InGaN as a Substrate for AC Photoelectrochemical Imaging.

AC photoelectrochemical imaging at electrolyte-semiconductor interfaces provides spatially resolved information such as surface potentials, ion concentrations and electrical impedance. In this work, thin films of InGaN/GaN were used successfully for AC photoelectrochemical imaging, and experimentally shown to generate a considerable photocurrent under illumination with a 405 nm modulated diode laser at comparatively high frequencies and low applied DC potentials, making this a promising substrate for bioimaging applications. Linear sweep voltammetry showed negligible dark currents. The imaging capabilities of the sensor substrate were demonstrated with a model system and showed a lateral resolution of 7 microns

Do infections with parasites and exposure to pollution affect susceptibility to predation in johnny darters (Etheostoma nigrum)?

Johnny darters (Etheostoma nigrum Rafinesque, 1820) were collected from five localities in the St. Lawrence River in southwestern Quebec to test the effects of natural parasite infections and exposure in situ to pollution on their antipredator behaviour. Three measures of antipredator behaviour were made: (1) capture time (i.e., the time taken to catch individual fish) was used as a proxy for the ability to evade predation, (2) capture order was the order in which fish kept in a single tank were taken from the tank, and (3) flight initiation distance was the distance at which the fish moved when approached by a model predator. Only capture time showed a significant correlation with parasitism or pollution status. A nonparametric permutational multivariate ANOVA showed that capture time was significantly correlated with capture location and the abundance of the brain-encysting trematode Ornithodiplostomum Dubois, 1936. Infection with Ornithodiplostomum sp. may have led to an increase in activity, which would be maladaptive for this cryptic, benthic fish under natural predation conditions. Pollution may have an indirect effect on predator susceptibility in johnny darters, by reducing the abundance of a behaviour-modifying parasite

Universality in D-brane Inflation

We study the six-field dynamics of D3-brane inflation for a general scalar potential on the conifold, finding simple, universal behavior. We numerically evolve the equations of motion for an ensemble of more than 7 \times 10^7 realizations, drawing the coefficients in the scalar potential from statistical distributions whose detailed properties have demonstrably small effects on our results. When prolonged inflation occurs, it has a characteristic form: the D3-brane initially moves rapidly in the angular directions, spirals down to an inflection point in the potential, and settles into single-field inflation. The probability of N_{e} e-folds of inflation is a power law, P(N_{e}) \propto N_{e}^{-3}, and we derive the same exponent from a simple analytical model. The success of inflation is relatively insensitive to the initial conditions: we find attractor behavior in the angular directions, and the D3-brane can begin far above the inflection point without overshooting. In favorable regions of the parameter space, models yielding 60 e-folds of expansion arise approximately once in 10^3 trials. Realizations that are effectively single-field and give rise to a primordial spectrum of fluctuations consistent with WMAP, for which at least 120 e-folds are required, arise approximately once in 10^5 trials. The emergence of robust predictions from a six-field potential with hundreds of terms invites an analytic approach to multifield inflation.Comment: 28 pages, 9 figure

Genomic and protein expression analysis reveals flap endonuclease 1 (FEN1) as a key biomarker in breast and ovarian cancer

FEN1 has key roles in Okazaki fragment maturation during replication, long patch base excision repair, rescue of stalled replication forks, maintenance of telomere stability and apoptosis. FEN1 may be dysregulated in breast and ovarian cancers and have clinicopathological significance in patients. We comprehensively investigated FEN1 mRNA expression in multiple cohorts of breast cancer [training set (128), test set (249), external validation (1952)]. FEN1 protein expression was evaluated in 568 oestrogen receptor (ER) negative breast cancers, 894 ER positive breast cancers and 156 ovarian epithelial cancers. FEN1 mRNA overexpression was highly significantly associated with high grade (p= 4.89 x 10 - 57) , high mitotic index (p= 5.25 x 10 - 28), pleomorphism (p= 6.31 x 10-19), ER negative (p= 9.02 x 10-35 ), PR negative (p= 9.24 x 10-24 ), triple negative phenotype (p= 6.67 x 10-21) , PAM50.Her2 (p=5.19 x 10-13 ), PAM50.Basal (p=2.7 x 10-41), PAM50.LumB (p=1.56 x 10-26), integrative molecular cluster 1 (intClust.1) ( p=7.47 x 10-12), intClust.5 (p=4.05 x 10-12) and intClust. 10 (p=7.59 x 10-38 ) breast cancers. FEN1 mRNA overexpression is associated with poor breast cancer specific survival in univariate (p=4.4 x 10-16) and multivariate analysis (p=9.19 x 10-7). At the protein level, in ER positive tumours , FEN1 overexpression remains significantly linked to high grade, high mitotic index and pleomorphism (ps< 0.01). In ER negative tumours, high FEN1 is significantly associated with pleomorphism, tumour type, lymphovascular invasion, triple negative phenotype, EGFR and HER2 expression (ps<0.05). In ER positive as well as in ER negative tumours, FEN1 protein over expression is associated with poor survival in univariate and multivariate analysis (ps<0.01). In ovarian epithelial cancers , similarly, FEN1 overexpression is associated with high grade, high stage and poor survival (ps<0.05). We conclude that FEN1 is a promising biomarker in breast and ovarian epithelial cancer

Ancient Bacterial Genomes Reveal a High Diversity of Treponema pallidum Strains in Early Modern Europe

Syphilis is a globally re-emerging disease, which has marked European history with a devastating epidemic at the end of the 15th century. Together with non-venereal treponemal diseases, like bejel and yaws, which are found today in subtropical and tropical regions, it currently poses a substantial health threat worldwide. The origins and spread of treponemal diseases remain unresolved, including syphilis' potential introduction into Europe from the Americas. Here, we present the first genetic data from archaeological human remains reflecting a high diversity of Treponema pallidumin early modern Europe. Our study demonstrates that a variety of strains related to both venereal syphilis and yaws-causing T. pallidum subspecies were already present in Northern Europe in the early modern period. We also discovered a previously unknown T. pallidum lineage recovered as a sister group to yaws- and bejel-causing lineages. These findings imply a more complex pattern of geographical distribution and etiology of early treponemal epidemics than previously understood.Peer reviewe

GNE Is Involved in the Early Development of Skeletal and Cardiac Muscle

UDP-N-acetylglucosamine 2 epimerase/N-acetylmannosamime kinase (GNE) is a bifunctional enzyme which catalyzes the two key sequential steps in the biosynthetic pathway of sialic acid, the most abundant terminal monosaccharide on glycoconjugates of eukaryotic cells. GNE knock out (GNE KO) mice are embryonically lethal at day E8.5. Although the role of GNE in the sialic pathway has been well established as well as the importance of sialylation in many diverse biological pathways, less is known about the involvement of GNE in muscle development. To address this issue we have studied the role of GNE during in vitro embryogenesis by comparing the developmental profile in culture of embryonic stem cells (ES) from wild type and from GNE KO E3.5 mice embryos, during 45 days. Neuronal cells appeared rarely in GNE KO ES cultures and did not reach an advanced differentiated stage. Although primary cardiac cells appeared at the same time in both normal and GNE KO ES cultures, GNE KO cardiac cells degraded very soon and their beating capacity decayed rapidly. Furthermore very rare skeletal muscle committed cells were detected in the GNE KO ES cultures at any stage of differentiation, as assessed by analysis of the expression of either Pax7, MyoD and MyHC markers. Beyond the supporting evidence that GNE plays an important role in neuronal cell and brain development, these results show that GNE is strongly involved in cardiac tissue and skeletal muscle early survival and organization. These findings could open new avenues in the understanding of muscle function mechanisms in health and in disease

Infection with the sheep gastrointestinal nematode Teladorsagia circumcincta increases luminal pathobionts

Abstract: Background: The multifaceted interactions between gastrointestinal (GI) helminth parasites, host gut microbiota and immune system are emerging as a key area of research within the field of host-parasite relationships. In spite of the plethora of data available on the impact that GI helminths exert on the composition of the gut microflora, whether alterations of microbial profiles are caused by direct parasite-bacteria interactions or, indirectly, by alterations of the GI environment (e.g. mucosal immunity) remains to be determined. Furthermore, no data is thus far available on the downstream roles that qualitative and quantitative changes in gut microbial composition play in the overall pathophysiology of parasite infection and disease. Results: In this study, we investigated the fluctuations in microbiota composition and local immune microenvironment of sheep vaccinated against, and experimentally infected with, the ‘brown stomach worm’ Teladorsagia circumcincta, a parasite of worldwide socio-economic significance. We compared the faecal microbial profiles of vaccinated and subsequently infected sheep with those obtained from groups of unvaccinated/infected and unvaccinated/uninfected animals. We show that alterations of gut microbial composition are associated mainly with parasite infection, and that this involves the expansion of populations of bacteria with known pro-inflammatory properties that may contribute to the immunopathology of helminth disease. Using novel quantitative approaches for the analysis of confocal microscopy-derived images, we also show that gastric tissue infiltration of T cells is driven by parasitic infection rather than anti-helminth vaccination. Conclusions: Teladorsagia circumcincta infection leads to an expansion of potentially pro-inflammatory gut microbial species and abomasal T cells. This data paves the way for future experiments aimed to determine the contribution of the gut flora to the pathophysiology of parasitic disease, with the ultimate aim to design and develop novel treatment/control strategies focused on preventing and/or restricting bacterial-mediated inflammation upon infection by GI helminths. DCvTgHLrMa4pPTvhPWGjhoVideo Abstrac

The LSST Dark Energy Science Collaboration (DESC) Science Requirements Document

The Large Synoptic Survey Telescope (LSST) Dark Energy Science Collaboration (DESC) will use five cosmological probes: galaxy clusters, large scale structure, supernovae, strong lensing, and weak lensing. This Science Requirements Document (SRD) quantifies the expected dark energy constraining power of these probes individually and together, with conservative assumptions about analysis methodology and follow-up observational resources based on our current understanding and the expected evolution within the field in the coming years. We then define requirements on analysis pipelines that will enable us to achieve our goal of carrying out a dark energy analysis consistent with the Dark Energy Task Force definition of a Stage IV dark energy experiment. This is achieved through a forecasting process that incorporates the flowdown to detailed requirements on multiple sources of systematic uncertainty. Future versions of this document will include evolution in our software capabilities and analysis plans along with updates to the LSST survey strategy.Comment: 32 pages + 60 pages of appendices. This is v1 of the DESC SRD, an internal collaboration document that is being made public and is not planned for submission to a journal. Data products for reproducing key plots are available at the LSST DESC Zenodo community, https://zenodo.org/communities/lsst-desc; see "Executive Summary and User Guide" for instructions on how to use and cite those product

Patterns of Gene Flow Define Species of Thermophilic Archaea

A genomic view of speciation in Archaea shows higher rates of gene flow within coexisting microbial species than between them

Compilation and Network Analyses of Cambrian Food Webs

A rich body of empirically grounded theory has developed about food webs—the networks of feeding relationships among species within habitats. However, detailed food-web data and analyses are lacking for ancient ecosystems, largely because of the low resolution of taxa coupled with uncertain and incomplete information about feeding interactions. These impediments appear insurmountable for most fossil assemblages; however, a few assemblages with excellent soft-body preservation across trophic levels are candidates for food-web data compilation and topological analysis. Here we present plausible, detailed food webs for the Chengjiang and Burgess Shale assemblages from the Cambrian Period. Analyses of degree distributions and other structural network properties, including sensitivity analyses of the effects of uncertainty associated with Cambrian diet designations, suggest that these early Paleozoic communities share remarkably similar topology with modern food webs. Observed regularities reflect a systematic dependence of structure on the numbers of taxa and links in a web. Most aspects of Cambrian food-web structure are well-characterized by a simple “niche model,” which was developed for modern food webs and takes into account this scale dependence. However, a few aspects of topology differ between the ancient and recent webs: longer path lengths between species and more species in feeding loops in the earlier Chengjiang web, and higher variability in the number of links per species for both Cambrian webs. Our results are relatively insensitive to the exclusion of low-certainty or random links. The many similarities between Cambrian and recent food webs point toward surprisingly strong and enduring constraints on the organization of complex feeding interactions among metazoan species. The few differences could reflect a transition to more strongly integrated and constrained trophic organization within ecosystems following the rapid diversification of species, body plans, and trophic roles during the Cambrian radiation. More research is needed to explore the generality of food-web structure through deep time and across habitats, especially to investigate potential mechanisms that could give rise to similar structure, as well as any differences