Complete DNA sequence and gene organization of the mitochondrial genome of the liverfluke, Fasciola hepatica L. (Platyhelminthes; Trematoda)

The complete nucleotide sequence of the mitochondrial (mt) DNA molecule of the liverfluke, Fasciola hepatica (phylum Platyhelminthes, class Trematoda, family Fasciolidae), was determined, It comprises 14462 bp, contains 12 protein-encoding, 2 ribosomal and 22 transfer RNA genes, and is the second complete flatworm (and the first trematode) mitochondrial sequence to be described in detail. All of the genes are transcribed from the same strand. Of the genes typically found in mitochondrial genomes of eumetazoans, only atp8 is absent. The nad4L and nad4 genes overlap by 40 nt. Most intergenic sequences are very short. Two larger non-coding regions are present. The longer one (817 nt) is located between trnG and cox3 and consists of 8 identical tandem repeats of 85 nt, rich in G and C, followed by 1 imperfect repeat. The shorter non-coding region (187 nt) exhibits no special features and is separated from the longer region by trnG. The gene arrangement resembles that of some other trematodes including the eastern Asian Schistosoma species (and cyclophyllidean cestode species) but it is strikingly different from that of the African schistosomes, represented by Schistosoma mansoni. The genetic code is as inferred previously for flatworms. Transfer RNA genes range in length from 58 to 70 nt, their products producing characteristic 'clover leaf' structures, except for tRNA(S-VON) and tRNA(S-AGN) lacking the DHU arm.

A dileucine motif targets E-cadherin to the basolateral cell surface in Madin-Darby canine kidney and LLC-PK1 epithelial cells

E-cadherin is a major adherens junction protein of epithelial cells, with a central role in cell-cell adhesion and cell polarity. Newly synthesized E-cadherin is targeted to the basolateral cell surface, We analyzed targeting information in the cytoplasmic tail of E-cadherin by utilizing chimeras of E-cadherin fused to the ectodo- main of the interleukin-2 alpha (IL-2 alpha) receptor expressed in Madin-Darby canine kidney and LLC-PK1 epithelial cells, Chimeras containing the full-length or membrane-proximal half of the E-cadherin cytoplasmic tail were correctly targeted to the basolateral domain. Sequence analysis of the membrane-proximal tail region revealed the presence of a highly conserved dileucine motif, which was analyzed as a putative targeting signal by mutagenesis. Elimination of this motif resulted in the loss of Tac/E-cadherin basolateral localization, pinpointing this dileucine signal as being both necessary and sufficient for basolateral targeting of E-cadherin, Truncation mutants unable to bind beta -catenin were correctly targeted, showing, contrary to current understanding, that beta -catenin is not required for basolateral trafficking. Our results also provide evidence that dileucine mediated targeting is maintained in UC-PK, cells despite the altered polarity of basolateral proteins with tyrosine-based signals in this cell line, These results provide the first direct insights into how E-cadherin is targeted to the basolateral membrane.

Ionic selectivity of native ATP-activated (P2X) receptor channels in dissociated neurones from rat parasympathetic ganglia

1. The relative permeability of the native P2X receptor channel to monovalent and divalent inorganic and organic cations was determined from reversal potential measurements of ATP-evoked currents in parasympathetic neurones dissociated from rat submandibular ganglia using the dialysed whole-cell patch clamp technique. 2. The P2X receptor-channel exhibited weak selectivity among the alkali metals with a selectivity sequence of Na+ > Li+ > Cs+ > Rb+ > K+, and permeability ratios relative to Cs+ (P-X/P-Cs) ranging from 1. 11 to 0.86. 3. The selectivity for the divalent alkaline earth cations was also weak with the sequence Ca2+ > Sr2+ > Ba2+ > Mn2+ > Mg2+. ATP-evoked currents were strongly inhibited when the extracellular divalent cation concentration was increased. 4, The calculated permeability ratios of different ammonium cations are higher than those of the alkali metal cations. The permeability sequence obtained for the saturated organic cations is inversely correlated with the size of the cation. The unsaturated organic cations have a higher permeability than that predicted by molecular size. 5. Acidification to pH 6.2 increased the ATP-induced current amplitude twofold, whereas alkalization to 8.2 and 9.2 markedly reduced current amplitude. Cell dialysis with either anti-P2X(2) and/or anti-P2X(4) but not anti-P2X(1) antibodies attenuated the ATP-evoked current amplitude. Taken together, these data are consistent with homomeric and/or heteromeric P2X(2) and P2X(4) receptor subtypes expressed in rat submandibular neurones. 6. The permeability ratios for the series of monovalent organic cations, with the exception of unsaturated cations, were approximately related to the ionic size. The relative permeabilities of the monovalent inoganic and organic cations tested are similar to those reported previously for cloned rat P2X2 receptors expressed in mammalian cells.

Compact clinical MRI magnet design using a multilayer current density approach

In this work, a new method of optimization is successfully applied to the theoretical design of compact, actively shielded, clinical MRI magnets. The problem is formulated as a two-step process in which the desired current densities on multiple, cc-axial surface layers are first calculated by solving Fredholm equations of the first kind. Non-linear optimization methods with inequality constraints are then invoked to fit practical magnet coils to the desired current densities. The current density approach allows rapid prototyping of unusual magnet designs. The emphasis of this work is on the optimal design of short, actively-shielded MRI magnets for whole-body imaging. Details of the hybrid numerical model are presented, and the model is used to investigate compact, symmetric, and asymmetric MRI magnets. Magnet designs are presented for actively-shielded, symmetric magnets of coil length 1.0 m, which is considerably shorter than currently available designs of comparable dsv size. Novel, actively-shielded, asymmetric magnet designs are also presented in which the beginning of a 50-cm dsv is positioned just 11 cm from the end of the coil structure, allowing much improved access to the patient and reduced patient claustrophobia. Magn Reson Med 45:331540, 2001. (C) 2001 Wiley-Liss, Inc.

Free field and parafermionic realizations of twisted su(3)(k)((2)) current algebra

Free field and twisted parafermionic representations of twisted su(3)(k)((2)) current algebra are obtained. The corresponding twisted Sugawara energy-momentum tensor is given in terms of three (beta, gamma) pairs and two scalar fields and also in terms of twisted parafermionic currents and one scalar field. Two screening currents of the first kind are presented in terms of the free fields.

A zero-augmented gamma mixed model for longitudinal data with many zeros

In many occupational safety interventions, the objective is to reduce the injury incidence as well as the mean claims cost once injury has occurred. The claims cost data within a period typically contain a large proportion of zero observations (no claim). The distribution thus comprises a point mass at 0 mixed with a non-degenerate parametric component. Essentially, the likelihood function can be factorized into two orthogonal components. These two components relate respectively to the effect of covariates on the incidence of claims and the magnitude of claims, given that claims are made. Furthermore, the longitudinal nature of the intervention inherently imposes some correlation among the observations. This paper introduces a zero-augmented gamma random effects model for analysing longitudinal data with many zeros. Adopting the generalized linear mixed model (GLMM) approach reduces the original problem to the fitting of two independent GLMMs. The method is applied to evaluate the effectiveness of a workplace risk assessment teams program, trialled within the cleaning services of a Western Australian public hospital.

Exact form factors for the Josephson tunneling current and relative particle number fluctuations in a model of two coupled Bose-Einstein condensates

Form factors are derived for a model describing the coherent Josephson tunneling between two coupled Bose-Einstein condensates. This is achieved by studying the exact solution of the model within the framework of the algebraic Bethe ansatz. In this approach the form factors are expressed through determinant representations which are functions of the roots of the Bethe ansatz equations.

Current density mapping approach for design of clinical magnetic resonance imaging magnets

Novel current density mapping (CDM) schemes are developed for the design of new actively shielded, clinical magnetic resonance imaging (MRI) magnets. This is an extended inverse method in which the entire potential solution space for the superconductors has been considered, rather than single current density layers. The solution provides an insight into the required superconducting coil pattern for a desired magnet configuration. This information is then used as an initial set of parameters for the magnet structure, and a previously developed hybrid numerical optimization technique is used to obtain the final geometry of the magnet. The CDM scheme is applied to the design of compact symmetric, asymmetric, and open architecture 1.0-1.5 T MRI magnet systems of novel geometry and utility. A new symmetric 1.0-T system that is just I m in length with a full 50-cm diameter of the active, or sensitive, volume (DSV) is detailed, as well as an asymmetric system in which a 50-cm DSV begins just 14 cm from the end of the coil structure. Finally a 1.0-T open magnet system with a full 50-cm DSV is presented. These new designs provide clinically useful homogeneous regions and have appropriately restricted stray fields but, in some of the designs, the DSV is much closer to the end of the magnet system than in conventional designs. These new designs have the potential to reduce patient claustrophobia and improve physician access to patients undergoing scans. (C) 2002 Wiley Periodicals, Inc.

Structural characterization of the N-terminal autoregulatory sequence of phenylalanine hydroxylase

Phenylalanine hydroxylase (PAH) is activated by its substrate phenylalanine, and through phosphorylation by cAMP-dependent protein kinase at Ser 16 in the N-terminal autoregulatory sequence of the enzyme. The crystal structures of phosphorylated and unphosphorylated forms of the enzyme showed that, in the absence of phenylalanine, in both cases the N-terminal 18 residues including the phosphorylation site contained no interpretable electron density. We used nuclear magnetic resonance (NMR) spectroscopy to characterize this N-terminal region of the molecule in different stages of the regulatory pathway. A number of sharp resonances are observed in PAH with an intact N-terminal region, but no sharp resonances are present in a truncation mutant lacking the N-terminal 29 residues. The N-terminal sequence therefore represents a mobile flexible region of the molecule. The resonances become weaker after the addition of phenylalanine, indicating a loss of mobility. The peptides corresponding to residues 2-20 of PAH have different structural characteristics in the phosphorylated and unphosphorylated forms, with the former showing increased secondary structure. Our results support the model whereby upon phenylalanine binding, the mobile N-terminal 18 residues of PAH associate with the folded core of the molecule; phosphorylation may facilitate this interaction.

Laying date and laying sequence influence the sex ratio of crimson rosella broods

We examine the patterns of sex allocation in crimson rosellas Platycercus elegans, a socially monogamous Australian parrot. Overall, 41.8% of nestlings were male, a significant female bias. However underlying this population-level bias were non-random patterns of sex allocation within broods. Broods produced early in the season were female-biased, but the proportion of males in a brood increased as the breeding season progressed. Female rosellas may obtain greater fitness benefits from early-fledging daughters than sons because daughters can breed as 1-year-olds whereas sons do not breed until they are at least 2 years old. Laying date and laying sequence also interacted to influence the sex ratio of eggs. The sex of early-laid eggs strongly followed the brood level pattern, whereas the sex of middle- and late-laid eggs did not change significantly as the season progressed. Nevertheless, late-laid eggs were very unlikely to be male at the end of the season. We argue these differing seasonal patterns reflect the relative costs and benefits to producing early-hatched males and females at different times of the season. Female rosellas appear to maximise the probability that daughters are able to breed early but to minimise competitive asymmetries within the brood. In particular, late-hatched male chicks are disadvantaged if their oldest sibling is male, explaining the dearth of broods containing late-hatched males at the end of the breeding season.

A Devonian (Givetian) fore-reef slope sequence at Liangshuijing and implication for Devonian platform-to-depression development in Guilin, South China

Three Bahama-like carbonate plaforms-the Guilin, Yangshuo and Yanshan-occurred in Guilin and the surrounding regions during Middle and Late Devonian, which, at a broad scale, are part of an extensive carbonate platform (Xiangzhou carbonate platform) facies in South China. The intraplatform depression facies, a unique characteristic of the Chinese Devonian depositional sequence, separates Bahama-like (platform-to-depression) carbonate subplatfonns. Intraplatform depressions resulted from syndepositional faulting that cut the basement of carbonate subplatforms and affected further platform development. The Liangshuijing section, located between the Guilin platform in the north and the Yangshuo platform in the south, is representative of the fore-reef slope facies neighboring an intraplatform. depression. The South edge of the fore-reef slope lies adjacent to the Yangshuo reef carbonate platform, and the north edge graded into the Yangdi pelagic depression facies. A detailed sedimentary and microfacies analysis work done in this study at the Liangshuijing section shows a distinct vertical facies change from back-reef, restricted platform, hemipelagic, to fore-reefslope facies, differing from either shallow-water benthic facies or typical pelagic facies. Various benthic and pelagic lithofacies and their associations have been recognized in the Liangshuijing section, including dolomitic rudstone, gastropod wackestone, Amphipora floatstone, tentaculitoid wackestone, stromatolite and oncoid limestone, Amphipora grainstone, grain flows, laminated limestone, flat-pebble and brachiopod floatstone, and carbonate turbidites. Eight types of sedimentary cycles composed of two or three lithofacies have been distinguished, which are able to indicate environment changes. Stromatolites, oncoids, grain flows, carbonate turbidites, and tentaculitoid limestones characterize the slope and intraplatform depression lithofacies. Analysis of the vertical sedimentary cycles in the Liangshuijinag section and the lateral stratigraphic equivalents suggest the differing facies patterns occurred at the middle Varcus Zone (Givetian) of Middle Devonian, coeval with the development of fore-reef slope facies in the Guilin area in response to syndeposifional faulting.