Symbiodinium Genotypic and Environmental Controls on Lipids in Reef Building Corals

BACKGROUND: Lipids in reef building corals can be divided into two classes; non-polar storage lipids, e.g. wax esters and triglycerides, and polar structural lipids, e.g. phospholipids and cholesterol. Differences among algal endosymbiont types are known to have important influences on processes including growth and the photobiology of scleractinian corals yet very little is known about the role of symbiont types on lipid energy reserves. METHODOLOGY/PRINCIPAL FINDINGS: The ratio of storage lipid and structural lipid fractions of Scott Reef corals were determined by thin layer chromatography. The lipid fraction ratio varied with depth and depended on symbiont type harboured by two corals (Seriatopora hystrix and Pachyseris speciosa). S. hystrix colonies associated with Symbiodinium C1 or C1/C# at deep depths (>23 m) had lower lipid fraction ratios (i.e. approximately equal parts of storage and structural lipids) than those with Symbiodinium D1 in shallow depths (<23 m), which had higher lipid fraction ratios (i.e. approximately double amounts of storage relative to structural lipid). Further, there was a non-linear relationship between the lipid fraction ratio and depth for S. hystrix with a modal peak at ∼23 m coinciding with the same depth as the shift from clade D to C types. In contrast, the proportional relationship between the lipid fraction ratio and depth for P. speciosa, which exhibited high specificity for Symbiodinium C3 like across the depth gradient, was indicative of greater amounts of storage lipids contained in the deep colonies. CONCLUSIONS/SIGNIFICANCE: This study has demonstrated that Symbiodinium exert significant controls over the quality of coral energy reserves over a large-scale depth gradient. We conclude that the competitive advantages and metabolic costs that arise from flexible associations with divergent symbiont types are offset by energetic trade-offs for the coral host

Divergent evolution of terrestrial locomotor abilities in extant Crocodylia

Extant Crocodylia are exceptional because they employ almost the full range of quadrupedal footfall patterns (“gaits”) used by mammals; including asymmetrical gaits such as galloping and bounding. Perhaps this capacity evolved in stem Crocodylomorpha, during the Triassic when taxa were smaller, terrestrial, and long-legged. However, confusion about which Crocodylia use asymmetrical gaits and why persists, impeding reconstructions of locomotor evolution. Our experimental gait analysis of locomotor kinematics across 42 individuals from 15 species of Crocodylia obtained 184 data points for a wide velocity range (0.15–4.35 ms−1). Our results suggest either that asymmetrical gaits are ancestral for Crocodylia and lost in the alligator lineage, or that asymmetrical gaits evolved within Crocodylia at the base of the crocodile line. Regardless, we recorded usage of asymmetrical gaits in 7 species of Crocodyloidea (crocodiles); including novel documentation of these behaviours in 5 species (3 critically endangered). Larger Crocodylia use relatively less extreme gait kinematics consistent with steeply decreasing athletic ability with size. We found differences between asymmetrical and symmetrical gaits in Crocodylia: asymmetrical gaits involved greater size-normalized stride frequencies and smaller duty factors (relative ground contact times), consistent with increased mechanical demands. Remarkably, these gaits did not differ in maximal velocities obtained: whether in Alligatoroidea or Crocodyloidea, trotting or bounding achieved similar velocities, revealing that the alligator lineage is capable of hitherto unappreciated extreme locomotor performance despite a lack of asymmetrical gait usage. Hence asymmetrical gaits have benefits other than velocity capacity that explain their prevalence in Crocodyloidea and absence in Alligatoroidea—and their broader evolution

A somatic-mutational process recurrently duplicates germline susceptibility loci and tissue-specific super-enhancers in breast cancers

Somatic rearrangements contribute to the mutagenized landscape of cancer genomes. Here, we systematically interrogated rearrangements in 560 breast cancers by using a piecewise constant fitting approach. We identified 33 hotspots of large (>100 kb) tandem duplications, a mutational signature associated with homologous-recombination-repair deficiency. Notably, these tandem-duplication hotspots were enriched in breast cancer germline susceptibility loci (odds ratio (OR) = 4.28) and breast-specific 'super-enhancer' regulatory elements (OR = 3.54). These hotspots may be sites of selective susceptibility to double-strand-break damage due to high transcriptional activity or, through incrementally increasing copy number, may be sites of secondary selective pressure. The transcriptomic consequences ranged from strong individual oncogene effects to weak but quantifiable multigene expression effects. We thus present a somatic-rearrangement mutational process affecting coding sequences and noncoding regulatory elements and contributing a continuum of driver consequences, from modest to strong effects, thereby supporting a polygenic model of cancer development.DG is supported by the EU-FP7-SUPPRESSTEM project. SN-Z is funded by a Wellcome Trust Intermediate Fellowship (WT100183MA) and is a Wellcome Beit Fellow. For more information, please visit the publisher's website

Dcas Supports Cell Polarization and Cell-Cell Adhesion Complexes in Development

Mammalian Cas proteins regulate cell migration, division and survival, and are often deregulated in cancer. However, the presence of four paralogous Cas family members in mammals (BCAR1/p130Cas, EFS/Sin1, NEDD9/HEF1/Cas-L, and CASS4/HEPL) has limited their analysis in development. We deleted the single Drosophila Cas gene, Dcas, to probe the developmental function of Dcas. Loss of Dcas had limited effect on embryonal development. However, we found that Dcas is an important modulator of the severity of the developmental phenotypes of mutations affecting integrins (If and mew) and their downstream effectors Fak56D or Src42A. Strikingly, embryonic lethal Fak56D-Dcas double mutant embryos had extensive cell polarity defects, including mislocalization and reduced expression of E-cadherin. Further genetic analysis established that loss of Dcas modified the embryonal lethal phenotypes of embryos with mutations in E-cadherin (Shg) or its signaling partners p120- and β-catenin (Arm). These results support an important role for Cas proteins in cell-cell adhesion signaling in development

Plant-Type Trehalose Synthetic Pathway in Cryptosporidium and Some Other Apicomplexans

The trehalose synthetic pathway is present in bacteria, fungi, plants and invertebrate animals, but is absent in vertebrates. This disaccharide mainly functions as a stress protectant against desiccation, heat, cold and oxidation. Genes involved in trehalose synthesis have been observed in apicomplexan parasites, but little was known about these enzymes. Study on trehalose synthesis in apicomplexans would not only shed new light into the evolution of this pathway, but also provide data for exploring this pathway as novel drug target.We have observed the presence of the trehalose synthetic pathway in Cryptosporidium and other apicomplexans and alveolates. Two key enzymes (trehalose 6-phosphate synthase [T6PS; EC 2.4.1.15] and trehalose phosphatase [TPase; EC 3.1.3.12] are present as Class II bifunctional proteins (T6PS-TPase) in the majority of apicomplexans with the exception of Plasmodium species. The enzyme for synthesizing the precursor (UDP-glucose) is homologous to dual-substrate UDP-galactose/glucose pyrophosphorylases (UGGPases), rather than the "classic" UDP-glucose pyrophosphorylase (UGPase). Phylogenetic recontructions indicate that both T6PS-TPases and UGGPases in apicomplexans and other alveolates are evolutionarily affiliated with stramenopiles and plants. The expression level of T6PS-TPase in C. parvum is highly elevated in the late intracellular developmental stage prior to or during the production of oocysts, implying that trehalose may be important in oocysts as a protectant against environmental stresses. Finally, trehalose has been detected in C. parvum oocysts, thus confirming the trehalose synthetic activity in this parasite.A trehalose synthetic pathway is described in the majority of apicomplexan parasites including Cryptosporidium and the presence of trehalose was confirmed in the C. parvum oocyst. Key enzymes in the pathway (i.e., T6PS-TPase and UGGPase) are plant-type and absent in humans and animals, and may potentially serve as novel drug targets in the apicomplexans

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Relic topological defects from brane annihilation simulated in superfluid He-3.

Although it is widely accepted that to resolve the 'horizon' problem the early Universe must have undergone a sudden expansion (cosmic inflation), what mechanism drove this process is less clear. In the braneworld scenario, it is suggested that inflationary epochs may have been initiated and terminated by brane collisions and annihilations. Branes are objects of lower dimensionality embedded in a higher-dimensional matrix. For example, we may live on a three-dimensional brane embedded in a four-dimensional matrix. However, such structures are so far removed from everyday reality that bringing physical insight to bear is difficult. Here we report laboratory experiments where we simulate brane annihilation using the closest brane analogue to which we have access, the coherent phase boundary between the two phases of superfluid He-3. When two branes collide or annihilate, topological defects may be created, whose influence may still be detectable today. By creating a brane-antibrane pair in superfluid He-3 and subsequently annihilating it, we can detect that defects are indeed created in the superfluid texture (the superfluid analogue of spacetime), thus confirming that the concept of defect formation after brane annihilation in the early Universe can be reproduced in analogous systems in the laboratory