Bmp2 instructs cardiac progenitors to form the heart-valve-inducing field

AbstractA hallmark of heart-valve development is the swelling and deposition of extracellular matrix in the heart-valve region. Only myocardium overlying this region can signal to underlying endothelium and cause it to lose cell–cell contacts, delaminate, and invade the extracellular space abutting myocardium and endocardium to form endocardial cushions (EC) in a process known as epithelial to mesenchymal transformation (EMT). The heart-valve myocardium expresses bone morphogenetic protein-2 (Bmp2) coincident with development of valve mesenchyme. BMPs belong to the transforming growth factor beta superfamily (TGF-β) and play a wide variety of roles during development. We show that conditional ablation of Bmp2 in cardiac progenitors results in cell fate changes in which the heart-valve region adopts the identity of differentiated chamber myocardium. Moreover, Bmp2-deficient hearts fail to induce production and deposition of matrix at the heart-valve-forming region, resulting in the inability of the endothelium to swell and impairing the development of ECs. Furthermore, in collagen invasion assays, Bmp2 mutant endothelium is incapable of undergoing EMT, and addition of BMP2 protein to mutant heart explants rescues this phenotype. Our results demonstrate that Bmp2 is both necessary and sufficient to specify a field of cardiac progenitor cells as the heart-valve-inducing region amid developing atria and ventricles

Contrasting Ordovician high- and low-pressure metamorphism related to a microcontinent-arc collision in the Eastern Cordillera of Perú (Tarma province)

High-pressure conditions of 11–13 kbar/500–540 °C during maximum burial were derived for garnet amphibolite in the Tapo Ultramafic Massif in the Eastern Cordillera of Peru using a PT pseudosection approach. A Sm–Nd mineral-whole rock isochron at 465 ± 24 Ma dates fluid influx at peak temperatures of ~600 °C and the peak of high pressure metamorphism in a rodingite of this ultramafic complex. The Tapo Ultramafic Complex is interpreted as a relic of oceanic crust which was subducted and exhumed in a collision zone along a suture. It was buried under a metamorphic geotherm of 12–13 °C/km during collision of the Paracas microcontinent with an Ordovician arc in the Peruvian Eastern Cordillera. The Ordovician arc is represented by the western Marañon Complex. Here, low PT conditions at 2.4–2.6 kbar, 300–330 °C were estimated for a phyllite–greenschist assemblage representing a contrasting metamorphic geotherm of 32–40 °C/km characteristic for a magmatic arc environment

Diseño de estructura de pavimento articulado por medio del método AASHTO 93 para 1 km del tramo empalme El Naranjo –empalme Sabana Larga y El Quebracho, comarca Santa Cruz, municipio de Estelí.

El estudio presenta el diseño de la estructura de pavimento articulado por medio del método AASHTO 93 para 1 km del tramo Empalme el Naranjo – Empalme Sabana larga y el Quebracho, comarca Santa Cruz, municipio de Estelí

Distinct Compartments of the Proepicardial Organ Give Rise to Coronary Vascular Endothelial Cells

SummaryThe proepicardial organ is an important transient structure that contributes cells to various cardiac lineages. However, its contribution to the coronary endothelium has been disputed, with conflicting data arising in chick and mouse. Here we resolve this conflict by identifying two proepicardial markers, Scleraxis (Scx) and Semaphorin3D (Sema3D), that genetically delineate heretofore uncharacterized proepicardial subcompartments. In contrast to previously fate-mapped Tbx18/WT-1-expressing cells that give rise to vascular smooth muscle, Scx- and Sema3D-expressing proepicardial cells give rise to coronary vascular endothelium both in vivo and in vitro. Furthermore, Sema3D+ and Scx+ proepicardial cells contribute to the early sinus venosus and cardiac endocardium, respectively, two tissues linked to vascular endothelial formation at later stages. Taken together, our studies demonstrate that the proepicardial organ is a molecularly compartmentalized structure, reconciling prior chick and mouse data and providing a more complete understanding of the progenitor populations that establish the coronary vascular endothelium

Identification and functional analysis of novel phosphorylation sites in the RNA surveillance protein Upf1.

One third of inherited genetic diseases are caused by mRNAs harboring premature termination codons as a result of nonsense mutations. These aberrant mRNAs are degraded by the Nonsense-Mediated mRNA Decay (NMD) pathway. A central component of the NMD pathway is Upf1, an RNA-dependent ATPase and helicase. Upf1 is a known phosphorylated protein, but only portions of this large protein have been examined for phosphorylation sites and the functional relevance of its phosphorylation has not been elucidated in Saccharomyces cerevisiae. Using tandem mass spectrometry analyses, we report the identification of 11 putative phosphorylated sites in S. cerevisiae Upf1. Five of these phosphorylated residues are located within the ATPase and helicase domains and are conserved in higher eukaryotes, suggesting a biological significance for their phosphorylation. Indeed, functional analysis demonstrated that a small carboxy-terminal motif harboring at least three phosphorylated amino acids is important for three Upf1 functions: ATPase activity, NMD activity and the ability to promote translation termination efficiency. We provide evidence that two tyrosines within this phospho-motif (Y-738 and Y-742) act redundantly to promote ATP hydrolysis, NMD efficiency and translation termination fidelity

Metalogenia asociada a los segmentos ofiolíticos de la Cordillera Oriental del Perú Central

Es bien conocida la aportación de las ofiolitas a la producción minera de sustancias como cromo y níquel (laterítico) o también rocas industriales, refractarios, asbestos, talco o sulfuros masivos, pero a pesar de constituir metalotectos de indudale importancia no suelen recibir la atención debida y, en general, se desconoce su significado como metalotecto de MP, metales preciosos (oro y EGP o elementos del grupo del platino). Por otra parte, raramente se habla de la exploración de terrenos ofiolíticos como estrategia minera, a pesar de las evidencias existentes, por ejemplo para oro (Ash et al., 1991, Ash, 2001, Castroviejo, 2004) o, en general, para MP (Pereira et al., 2004). A ello han contribuido, con toda probabilidad, las dificultades que entraña el reconocimiento y la investigación de terrenos ofiolíticos, por las que diversos yacimientos ofiolíticos no fueron reconocidos como tales hasta la realización de estudios específicos, como ahora ha ocurrido (Tapo). En este resumen se hará en primer lugar una breve exposición de algunos conceptos básicos acerca de la metalogenia y exploración de terrenos ofiolíticos. A continuación, se hará una aplicación de los mismos a las ofiolitas conocidas en la Cordillera Oriental del Perú (Deptºs. Junín y Huánuco), sintetizando los resultados de los trabajos realizados a la fecha, a partir de la información básica (cartografía, geología) presentada en este simposio (en especial, por JF Rodrigues y cols)

Developmental Bias in Cleavage-Stage Mouse Blastomeres

The cleavage stage mouse embryo is composed of superficially equivalent blastomeres that will generate both the embryonic inner cell mass (ICM) and the supportive trophectoderm (TE). However, it remains unsettled whether the contribution of each blastomere to these two lineages can be accounted for by chance. Addressing the question of blastomere cell fate may be of practical importance, as preimplantation genetic diagnosis (PGD) requires removal of blastomeres from the early human embryo. To determine if blastomere allocation to the two earliest lineages is random, we developed and utilized a recombination-mediated, non-invasive combinatorial fluorescent labeling method for embryonic lineage tracing

Labranza, propiedades físicas de una arcilla y los rendimientos de plátano y batata

The only physical property of Coto clay found to be affected by the tillage method was soil resistance, which was greater for the no-till than for the other tillage treatments. The upper 10 cm were the most affected. Tillage methods did not affect plantain yields; thus, minimum tillage can be recommended for this crop.  On the other hand, significantly higher sweet potato yields were obtained when the soil was plowed and disced twice.Se midieron los efectos de 4 métodos de labranza sobre las propiedades físicas del suelo Coto (Oxisol) y los rendimientos de plátano y batata. Los tratamientos fueron los siguientes: 1) sin labranza; 2) arado y rastrillado 2 veces a 15 cm. cada semana; 3) arado y rastrillado 4 veces a 45 cm. cada semana; y 4) labrado con arado de cinceles una sola vez a 45 cm. Los datos de las propiedades físicas del suelo se tomaron a las 1, 12, 24 y 40 semanas después de sembrar a profundidades de 0-10, 10-20 y 20-30 cm. Se midió el pH, la materia orgánicca, la estabilidad de los agregados, la densidad aparente del suelo, la resistencia a la penetración y el contenido de humedad. La labranza no afectó significativamente ninguna de las propiedades físicas, excepto la resistencia a la penetración, la que fue mayor en el tratamiento sin labranza. Los primeros 10 cm. de profundidad fueron los más afectados. La labranza no mejoró los rendimientos de plátano, lo cual indica que en un Oxisol se pueden obtener buenos rendimientos de este cultivo con la labranza mínima. Por el contrario, los mayores rendimientos de batata se obtuvieron cuando se labró convencionalmente, lo que indica que en este Oxisol, y quizás en otros suelos de condiciones similares, es necesario arar el suelo para obtener buenos rendimientos. Aparentemente, en los Oxisol, la resistencia a la penetración es un mejor índice de la compactación que la densidad aparente

Apocynin combined with drugs as coadjuvant could be employed to prevent and/or treat the chronic kidney disease

A worldwide public health problem is chronic kidney disease (CKD) presenting alarming epidemiological data. It currently affects about 10% of the adult population worldwide and has a high mortality rate. It is now known that oxidative stress represents one of the most important mechanisms in its pathophysiology, from the early stages to the terminal phase. Oxidation increases inflammation and reduces the capacity of NO• to relax vascular smooth muscle, in part by decreasing bioavailability of tetrahydrobiopterin (BH4), leading to endothelial dysfunction and high blood pressure, and due to the limited effectiveness of existing treatments, new drugs are needed to prevent and/or treat these mechanisms. The aim of this study was to test apocynin in a 5/6 nephrectomy mouse model of CKD to investigate whether its known antioxidant effect can improve the disease outcome. This effect results from the inhibition of NADPH oxidase and consequently a reduced production of the superoxide anion (). Animals were divided into five groups: sham, 5/6 nephrectomy only, and 5/6 nephrectomy followed by treatment with captopril, losartan or apocynin. The parameters evaluated were blood pressure and markers of oxidative stress () and endothelial function (BH4). There were significantly lower levels of and a greater availability of serum BH4 in the apocynin-treated animals versus the control group and the two other drug treatments. The present findings suggest that apocynin in conjunction with a coadjuvant for modulating blood pressure may be useful for controlling the progression of CRF

The role of HuR in the post-transcriptional regulation of interleukin-3 in T cells.

Human Interleukin-3 (IL-3) is a lymphokine member of a class of transiently expressed mRNAs harboring Adenosine/Uridine-Rich Elements (ARE) in their 3' untranslated regions (3'-UTRs). The regulatory effects of AREs are often mediated by specific ARE-binding proteins (ARE-BPs). In this report, we show that the human IL-3 3'-UTR plays a post-transcriptional regulation role in two human transformed cell lines. More specifically, we demonstrate that the hIL-3 3'-UTR represses the translation of a luciferase reporter both in HeLa and Jurkat T-cells. These results also revealed that the hIL-3 3'-UTR-mediated translational repression is exerted by an 83 nt region comprised mainly by AREs and some non-ARE sequences. Moreover, electrophoretic mobility shift assays (EMSAs) and UV-crosslinking analysis show that this hIL-3 ARE-rich region recruits five specific protein complexes, including the ARE-BPs HuR and TIA-1. HuR binding to this ARE-rich region appears to be spatially modulated during T-cell activation. Together, these results suggest that HuR recognizes the ARE-rich region and plays a role in the IL-3 3'-UTR-mediated post-transcriptional control in T-cells