Vitronectin regulates Sonic hedgehog activity during cerebellum development through CREB phosphorylation

12 páginas, 7 figuras.During development of the cerebellum, Sonic hedgehog (SHH) is expressed in migrating and settled Purkinje neurons and is directly responsible for proliferation of granule cell precursors in the external germinal layer. We have previously demonstrated that SHH interacts with vitronectin in the differentiation of spinal motor neurons. Here, we analysed whether similar interactions between SHH and extracellular matrix glycoproteins regulate subsequent steps of granule cell development. Laminins and their integrin receptor subunit alpha6 accumulate in the outer most external germinal layer where proliferation of granule cell precursors is maximal. Consistent with this expression pattern, laminin significantly increases SHH-induced proliferation in primary cultures of cerebellar granule cells. Vitronectin and its integrin receptor subunits alpha(v) are expressed in the inner part of the external germinal layer where granule cell precursors exit the cell cycle and commence differentiation. In cultures, vitronectin is able to overcome SHH-induced proliferation, thus allowing granule cell differentiation. Our studies indicate that the pathway in granule cell precursors responsible for the conversion of a proliferative SHH-mediated response to a differentiation signal depends on CREB. Vitronectin stimulates phosphorylation of cyclic-AMP responsive element-binding protein (CREB), and over-expression of CREB is sufficient to induce granule cell differentiation in the presence of SHH. Taken together, these data suggest that granule neuron differentiation is regulated by the vitronectin-induced phosphorylation of CREB, a critical event that terminates SHH-mediated proliferation and permits the differentiation program to proceed in these cells.This research was supported by grant PM97-0018 to Dr Ignacio Torres Alemán and by grants PM97-0019 and BIO4-CT98-0399 to Dr Paola Bovolenta, in whose laboratories this research was carried out.Peer reviewe

Extraction of user's navigation commands from upper body force interaction in walker assisted gait

<p>Abstract</p> <p>Background</p> <p>The advances in technology make possible the incorporation of sensors and actuators in rollators, building safer robots and extending the use of walkers to a more diverse population. This paper presents a new method for the extraction of navigation related components from upper-body force interaction data in walker assisted gait. A filtering architecture is designed to cancel: (i) the high-frequency noise caused by vibrations on the walker's structure due to irregularities on the terrain or walker's wheels and (ii) the cadence related force components caused by user's trunk oscillations during gait. As a result, a third component related to user's navigation commands is distinguished.</p> <p>Results</p> <p>For the cancelation of high-frequency noise, a Benedict-Bordner g-h filter was designed presenting very low values for Kinematic Tracking Error ((2.035 ± 0.358)·10^-2<it>kgf</it>) and delay ((1.897 ± 0.3697)·10¹<it>ms</it>). A <it>Fourier Linear Combiner </it>filtering architecture was implemented for the adaptive attenuation of about 80% of the cadence related components' energy from force data. This was done without compromising the information contained in the frequencies close to such notch filters.</p> <p>Conclusions</p> <p>The presented methodology offers an effective cancelation of the undesired components from force data, allowing the system to extract in real-time voluntary user's navigation commands. Based on this real-time identification of voluntary user's commands, a classical approach to the control architecture of the robotic walker is being developed, in order to obtain stable and safe user assisted locomotion.</p

Extraction of user's navigation commands from upper body force interaction in walker assisted gait

<p>Abstract</p> <p>Background</p> <p>The advances in technology make possible the incorporation of sensors and actuators in rollators, building safer robots and extending the use of walkers to a more diverse population. This paper presents a new method for the extraction of navigation related components from upper-body force interaction data in walker assisted gait. A filtering architecture is designed to cancel: (i) the high-frequency noise caused by vibrations on the walker's structure due to irregularities on the terrain or walker's wheels and (ii) the cadence related force components caused by user's trunk oscillations during gait. As a result, a third component related to user's navigation commands is distinguished.</p> <p>Results</p> <p>For the cancelation of high-frequency noise, a Benedict-Bordner g-h filter was designed presenting very low values for Kinematic Tracking Error ((2.035 ± 0.358)·10^-2<it>kgf</it>) and delay ((1.897 ± 0.3697)·10¹<it>ms</it>). A <it>Fourier Linear Combiner </it>filtering architecture was implemented for the adaptive attenuation of about 80% of the cadence related components' energy from force data. This was done without compromising the information contained in the frequencies close to such notch filters.</p> <p>Conclusions</p> <p>The presented methodology offers an effective cancelation of the undesired components from force data, allowing the system to extract in real-time voluntary user's navigation commands. Based on this real-time identification of voluntary user's commands, a classical approach to the control architecture of the robotic walker is being developed, in order to obtain stable and safe user assisted locomotion.</p

Eudragit E100® potentiates the bactericidal action of ofloxacin against fluoroquinolone-resistant Pseudomonas aeruginosa

We report the enhanced bactericidal activity of ofloxacin in drug-containing Eudragit E100® dispersions (EuCl-OFX) against Pseudomonas aeruginosa and the effect of the cationic polymer on bacterial membrane. Organisms treated with EuCl-OFX showed changes in cell morphology, altered outer membrane (OM) and cytoplasm with low electrodensity areas. Zeta potential of bacterial surface was shifted to positive. Sensitization to lytic agents was also observed. A profound effect on bacterial size, granularity and membrane depolarization was found by flow cytometry. Cultures exposed to drug-free polymer also showed some damaged bacterial membranes, but there was no significant cell death. Inhibition of P. aeruginosa by EuCl-OFX may involve surface effect and, to some extent, permeation effect. The cationic polymer act to mitigate the electronegativity of cell surface in the process of disorganizing the OM, rendering it more permeable to antibiotic. In addition, cytoplasmic membrane depolarization turns bacterial cell more vulnerable. The effects on membranes combined with the mechanism of action of quinolone explain the improved bactericidal action exhibited by EuCl-OFX. The behavior described for Eudragit E100® against P. aeruginosa may be a useful tool to broaden the spectrum of antibiotics whose clinical use is limited by the impermeability of the bacterial OM.Fil: Romero, Verónica Leonor. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Pons, Patricia. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Microscopía Electrónica; ArgentinaFil: Bocco, José L.. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; ArgentinaFil: Manzo, Rubén H.. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; ArgentinaFil: Alovero, Fabiana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

Electrical Stimulation of Afferent Pathways for the Suppression of Pathological Tremor

Pathological tremors are involuntary oscillatory movements which cannot be fully attenuated using conventional treatments. For this reason, several studies have investigated the use of neuromuscular electrical stimulation for tremor suppression. In a recent study, however, we found that electrical stimulation below the motor threshold also suppressed tremor, indicating involvement of afferent pathways. In this study, we further explored this possibility by systematically investigating how tremor suppression by afferent stimulation depends on the stimulation settings. In this way, we aimed at identifying the optimal stimulation strategy, as well as to elucidate the underlying physiological mechanisms of tremor suppression. Stimulation strategies varying the stimulation intensity and pulse timing were tested in nine tremor patients using either intramuscular or surface stimulation. Significant tremor suppression was observed in six patients (tremor suppression > 75% was observed in three patients) and the average optimal suppression level observed across all subjects was 52%. The efficiency for each stimulation setting, however, varied substantially across patients and it was not possible to identify a single set of stimulation parameters that yielded positive results in all patients. For example, tremor suppression was achieved both with stimulation delivered in an out-of-phase pattern with respect to the tremor, and with random timing of the stimulation. Overall, these results indicate that low-current stimulation of afferent fibers is a promising approach for tremor suppression, but that further research is required to identify how the effect can be maximized in the individual patient.This work has been supported by the Commission of the European Union through the grant ICT-2011-287739 (NeuroTREMOR).Peer reviewedPeer Reviewe

Effects of robotic guidance on the coordination of locomotion

Functional integration of motor activity patterns enables the production of coordinated movements, such as walking. The activation of muscles by weightened summation of activation signals has been demonstrated to represent the spatiotemporal components that determine motor behavior during walking. Exoskeleton robotic devices are now often used in the rehabilitation practice to assist physical therapy of individuals with neurological disorders. These devices are used to promote motor recovery by providing guidance force to the patients. The guidance should in principle lead to a muscle coordination similar to physiological human walking. However, the influence of robotic devices on locomotor patterns needs still to be characterized. The aim of this study was to analyze the effect of force guidance and gait speed on the modular organization of walking in a group of eight healthy subjects.This project is funded by the European Commission, project "BETTER" (contract number 247935) and Spanish Consolider-Ingenio Programme, project "HYPER" (contract number CSD2009-00067) and Universita Degli Studi di Roma "Foro Italico", research project "Dynamic sensorimotor interaction during locomotion: influences of perturbations and/or body unloading"

Evaluación de la mama contralateral mediante resonancia magnética en pacientes con diagnóstico reciente de cáncer mamario unilateral

Breast Magnetic Resonance (BMR) imaging is a useful tool in the evaluation of breast cancer before surgical treatment. BMR imaging plays an important role in the evaluation of the extension of the malignant lesions, and the study of multifocality and multicentricity. BMR may have a role in the detection of synchronous contralateral breast cancer that is occult to conventional imaging methods (mammography and ultrasonography). In this study we review 13 series of different authors in which they have used BMR in the evaluation of the contralateral breast in patients with newly diagnosed breast cancer. Two thousand five hundred and eleven patients were evaluated with BMR and 123 contralateral cancers, that were occult to conventional methods, were detected with this technique (4,9 %). Therefore, BMR imaging of the breast is useful as a complementary tool because of its high sensitivity in local staging of a breast cancer and its ability in the detection of synchronous contralateral breast cancer in patients with newly diagnosed breast cance

One central oscillatory drive is compatible with experimental motor unit behaviour in essential and Parkinsonian tremor

Pathological tremors are symptomatic to several neurological disorders that are difficult to differentiate and the way by which central oscillatory networks entrain tremorogenic contractions is unknown. We considered the alternative hypotheses that tremor arises from one oscillator (at the tremor frequency) or, as suggested by recent findings from the superimposition of two separate inputs (at the tremor frequency and twice that frequency). Approach. Assuming one central oscillatory network we estimated analytically the relative amplitude of the harmonics of the tremor frequency in the motor neuron output for different temporal behaviors of the oscillator. Next, we analyzed the bias in the relative harmonics amplitude introduced by superimposing oscillations at twice the tremor frequency. These findings were validated using experimental measurements of wrist angular velocity and surface electromyography (EMG) from 22 patients (11 essential tremor, 11 Parkinson’s disease). The ensemble motor unit action potential trains identified from the EMG represented the neural drive to the muscles. Main results. The analytical results showed that the relative power of the tremor harmonics in the analytical models of the neural drive was determined by the variability and duration of the tremor bursts and the presence of the second oscillator biased this power towards higher values. The experimental findings accurately matched the analytical model assuming one oscillator, indicating a negligible functional role of secondary oscillatory inputs. Furthermore, a significant difference in the relative power of harmonics in the neural drive was found across the patient groups, suggesting a diagnostic value of this measure (classification accuracy: 86%). This diagnostic power decreased substantially when estimated from limb acceleration or the EMG. Signficance. The results indicate that the neural drive in pathological tremor is compatible with one central network providing neural oscillations at the tremor frequency. Moreover, the regularity of this neural oscillation varies across tremor pathologies, making the relative amplitude of tremor harmonics a potential biomarker for diagnostic use

A Review of fMRI as a Tool for Enhancing Eeg-Based Brain-Machine Interfaces

Human-robot interaction has been going stronger and stronger, up to find a notorious level on brain-machines interfaces. This assistive technology offers a great hope for patients suffering severe neuromuscular disorders. Starting from the current limitations hindering its extensive application outside the research laboratories, this paper reviews findings and prospects on functional magnetic resonance imaging showing how fMRI can help to overcome those limitations, while playing a key role on improving the development of brain-machine interfaces based on electroencephalography. The different types of derived benefits for this interfaces, as well as the different kinds of impact on their components, are presented under a field classification that reveals the distinctive roles that fMRI can play on the present context. The review concludes that fMRI provides complementary knowledge of immediate application, and that a greater profit could be obtained from the own EEG signal by integrating both neuroimaging modalities