Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells

The POU domain transcription factor OCT4 is a key regulator of pluripotency in the early mammalian embryo and is highly expressed in the inner cell mass of the blastocyst. Consistent with its essential role in maintaining pluripotency, Oct4 expression is rapidly downregulated during formation of the trophoblast lineage. To enhance our understanding of the molecular basis of this differentiation event in humans, we used a functional genomics approach involving RNA interference-mediated suppression of OCT4 function in a human ESC line and analysis of the resulting transcriptional profiles to identify OCT4-dependent genes in human cells. We detected altered expression of >1,000 genes, including targets regulated directly by OCT4 either positively (NANOG, SOX2, REX1, LEFTB, LEFTA/EBAF DPPA4, THY1, and TDGF1) or negatively (CDX2, EOMES, BMP4, TBX18, Brachyury [T], DKK1, HLX1, GATA6, ID2, and DLX5), as well as targets for the OCT4-associated stem cell regulators SOX2 and NANOG. Our data set includes regulators of ACTIVIN, BMP, fibroblast growth factor, and WNT signaling. These pathways are implicated in regulating human ESC differentiation and therefore further validate the results of our analysis. In addition, we identified a number of differentially expressed genes that are involved in epigenetics, chromatin remodeling, apoptosis, and metabolism that may point to underlying molecular mechanisms that regulate pluripotency and trophoblast differentiation in humans. Significant concordance between this data set and previous comparisons between inner cell mass and trophectoderm in human embryos indicates that the study of human ESC differentiation in vitro represents a useful model of early embryonic differentiation in humans

What are the costs and benefits of biodiversity recovery in a highly polluted estuary?

Biodiversity recovery measures have often been ignored when dealing with the restoration of degraded aquatic systems. Furthermore, biological valuation methods have been applied only spatially in previous studies, and not jointly on a temporal and spatial scale. The intense monitoring efforts carried out in a highly polluted estuary, in northern Spain (Nervión estuary), allowed for the economic valuation of the costs and the biological valuation of the benefits associated with a 21 years sewage scheme application. The analysis show that the total amount of money invested into the sewage scheme has contributed to the estuary's improvement of both environmental and biological features, as well as to an increase in the uses and services provided by the estuary. However, the inner and outer parts of the estuary showed different responses. An understanding of the costs and trajectories of the environmental recovery of degraded aquatic systems is increasingly necessary to allow policy makers and regulators to formulate robust, cost-efficient and feasible management decisions

Marine ecosystem services: Linking indicators to their classification

© 2014 Elsevier Ltd. All rights reserved. There is a multitude of ecosystem service classifications available within the literature, each with its own advantages and drawbacks. Elements of them have been used to tailor a generic ecosystem service classification for the marine environment and then for a case study site within the North Sea: the Dogger Bank. Indicators for each of the ecosystem services, deemed relevant to the case study site, were identified. Each indicator was then assessed against a set of agreed criteria to ensure its relevance and applicability to environmental management. This paper identifies the need to distinguish between indicators of ecosystem services that are entirely ecological in nature (and largely reveal the potential of an ecosystem to provide ecosystem services), indicators for the ecological processes contributing to the delivery of these services, and indicators of benefits that reveal the realized human use or enjoyment of an ecosystem service. It highlights some of the difficulties faced in selecting meaningful indicators, such as problems of specificity, spatial disconnect and the considerable uncertainty about marine species, habitats and the processes, functions and services they contribute to

Weather information network including graphical display

An apparatus for providing weather information onboard an aircraft includes a processor unit and a graphical user interface. The processor unit processes weather information after it is received onboard the aircraft from a ground-based source, and the graphical user interface provides a graphical presentation of the weather information to a user onboard the aircraft. Preferably, the graphical user interface includes one or more user-selectable options for graphically displaying at least one of convection information, turbulence information, icing information, weather satellite information, SIGMET information, significant weather prognosis information, and winds aloft information

The effect of polar lipids on tear film dynamics

In this paper we present a mathematical model describing the effect of polar lipids on the evolution of a precorneal tear film, with the aim of explaining the interesting experimentally observed phenomenon that the tear film continues to move upwards even after the upper eyelid has become stationary. The polar lipid is an insoluble surface species that locally alters the surface tension of the tear film. In the lubrication limit, the model reduces to two coupled nonlinear partial differential equations for the film thickness and the concentration of lipid. We solve the system numerically and observe that the presence of the lipid causes an increase in flow of liquid up the eye. We further exploit the size of the parameters in the problem to explain the initial evolution of the system

“And DPSIR begat DAPSI(W)R(M)!” - A unifying framework for marine environmental management

The marine environment is a complex system formed by interactions between ecological structure and functioning, physico-chemical processes and socio-economic systems. An increase in competing marine uses and users requires a holistic approach to marine management which considers the environmental, economic and societal impacts of all activities. If managed sustainably, the marine environment will deliver a range of ecosystem services which lead to benefits for society. In order to understand the complexity of the system, the DPSIR (Driver-Pressure-State-Impact-Response) approach has long been a valuable problem-structuring framework used to assess the causes, consequences and responses to change in a holistic way. Despite DPSIR being used for a long time, there is still confusion over the definition of its terms and so to be appropriate for current marine management, we contend that this confusion needs to be addressed. Our viewpoint advocates that DPSIR should be extended to DAPSI(W)R(M) (pronounced dap-see-worm) in which Drivers of basic human needs require Activities which lead to Pressures. The Pressures are the mechanisms of State change on the natural system which then leads to Impacts (on human Welfare). Those then require Responses (as Measures). Furthermore, because of the complexity of any managed sea area in terms of multiple Activities, there is the need for a linked-DAPSI(W)R(M) framework, and then the connectivity between marine ecosystems and ecosystems in the catchment and further at sea, requires an interlinked, nested-DAPSI(W)R(M) framework to reflect the continuum between adjacent ecosystems. Finally, the unifying framework for integrated marine management is completed by encompassing ecosystem structure and functioning, ecosystem services and societal benefits. Hence, DAPSI(W)R(M) links the socio-ecological system of the effects of changes to the natural system on the human uses and benefits of the marine system. However, to deliver these sustainably in the light of human activities requires a Risk Assessment and Risk Management framework; the ISO-compliant Bow-Tie method is used here as an example. Finally, to secure ecosystem health and economic benefits such as Blue Growth, successful, adaptive and sustainable marine management Responses (as Measures) are delivered using the 10-tenets, a set of facets covering all management disciplines and approaches

Host pathogen interactions in relation to management of light leaf spot disease (caused by Pyrenopeziza brassicae) on Brassica species

Light leaf spot, caused by Pyrenopeziza brassicae, is currently the most damaging disease problem in oilseed rape in the UK. According to recent survey data, the severity of epidemics has increased progressively across the UK, with current yield losses of up to £160M per annum in England and more severe epidemics in Scotland. Light leaf spot is a polycyclic disease with primary inoculum consisting of air-borne ascospores produced on diseased debris from the previous cropping season. Splash-dispersed conidia produced on diseased leaves are the main component of the secondary inoculum. P. brassicae is also able to infect and cause considerable yield losses on vegetable brassicas, especially Brussels sprouts. There may be spread of light leaf spot among different brassica species. Since they have a wide host range, Pyrenopeziza brassicae populations are likely to have considerable genetic diversity and there is evidence suggesting population variations between different regions, which need further study. Available disease-management tools are not sufficient to provide adequate control of the disease. There is a need to identify new sources of resistance, which can be integrated with fungicide applications to achieve sustainable management of light leaf spot. Several major resistance genes and quantitative trait loci have been identified in previous studies, but rapid improvements in the understanding of molecular mechanisms underpinning B. napus – P. brassicae interactions can be expected through exploitation of novel genetic and genomic information for brassicas and extracellular fungal pathogens.Peer reviewe

Genetic association at the 9p21 glaucoma locus contributes to sex bias in normal-tension glaucoma

Purpose: Many genome-wide association studies have identified common single nucleotide polymorphisms (SNPs) at the 9p21 glaucoma locus (CDKN2B/CDKN2B-AS1) to be significantly associated with primary open-angle glaucoma (POAG), with association being stronger in normal tension glaucoma (NTG) and advanced glaucoma. We aimed to determine whether any observed differences in genetic association at the 9p21 locus are influenced by sex. Methods: Sex was assessed as a risk factor for POAG for 2241 glaucoma participants from the Australian and New Zealand Registry of Advanced Glaucoma, the Glaucoma Inheritance Study in Tasmania, and the Flinders Medical Centre. A total of 3176 controls were drawn from the Blue Mountains Eye Study and South Australia: 1523 advanced POAG and 718 nonadvanced POAG cases were genotyped along with 3176 controls. We selected 13 SNPs at the 9p21 locus, and association results were subanalyszd by sex for high-tension glaucoma (HTG) and NTG. Odds ratios (ORs) between sexes were compared. Results: A sex bias was present within advanced NTG cases (57.1% female versus 42.9% male, P = 0.0026). In all POAG cases, the strongest associated SNP at 9p21 was rs1063192 (OR, 1.43; P = 4 × 10⁻¹⁸). This association was stronger in females (OR, 1.5; P = 5 × 10⁻¹³) than in males (OR, 1.35; P = 7 × 10⁻⁷), with a statistically significant difference in female to male OR comparison (P = 1.0 × 10⁻²). An NTG to HTG subanalysis yielded statistically significant results only in females (OR, 1.63; P = 1.5 × 10⁻⁴) but not in males (OR, 1.15; P = 2.8 × 10⁻¹), with a statistically significant difference in female to male OR comparison (P = 1.4 × 10⁻⁴). Conclusions: This study demonstrated that female sex is a risk factor for developing advanced NTG. The stronger genetic signals at the 9p21 locus among females may contribute at least in part to the observed sex bias for NTG.Soo Khai Ng, Kathryn P. Burdon, Jude T. Fitzgerald, Tiger Zhou, Rhys Fogarty, Emmanuelle Souzeau, John Landers, Richard A. Mills, Robert J. Casson, Bronwyn Ridge, Stuart L. Graham, Alex W. Hewitt, David A. Mackey, Paul R. Healey, Jie Jin Wang, Paul Mitchell, Stuart MacGregor, and Jamie E. Crai

Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article