The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin.

Trypanosoma cruzi glutathione-dependent peroxidase I (TcGPXI) can reduce fatty acid, phospholipid, and short chain organic hydroperoxides utilizing a novel redox cycle in which enzyme activity is linked to the reduction of trypanothione, a parasite-specific thiol, by glutathione. Here we show that TcGPXI activity can also be linked to trypanothione reduction by an alternative pathway involving the thioredoxin-like protein tryparedoxin. The presence of this new pathway was first detected using dialyzed soluble fractions of parasite extract. Tryparedoxin was identified as the intermediate molecule following purification, sequence analysis, antibody studies, and reconstitution of the redox cycle in vitro. The system can be readily saturated by trypanothione, the rate-limiting step being the interaction of trypanothione with the tryparedoxin. Both tryparedoxin and TcGPXI operate by a ping-pong mechanism. Overexpression of TcGPXI in transfected parasites confers increased resistance to exogenous hydroperoxides. TcGPXI contains a carboxyl-terminal tripeptide (ARI) that could act as a targeting signal for the glycosome, a kinetoplastid-specific organelle. Using immunofluorescence, tagged fluorescent proteins, and biochemical fractionation, we have demonstrated that TcGPXI is localized to both the glycosome and the cytosol. The ability of TcGPXI to use alternative electron donors may reflect their availability at the corresponding subcellular sites

The Receptor-Like Kinase SERK3/BAK1 Is Required for Basal Resistance against the Late Blight Pathogen Phytophthora infestans in Nicotiana benthamiana

BACKGROUND The filamentous oomycete plant pathogen Phytophthora infestans causes late blight, an economically important disease, on members of the nightshade family (Solanaceae), such as the crop plants potato and tomato. The related plant Nicotiana benthamiana is a model system to study plant-pathogen interactions, and the susceptibility of N. benthamiana to Phytophthora species varies from susceptible to resistant. Little is known about the extent to which plant basal immunity, mediated by membrane receptors that recognise conserved pathogen-associated molecular patterns (PAMPs), contributes to P. infestans resistance. PRINCIPAL FINDINGS We found that different species of Phytophthora have varying degrees of virulence on N. benthamiana ranging from avirulence (incompatible interaction) to moderate virulence through to full aggressiveness. The leucine-rich repeat receptor-like kinase (LRR-RLK) BAK1/SERK3 is a major modulator of PAMP-triggered immunity (PTI) in Arabidopsis thaliana and N. benthamiana. We cloned two NbSerk3 homologs, NbSerk3A and NbSerk3B, from N. benthamiana based on sequence similarity to the A. thaliana gene. N. benthamiana plants silenced for NbSerk3 showed markedly enhanced susceptibility to P. infestans infection but were not altered in resistance to Phytophthora mirabilis, a sister species of P. infestans that specializes on a different host plant. Furthermore, silencing of NbSerk3 reduced the cell death response triggered by the INF1, a secreted P. infestans protein with features of PAMPs. CONCLUSIONS/SIGNIFICANCE We demonstrated that N. benthamiana NbSERK3 significantly contributes to resistance to P. infestans and regulates the immune responses triggered by the P. infestans PAMP protein INF1. In the future, the identification of novel surface receptors that associate with NbSERK3A and/or NbSERK3B should lead to the identification of new receptors that mediate recognition of oomycete PAMPs, such as INF1.This work was supported by the Gatsby Charitable Foundation, BBSRC, Nuffield Foundation and the German Research Foundation (DFG). SS was supported by a personal research fellowship (SCHO1347/1-1). JPR is an Australian Research Council Future Fellow (FT0992129). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Acaparamiento de tierras y acumulación capitalista: aspectos clave en América Latina

__Abstract__ We introduce this special issue by explaining seven characteristics of land grabbing in Latin America. These features are not unique to the region. By highlighting them – arguing, for instance, that a key aspect in Latin America is intra-regional land grabbing driven by (trans)Latina companies – we hope to inspire new cross-regional comparisons to understand the dynamics of “global” land grabbing. Our focus on Latin America challenges some problematic generalisations in the literature, for instance, that land grabs occur mainly in fragile states. We interrogate the relationship between land grabbing and the “foreignisation” narrative, and the need to revisit the broader question of land concentration. Thus we build upon the literature locating land grabs and the land question within the political economy of global capitalism

The Extreme Ultraviolet Spectrograph Sounding Rocket Payload: Recent Modifications for Planetary Observations in the EUV/FUV

We report on the status of modifications to an existing extreme ultraviolet (EUV) telescope/spectrograph sounding rocket payload for planetary observations in the 800 - 1200 A wavelength band. The instrument is composed of an existing Wolter Type 2 grazing incidence telescope, a newly built 0.4-m normal incidence Rowland Circle spectrograph, and an open-structure resistive-anode microchannel plate detector. The modified payload has successfully completed three NASA sounding rocket flights within 1994-1995. Future flights are anticipated for additional studies of planetary and cometary atmospheres and interstellar absorption. A detailed description of the payload, along with the performance characteristics of the integrated instrument are presented. In addition, some preliminary flight results from the above three missions are also presented

Benznidazole-Resistance in Trypanosoma cruzi Is a Readily Acquired Trait That Can Arise Independently in a Single Population

Benznidazole is the frontline drug used against Trypanosoma cruzi, the causative agent of Chagas disease. However, treatment failures are often reported. Here, we demonstrate that independently acquired mutations in the gene encoding a mitochondrial nitroreductase (TcNTR) can give rise to distinct drug-resistant clones within a single population. Following selection of benznidazole-resistant parasites, all clones examined had lost one of the chromosomes containing the TcNTR gene. Sequence analysis of the remaining TcNTR allele revealed 3 distinct mutant genes in different resistant clones. Expression studies showed that these mutant proteins were unable to activate benznidazole. This correlated with loss of flavin mononucleotide binding. The drug-resistant phenotype could be reversed by transfection with wild-type TcNTR. These results identify TcNTR as a central player in acquired resistance to benznidazole. They also demonstrate that T. cruzi has a propensity to undergo genetic changes that can lead to drug resistance, a finding that has implications for future therapeutic strategies

A multi-centre qualitative study exploring the experiences of UK South Asian and White Diabetic Patients referred for renal care

Background An exploration of renal complications of diabetes from the patient perspective is important for developing quality care through the diabetic renal disease care pathway. Methods Newly referred South Asian and White diabetic renal patients over 16 years were recruited from nephrology outpatient clinics in three UK centres - Luton, West London and Leicester – and their experiences of the diabetes and renal care recorded. A semi-structured qualitative interview was conducted with 48 patients. Interview transcripts were analysed thematically and comparisons made between the White and South Asian groups. Results 23 South Asian patients and 25 White patients were interviewed. Patient experience of diabetes ranged from a few months to 35 years with a mean time since diagnosis of 12.1 years and 17.1 years for the South Asian and White patients respectively. Confusion emerged as a response to referral shared by both groups. This sense of confusion was associated with reported lack of information at the time of referral, but also before referral. Language barriers exacerbated confusion for South Asian patients. Conclusions The diabetic renal patients who have been referred for specialist renal care and found the referral process confusing have poor of awareness of kidney complications of diabetes. Healthcare providers should be more aware of the ongoing information needs of long term diabetics as well as the context of any information exchange including language barriers

Benznidazole-resistance in Trypanosoma cruzi: evidence that distinct mechanisms can act in concert.

Benznidazole is the main drug used to treat Trypanosoma cruzi infections. However, frequent instances of treatment failure have been reported. To better understand potential resistance mechanisms, we analysed three clones isolated from a single parasite population that had undergone benznidazole-selection. These clones exhibited differing levels of benznidazole-resistance (varying between 9 and 26-fold), and displayed cross-resistance to nifurtimox (2 to 4-fold). Each clone had acquired a stop-codon-generating mutation in the gene which encodes the nitroreductase (TcNTR) that is responsible for activating nitroheterocyclic pro-drugs. In addition, one clone had lost a copy of the chromosome containing TcNTR. However, these processes alone are insufficient to account for the extent and diversity of benznidazole-resistance. It is implicit from our results that additional mechanisms must also operate and that T. cruzi has an intrinsic ability to develop drug-resistance by independent sequential steps, even within a single population. This has important implications for drug development strategies

Optical Structure and Proper-Motion Age of the Oxygen-rich Supernova Remnant 1E 0102-7219 in the Small Magellanic Cloud

We present new optical emission-line images of the young SNR 1E 0102-7219 (E0102) in the SMC obtained with the HST Advanced Camera for Surveys (ACS). E0102 is a member of the oxygen-rich class of SNRs showing strong oxygen, neon , and other metal-line emissions in its optical and X-ray spectra, and an absence of H and He. The progenitor of E0102 may have been a Wolf-Rayet star that underwent considerable mass loss prior to exploding as a Type Ib/c or IIL/b SN. The ejecta in this SNR are fast-moving (V > 1000 km/s) and emit as they are compressed and heated in the reverse shock. In 2003, we obtained optical [O III], H-alpha, and continuum images with the ACS Wide Field Camera. The [O III] image captures the full velocity range of the ejecta, and shows considerable high-velocity emission projected in the middle of the SNR that was Doppler-shifted out of the narrow F502N bandpass of a previous Wide Field and Planetary Camera 2 image from 1995. Using these two epochs separated by ~8.5 years, we measure the transverse expansion of the ejecta around the outer rim in this SNR for the first time at visible wavelengths. From proper-motion measurements of 12 ejecta filaments, we estimate a mean expansion velocity for the bright ejecta of ~2000 km/s and an inferred kinematic age for the SNR of \~2050 +/- 600 years. The age we derive from HST data is about twice that inferred by Hughes et al.(2000) from X-ray data, though our 1-sigma error bars overlap. Our proper-motion age is consistent with an independent optical kinematic age derived by Eriksen et al.(2003) using spatially resolved [O III] radial-velocity data. We derive an expansion center that lies very close to X-ray and radio hotspots, which could indicate the presence of a compact remnant (neutron star or black hole).Comment: 28 pages, 8 figures. Accepted to the Astrophysical Journal, to appear in 20 April 2006 issue. Full resolution figures are posted at: http://stevenf.asu.edu/figure