Overexpression of a Slit homologue impairs convergent extension of the mesoderm and causes cyclopia in embryonic zebrafish

Slit is expressed in the midline of the central nervous system both in vertebrates and invertebrates. In Drosophila, it is the midline repellent acting as a ligand for the Roundabout (Robo) protein, the repulsive receptor which is expressed on the growth cones of the commissural neurons. We have isolated cDNA fragments of the zebrafish slit2 and slit3 homologues and found that both genes start to be expressed by the midgastrula stage well before the axonogenesis begins in the nervous system, both in the axial mesoderm, and slit2 in the anterior margin of the neural plate and slit3 in the polster at the anterior end of the prechordal mesoderm. Later, expression of slit2 mRNA is detected mainly in midline structures such as the floor plate cells and the hypochord, and in the anterior margins of the neural plates in the zebrafish embryo, while slit3 expression is observed in the anterior margin of the prechordal plate, the floorplate cells in the hindbrain, and the motor neurons both in the hindbrain and the spinal cord. To study the role of Slit in early embryos, we overexpressed Slit2 in the whole embryos either by injection of its mRNA into one-cell stage embryos or by heat-shock treatment of the transgenic embryos which carries the slit2 gene under control of the heat-shock promoter. Overexpression of Slit2 in such ways impaired the convergent extension movement of the mesoderm and the rostral migration of the cells in the dorsal diencephalon and resulted in cyclopia. Our results shed light on a novel aspect of Slit function as a regulatory factor of mesodermal cell movement during gastrulation. (C) 2001 Academic Press.

Do generalized visual training programmes for sport really work? An experimental investigation

We assessed the effectiveness of two generalized visual training programmes in enhancing visual and motor performance for racquet sports. Forty young participants were assigned equally to groups undertaking visual training using Revien and Gabor's Sports Vision programme (Group 1), visual training using Revien's Eyerobics (Group 2), a placebo condition involving reading (Group 3) and a control condition involving physical practice only (Group 4). Measures of basic visual function and of sport-specific motor performance were obtained from all participants before and immediately after a 4-week training period. Significant pre- to post-training differences were evident on some of the measures; however, these were not group-dependent. Contrary to the claims made by proponents of generalized visual training, we found no evidence that the visual training programmes led to improvements in either vision or motor performance above and beyond those resulting simply from test familiarity.

Cavity QED analog of the harmonic-oscillator probability distribution function and quantum collapses

We establish a connection between the simple harmonic oscillator and a two-level atom interacting with resonant, quantized cavity and strong driving fields, which suggests an experiment to measure the harmonic-oscillator's probability distribution function. To achieve this, we calculate the Autler-Townes spectrum by coupling the system to a third level. We find that there are two different regions of the atomic dynamics depending on the ratio of the: Rabi frequency Omega (c) of the cavity field to that of the Rabi frequency Omega of the driving field. For Omega (c)

Gag-Pol supplied in trans is efficiently packaged and supports viral function in human immunodeficiency virus type 1

The intracellular trafficking and subsequent incorporation of Gag-Pol into human immunodeficiency virus type 1 (HIV-1) remains poorly defined. Gag-Pol is encoded by the same mRNA as Gag and is generated by ribosomal frameshifting. The multimerization of Gag and Gag-Pol is an essential step in the formation of infectious viral particles. In this study, we examined whether the interaction between Gag and Gag-Pol is initiated during protein translation in order to facilitate the trafficking and subsequent packaging of Gag-Pol into the virion. A conditional cotransfection system was developed in which virion formation required the coexpression of two HIV-1-based plasmids, one that produces both Gag and Gag-Pol and one that only produces Gag-Pol. The Gag-Pol proteins were either immunotagged with a His epitope or functionally tagged with a mutation (K65R) in reverse transcriptase that is associated with drug resistance. Gag-Pol packaging was assessed to determine whether the Gag-Pol incorporated into the virion was preferentially packaged from the plasmid that expressed both Gag and Gag-Pol or whether it could be packaged from either plasmid. Our data show that translation of Gag and Gag-Pol from the same mRNA is not critical for virion packaging of the Gag-Pol polyprotein or for viral function.

Subcortical brain mechanisms in speech and language

This paper reviews current research and contemporary theories of subcortical participation in the motor control of speech production and language processing. As a necessary precursor to the discussion of the functional roles of the basal ganglia and thalamus, the neuroanatomy of the basal ganglial-thalamocortical circuitry is described. Contemporary models of hypokinetic and hyperkinetic movement disorders based on recent neuroanatomical descriptions of the multi-segmented circuits that characterise basal ganglion anatomy are described. Reported effects of surgically induced lesions in the globus pallidus and thalamus on speech production are reviewed. In addition, contemporary models proposed to explain the possible contribution of various subcortical structures to language processing are described and discussed in the context of evidence gained from observation of the effects of circumscribed surgically induced lesions in the basal ganglia and thalamus on language function. The potential of studies based on examination of the speech/language outcomes of patients undergoing pallidotomy and thalamotomy to further inform the debate relating to the role of subcortical structures in speech motor control and language processing is highlighted. Copyright (C) 2001 S. Karger AG, Basel.

Mass balance characterisation of Al-7Si-Mg alloy microstructures as a function of solution treatment time

Mass balance calculations were performed to model the effect of solution treatment time on A356 and A357 alloy microstructures. Image analysis and electron probe microanalysis were used to characterise microstructures and confirm model predictions. In as-cast microstructures, up to 8 times more Mg is tied up in the pi-phase than in Mg2Si. The dissolution of pi is accompanied by a corresponding increase in the amount of beta-phase. This causes the rate of pi dissolution to be limited by the rate of beta formation. It is predicted that solution treatments of the order of tens of minutes at 540degreesC produce near-maximum T6 yield strengths, and that Mg contents in excess of 0.52 wt% have no advantage.

Changes in motor planning of feedforward postural responses of the trunk muscles in low back pain

Changes in trunk muscle recruitment have been identified in people with low-back pain (LBP). These differences may be due to changes in the planning of the motor response or due to delayed transmission of the descending motor command in the nervous system. These two possibilities were investigated by comparison of the effect of task complexity on the feedforward postural response of the trunk muscles associated with rapid arm movement in people with and without LBP. Task complexity was increased by variation of the expectation for a command to either abduct or flex the upper limb. The onsets of electromyographic activity (EMG) of the abdominal and deltoid muscles were measured. In control subjects, while the reaction time of deltoid and the superficial abdominal muscles increased with task complexity, the reaction time of transversus abdominis (TrA) was constant. However, in subjects with LBP, the reaction time of TrA increased along with the other muscles as task complexity was increased. While inhibition of the descending motor command cannot be excluded, it is more likely that the change in recruitment M of TrA represents a more complex change in organisation of the postural response.

Muscle strength and function before and after anterior cruciate ligament reconstruction using semitendonosus and gracilis

This study assessed the quadriceps and hamstring strength before and 6 months after anterior cruciate ligament (ACL) reconstructive surgery using the hamstrings and related the findings to functional performance. Six months after surgery is a critical time for assessment as this is when players are returning to sport. Maximum isokinetic strength of 31 patients with complete unilateral ACL ruptures was measured at speeds of 60 degrees and 120 degrees per second. Functional assessment included the single hop, the triple hop, the shuttle run, side-step and carioca tests. All patients underwent a controlled quadriceps emphasized home-based physiotherapy program both before and after surgery. Results show that before surgery there was a 7.3% quadriceps strength deficit at 60 degrees per second compared to the uninjured leg but no hamstring strength deficit. After surgery there was a statistically significant but relatively small loss of muscle strength. The quadriceps strength deficit had increased to 12% and there was a 10% hamstring deficit. Post-operatively there was an 11% and 6.3% improvement in the hop tests, a 9% (P < 0.01) improvement in the shuttle run, a 15% (P < 0.001) improvement in the side step and a 24% (P < 0.001) improvement in the carioca tests (P < 0.001) despite the loss of muscle strength. (C) 2001 Elsevier Science B.V. All rights reserved.

Effect of the toxic milk mutation (tx) on the function and intracellular localization of Wnd, the murine homologue of the Wilson copperATPase

Wilson disease is an autosomal recessive copper transport disorder resulting from defective biliary excretion of copper and subsequent hepatic copper accumulation and liver failure if not treated. The disease is caused by mutations in the ATP7B (WND) gene, which is expressed predominantly in the liver and encodes a copper-transporting P-type ATPase that is structurally and functionally similar to the Menkes protein (MNK), which is defective in the X-linked copper transport disorder Menkes disease. The toxic milk (tx) mouse has a clinical phenotype similar to Wilson disease patients and, recently, the tx mutation within the murine WND homologue (Wnd) of this mouse was identified, establishing it as an animal model for Wilson disease. In this study, cDNA constructs encoding the wild-type (Wnd-wt) and mutant (Wnd-tx) Wilson proteins (Wnd) were generated and expressed in Chinese hamster ovary (CHO) cells. The fx mutation disrupted the copper-induced relocalization of Wnd in CHO cells and abrogated Wnd-mediated copper resistance of transfected CHO cells. In addition, co-localization experiments demonstrated that while Wnd and MNK are located in the trans-Golgi network in basal copper conditions, with elevated copper, these proteins are sorted to different destinations within the same cell, Ultrastructural studies showed that with elevated copper levels, Wnd accumulated in large multivesicular structures resembling late endosomes that may represent a novel compartment for copper transport. The data presented provide further support for a relationship between copper transport activity and the copper-induced relocalization response of mammalian copper ATPases, and an explanation at a molecular level for the observed phenotype of fx mice.

RelB nuclear translocation mediated by C-terminal activator reigons of Epstein Barr virus-encoded latent membrane protein 1 and its effect on antigen-presenting function in B cells

Previous studies have shown that Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) is uniquely able to up-regulate the expression of the peptide transporters (referred to as TAP-1 and TAP-2) and major histocompatibility complex (MHC) class I in Burkitt's lymphoma (BL) cell lines. This up-regulation is often accompanied by a restoration of antigen-presenting function as measured by the ability of these cells to present endogenously expressed viral antigen to cytotoxic T lymphocytes. Here we show that the expression of LMP1 resulted in up-regulation and nuclear translocation of RelB that were coincident with increased expression of MHC class I in BL cells. Deletion of the C-terminal activator regions (CTARs) of LMP1 significantly impaired the abilities of LMP1 to translocate RelB into the nucleus and to up-regulate the expression of antigen-processing genes. Further analysis with single-point mutations within the CTARs confirmed that the residues critical for NF-kappaB activation directly contribute to antigen-processing function regulation in BL cells. This LMP1-mediated effect was blocked following expression of either dominant negative IkappaBalpha S32/36A, an NF-kappaB inhibitor, or antisense RelB. These observations indicate that upregulation of antigen-presenting function in B cells mediated by LMP1 is signaled through the NF-kappaB subunit RelB. The data provide a mechanism by which LMP1 modulates immunogenicity of Epstein-Barr virus-infected normal and malignant cells.

Analysis of the microbial community structure and function of a laboratory scale enhanced biological phosphorus removal reactor

A laboratory scale sequencing batch reactor (SBR) operating for enhanced biological phosphorus removal (EBPR) and fed with a mixture of volatile fatty acids (VFAs) showed stable and efficient EBPR capacity over a four-year-period. Phosphorus (P), poly-beta-hydroxyalkanoate (PHA) and glycogen cycling consistent with classical anaerobic/aerobic EBPR were demonstrated with the order of anaerobic VFA uptake being propionate, acetate then butyrate. The SBR was operated without pH control and 63.67+/-13.86 mg P l(-1) was released anaerobically. The P% of the sludge fluctuated between 6% and 10% over the operating period (average of 8.04+/-1.31%). Four main morphological types of floc-forming bacteria were observed in the sludge during one year of in-tensive microscopic observation. Two of them were mainly responsible for anaerobic/aerobic P and PHA transformations. Fluorescence in situ hybridization (FISH) and post-FISH chemical staining for intracellular polyphosphate and PHA were used to determine that 'Candidatus Accumulibacter phosphatis' was the most abundant polyphosphate accumulating organism (PAO), forming large clusters of coccobacilli (1.0-1.5 mum) and comprising 53% of the sludge bacteria. Also by these methods, large coccobacillus-shaped gammaproteobacteria (2.5-3.5 mum) from a recently described novel cluster were glycogen-accumulating organisms (GAOs) comprising 13% of the bacteria. Tetrad-forming organisms (TFOs) consistent with the 'G bacterium' morphotype were alphaproteobacteria , but not Amaricoccus spp., and comprised 25% of all bacteria. According to chemical staining, TFOs were occasionally able to store PHA anaerobically and utilize it aerobically.

Existence of a semicontinuous or continuous utility function: a unified approach and an elementary proof

In this paper, we present a new unified approach and an elementary proof of a very general theorem on the existence of a semicontinuous or continuous utility function representing a preference relation. A simple and interesting new proof of the famous Debreu Gap Lemma is given. In addition, we prove a new Gap Lemma for the rational numbers and derive some consequences. We also prove a theorem which characterizes the existence of upper semicontinuous utility functions on a preordered topological space which need not be second countable. This is a generalization of the classical theorem of Rader which only gives sufficient conditions for the existence of an upper semicontinuous utility function for second countable topological spaces. (C) 2002 Elsevier Science B.V. All rights reserved.

The non-existence of a utility function and the structure of non-representable preference relations

In this paper we investigate the structure of non-representable preference relations. While there is a vast literature on different kinds of preference relations that can be represented by a real-valued utility function, very little is known or understood about preference relations that cannot be represented by a real-valued utility function. There has been no systematic analysis of the non-representation problem. In this paper we give a complete description of non-representable preference relations which are total preorders or chains. We introduce and study the properties of four classes of non-representable chains: long chains, planar chains, Aronszajn-like chains and Souslin chains. In the main theorem of the paper we prove that a chain is non-representable if and only it is a long chain, a planar chain, an Aronszajn-like chain or a Souslin chain. (C) 2002 Published by Elsevier Science B.V.