The Toxoplasma gondii plastid replication and repair enzyme complex, PREX

A plastid-like organelle, the apicoplast, is essential to the majority of medically and veterinary important apicomplexan protozoa including Toxoplasma gondii and Plasmodium. The apicoplast contains multiple copies of a 35 kb genome, the replication of which is dependent upon nuclear-encoded proteins that are imported into the organelle. In P. falciparum an unusual multi-functional gene, pfprex, was previously identified and inferred to encode a protein with DNA primase, DNA helicase and DNA polymerase activities. Herein, we report the presence of a prex orthologue in T. gondii. The protein is predicted to have a bi-partite apicoplast targeting sequence similar to that demonstrated on the PfPREX polypeptide, capable of delivering marker proteins to the apicoplast. Unlike the P. falciparum gene that is devoid of introns, the T. gondii prex gene carries 19 introns, which are spliced to produce a contiguous mRNA. Bacterial expression of the polymerase domain reveals the protein to be active. Consistent with the reported absence of a plastid in Cryptosporidium species, in silico analysis of their genomes failed to demonstrate an orthologue of prex. These studies indicate that prex is conserved across the plastid-bearing apicomplexans and may play an important role in the replication of the plastid genome

Revisiting the Zingiberales: Using Multiplexed Exon Capture to Resolve Ancient and Recent Phylogenetic Splits in a Charismatic Plant Lineage

The Zingiberales are an iconic order of monocotyledonous plants comprising eight families with distinctive and diverse floral morphologies and representing an important ecological element of tropical and subtropical forests. While the eight families are demonstrated to be monophyletic, phylogenetic relationships among these families remain unresolved. Neither combined morphological and molecular studies nor recent attempts to resolve family relationships using sequence data from whole plastomes has resulted in a well-supported, family-level phylogenetic hypothesis of relationships. Here we approach this challenge by leveraging the complete genome of one member of the order, Musa acuminata, together with transcriptome information from each of the other seven families to design a set of nuclear loci that can be enriched from highly divergent taxa with a single array-based capture of indexed genomic DNA. A total of 494 exons from 418 nuclear genes were captured for 53 ingroup taxa. The entire plastid genome was also captured for the same 53 taxa. Of the total genes captured, 308 nuclear and 68 plastid genes were used for phylogenetic estimation. The concatenated plastid and nuclear dataset supports the position of Musaceae as sister to the remaining seven families. Moreover, the combined dataset recovers known intra- and inter-family phylogenetic relationships with generally high bootstrap support. This is a flexible and cost effective method that gives the broader plant biology community a tool for generating phylogenomic scale sequence data in non-model systems at varying evolutionary depths

Ancient Polyploidy and Genome Evolution in Palms

Mechanisms of genome evolution are fundamental to our understanding of adaptation and the generation and maintenance of biodiversity, yet genome dynamics are still poorly characterized in many clades. Strong correlations between variation in genomic attributes and species diversity across the plant tree of life suggest that polyploidy or other mechanisms of genome size change confer selective advantages due to the introduction of genomic novelty. Palms (order Arecales, family Arecaceae) are diverse, widespread, and dominant in tropical ecosystems, yet little is known about genome evolution in this ecologically and economically important clade. Here, we take a phylogenetic comparative approach to investigate palm genome dynamics using genomic and transcriptomic data in combination with a recent, densely sampled, phylogenetic tree. We find conclusive evidence of a paleopolyploid event shared by the ancestor of palms but not with the sister clade, Dasypogonales. We find evidence of incremental chromosome number change in the palms as opposed to one of recurrent polyploidy. We find strong phylogenetic signal in chromosome number, but no signal in genome size, and further no correlation between the two when correcting for phylogenetic relationships. Palms thus add to a growing number of diverse, ecologically successful clades with evidence of whole-genome duplication, sister to a species-poor clade with no evidence of such an event. Disentangling the causes of genome size variation in palms moves us closer to understanding the genomic conditions facilitating adaptive radiation and ecological dominance in an evolutionarily successful, emblematic tropical clade

Localized retroprocessing as a model of intron loss in the plant mitochondrial genome

Loss of introns in plant mitochondrial genes is commonly explained by retroprocessing. Under this model, an mRNA is reverse transcribed and integrated back into the genome, simultaneously affecting the contents of introns and edited sites. To evaluate the extent to which retroprocessing explains intron loss, we analyzed patterns of intron content and predicted RNA editing for whole mitochondrial genomes of 30 species in the monocot order Alismatales. In this group, we found an unusually high degree of variation in the intron content, even expanding the hitherto known variation among angiosperms. Some species have lost some two-third of the cis-spliced introns. We found a strong correlation between intron content and editing frequency, and detected 27 events in which intron loss is consistent with the presence of nucleotides in an edited state, supporting retroprocessing. However, we also detected seven cases of intron loss not readily being explained by retroprocession. Our analyses are also not consistent with the entire length of a fully processed cDNA copy being integrated into the genome, but instead indicate that retroprocessing usually occurs for only part of the gene. In some cases, several rounds of retroprocessing may explain intron loss in genes completely devoid of introns. A number of taxa retroprocessing seem to be very common and a possibly ongoing process. It affects the entire mitochondrial genome

Mitochondrial genome evolution in Alismatales: Size reduction and extensive loss of ribosomal protein genes

<div><p>The order Alismatales is a hotspot for evolution of plant mitochondrial genomes characterized by remarkable differences in genome size, substitution rates, RNA editing, retrotranscription, gene loss and intron loss. Here we have sequenced the complete mitogenomes of <i>Zostera marina</i> and <i>Stratiotes aloides</i>, which together with previously sequenced mitogenomes from <i>Butomus</i> and <i>Spirodela</i>, provide new evolutionary evidence of genome size reduction, gene loss and transfer to the nucleus. The <i>Zostera</i> mitogenome includes a large portion of DNA transferred from the plastome, yet it is the smallest known mitogenome from a non-parasitic plant. Using a broad sample of the Alismatales, the evolutionary history of ribosomal protein gene loss is analyzed. In <i>Zostera</i> almost all ribosomal protein genes are lost from the mitogenome, but only some can be found in the nucleus.</p></div

Warming experiments elucidate the drivers of observed directional changes in tundra vegetation

Few studies have clearly linked long-term monitoring with insitu experiments to clarify potential drivers of observed change at a given site. This is especially necessary when findings from a site are applied to a much broader geographic area. Here, we document vegetation change at Barrow and Atqasuk, Alaska, occurring naturally and due to experimental warming over nearly two decades. An examination of plant cover, canopy height, and community indices showed more significant differences between years than due to experimental warming. However, changes with warming were more consistent than changes between years and were cumulative in many cases. Most cases of directional change observed in the control plots over time corresponded with a directional change in response to experimental warming. These included increases in canopy height and decreases in lichen cover. Experimental warming resulted in additional increases in evergreen shrub cover and decreases in diversity and bryophyte cover. This study suggests that the directional changes occurring at the sites are primarily due to warming and indicates that further changes are likely in the next two decades if the regional warming trend continues. These findings provide an example of the utility of coupling insitu experiments with long-term monitoring to accurately document vegetation change in response to global change and to identify the underlying mechanisms driving observed changes

A Bell Inequality Analog in Quantum Measure Theory

One obtains Bell's inequalities if one posits a hypothetical joint probability distribution, or {\it measure}, whose marginals yield the probabilities produced by the spin measurements in question. The existence of a joint measure is in turn equivalent to a certain causality condition known as ``screening off''. We show that if one assumes, more generally, a joint {\it quantal measure}, or ``decoherence functional'', one obtains instead an analogous inequality weaker by a factor of $\sqrt{2}$. The proof of this ``Tsirel'son inequality'' is geometrical and rests on the possibility of associating a Hilbert space to any strongly positive quantal measure. These results lead both to a {\it question}: ``Does a joint measure follow from some quantal analog of `screening off'?'', and to the {\it observation} that non-contextual hidden variables are viable in histories-based quantum mechanics, even if they are excluded classically.Comment: 38 pages, TeX. Several changes and added comments to bring out the meaning more clearly. Minor rewording and extra acknowledgements, now closer to published versio

Structure-based design of a novel class of autotaxin inhibitors based on endogenous allosteric modulators

Autotaxin (ATX) facilitates the hydrolysis of lysophosphatidylcholine to lysophosphatidic acid (LPA), a bioactive phospholipid, which facilitates a diverse range of cellular effects in multiple tissue types. Abnormal LPA expression can lead to the progression of diseases such as cancer and fibrosis. Previously, we identified a potent ATX steroid-derived hybrid (partially orthosteric and allosteric) inhibitor which did not form interactions with the catalytic site. Herein, we describe the design, synthesis, and biological evaluation of a focused library of novel steroid-derived analogues targeting the bimetallic catalytic site, representing an entirely unique class of ATX inhibitors of type V designation, which demonstrate significant pathway-relevant biochemical and phenotypic biological effects. The current compounds modulated LPA-mediated ATX allostery and achieved indirect blockage of LPA1 internalization, in line with the observed reduction in downstream signaling cascades and chemotaxis induction. These novel type V ATX inhibitors represent a promising tool to inactivate the ATX-LPA signaling axis

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Lafite in China

Increased economic power has positioned China within the global elite, yet China’s legitimacy remains low with regard to hierarchies of taste. Drawing from Bourdieu and Elias, this article offers an account of the global dynamics of status contests, and the role played by cultural capital and notions of civility and vulgarity. Specifically, we examine how U.S., UK, and Chinese media represent Chinese consumption of fine wine, and particularly that of Château Lafite, in the 2000 to 2013 period. Our analysis reveals four major ways in which Chinese fine wine consumption is framed—as vulgar, popular, functional, and discerning—and highlights tensions between Western and Chinese terms of cultural legitimacy. The research uncovers nuanced dimensions to the “East/West” divide in terms of the grades of cultural capital, competing logics of valuation, and modes of civility at play. Macromarketing implications of fine wine consumption in a fragmented and complex market are discussed