The Origin and Initial Rise of Pelagic Cephalopods in the Ordovician

BACKGROUND: During the Ordovician the global diversity increased dramatically at family, genus and species levels. Partially the diversification is explained by an increased nutrient, and phytoplankton availability in the open water. Cephalopods are among the top predators of today's open oceans. Their Ordovician occurrences, diversity evolution and abundance pattern potentially provides information on the evolution of the pelagic food chain. METHODOLOGY/PRINCIPAL FINDINGS: We reconstructed the cephalopod departure from originally exclusively neritic habitats into the pelagic zone by the compilation of occurrence data in offshore paleoenvironments from the Paleobiology Database, and from own data, by evidence of the functional morphology, and the taphonomy of selected cephalopod faunas. The occurrence data show, that cephalopod associations in offshore depositional settings and black shales are characterized by a specific composition, often dominated by orthocerids and lituitids. The siphuncle and conch form of these cephalopods indicate a dominant lifestyle as pelagic, vertical migrants. The frequency distribution of conch sizes and the pattern of epibionts indicate an autochthonous origin of the majority of orthocerid and lituitid shells. The consistent concentration of these cephalopods in deep subtidal sediments, starting from the middle Tremadocian indicates the occupation of the pelagic zone early in the Early Ordovician and a subsequent diversification which peaked during the Darriwilian. CONCLUSIONS/SIGNIFICANCE: The exploitation of the pelagic realm started synchronously in several independent invertebrate clades during the latest Cambrian to Middle Ordovician. The initial rise and diversification of pelagic cephalopods during the Early and Middle Ordovician indicates the establishment of a pelagic food chain sustainable enough for the development of a diverse fauna of large predators. The earliest pelagic cephalopods were slowly swimming vertical migrants. The appearance and early diversification of pelagic cephalopods is interpreted as a consequence of the increased food availability in the open water since the latest Cambrian

Optimal deployment of components of cloud-hosted application for guaranteeing multitenancy isolation

One of the challenges of deploying multitenant cloud-hosted services that are designed to use (or be integrated with) several components is how to implement the required degree of isolation between the components when there is a change in the workload. Achieving the highest degree of isolation implies deploying a component exclusively for one tenant; which leads to high resource consumption and running cost per component. A low degree of isolation allows sharing of resources which could possibly reduce cost, but with known limitations of performance and security interference. This paper presents a model-based algorithm together with four variants of a metaheuristic that can be used with it, to provide near-optimal solutions for deploying components of a cloud-hosted application in a way that guarantees multitenancy isolation. When the workload changes, the model based algorithm solves an open multiclass QN model to determine the average number of requests that can access the components and then uses a metaheuristic to provide near-optimal solutions for deploying the components. Performance evaluation showed that the obtained solutions had low variability and percent deviation when compared to the reference/optimal solution. We also provide recommendations and best practice guidelines for deploying components in a way that guarantees the required degree of isolation

Field pathogenomics reveals the emergence of a diverse wheat yellow rust population

BACKGROUND: Emerging and re-emerging pathogens imperil public health and global food security. Responding to these threats requires improved surveillance and diagnostic systems. Despite their potential, genomic tools have not been readily applied to emerging or re-emerging plant pathogens such as the wheat yellow (stripe) rust pathogen Puccinia striiformis f. sp. tritici (PST). This is due largely to the obligate parasitic nature of PST, as culturing PST isolates for DNA extraction remains slow and tedious. RESULTS: To counteract the limitations associated with culturing PST, we developed and applied a field pathogenomics approach by transcriptome sequencing infected wheat leaves collected from the field in 2013. This enabled us to rapidly gain insights into this emerging pathogen population. We found that the PST population across the United Kingdom (UK) underwent a major shift in recent years. Population genetic structure analyses revealed four distinct lineages that correlated to the phenotypic groups determined through traditional pathology-based virulence assays. Furthermore, the genetic diversity between members of a single population cluster for all 2013 PST field samples was much higher than that displayed by historical UK isolates, revealing a more diverse population of PST. CONCLUSIONS: Our field pathogenomics approach uncovered a dramatic shift in the PST population in the UK, likely due to a recent introduction of a diverse set of exotic PST lineages. The methodology described herein accelerates genetic analysis of pathogen populations and circumvents the difficulties associated with obligate plant pathogens. In principle, this strategy can be widely applied to a variety of plant pathogens

Lysophosphatidic acid and sphingosine-1-phosphate promote morphogenesis and block invasion of prostate cancer cells in three-dimensional organotypic models

Normal prostate and some malignant prostate cancer (PrCa) cell lines undergo acinar differentiation and form spheroids in three-dimensional (3-D) organotypic culture. Acini formed by PC-3 and PC-3M, less pronounced also in other PrCa cell lines, spontaneously undergo an invasive switch, leading to the disintegration of epithelial structures and the basal lamina, and formation of invadopodia. This demonstrates the highly dynamic nature of epithelial plasticity, balancing epithelial-to-mesenchymal transition against metastable acinar differentiation. This study assessed the role of lipid metabolites on epithelial maturation. PC-3 cells completely failed to form acinar structures in delipidated serum. Adding back lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) rescued acinar morphogenesis and repressed invasion effectively. Blocking LPA receptor 1 (LPAR1) functions by siRNA (small interference RNA) or the specific LPAR1 inhibitor Ki16425 promoted invasion, while silencing of other G-protein-coupled receptors responsive to LPA or S1P mainly caused growth arrest or had no effects. The G-proteins Gα12/13 and Gαi were identified as key mediators of LPA signalling via stimulation of RhoA and Rho kinases ROCK1 and 2, activating Rac1, while inhibition of adenylate cyclase and accumulation of cAMP may be secondary. Interfering with these pathways specifically impeded epithelial polarization in transformed cells. In contrast, blocking the same pathways in non-transformed, normal cells promoted differentiation. We conclude that LPA and LPAR1 effectively promote epithelial maturation and block invasion of PrCa cells in 3-D culture. The analysis of clinical transcriptome data confirmed reduced expression of LPAR1 in a subset of PrCa's. Our study demonstrates a metastasis-suppressor function for LPAR1 and Gα12/13 signalling, regulating cell motility and invasion versus epithelial maturation

Dormancy within Staphylococcus epidermidis biofilms : a transcriptomic analysis by RNA-seq

The proportion of dormant bacteria within Staphylococcus epidermidis biofilms may determine its inflammatory profile. Previously, we have shown that S. epidermidis biofilms with higher proportions of dormant bacteria have reduced activation of murine macrophages. RNA-sequencing was used to identify the major transcriptomic differences between S. epidermidis biofilms with different proportions of dormant bacteria. To accomplish this goal, we used an in vitro model where magnesium allowed modulation of the proportion of dormant bacteria within S. epidermidis biofilms. Significant differences were found in the expression of 147 genes. A detailed analysis of the results was performed based on direct and functional gene interactions. Biological processes among the differentially expressed genes were mainly related to oxidation-reduction processes and acetyl-CoA metabolic processes. Gene set enrichment revealed that the translation process is related to the proportion of dormant bacteria. Transcription of mRNAs involved in oxidation-reduction processes was associated with higher proportions of dormant bacteria within S. epidermidis biofilm. Moreover, the pH of the culture medium did not change after the addition of magnesium, and genes related to magnesium transport did not seem to impact entrance of bacterial cells into dormancy.The authors thank Stephen Lorry at Harvard Medical School for providing CLC Genomics software. This work was funded by Fundacao para a Ciencia e a Tecnologia (FCT) and COMPETE grants PTDC/BIA-MIC/113450/2009, FCOMP-01-0124-FEDER-014309, FCOMP-01-0124-FEDER-022718 (FCT PEst-C/SAU/LA0002/2011), QOPNA research unit (project PEst-C/QUI/UI0062/2011), and CENTRO-07-ST24-FEDER-002034. The following authors had an individual FCT fellowship: VC (SFRH/BD/78235/2011) and AF (2SFRH/BD/62359/2009)

Heart valve disease: investigation by cardiovascular magnetic resonance

Cardiovascular magnetic resonance (CMR) has become a valuable investigative tool in many areas of cardiac medicine. Its value in heart valve disease is less well appreciated however, particularly as echocardiography is a powerful and widely available technique in valve disease. This review highlights the added value that CMR can bring in valve disease, complementing echocardiography in many areas, but it has also become the first-line investigation in some, such as pulmonary valve disease and assessing the right ventricle. CMR has many advantages, including the ability to image in any plane, which allows full visualisation of valves and their inflow/outflow tracts, direct measurement of valve area (particularly for stenotic valves), and characterisation of the associated great vessel anatomy (e.g. the aortic root and arch in aortic valve disease). A particular strength is the ability to quantify flow, which allows accurate measurement of regurgitation, cardiac shunt volumes/ratios and differential flow volumes (e.g. left and right pulmonary arteries). Quantification of ventricular volumes and mass is vital for determining the impact of valve disease on the heart, and CMR is the 'Gold standard' for this. Limitations of the technique include partial volume effects due to image slice thickness, and a low ability to identify small, highly mobile objects (such as vegetations) due to the need to acquire images over several cardiac cycles. The review examines the advantages and disadvantages of each imaging aspect in detail, and considers how CMR can be used optimally for each valve lesion

Motives and comprehension in a public goods game with induced emotions

This study analyses the sensitivity of public goods contributions through the lens of psychological motives. We report the results of a public goods experiment in which subjects were induced with the motives of care and anger through autobiographical recall. Subjects' preferences, beliefs, and perceptions under each motive are compared with those of subjects experiencing a neutral autobiographical recall control condition. We find, but only for those subjects with the highest comprehension of the game, that care elicits significantly higher contributions than anger, with the control treatment in between. This positive influence of the care motive on unconditional giving is accounted for partly by preferences for giving and partly by the beliefs concerning greater contributions by others. Anger also affects attention to own and other's payoffs (using mouse tracking) and perceptions of the game's incentive structure (cooperative or competitive)

Myosin binding protein C: implications for signal-transduction

Myosin binding protein C (MYBPC) is a crucial component of the sarcomere and an important regulator of muscle function. While mutations in different myosin binding protein C (MYBPC) genes are well known causes of various human diseases, such as hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy as well as skeletal muscular disorders, the underlying molecular mechanisms remain not well understood. A variety of MYBPC3 (cardiac isoform) mutations have been studied in great detail and several corresponding genetically altered mouse models have been generated. Most MYBPC3 mutations may cause haploinsufficiency and with it they may cause a primary increase in calcium sensitivity which is potentially able to explain major features observed in HCM patients such as the hypercontractile phenotype and the well known secondary effects such as myofibrillar disarray, fibrosis, myocardial hypertrophy and remodelling including arrhythmogenesis. However the presence of poison peptides in some cases cannot be fully excluded and most probably other mechanisms are also at play. Here we shall discuss MYBPC interacting proteins and possible pathways linked to cardiomyopathy and heart failure

Expression profiling during arabidopsis/downy mildew interaction reveals a highly-expressed effector that attenuates responses to salicylic acid

Plants have evolved strong innate immunity mechanisms, but successful pathogens evade or suppress plant immunity via effectors delivered into the plant cell. Hyaloperonospora arabidopsidis (Hpa) causes downy mildew on Arabidopsis thaliana, and a genome sequence is available for isolate Emoy2. Here, we exploit the availability of genome sequences for Hpa and Arabidopsis to measure gene-expression changes in both Hpa and Arabidopsis simultaneously during infection. Using a high-throughput cDNA tag sequencing method, we reveal expression patterns of Hpa predicted effectors and Arabidopsis genes in compatible and incompatible interactions, and promoter elements associated with Hpa genes expressed during infection. By resequencing Hpa isolate Waco9, we found it evades Arabidopsis resistance gene RPP1 through deletion of the cognate recognized effector ATR1. Arabidopsis salicylic acid (SA)-responsive genes including PR1 were activated not only at early time points in the incompatible interaction but also at late time points in the compatible interaction. By histochemical analysis, we found that Hpa suppresses SA-inducible PR1 expression, specifically in the haustoriated cells into which host-translocated effectors are delivered, but not in non-haustoriated adjacent cells. Finally, we found a highly-expressed Hpa effector candidate that suppresses responsiveness to SA. As this approach can be easily applied to host-pathogen interactions for which both host and pathogen genome sequences are available, this work opens the door towards transcriptome studies in infection biology that should help unravel pathogen infection strategies and the mechanisms by which host defense responses are overcome