122 research outputs found
PCN349 Evaluation Of A Payment By Results Scheme In A Catalan Cancer Center: Gefinitib In Egfr Mutation-Positive Advanced Non-Small Cell Lung Cancer
Lithium and boron in calcified tissues of vicuna and its relation to the chronic exposure by water ingestion in the Andean lithium triangle
Vicuna is a wild, endangered species of Andean camelid living in the hyperarid Andean plateau. In the central part of the plateau, the Lithium Triangle defines a zone with lithium‐rich salt pans. Brine pools naturally form within the salt pans, and the adaptation strategy of vicuna consists of drinking from brine pools. Together with reporting the first chemical data on vicuna bones and teeth, we analyzed lithium, boron, and arsenic in water and brines, with the aim of assessing their relation to chronic exposure by water ingestion. We collected and analyzed bones of vicuna specimens lying in an Andean salt pan, together with brine and water samples. Brine and water samples are highly saline and contain large amounts of lithium, boron, and arsenic. Lithium (13.50–40 mg kg–1 ) and boron (40–46.80 mg kg–1 ), but not arsenic, were found in the vicuna bones and teeth. Based on our results and on previously reported data on human tissues in the Andes, we conducted statistical assessments of the relationships between lithium and boron in body tissues and water samples, and discuss their environmental significance in the context of the Lithium Triangle.Fil: López Steinmetz, Romina Lucrecia. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; Argentina. Universidad Nacional de Jujuy. Instituto de Geología Minera; ArgentinaFil: Fong, Shao Bing. University of Melbourne; AustraliaFil: Boyer, Emile. Universite de Rennes I; FranciaFil: López Steinmetz, Lorena Cecilia. Universidad Nacional de Córdoba. Instituto de Investigaciones Psicológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Psicológicas; ArgentinaFil: Tejerina, Norberto Elio. Universidad Nacional de Jujuy. Instituto de Geología Minera; ArgentinaFil: Meuric, Vincent. Universite de Rennes I; Franci
Isolation of chick retina cones and study of their diversity based on oil droplet colour and nucleus position
The chick retina has four morphological cone types that differ not only in shape, but also in the visual pigment in the outer segment, in the colour of the oil droplet in the inner segment and in synaptic connectivity. Neither the type of droplet nor the visual pigment has been definitively established for the four cone types. The main aim of the present work has been the isolation of entire live photoreceptors in order to study the oil droplet colour in each cone type and to quantify each type. We have improved an earlier retinal cell isolation method and obtained large numbers of entire cones. Principal cones (27% of the cones) possess a yellow or colourless droplet. Accessory cones (27% of the cones) all contain a small pale green droplet. Straight cones (44% of the cones) have a red, orange, yellow, or colourless droplet. Oblique cones (1.66% of the cones) all have a colourless droplet. We have found that straight cones with a red, orange, or yellow droplet differ in terms of the position of the nucleus and their percentage and conclude that they are distributed in three rows in the outer nuclear layer (ONL) of the central retina. Our study of 4,6-diamidino-2-phenylindole-stained retinal sections has revealed three rows of nuclei instead of the two currently thought to form the ONL. Together, our results show a larger cone diversity than previously known, suggest a larger functional diversity and provide an efficient method for isolating entire chick photoreceptors
Neocortical Axon Arbors Trade-off Material and Conduction Delay Conservation
The brain contains a complex network of axons rapidly communicating information between billions of synaptically connected neurons. The morphology of individual axons, therefore, defines the course of information flow within the brain. More than a century ago, Ramón y Cajal proposed that conservation laws to save material (wire) length and limit conduction delay regulate the design of individual axon arbors in cerebral cortex. Yet the spatial and temporal communication costs of single neocortical axons remain undefined. Here, using reconstructions of in vivo labelled excitatory spiny cell and inhibitory basket cell intracortical axons combined with a variety of graph optimization algorithms, we empirically investigated Cajal's conservation laws in cerebral cortex for whole three-dimensional (3D) axon arbors, to our knowledge the first study of its kind. We found intracortical axons were significantly longer than optimal. The temporal cost of cortical axons was also suboptimal though far superior to wire-minimized arbors. We discovered that cortical axon branching appears to promote a low temporal dispersion of axonal latencies and a tight relationship between cortical distance and axonal latency. In addition, inhibitory basket cell axonal latencies may occur within a much narrower temporal window than excitatory spiny cell axons, which may help boost signal detection. Thus, to optimize neuronal network communication we find that a modest excess of axonal wire is traded-off to enhance arbor temporal economy and precision. Our results offer insight into the principles of brain organization and communication in and development of grey matter, where temporal precision is a crucial prerequisite for coincidence detection, synchronization and rapid network oscillations
Genetically-Directed, Cell Type-Specific Sparse Labeling for the Analysis of Neuronal Morphology
Background: In mammals, genetically-directed cell labeling technologies have not yet been applied to the morphologic analysis of neurons with very large and complex arbors, an application that requires extremely sparse labeling and that is only rendered practical by limiting the labeled population to one or a few predetermined neuronal subtypes. Methods and Findings: In the present study we have addressed this application by using CreER technology to noninvasively label very small numbers of neurons so that their morphologies can be fully visualized. Four lines of IRES-CreER knock-in mice were constructed to permit labeling selectively in cholinergic or catecholaminergic neurons [choline acetyltransferase (ChAT)-IRES-CreER or tyrosine hydroxylase (TH)-IRES-CreER], predominantly in projection neurons [neurofilament light chain (NFL)-IRES-CreER], or broadly in neurons and some glia [vesicle-associated membrane protein2 (VAMP2)-IRES-CreER]. When crossed to the Z/AP reporter and exposed to 4-hydroxytamoxifen in the early postnatal period, the number of neurons expressing the human placental alkaline phosphatase reporter can be reproducibly lowered to fewer than 50 per brain. Sparse Cre-mediated recombination in ChAT-IRES-CreER;Z/AP mice shows the full axonal and dendritic arbors of individual forebrain cholinergic neurons, the first time that the complete morphologies of these very large neurons have been revealed in any species. Conclusions: Sparse genetically-directed, cell type-specific neuronal labeling with IRES-creER lines should prove useful fo
Visualizing the Distribution of Synapses from Individual Neurons in the Mouse Brain
BACKGROUND:Proper function of the mammalian brain relies on the establishment of highly specific synaptic connections among billions of neurons. To understand how complex neural circuits function, it is crucial to precisely describe neuronal connectivity and the distributions of synapses to and from individual neurons. METHODS AND FINDINGS:In this study, we present a new genetic synaptic labeling method that relies on expression of a presynaptic marker, synaptophysin-GFP (Syp-GFP) in individual neurons in vivo. We assess the reliability of this method and use it to analyze the spatial patterning of synapses in developing and mature cerebellar granule cells (GCs). In immature GCs, Syp-GFP is distributed in both axonal and dendritic regions. Upon maturation, it becomes strongly enriched in axons. In mature GCs, we analyzed synapses along their ascending segments and parallel fibers. We observe no differences in presynaptic distribution between GCs born at different developmental time points and thus having varied depths of projections in the molecular layer. We found that the mean densities of synapses along the parallel fiber and the ascending segment above the Purkinje cell (PC) layer are statistically indistinguishable, and higher than previous estimates. Interestingly, presynaptic terminals were also found in the ascending segments of GCs below and within the PC layer, with the mean densities two-fold lower than that above the PC layer. The difference in the density of synapses in these parts of the ascending segment likely reflects the regional differences in postsynaptic target cells of GCs. CONCLUSIONS:The ability to visualize synapses of single neurons in vivo is valuable for studying synaptogenesis and synaptic plasticity within individual neurons as well as information flow in neural circuits
Peripheral Nervous System Genes Expressed in Central Neurons Induce Growth on Inhibitory Substrates
Trauma to the spinal cord and brain can result in irreparable loss of function. This failure of recovery is in part due to inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans (CSPGs). Peripheral nervous system (PNS) neurons exhibit increased regenerative ability compared to central nervous system neurons, even in the presence of inhibitory environments. Previously, we identified over a thousand genes differentially expressed in PNS neurons relative to CNS neurons. These genes represent intrinsic differences that may account for the PNS’s enhanced regenerative ability. Cerebellar neurons were transfected with cDNAs for each of these PNS genes to assess their ability to enhance neurite growth on inhibitory (CSPG) or permissive (laminin) substrates. Using high content analysis, we evaluated the phenotypic profile of each neuron to extract meaningful data for over 1100 genes. Several known growth associated proteins potentiated neurite growth on laminin. Most interestingly, novel genes were identified that promoted neurite growth on CSPGs (GPX3, EIF2B5, RBMX). Bioinformatic approaches also uncovered a number of novel gene families that altered neurite growth of CNS neurons
Neuroregeneration in neurodegenerative disorders
<p>Abstract</p> <p>Background</p> <p>Neuroregeneration is a relatively recent concept that includes neurogenesis, neuroplasticity, and neurorestoration - implantation of viable cells as a therapeutical approach.</p> <p>Discussion</p> <p>Neurogenesis and neuroplasticity are impaired in brains of patients suffering from Alzheimer's Disease or Parkinson's Disease and correlate with low endogenous protection, as a result of a diminished growth factors expression. However, we hypothesize that the brain possesses, at least in early and medium stages of disease, a "neuroregenerative reserve", that could be exploited by growth factors or stem cells-neurorestoration therapies.</p> <p>Summary</p> <p>In this paper we review the current data regarding all three aspects of neuroregeneration in Alzheimer's Disease and Parkinson's Disease.</p
Analysis of two methods of isometric muscle contractions during the anti-G straining maneuver
This study investigated the difference in Mean Arterial Pressure (MAP) and Cardiac Output (CO) between two methods of isometric muscle contractions during the Anti-G Straining Maneuver (AGSM). 12 subjects (ages 18 to 38 yrs, height 176.8 +/- 7.4 cm, body mass 78.8 +/- 15.6 kg, percent body fat 14.3 +/- 6.6%) participated in the study. The study was a one-way within-subject design with test conditions counterbalanced. Two methods of isometric muscle contractions lasting 30 seconds each were assessed; an isometric push contraction and an isometric muscle tensing contraction. The dependent parameters were MAP and CO. The average MAP during the push contraction was 123 mmHg, SD +/- 11 and for tense was 118 mmHg, SD +/- 8. CO was 7.6 L/min, SD +/- 1.6 for push and 7.9 L/min, SD +/- 2.0 for tense method. Dependent t-tests revealed t(11) = 1.517, p = 0.157 for MAP and t(11) = 0.875, p = 0.400 for CO. This study demonstrated that the two methods of isometric muscle contractions were not statistically different with regards to MAP and CO. Therefore, both forms of isometric contractions may be potentially useful when performing the muscle contraction portion of the AGSM
- …