Overview of the Opportunity Mars Exploration Rover mission to Meridiani Planum: Eagle crater to Purgatory ripple

The Mars Exploration Rover Opportunity touched down at Meridiani Planum in January 2004 and since then has been conducting observations with the Athena science payload. The rover has traversed more than 5 km, carrying out the first outcrop-scale investigation of sedimentary rocks on Mars. The rocks of Meridiani Planum are sandstones formed by eolian and aqueous reworking of sand grains that are composed of mixed fine-grained siliciclastics and sulfates. The siliciclastic fraction was produced by chemical alteration of a precursor basalt. The sulfates are dominantly Mg-sulfates and also include Ca-sulfates and jarosite. The stratigraphic section observed to date is dominated by eolian bedforms, with subaqueous current ripples exposed near the top of the section. After deposition, interaction with groundwater produced a range of diagenetic features, notably the hematite-rich concretions known as ‘‘blueberries.’’ The bedrock at Meridiani is highly friable and has undergone substantial erosion by wind-transported basaltic sand. This sand, along with concretions and concretion fragments eroded from the rock, makes up a soil cover that thinly and discontinuously buries the bedrock. The soil surface exhibits both ancient and active wind ripples that record past and present wind directions. Loose rocks on the soil surface are rare and include both impact ejecta and meteorites. While Opportunity’s results show that liquid water was once present at Meridiani Planum below and occasionally at the surface, the environmental conditions recorded were dominantly arid, acidic, and oxidizing and would have posed some significant challenges to the origin of life.Additional co-authors: J Farmer, WH Farrand, W Folkner, R Gellert, TD Glotch, M Golombek, S Gorevan, JA Grant, R Greeley, J Grotzinger, KE Herkenhoff, S Hviid, JR Johnson, G Klingelhöfer, AH Knoll, G Landis, M Lemmon, R Li, MB Madsen, MC Malin, SM McLennan, HY McSween, DW Ming, J Moersch, RV Morris, T Parker, JW Rice Jr, L Richter, R Rieder, M Sims, M Smith, P Smith, LA Soderblom, R Sullivan, NJ Tosca, H Wnke, T Wdowiak, M Wolff, A Ye

The conformation of purified Toxoplasma gondii SAG1 antigen, secreted from engineered Pichia pastoris, is adequate for serorecognition and cell proliferation.

A truncated form of SAG1, the immunodominant surface antigen of Toxoplasma gondii, has been produced in the methylotrophic yeast, Pichia pastoris. By construction, the recombinant protein lacks C-terminal residues 308-336 which, in native SAG1, encompass the glycosylphosphatidylinositol anchorage site. Secretion of anchor-less SAG1 proceeded via the yeast prepro alpha-mating factor signal peptide and yielded two immunoreactive protein species having apparent molecular masses of 31.5 and 34.5 kDa, respectively, and differing only by N-glycosylation of the single Asn-X-Ser site present in the molecule. Purification of the anchor-less SAG1 was achieved by a combination of ion-exchange and size-exclusion chromatographies. N-terminal amino acid sequencing of the products indicated the presence of additional residues glutamic acid--alanine at the N-terminal end of the products. Despite incomplete processing and unnatural glycosylation, anchor-less SAG1 proteins apparently adopted a suitable conformation recognized by monoclonal and human serum-derived antibodies, specific for the native SAG1. In addition, the recombinant anchor-less SAG1 proved competent for inducing proliferation, in vitro, of mononuclear cells from seropositive individuals. Finally, properly adjuvanted anchor-less SAG1 was able to induce protection of mice against a lethal challenge with T. gondii tachyzoites.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Immunogenicity of a recombinant varicella-zoster virus gE-IE63 fusion protein, a putative vaccine candidate against primary infection and zoster reactivation.

The varicella-zoster virus (VZV) envelope glycoprotein E (gE) and immediate early protein 63 (IE63) are well known targets for specific humoral and cell-mediated immune responses during VZV infection and latency, respectively. The present study evaluated the immunogenicity of an engineered chimeric recombinant gE-IE63 (recgE-IE63) protein secreted from CHO cells, wherein a soluble form of gE, deleted of its anchor and cytoplasmic domains was fused to IE63. Guinea pig vaccinations with adjuvanted recgE-IE63 elicited a strong and specific humoral immune response directed to each counterpart. Sera from recgE-IE63-immunized animals neutralized cell-free VZV. This neutralizing capacity was dependent only on the recgE moiety as serum depletions on recgE-immobilized sepharose totally abolished VZV neutralization. The cell-mediated immune response induced by recgE-IE63 was evaluated in lymphoproliferation assays. An antigen-specific proliferative response was demonstrated after lymphocyte stimulation with recIE63 but not with recgE. We conclude that recombinant chimeric recgE-IE63 induced both humoral and cell-mediated immune responses and thus could constitute a putative subunit vaccine candidate against VZV primary infection and zoster reactivation.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Genome-wide association analysis identifies a mutation in the thiamine transporter 2 (SLC19A3) gene associated with Alaskan Husky encephalopathy.

Alaskan Husky Encephalopathy (AHE) has been previously proposed as a mitochondrial encephalopathy based on neuropathological similarities with human Leigh Syndrome (LS). We studied 11 Alaskan Husky dogs with AHE, but found no abnormalities in respiratory chain enzyme activities in muscle and liver, or mutations in mitochondrial or nuclear genes that cause LS in people. A genome wide association study was performed using eight of the affected dogs and 20 related but unaffected control AHs using the Illumina canine HD array. SLC19A3 was identified as a positional candidate gene. This gene controls the uptake of thiamine in the CNS via expression of the thiamine transporter protein THTR2. Dogs have two copies of this gene located within the candidate interval (SLC19A3.2 - 43.36-43.38 Mb and SLC19A3.1 - 43.411-43.419 Mb) on chromosome 25. Expression analysis in a normal dog revealed that one of the paralogs, SLC19A3.1, was expressed in the brain and spinal cord while the other was not. Subsequent exon sequencing of SLC19A3.1 revealed a 4bp insertion and SNP in the second exon that is predicted to result in a functional protein truncation of 279 amino acids (c.624 insTTGC, c.625 C>A). All dogs with AHE were homozygous for this mutation, 15/41 healthy AH control dogs were heterozygous carriers while 26/41 normal healthy AH dogs were wild type. Furthermore, this mutation was not detected in another 187 dogs of different breeds. These results suggest that this mutation in SLC19A3.1, encoding a thiamine transporter protein, plays a critical role in the pathogenesis of AHE

Respiratory chain enzyme rates in liver of dogs with AHE.

*<p>CI+III (complex I+III), NADH: cytochrome c reductase; CII+III (complex II+III), succinate:cytochrome c reductase; CIV (complex IV), cytochrome oxidase; CS (citrate synthase).</p

DNA sequence of the mutation identified in AHE.

<p>A. wildtype sequence, B. Heterozygous carrier, C. Mutant sequence.</p

The relative tissue specific expression levels of the two paralogs of <i>SLC19A3</i> and GAPDH.

<p>RT PCR products obtained from equal amounts of cDNA are shown from the following tissues: 1 spleen, 2 skin, 3 cerebellum, 4 thymus, 5 testis, 6 spinal cord, 7 heart, 8 muscle, 9 cerebral cortex, 10 kidney, and 11 liver.</p

Brain of dog #6.

<p><b>A</b>. Transverse section of brain with bilaterally symmetrical areas of cavitation due to encephalomalacia in the thalamus. <b>B.</b> Same dog; macrophotograph of a transverse section of brain rostral to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057195#pone-0057195-g002" target="_blank">Figure 2A</a> illustrating bilaterally symmetrical areas of polioencephalomalacia <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057195#pone.0057195-Brenner1" target="_blank">[2]</a> or of necrosis with incipient malacia <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057195#pone.0057195-Wakshlag1" target="_blank">[1]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057195#pone.0057195-Baiker1" target="_blank">[3]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057195#pone.0057195-Finsterer1" target="_blank">[4]</a> in cortex deep in the sulci <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057195#pone.0057195-Wakshlag1" target="_blank">[1]</a>, in the claustrum <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057195#pone.0057195-Brenner1" target="_blank">[2]</a>, in caudate nucleus <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057195#pone.0057195-Baiker1" target="_blank">[3]</a> and the globus pallidus <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057195#pone.0057195-Finsterer1" target="_blank">[4]</a> (HE-LFB stain).</p