Biometría histórica de los jóvenes varones castellanos. La incidencia en su estatura de los salarios y la nutrición, 1858-1959 / Historical biometrics of young Castilian males: the impact of income and Nutrition on their height, 1858-1959

Antecedentes: los estudios antropométricos han permitido medir la evolución del bienestar en España y en perspectiva histórica, pero aún no se ha calculado el efecto preciso de los ingresos económicos en la talla. Objetivo: el propósito del este trabajo es identificar los periodos en la trayectoria vital de los jóvenes en los que las disponibilidades alimentación fueron más determinantes en su crecimiento físico. Resultados: el modelo estimado mediante mínimos cuadrados ordinarios demostraría que los ingresos salariales percibidos por sus progenitores por el joven varón en los tres primeros años de vida y los tres inmediatamente anteriores al comienzo de la adolescencia explican hasta un 60 % de su talla al cumplir los 18 años. Todos los coeficientes de los regresores de los modelos planteados son significativos al 0,99 %. Conforme a estos cálculos, el tipo de alimentación del joven en el periodo comprendido entre los 11 y los 14 años fue determinante en su proceso evolutivo. Adicionalmente, los cálculos presentan a las carencias alimentarias como el culpable de los recurrentes periodos de pérdida del bienestar, especialmente en la segunda mitad del siglo XIX. Conclusión: las carencias nutricionales causadas por los bajos salarios y la nutrición deficiente han obstaculizado secularmente el crecimiento físico de los jóvenes castellanos. (AU)

Background: anthropometric studies have made it possible to measure the evolution of well-being in Spain and under a historical perspective, but the precise effect of income on height has not yet been calculated. Objective: the purpose of this paper is to identify the periods in the life trajectory of young people in which food availability was the most important determinant of their physical growth. Results: the model estimated using ordinary least squares shows that the wage income received by the parents of the young male in the first three years of life and the three years immediately prior to the onset of adolescence explain up to 60 % of his height at the age of 18. All the coefficients of the regressors of the models presented are significant at 0.99 %. According to these calculations, the type of Nutrition received by the young person in the period between 11 to 14 years of age was a determining factor in his or her evolutionary process. In addition, the calculations show that food deficiencies were to blame for recurrent periods of loss of well-being, especially in the second half of the 19th century. Conclusion: Nutritional deficiencies caused by low wages and poor Nutrition have for centuries hampered the physical growth of Castilian youth. (AU)

[Historical biometrics of young Castilian males: the impact of income and nutrition on their height, 1858-1959]. / Biometría histórica de los jóvenes varones castellanos. La incidencia en su estatura de los salarios la nutrición, 1858-1959.

Introduction: Background: anthropometric studies have made it possible to measure the evolution of well-being in Spain and under a historical perspective, but the precise effect of income on height has not yet been calculated. Objective: the purpose of this paper is to identify the periods in the life trajectory of young people in which food availability was the most important determinant of their physical growth. Results: the model estimated using ordinary least squares shows that the wage income received by the parents of the young male in the first three years of life and the three years immediately prior to the onset of adolescence explain up to 60 % of his height at the age of 18. All the coefficients of the regressors of the models presented are significant at 0.99 %. According to these calculations, the type of nutrition received by the young person in the period between 11 to 14 years of age was a determining factor in his or her evolutionary process. In addition, the calculations show that food deficiencies were to blame for recurrent periods of loss of well-being, especially in the second half of the 19th century. Conclusion: nutritional deficiencies caused by low wages and poor nutrition have for centuries hampered the physical growth of Castilian youth.

Introducción: Antecedentes: los estudios antropométricos han permitido medir la evolución del bienestar en España y en perspectiva histórica, pero aún no se ha calculado el efecto preciso de los ingresos económicos en la talla. Objetivo: el propósito del este trabajo es identificar los periodos en la trayectoria vital de los jóvenes en los que las disponibilidades alimentación fueron más determinantes en su crecimiento físico. Resultados: el modelo estimado mediante mínimos cuadrados ordinarios demostraría que los ingresos salariales percibidos por sus progenitores por el joven varón en los tres primeros años de vida y los tres inmediatamente anteriores al comienzo de la adolescencia explican hasta un 60 % de su talla al cumplir los 18 años. Todos los coeficientes de los regresores de los modelos planteados son significativos al 0,99 %. Conforme a estos cálculos, el tipo de alimentación del joven en el periodo comprendido entre los 11 y los 14 años fue determinante en su proceso evolutivo. Adicionalmente, los cálculos presentan a las carencias alimentarias como el culpable de los recurrentes periodos de pérdida del bienestar, especialmente en la segunda mitad del siglo XIX. Conclusión: las carencias nutricionales causadas por los bajos salarios y la nutrición deficiente han obstaculizado secularmente el crecimiento físico de los jóvenes castellanos.

Control preconcepcional y diabetes gestacional. Revisión sistemática y estado del arte / Preconceptional control and gestational diabetes. Systematic review and state of the art

Introducción: La diabetes mellitus gestacional se manifiesta con una intolerancia a los carbohidratos, ocasionada por una alteración en la secreción de insulina, con descontrol de los niveles de glucosa en sangre, caracterizada por ser una condición temporal y que se desarrolla por primera vez durante el embarazo; suele desaparecer después del parto, pero puede desarrollarse diabetes mellitus en un futuro. Metodología: Se realizó un estudio investigativo tipo documental, sistematizada, descriptiva, prospectiva en un periodo de revisión de cinco años, del 2013 a 2018. Discusión: Entre los trastornos más comunes en el feto esta la macrostomia, posterior al nacimiento se puede desarrollar hipoglu-cemia. Por parte de la madre también se han documentado complicaciones que pueden percutir al momento del parto como la preeclampsia y el síndrome metabólico. Conclusiones: La diabetes gestacional puede cursar asintomática, por lo que se recomienda realizar pruebas de medición de glucosa en sangre durante las semanas 24 y 28 de gestación. Hay factores que pueden incrementar los riesgos de desarrollar diabetes gestacional, como: la edad avanzada de la madre, sobrepeso u obesidad, antecedentes familiares de diabetes mellitus, entre otros. Por lo tanto, someterse a la prueba de tamizaje sigue siendo el método más seguro de detección.

Introduction: Gestational diabetes mellitus manifests itself with a carbohydrate intolerance, caused by an alteration in insulin secretion, with uncontrolled blood glucose levels, characterized by being a temporary condition, which develops for the first time during pregnancy; It usually disappears after childbirth, although diabetes mellitus may develop later. Methodology: A documentary, systematic, descriptive, prospective research study was conducted in a five-year review period, from 2013 to 2018. Discussion: Among the most common disorders in the fetus is macrostomia, hypoglycemia may develop after birth. On the part of the mother complications have also been documented that can affect the moment of delivery such as preeclampsia and metabolic syndrome. Conclusions:Gestational diabetes can be asymptomatic, so it is recommended to perform blood glucose measu-rement tests during weeks 24 and 28 of gestation. There are factors that can increase the risks of developing gestational diabetes, such as: the mother's advanced age, overweight or obesity, family history of diabetes mellitus, among others. Therefore, undergoing the screening test remains the safest method of detection

Effect of soluble factors derived from ZR 75.30 breast cancer cells on endothelial activation.

In this study, we analyzed soluble factors secreted by two Estrogen Receptor Positive (ER-α) human breast cancer cell lines, ZR 75.30 (luminal B) and MCF7 (luminal A), and evaluated their effect on endothelial activation. The composition of tumoral soluble factors (TSFs) was analyzed by ELISA (Bio-Plex). TSFs from ZR 75.30 cells expressed higher levels of TNF, IFN-γ, IL-6, and IL-8 compared to TSFs from MCF-7 cells. TSFs from ZR 75.30 cells induced a pro-adhesive phenotype in human umbilical vein endothelial cells (HUVECs), as characterized by increased monocytic cell adhesion, adhesion molecule expression and NF-κB activation and decreased IκB-α expression. Conversely, TSFs from MCF-7 cells exerted none of these effects on HUVECs. We then added TNF, IFN-γ, IL-6 or IL-8 alone or in combination with TSFs from MCF-7 cells to HUVECs. Only the combinations that included TNF induced endothelial activation. A neutralizing antibody against IL-1ß (this cytokine was not measured in the ELISA) had a modest blocking effect on cellular adhesion or the expression of adhesion molecules induced by TSFs from ZR 75.30 cells in HUVECs. However neutralizing antibodies against TNF, IFN-γ, IL-6 or IL-8 had no effect. Our results suggest that although TNF is an inducer of endothelial cell activation, it is not the only molecule that is responsible for this effect in TSFs from ZR 75.30 cells.

Endothelial RhoGEFs: A systematic analysis of their expression profiles in VEGF-stimulated and tumor endothelial cells.

Rho guanine nucleotide exchange factors (RhoGEFs) integrate cell signaling inputs into morphological and functional responses. However, little is known about the endothelial repertoire of RhoGEFs and their regulation. Thus, we assessed the expression of 81 RhoGEFs (70 homologous to Dbl and 11 of the DOCK family) in endothelial cells. Further, in the case of DH-RhoGEFs, we also determined their responses to VEGF exposure in vitro and in the context of tumors. A phylogenetic analysis revealed the existence of four groups of DH-RhoGEFs and two of the DOCK family. Among them, we found that the most abundant endothelial RhoGEFs were: Tuba, FGD5, Farp1, ARHGEF17, TRIO, P-Rex1, ARHGEF15, ARHGEF11, ABR, Farp2, ARHGEF40, ALS, DOCK1, DOCK7 and DOCK6. Expression of RASGRF2 and PREX2 increased significantly in response to VEGF, but most other RhoGEFs were unaffected. Interestingly murine endothelial cells isolated from tumors showed that all four phylogenetic subgroups of DH-RhoGEFs were altered when compared to non-tumor endothelial cells. In summary, our results provide a detailed assessment of RhoGEFs expression profiles in the endothelium and set the basis to systematically address their regulation in vascular signaling.

Phosphatidylinositol 3,4,5-triphosphate-dependent Rac exchanger 1 (P-Rex-1), a guanine nucleotide exchange factor for Rac, mediates angiogenic responses to stromal cell-derived factor-1/chemokine stromal cell derived factor-1 (SDF-1/CXCL-12) linked to Rac activation, endothelial cell migration, and in vitro angiogenesis.

Stromal cell-derived factor-1 (SDF-1/CXCL-12) and vascular endothelial growth factor (VEGF), which can be secreted by hypoxic tumors, promote the generation of new blood vessels. These potent angiogenic factors stimulate endothelial cell migration via the activation of Rho GTPases and the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. Thus, characterization of guanine nucleotide exchange factors critical in the angiogenic signaling cascades offers the possibility of identifying novel molecular targets. We demonstrated previously that mammalian target of rapamycin, an important effector and regulator of PI3K/AKT, activates phosphatidylinositol 3,4,5-triphosphate-dependent Rac exchanger 1 (P-Rex1), a Rac guanine nucleotide exchange factor identified as a target of G betagamma and PI3K, via direct interactions. In this study, we tested the hypothesis that P-Rex1 is involved in the angiogenic responses elicited by SDF-1 and VEGF. Using a knockdown approach, we demonstrate that P-Rex1 is indeed required for SDF-1 promoted signaling pathway, because there is decreased Rac activation, cell migration, and in vitro angiogenesis in P-Rex1 knockdown cells stimulated with SDF-1. In contrast, P-Rex1 knockdown does not affect responses to VEGF, and signaling to extracellular signal-regulated kinase in response to either angiogenic factor is not sensitive to P-Rex1 knockdown. We also demonstrate that in endothelial cells, VEGF promotes an increase in the expression of endogenous P-Rex1 and the SDF-1 receptor CXCR4, In addition, VEGF-pretreated cells show an increased migratory and angiogenic response to SDF-1, suggesting that VEGF stimulation can complement SDF-1/CXCR4 signaling to induce angiogenesis. We conclude that P-Rex1 is a key element in SDF-1-induced angiogenic responses and a potential target for therapeutic intervention.

Differential inhibitor of Gbetagamma signaling to AKT and ERK derived from phosducin-like protein: effect on sphingosine 1-phosphate-induced endothelial cell migration and in vitro angiogenesis.

Differential inhibitors of Gbetagamma-effector regions are required to dissect the biological contribution of specific Gbetagamma-initiated signaling pathways. Here, we characterize PhLP-M1-G149, a Gbetagamma-interacting construct derived from phosducin-like protein 1 (PhLP) as a differential inhibitor of Gbetagamma, which, in endothelial cells, prevented sphingosine 1-phosphate-induced phosphorylation of AKT, glycogen synthase kinase 3beta, cell migration, and tubulogenesis, while having no effect on ERK phosphorylation or hepatocyte growth factor-dependent responses. This construct attenuated the recruitment of phosphoinositide 3-kinase gamma (PI3Kgamma) to the plasma membrane and the signaling to AKT in response to Gbetagamma overexpression. In coimmunoprecipitation experiments, PhLP-M1-G149 interfered with the interaction between PI3Kgamma and Gbetagamma. Other PhLP-derived constructs interacted with Gbetagamma but were not effective inhibitors of Gbetagamma signaling to AKT or ERK. Our results indicate that PhLP-M1-G149 is a suitable tool to differentially modulate the Gbetagamma-initiated pathway linking this heterodimer to AKT, endothelial cell migration, and in vitro angiogenesis. It can be also useful to further characterize the molecular determinants of the Gbetagamma-PI3Kgamma interaction.

P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration.

Polarized cell migration results from the transduction of extra-cellular cues promoting the activation of Rho GTPases with the intervention of multidomain proteins, including guanine exchange factors. P-Rex1 and P-Rex2 are Rac GEFs connecting Gbetagamma and phosphatidylinositol 3-kinase signaling to Rac activation. Their complex architecture suggests their regulation by protein-protein interactions. Novel mechanisms of activation of Rho GTPases are associated with mammalian target of rapamycin (mTOR), a serine/threonine kinase known as a central regulator of cell growth and proliferation. Recently, two independent multiprotein complexes containing mTOR have been described. mTORC1 links to the classical rapamycin-sensitive pathways relevant for protein synthesis; mTORC2 links to the activation of Rho GTPases and cytoskeletal events via undefined mechanisms. Here we demonstrate that P-Rex1 and P-Rex2 establish, through their tandem DEP domains, interactions with mTOR, suggesting their potential as effectors in the signaling of mTOR to Rac activation and cell migration. This possibility was consistent with the effect of dominant-negative constructs and short hairpin RNA-mediated knockdown of P-Rex1, which decreased mTOR-dependent leucine-induced activation of Rac and cell migration. Rapamycin, a widely used inhibitor of mTOR signaling, did not inhibit Rac activity and cell migration induced by leucine, indicating that P-Rex1, which we found associated to both mTOR complexes, is only active when in the mTORC2 complex. mTORC2 has been described as the catalytic complex that phosphorylates AKT/PKB at Ser-473 and elicits activation of Rho GTPases and cytoskeletal reorganization. Thus, P-Rex1 links mTOR signaling to Rac activation and cell migration.

AMSH regulates calcium-sensing receptor signaling through direct interactions.

Calcium-sensing receptor (CaR) activates intracellular pathways controlling calcium homeostasis. CaR carboxyl-terminal mutants associated with metabolic diseases suggest that unidentified proteins interact with the carboxyl-terminal region of this receptor. To address this possibility, we screened for CaR-interacting proteins using the carboxyl terminus of CaR (CaRDelta895-1075 deletion mutant). We identified AMSH, an ubiquitin isopeptidase, as a CaR-interacting partner. AMSH caused a decrease on the signaling properties of wild-type and mutant CaR. Our results indicate that AMSH, which has been recently characterized as a regulator of the endosomal sorting of epidermal growth factor receptor, represents a novel modulator of CaR signaling.