Redox-freezing and nucleation of diamond via magnetite formation in the Earth’s mantle

Diamonds and their inclusions are unique probes into the deep Earth, tracking the deep carbon cycle to >800 km. Understanding the mechanisms of carbon mobilization and freezing is a prerequisite for quantifying the fluxes of carbon in the deep Earth. Here we show direct evidence for the formation of diamond by redox reactions involving FeNi sulfides. Transmission Kikuchi Diffraction identifies an arrested redox reaction from pyrrhotite to magnetite included in diamond. The magnetite corona shows coherent epitaxy with relict pyrrhotite and diamond, indicating that diamond nucleated on magnetite. Furthermore, structures inherited from h-Fe3O4 define a phase transformation at depths of 320–330 km, the base of the Kaapvaal lithosphere. The oxidation of pyrrhotite to magnetite is an important trigger of diamond precipitation in the upper mantle, explaining the presence of these phases in diamonds

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology

Single nucleotide polymorphism discovery in elite north american potato germplasm

BACKGROUND: Current breeding approaches in potato rely almost entirely on phenotypic evaluations; molecular markers, with the exception of a few linked to disease resistance traits, are not widely used. Large-scale sequence datasets generated primarily through Sanger Expressed Sequence Tag projects are available from a limited number of potato cultivars and access to next generation sequencing technologies permits rapid generation of sequence data for additional cultivars. When coupled with the advent of high throughput genotyping methods, an opportunity now exists for potato breeders to incorporate considerably more genotypic data into their decision-making. RESULTS: To identify a large number of Single Nucleotide Polymorphisms (SNPs) in elite potato germplasm, we sequenced normalized cDNA prepared from three commercial potato cultivars: 'Atlantic', 'Premier Russet' and 'Snowden'. For each cultivar, we generated 2 Gb of sequence which was assembled into a representative transcriptome of (~)28-29 Mb for each cultivar. Using the Maq SNP filter that filters read depth, density, and quality, 575,340 SNPs were identified within these three cultivars. In parallel, 2,358 SNPs were identified within existing Sanger sequences for three additional cultivars, 'Bintje', 'Kennebec', and 'Shepody'. Using a stringent set of filters in conjunction with the potato reference genome, we identified 69,011 high confidence SNPs from these six cultivars for use in genotyping with the Infinium platform. Ninety-six of these SNPs were used with a BeadXpress assay to assess allelic diversity in a germplasm panel of 248 lines; 82 of the SNPs proved sufficiently informative for subsequent analyses. Within diverse North American germplasm, the chip processing market class was most distinct, clearly separated from all other market classes. The round white and russet market classes both include fresh market and processing cultivars. Nevertheless, the russet and round white market classes are more distant from each other than processing are from fresh market types within these two groups. CONCLUSIONS: The genotype data generated in this study, albeit limited in number, has revealed distinct relationships among the market classes of potato. The SNPs identified in this study will enable high-throughput genotyping of germplasm and populations, which in turn will enable more efficient marker-assisted breeding efforts in potato

Next generation transcriptomes for next generation genomes using est2assembly

<p>Abstract</p> <p>Background</p> <p>The decreasing costs of capillary-based Sanger sequencing and next generation technologies, such as 454 pyrosequencing, have prompted an explosion of transcriptome projects in non-model species, where even shallow sequencing of transcriptomes can now be used to examine a range of research questions. This rapid growth in data has outstripped the ability of researchers working on non-model species to analyze and mine transcriptome data efficiently.</p> <p>Results</p> <p>Here we present a semi-automated platform '<it>est2assembly</it>' that processes raw sequence data from Sanger or 454 sequencing into a hybrid <it>de-novo </it>assembly, annotates it and produces GMOD compatible output, including a SeqFeature database suitable for GBrowse. Users are able to parameterize assembler variables, judge assembly quality and determine the optimal assembly for their specific needs. We used <it>est2assembly </it>to process <it>Drosophila </it>and <it>Bicyclus </it>public Sanger EST data and then compared them to published 454 data as well as eight new insect transcriptome collections.</p> <p>Conclusions</p> <p>Analysis of such a wide variety of data allows us to understand how these new technologies can assist EST project design. We determine that assembler parameterization is as essential as standardized methods to judge the output of ESTs projects. Further, even shallow sequencing using 454 produces sufficient data to be of wide use to the community. <it>est2assembly </it>is an important tool to assist manual curation for gene models, an important resource in their own right but especially for species which are due to acquire a genome project using Next Generation Sequencing.</p

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

Vaccine Potential of Nipah Virus-Like Particles

Nipah virus (NiV) was first recognized in 1998 in a zoonotic disease outbreak associated with highly lethal febrile encephalitis in humans and a predominantly respiratory disease in pigs. Periodic deadly outbreaks, documentation of person-to-person transmission, and the potential of this virus as an agent of agroterror reinforce the need for effective means of therapy and prevention. In this report, we describe the vaccine potential of NiV virus-like particles (NiV VLPs) composed of three NiV proteins G, F and M. Co-expression of these proteins under optimized conditions resulted in quantifiable amounts of VLPs with many virus-like/vaccine desirable properties including some not previously described for VLPs of any paramyxovirus: The particles were fusogenic, inducing syncytia formation; PCR array analysis showed NiV VLP-induced activation of innate immune defense pathways; the surface structure of NiV VLPs imaged by cryoelectron microscopy was dense, ordered, and repetitive, and consistent with similarly derived structure of paramyxovirus measles virus. The VLPs were composed of all the three viral proteins as designed, and their intracellular processing also appeared similar to NiV virions. The size, morphology and surface composition of the VLPs were consistent with the parental virus, and importantly, they retained their antigenic potential. Finally, these particles, formulated without adjuvant, were able to induce neutralizing antibody response in Balb/c mice. These findings indicate vaccine potential of these particles and will be the basis for undertaking future protective efficacy studies in animal models of NiV disease

Mantle Pb paradoxes : the sulfide solution

Author Posting. © Springer, 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Contributions to Mineralogy and Petrology 152 (2006): 295-308, doi:10.1007/s00410-006-0108-1.There is growing evidence that the budget of Pb in mantle peridotites is largely contained in sulfide, and that Pb partitions strongly into sulfide relative to silicate melt. In addition, there is evidence to suggest that diffusion rates of Pb in sulfide (solid or melt) are very fast. Given the possibility that sulfide melt ‘wets’ sub-solidus mantle silicates, and has very low viscosity, the implications for Pb behavior during mantle melting are profound. There is only sparse experimental data relating to Pb partitioning between sulfide and silicate, and no data on Pb diffusion rates in sulfides. A full understanding of Pb behavior in sulfide may hold the key to several long-standing and important Pb paradoxes and enigmas. The classical Pb isotope paradox arises from the fact that all known mantle reservoirs lie to the right of the Geochron, with no consensus as to the identity of the “balancing” reservoir. We propose that long-term segregation of sulfide (containing Pb) to the core may resolve this paradox. Another Pb paradox arises from the fact that the Ce/Pb ratio of both OIB and MORB is greater than bulk earth, and constant at a value of 25. The constancy of this “canonical ratio” implies similar partition coefficients for Ce and Pb during magmatic processes (Hofmann et al. 1986), whereas most experimental studies show that Pb is more incompatible in silicates than Ce. Retention of Pb in residual mantle sulfide during melting has the potential to bring the bulk partitioning of Ce into equality with Pb if the sulfide melt/silicate melt partition coefficient for Pb has a value of ~ 14. Modeling shows that the Ce/Pb (or Nd/Pb) of such melts will still accurately reflect that of the source, thus enforcing the paradox that OIB and MORB mantles have markedly higher Ce/Pb (and Nd/Pb) than the bulk silicate earth. This implies large deficiencies of Pb in the mantle sources for these basalts. Sulfide may play other important roles during magmagenesis: 1). advective/diffusive sulfide networks may form potent metasomatic agents (in both introducing and obliterating Pb isotopic heterogeneities in the mantle); 2). silicate melt networks may easily exchange Pb with ambient mantle sulfides (by diffusion or assimilation), thus ‘sampling’ Pb in isotopically heterogeneous mantle domains differently from the silicate-controlled isotope tracer systems (Sr, Nd, Hf), with an apparent ‘de-coupling’ of these systems.Our intemperance should not be blamed on the support we gratefully acknowledge from NSF: EAR- 0125917 to SRH and OCE-0118198 to GAG

Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors

Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.ope