efluente de estação de tratamento de esgoto doméstico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Conservação genética in situ de espécies arbóreas que ocorrem na transição da floresta estacional semidecidual e o cerrado em Selvíria – MS

Pós-graduação em Agronomia - FEIS