The longitude problem from the 1700s to today: An international and general education physics course

For instructors wishing to use physics as part of an international or general education course, the framework for a course based on the “longitude problem” from the 1700s is described. The longitude problem is teeming with basic principles of physics and astronomy, which makes it ideal for a non-science-major-based college-level course. This paper summarizes the longitude problem in the context of conceptual physics and astronomy and outlines an appropriate curriculum. Specifics on teaching such a course in London, as part of an international studies program, are discussed

(Certified) Humane Violence? Animal Production, the Ambivalence of Humanizing the Inhumane, and What International Humanitarian Law Has to Do with It

The chapter draws a comparison with the self-certifying of production methods as ‘humane’ or animal-friendly in the labelling of animal products—that is, according to companies’ own self-imposed codes of conduct. It likens the idea of humanizing animal slaughter, factory farms, and other forms of production to the notion of humanizing warfare. Like international humanitarian law (IHL), animal welfare law is marked by the tension inherent in its attempt to humanize innately inhumane practices. Given these parallels, the analysis of animal welfare law might benefit from existing insights into the potential and limits of IHL. Both areas of law endorse a principle of ‘humanity’ while arguably facilitating and legitimizing the use of violence, and might thereby ultimately perpetuate the suffering of living beings. The implicit justification of violence percolating from the IHL-like animal ‘protection’ laws could only be outweighed by complementing this body of law with a ius contra bellum for animals

Mechanism and timing of Mcm2–7 ring closure during DNA replication origin licensing

The opening and closing of two ring-shaped Mcm2-7 DNA helicases is necessary to license eukaryotic origins of replication, although the mechanisms controlling these events are unclear. The origin-recognition complex (ORC), Cdc6 and Cdt1 facilitate this process by establishing a topological link between each Mcm2-7 hexamer and origin DNA. Using colocalization single-molecule spectroscopy and single-molecule Förster resonance energy transfer (FRET), we monitored ring opening and closing of Saccharomyces cerevisiae Mcm2-7 during origin licensing. The two Mcm2-7 rings were open during initial DNA association and closed sequentially, concomitant with the release of their associated Cdt1. We observed that ATP hydrolysis by Mcm2-7 was coupled to ring closure and Cdt1 release, and failure to load the first Mcm2-7 prevented recruitment of the second Mcm2-7. Our findings identify key mechanisms controlling the Mcm2-7 DNA-entry gate during origin licensing, and reveal that the two Mcm2-7 complexes are loaded via a coordinated series of events with implications for bidirectional replication initiation and quality control.National Institutes of Health (U.S.) (Grant R01 GM52339)National Institutes of Health (U.S.) (Pre-Doctoral Training Grant GM007287)National Cancer Institute (U.S.) (Koch Institute Support Grant P30-CA14051

Clamp loader ATPases and the evolution of DNA replication machinery

Clamp loaders are pentameric ATPases of the AAA+ family that operate to ensure processive DNA replication. They do so by loading onto DNA the ring-shaped sliding clamps that tether the polymerase to the DNA. Structural and biochemical analysis of clamp loaders has shown how, despite differences in composition across different branches of life, all clamp loaders undergo the same concerted conformational transformations, which generate a binding surface for the open clamp and an internal spiral chamber into which the DNA at the replication fork can slide, triggering ATP hydrolysis, release of the clamp loader, and closure of the clamp round the DNA. We review here the current understanding of the clamp loader mechanism and discuss the implications of the differences between clamp loaders from the different branches of life

Differential DARC/ACKR1 expression distinguishes venular from non-venular endothelial cells in murine tissues

This work was supported by the National Institutes of Health (NIH) grant AI112521 and the John and Virginia Kaneb Fellowship