Reduced retinal deficits in an albino mammal with a cone rich retina: A study of the ganglion cell layer at the area centralis of pigmented and albino grey squirrels

In all albino mammals studied the central retina is underdeveloped and there is a rod deficit. Central ganglion cell density is ∼25% below normal. This is not seen in birds, which have a cone dominated retina. Here we examine the ganglion cell layer in a cone rich mammal, the squirrel Sciurus carolinensis leucotis. Central cell densities were only < 5% lower in the albinos than in pigmented squirrels. Squirrels are the only known albino mammal to survive successfully in the wild, reinforcing the notion that their visual deficits are minor. The relative immunity of these albino retinae from this deficits may be related to different patterns of cell production between rod and cone dominated eyes

Representing youth migration. Comparative study of its symbolic imaginary on television and digital social networks

El artículo describe las dinámicas de creación de identidades que se fusionan entre las personas jóvenes que han emigrado a Londres en busca de trabajo. Se analizan los discursos y los imaginarios que se desprenden de los medios de comunicación generalistas y de las auto-representaciones que hacen los propios jóvenes de su éxodo. El objetivo del trabajo es entender cómo se negocia la identidad en un contexto mundial interconectado entre sí, arbitrado por las representaciones mediáticas y en el que el Estado-nación ha dejado de tener el monopolio de la construcción de las imágenes identitarias.This article describes the identity creation that emerges among young people who have emigrated to London searching for work. The discourse and imaginary arising from the general media and self-representations of young people are analysed, with a view to understanding how identity is negotiated in an interconnected global context, with media arbitration and where the nation state has lost its monopoly over the construction of images of identity

Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice

DYRK1A is the human orthologue of the Drosophila minibrain (mnb) gene, which is involved in postembryonic neurogenesis in flies. Because of its mapping position on chromosome 21 and the neurobehavioral alterations shown by mice overexpressing this gene, involvement of DYRK1A in some of the neurological defects of Down syndrome patients has been suggested. To gain insight into its physiological role, we have generated mice deficient in Dyrk1A function by gene targeting. Dyrk1A(−/−) null mutants presented a general growth delay and died during midgestation. Mice heterozygous for the mutation (Dyrk1A(+/−)) showed decreased neonatal viability and a significant body size reduction from birth to adulthood. General neurobehavioral analysis revealed preweaning developmental delay of Dyrk1A(+/−) mice and specific alterations in adults. Brains of Dyrk1A(+/−) mice were decreased in size in a region-specific manner, although the cytoarchitecture and neuronal components in most areas were not altered. Cell counts showed increased neuronal densities in some brain regions and a specific decrease in the number of neurons in the superior colliculus, which exhibited a significant size reduction. These data provide evidence about the nonredundant, vital role of Dyrk1A and suggest a conserved mode of action that determines normal growth and brain size in both mice and flies

IGF-1R/epithelial-to-mesenchymal transition (EMT) crosstalk suppresses the erlotinib-sensitizing effect of EGFR exon 19 deletion mutations

Using non-small cell lung carcinoma (NSCLC) cells harboring the erlotinib-sensitizing Epidermal Growth Factor Receptor (EGFR) exon 19 mutation delE746-A750, we developed erlotinib-refractory derivatives in which hyperactive Insulin-like Growth Factor-1 Receptor (IGF-1R) signaling associated with enrichment in epithelial-to-mesenchymal transition (EMT)-related morphological and transcriptional features. We then explored whether an IGF-1R/EMT crosstalk was sufficient to promote erlotinib refractoriness in the absence of second-site EGFR mutations, MET and AXL hyperactivation. Transforming Growth Factor-beta1 (TGF beta 1)-induced mesenchymal trans-differentiation was sufficient to impede erlotinib functioning in the presence of drug-sensitive delE746-A750 EGFR mutation. Pharmacological blockade of IGF-1R fully prevented the TGF beta 1's ability to activate an EMT protein signature [E-cadherin low/vimentin high]. The sole presence of erlotinib was capable of rapidly activate an IGF-1R-dependent, vimentin-enriched mesenchymal-like phenotype in delE746-A750-mutated epithelial cells. Even if transient, NSCLC cells' intrinsic plasticity to undergo crosstalk between IGF-1R and EMT signaling pathways can sufficiently eliminate the erlotinib-sensitizing effect of highly prevalent EGFR mutations and suggests the urgent need for dual IGF-1R/EMT-targeting strategies to circumvent erlotinib resistance

Silibinin suppresses EMT-driven erlotinib resistance by reversing the high miR-21/low miR-200c signature in vivo

The flavolignan silibinin was studied for its ability to restore drug sensitivity to EGFR-mutant NSCLC xenografts with epithelial-to-mesenchymal transition (EMT)-driven resistance to erlotinib. As a single agent, silibinin significantly decreased the tumor volumes of erlotinib-refractory NSCLC xenografts by approximately 50%. Furthermore, the complete abrogation of tumor growth was observed with the co-treatment of erlotinib and silibinin. Silibinin fully reversed the EMT-related high miR-21/low miR-200c microRNA signature and repressed the mesenchymal markers SNAIL, ZEB, and N-cadherin observed in erlotinib-refractory tumors. Silibinin was sufficient to fully activate a reciprocal mesenchymal-to-epithelial transition (MET) in erlotinib-refractory cells and prevent the highly migratogenic phenotype of erlotinib-resistant NSCLC cells. Given that the various mechanisms of resistance to erlotinib result from EMT, regardless of the EGFR mutation status, a water-soluble, silibinin-rich milk thistle extract might be a suitable candidate therapy for upcoming clinical trials aimed at preventing or reversing NSCLC progression following erlotinib treatment