Antoni Gaudí (1852-1926): The manuscript of Reus

Many of Gaudí’s original documents (writings, drawings, etc.) were destroyed during the Spanish Civil War (1936–1939) when riots erupted in the architect’s studio located inside the Sagrada Família temple in Barcelona. Fortunately, surviving documents had been relocated long before to other places by architect Domènech Sugrañes Gras (1878–1938). Among those documents rescued was Gaudí’s notebook, also known as El manuscrit de Reus (The Manuscript of Reus), rediscovered by Catalan architect Cèsar Martinell (1888–1973) during the preparation of his book, Gaudí. His life, his theory, his work, published in 1967

Role of the single nucleotide polymorphism rs7903146 of TCF7L2 in inducing nonsense-mediated decay.

Background The single nucleotide polymorphism (SNP) rs7903146 (C/T), located in intron 4 of the transcription factor 7-like 2 gene (TCF7L2), has been associated with an increased risk of developing Type 2 Diabetes, although the molecular mechanism remain elusive. The TCF7L2 gene is alternatively spliced but an association between genotype and splice variants has not been shown convincingly. We hypothesized that a yet unknown extra exon, containing either the C or T genotype of the SNP rs7903146, could introduce a premature stop codon and consequently result in nonsense-mediated decay (NMD). Findings Running the sequences C and T of the SNP region in different servers we found that the two alleles could display differential recognition by splicing factors. The C variant showed the possible inclusion of an unknown exon. This unknown exon contained a stop codon and thus could induce NMD. We then determined that the splicing pattern in isolated mouse islets and MIN6 cells was similar to that in human pancreatic islets. Therefore, we used MIN6 cells to study the splicing of human intron 4: two mini-genes of intron 4 containing either the C/C genotype or the T/T genotype were transfected into MIN6 cells. Our constructs were spliced normally, excluding intron 4, but we did not observe the presence of an extra exon with either construct. Conclusions We found that an extra exon could theoretically exist, although we were not able to capture it in our model. A better model is needed to determine whether a theoretical extra exon can induce NMD

Quinoa (Chenopodium Quinoa Willd), from Nutritional Value to Potential Health Benefits: An Integrative Review

Chenopodium quinoa Willd, known as quinoa, has been cultivated and consumed by humans for the last 5,000-7,000 years. Quinoa was important to pre-Columbian Andean civilizations, as the Incas considered it a gift from their gods. Quinoa has potential health benefits and exceptional nutritional value: a high concentration of protein (all essential amino acids highly bioavailable), unsaturated fatty acids, a low glycemic index; vitamins, minerals and other beneficial compounds; it is also gluten-free; furthermore, quinoa is a sustainable food, as plants exhibit a carbon and water food print that is between 30 and 60 times lower than that of beef. Quinoa is easy to cook, has versatility in preparation, and could be cultivated in different environments. For these reasons, quinoa, previously considered a food of low social prestige, is now the focus of attention of many countries worldwide. However, few studies exist on quinoa or quinoa compounds, in vitro, in vivo and clinical trials, for assessing its potential clinical applications supported by strong scientific evidence; thus, there is a need for well-designed clinical trials and increased scientific research in this field

Differential transcriptional and post-translational transcription factor 7-like regulation among nondiabetic individuals and type 2 diabetic patients.

Human genetic studies have revealed that the T minor allele of single nucleotide polymorphism rs7903146 in the transcription factor 7-like 2 (TCF7L2) gene is strongly associated with an increased risk of diabetes by 30%-40%. Molecular and clinical studies are of great importance for understanding how this unique variation in TCF7L2 influences type 2 diabetes (T2D) onset and progression. At the molecular level, some studies have been performed in diabetic mice and pancreatic islets from healthy human donors. Whereas TCF7L2 mRNA levels are up-regulated in islets, protein levels are down-regulated. We performed studies on TCF7L2 splicing, mRNA expression, and protein levels in immortalized human lymphocytes from nondiabetic individuals and T2D patients carrying the C/C or the at-risk T/T genotype. Our results show differential expression of TCF7L2 splice variants between nondiabetic and T2D patients carrying the at-risk genotype, as well as differences in protein levels. Therefore, we investigated the regulation of splice variants, and our results propose that splicing of exon 4 is under control of the serine-arginine-rich factor transformer 2 β (TRA2B). Finally, we studied the endoplasmic reticulum stress pathways, looking for a posttranslational explanation. We saw a shift in the activation of these pathways between nondiabetic individuals and T2D patients carrying the at-risk genotype. These results suggest that, in human immortalized lymphocytes carrying the at-risk T/T genotype, first the differential expression of TCF7L2 splice variants implies a regulation, at least for exon 4, by TRA2B and second, the differential protein levels between both T/T carriers point to a different activation of endoplasmic reticulum stress pathways

Protein tyrosine phosphatase-1B modulates pancreatic β-cell mass

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin signalling pathway. It has been demonstrated that PTP1B deletion protects against the development of obesity and Type 2 Diabetes, mainly through its action on peripheral tissues. However, little attention has been paid to the role of PTP1B in β-cells. Therefore, our aim was to study the role of PTP1B in pancreatic β-cells. Silencing of PTP1B expression in a pancreatic β-cell line (MIN6 cells) reveals the significance of this endoplasmic reticulum bound phosphatase in the regulation of cell proliferation and apoptosis. Furthermore, the ablation of PTP1B is able to regulate key proteins involved in the proliferation and/or apoptosis pathways, such as STAT3, AKT, ERK1/2 and p53 in isolated islets from PTP1B knockout (PTP1B (-)/(-)) mice. Morphometric analysis of pancreatic islets from PTP1B (-)/(-) mice showed a higher β-cell area, concomitantly with higher β-cell proliferation and a lower β-cell apoptosis when compared to islets from their respective wild type (WT) littermates. At a functional level, isolated islets from 8 weeks old PTP1B (-)/(-) mice exhibit enhanced glucose-stimulated insulin secretion. Moreover, PTP1B (-)/(-) mice were able to partially reverse streptozotocin-induced β-cell loss. Together, our data highlight for the first time the involvement of PTP1B in β-cell physiology, reinforcing the potential of this phosphatase as a therapeutical target for the treatment of β-cell failure, a central aspect in the pathogenesis of Type 2 Diabete