VEGF-mediated angiogenesis stimulates neural stem cell proliferation and differentiation in the premature brain

This study investigated the effects of angiogenesis on the proliferation and differentiation of neural stem cells in the premature brain. We observed the changes in neurogenesis that followed the stimulation and inhibition of angiogenesis by altering vascular endothelial growth factor (VEGF) expression in a 3-day-old rat model. VEGF expression was overexpressed by adenovirus transfection and down-regulated by siRNA interference. Using immunofluorescence assays, Western blot analysis, and real-time PCR methods, we observed angiogenesis and the proliferation and differentiation of neural stem cells. Immunofluorescence assays showed that the number of vWF-positive areas peaked at day 7, and they were highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at every time point. The number of neural stem cells, neurons, astrocytes, and oligodendrocytes in the subventricular zone gradually increased over time in the VEGF up-regulation group. Among the three groups, the number of these cells was highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at the same time point. Western blot analysis and real-time PCR confirmed these results. These data suggest that angiogenesis may stimulate the proliferation of neural stem cells and differentiation into neurons, astrocytes, and oligodendrocytes in the premature brain.     

A lead dependent ischemic episodes detection strategy using Hermite functions

In this work a new strategy for automatic detection of ischemic episodes is proposed. A new measure for ST deviation based on the time–frequency analysis of the ECG and the use of a reduced set of Hermite basis functions for T wave and QRS complex morphology characterization, are the key points of the proposed methodology.Usually, ischemia manifests itself in the ECG signal by ST segment deviation or by QRS complex and T wave changes in morphology. These effects might occur simultaneously. Time–frequency methods are especially adequate for the detection of small transient characteristics hidden in the ECG, such as ST segment alterations. A Wigner–Ville transform-based approach is proposed to estimate the ST shift. To characterize the alterations in the T wave and the QRS morphologies, each cardiac beat is described by expansions in Hermite functions. These demonstrated to be suitable to capture the most relevant morphologic characteristics of the signal. A lead dependent neural network classifier considers, as inputs, the ST segment deviation and the Hermite expansion coefficients. The ability of the proposed method in ischemia episodes detection is evaluated using the European Society of Cardiology ST–T database. A sensitivity of 96.7% and a positive predictivity of 96.2% reveal the capacity of the proposed strategy to perform ischemic episodes identification.     

Separation and enrichment of neural stem cells using segregation in an expanded bed

An expanded bed system has been developed for a novel application in which the separation and enrichment of neural stem cells from a sample containing a mixture of stem and progenitor cells is achieved based on the difference in the sizes of the aggregates of these types of cells. Inert Sephadex beads and flocculated yeast cells were used as experimental controls and references. The characteristics of the separation of neural stem cell aggregates based on size are similar to those achieved with flocculated yeast where cell-to-cell aggregation controls the pattern of size separation different from those of inert Sephadex beads.     

A mathematical framework for inferring connectivity in probabilistic neuronal networks

We describe an approach for determining causal connections among nodes of a probabilistic network even when many nodes remain unobservable. The unobservable nodes introduce ambiguity into the estimate of the causal structure. However, in some experimental contexts, such as those commonly used in neuroscience, this ambiguity is present even without unobservable nodes. The analysis is presented in terms of a point process model of a neuronal network, though the approach can be generalized to other contexts. The analysis depends on the existence of a model that captures the relationship between nodal activity and a set of measurable external variables. The mathematical framework is sufficiently general to allow a large class of such models. The results are modestly robust to deviations from model assumptions, though additional validation methods are needed to assess the success of the results.     

Evidence for new Neanderthal teeth in Tabun Cave (Israel) by the application of self-organizing maps (SOMs)

Morphological and metrical study suggested that seven human teeth from Tabun Cave, Israel were part of the upper dentition of a single, probably Neanderthal, individual renumbered as Tabun BC7. An enamel fragment gave ESR age estimates of 82+/-14 ka (early U-uptake) and 92+/-18 ka (linear uptake) and an age estimate of 90(+30)(-16) ka using U-series disequilibrium. Although metrical analyses suggested Neanderthal affinities, definitive assessment was difficult as the values often fell into the ranges of both Neanderthal and Levantine early modern human samples. Therefore, two further classification analyses were conducted (neural networks using self-organizing maps and homogeneity analysis). Both identify Tabun BC7 as a Neanderthal. Neural networks are a promising tool for paleoanthropological studies as they can provide reliable classifications even with incomplete data.     

Reduced sialylation status in UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE)-deficient mice

Sialic acids are widely expressed as terminal carbohydrates on glycoconjugates of eukaryotic cells. They are involved in a variety of cellular functions, such as cell adhesion or signal recognition. The key enzyme of sialic acid biosynthesis is the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE), which catalyzes the first two steps of sialic acid biosynthesis in the cytosol. Previously, we have shown that inactivation of the GNE by gene targeting causes early embryonic lethality in mice, whereas heterozygous GNE-deficient mice are vital. In this study we compared the amount of membrane-bound sialic acids of wildtype mice with those of heterozygous GNE-deficient mice. For that we quantified membrane-bound sialic acid concentration in various organs of wildtype- and heterozygous GNE-deficient mice. We found an organ-specific reduction of membrane-bound sialic acids in heterozygous GNE-deficient mice. The overall reduction was 25%. Additionally, we analyzed transferrin and polysialylated neural cell adhesion molecule (NCAM) by one- or two-dimensional gel electrophoresis. Transferrin-expression was unchanged in heterozygous GNE-deficient mice; however the isoelectric point of transferrin was shifted towards basic pH, indicating a reduced sialylation. Furthermore, the expression of polysialic acids on NCAM was reduced in GNE-deficient mice. Daniel Gagiannis and André Orthmann have contributed equally to this work.     

Defective cholesterol traffic and neuronal differentiation in neural stem cells of Niemann-Pick type C disease improved by valproic acid, a histone deacetylase inhibitor

Niemann-Pick type C disease (NPC) is a neurodegenerative and lipid storage disorder for which no effective treatment is known. We previously reported that neural stem cells derived from NPC1 mice showed impaired self-renewal and differentiation. We examined whether valproic acid (VPA), a histone deacetylase inhibitor, could enhance neuronal differentiation and recover defective cholesterol metabolism in neural stem cells (NSCs) from NPC1-deficient mice (NPC1(-/-)). VPA could induce neuronal differentiation and restore impaired astrocytes in NSCs from NPC1(-/-) mice. Importantly, an increasing level of cholesterol within NSCs from NPC1(-/-) mice could be reduced by VPA. Moreover, essential neurotrophic genes (TrkB, BDNF, MnSoD, and NeuroD) were up-regulated through the repression of the REST/NRSF and HDAC complex by the VPA treatment. Up-regulated neurotrophic genes were able to enhance neural differentiation and cholesterol homeostasis in neural stem cells from NPC1(-/-) mice. In this study, we suggested that, along with cholesterol homeostasis, impaired neuronal differentiation and abnormal morphology of astrocytes could be rescued by the inhibition of HDAC and REST/NRSF activity induced by VPA treatment.     

Theoretical investigations on the functionalization of carbon nanotubes

In this paper, our recent work concerning theoretical studies on the functionalization of carbon nanotubes (CNTs) is reviewed. In particular, two different aspects of the functionalization process are taken into account. On the one hand, the chemical functionalization of the sidewall is exploited as a way to develop nanostructured gas sensing devices. On the other hand, we investigated the possibility of functionalizing the sidewall with transition metal complexes, thus extending the concepts of organometallic chemistry to CNTs. Calculations were performed by applying statical and dynamical (Car-Parrinello) density functional theory methods, as well as hybrid (quantum mechanics/molecular mechanics) schemes. The structural and electronic peculiarities of the CNT model under study, due, for example to the presence of defects, were found to play a crucial role in the modelization of the functionalization process. In most cases, the use of realistic models was essential to achieve a full agreement with experiments.     

Efficient inhibition of bursts by bursts in the auditory system of crickets

In crickets, auditory information about ultrasound is carried bilaterally to the brain by the AN2 neurons. The ON1 neuron provides contralateral inhibitory input to AN2, thereby enhancing bilateral contrast between the left and right AN2s, an important cue for sound localization. We examine how the structures of the spike trains of these neurons affect this inhibitory interaction. As previously shown for AN2, ON1 responds to salient peaks in stimulus amplitude with bursts of spikes. Spike bursts, but not isolated spikes, reliably signal the occurrence of specific features of the stimulus. ON1 and AN2 burst at similar times relative to the amplitude envelope of the stimulus, and bursts are more tightly time-locked to stimulus feature than the isolated spikes. As a consequence, spikes that, in the absence of contralateral inhibition, would occur within AN2 bursts are more likely to be preceded by spikes in ON1 (mainly also in bursts) than are isolated AN2 spikes. This leads to a large decrease in the burst rate of the inhibited AN2. We conclude that the match in coding properties of ON1 and AN2 allows contralateral inhibition to be most efficient for those portions of the response that carry the behaviourally relevant information, i.e. for bursts. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.