p53 and TAp63 promote terminal keratinocyte differentiation in breeding tubercles of the zebrafish

p63, a member of the p53 family of transcription factors, is crucial for vertebrate epidermal development. However, different isoforms of p63 are supposed to have different if not opposing functions. There is compelling genetic evidence that ∆Np63 isoforms are needed to enhance keratinocyte proliferation and stemness. However, the role of TAp63 isoforms is not fully understood, and TAp63 knockout mice display normal epidermal development. In this thesis, we describe the epidermal defects of zebrafish mutants specifically lacking TAp63 isoforms. TAp63 as well as p53 mutant zebrafish present with compromised development of breeding tubercles, epidermal appendages with more advanced stratification and keratinocyte differentiation than in regular epidermis, including continuous desquamation and renewal of superficial cells by derivatives of basal keratinocytes. Additionally, those defects are further enhanced in TAp63/p53 double mutants. Furthermore, molecular analyses, treatments with chemical inhibitors and epistasis studies indicate the existence of a linear TAp63/p53-Notch- Caspase 3 pathway required for enhanced proliferation of keratinocytes at the base of the tubercles and their subsequent differentiation in the absence of complete cell death. In summary, these studies identify the zebrafish breeding tubercles as specific epidermal structures sharing crucial features with cornified mammalian epidermis. In addition, they demonstrate essential and partially redundant roles of TAp63 and p53 to promote keratinocyte proliferation and their terminal differentiation, involving a pathway that might be conserved between fish and mammals

Nocturnal nitrogen oxides at a rural mountain-site in south-western Germany

A new, two-channel instrument for simultaneous NO3 and N2O5 monitoring was used to make the first comprehensive set of nocturnal NOx measurements (NO, NO2, NO3 and N2O5) at the Taunus Observatory, a rural mountain site (Kleiner Feldberg) in South-western Germany. In May 2008, NO3 and N2O5 mixing ratios were well above the instrumental detection limit (a few ppt) on all nights of the campaign and were characterised by large variability. The concentrations of NO3, N2O5 and NO2 were consistent with the equilibrium constant, K2, defining the rates of formation and thermal dissociation of N2O5. A steady-state lifetime analysis is consistent with the loss of nocturnal NOx being dominated by the reaction of NO3 with volatile organic compounds in this forested region, with N2O5 uptake to aerosols of secondary importance. Analysis of a limited dataset obtained at high relative humidity indicated that the loss of N2O5 by reaction with water vapour is less efficient (>factor 3) than derived using laboratory kinetic data. The fraction of NOx present as NO3 and N2O5 reached ~20% on some nights, with night-time losses of NOx competing with daytime losses

Diseño aplicación y evaluación de un programa de enseñanza básica de polo acuático.

Documento en pdf.La Provincia del Guayas cuenta con escenarios deportivos para la natación, públicos y privados; hace aproximadamente 40 años se inició el polo acuático, con la participación de nadadores salidos de academias y clubes que decidieron pasar a la práctica competitiva del polo acuático, complementando la técnica de natación con las técnicas específicas de nado del Polo Acuático, el dominio del balón y las tácticas de juego. Pero estos deportistas jóvenes desafiaban el nivel técnico-táctico de otros países obteniendo pocos resultados. Por ello surgió la elaboración de un programa de enseñanza básica para llegar a la masificación de este deporte, con ejecución de un plan práctico, que lleve desde el inicio una secuencia en la formación y enseñanza de la natación, hasta la aplicación de las diferentes técnicas de nado y dominio de balón; habiéndose invitado a técnicos, monitores de natación y profesores de Cultura Física a involucrarse en el presente proyecto, con el fin de lograr el fomento y desarrollo del Polo Acuático competitivo a nivel local y provincial. La ejecución de este programa, que tuvo el apoyo de la Federación Deportiva del Guayas y un técnico docente en actividades acuáticas y deportivas, involucró a 30 participantes menores de 12 años durante el período 2013

Mutations in the MTHFR gene are not associated with Methotrexate intolerance in patients with juvenile idiopathic arthritis

BACKGROUND: Methotrexate (MTX) intolerance is a frequent problem of long-term treatment in juvenile idiopathic arthritis (JIA). Mutations in the methylentetrahydrofolate reductase (MTHFR) gene may increase toxicity of MTX, potentially constituting an initial stimulus for this conditioned response. The objective of this study was to investigate the relationship of common MTHFR gene mutations and occurrence of MTX intolerance in pediatric patients with JIA treated with MTX. METHODS: Consecutive JIA patients on at least 3 months of MTX treatment were included in this study. Intolerance to MTX was determined using the Methotrexate Intolerance Severity Score (MISS) questionnaire, and MTX intolerance was defined as MISS values of >= 6. Presence of the two most common mutations in the MTHFR gene (C677T and A1298C) was tested using a PCR assay. Results were analyzed using descriptive and non-parametric statistics. RESULTS: 196 patients were included (73 % female). Of those, 93 (46 %) showed MTX intolerance. 168 patients were genotyped for C677T and A1298C. MTX intolerance was not found to be significantly more frequent among patients with hetero- and homozygous or homozygous mutations C677T or A1298C compared to wild type or heterozygous mutations. Analysis of the correlation between numbers of mutations in these two loci to the MISS score did not yield a statistically significant correlation. CONCLUSION: Mutations in the MTHFR gene were not found to be significantly more frequent in JIA patients intolerant to MTX. Toxicity associated with the MTHFR gene seems to result from mechanisms different to those involved in clinical MTX intolerance

Mutations in the MTHFR gene are not associated with Methotrexate intolerance in patients with juvenile idiopathic arthritis

BACKGROUND: Methotrexate (MTX) intolerance is a frequent problem of long-term treatment in juvenile idiopathic arthritis (JIA). Mutations in the methylentetrahydrofolate reductase (MTHFR) gene may increase toxicity of MTX, potentially constituting an initial stimulus for this conditioned response. The objective of this study was to investigate the relationship of common MTHFR gene mutations and occurrence of MTX intolerance in pediatric patients with JIA treated with MTX. METHODS: Consecutive JIA patients on at least 3 months of MTX treatment were included in this study. Intolerance to MTX was determined using the Methotrexate Intolerance Severity Score (MISS) questionnaire, and MTX intolerance was defined as MISS values of >= 6. Presence of the two most common mutations in the MTHFR gene (C677T and A1298C) was tested using a PCR assay. Results were analyzed using descriptive and non-parametric statistics. RESULTS: 196 patients were included (73 % female). Of those, 93 (46 %) showed MTX intolerance. 168 patients were genotyped for C677T and A1298C. MTX intolerance was not found to be significantly more frequent among patients with hetero- and homozygous or homozygous mutations C677T or A1298C compared to wild type or heterozygous mutations. Analysis of the correlation between numbers of mutations in these two loci to the MISS score did not yield a statistically significant correlation. CONCLUSION: Mutations in the MTHFR gene were not found to be significantly more frequent in JIA patients intolerant to MTX. Toxicity associated with the MTHFR gene seems to result from mechanisms different to those involved in clinical MTX intolerance

Stable two-dimensional solitons in nonlinear lattices

We address the existence and stability of two-dimensional solitons in optical or matter-wave media, which are supported by purely nonlinear lattices in the form of a periodic array of cylinders with self-focusing nonlinearity, embedded into a linear material. We show that such lattices can stabilize two-dimensional solitons against collapse. We also found that stable multipoles and vortex solitons are also supported by the nonlinear lattices, provided that the nonlinearity exhibits saturation.Comment: 12 pages, 3 figures, to appear in Optics Letter