Human CST promotes telomere duplex replication and general replication restart after fork stalling

Mammalian CST (CTC1-STN1-TEN1) associates with telomeres and depletion of CTC1 or STN1 causes telomere defects. However, the function of mammalian CST remains poorly understood. We show here that depletion of CST subunits leads to both telomeric and non-telomeric phenotypes associated with DNA replication defects. Stable knockdown of CTC1 or STN1 increases the incidence of anaphase bridges and multi-telomeric signals, indicating genomic and telomeric instability. STN1 knockdown also delays replication through the telomere indicating a role in replication fork passage through this natural barrier. Furthermore, we find that STN1 plays a novel role in genome-wide replication restart after hydroxyurea (HU)-induced replication fork stalling. STN1 depletion leads to reduced EdU incorporation after HU release. However, most forks rapidly resume replication, indicating replisome integrity is largely intact and STN1 depletion has little effect on fork restart. Instead, STN1 depletion leads to a decrease in new origin firing. Our findings suggest that CST rescues stalled replication forks during conditions of replication stress, such as those found at natural replication barriers, likely by facilitating dormant origin firing

Nietzsche or Aristotle: The implications for social psychology

YesIn this article, I argue that there is a divide in social psychology between a mainstream paradigm for investigating the flow of power in a largely competitive social life (such as social cognition, social identity theory, and discourse analysis) and a fringe paradigm for investigating the experience of flourishing in conditions of social learning (such as ‘the community of practice metaphor’, ‘dialogical theory’, ‘phenomenological analysis’). Assumptions of power and flourishing demand different conceptions of the self and the social world (e.g. a strategic subject or motivated tactician in a social group versus a reflective learner/artist in a community of practice). The first goal of this article is to reveal the assumptions that lead to this new classification. The second goal is to draw dotted lines to the blind-spots within these paradigms that each reveals. These blind spots are: 1) internal goods could be useful to consider for the power paradigm and external goods for the flourishing paradigm; 2) communicative rationality is underplayed within the power paradigm; while instrumental rationality is underplayed for the flourishing paradigm; 3) judgements and skill are underplayed in the power paradigm; self-interested motivations are underplayed in the flourishing paradigm

Nietzsche or Aristotle: The implications for social psychology

YesIn this article, I argue that there is a divide in social psychology between a mainstream paradigm for investigating the flow of power in a largely competitive social life (such as social cognition, social identity theory, and discourse analysis) and a fringe paradigm for investigating the experience of flourishing in conditions of social learning (such as ‘the community of practice metaphor’, ‘dialogical theory’, ‘phenomenological analysis’). Assumptions of power and flourishing demand different conceptions of the self and the social world (e.g. a strategic subject or motivated tactician in a social group versus a reflective learner/artist in a community of practice). The first goal of this article is to reveal the assumptions that lead to this new classification. The second goal is to draw dotted lines to the blind-spots within these paradigms that each reveals. These blind spots are: 1) internal goods could be useful to consider for the power paradigm and external goods for the flourishing paradigm; 2) communicative rationality is underplayed within the power paradigm; while instrumental rationality is underplayed for the flourishing paradigm; 3) judgements and skill are underplayed in the power paradigm; self-interested motivations are underplayed in the flourishing paradigm

P-cadherin expression in breast cancer: a review

P-cadherin is frequently over-expressed in high-grade invasive breast carcinomas and has been reported to be an enhancer of migration and invasion of breast cancer cells, being correlated with tumour aggressiveness. In addition, expression of P-cadherin is well established as an indicator of poor prognosis in human breast cancer, which has stimulated our interest in studying its role in this setting. This review describes the most important findings on P-cadherin expression and function in normal mammary tissue and breast cancer cells, emphasizing that further research is required to elucidate the role played by this protein in human mammary tumours

Advanced Colloids Experiment (ACE) Science Overview

The Advanced Colloids Experiment is being conducted on the International Space Station (ISS) using the Light Microscopy Module (LMM) in the Fluids Integrated Rack (FIR). Work to date will be discussed and future plans and opportunities will be highlighted. The LMM is a microscope facility designed to allow scientists to process, manipulate, and characterize colloidal samples in micro-gravity where the absence of gravitational settling and particle jamming enables scientists to study such things as:a.The role that disordered and ordered-packing of spheres play in the phase diagram and equation of state of hard sphere systems,b.crystal nucleation and growth, growth instabilities, and the glass transition, c.gelation and phase separation of colloid polymer mixtures,d.crystallization of colloidal binary alloys,e.competition between crystallization and phase separation,f.effects of anisotropy and specific interactions on packing, aggregation, frustration and crystallization,g.effects of specific reversible and irreversible interactions mediated in the first case by hybridization of complementary DNA strands attached to separate colloidal particles,h.Lock and key interactions between colloids with dimples and spheres which match the size and shape of the dimples,i.finding the phase diagrams of isotropic and interacting particles,j.new techniques for complex self-assembly including scenarios for self-replication, k.critical Casimir forces,l.biology (real and model systems) in microgravity,m.etc. By adding additional microscopy capabilities to the existing LMM, NASA will increase the tools available for scientists that fly experiments on the ISS enabling scientists to observe directly what is happening at the particle level. Presently, theories are needed to bridge the gap between what is being observed (at a macroscopic level when photographing samples) with what is happening at a particle (or microscopic) level. What is happening at a microscopic level will be directly accessible with the availability of the Light Microscopy Module (LMM) on ISS. To meet these goals, the ACE experiment is being built-up in stages, with the availability of confocal microscopy being the ultimate objective. Supported by NASAs Physical Sciences Research Program, ESAESTEC, and the authors respective governments