Determination of transmitter function by neuronal activity

The role of neuronal activity in the determination of transmitter function was studied in cultures of dissociated sympathetic neurons from newborn rat superior cervical ganglia. Cholinergic and adrenergic differentiation were assayed by incubating the cultures with radioactive choline and tyrosine and determining the rate of synthesis and accumulation of labelled acetylcholine and catecholamines. As in previous studies, pure neuronal cultures grown in control medium displayed much lower ratios of acetylcholine synthesis to catecholamine synthesis than did sister cultures grown in medium previously conditioned by incubation on appropriate nonneuronal cells (conditioned medium). However, here we report that neurons treated with the depolarizing agents elevated K+ or veratridine, or stimulated directly with electrical current, either before or during application of conditioned medium, displayed up to 300-fold lower acetylcholine/catecholamine ratios than they would have without depolarization, and thus remained primarily adrenergic. Elevated K+ and veratridine produced this effect on cholinergic differentiation without significantly altering neuronal survival. Because depolarization causes Ca2+ entry in a number of cell types, the effects of several Ca2+ agonists and antagonists were investigated. In the presence of the Ca2+ antagonists D600 or Mg2+, K+ did not prevent the induction of cholinergic properties by conditioned medium. Thus depolarization, either steady or accompanying activity, is one of the factors determining whether cultured sympathetic neurons become adrenergic or cholinergic, and this effect may be mediated by Ca2+

Critique: A Defendant\u27s View

In ten years, employers have become subject to an imposing body of law regulating employment practices. This law has created two immense problems for the employer. First, enforcement of these laws is frequently capricious, arbitrary and unfair. Second, recent decisions strip the employer of his most reliable methods for selecting skilled, productive workers and threaten the efficiency of American industry

Using Social Construction Theory as a Foundation for Macro-Level Interventions in Communities Impacted by HIV and Addictions

Many professionals working with people living with HIV and alcohol and other drug addictions rely heavily on micro and mezzo-level interventions. The authors argue that although these approaches are effective for helping people living with some social problems they are too narrow for working effectively with HIV-positive and alcohol and other drug-addicted individuals. The authors use social construction theory to analyze the social problems of HIV/AIDS and addictions and make recommendations for macro-level interventions that may help curtail the dual problems of HIV and addictions

Maternal Influenza Infection Causes Marked Behavioral and Pharmacological Changes in the Offspring

Maternal viral infection is known to increase the risk for schizophrenia and autism in the offspring. Using this observation in an animal model, we find that respiratory infection of pregnant mice (both BALB/c and C57BL/6 strains) with the human influenza virus yields offspring that display highly abnormal behavioral responses as adults. As in schizophrenia and autism, these offspring display deficits in prepulse inhibition (PPI) in the acoustic startle response. Compared with control mice, the infected mice also display striking responses to the acute administration of antipsychotic (clozapine and chlorpromazine) and psychomimetic (ketamine) drugs. Moreover, these mice are deficient in exploratory behavior in both open-field and novel-object tests, and they are deficient in social interaction. At least some of these behavioral changes likely are attributable to the maternal immune response itself. That is, maternal injection of the synthetic double-stranded RNA polyinosinic-polycytidylic acid causes a PPI deficit in the offspring in the absence of virus. Therefore, maternal viral infection has a profound effect on the behavior of adult offspring, probably via an effect of the maternal immune response on the fetus

Rapid Oscillations in Cataclysmic Variables. XV. HT Camelopardalis (= RX J0757.0+6306)

We present photometry and spectroscopy of HT Camelopardalis, a recently discovered X-ray-bright cataclysmic variable. The spectrum shows bright lines of H, He I, and He II, all moving with a period of 0.059712(1) d, which we interpret as the orbital period. The star's brightness varies with a strict period of 515.0592(2) s, and a mean full amplitude of 0.11 mag. These properties qualify it as a /bona fide/ DQ Herculis star (intermediate polar) -- in which the magnetism of the rapidly rotating white dwarf channels accretion flow to the surface. Normally at V=17.8, the star shows rare and very brief outbursts to V=12-13. We observed one in December 2001, and found that the 515 s pulse amplitude had increased by a factor of ~100 (in flux units). A transient orbital signal may also have appeared.Comment: PDF, 19 pages, 3 tables, 6 figures; accepted, in press, to appear June 2002, PASP; more info at http://cba.phys.columbia.edu

Movement of Red Snapper, Lutjanus campechanus, in the North Central Gulf of Mexico: Potential Effects of Hurricanes

Site fidelity and movement of red snapper, Lutjanus campechanus, were estimated from a tagging study conducted off the coast of Alabama from March 1995 to January 1997. Red snapper were caught using rod and reel over nine artificial reef sites, with three reefs each located at 21-m, 27-m, and 32-m depths. During the study, 1,604 fish were tagged, and 174 recaptures were made of 167 individuals. On 4 October 1995, the eye of Hurricane Opal passed within 40 km of the artificial reef sites. When recaptures were stratified according to whether or not they were at liberty during Opal, storm effect was the most significant factor in predicting the likelihood of movement and magnitude of movement by tagged red snapper. Eighty percent of recaptured red snapper that were not at liberty during Opal were recaptured at their site of release. Fish that were at liberty during Opal, however, had a significantly higher likelihood of movement away from their site of release (P \u3c 0.001). These fish also moved significantly further than those that were not at liberty during Opal (P \u3c 0.001). Fish that were at liberty during Opal moved a mean distance (± SE) of 32.6 km (± 6.81), compared to a mean distance (± SE) of 2.5 km (± 1.10) for fish that were tagged and recaptured before Opal, and a mean distance (± SE) of 1.7 km (± 0.43) for fish that were tagged and recaptured after Opal. Heretofore, it has generally been accepted that adult red snapper demonstrate strong site fidelity and genetic homogeneity in the stock was hypothesized to result from larval drift or due to historic mixing on longer time scales. This study documents movement of adult red snapper on spatial scales that would facilitate stock mixing and implicates large-scale climatic events, such as hurricanes, as important factors in stock mixing dynamics

Crystal Structure and Computational Analysis of a Two-Dimensional Coordination Polymer, BiI3(DppeO2)3/2

Catena-poly[fac-triiodobismuth(III)-tris-(µ-ethane-1,2-diylbis(diphenylphosphane oxide-κ2O,O′))], a 2-D sheet network of BiI3 was synthesized from BiI3 and ethane-1,2-diylbis(diphenylphosphane oxide) (DppeO2) in tetrahydrofuran. The crystal structure revealed a trigonal structure with three-fold symmetry at Bi. Bismuth centers show fac-BiI3O3 coordination, with Bi–I = 2.9416(2) Å and Bi–O = 2.4583(17) Å. The I–Bi–I and O–Bi–O angles (95.520(7)° and 79.04(6)°, respectively) indicate trigonal distortion in the Bi octahedron. Bridging DppeO2 ligands centered on inversion centers give rise to a 2-D sheet polymer. The 8.3 Å thick sheets consist of three layers in a sandwich structure. The outer layers are composed of phenyl rings and BiI3 groups with the iodide atoms pointing outward. The central layer consists of the O=PCH2CH2P=O bridging groups. Computational results suggest that semi-conducting behavior arises from Bi(III) centers. A halide to DppeO2 π* transition is suggested by theoretical results

The interaction between maternal immune activation and alpha 7 nicotinic acetylcholine receptor in regulating behaviors in the offspring

Mutation of human chromosome 15q13.3 increases the risk for autism and schizophrenia. One of the noteworthy genes in 15q13.3 is CHRNA7, which encodes the nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) associated with schizophrenia in clinical studies and rodent models. This study investigates the role of α7nAChR in maternal immune activation (MIA) mice model, a murine model of environmental risk factor for autism and schizophrenia. We provided choline, a selective α7nAChR agonist among its several developmental roles, in the diet of C57BL/6N wild-type dams throughout the gestation and lactation period and induced MIA at mid-gestation. The adult offspring behavior and gene expression profile in the maternal splenic-placenta-fetal brain axis at mid-gestation were investigated. We found that choline supplementation prevented several MIA behavioral abnormalities in the wild-type offspring. Pro-inflammatory cytokine interleukin-6 (IL-6) and Chrna7 gene expression in the wild-type fetal brain were elevated by poly(I:C) injection and were suppressed by gestational choline supplementation. We further investigated the gene expression level of IL-6 in Chrna7 mutant mice. We found that the basal level of IL-6 was higher in Chrna7 mutant fetal brain, which suggests that α7nAChR may serve an anti-inflammatory role in the fetal brain during development. Lastly, we induced MIA in Chrna7+/− offspring. The Chrna7+/− offspring were more vulnerable to MIA, with increased behavioral abnormalities. Our study shows that α7nAChR modulates inflammatory response affecting the fetal brain and demonstrates its effects on offspring behavior development after maternal infection

Assessment of digital image correlation measurement errors: methodology and results

Optical full-field measurement methods such as Digital Image Correlation (DIC) are increasingly used in the field of experimental mechanics, but they still suffer from a lack of information about their metrological performances. To assess the performance of DIC techniques and give some practical rules for users, a collaborative work has been carried out by the Workgroup “Metrology” of the French CNRS research network 2519 “MCIMS (Mesures de Champs et Identification en Mécanique des Solides / Full-field measurement and identification in solid mechanics, http://www.ifma.fr/lami/gdr2519)”. A methodology is proposed to assess the metrological performances of the image processing algorithms that constitute their main component, the knowledge of which being required for a global assessment of the whole measurement system. The study is based on displacement error assessment from synthetic speckle images. Series of synthetic reference and deformed images with random patterns have been generated, assuming a sinusoidal displacement field with various frequencies and amplitudes. Displacements are evaluated by several DIC packages based on various formulations and used in the French community. Evaluated displacements are compared with the exact imposed values and errors are statistically analyzed. Results show general trends rather independent of the implementations but strongly correlated with the assumptions of the underlying algorithms. Various error regimes are identified, for which the dependence of the uncertainty with the parameters of the algorithms, such as subset size, gray level interpolation or shape functions, is discussed

An efficient assay for identification and quantitative evaluation of potential polysialyltransferase inhibitors

YesThe polysialyltransferases (polySTs) catalyse the polymerisation of polysialic acid, which plays an important role in tumour metastasis. While assays are available to assess polyST enzyme activity, there is no methodology available specifically optimised for identification and quantitative evaluation of potential polyST inhibitors. The development of an HPLC-fluorescence-based enzyme assay described within includes a comprehensive investigation of assay conditions, including evaluation of metal ion composition, enzyme, substrate and acceptor concentrations, temperature, pH, and tolerance to DMSO, followed by validation using known polyST inhibitors. Thorough analysis of each of the assay components provided a set of optimised conditions. Under these optimised conditions, the experimentally observed Ki value for CMP, a competitive polyST inhibitor, was strongly correlated with the predicted Ki value, based on the classical Cheng-Prusoff equation [average fold error (AFE) = 1.043]. These results indicate that this assay can provide medium-throughput analysis for enzyme inhibitors with high accuracy, through determining the corresponding IC50 values with substrate concentration at the KM, without the need to perform extensive kinetic studies for each compound. In conclusion, an in vitro cell-free assay for accurate assessment of polyST inhibition is described. The utility of the assay for routine identification of potential polyST inhibitors is demonstrated, allowing quantitative measurement of inhibition to be achieved, and exemplified through assessment of full competitive inhibition. Given the considerable and growing interest in the polySTs as important anti-metastatic targets in cancer drug discovery, this is a vital tool to enable preclinical identification and evaluation of novel polyST inhibitors.Yorkshire Cancer Research, Wellcome Trus