Unraveling the Conformational Determinants of Peptide Dendrimers Using Molecular Dynamics Simulations

Peptide dendrimers are synthetic tree-like molecules composed of amino acids. There are at least two kinds of preferential structural behaviors exhibited by these molecules, which acquire either compact or noncompact shapes. However, the key structural determinants of such behaviors remained, until now, unstudied. Herein, we conduct a comprehensive investigation of the structural determinants of peptide dendrimers by employing long molecular dynamics simulations to characterize an extended set of third generation dendrimers. Our results clearly show that a trade-off between electrostatic effects and hydrogen bond formation controls structure acquisition in these systems. Moreover, by selectively changing the dendrimers charge we are able to manipulate the exhibited compactness. In contrast, the length of branching residues does not seem to be a major structural determinant. Our results are in accordance with the most recent experimental evidence and shed some light on the key molecular level interactions controlling structure acquisition in these systems. Thus, the results presented constitute valuable insights that can contribute to the development of truly tailor-made dendritic systems.

Motivación del personal de enfermería relacionado con la atención a pacientes con EPOC que requieren ventilación mecánica no invasiva

La presente investigación se realiza en el servicio de Terapia Intensiva del Hospital Luis C. Lagomaggiore e intenta demostrar la importancia de recuperar la motivación del personal de enfermería que trabaja con los pacientes con EPOC ventilados mediante VNI (ventilación no invasiva) aspecto que redunda directamente en la calidad de vida y atención de los pacientes. Los objetivos específicos de este estudio son: identificar los aspectos principales del rol de enfermería en la asistencia de los pacientes con EPOC; identificar los factores que influyen en la motivación del personal y relacionar los factores de motivación con el desempeño laboral.

Connexin-43 prevents hematopoietic stem cell senescence through transfer of reactive oxygen species to bone marrow stromal cells

Hematopoietic stem cell (HSC) aging has become a concern in chemotherapy of older patients. Humoral and paracrine signals from the bone marrow (BM) hematopoietic microenvironment (HM) control HSC activity during regenerative hematopoiesis. Connexin-43 (Cx43), a connexin constituent of gap junctions (GJs) is expressed in HSCs, down-regulated during differentiation, and postulated to be a self-renewal gene. Our studies, however, reveal that hematopoietic-specific Cx43 deficiency does not result in significant long-term competitive repopulation deficiency. Instead, hematopoietic Cx43 (H-Cx43) deficiency delays hematopoietic recovery after myeloablation with 5-fluorouracil (5-FU). 5-FU-treated H-Cx43-deficient HSC and progenitors (HSC/P) cells display decreased survival and fail to enter the cell cycle to proliferate. Cell cycle quiescence is associated with down-regulation of cyclin D1, up-regulation of the cyclin-dependent kinase inhibitors, p21cip1. and p16INK4a, and Forkhead transcriptional factor 1 (Foxo1), and activation of p38 mitogen-activated protein kinase (MAPK), indicating that H-Cx43-deficient HSCs are prone to senescence. The mechanism of increased senescence in H-Cx43-deficient HSC/P cells depends on their inability to transfer reactive oxygen species (ROS) to the HM, leading to accumulation of ROS within HSCs. In vivo antioxidant administration prevents the defective hematopoietic regeneration, as well as exogenous expression of Cx43 in HSC/P cells. Furthermore, ROS transfer from HSC/P cells to BM stromal cells is also rescued by reexpression of Cx43 in HSC/P. Finally, the deficiency of Cx43 in the HM phenocopies the hematopoietic defect in vivo. These results indicate that Cx43 exerts a protective role and regulates the HSC/P ROS content through ROS transfer to the HM, resulting in HSC protection during stress hematopoietic regeneration.

Connexin-43 in the osteogenic BM niche regulates its cellular composition and the bidirectional traffic of hematopoietic stem cells and progenitors

Connexin-43 (Cx43), a gap junction protein involved in control of cell proliferation, differentiation and migration, has been suggested to have a role in hematopoiesis. Cx43 is highly expressed in osteoblasts and osteogenic progenitors (OB/P). To elucidate the biologic function of Cx43 in the hematopoietic microenvironment (HM) and its influence in hematopoietic stem cell (HSC) activity, we studied the hematopoietic function in an in vivo model of constitutive deficiency of Cx43 in OB/P. The deficiency of Cx43 in OB/P cells does not impair the steady state hematopoiesis, but disrupts the directional trafficking of HSC/progenitors (Ps) between the bone marrow (BM) and peripheral blood (PB). OB/P Cx43 is a crucial positive regulator of transstromal migration and homing of both HSCs and progenitors in an irradiated microenvironment. However, OB/P Cx43 deficiency in nonmyeloablated animals does not result in a homing defect but induces increased endosteal lodging and decreased mobilization of HSC/Ps associated with proliferation and expansion of Cxcl12-secreting mesenchymal/osteolineage cells in the BM HM in vivo. Cx43 controls the cellular content of the BM osteogenic microenvironment and is required for homing of HSC/Ps in myeloablated animals

Puente ferroviario sobre el Arroyo del Molino (Burgos)

El objeto del presente Proyecto es la definición del puente que servirá para que la vía del ferrocarril, pueda salvar el Arroyo del Molino a la altura del pk 9+200 del tramo Fresno de Rodilla - Quintanavides. Este tramo, a su vez, forma parte de la línea de alta velocidad Valladolid - Burgos - Vitoria. La nueva Línea de Alta Velocidad está incluida dentro de la red de altas prestaciones del Plan Estratégico de Infraestructuras y Transporte (PEIT) del Ministerio de Fomento para el periodo 2005-2020. Este recorrido discurre por los términos municipales de Fresno de Rodilla, Santa María del Invierno, Monasterio de Rodilla, Santa Olalla de Bureba y Quintanavides con una longitud de 8,2 km. La estructura objeto de estudio es un puente de un sólo vano de 38 metros de luz entre apoyos que salva el arroyo del Molino y un camino que discurre próximo a dicho arroyo. La solución propuesta consiste en un tablero formado por una artesa de hormigón prefabricado sobre la que se construye la losa de hormigón «in situ». Dicho tablero se apoya, a través de cuatro aparatos de tipo «pot» sobre sendos estribos de hormigon armado cimentados sobre pilotes. Estos estribos están dotados de muros en vuelta que sirven para contener el derrame del terraplén. El tablero se completa con las aceras, compuesta cada una de ellas por una imposta prefabricada anclada y una banda de 15 cm de hormigón «in situ», dos canaletas para cables de comunicaciones, los muretes guardabalasto, las juntas de dilatación en estribos y los anclajes para postes de las catenarias, dispuestos conforme a los diseños normalizados respectivos.

Oracion fúnebre de Luis XVI, rey de Francia y de Navarra

Sign.: [A]12

Oracion funebre, que en las exequias, hechas por los comerciantes franceses establecidos en la Ciudad de Valencia, al difunto rey de Francia Luis XV de Borbon ... de 1774 en el Convento de los Minimos ...

Sign. : A-C4

Glutathione biosynthesis in Arabidopsis trichome cells

In Arabidopsis thaliana, trichome cells are specialized unicellular structures with uncertain functions. Based on earlier observations that one of the genes involved in cysteine biosynthesis (Atcys-3A) is highly expressed in trichomes, we have extended our studies in trichome cells to determine their capacity for glutathione (GSH) biosynthesis. First, we have analyzed by in situ hybridization the tissue-specific expression of the genes Atcys-3A and sat5, which encode O-acetylserine(thio)lyase (OASTL) and serine acetyltransferase (SAT), respectively, as well as gsh1 and gsh2, which encode γ-glutamylcysteine synthetase and glutathione synthetase, respectively. The four genes are highly expressed in leaf trichomes of Arabidopsis, and their mRNA accumulate to high levels. Second, we have directly measured cytoplasmic GSH concentration in intact cells by laser-scanning microscopy after labeling with monochlorobimane as a GSH-specific probe. From these measurements, cytosolic GSH concentrations of 238 ± 25, 80 ± 2, and 144 ± 19 μM were estimated for trichome, basement, and epidermal cells, respectively. Taking into account the volume of the cells measured using stereological techniques, the trichomes have a total GSH content more than 300-fold higher than the basement and epidermal cells. Third, after NaCl treatment, GSH biosynthesis is markedly decreased in trichomes. Atcys-3A, sat5, gsh1, and gsh2 mRNA levels show a decrease in transcript abundance, and [GSH]cyt is reduced to 47 ± 5 μM. These results suggest the important physiological significance of trichome cells related to GSH biosynthesis and their possible role as a sink during detoxification processes.

Por el Atajo...

Poems.

Los recursos naturales de la Tierra del Fuego.

At head of title: Republica Argentina. Ministerio del Interior. Dirección General de Territorios Nacionales.

Peptidomic approach identifies cruzioseptins, a new family of potent antimicrobial peptides in the splendid leaf frog, Cruziohyla calcarifer

Phyllomedusine frogs are an extraordinary source of biologically active peptides. At least 8 families of antimicrobial peptides have been reported in this frog clade, the dermaseptins being the most diverse. By a peptidomic approach, integrating molecular cloning, Edman degradation sequencing and tandem mass spectrometry, a new family of antimicrobial peptides has been identified in Cruziohyla calcarifer. These 15 novel antimicrobial peptides of 20–32 residues in length are named cruzioseptins. They are characterized by having a unique shared N-terminal sequence GFLD– and the sequence motifs –VALGAVSK– or –GKAAL(N/G/S) (V/A)V– in the middle of the peptide. Cruzioseptins have a broad spectrum of antimicrobial activity and low haemolytic effect. The most potent cruzioseptin was CZS-1 that had a MIC of 3.77 μM against the Gram positive bacterium, Staphylococcus aureus and the yeast Candida albicans. In contrast, CZS-1 was 3–fold less potent against the Gram negative bacterium, Escherichia coli (MIC 15.11 μM). CZS-1 reached 100% haemolysis at 120.87 μM. Skin secretions from unexplored species such as C. calcarifer continue to demonstrate the enormous molecular diversity hidden in the amphibian skin. Some of these novel peptides may provide lead structures for the development of a new class of antibiotics and antifungals of therapeutic use.

Aplicación de la econometría espacial para el análisis de la miseria en los municipios del Departamento de Antioquia.

Este artículo comprueba la existencia de autocorrelación espacial al considerar la proporción de personas que viven en situación de miseria en los municipios del departamento de Antioquia, Colombia. Para ello se utiliza el test I de Moran y se propone un algoritmo para descartar la posibilidad de que la dependencia espacial sea espuria. Los resultados demuestran la necesidad de tener en cuenta la econometría espacial para determinar la asignación óptima del gasto social, destinado a intervenir en forma efectiva la situación de miseria en los municipios del departamento de Antioquia

A Física aplicada à qualidade alimentar: identificação de metais por “pixe” em castanhas

A concentração na castanha de minerais como o cálcio, potássio, o magnésio e outros tem sido estudada tradicionalmente por absorção atómica ou por espectrofotometria de UV-VIS [1-2]. Neste trabalho foi estudada a composição elementar de duas variedades (Longal e Judia) de castanha europeia (Castanea sativa Mill.) com a técnica PIXE (Proton Induced X-ray Emission). Os resultados preliminares mostram que a composição difere de acordo com a variedade, nos elementos maioritários e nos minoritários. Este estudo é parte de um projecto mais amplo, que visa avaliar o efeito do processamento pós-colheita de alimentos com feixe de electrões e raios-X.