The effects of Bisphenol A on the Zebrafish embryo

Abstract only availableEndocrine disruptors are compounds that mimic hormones found in the endocrine system and, in doing so, alter the physiology of living organisms by affecting this regulatory system. Bisphenol A, a monomer used in polycarbonate plastics that is at the center of international controversy, is thought to act as an endocrine disruptor. Its application in shatterproof dishware is especially hazardous, due to the widespread use of polycarbonate plastics in the production of cups for infants and toddlers. This age group is especially prone to the acute effects of endocrine disruptors due to a weaker feedback regulatory system than in adults. Thus, my project focuses on the action of Bisphenol A in the developing organism, specifically, the zebrafish (Danio rerio) embryo. My previous work has shown that BPA treatment caused a 50-75% reduction in heart rate, a transient effect that is fully reversed upon its removal from the culture medium. Other symptoms of BPA treatment included cardiac edemas, muscular malformation, depigmentation, slow response time, and retardation of swim bladder inflation; all reported symptoms of other endocrine disruptors. Other previous experiments have also shown that this effect (in zebrafish) is not due to estrogen agonism and may be caused by a yet uninvestigated mechanism. To determine the chemical specificity required for heart rate reduction, I investigated several structural analogs of BPA. These experiments showed that while IDP and BPAF cause a similar (or more gravid) effect, BPS shows no activity in reducing heart rate. Since underlying cellular irregularities could cause the heart rate reduction seen with BPA treatment, I also used Immunohistochemical techniques on transgenic fish to study any defects in the developing vascular endothelium. My results illustrate that vascular endothelial development is not affected due to BPA treatment and does not cause the heart rate reduction seen in BPA treated fish

Alfven node-free vibrations of white dwarf in the model of solid star with toroidal magnetic field

In the context of the white dwarf asteroseismology, we investigate vibrational properties of a non-convective solid star with an axisymmetric purely toroidal intrinsic magnetic field of two different shapes. Focus is laid on regime of node-free global Lorentz-force-driven vibrations about symmetry axis at which material displacements have one and the same form as those for nodeless spheroidal and torsional vibrations restored by Hooke's force of elastic shear stresses. Particular attention is given to the even-parity poloidal Alfven modes whose frequency spectra are computed in analytic form showing how the purely toroidal magnetic fields completely buried beneath the star surface can manifest itself in seismic vibrations of non-magnetic white dwarfs. The obtained spectral formulae are discussed in juxtaposition with those for Alfven modes in the solid star model with the poloidal, homogeneous internal and dipolar external, magnetic field whose inferences are relevant to Alfven vibrations in magnetic white dwarfs.Comment: Accepted for publication in Astrophysics & Space Scienc

The cell adhesion molecule Tag1, transmembrane protein Stbm/Vangl2, and Lamininα1 exhibit genetic interactions during migration of facial branchiomotor neurons in zebrafish

AbstractInteractions between a neuron and its environment play a major role in neuronal migration. We show here that the cell adhesion molecule Transient Axonal Glycoprotein (Tag1) is necessary for the migration of the facial branchiomotor neurons (FBMNs) in the zebrafish hindbrain. In tag1 morphant embryos, FBMN migration is specifically blocked, with no effect on organization or patterning of other hindbrain neurons. Furthermore, using suboptimal morpholino doses and genetic mutants, we found that tag1, lamininα1 (lama1) and stbm, which encodes a transmembrane protein Vangl2, exhibit pairwise genetic interactions for FBMN migration. Using time-lapse analyses, we found that FBMNs are affected similarly in all three single morphant embryos, with an inability to extend protrusions in a specific direction, and resulting in the failure of caudal migration. These data suggest that tag1, lama1 and vangl2 participate in a common mechanism that integrates signaling between the FBMN and its environment to regulate migration

Transient axonal glycoprotein-1 (TAG-1) and laminin-α1 regulate dynamic growth cone behaviors and initial axon direction in vivo

<p>Abstract</p> <p>Background</p> <p>How axon guidance signals regulate growth cone behavior and guidance decisions in the complex <it>in vivo </it>environment of the central nervous system is not well understood. We have taken advantage of the unique features of the zebrafish embryo to visualize dynamic growth cone behaviors and analyze guidance mechanisms of axons emerging from a central brain nucleus <it>in vivo</it>.</p> <p>Results</p> <p>We investigated axons of the nucleus of the medial longitudinal fascicle (nucMLF), which are the first axons to extend in the zebrafish midbrain. Using <it>in vivo </it>time-lapse imaging, we show that both positive axon-axon interactions and guidance by surrounding tissue control initial nucMLF axon guidance. We further show that two guidance molecules, transient axonal glycoprotein-1 (TAG-1) and laminin-α1, are essential for the initial directional extension of nucMLF axons and their subsequent convergence into a tight fascicle. Fixed tissue analysis shows that TAG-1 knockdown causes errors in nucMLF axon pathfinding similar to those seen in a laminin-α1 mutant. However, <it>in vivo </it>time-lapse imaging reveals that while some defects in dynamic growth cone behavior are similar, there are also defects unique to the loss of each gene. Loss of either TAG-1 or laminin-α1 causes nucMLF axons to extend into surrounding tissue in incorrect directions and reduces axonal growth rate, resulting in stunted nucMLF axons that fail to extend beyond the hindbrain. However, defects in axon-axon interactions were found only after TAG-1 knockdown, while defects in initial nucMLF axon polarity and excessive branching of nucMLF axons occurred only in laminin-α1 mutants.</p> <p>Conclusion</p> <p>These results demonstrate how two guidance cues, TAG-1 and laminin-α1, influence the behavior of growth cones during axon pathfinding <it>in vivo</it>. Our data suggest that TAG-1 functions to allow growth cones to sense environmental cues and mediates positive axon-axon interactions. Laminin-α1 does not regulate axon-axon interactions, but does influence neuronal polarity and directional guidance.</p

Beyond Trophic Factors: Exploiting the Intrinsic Regenerative Properties of Adult Neurons

Injuries and diseases of the peripheral nervous system (PNS) are common but frequently irreversible. It is often but mistakenly assumed that peripheral neuron regeneration is robust without a need to be improved or supported. However, axonal lesions, especially those involving proximal nerves rarely recover fully and injuries generally are complicated by slow and incomplete regeneration. Strategies to enhance the intrinsic growth properties of reluctant adult neurons offer an alternative approach to consider during regeneration. Since axons rarely regrow without an intimately partnered Schwann cell (SC), approaches to enhance SC plasticity carry along benefits to their axon partners. Direct targeting of molecules that inhibit growth cone plasticity can inform important regenerative strategies. A newer approach, a focus of our laboratory, exploits tumor suppressor molecules that normally dampen unconstrained growth. However several are also prominently expressed in stable adult neurons. During regeneration their ongoing expression “brakes” growth, whereas their inhibition and knockdown may enhance regrowth. Examples have included phosphatase and tensin homolog deleted on chromosome ten (PTEN), a tumor suppressor that inhibits PI3K/pAkt signaling, Rb1, the protein involved in retinoblastoma development, and adenomatous polyposis coli (APC), a tumor suppressor that inhibits β-Catenin transcriptional signaling and its translocation to the nucleus. The identification of several new targets to manipulate the plasticity of regenerating adult peripheral neurons is exciting. How they fit with canonical regeneration strategies and their feasibility require additional work. Newer forms of nonviral siRNA delivery may be approaches for molecular manipulation to improve regeneration

Alterations in phenotype and gene expression of adult human aneurysmal smooth muscle cells by exogenous nitric oxide

International audienceAbdominal aortic aneurysms (AAA) are characterized by matrix remodeling, elastin degradation, absence of nitric oxide (NO) signaling, and inflammation, influencing smooth muscle cell (SMC) phenotype and gene expression. Little is known about the biomolecular release and intrinsic biomechanics of human AAA-SMCs. NO delivery could be an attractive therapeutic strategy to restore lost functionality of AAA-SMCs by inhibiting inflammation and cell stiffening. We aim to establish the differences in phenotype and gene expression of adult human AAA-SMCs from healthy SMCs. Based on our previous study which showed benefits of optimal NO dosage delivered via S-Nitrosoglutathione (GSNO) to healthy aortic SMCs, we tested whether such benefits would occur in AAA-SMCs. The mRNA expression of three genes involved in matrix degradation (ACE, ADAMTS5 and ADAMTS8) was significantly downregulated in AAA-SMCs. Total protein and glycosaminoglycans synthesis were higher in AAA-SMCs than healthy-SMCs (p < 0.05 for AAA-vs. healthy-SMC cultures) and was enhanced by GSNO and 3D cultures (p < 0.05 for 3D vs. 2D cultures; p < 0.05 for GSNO vs. non-GSNO cases). Elastin gene expression, synthesis and deposition, desmosine crosslinker levels, and lysyl oxidase (LOX) functional activity were lower, while cell proliferation, iNOS, LOX and fibrillin-1 gene expressions were higher in AAA-SMCs (p < 0.05 between respective cases), with differential benefits from GSNO exposure. GSNO and 3D cultures reduced MMPs −2, −9, and increased TIMP-1 release in AAA-SMC cultures (p < 0.05 for GSNO vs. non-GSNO cultures). AAA-SMCs were inherently stiffer and had smoother surface than healthy SMCs (p < 0.01 in both cases), but GSNO reduced stiffness (~25%; p < 0.01) and increased roughness (p < 0.05) of both cell types. In conclusion, exogenously-delivered NO offers an attractive strategy by providing therapeutic benefits to AAA-SMCs

Development of a water-based cooling system for the Muon Chamber detector system of the CBM experiment

A water-based cooling system is being investigated to meet the cooling requirement of the Gas Electron Multiplier (GEM) based Muon Chamber (MuCh) detector system of the Compressed Baryonic Matter (CBM) experiment at GSI, Germany. The system is based on circulating cold water through the channels inside an aluminium plate. The aluminium plate is attached to a GEM chamber. A feasibility study is conducted on one small and two real-size prototype cooling plates. A microcontroller based unit has been built and integrated into the system to achieve automatic control and monitoring of temperature on plate surface. The real-size prototypes have been used in a test beam experiment at the CERN SPS (Super Proton Synchrotron) with the lead beam on a lead target. A setup using three prototype modules has been prepared in the lab for testing in a simulated real life environment. This paper discusses the working principle, mechanical design, fabrication, and test results of the cooling prototypes in detail.Comment: 8 pages, 12 figures, 2 table

Radial Oscillations of Neutron Stars in Strong Magnetic Fields

The eigen frequencies of radial pulsations of neutron stars are calculated in a strong magnetic field. At low densities we use the magnetic BPS equation of state(EOS) similar to that obtained by Lai and Shapiro while at high densities the EOS obtained from the relativistic nuclear mean field theory is taken and extended to include strong magnetic field. It is found that magnetised neutron stars support higher maximum mass where as the effect of magnetic field on radial stability for observed neutron star masses is minimal.Comment: latex2e file with five postscript figure

The mouse Wnt/PCP protein Vangl2 is necessary for migration of facial branchiomotor neurons, and functions independently of Dishevelled

AbstractDuring development, facial branchiomotor (FBM) neurons, which innervate muscles in the vertebrate head, migrate caudally and radially within the brainstem to form a motor nucleus at the pial surface. Several components of the Wnt/planar cell polarity (PCP) pathway, including the transmembrane protein Vangl2, regulate caudal migration of FBM neurons in zebrafish, but their roles in neuronal migration in mouse have not been investigated in detail. Therefore, we analyzed FBM neuron migration in mouse looptail (Lp) mutants, in which Vangl2 is inactivated. In Vangl2Lp/+ and Vangl2 Lp/Lp embryos, FBM neurons failed to migrate caudally from rhombomere (r) 4 into r6. Although caudal migration was largely blocked, many FBM neurons underwent normal radial migration to the pial surface of the neural tube. In addition, hindbrain patterning and FBM progenitor specification were intact, and FBM neurons did not transfate into other non-migratory neuron types, indicating a specific effect on caudal migration.Since loss-of-function in some zebrafish Wnt/PCP genes does not affect caudal migration of FBM neurons, we tested whether this was also the case in mouse. Embryos null for Ptk7, a regulator of PCP signaling, had severe defects in caudal migration of FBM neurons. However, FBM neurons migrated normally in Dishevelled (Dvl) 1/2 double mutants, and in zebrafish embryos with disrupted Dvl signaling, suggesting that Dvl function is essentially dispensable for FBM neuron caudal migration. Consistent with this, loss of Dvl2 function in Vangl2Lp/+ embryos did not exacerbate the Vangl2Lp/+ neuronal migration phenotype. These data indicate that caudal migration of FBM neurons is regulated by multiple components of the Wnt/PCP pathway, but, importantly, may not require Dishevelled function. Interestingly, genetic-interaction experiments suggest that rostral FBM neuron migration, which is normally suppressed, depends upon Dvl function

On the Synergistic Catalytic Properties of Bimetallic Mesoporous Materials Containing Aluminum and Zirconium: The Prins Cyclisation of Citronellal

Bimetallic three-dimensional amorphous mesoporous materials, Al-Zr-TUD-1 materials, were synthesised by using a surfactant-free, one-pot procedure employing triethanolamine (TEA) as a complexing reagent. The amount of aluminium and zirconium was varied in order to study the effect of these metals on the Brønsted and Lewis acidity, as well as on the resulting catalytic activity of the material. The materials were characterised by various techniques, including elemental analysis, X-ray diffraction, high-resolution TEM, N2 physisorption, temperature-programmed desorption (TPD) of NH3, and 27Al MAS NMR, XPS and FT-IR spectroscopy using pyridine and CO as probe molecules. Al-Zr-TUD-1 materials are mesoporous with surface areas ranging from 700–900 m2 g−1, an average pore size of around 4 nm and a pore volume of around 0.70 cm3 g−1. The synthesised Al-Zr-TUD-1 materials were tested as catalyst materials in the Lewis acid catalysed Meerwein–Ponndorf–Verley reduction of 4-tert-butylcyclohexanone, the intermolecular Prins synthesis of nopol and in the intramolecular Prins cyclisation of citronellal. Although Al-Zr-TUD-1 catalysts possess a lower amount of acid sites than their monometallic counterparts, according to TPD of NH3, these materials outperformed those of the monometallic Al-TUD-1 as well as Zr-TUD-1 in the Prins cyclisation of citronellal. This proves the existence of synergistic properties of Al-Zr-TUD-1. Due to the intramolecular nature of the Prins cyclisation of citronellal, the hydrophilic surface of the catalyst as well as the presence of both Brønsted and Lewis acid sites synergy could be obtained with bimetallic Al-Zr-TUD-1. Besides spectroscopic investigation of the active sites of the catalyst material a thorough testing of the catalyst in different types of reactions is crucial in identifying its specific active sites