Human basophils activated by mast cell-derived IL-3 express retinaldehyde dehydrogenase-II and produce the immunoregulatory mediator retinoic acid

The vitamin A metabolite retinoic acid (RA) plays a fundamental role in cellular functions by activating nuclear receptors. Retinaldehyde dehydrogenase-II (RALDH2) creates localized RA gradients needed for proper embryonic development, but very little is known regarding its regulated expression in adults. Using a human ex vivo model of allergic inflammation by coincubating IgE receptor-activated mast cells (MCs) with blood basophils, we observed prominent induction of a protein that was identified as RALDH2 by mass spectroscopy. RALDH2 was selectively induced in basophils by MC-derived interleukin-3 (IL-3) involving PI3-kinase and NF-kappaB pathways. Importantly, neither constitutive nor inducible RALDH2 expression was detectable in any other human myeloid or lymphoid leukocyte, including dendritic cells. RA generated by RALDH2 in basophils modulates IL-3-induced gene expression in an autocrine manner, providing positive (CD25) as well as negative (granzyme B) regulation. It also acts in a paracrine fashion on T-helper cells promoting the expression of CD38 and alpha4/beta7 integrins. Furthermore, RA derived from IL-3-activated basophils provides a novel mechanism of Th2 polarization. Thus, RA must be viewed as a tightly controlled basophil-derived mediator with a high potential for regulating diverse functions of immune and resident cells in allergic diseases and other Th2-type immune responses.

Reconstituted high-density lipoprotein modulates activation of human leukocytes

An anti-inflammatory effect of reconstituted High Density Lipoprotein (rHDL) has been demonstrated in atherosclerosis and in sepsis models. An increase of adhesion molecules as well as tissue factor expression on endothelial cells in response to inflammatory or danger signals are attenuated by the treatment with rHDL. Here we show the inhibitory effect of rHDL on the activation of human leukocytes in a whole blood assay as well as on monocyte-derived human dendritic cells (DC). Multiplex analysis of human whole blood showed that phytohaemagglutinin (PHA)-induced secretion of the cytokines IL-1β, IL-1RA, IL-2R, IL-6, IL-7, IL-12(p40), IL-15 and IFN-α was inhibited. Furthermore, an inhibitory effect on the production of the chemokines CCL-2, CCL-4, CCL-5, CXCL-9 and CXCL-10 was observed. Activation of granulocytes and CD14+ monocytes by PHA is inhibited dose-dependently by rHDL shown as decreased up-regulation of ICAM-1 surface expression. In addition, we found a strong inhibitory effect of rHDL on toll-like receptor 2 (TLR2)- and TLR4-mediated maturation of DC. Treatment of DC with rHDL prevented the up-regulation of cell surface molecules CD80, CD83 and CD86 and it inhibited the TLR-driven activation of inflammatory transcription factor NF-κB. These findings suggest that rHDL prevents activation of crucial cellular players of cellular immunity and could therefore be a useful reagent to impede inflammation as well as the link between innate and adaptive immunity.

Evidence for extinct Cs-135 from Ba isotopes in Allende CAIs?

he abundance and distribution of isotopes throughout the Solar System can be used to constrain the number and type of nucleosynthetic events that contributed material to the early nebula. Barium is particularly well suited to quantifying the degree of isotope heterogeneity in the Solar System because it comprises seven stable isotopes that were synthesized by three different nucleosynthetic processes (s-, r-, and p-processes), all of which contributed material to the Solar System. There is also potential contribution to 135Ba from short-lived radioisotope 135Cs, conclusive evidence for which is yet to be reported. Four Allende (CV3) Ca,Al-rich inclusions (CAI 1, CAI 2, CAI 4, CAI 5) and one Allende dark inclusion (DI) were analyzed for Ba isotope variability. Two CAIs (CAI 2 and CAI 5) display 135Ba excesses that are not accompanied by 137Ba anomalies. Calcium–aluminum-rich inclusion 1 displays a 135Ba excess that is possibly coupled with a 137Ba excess, and the remaining refractory inclusions (CAI 2 and DI) have terrestrial Ba isotope compositions. These Ba isotope data are presented in conjunction with published whole rock Ba isotope data from individual Allende CAIs. The enrichment in 135Ba and absence of coupled 137Ba excesses in CAI 2 and CAI 5 is interpreted to indicate that the anomalies are not purely nucleosynthetic in origin but also contain contributions (16–48 ppm) from the decay of short-lived 135Cs. The majority of Allende CAIs studied to date may also have similar contributions from 135Cs on the basis of higher than expected 135Ba excesses if the Ba isotope anomalies were purely nucleosynthetic in origin. The 135Ba anomalies appear not to be coupled with superchondritic Cs/Ba, which may imply that the contribution to 135Ba did not occur via in situ decay of live 135Cs. However, it is feasible that the CAIs had a superchondritic Cs/Ba during decay of 135Cs, but Cs was subsequently removed from the system during aqueous alteration on the parent body. An alternative scenario is the potential existence of a transient high-temperature reservoir having superchondritic Cs/Ba in the early Solar System while 135Cs was extant, which enabled a radiogenic 135Ba signature to develop in some early condensates. The nucleosynthetic source of 135Cs can be determined by reconciling the predicted astrophysical 135Cs abundance with its measured abundance in meteorites. Further, the currently accepted initial 135Cs/133Cs of the Solar System, [135Cs/133Cs]0, may be underestimated because the spread of Cs/Ba among samples is small and the range of excess 135Ba is limited thus leading to inaccuracies when estimating [135Cs/133Cs]0. If the initial meteoritic abundance of 135Cs was indeed higher than is currently thought, the most probable stellar source of short-lived radioisotopes was a nearby core-collapse supernova and/or the Wolf–Rayet wind driven by its progenitor.

Desarrollo de un sistema automático de detección de disgrafías en niños de 4 a 5 años

La escritura es una actividad psicomotora muy importante en el desarrollo infantil. Tanto es así que su correcto aprendizaje condicionará el futuro de una persona, pues estará presente en todo tipo de situaciones cotidianas. La disgrafía es el término utilizado para referirse a los problemas relacionados con la escritura, y se manifiesta cuando la escritura de un determinado sujeto es ilegible o lenta como resultado de un aprendizaje fallido de los procesos motores de la escritura. Estos problemas intentan resolverse durante el desarrollo infantil mediante diferentes pruebas que miden las capacidades visomotoras de los niños basándose en criterios de forma (número y posición correcta de trazos). Sin embargo, a lo largo de los años estos criterios han demostrado no ser totalmente precisos en la detección prematura de posibles casos de disgrafía. Por ello, en este proyecto se ha desarrollado una aplicación que ayuda a ampliar la fiabilidad de los test actuales, utilizando un criterio cinemático. Esta aplicación, desarrollada para una tableta Android, muestra al niño una serie de figuras que él debe copiar en la tableta haciendo uso de un lápiz óptico. Los trazos registrados por la aplicación son analizados para valorar aspectos como la fluidez, continuidad y regularidad, ampliando así la fiabilidad de los test actuales, lo que permite desechar falsos positivos y detectar irregularidades que antes no podían ser detectadas. La aplicación desarrollada ha sido validada con un total de ocho niños de cuatro años y siete meses de media de edad, confirmando que cumple con las expectativas planteadas. ABSTRACT. Writing is a very important psychomotor activity in child development because it will be present in all kinds of everyday situations; therefore its proper learning will determine the future of the individual. Dysgraphia is the term used to refer to the problems related to writing, and it takes place when a particular person’s writing is unreadable or slow-moving as a result of a failed learning of writing motor processes. These problems are usually detected by different tests that measure children’s visual motor abilities based on shape criteria (correct number and position of strikes). However, over the years these criteria haven’t proved to be completely accurate in the early detection of possible cases of dysgraphia. Therefore, in this project is presented an application that extends the reliability of current test, using a kinematic approach. This application, developed for an Android tablet, displays a series of figures that the child must copy to the tablet by using a stylus. Strokes recorded by the application are then analyzed to assess aspects such as fluidity, continuity and regularity, expanding the reliability of the current test, discarding false positives created by the conventional criteria and detecting irregularities that previously could not be detected. The developed application has been validated with a total of eight children about four years and seven months in average age, confirming that the application fulfills the initial expectations.

Why Schumpeter's Creative Destruction? Everything has changed, so it is the same: Towards "Mode 3". ACES Working Paper (Report) No. 5, 2007

Of what value is examining creative destruction and diffusion theories that Schumpeter introduced to the world? A variety of factors causes economic changes, but he argued that entrepreneurial innovation was central. Today, even those who create new products and processes hardly know who Schumpeter was, or what he did. It is difficult to believe that his contributions are not more popularly recognized today. Schumpeter's theories are as valuable and important within the contemporary environment as they were when he wrote about them over four score or seventy years ago.

Histoire de la Révolution française /

Contiene: t. 2, t. 4, t. 5, t. 6, t. 7, t. 8, t.9, t. 10.

Histoire de la Révolution française /

Contiene: t. 1, t. 2, t. 4, t. 5, t. 6, t. 8, t.9, t. 10.

Historia de los Papas : crímenes, muertes, envenenamientos, parricidios, adulterios e incestos, cometidos por los romanos pontífices, desde San Pedro hasta nuestros días : inquiedades de la Corte romana ... /

Tomos 10 y 11 A. Ronchi, editor.

Field and depot maintenance manual : shop equipment, contact maintenance, truck mounted, set no. 3, (Southwest model SECM), serial no. S-3-628 through S-3-730 and (Davey model CMU-5), serial no. 33343 through 33343-234, FSN 4940-294-9518.

Includes index.

U.S. policy in the Persian Gulf : hearing before the Committee on Foreign Relations, United States Senate, One Hundred First Congress, second session ....

Item 1039-A, 1039-B (MF)