Secretion and processing of a novel multi-domain cystatin-like protein by intracellular stages of Trichinella spiralis

The excretory-secretory (ES) proteins of nematode parasites are of major interest as they function at the host-parasite interface and are likely to have roles crucial for successful parasitism. Furthermore, the ES proteins of intracellular nematodes such as Trichinella spiralis may also function to regulate gene expression in the host cell. In a recent proteomic analysis we identified a novel secreted cystatin-like protein from T. spiralis L1 muscle larva. Here we show that the protein, MCD-1 (multi-cystatin-like domain protein 1), contains three repeating cystatin-like domains and analysis of the mcd-1 gene structure suggests that the repeated domains arose from duplication of an ancestral cystatin gene. Cystatins are a diverse group of cysteine protease inhibitors and those secreted by parasitic nematodes are important immuno-modulatory factors. The cystatin superfamily also includes cystatin-like proteins that have no cysteine protease inhibitory activity. A recombinant MCD-1 protein expressed as a GST-fusion protein in Escherichia coli failed to inhibit papain in vitro suggesting that the T. spiralis protein is a new member of the non-inhibitory cystatin-related proteins. MCD-1 secreted from T. spiralis exists as high- and low-molecular weight isoforms and we show that a recombinant MCD-1 protein secreted by HeLa cells undergoes pH-dependent processing that may result in the release of individual cystatin-like domains. Furthermore, we found that mcd-1 gene expression is largely restricted to intracellular stages with the highest levels of expression in the adult worms. It is likely that the major role of the protein is during the intestinal stage of T. spiralis infections.

Cognitive functioning in subjects with recent-onset psychosis from a low-middle-income environment: Multiple-domain deficits and longitudinal evaluation

Cognitive deficits are a key feature of recent-onset psychosis, but there is no consensus on whether such deficits are generalized or confined to specific domains. Besides, it is unclear whether cognitive deficits: a) are found in psychotic patients in samples from outside high-income countries; and b) whether they progress uniformly over time in schizophrenia and affective psychoses. We applied 12 tests organized into eight cognitive domains, comparing psychosis patients (n = 56, time from initial contact = 677.95+/-183.27 days) versus healthy controls (n = 70) recruited from the same area of Sao Paulo, Brazil. Longitudinal comparisons (digit span and verbal fluency) were conducted between a previous assessment of the subjects carried out at their psychosis onset, and the current follow-up evaluation. Psychosis patients differed significantly from controls on five domains, most prominently on verbal memory. Cognitive deficits remained detectable in separate comparisons of the schizophrenia subgroup and, to a lesser extent, the affective psychosis subjects against controls. Longitudinal comparisons indicated significant improvement in schizophrenia, affective psychoses, and control subjects, with no significant group-by-time interactions. Our results reinforce the view that there are generalized cognitive deficits in association with recent-onset psychoses, particularly of non-affective nature, which persist over time. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Crack detection of steel girders using Brillouin optical time domain analysis

This article presents the results from an experimental program designed to evaluate the performance of a system consisting of a readout unit and a ribbon type Fiber Optic Sensor (FOS) based on Brillouin Optical Time Domain Analysis (BOTDA). The system is intended for the detection of cracks as well as the monitoring of long-term performance for steel bridge girders. The program consisted of introducing a crack at the center of a 3-m-long steel beam and monitoring its progression using static loading tests performed at ambient and sub-zero temperatures. For sensor lengths similar to those used in the field, the resonant frequency shifts per unit increase in crack width were found to decrease from 114 MHz/mm at ambient temperature (~25C) to 65 MHz/mm at -10C. Results also revealed nonlinearity and variability, which can be attributed to an incompatibility between the settings of the laser pump in the readout unit and the sensor length. Significant losses were detected along the bonded segments of the sensor and were attributed to the presence of ripples along the sensor. These undulations worsen with a reduction in temperature and are induced by the bonding procedure as well as the slack provided in the plastic sleeves containing the splices.

Turning the tide: A critique of Natural Semantic Metalanguage from a translation studies perspective

Starting from the premise that human communication is predicated on translational phenomena, this paper applies theoretical insights and practical findings from Translation Studies to a critique of Natural Semantic Metalanguage (NSM), a theory of semantic analysis developed by Anna Wierzbicka. Key tenets of NSM, i.e. (1) culture-specificity of complex concepts; (2) the existence of a small set of universal semantic primes; and (3) definition by reductive paraphrase, are discussed critically with reference to the notions of untranslatability, equivalence, and intra-lingual translation, respectively. It is argued that a broad spectrum of research and theoretical reflection in Translation Studies may successfully feed into the study of cognition, meaning, language, and communication. The interdisciplinary exchange between Translation Studies and linguistics may be properly balanced, with the former not only being informed by but also informing and interrogating the latter.

Extracting Query Interfaces Based on Form Structures and Semantic Similarity

Web databases are now pervasive. Such a database can be accessed via its query interface (usually HTML query form) only. Extracting Web query interfaces is a critical step in data integration across multiple Web databases, which creates a formal representation of a query form by extracting a set of query conditions in it. This paper presents a novel approach to extracting Web query interfaces. In this approach, a generic set of query condition rules are created to define query conditions that are semantically equivalent to SQL search conditions. Query condition rules represent the semantic roles that labels and form elements play in query conditions, and how they are hierarchically grouped into constructs of query conditions. To group labels and form elements in a query form, we explore both their structural proximity in the hierarchy of structures in the query form, which is captured by a tree of nested tags in the HTML codes of the form, and their semantic similarity, which is captured by various short texts used in labels, form elements and their properties. We have implemented the proposed approach and our experimental results show that the approach is highly effective.

Domain configuration of permalloy ellipses in a rotating magnetic field

The domain configuration of micron-sized permalloy ellipses was studied under the influence of an in-plane rotating magnetic field using magnetic force microscopy. The field amplitude was chosen such that when the field is applied parallel to the long axis of the ellipses they are saturated, but when the field is perpendicular to the long axis they exhibit multi-domain states. The rotation angle for nucleation and annihilation of domains was determined for different magnitudes of the applied magnetic field and for two different lateral sizes of ellipses, 6 Am x 2 Am and 3 Am x 1 Am. It was found that both nucleation and annihilation occur over a range of angles for both lateral sizes of ellipses. Saturated states are stable for a wider range of angles for larger values of the applied field.

Exotic Domain States in Ferroelectrics: Searching for Vortices and Skyrmions

Very recent experimental and theoretical work has sought to find out whether or not complex arrangements of dipoles (such as flux-closure, vortex or skyrmion patterns) exist in ferroelectrics. While there is undoubtedly still considerable work to be done, enough insight has now been gained to warrant a brief discussion of progress to date. This review article attempts to undertake such a discussion.

Multiferroic domain dynamics in strained strontium titanate

Multiferroicity can be induced in strontium titanate by applying biaxial strain. Using optical second harmonic generation, we report a transition from 4/mmm to the ferroelectric mm2 phase, followed by a transition to a ferroelastic-ferroelectric mm2 phase in a strontium titanate thin film. Piezoelectric force microscopy is used to study ferroelectric domain switching. Second harmonic generation, combined with phase-field modeling, is used to reveal the mechanism of coupled ferroelectric-ferroelastic domain wall motion. These studies have relevance to multiferroics with coupled polar and axial phenomena.

Substrate Clamping Effects on Irreversible Domain Wall Dynamics in Lead Zirconate Titanate Thin Films

The role of long-range strain interactions on domain wall dynamics is explored through macroscopic and local measurements of nonlinear behavior in mechanically clamped and released polycrystalline lead zirconate-titanate (PZT) films. Released films show a dramatic change in the global dielectric nonlinearity and its frequency dependence as a function of mechanical clamping. Furthermore, we observe a transition from strong clustering of the nonlinear response for the clamped case to almost uniform nonlinearity for the released film. This behavior is ascribed to increased mobility of domain walls. These results suggest the dominant role of collective strain interactions mediated by the local and global mechanical boundary conditions on the domain wall dynamics. The work presented in this Letter demonstrates that measurements on clamped films may considerably underestimate the piezoelectric coefficients and coupling constants of released structures used in microelectromechanical systems, energy harvesting systems, and microrobots.

Stripe domain structure in epitaxial (001) BiFeO3 thin films on orthorhombic TbScO3 substrate

We have analyzed the ferroelastic and ferroelectric domain structure of high crystalline quality (001) BiFeO3 films on orthorhombic (110) TbScO3 substrates. Two domains were present in stripes separated by (010) vertical boundaries, with spontaneous polarizations in adjacent domains rotated by 109 degrees. The striped morphology was caused by nucleation of only two ferroelastic domains on the low symmetry GdFeO3-type substrate. Domain engineering through substrate symmetry is an important finding for rhombohedral ferroelectric epitaxial thin films. The stripe pattern with vertical walls may be useful for extracting domain wall contributions to magnetism and electrical transport properties of BiFeO3 materials.

Comparison of Wavelet Transform and Time-Domain Analysis of Second Trimester Uterine Artery Doppler Waveforms in Screening for Pre-Eclampsia

The aim of this study was to compare time-domain waveform analysis of second-trimester uterine artery Doppler using the resistance index (RI) with waveform analysis using a mathematical tool known as wavelet transform for the prediction of pre-eclampsia (PE). This was a retrospective, nested case-cohort study of 336 women, 37 of whom subsequently developed PE. Uterine artery Doppler waveforms were analysed using both RI and waveform analysis. The utility of these indices in screening for PE was then evaluated using receiver operating characteristic curves. There were significant differences in uterine artery RI between the PE women and those with normal pregnancy outcome. After wavelet analysis, significant difference in the mean amplitude in wavelet frequency band 4 was noted between the 2 groups. The sensitivity for both Doppler RI and frequency band 4 for the detection of PE at a 10% false-positive rate was 45%. This small study demonstrates the application of wavelet transform analysis of uterine artery Doppler waveforms in screening for PE. Further prospective studies are needed in order to clearly define if this analytical approach to waveform analysis may have the potential to improve the detection of PE by uterine artery Doppler screening.

Phosphorylation of plant actin-depolymerising factor by calmodulin-like domain protein kinase

actin-depolymerising factor (ADF)/cofilin group of proteins are stimulus-responsive actin-severing proteins, members of which are regulated by reversible phosphorylation. The phosphorylation site on the maize ADF, ZmADF3, is Ser-6 but the kinase responsible is unknown [Smertenko et al,, Plant J. 14 (1998) 187-193]. We have partially purified the ADF kinase(s) and found it to be calcium-regulated and inhibited by N-(6-aminohesyl)-[H-3]5-chloro-1-naphthalenesulphonamide. Immunoblotting reveals that calmodulin-like domain protein kinase(s) (CDPK) are enriched in the purified preparation and addition of anti-CDPK to in vitro phosphorylation assays results in the inhibition of ADF phosphorylation, These data strongly suggest that plant ADP is phosphorylation by CDPK(s), a class of protein kinases unique to plants and protozoa. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Association Study of 167 Candidate Genes for Schizophrenia Selected by a Multi-Domain Evidence-Based Prioritization Algorithm and Neurodevelopmental Hypothesis

Integrating evidence from multiple domains is useful in prioritizing disease candidate genes for subsequent testing. We ranked all known human genes (n = 3819) under linkage peaks in the Irish Study of High-Density Schizophrenia Families using three different evidence domains: 1) a meta-analysis of microarray gene expression results using the Stanley Brain collection, 2) a schizophrenia protein-protein interaction network, and 3) a systematic literature search. Each gene was assigned a domain-specific p-value and ranked after evaluating the evidence within each domain. For comparison to this
ranking process, a large-scale candidate gene hypothesis was also tested by including genes with Gene Ontology terms related to neurodevelopment. Subsequently, genotypes of 3725 SNPs in 167 genes from a custom Illumina iSelect array were used to evaluate the top ranked vs. hypothesis selected genes. Seventy-three genes were both highly ranked and involved in neurodevelopment (category 1) while 42 and 52 genes were exclusive to neurodevelopment (category 2) or highly ranked (category 3), respectively. The most significant associations were observed in genes PRKG1, PRKCE, and CNTN4 but no individual SNPs were significant after correction for multiple testing. Comparison of the approaches showed an excess of significant tests using the hypothesis-driven neurodevelopment category. Random selection of similar sized genes from two independent genome-wide association studies (GWAS) of schizophrenia showed the excess was unlikely by chance. In a further meta-analysis of three GWAS datasets, four candidate SNPs reached nominal significance. Although gene ranking using integrated sources of prior information did not enrich for significant results in the current experiment, gene selection using an a priori hypothesis (neurodevelopment) was superior to random selection. As such, further development of gene ranking strategies using more carefully selected sources of information is warranted.