HDP-a novel heme detoxification protein from the malaria parasite

When malaria parasites infect host red blood cells (RBC) and proteolyze hemoglobin, a unique, albeit poorly understood parasite-specific mechanism, detoxifies released heme into hemozoin (Hz). Here, we report the identification and characterization of a novel Plasmodium Heme Detoxification Protein (HDP) that is extremely potent in converting heme into Hz. HDP is functionally conserved across Plasmodium genus and its gene locus could not be disrupted. Once expressed, the parasite utilizes a circuitous "Outbound-Inbound" trafficking route by initially secreting HDP into the cytosol of infected RBC. A subsequent endocytosis of host cytosol (and hemoglobin) delivers HDP to the food vacuole (FV), the site of Hz formation. As Hz formation is critical for survival, involvement of HDP in this process suggests that it could be a malaria drug target.     

Expression of Antizyme Inhibitor 2 in Mast Cells and Role of Polyamines as Selective Regulators of Serotonin Secretion

Background

Upon IgE-mediated activation, mast cells (MC) exocytose their cytoplasmic secretory granules and release a variety of bioactive substances that trigger inflammatory responses. Polyamines mediate numerous cellular and physiological functions. We report here that MCs express antizyme inhibitor 2 (AZIN2), an activator of polyamine biosynthesis, previously reported to be exclusively expressed in the brain and testis. We have investigated the intracellular localization of AZIN2 both in resting and activated MCs. In addition, we have examined the functional role of polyamines, downstream effectors of AZIN2, as potential regulators of MC activity.

Methodology/Principal Findings

Immunostainings show that AZIN2 is expressed in primary and neoplastic human and rodent MCs. We demonstrate that AZIN2 localizes in the Vamp-8 positive, serotonin-containing subset of MC granules, but not in tryptase-containing granules, as revealed by double immunofluorescence stainings. Furthermore, activation of MCs induces rapid upregulation of AZIN2 expression and its redistribution, suggesting a role for AZIN2 in secretory granule exocytosis. We also demonstrate that release of serotonin from activated MCs is polyamine-dependent whereas release of histamine and β-hexosaminidase is not, indicating a granule subtype-specific function for polyamines.

Conclusions/Significance

The study reports for the first time the expression of AZIN2 outside the brain and testis, and demonstrates the intracellular localization of endogenous AZIN2 in MCs. The granule subtype-specific expression and its induction after MC activation suggest a role for AZIN2 as a local, in situ regulator of polyamine biosynthesis in association with serotonin-containing granules of MCs. Furthermore, our data indicates a novel function for polyamines as selective regulators of serotonin release from MCs.     

GeneMesh: a web-based microarray analysis tool for relating differentially expressed genes to MeSH terms

Background  

An important objective of DNA microarray-based gene expression experimentation is determining inter-relationships that exist between differentially expressed genes and biological processes, molecular functions, cellular components, signaling pathways, physiologic processes and diseases.     

Combining taxon‐by‐trait and taxon‐by‐site matrices for analysing trait patterns of macroinvertebrate communities: a rejoinder to Monaghan & Soares ()

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Microsecond scale replica exchange molecular dynamic simulation of villin headpiece: an insight into the folding landscape

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Effects of a range expansion on adaptive and neutral genetic diversity in dispersal limited Hazel grouse (<Emphasis Type="Italic">Bonasa bonasia</Emphasis>) in the French Alps

Biogeographic range expansions, when related to dispersal limitation, may have counter intuitive effects on genetic diversity. At range margins the relative roles of demographic changes, connectivity and genetic diversity need to be integrated for a successful assessment of population viability. Historically the Hazel grouse (Bonasa bonasia) in France was found in the north of the French Alps and also in a disjunct population in the nearby Jura Mountains. The species has recently undergone a range expansion in a north to south axis in the Alps. Local population size estimates and migration patterns during expansion have previously been studied. In this study, we performed genotyping at neutral (microsatellite) and adaptive (MHC) genetic markers in Hazel grouse. We compared diversity and differentiation (F_ST and D_EST) at three sampling localities along the expansion axis in the French Alps and Jura, as well as at two sampling localities in Sweden, where the population has had a long-term continuous and stable distribution. Strong serial founder effects were found between the French localities, resulting in stronger isolation further south, with a relatively high neutral differentiation (pair-wise F_ST = 0.117). However, the loss of adaptive diversity MHC was slight. No adaptive differentiation (MHC D_EST = ?0.015) was observed, thus, the French localities can be considered uniform units with regard to MHC diversity, a criterion to treat populations in these localities as a management unit.