The crystal structure of superoxide dismutase from Plasmodium falciparum

Background  

Superoxide dismutases (SODs) are important enzymes in defence against oxidative stress. In Plasmodium falciparum, they may be expected to have special significance since part of the parasite life cycle is spent in red blood cells where the formation of reactive oxygen species is likely to be promoted by the products of haemoglobin breakdown. Thus, inhibitors of P. falciparum SODs have potential as anti-malarial compounds. As a step towards their development we have determined the crystal structure of the parasite's cytosolic iron superoxide dismutase.     

Cellular analysis of host cell infection by different developmental stages of Trypanosoma cruzi

Trypanosoma cruzi is an obligate intracellular parasite that infects phagocytic and non-phagocytic mammalian cells by a complex process that appears to involve several discrete steps. Even though the infection process was described many years ago, the molecular mechanisms involved remain poorly understood. As fluorescent proteins have proven to be excellent tools for live-cell imaging, we used EGFP- and DsRed1-1-transfected trypomastigotes, amastigotes and epimastigotes to study the infection process in living cells. Contrary to what has been reported, our results showed that epimastigotes are as infective as trypomastigotes and amastigotes. Besides, differences in replication, differentiation and parasite release times were observed among the stages. Our results suggest that the different developmental stages use distinct attachment and invasion mechanisms. We propose that fluorescent-based plasmid expression systems are good models for studying the infection process of intracellular microorganisms and could offers insights about the molecular mechanisms involved.     

The 'lipid raft' microdomain proteins reggie-1 and reggie-2 (flotillins) are scaffolds for protein interaction and signalling

Reggie-1 and reggie-2 are two evolutionarily highly conserved proteins which are up-regulated in retinal ganglion cells during regeneration of lesioned axons in the goldfish optic nerve. They are located at the cytoplasmic face of the plasma membrane and are considered to be 'lipid raft' constituents due to their insolubility in Triton X-100 and presence in the 'floating fractions'; hence they were independently named flotillins. According to our current view, the reggies subserve functions as protein scaffolds which form microdomains in neurons, lymphocytes and many other cell types across species as distant as flies and humans. These microdomains are of a surprisingly constant size of less than or equal to 0.1 mm in all cell types, whereas the distance between them is variable. The microdomains co-ordinate signal transduction of specific cell-surface proteins and especially of GPI (glycosylphosphatidylinositol)-anchored proteins into the cell, as is demonstrated for PrP(c) (cellular prion protein) in T-lymphocytes. These cells possess a pre-formed reggie cap scaffold consisting of densely packed reggie microdomains. PrP(c) is targeted to the lymphocyte reggie cap when activated by antibody cross-linking, and induces a distinct Ca(2+) signal. In developing zebrafish, reggies become concentrated in neurons and axon tracts, and their absence, after morpholino antisense RNA-knockdown, results in deformed embryos with reduced brains. Likewise, defects in Drosophila eye morphogenesis occur upon reggie overexpression in mutant flies. The defects observed in the organism, as well as in single cells in culture, indicate a morphogenetic function of the reggies, with emphasis on the nervous system. This complies with their role as scaffolds for the formation of multiprotein complexes involved in signalling across the plasma membrane.     

Chemistry of Two Distinct Aeolid Spurilla Species: Ecological Implications

The lipophilic extracts of two marine aeolid nudibranch molluscs of the genus Spurilla collected in distinct geographical areas have been chemically analyzed. The Et₂O extracts of the nudibranchs were dominated by the presence of usual fatty acids and sterols and contained terpenoid compounds 1  –  3 as minor metabolites. Spurillin A ( 1 ) and spurillin B ( 3 ) were new molecules whereas cis‐γ‐monocyclofarnesol ( 2 ) was already reported in the literature as a synthesis product. Interestingly, bursatellin ( 4 ), previously isolated from anaspidean molluscs of the genus Bursatella, was found in the butanol extract of both Spurilla species. Compounds 1  –  4 were not detected in the extracts of the sea‐anemone preys collected together with the molluscs.     

Synthesis and biological investigation of S-aryl-S-DABO derivatives as HIV-1 inhibitors

S-Aryl-S-DABO derivatives, a novel subclass of S-DABO anti-HIV-1 agents, were synthesized via Ullmann type reaction starting from the corresponding 2-thiouracils by the aid of microwave irradiation. The results of their evaluation as inhibitors of RT are reported together with their antiviral activity in cellular assays.     

Allogeneic Non-Adherent Bone Marrow Cells Facilitate Hematopoietic Recovery but Do Not Lead to Allogeneic Engraftment

Background

Non adherent bone marrow derived cells (NA-BMCs) have recently been described to give rise to multiple mesenchymal phenotypes and have an impact in tissue regeneration. Therefore, the effects of murine bone marrow derived NA-BMCs were investigated with regard to engraftment capacities in allogeneic and syngeneic stem cell transplantation using transgenic, human CD4⁺, murine CD4^−/−, HLA-DR3⁺ mice.

Methodology/Principal Findings

Bone marrow cells were harvested from C57Bl/6 and Balb/c wild-type mice, expanded to NA-BMCs for 4 days and characterized by flow cytometry before transplantation in lethally irradiated recipient mice. Chimerism was detected using flow cytometry for MHC-I (H-2D[b], H-2K[d]), mu/huCD4, and huHLA-DR3). Culturing of bone marrow cells in a dexamethasone containing DMEM medium induced expansion of non adherent cells expressing CD11b, CD45, and CD90. Analysis of the CD45⁺ showed depletion of CD4⁺, CD8⁺, CD19⁺, and CD117⁺ cells. Expanded syngeneic and allogeneic NA-BMCs were transplanted into triple transgenic mice. Syngeneic NA-BMCs protected 83% of mice from death (n = 8, CD4⁺ donor chimerism of 5.8±2.4% [day 40], P<.001). Allogeneic NA-BMCs preserved 62.5% (n = 8) of mice from death without detectable hematopoietic donor chimerism. Transplantation of syngeneic bone marrow cells preserved 100%, transplantation of allogeneic bone marrow cells 33% of mice from death.

Conclusions/Significance

NA-BMCs triggered endogenous hematopoiesis and induced faster recovery compared to bone marrow controls. These findings may be of relevance in the refinement of strategies in the treatment of hematological malignancies.     

A comparison of the wood anatomy of 11 species from two cerrado habitats (cerrado s.s. and adjacent gallery forest)

A comparative study of the secondary xylem (wood) anatomy of 11 species (38 specimens) occurring in cerrado s.s. and the adjacent gallery forest (both cerrado s.l. habitat) was made with the aim of identifying the anatomical characteristics of ecological value and correlating them with the environmental conditions. The anatomical features that vary, in general, between the two habitats are: growth ring distinctness (well or poorly defined); tyloses and deposits (more abundant in cerrado specimens); gelatinous fibres (more evident in cerrado specimens and in different patterns between habitats); variation in paratracheal and banded parenchyma (more abundant in cerrado); and more cells per parenchyma strand in cerrado. In general, gallery forest specimens have wider vessels, fewer vessels per square millimetre and larger intervessel pits, indicating more efficient water conduction, whereas cerrado s.s. specimens are the opposite, with low vulnerability and mesomorphy indices, demonstrating greater safety under conditions of water stress. © 2012 The Linnean Society of London, Botanical Journal of the Linnean Society, 2012, ?? , ??–??.