Modeling Edar expression reveals the hidden dynamics of tooth signaling center patterning.

When patterns are set during embryogenesis, it is expected that they are straightly established rather than subsequently modified. The patterning of the three mouse molars is, however, far from straight, likely as a result of mouse evolutionary history. The first-formed tooth signaling centers, called MS and R2, disappear before driving tooth formation and are thought to be vestiges of the premolars found in mouse ancestors. Moreover, the mature signaling center of the first molar (M1) is formed from the fusion of two signaling centers (R2 and early M1). Here, we report that broad activation of Edar expression precedes its spatial restriction to tooth signaling centers. This reveals a hidden two-step patterning process for tooth signaling centers, which was modeled with a single activator-inhibitor pair subject to reaction-diffusion (RD). The study of Edar expression also unveiled successive phases of signaling center formation, erasing, recovering, and fusion. Our model, in which R2 signaling center is not intrinsically defective but erased by the broad activation preceding M1 signaling center formation, predicted the surprising rescue of R2 in Edar mutant mice, where activation is reduced. The importance of this R2-M1 interaction was confirmed by ex vivo cultures showing that R2 is capable of forming a tooth. Finally, by introducing chemotaxis as a secondary process to RD, we recapitulated in silico different conditions in which R2 and M1 centers fuse or not. In conclusion, pattern formation in the mouse molar field relies on basic mechanisms whose dynamics produce embryonic patterns that are plastic objects rather than fixed end points

Trabajo, empleo, calificaciones profesionales, relaciones de trabajo e identidades laborales. Vol. I

CLACSO ha apoyado desde sus inicios la constitución y desarrollo de grupos de reflexión centrados en la problemática del mundo del trabajo. Los temas abordados sucesivamente han sido el empleo y el desempleo, los movimientos laborales, las relaciones de trabajo, las condiciones y medio ambiente de trabajo. Las reuniones y seminarios se han desarrollado en las principales ciudades del continente: México DF, La Habana, Medellín, Santiago de Chile, Río de Janeiro, San Pablo, Buenos Aires y Montevideo. Los objetivos son facilitar los encuentros, el debate y las acciones de cooperación entre los especialistas mas reconocidos y con los jóvenes investigadores, becarios, maestrandos y doctorandos y nutrir una comunidad muy diversa, y pluralista de científicos sociales que no han cesado de crecer. Los grupos han reunido a destacados especialistas de la casi totalidad de países de la región, con una composición multidisciplinaria y pluralista que abarca a sociólogos del trabajo y de la educación, cientistas políticos, economístas del trabajo y del desarrollo, abogados laboralistas y psicólogos del trabajo, entre otras. Sus estudios han dado lugar a numerosas publicaciones editadas por CLACSO, la UAM, el PREALC de la OIT, el CEIL PIETTE del CONICET y Trabajo y Sociedad de Argentina, y forman parte de las bibliografías de aquellas disciplinas. Desde 2007 se constituyó el actual grupo "Trabajo, empleo, calificaciones profesionales, relaciones de trabajo e identidades laborales" con sede en la UNAM, sede Iztapalapa y en el CEIL-PIETTE del CONICET. Los dos volúmenes que ofrecemos a la comunidad académica y a los actores sociales contienen la mayoría de las ponencias presentadas en el Seminario de Buenos Aires, realizado en noviembre de 2007.INDICE Presentación del Grupo de Trabajo: Trabajo, empleo, calificaciones profesionales, relaciones de trabajo e identidades laborales Julio César Neffa y Enrique de la Garza Toledo 11 Presentación de la obra: Nuevos y viejos escenarios en el mundo laboral latinoamericano: distintas miradas para su estudio Leticia Muñiz Terra 15 Primera parte Dimensiones teóricas y metodológicas Diez tesis sobre el trabajo del presente (y el futuro del trabajo) Ricardo Antunes 29 Aportes a una teoría del cambio: gubernamentalidad, fuerzas productivas y praxis de sujetos colectivos en nueva época Alberto L. Bialakowsky, María Ignacia Costa y M. Mercedes Patrouilleau 45 um ensaio sobre inércia social Adalberto Cardoso 83 Hacia un concepto ampliado de trabajo Enrique de la Garza Toledo 111 Comentarios: Del trabajo esclavo a las nuevas formas de esclavitud en el trabajo Irene Vasilachis de Gialdino 141 Segunda parte Trabajo, identidad y subjetividad Cuando el trabajo informal es espacio para la construcción de identificaciones colectivas. Un estudio sobre ferias comerciales urbanas Mariana Busso 159 Construcción del sujeto de trabajo en la condición de precariedad Karina Arellano, Diego Baccarelli, Cecilia Dallacia, Lucía De Gennaro, Soraya Giradles y Emilio Sadier 193 Comentarios: Comentarios críticos de las ponencias presentadas en la Mesa Trabajo, identidad y subjetividad Juan Montes Cató 203 Tercera parte Educación, calificación profesional, productividad y salarios Fuentes de la valorización del capital: la relación entre productividad y salarios. Argentina 1993-2006 Javier Lindenboim, Juan M. Graña y Damián Kennedy 215 Demandas empresariales en las estrategias de formación de los ingenieros en dos zonas argentinas Marta Panaia 243 Saberes, intervenciones profesionales y clasificaciones profesionales: nuevos requerimientos a idóneos, técnicos e ingenieros Julio Testa; Claudia Figari y Martín Spinosa 275 Pautas de desigualdad en el mundo social productivo uruguayo. Aportes para el debate en torno a la gestión por competencias Mariela Quiñones Montoro 309 Cuarta parte La nueva dinámica empresarial. Innovación y flexibilización en la industria Trabajo de organización y cadenas de valor. El caso de la vestimenta uruguaya Marcos Supervielle y Emiliano Rojido 337 Potencialidades y limitaciones de sectores dinámicos de alto valor agregado: la industria aeroespacial en México, Jorge Carrillo y Alfredo Hualde 373 La industria del salmón en Chile: ¿crecimiento social o explotación laboral?, Antonio Aravena 397 Rasgos posfordistas en el paisaje laboral de la gran industria del Valle del Cauca colombiano Carlos Mejía Sanabria 42

A genome-wide association scan implicates <i>DCHS2, RUNX2, GLI3, PAX1</i> and <i>EDAR</i> in human facial variation

We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values−8) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar function

Polyenylpyrrole Derivatives Inhibit NLRP3 Inflammasome Activation and Inflammatory Mediator Expression by Reducing Reactive Oxygen Species Production and Mitogen-Activated Protein Kinase Activation

10.1371/journal.pone.0076754PLoS ONE810-POLN

Aspergillus fumigatus Stimulates the NLRP3 Inflammasome through a Pathway Requiring ROS Production and the Syk Tyrosine Kinase

Invasive aspergillosis (IA) is a life-threatening disease that occurs in immunodepressed patients when infected with Aspergillus fumigatus. This fungus is the second most-common causative agent of fungal disease after Candida albicans. Nevertheless, much remains to be learned about the mechanisms by which A. fulmigatus activates the innate immune system. We investigated the inflammatory response to conidia and hyphae of A. fumigatus and specifically, their capacity to trigger activation of an inflammasome. Our results show that in contrast to conidia, hyphal fragments induce NLRP3 inflammasome assembly, caspase-1 activation and IL-1β release from a human monocyte cell line. The ability of Aspergillus hyphae to activate the NLRP3 inflammasome in the monocytes requires K+ efflux and ROS production. In addition, our data show that NLRP3 inflammasome activation as well as pro-IL-1β expression relies on the Syk tyrosine kinase, which is downstream from the pathogen recognition receptor Dectin-1, reinforcing the importance of Dectin-1 in the innate immune response against fungal infection. Furthermore, we show that treatment of monocytes with corticosteroids inhibits transcription of the gene encoding IL-1β. Thus, our data demonstrate that the innate immune response against A. fumigatus infection involves a two step activation process, with a first signal promoting expression and synthesis of pro-IL-1β; and a second signal, involving Syk-induced activation of the NLRP3 inflammasome and caspase-1, allowing processing and secretion of the mature cytokine

Host genetic signatures of susceptibility to fungal disease

Our relative inability to predict the development of fungal disease and its clinical outcome raises fundamental questions about its actual pathogenesis. Several clinical risk factors are described to predispose to fungal disease, particularly in immunocompromised and severely ill patients. However, these alone do not entirely explain why, under comparable clinical conditions, only some patients develop infection. Recent clinical and epidemiological studies have reported an expanding number of monogenic defects and common polymorphisms associated with fungal disease. By directly implicating genetic variation in the functional regulation of immune mediators and interacting pathways, these studies have provided critical insights into the human immunobiology of fungal disease. Most of the common genetic defects reported were described or suggested to impair fungal recognition by the innate immune system. Here, we review common genetic variation in pattern recognition receptors and its impact on the immune response against the two major fungal pathogens Candida albicans and Aspergillus fumigatus. In addition, we discuss potential strategies and opportunities for the clinical translation of genetic information in the field of medical mycology. These approaches are expected to transfigure current clinical practice by unleashing an unprecedented ability to personalize prophylaxis, therapy and monitoring for fungal disease.This work was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), the Fundação para a Ciência e Tecnologia (FCT) (IF/00735/2014 to AC, and SFRH/BPD/96176/2013 to CC), the Institut Mérieux (Mérieux Research Grant 2017 to CC), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Research Grant 2017 to AC)

Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection

Contact with HIV-1 envelope protein elicits release of ATP through pannexin-1 channels on target cells; by activating purinergic receptors and Pyk2 kinase in target cells, this extracellular ATP boosts HIV-1 infectivity