Expression profiling of human melanocytes in response to UV-B irradiation

AbstractA comprehensive gene expression analysis of human melanocytes was performed assessing the transcriptional profile of dark melanocytes (DM) and light melanocytes (LM) at basal conditions and after UV-B irradiation at different time points (6, 12 and 24h), and in culture with different keratinocyte-conditioned media (KCM+ and KCM−). The data, previously published in [1], have been deposited in NCBI's Gene Expression Omnibus (GEO accession number: GSE70280)

¿Quiénes son los padres del niño abandonado?

Capítulo 9 del libro: Guisasola, Jenaro ; Garmendia, Mikel (eds.) "Aprendizaje basado en problemas, proyectos y casos: diseño e implementación de experiencias en la universidad" (ISBN: 978-84-9860-959-2)Este capítulo corresponde a un diseño ABP para Genética Humana (Biología)

Complex signatures of selection for the melanogenic loci TYR, TYRP1 and DCT in humans

<p>Abstract</p> <p>Background</p> <p>The observed correlation between ultraviolet light incidence and skin color, together with the geographical apportionment of skin reflectance among human populations, suggests an adaptive value for the pigmentation of the human skin. We have used Affymetrix U133a v2.0 gene expression microarrays to investigate the expression profiles of a total of 9 melanocyte cell lines (5 from lightly pigmented donors and 4 from darkly pigmented donors) plus their respective unirradiated controls. In order to reveal signatures of selection in loci with a bearing on skin pigmentation in humans, we have resequenced between 4 to 5 kb of the proximal regulatory regions of three of the most differently expressed genes, in the expectation that variation at regulatory regions might account for intraespecific morphological diversity, as suggested elsewhere.</p> <p>Results</p> <p>Contrary to our expectations, expression profiles did not cluster the cells into unirradiated versus irradiated melanocytes, or into lightly pigmented versus darkly pigmented melanocytes. Instead, expression profiles correlated with the presence of Bovine Pituitary Extract (known to contain α-MSH) in the media. This allowed us to differentiate between melanocytes that are synthesizing melanin and those that are not. <it>TYR, TYRP1 </it>and <it>DCT </it>were among the five most differently expressed genes between these two groups. Population genetic analyses of sequence haplotypes of the proximal regulatory flanking-regions included Tajima's D, HEW and DHEW neutrality tests analysis. These were complemented with EHH tests (among others) in which the significance was obtained by a novel approach using extensive simulations under the coalescent model with recombination. We observe strong evidence for positive selection for <it>TYRP1 </it>alleles in Africans and for <it>DCT </it>and <it>TYRP1 </it>in Asians. However, the overall picture reflects a complex pattern of selection, which might include overdominance for <it>DCT </it>in Europeans.</p> <p>Conclusion</p> <p>Diversity patterns clearly evidence adaptive selection in pigmentation genes in Africans and Asians. In Europeans, the evidence is more complex, and both directional and balancing selection may be involved in light skin. As a result, different non-African populations may have acquired light skin by alternative ways, and so light skin, and perhaps dark skin too, may be the result of convergent evolution.</p

BRAF V600E mutational load as a prognosis biomarker in malignant melanoma

Analyzing the mutational load of driver mutations in melanoma could provide valuable information regarding its progression. We aimed at analyzing the heterogeneity of mutational load of BRAF V600E in biopsies of melanoma patients of different stages, and investigating its potential as a prognosis factor. Mutational load of BRAF V600E was analyzed by digital PCR in 78 biopsies of melanoma patients of different stages and 10 nevi. The BRAF V600E load was compared among biopsies of different stages. Results showed a great variability in the load of V600E (0%-81%). Interestingly, we observed a significant difference in the load of V600E between the early and late melanoma stages, in the sense of an inverse correlation between BRAF V600E mutational load and melanoma progression. In addition, a machine learning approach showed that the mutational load of BRAF V600E could be a good predictor of metastasis in stage II patients. Our results suggest that BRAF V600E is a promising biomarker of prognosis in stage II patients.This research was supported by the Basque Government (grants ELKARTEK-KK2016-036 and KK2017-041 to MDB, grant IT1138-16 to SA and predoctoral fellowship PRE_2014_1_419 to AS), and by the University of the Basque Country (UPV/EHU) (grant GIU17/066). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

¿Quiénes son los padres del niño abandonado?

Capítulo 9 del libro: Guisasola, Jenaro ; Garmendia, Mikel (eds.) "Aprendizaje basado en problemas, proyectos y casos: diseño e implementación de experiencias en la universidad" (ISBN: 978-84-9860-959-2)Este capítulo corresponde a un diseño ABP para Genética Humana (Biología)

El Inventario de conceptos como instrumento para definir el perfil de ingreso en la universida

El Bachillerato debería propiciar en los nuevos universitarios un perfil de ingreso (PI) adecuado para el desarrollo de los procesos formativos subsiguientes. Las Olimpiadas Científicas acogen a los mejores estudiantes de Bachillerato por comunidades, por lo que constituyen un excepcional exponente del PI de los mejores estudiantes. Con esta hipótesis y mediante un Inventario de Conceptos, hemos definido un “perfil máximo” de los participantes, indicativo de las materias cursadas en la mayoría de los centros, y por tanto comunes al PI del estudiante medio. Las carencias en este perfil señalarían las materias susceptibles de incidencia formativa especial en los primeros cursos de Universida

La Iniciación a la experimentación: una oportunidad para abordar el trabajo fin de grado de manera colaborativa e integradora

En la UPV/EHU, el Trabajo Fin de Grado (TFG) en Biología se ha estructurado en dos etapas secuenciales: el Módulo I, de iniciación a la experimentación; y el Módulo II, correspondiente a un trabajo individual. En esta comunicación se presenta el trabajo que un grupo de profesores de las áreas de Genética, Biología Celular y Antropología Física hemos desarrollado para diseñar, implementar y valorar la calidad, en términos de aprendizaje, de una propuesta formativa transversal y original desarrollada para el Módulo I del Grado en Biología (GBIOL), basada en la realización de un proyecto experimental enmarcado en la especialidad denominada Biología Celular, Molecular y Genética (BIOCELMOLGEN

Comparison of the Transcriptional Profiles of Melanocytes from Dark and Light Skinned Individuals under Basal Conditions and Following Ultraviolet-B Irradiation

We analysed the whole-genome transcriptional profile of 6 cell lines of dark melanocytes (DM) and 6 of light melanocytes (LM) at basal conditions and after ultraviolet-B (UVB) radiation at different time points to investigate the mechanisms by which melanocytes protect human skin from the damaging effects of UVB. Further, we assessed the effect of different keratinocyte-conditioned media (KCM+ and KCM-) on melanocytes. Our results suggest that an interaction between ribosomal proteins and the P53 signaling pathway may occur in response to UVB in both DM and LM. We also observed that DM and LM show differentially expressed genes after irradiation, in particular at the first 6h after UVB. These are mainly associated with inflammatory reactions, cell survival or melanoma. Furthermore, the culture with KCM+ compared with KCM- had a noticeable effect on LM. This effect includes the activation of various signaling pathways such as the mTOR pathway, involved in the regulation of cell metabolism, growth, proliferation and survival. Finally, the comparison of the transcriptional profiles between LM and DM under basal conditions, and the application of natural selection tests in human populations allowed us to support the significant evolutionary role of MIF and ATP6V0B in the pigmentary phenotype.This work was supported by the former Spanish Ministerio de Ciencia e Innovacion, project CGL2008-04066/BOS to S.A.; by the Dept. Educacion, Universidades e Investigacion of the Basque Government, project IT542-10 to C.R.; the University of the Basque Country program UFI11/09; a predoctoral fellowship from the Dept. Educacion, Universidades e Investigacion of the Basque Government to S.L. (BFI09.248). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Proposed mechanism for the involvement of ribosomal proteins, MDM2 and p53 signaling pathway in the response to UVB irradiation.

<p>Proposed mechanism for the involvement of ribosomal proteins, MDM2 and p53 signaling pathway in the response to UVB irradiation.</p