GABA IN THE NERVOUS-SYSTEM OF PARASITIC FLATWORMS

In an immunocytochemical study, using an antiserum and a monoclonal antibody specific for the amino acid, gamma-aminobutyric acid (GABA), GABA-like immunoreactivity (GLIR) has been demonstrated for the first time in parasitic flatworms. In Moniezia expansa (Cestoda), GLIR was seen in nerve nets which were closely associated with the body wall musculature and in the longitudinal nerve cords. In the liver fluke Fasciola hepatica (Trematoda), the GLIR occurred in the longitudinal nerve cords and lateral nerves in the posterior half of the worm. GLIR was also detected in subtegumental fibres in F. hepatica. The presence of GABA was verified, using high-pressure liquid chromatography coupled with fluorescence detection. The concentration of GABA (mean+/-S.D.) in M. expansa anterior region was 124.8+/-15.3 picomole/mg wet weight, while in F. hepatica it was 16.8+/-4.9 picomole/mg. Since several insecticides and anti-nematodal drugs are thought to interfere with GABA-receptors, the findings indicate that GABAergic neurotransmission may be a potential target for chemotherapy in flatworms too.

KSAYMRFAMIDE - A NOVEL FMRFAMIDE-RELATED HEPTAPEPTIDE FROM THE FREE-LIVING NEMATODE, PANAGRELLUS-REDIVIVUS, WHICH IS MYOACTIVE IN THE PARASITIC NEMATODE, ASCARIS-SUUM

In nematodes, FMRFamide-related peptides (FaRPs) have been structurally characterised from the parasite, Ascaris suum, and from two free-living species, Panagrellus redivivus and Caenorhabditis elegans. While both FaRPs isolated from P. redivivus (PF1 and PF2) have been identified in C. elegans the two heptapeptides isolated from A. suum (AF1 and AF2) have until recently been considered unique to this parasitic species. We have recently isolated AF2 from P. redivivus and, during this study, an additional novel heptapeptide amide, Lys-Ser-Ala-Tyr-Met-Arg-Phe amide (KSAYMRFamide), was structurally characterised. A synthetic replicate of this peptide induced a rapid concentration-dependent muscle tension increase in an isolated A. suum somatic muscle preparation, with a threshold of approximately 0.1 mu M. These data suggest that the complement of FaRPs in parasitic and free-living nematodes may not be as radically different as preliminary studies would suggest, and that the absence of AF1, AF2 and KSAYMRFamide on the C. elegans FMRFamide-related peptide gene (flp-1) may imply the presence of at least two different FaRP genes in nematodes. (C) 1994 Academic Press, Inc.

Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepatica

The helminth parasite Fasciola hepatica secretes cysteine proteases to facilitate tissue invasion, migration, and development within the mammalian host. The major proteases cathepsin L1 (FheCL1) and cathepsin L2 (FheCL2) were recombinantly produced and biochemically characterized. By using site-directed mutagenesis, we show that residues at position 67 and 205, which lie within the S2 pocket of the active site, are critical in determining the substrate and inhibitor specificity. FheCL1 exhibits a broader specificity and a higher substrate turnover rate compared with FheCL2. However, FheCL2 can efficiently cleave substrates with a Pro in the P2 position and degrade collagen within the triple helices at physiological pH, an activity that among cysteine proteases has only been reported for human cathepsin K. The 1.4-A three-dimensional structure of the FheCL1 was determined by x-ray crystallography, and the three-dimensional structure of FheCL2 was constructed via homology-based modeling. Analysis and comparison of these structures and our biochemical data with those of human cathepsins L and K provided an interpretation of the substrate-recognition mechanisms of these major parasite proteases. Furthermore, our studies suggest that a configuration involving residue 67 and the "gatekeeper" residues 157 and 158 situated at the entrance of the active site pocket create a topology that endows FheCL2 with its unusual collagenolytic activity. The emergence of a specialized collagenolytic function in Fasciola likely contributes to the success of this tissue-invasive parasite.

Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection

Virus infection-induced global protein synthesis suppression is linked to assembly of stress granules (SGs), cytosolic aggregates of stalled translation preinitiation complexes. To study long-term stress responses, we developed an imaging approach for extended observation and analysis of SG dynamics during persistent hepatitis C virus (HCV) infection. In combination with type 1 interferon, HCV infection induces highly dynamic assembly/disassembly of cytoplasmic SGs, concomitant with phases of active and stalled translation, delayed cell division, and prolonged cell survival. Double-stranded RNA (dsRNA), independent of viral replication, is sufficient to trigger these oscillations. Translation initiation factor eIF2a phosphorylation by protein kinase R mediates SG formation and translation arrest. This is antagonized by the upregulation of GADD34, the regulatory subunit of protein phosphatase 1 dephosphorylating eIF2a. Stress response oscillation is a general mechanism to prevent long-lasting translation repression and a conserved host cell reaction to multiple RNA viruses, which HCV may exploit to establish persistence.

Influence of the Pacific Decadal Oscillation, El Niño-Southern Oscillation and solar forcing on climate and primary productivity changes in the northeast Pacific

Evidence of 11-year Schwabe solar sunspot cycles, El Niño-Southern Oscillation (ENSO) and the Pacific Decadal Oscillation (PDO) were detected in an annual record of diatomaceous laminated sediments from anoxic Effingham Inlet, Vancouver Island, British Columbia. Radiometric dating and counting of annual varves dates the sediments from AD 1947-1993. Intact sediment slabs were X-rayed for sediment structure (lamina thickness and composition based on gray-scale), and subsamples were examined for diatom abundances and for grain size. Wavelet analysis reveals the presence of ~2-3, ~4.5, ~7 and ~9-12-year cycles in the diatom record and an w11e13 year record in the sedimentary varve thickness record. These cycle lengths suggest that both ENSO and the sunspot cycle had an influence on primary productivity and sedimentation patterns. Sediment grain size could not be correlated to the sunspot cycle although a peak in the grain size data centered around the mid-1970s may be related to the 1976-1977 Pacific climate shift, which occurred when the PDO index shifted from negative (cool conditions) to positive (warm conditions). Additional evidence of the PDO regime shift is found in wavelet and cross-wavelet results for Skeletonema costatum, a weakly silicified variant of S. costatum, annual precipitation and April to June precipitation. Higher spring (April/May) values of the North Pacific High pressure index during sunspot minima suggest that during this time, increased cloud cover and concomitant suppression of the Aleutian Low (AL) pressure system led to strengthened coastal upwelling and enhanced diatom production earlier in the year. These results suggest that the 11-year solar cycle, amplified by cloud cover and upwelling changes, as well as ENSO, exert significant influence on marine primary productivity in the northeast Pacific. The expression of these cyclic phenomena in the sedimentary record were in turn modulated by the phase of PDO, as indicated by the change in period of ENSO and suppression of the solar signal in the record after the 1976-1977 regime shift. © 2013 Elsevier Ltd and INQUA. All rights reserved.

The effects of climate change on ovine parasitic gastroenteritis determined using veterinary surveillance and meteorological data for Northern Ireland over the period 1999-2009

While the influence of temperature and moisture on the free-living stages of gastrointestinal nematodes have been described in detail, and evidence for global climate change is mounting, there have been only a few attempts to relate altered incidence or seasonal patterns of disease to climate change. Studies of this type have been completed for England Scotland and Wales, but not for Northern Ireland (NI). Here we present an analysis of veterinary diagnostic data that relates three categories of gastrointestinal nematode infection in sheep to historical meteorological data for NI. The infections are: trichostrongylosis/teladorsagiosis (Teladorsagia/Trichostrongylus), strongyloidosis and nematodirosis. This study aims to provide a baseline for future climate change analyses and to provide basic information for the development of nematode control programmes. After identifying and evaluating possible sources of bias, climate change was found to be the most likely explanation for the observed patterns of change in parasite epidemiology, although other hypotheses could not be refuted. Seasonal rates of diagnosis showed a uniform year-round distribution for Teladorsagia and Trichostrongylus infections, suggesting consistent levels of larval survival throughout the year and extension of the traditionally expected seasonal transmission windows. Nematodirosis showed a higher level of autumn than Spring infection, suggesting that suitable conditions for egg and larval development occurred after the Spring infection period. Differences between regions within the Province were shown for strongyloidosis, with peaks of infection falling in the period September-November. For all three-infection categories (trichostrongylosis/teladorsagiosis, strongyloidosis and nematodirosis), significant differences in the rates of diagnosis, and in the seasonality of disease, were identified between regions. (C) 2012 Elsevier B.V. All rights reserved.

Measurement-based Method for Wind Farm Power System Oscillation Monitoring

The global increase in the penetration of renewable energy is pushing electrical power systems into uncharted territory, especially in terms of transient and dynamic stability. In particular, the greater penetration of wind generation in European power networks is, at times, displacing a significant capacity of conventional synchronous generation with fixed-speed induction generation and now more commonly, doubly-fed induction generators. The impact of such changes in the generation mix requires careful monitoring to assess the impact on transient and dynamic stability. This paper presents a measurement based method for the early detection of power system oscillations, with attention to mode damping, in order to raise alarms and develop strategies to actively improve power system dynamic stability and security. A method is developed based on wavelet transform and support vector data description (SVDD) to detect oscillation modes in wind farm output power, which may excite dynamic instabilities in the wider system. The wavelet transform is used as a filter to identify oscillations in different frequency bands, while SVDD is used to extract dominant features from different scales and generate an assessment boundary according to the extracted features. Poorly damped oscillations of a large magnitude or that are resonant can be alarmed to the system operator, to reduce the risk of system instability. Method evaluation is exemplified used real data from a chosen wind farm.