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.

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.

Aspectos clínicos e radiográficos da coluna cervical de bezerros submetidos a Prova do Laço

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Sustentabilidade ambiental das universidades: avaliação de seis universidades sediadas no Estado de São Paulo à partir da análise das informações em seus websites

Pós-graduação em Engenharia de Produção - FEB

What kind of microfoundations? Notes on the evolutionary approach

The microfoundations of economic models are a hotly debated topic in the literature. The debate is important because microfoundations —the ways in which agents decide and behave— have implications that go beyond a specific firm, market or activity; they strongly condition macroeconomic outcomes. This document addresses the classical problems of rationality, uncertainty and institutions: when there is Keynes-Knight uncertainty and rationality is bounded, decision making adopts the form of conventional rules or heuristics. The hyper-rational representative agent of the rational expectations world could generate highly misleading outcomes in macro models. Section 2 applies this discussion to the study of technical change and to innovation and diffusion of technology in the international system, which transform the patterns of specialization. Section 3 discusses the forces that may trap a country in a low-growth trap and the crucial role of institutions in escaping from this trap.

A busca do ser e da arte em O Cavaleiro Inexistente de Ítalo Calvino

Pós-graduação em Letras - IBILCE

Indivisíveis, intangíveis, impossíveis: mundos ficcionais em I nostri antenati, de Italo Calvino

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Initial Development of a Web-Based Tool to Increase Hunter Harvest of Female Ungulates

Landowners and agencies have expressed difficulty finding hunters willing to harvest the female portion of the ungulate populations, and likewise, hunters have expressed difficulty achieving access to private lands. Since 2003, the Montana “DoeCowHunt” website (www.doecowhunt.montana.edu) has provided an avenue to improve hunter-landowner contact and wild ungulate population management. A product of Montana State University Extension Wildlife Program, this website provides a means for hunters and landowners in Montana to contact each other by listing contact information (email address, physical address, and telephone number) for the purpose of harvesting antlerless ungulates. In the first year over 10,000 users visited the site. Of those who actually registered, 11 were landowners and 1334 were hunters. An evaluation survey resulted in a 40% response rate. The survey indicated the average registered landowner had 20 hunter contacts. Many landowners contacted hunters through use of the website but did not register or list their contact information on the site.

Modifying Fences to Prevent Ungulate Use of Cropland and High-Value Pastures

Big game can damage crops and compete with livestock for valuable forage. Ranchers have reported their tolerance for big game would increase if the animals could be prevented from using key areas critical for spring livestock use. Likewise, some farmers have high value areas that must be protected. Fences provide the most consistent long term control compared to other deterrent methods, but are costly to erect. Many designs of woven wire and electric fences are currently used. Costs of erecting deer proof fencing could be greatly reduced if an existing fence could be modified instead of being replaced entirely. This study investigates the possibility of modifying existing fences to prohibit deer and elk crossings. Preliminary results indicate effective modifications can be made to existing fences for $1300- $3500 per mile for materials. Traditional complete construction of game fences cost more than $10,000 per mile. These fences may be used in lieu of compensation programs for ranchers. Also, if farmers and ranchers can keep big game out of important foraging areas, their tolerance for these animals on the rest of their property may greatly increase.

Cellular interference in craniofrontonasal syndrome: males mosaic for mutations in the X-linked EFNB1 gene are more severely affected than true hemizygotes

Craniofrontonasal syndrome (CFNS), an X-linked disorder caused by loss-of-function mutations of EFNB1, exhibits a paradoxical sex reversal in phenotypic severity: females characteristically have frontonasal dysplasia, craniosynostosis and additional minor malformations, but males are usually more mildly affected with hypertelorism as the only feature. X-inactivation is proposed to explain the more severe outcome in heterozygous females, as this leads to functional mosaicism for cells with differing expression of EPHRIN-B1, generating abnormal tissue boundaries-a process that cannot occur in hemizygous males. Apparently challenging this model, males occasionally present with a more severe female-like CFNS phenotype. We hypothesized that such individuals might be mosaic for EFNB1 mutations and investigated this possibility in multiple tissue samples from six sporadically presenting males. Using denaturing high performance liquid chromatography, massively parallel sequencing and multiplex-ligation-dependent probe amplification (MLPA) to increase sensitivity above standard dideoxy sequencing, we identified mosaic mutations of EFNB1 in all cases, comprising three missense changes, two gene deletions and a novel point mutation within the 5' untranslated region (UTR). Quantification by Pyrosequencing and MLPA demonstrated levels of mutant cells between 15 and 69%. The 5' UTR variant mutates the stop codon of a small upstream open reading frame that, using a dual-luciferase reporter construct, was demonstrated to exacerbate interference with translation of the wild-type protein. These results demonstrate a more severe outcome in mosaic than in constitutionally deficient males in an X-linked dominant disorder and provide further support for the cellular interference mechanism, normally related to X-inactivation in females.

O efeito do grau de internacionalização nas competências internacionais e no desempenho financeiro da PME brasileira

O objetivo deste artigo é identificar a relação entre o Grau de internacionalização (GRI), o desempenho financeiro e o desenvolvimento de competências internacionais das Pequenas e Médias Empresas (PMEs) brasileiras. O aumento do GRI, mediado pelo desenvolvimento das habilidades em lidar com o mercado internacional (Knight & Kim, 2009), assegura competências internacionais que podem distinguir as PMEs com alto GRI das PMEs que operam localmente (Penrose, 1959; Teece, Pisano, & Shuen, 1997). Por meio de uma survey aplicada em 114 empresas de até 200 funcionários (Ministério do Desenvolvimento da Indústria e do Comércio Exterior [MDIC], 2010), esta pesquisa testou a hipótese que o aumento do GRI desenvolve competências internacionais e melhora o desempenho financeiro. Devido à utilização de construtos de natureza complexa, a existência de erros e a necessidade de se identificarem múltiplas relações simultaneamente, a modelagem de equações estruturais (SEM) foi utilizada como técnica estatística. Os resultados indicam que, com o aumento do grau de internacionalização, a PME desenvolve competências internacionais e, assim, apresenta um desempenho superior. A relação de mediação do desenvolvimento de novas competências entre o aumento do GRI e o desempenho financeiro organizacional explora uma nova abordagem nos negócios internacionais, principalmente para as PMEs.

Reflexiones sobre el valor actual del gobierno de Baratiaria y la quijotización de Sancho

[ES]En este artículo exploramos el quijotismo que aflora en Sancho Panza al aceptar el trabajo como escudero bajo la promesa del gobierno de la ínsula Barataria. Esta “tierra prometida” se convierte en el objeto de deseo de este rústico campesino que desea adoptar una nueva identidad de la misma manera que su amo deviene un caballero andante bajo la influencia libresca de las caballerías. Se analiza también el valor actual del gobierno de Sancho Panza, con sus aciertos y desaciertos, sus logros y sus dificultades.[EN]In this article we explore the outcropping quixotic Sancho Panza in accepting the job as squire under the government's promise of the island of Barataria. This "promised land" becomes the object of desire of this rustic peasant who wishes to adopt a new identity in the same way that his master becomes a bookish knight under the influence of epic tale. The present value of the government of Sancho Panza, with its successes and failures, achievements and difficulties are also analyzed.

Libro, diaspora e ri-costruzioni identitarie. Per una storia della tipografia sefardita portoghese nell'Italia del Cinquecento

Il lavoro ripercorre le tracce che gli ebrei portoghesi, esuli dopo il biennio 1496-97, lasciarono nel loro cammino attraverso l'Europa. In particolare, l'interesse si concentra sulla breve parentesi italiana, che grazie all'apertura e alla disponibilità  di alcuni Signori, come i Gonzaga di Mantova, i Medici, i Dogi della Serenissima e gli Este, risulta ricchissima di avvenimenti e personaggi, decisivi anche per la storia culturale del Portogallo. L'analisi parte evidenziando l'importanza che ebbe la tipografia ebraica in Portogallo all'epoca della sua introduzione nel Paese; in secondo luogo ripercorre la strada che, dal biennio del primo decreto di espulsione e del conseguente battesimo di massa, porta alla nascita dell'€™Inquisizione in Portogallo. Il secondo capitolo tenta di fare una ricostruzione, il più possibile completa e coerente, dei movimenti degli esuli, bollati come marrani e legati alle due maggiori famiglie, i Mendes e i Bemveniste, delineando poi il primo nucleo di quella che diventerà  nel Seicento la comunità  sefardita portoghese di Amsterdam, dove nasceranno le personalità  dissidenti di Uriel da Costa e del suo allievo Spinoza. Il terzo capitolo introduce il tema delle opere letterarie, effettuando una rassegna dei maggiori volumi editi dalle officine tipografiche ebraiche stanziatesi in Italia fra il 1551 e il 1558, in modo particolare concentrando l'attenzione sull'€™attività  della tipografia Usque, da cui usciranno numerosi testi di precettistica in lingua ebraica, ma soprattutto opere cruciali come la famosa «Bibbia Ferrarese» in castigliano, la «Consolação às Tribulações de Israel», di Samuel Usque e la raccolta composta dal romanzo cavalleresco «Menina e Moça» di Bernardim Ribeiro e dall'ecloga «Crisfal», di un autore ancora non accertato. L'ultimo capitolo, infine, si propone di operare una disamina di queste ultime tre opere, ritenute fondamentali per ricostruire il contesto letterario e culturale in cui la comunità  giudaica in esilio agiva e proiettava le proprie speranze di futuro. Per quanto le opere appartengano a generi diversi e mostrino diverso carattere, l'€™ipotesi è che siano parte di un unicum filosofico e spirituale, che intendeva sostanzialmente indicare ai confratelli sparsi per l'Europa la direzione da prendere, fornendo un sostegno teoretico, psicologico ed emotivo nelle difficili condizioni di sopravvivenza, soprattutto dell'integrità religiosa, di ciascun membro della comunità.