Re-defining the Golgi complex in Plasmodium falciparum using the novel Golgi marker PfGRASP

Plasmodium falciparum, the causative agent of malaria, relies on a sophisticated protein secretion system for host cell invasion and transformation. Although the parasite displays a secretory pathway similar to those of all eukaryotic organisms, a classical Golgi apparatus has never been described. We identified and characterised the putative Golgi matrix protein PfGRASP, a homologue of the Golgi re-assembly stacking protein (GRASP) family. We show that PfGRASP is expressed as a 70 kDa protein throughout the asexual life cycle of the parasite. We generated PfGRASP-GFP-expressing transgenic parasites and showed that this protein is localised to a single, juxtanuclear compartment in ring-stage parasites. The PfGRASP compartment is distinct from the ER, restricted within the boundaries of the parasite and colocalises with the cis-Golgi marker ERD2. Correct subcellular localisation of this Golgi matrix protein depends on a cross-species conserved functional myristoylation motif and is insensitive to Brefeldin A. Taken together our results define the Golgi apparatus in Plasmodium and depict the morphological organisation of the organelle throughout the asexual life cycle of the parasite

Formation of Topological Defects in a Second Order Phase Transition

The classical evolution equations of the Abelian Higgs model are studied at temperatures below the Ginsburg temperature of a phase transition which is assumed to be second order. It is shown that the initial thermal fluctuations provide a domain structure which is stable against late time fluctuations. This result lends support to the Kibble mechanism for the formation of topological defects.Comment: Brown preprint BROWN-HET-934 (March 1994), 12 pages, uses phyzz

Impaired Cardiac Baroreflex Sensitivity Predicts Response to Renal Sympathetic Denervation in Patients With Resistant Hypertension

ObjectivesThis study sought to evaluate cardiac baroreflex sensitivity (BRS) as a predictor of response to renal sympathetic denervation (RDN).BackgroundCatheter-based RDN is a novel treatment option for patients with resistant arterial hypertension. It is assumed that RDN reduces efferent renal and central sympathetic activity.MethodsFifty patients (age 60.3 ± 13.8 years [mean ± SD mean systolic blood pressure (BP) on ambulatory blood pressure monitoring (ABPM) 157 ± 22 mm Hg, despite medication with 5.4 ± 1.4 antihypertensive drugs) underwent RDN. Prior to RDN, a 30-min recording of continuous arterial BP (Finapres; TNO-TPD Biomedical Instrumentation, Amsterdam, the Netherlands) and high-resolution electrocardiography (1.6 kHz in orthogonal XYZ leads) was performed in all patients under standardized conditions. Cardiac BRS was assessed by phase-rectified signal averaging (BRSPRSA) according to previously published technologies. Response to RDN was defined as a reduction of mean systolic BP on ABPM by 10 mm Hg or more at 6 months after RDN.ResultsSix months after RDN, mean systolic BP on ABPM was significantly reduced from 157 ± 22 mm Hg to 149 ± 20 mm Hg (p = 0.003). Twenty-six of the 50 patients (52%) were classified as responders. BRSPRSA was significantly lower in responders than nonresponders (0.16 ± 0.75 ms/mm Hg vs. 1.54 ± 1.73 ms/mm Hg; p < 0.001). Receiver-operator characteristics analysis revealed an area under the curve for prediction of response to RDN by BRSPRSA of 81.2% (95% confidence interval: 70.0% to 90.1%; p < 0.001). On multivariable logistic regression analysis, reduced BRSPRSA was the strongest predictor of response to RDN, which was independent of all other variables tested.ConclusionsImpaired cardiac BRS identifies patients with resistant hypertension who respond to RDN

Pleasure and meaningful discourse: an overview of research issues

The concept of pleasure has emerged as a multi-faceted social and cultural phenomenon in studies of media audiences since the 1980s. In these studies different forms of pleasure have been identified as explaining audience activity and commitment. In the diverse studies pleasure has emerged as a multi-faceted social and cultural concept that needs to be contextualized carefully. Genre and genre variations, class, gender, (sub-)cultural identity and generation all seem to be instrumental in determining the kind and variety of pleasures experienced in the act of viewing. This body of research has undoubtedly contributed to a better understanding of the complexity of audience activities, but it is exactly the diversity of the concept that is puzzling and poses a challenge to its further use. If pleasure is maintained as a key concept in audience analysis that holds much explanatory power, it needs a stronger theoretical foundation. The article maps the ways in which the concept of pleasure has been used by cultural theorists, who have paved the way for its application in reception analysis, and it goes on to explore the ways in which the concept has been used in empirical studies. Central to our discussion is the division between the ‘public knowledge’ and the ‘popular culture’ projects in reception analysis which, we argue, have major implications for the way in which pleasure has come to be understood as divorced from politics, power and ideology. Finally, we suggest ways of bridging the gap between these two projects in an effort to link pleasure to the concepts of hegemony and ideology

Contrasting macrophage activation by fine and ultrafine titanium dioxide particles is associated with different uptake mechanisms

Inhalation of (nano)particles may lead to pulmonary inflammation. However, the precise mechanisms of particle uptake and generation of inflammatory mediators by alveolar macrophages (AM) are still poorly understood. The aim of this study was to investigate the interactions between particles and AM and their associated pro-inflammatory effects in relation to particle size and physico-chemical properties

Mitochondrial dysfunction in liver failure requiring transplantation.

Liver failure is a heterogeneous condition which may be fatal and the primary cause is frequently unknown. We investigated mitochondrial oxidative phosphorylation in patients undergoing liver transplantation. We studied 45 patients who had liver transplantation due to a variety of clinical presentations. Blue native polyacrylamide gel electrophoresis with immunodetection of respiratory chain complexes I-V, biochemical activity of respiratory chain complexes II and IV and quantification of mitochondrial DNA (mtDNA) copy number were investigated in liver tissue collected from the explanted liver during transplantation. Abnormal mitochondrial function was frequently present in this cohort: ten of 40 patients (25 %) had a defect of one or more respiratory chain enzyme complexes on blue native gels, 20 patients (44 %) had low activity of complex II and/or IV and ten (22 %) had a reduced mtDNA copy number. Combined respiratory chain deficiency and reduced numbers of mitochondria were detected in all three patients with acute liver failure. Low complex IV activity in biliary atresia and complex II defects in cirrhosis were common findings. All six patients diagnosed with liver tumours showed variable alterations in mitochondrial function, probably due to the heterogeneity of the presenting tumour. In conclusion, mitochondrial dysfunction is common in severe liver failure in non-mitochondrial conditions. Therefore, in contrast to the common practice detection of respiratory chain abnormalities in liver should not restrict the inclusion of patients for liver transplantation. Furthermore, improving mitochondrial function may be targeted as part of a complex therapy approach in different forms of liver diseases

Host age and expression of genes involved in red blood cell invasion in Plasmodium falciparum field isolates

Plasmodium falciparum proteins involved in erythrocyte invasion are main targets of acquired immunity and important vaccine candidates. We hypothesized that anti-parasite immunity acquired upon exposure would limit invasion-related gene (IRG) expression and affect the clinical impact of the infection. 11 IRG transcript levels were measured in P. falciparum isolates by RT-PCR, and IgG/IgM against invasion ligands by Luminex(R), in 50 Mozambican adults, 25 children with severe malaria (SM) and 25 with uncomplicated malaria (UM). IRG expression differences among groups and associations between IRG expression and clinical/immunologic parameters were assessed. IRG expression diversity was higher in parasites infecting children than adults (p = 0.022). eba140 and ptramp expression decreased with age (p = 0.003 and 0.007, respectively) whereas p41 expression increased (p = 0.022). pfrh5 reduction in expression was abrupt early in life. Parasite density decreased with increasing pfrh5 expression (p < 0.001) and, only in children, parasite density increased with p41 expression (p = 0.007), and decreased with eba175 (p = 0.013). Antibody responses and IRG expression were not associated. In conclusion, IRG expression is associated with age and parasite density, but not with specific antibody responses in the acute phase of infection. Our results confirm the importance of multi-antigen vaccines development to avoid parasite immune escape when tested in malaria-exposed individuals

Anisotropic Panglial Coupling Reflects Tonotopic Organization in the Inferior Colliculus

Astrocytes and oligodendrocytes in different brain regions form panglial networks and the topography of such networks can correlate with neuronal topography and function. Astrocyte-oligodendrocyte networks in the lateral superior olive (LSO)—an auditory brainstem nucleus—were found to be anisotropic with a preferred orientation orthogonally to the tonotopic axis. We hypothesized that such a specialization might be present in other tonotopically organized brainstem nuclei, too. Thus, we analyzed gap junctional coupling in the center of the inferior colliculus (IC)—another nucleus of the auditory brainstem that exhibits tonotopic organization. In acute brainstem slices obtained from mice, IC networks were traced employing whole-cell patch-clamp recordings of single sulforhodamine (SR) 101-identified astrocytes and concomitant intracellular loading of the gap junction-permeable tracer neurobiotin. The majority of dye-coupled networks exhibited an oval topography, which was preferentially oriented orthogonal to the tonotopic axis. Astrocyte processes showed preferentially the same orientation indicating a correlation between astrocyte and network topography. In addition to SR101-positive astrocytes, IC networks contained oligodendrocytes. Using Na+ imaging, we analyzed the capability of IC networks to redistribute small ions. Na+ bi-directionally diffused between SR101-positive astrocytes and SR101-negative cells—presumably oligodendrocytes—showing the functionality of IC networks. Taken together, our results demonstrate that IC astrocytes and IC oligodendrocytes form functional anisotropic panglial networks that are preferentially oriented orthogonal to the tonotopic axis. Thus, our data indicate that the topographic specialization of glial networks seen in IC and LSO might be a general feature of tonotopically organized auditory brainstem nuclei