A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation

Gait freezing is an episodic arrest of locomotion due to an inability to take normal steps. Pedunculopontine nucleus stimulation is an emerging therapy proposed to improve gait freezing, even where refractory to medication. However, the efficacy and precise effects of pedunculopontine nucleus stimulation on Parkinsonian gait disturbance are not established. The clinical application of this new therapy is controversial and it is unknown if bilateral stimulation is more effective than unilateral. Here, in a double-blinded study using objective spatiotemporal gait analysis, we assessed the impact of unilateral and bilateral pedunculopontine nucleus stimulation on triggered episodes of gait freezing and on background deficits of unconstrained gait in Parkinson’s disease. Under experimental conditions, while OFF medication, Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions; off stimulation, unilateral stimulation and bilateral stimulation. Results were compared to Parkinsonian patients without gait freezing matched for disease severity and healthy controls. Pedunculopontine nucleus stimulation improved objective measures of gait freezing, with bilateral stimulation more effective than unilateral. During unconstrained walking, Parkinsonian patients who experience gait freezing had reduced step length and increased step length variability compared to patients without gait freezing; however, these deficits were unchanged by pedunculopontine nucleus stimulation. Chronic pedunculopontine nucleus stimulation improved Freezing of Gait Questionnaire scores, reflecting a reduction of the freezing encountered in patients’ usual environments and medication states. This study provides objective, double-blinded evidence that in a specific subgroup of Parkinsonian patients, stimulation of a caudal pedunculopontine nucleus region selectively improves gait freezing but not background deficits in step length. Bilateral stimulation was more effective than unilateral

RTVP-1 regulates glioma cell migration and invasion via interaction with N-WASP and hnRNPK

Glioblastoma (GBM) are characterized by increased invasion into the surrounding normal brain tissue. RTVP-1 is highly expressed in GBM and regulates the migration and invasion of glioma cells. To further study RTVP-1 effects we performed a pull-down assay using His-tagged RTVP-1 followed by mass spectrometry and found that RTVP-1 was associated with the actin polymerization regulator, N-WASP. This association was further validated by co-immunoprecipitation and FRET analysis. We found that RTVP-1 increased cell spreading, migration and invasion and these effects were at least partly mediated by N-WASP. Another protein which was found by the pull-down assay to interact with RTVP-1 is hnRNPK. This protein has been recently reported to associate with and to inhibit the effect of N-WASP on cell spreading. hnRNPK decreased cell migration, spreading and invasion in glioma cells. Using co-immunoprecipitation we validated the interactions of hnRNPK with N-WASP and RTVP-1 in glioma cells. In addition, we found that overexpression of RTVP-1 decreased the association of N-WASP and hnRNPK. In summary, we report that RTVP-1 regulates glioma cell spreading, migration and invasion and that these effects are mediated via interaction with N-WASP and by interfering with the inhibitory effect of hnRNPK on the function of this protein

GUI Matlab para o cálculo de funções de Bessel usando frações continuadas

[EN] Higher order Bessel functions are prevalent in physics and engineering and there exist different methods to evaluate them quickly and efficiently. Two of these methods are Miller's algorithm and the continued fractions algorithm. Miller's algorithm uses arbitrary starting values and normalization constants to evaluate Bessel functions. The continued fractions algorithm directly computes each value, keeping the error as small as possible. Both methods respect the stability of the Bessel function recurrence relations. Here we outline both methods and explain why the continued fractions algorithm is more efficient. The goal of this paper is both (1) to introduce the continued fractions algorithm to physics and engineering students and (2) to present a MATLAB GUI (Graphic User Interface) where this method has been used for computing the Semi-integer Bessel Functions and their zeros.[PT] Funções de Bessel de ordem mais alta são recorrentes em física e nas engenharias, sendo que há diferentes métodos para calculá-las de maneira rápida e eficiente. Dois destes métodos são o algoritmo de Miller e o algoritmo de frações continuadas. O primeiro faz uso de valores iniciais e constantes de normalização arbitrários, enquanto o segundo o faz calculando cada valor diretamente, minimizando tanto quanto possível o erro. Ambos respeitam a estabilidade das relações de recorrência das funções de Bessel. Neste trabalho descrevemos ambos os métodos e explicamos a razão pela qual o algoritmo das frações continuadas é mais eficiente. O objetivo do artigo é (1) introduzir o algoritmo de frações continuadas para estudantes de física e das engenharias e (2) apresentar um GUI (Graphic User Interface) em Matlab no qual este método foi utilizado para calcular funções de Bessel semi-inteiras e seus zeros.The authors wish to thank the financial support received from the Universidad Politécnica de Valencia under grant PAID-06-09-2734, from the Ministerio de Ciencia e Innovación through grant ENE2008-00599 and specially from the Generalitat Valenciana under grant reference 3012/2009.Hernandez Vargas, E.; Commeford, K.; Pérez Quiles, MJ. (2011). MATLAB GUI for computing Bessel functions using continued fractions algorithm. Revista Brasileira de Ensino de Física. 33(1):1303-1311. https://doi.org/10.1590/S1806-11172011000100003S13031311331Giladi, E. (2007). Asymptotically derived boundary elements for the Helmholtz equation in high frequencies. Journal of Computational and Applied Mathematics, 198(1), 52-74. doi:10.1016/j.cam.2005.11.024Havemann, S., & Baran, A. J. (2004). Calculation of the phase matrix elements of elongated hexagonal ice columns using the T-matrix method. Journal of Quantitative Spectroscopy and Radiative Transfer, 89(1-4), 87-96. doi:10.1016/j.jqsrt.2004.05.014Segura, J., Fernández de Córdoba, P., & Ratis, Y. L. (1997). A code to evaluate modified bessel functions based on thecontinued fraction method. Computer Physics Communications, 105(2-3), 263-272. doi:10.1016/s0010-4655(97)00069-6Bastardo, J. L., Abraham Ibrahim, S., Fernández de Córdoba, P., Urchueguía Schölzel, J. F., & Ratis, Y. L. (2005). Evaluation of Fresnel integrals based on the continued fractions method. Applied Mathematics Letters, 18(1), 23-28. doi:10.1016/j.aml.2003.12.009Barnett, A. R., Feng, D. H., Steed, J. W., & Goldfarb, L. J. B. (1974). Coulomb wave functions for all real η and ϱ. Computer Physics Communications, 8(5), 377-395. doi:10.1016/0010-4655(74)90013-

Direct microscopic examination of imprints in patients undergoing cardiac valve replacement

BACKGROUND: Bacteriological analysis of cardiac valves might be indicated in patients with suspected endocarditis. METHODS: We report here a prospective study on fifty-three consecutive patients whose native valves were sent to the bacteriological and pathological laboratories, to investigate the performance of direct microscopic examination of imprints and valve culture. RESULTS: On the basis of a histopathological gold standard to classify the inflammatory valve process, the sensitivity, the specificity, the positive and the negative predictive values of direct microscopic examination of imprints and valve culture were 21%, 100%, 100%, 60%, and 21%, 72%, 38%, 52% respectively. This weak threshold of the direct microscopic examination of imprints could be due to antimicrobial therapy prescribed before cardiac surgery and the fact that the patients came from a tertiary hospital receiving patients with a prolonged history of endocarditis. CONCLUSION: Clinical context and histopathology are indispensable when analyzing the imprints and valve culture

Dynamic Analysis of Vascular Morphogenesis Using Transgenic Quail Embryos

Background: One of the least understood and most central questions confronting biologists is how initially simple clusters or sheet-like cell collectives can assemble into highly complex three-dimensional functional tissues and organs. Due to the limits of oxygen diffusion, blood vessels are an essential and ubiquitous presence in all amniote tissues and organs. Vasculogenesis, the de novo self-assembly of endothelial cell (EC) precursors into endothelial tubes, is the first step in blood vessel formation [1]. Static imaging and in vitro models are wholly inadequate to capture many aspects of vascular pattern formation in vivo, because vasculogenesis involves dynamic changes of the endothelial cells and of the forming blood vessels, in an embryo that is changing size and shape. Methodology/Principal Findings: We have generated Tie1 transgenic quail lines Tg(tie1:H2B-eYFP) that express H2B-eYFP in all of their endothelial cells which permit investigations into early embryonic vascular morphogenesis with unprecedented clarity and insight. By combining the power of molecular genetics with the elegance of dynamic imaging, we follow the precise patterning of endothelial cells in space and time. We show that during vasculogenesis within the vascular plexus, ECs move independently to form the rudiments of blood vessels, all while collectively moving with gastrulating tissues that flow toward the embryo midline. The aortae are a composite of somatic derived ECs forming its dorsal regions and the splanchnic derived ECs forming its ventral region. The ECs in the dorsal regions of the forming aortae exhibit variable mediolateral motions as they move rostrally; those in more ventral regions show significant lateral-to-medial movement as they course rostrally. Conclusions/Significance: The present results offer a powerful approach to the major challenge of studying the relative role(s) of the mechanical, molecular, and cellular mechanisms of vascular development. In past studies, the advantages of the molecular genetic tools available in mouse were counterbalanced by the limited experimental accessibility needed for imaging and perturbation studies. Avian embryos provide the needed accessibility, but few genetic resources. The creation of transgenic quail with labeled endothelia builds upon the important roles that avian embryos have played in previous studies of vascular development

Non-reductivism and the Metaphilosophy of Mind

This paper discusses the metaphilosophical assumptions that have dominated analytic philosophy of mind, and how they gave rise to the central question that the best-known forms of non-reductivism available have sought to answer, namely: how can mind fit within nature? Its goal is to make room for forms of non-reductivism that have challenged the fruitfulness of this question, and which have taken a different approach to the so-called “placement” problem. Rather than trying to solve the placement problem, the forms of non-reductivism discussed in this paper have put pressure on the metaphilosophical assumptions that have given rise to the question of the place of mind in nature in the first instance

Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in parkinson patients

Patients with Parkinson's disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular