Nervous System

Griscelli syndrome (GS) is caused by mutations in the MYO5A (GS1), RAB27A (GS2), or MLPH (GS3) genes, all of which lead to a similar pigmentary dilution. In addition, GS1 patients show primary neurological impairment, whereas GS2 patients present immunodeficiency and periods of lymphocyte proliferation and activation, leading to their infiltration in many organs, such as the nervous system, causing secondary neurological damage. We report the diagnosis of GS2 in a 4-year-old child with haemophagocytic syndrome, immunodeficiency, and secondary neurological disorders. Typical melanosome accumulation was found in skin melanocytes and pigment clumps were observed in hair shafts. Two heterozygous mutant alleles of the RAB27A gene were found, a C-T transition (C352T) that leads to Q118stop and a G-C transversion on the exon 5 splicing donor site (G467+1C). Functional assays showed increased cellular activation and decreased cytotoxic activity of NK and CD8+ T cells, associated with defective lytic granules release. Myosin-Va expression and localization in the patient lymphocytes were also analyzed. Most importantly, we show that cytotoxic activity of the patient's CD8+ T lymphocytes can be rescued in vitro by RAB27A gene transfer mediated by a recombinant retroviral vector, a first step towards a potential treatment of the acute phase of GS2 by RAB27A transduced lymphocytes.

Neuronal growth cones navigate over long distances along specific pathways to find their correct targets. The mechanisms and molecules that direct this pathfinding are the topics of this review. Growth cones appear to be guided by at least four different mechanisms: contact ...

Abstract: As a group, heavy metals include both those essential for normal biological functioning (e.g., Cu and Zn), and nonessential metals (e.g., Cd, Hg, and Pb). Both essential and nonessential metals can be present at concentrations that disturb normal biological functions, and which evoke cellular stress responses. The cellular targets for metal toxicity include tissues of the kidney, liver, heart, and the immune response and nervous systems. Intriguingly, manipulations of specific metals, their reservoirs, and the cellular stress response can have therapeutic effects on certain diseases. In this minireview, we will consider both the biological responses to stressful levels of heavy metal cations, and experimental and clinical manipulations of these cations as a means to improve human health parameters.

Responses in the external anal and urethral sphincters as well as in the bulbocavernosus muscle have been evoked by supramaximal electrical stimulation of the penis (or clitoris), perineum and the peri-anal region and recorded electromyographically in 82 male subjects 5 to 73 years old and in nine female subjects 18 to 55 years old, who had no systemic diseases or demonstrable sacral nervous system lesion. On perineal stimulation (including the penis or clitoris) reflex responses with a typical latency of 33 ms and which exhibit no habituation were obtained in all muscles examined. Stimulation of the peri-anal region gave habituating reflex responses with a typical latency of 55 ms in all muscles examined. On perineal, and sometimes also peri-anal stimulation, stable short latency responses with typical latencies of 5 and 13 ms were recorded; both were considered to be direct responses. The different evoked muscle responses obtained by stimulation in the perineal and peri-anal regio...

The Spemann organizer induces neural tissue from dorsal ectoderm and dorsalizes lateral and ventral mesoderm in Xenopus. The secreted factor noggin, which is expressed in the organizer, can mimic the dorsalizing signal of the organizer. Data are presented showing that noggin directly induces neural tissue, that it induces neural tissue in the absence of dorsal mesoderm, and that it acts at the appropriate stage to be an endogenous neural inducing signal. Noggin induces cement glands and anterior brain markers, but not hindbrain or spinal cord markers. Thus, noggin has the expression pattern and activity expected of an endogenous neural inducer.

The differentiation and proliferation of neural stem/progenitor cells (NPCs) depend on various in vivo environmental factors or cues, which may include an endogenous electrical field (EF), as observed during nervous system development and repair. In this study, we investigate the morphologic, phenotypic, and mitotic alterations of adult hippocampal NPCs that occur when exposed to two EFs of estimated endogenous strengths. NPCs treated with a 437 mV/mm direct current (DC) EF aligned perpendicularly to the EF vector and had a greater tendency to differentiate into neurons, but not into oligodendrocytes or astrocytes, compared to controls. Furthermore, NPC process growth was promoted perpendicularly and inhibited anodally in the 437 mV/mm DC EF. Yet fewer cells were observed in the DC EF, which in part was due to a decrease in cell viability. The other EF applied was a 46 mV/mm alternating current (AC) EF. However, the 46 mV/mm AC EF showed no major differences in alignment or differentiation, compared to control conditions. For both EF treatments, the percent of mitotic cells during the last 14 h of the experiment were statistically similar to controls. Reported here, to our knowledge, is the first evidence of adult NPC differentiation affected in an EF in vitro. Further investigation and application of EFs on stem cells is warranted to elucidate the utility of EFs to control phenotypic behavior. With progress, the use of EFs may be engineered to control differentiation and target the growth of transplanted cells in a stem cell-based therapy to treat nervous system disorders.

Background: Whether long-chain polyunsaturated fatty acids (LCPs) play a role in the development of the young nervous sys- tem in term infants is debated. Objective: We investigated whether supplementation of formula with LCPs for 2 mo improves the quality of general movements (GMs) in healthy term infants at 3 mo of age. Design: A prospective, double-blind, randomized controlled study was

An artificial neural network (hence after, ANN) is an information processing paradigm that is inspired by the way biological nervous systems, such as the brain, process information. In previous two decades, ANN applications in economics and finance; for such tasks as pattern reorganization, and time series forecasting, have dramatically increased. Many central banks use forecasting models based on ANN methodology for predicting various macroeconomic indicators, like inflation, GDP Growth and currency in circulation etc. In this paper, we have attempted to forecast monthly YoY inflation for Pakistan by using ANN for FY08 on the basis of monthly data of July 1993 to June 2007. We also compare the forecast performance of the ANN model with conventional univariate time series forecasting models such as AR(1) and ARIMA based models and observed that RMSE of ANN based forecasts is much less than the RMSE of forecasts based on AR(1) and ARIMA models. At least by this criterion forecast bas...

The effects of pyrantel and the febantel metabolite fenbendazole - pyrantel and febantel are both constituents of Drontal® Plus and Welpan® - against Toxocara canis in-vitro were investigated by studying changes in worm motility and tissue damage. Pyrantel (P) (range : 12.2, 25 or 50 μg/ml) and fenbendazole (F) (range : 50, 100 or 200 μg/ml) were added to the worms at different concentrations corresponding to plasma levels in different target animals obtained after oral dosing of the single drugs. Regarding motility changes there were no significant differences observable between pyrantel or fenbendazole given as single drugs and the pyrantel/fenbendazole combination. By contrast, when changes in tissue damages were studied there were significant differences detectable. Thus, hypodermis, muscles, gut, genital organs and nervous system got damaged severely at the concentrations of drug combinations P/F of 25/100 μg/ml. Similar effects could only be seen with the individual compounds at their highest level of concentration, e.g. 50 μg/ml of pyrantel or 200 μg/ml of fenbendazole. In comparative analyses of irreversible tissue damages the synergistic effects observed were regarded as being so important that the conclusion must be drawn that these effects are also be present in-vivo in Drontal® Plus and Welpan® treated dogs resulting in a complete worm destruction.

The Drosophila pair-rule gene odz (Tenm) has many patterning roles throughout development. We have identified four mammalian homologs of this gene, including one previously described as a mouse ER stress response gene, Doc4 (Wang et al., 1998). The Odz genes encode large polypeptides displaying the hallmarks of Drosophila Odz: a putative signal peptide; eight EGF-like repeats; and a putative transmembrane domain followed by a 1800-amino-acid stretch without homology to any proteins outside of this family. The mouse genes Odz3 and Doc4/Odz4 exhibit partially overlapping, but clearly distinct, embryonic expression patterns. The major embryonic sites of expression are in the nervous system, including the tectum, optic recess, optic stalk, and developing eye. Additional sites of expression include trachea and mesodermally derived tissues, such as mesentery, and forming limb and bone. Expression of the Odz2 gene is restricted to the nervous system. The expression patterns suggest that each of the genes has its own distinct developmental role. Comparisons of Drosophila and vertebrate Odz expression patterns suggest evolutionarily conserved functions.