Trypanosoma brucei Bloodstream Forms Depend upon Uptake of myo-Inositol for Golgi Complex Phosphatidylinositol Synthesis and Normal Cell Growth

myo-Inositol is a building block for all inositol-containing phospholipids in eukaryotes. It can be synthesized de novo from glucose-6-phosphate in the cytosol and endoplasmic reticulum. Alternatively, it can be taken up from the environment via Na(+)- or H(+)-linked myo-inositol transporters. While Na(+)-coupled myo-inositol transporters are found exclusively in the plasma membrane, H(+)-linked myo-inositol transporters are detected in intracellular organelles. In Trypanosoma brucei, the causative agent of human African sleeping sickness, myo-inositol metabolism is compartmentalized. De novo-synthesized myo-inositol is used for glycosylphosphatidylinositol production in the endoplasmic reticulum, whereas the myo-inositol taken up from the environment is used for bulk phosphatidylinositol synthesis in the Golgi complex. We now provide evidence that the Golgi complex-localized T. brucei H(+)-linked myo-inositol transporter (TbHMIT) is essential in bloodstream-form T. brucei. Downregulation of TbHMIT expression by RNA interference blocked phosphatidylinositol production and inhibited growth of parasites in culture. Characterization of the transporter in a heterologous expression system demonstrated a remarkable selectivity of TbHMIT for myo-inositol. It tolerates only a single modification on the inositol ring, such as the removal of a hydroxyl group or the inversion of stereochemistry at a single hydroxyl group relative to myo-inositol.

TrypanoCyc: a community-led biochemical pathways database for Trypanosoma brucei.

The metabolic network of a cell represents the catabolic and anabolic reactions that interconvert small molecules (metabolites) through the activity of enzymes, transporters and non-catalyzed chemical reactions. Our understanding of individual metabolic networks is increasing as we learn more about the enzymes that are active in particular cells under particular conditions and as technologies advance to allow detailed measurements of the cellular metabolome. Metabolic network databases are of increasing importance in allowing us to contextualise data sets emerging from transcriptomic, proteomic and metabolomic experiments. Here we present a dynamic database, TrypanoCyc (http://www.metexplore.fr/trypanocyc/), which describes the generic and condition-specific metabolic network of Trypanosoma brucei, a parasitic protozoan responsible for human and animal African trypanosomiasis. In addition to enabling navigation through the BioCyc-based TrypanoCyc interface, we have also implemented a network-based representation of the information through MetExplore, yielding a novel environment in which to visualise the metabolism of this important parasite.

How to measure Narcissism – an ongoing discussion

Over the last decades, research on narcissism was dominated with a focus on grandiose narcissism as measured by the NPI (Raskin & Terry, 1988), however, recent discussions emphasize the broad range of manifestations of narcissism, in particular more vulnerable aspects. As a result, new questionnaires were developed to cover the full range of these aspects. One example is the Pathological Narcissism Scale (PNI, Pincus et al. 2009), a 52 item questionnaire with seven subscales covering both grandiose and vulnerable aspects. Validation studies show that narcissism as measured with the PNI differs substantially from narcissism as measured with the NPI. Moreover, a discussion concerning the composition of grandiose and vulnerable narcissism has evolved from these data. In our study we demonstrate how scores on narcissism and narcissism subtypes are associated with a broad variety of personality and clinical measures. In a sample of 1837 participants (1240 female, 597 male; mean age 26.8 years) we investigated the correlation patterns of both PNI and NPI subscales with constructs like FFM, aggression, emotions, clinical symptoms, and well-being. Results show that the assignment of subscales to grandiose and vulnerable subtypes are not unambiguous. We therefore conclude that the decision of how to measure narcissism needs further investigation.