Lung myofibroblasts are characterized by down-regulated cyclooxygenase-2 and its main metabolite, prostaglandin E2.

Background: Prostaglandin E2 (PGE2), the main metabolite of cyclooxygenase (COX), is a well-known anti-fibrotic agent. Moreover, myofibroblasts expressing a-smooth muscle actin (a-SMA), fibroblast expansion and epithelial-mesenchymal transition (EMT) are critical to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our aim was to investigate the expression of COX-2 and PGE2 in human lung myofibroblasts and establish whether fibroblast-myofibroblast transition (FMT) and EMT are associated with COX-2 and PGE2 down-regulation. Methods: Fibroblasts obtained from IPF patients (n = 6) and patients undergoing spontaneous pneumothorax (control,n = 6) and alveolar epithelial cell line A549 were incubated with TGF-b1 and FMT and EMT markers were evaluated. COX-2 and a-SMA expression, PGE2 secretion and cell proliferation were measured after IL-1b and PGE2 incubation. Results: Myofibroblasts from both control and IPF fibroblast cultures stimulated with IL-1b showed no COX-2 expression. IPF fibroblasts showed increased myofibroblast population and reduced COX-2 expression in response to IL-1b. TGF-b1 increased the number of myofibroblasts in a time-dependent manner. In contrast, TGF-b1 induced slight COX-2 expression at 4 h (without increase in myofibroblasts) and 24 h, but not at 72 h. Both IPF and control cultures incubated with TGF-b1 for 72 h showed diminished COX-2 induction, PGE2 secretion and a-SMA expression after IL-1b addition. The latter decreased proliferation in fibroblasts but not in myofibroblasts. A549 cells incubated with TGF-b1 for 72 h showed downregulated COX-2 expression and low basal PGE2 secretion in response to IL-1b. Immuno-histochemical analysis of IPF lung tissue showed no COX-2 immuno-reactivity in myofibroblast foci. Conclusions: Myofibroblasts are associated with COX-2 down-regulation and reduced PGE2 production, which could be crucial in IPF development and progression

Estudio de la rugosidad superficial de implantes dentales de titanio blastinizados mediante microscopía electrónica de barrido en 3D

Una de las actividades más importantes en el estudio de los implantes dentales de Ti c.p. se encuentra enfocada al uso de modificaciones superficiales mediante métodos físicos o químicos, debido a que ensayos in vivo han puesto de manifiesto que ciertas superficies rugosas producen una mejor fijación por osteoaposición de hueso que la correspondiente a superficies lisas, por lo que resulta necesario realizar una adecuada caracterización de la rugosidad de los mismos. Una gran variedad de tratamientos superficiales son utilizados para incrementar la rugosidad de los implantes dentales de Ti c.p.. De todos ellos, el más utilizado es el blastinizado. En éste, las partículas abrasivas son arrastradas por una corriente de aire hasta impactar con el material siendo algunas de las diferentes variables operativas del proceso el tamaño de partícula y la presión. Existe una gran variedad de parámetros que describen la topografía de las superficies entre los cuales se encuentran los grupos de parámetros de amplitud, híbridos y funcionales. La correcta elección de los parámetros más significativos dependerá de las características del tratamiento superficial utilizado y del objetivo del estudio realizado. En el presente trabajo se realiza una caracterización, por microscopía electrónica de barrido 3D, de la superficie de muestras de Ti c.p. sometidas a diferentes condiciones de blastinizado, proporcionadas por una empresa fabricante de implantes dentalesFil: Kang, Kyung W.. Universidad Nacional de La Plata. Facultad de ingenieria. Laboratorio de Investigaciones de Metalurgia Física; ArgentinaFil: Pereda, Maria D.. Universidad Nacional de La Plata. Facultad de ingenieria. Laboratorio de Investigaciones de Metalurgia Física; ArgentinaFil: Lemos, Adriana. Universidad Nacional de La Plata. Facultad de ingenieria. Laboratorio de Investigaciones de Metalurgia Física; ArgentinaFil: Bilmes, Pablo David. Universidad Nacional de La Plata. Facultad de ingenieria. Laboratorio de Investigaciones de Metalurgia Física; ArgentinaFil: Bonetto, Rita Dominga. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas; ArgentinaFil: Scarano, Mariano. Kinetical SRL Insumos Medicos; Argentin

Comparative study of nonlinear properties of EEG signals of a normal person and an epileptic patient

Background: Investigation of the functioning of the brain in living systems has been a major effort amongst scientists and medical practitioners. Amongst the various disorder of the brain, epilepsy has drawn the most attention because this disorder can affect the quality of life of a person. In this paper we have reinvestigated the EEGs for normal and epileptic patients using surrogate analysis, probability distribution function and Hurst exponent. Results: Using random shuffled surrogate analysis, we have obtained some of the nonlinear features that was obtained by Andrzejak \textit{et al.} [Phys Rev E 2001, 64:061907], for the epileptic patients during seizure. Probability distribution function shows that the activity of an epileptic brain is nongaussian in nature. Hurst exponent has been shown to be useful to characterize a normal and an epileptic brain and it shows that the epileptic brain is long term anticorrelated whereas, the normal brain is more or less stochastic. Among all the techniques, used here, Hurst exponent is found very useful for characterization different cases. Conclusions: In this article, differences in characteristics for normal subjects with eyes open and closed, epileptic subjects during seizure and seizure free intervals have been shown mainly using Hurst exponent. The H shows that the brain activity of a normal man is uncorrelated in nature whereas, epileptic brain activity shows long range anticorrelation.Comment: Keywords:EEG, epilepsy, Correlation dimension, Surrogate analysis, Hurst exponent. 9 page

Influence of common synaptic input to motor neurons on the neural drive to muscle in essential tremor

Tremor in essential tremor (ET) is generated by pathological oscillations at 4 to 12 Hz, likely originating at cerebello-thalamo-cortical pathways. However, the way in which tremor is represented in the output of the spinal cord circuitries is largely unknown because of the difficulties in identifying the behavior of individual motor units from tremulous muscles. By using novel methods for the decomposition of multichannel surface EMG, we provide a systematic analysis of the discharge properties of motor units in 9 ET patients, with concurrent recordings of EEG activity. This analysis allowed inferring the contribution of common synaptic inputs to motor neurons in ET. Motor unit short-term synchronization was significantly greater in ET patients than in healthy subjects. Further, the strong association between the degree of synchronization and the peak in coherence between motor unit spike trains at the tremor frequency indicated that the high synchronization levels were generated mainly by common synaptic inputs specifically at the tremor frequency. The coherence between EEG and motor unit spike trains demonstrated the presence of common cortical input to the motor neurons at the tremor frequency. Nonetheless, the strength of this input was uncorrelated to the net common synaptic input at the tremor frequency, suggesting a contribution of spinal afferents or secondary supraspinal pathways in projecting common input at the tremor frequency. These results provide the first systematic analysis of the neural drive to the muscle in ET and elucidate some of its characteristics that determine the pathological tremulous muscle activity.This work was funded by the EU Commission [grant number EU-FP7-2011-287739 (NeuroTREMOR)].Peer reviewe

A Fuzzy Inference System for Closed-Loop Deep Brain Stimulation in Parkinson’s Disease

Parkinsons disease is a complex neurodegenerative disorder for which patients present many symptoms, tremor being the main one. In advanced stages of the disease, Deep Brain Stimulation is a generalized therapy which can significantly improve the motor symptoms. However despite its beneficial effects on treating the symptomatology, the technique can be improved. One of its main limitations is that the parameters are fixed, and the stimulation is provided uninterruptedly, not taking into account any fluctuation in the patients state. A closed-loop system which provides stimulation by demand would adjust the stimulation to the variations in the state of the patient, stimulating only when it is necessary. It would not only perform a more intelligent stimulation, capable of adapting to the changes in real time, but also extending the devices battery life, thereby avoiding surgical interventions. In this work we design a tool that learns to recognize the principal symptom of Parkinsons disease and particularly the tremor. The goal of the designed system is to detect the moments the patient is suffering from a tremor episode and consequently to decide whether stimulation is needed or not. For that, local field potentials were recorded in the subthalamic nucleus of ten Parkinsonian patients, who were diagnosed with tremor-dominant Parkinsons disease and who underwent surgery for the implantation of a neurostimulator. Electromyographic activity in the forearm was simultaneously recorded, and the relation between both signals was evaluated using two different synchronization measures. The results of evaluating the synchronization indexes on each moment represent the inputs to the designed system. Finally, a fuzzy inference system was applied with the goal of identifying tremor episodes. Results are favourable, reaching accuracies of higher 98.7 % in 70 % of the patients.Centro de Investigación Biomédica en RedDepto. de Psicología Experimental, Procesos Cognitivos y LogopediaDepto. de Radiología, Rehabilitación y FisioterapiaFac. de PsicologíaFac. de MedicinaTRUEpu

Stereoselective Synthesis of (-)-Spicigerolide

(-)-Spicigerolide was enantioselectively synthesized from a protected (S)-lactaldehyde. The synthesis of the polyacetylated framework relied on two Zn-mediated stereoselective additions of alkynes to aldehydes as well as a regiocontrolled [3,3]-sigmatropic rearrangement of an allylic acetate. The pyranone moiety was constructed via ring-closing metathesis

Hemangioblastic foci in human first trimester placenta: distribution and gestational profile

INTRODUCTION: The human placenta is a site of both hematopoiesis and vasculogenesis. There are reports of hemangioblastic foci (HAF) in the first trimester placenta, but little published information about their spatiotemporal incidence. METHODS: We have used semi-thin sections and whole mount staining techniques on archival early pregnancy hysterectomy material as well as freshly-collected termination tissue. RESULTS: We report a description of the distribution of HAF, their gestational profile, and some characteristics of the constituent cells. We show crypt-shaped HAF are present in villi at different levels from 4 to 11 weeks and in the chorionic plate from 4 to 9 weeks. In the villous placenta, the foci often approach closely at one end to the trophoblast basement membrane. Morphologically they show remarkable similarity to those found in the yolk sac at similar stages. In some crypts, all cells are CD34+, but CD34 and nestin progressively segregate into the endothelial lineage. Brachyury is present in less differentiated cells. The erythroid lineage is dominant, as shown by the widespread expression of CD235a/glycophorin and characteristic erythroid morphologies, indicating various degrees of differentiation. However, CD41 is also present in non-endothelial cells. Initially a discontinuous UEA-1/CD31-positive endothelium forms at the periphery of the foci. These cells appear to become integrated into the developing vasculogenic/angiogenic vessel network. We also demonstrate that, independent of HAF, vasculogenesis occurs near the tips of growing villi during the first trimester. DISCUSSION: We suggest HAF interface with the developing vascular network, producing communication channels that allow erythrocytes to enter the placental-embryonic circulation. We speculate that the erythroid cells act as oxygen reservoirs during the period before flow of maternal blood through the intervillous space of the placenta, allowing a slow feed of oxygen-rich cells to the developing embryo

HERMES: Towards an Integrated Toolbox to Characterize Functional and Effective Brain Connectivity

The analysis of the interdependence between time series has become an important field of research in the last years, mainly as a result of advances in the characterization of dynamical systems from the signals they produce, the introduction of concepts such as generalized and phase synchronization and the application of information theory to time series analysis. In neurophysiology, different analytical tools stemming from these concepts have added to the ‘traditional’ set of linear methods, which includes the cross-correlation and the coherency function in the time and frequency domain, respectively, or more elaborated tools such as Granger Causality. This increase in the number of approaches to tackle the existence of functional (FC) or effective connectivity (EC) between two (or among many) neural networks, along with the mathematical complexity of the corresponding time series analysis tools, makes it desirable to arrange them into a unified-easy-to-use software package. The goal is to allow neuroscientists, neurophysiologists and researchers from related fields to easily access and make use of these analysis methods from a single integrated toolbox. Here we present HERMES (http://hermes.ctb.upm.es), a toolbox for the Matlab® environment (The Mathworks, Inc), which is designed to study functional and effective brain connectivity from neurophysiological data such as multivariate EEG and/or MEG records. It includes also visualization tools and statistical methods to address the problem of multiple comparisons. We believe that this toolbox will be very helpful to all the researchers working in the emerging field of brain connectivity analysis

Molecular interaction of BMP-4, TGF-β, and estrogens in lactotrophs: Impact on the PRL promoter

The regulatory role of estrogen, bone morphogenetic protein-4 (BMP-4), and TGF-β has a strong impact on hormone secretion, gene transcription, and cellular growth of prolactin (PRL)-producing cells. In contrast to TGF-β, BMP-4 induces the secretion of PRL in GH3 cells. Therefore, we studied the mechanism of their transcriptional regulation. Both BMP-4 and TGF-β inhibited the transcriptional activity of the estrogen receptor (ER). Estrogens had no effect on TGF-β-specific Smad protein transcriptional activity but presented a stimulatory action on the transcriptional activity of the BMP-4-specific Smads. BMP-4/estrogen cross talk was observed both on PRL hormone secretion and on the PRL promoter. This cross talk was abolished by the expression of a dominant-negative form for Smad-1 and treatment with ICI 182780 but not by point mutagenesis of the estrogen response element site within the promoter, suggesting that Smad/ER interaction might be dependent on the ER and a Smad binding element. By serial deletions of the PRL promoter, we observed that indeed a region responsive to BMP-4 is located between -2000 and -1500 bp upstream of the transcriptional start site. Chromatin immunoprecipitation confirmed Smad-4 binding to this region, and by specific mutation and gel shift assay, a Smad binding element responsible site was characterized. These results demonstrate that the different transcriptional factors involved in the Smad/ER complexes regulate their transcriptional activity in differential ways and may account for the different regulatory roles of BMP-4, TGF-β, and estrogens in PRL-producing cells. Copyright © 2009 by The Endocrine Society.Fil:Giacomini, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Páez-Pereda, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

First Thing, Everything: InterDesign Manifesto

In this manifesto, we explore the idea that Design facilitates optimal interventions to any problem that relates to human activity. This could take the form of innovating communication or usability problems, critically engaging with a concept or idea, or selling a product or brand. As diverse as this sounds, this manifesto argues that Design is about innovation through informed processes while engaging with all areas of society