© 2015 Elsevier Inc.Toxoplasma gondii is a protozoan pathogen in the phylum Apicomplexa that resides within an intracellular parasitophorous vacuole that is selectively permeable to small molecules through unidentified mechanisms. We have identified GRA17 as a Toxoplasma-secreted protein that localizes to the parasitophorous vacuole membrane and mediates passive transport of small molecules across the PVM. GRA17 is related to the putative Plasmodium translocon protein EXP2 and conserved across PV-residing Apicomplexa. The PVs of GRA17-deficient parasites have aberrant morphology, reduced permeability to (...) small molecules, and structural instability. GRA17-deficient parasites proliferate slowly and are avirulent in mice. These GRA17-deficient phenotypes are rescued by complementation with Plasmodium EXP2. GRA17 functions synergistically with a related protein, GRA23. Exogenous expression of GRA17 or GRA23 alters the membrane conductance properties of Xenopus oocytes in a manner consistent with a large non-selective pore. Thus, GRA17 and GRA23 provide a molecular basis for PVM permeability and nutrient access. (shrink)

This work combines two early pamphlets by F. H. Bradley , the foremost philosopher of the British Idealist movement. The first essay, published in 1874, deals with the nature of professional history, and foreshadows some of Bradley's later ideas in metaphysics. He argues that history cannot be subjected to scientific scrutiny because it is not directly available to the senses, meaning that all history writing is inevitably subjective. Though not widely discussed at the time of publication, the pamphlet (...) was influential on historian and philosopher R. G. Collingwood. The second pamphlet is Bradley's critique of Henry Sidgwick's The Methods of Ethics. Sidgwick was the first to propose the paradox of hedonism, which is the idea in ethics that pleasure can only be acquired indirectly. Published in 1877, this work is divided into three parts, treating Sidgwick's definitions, arguments, and his view of ethical science. (shrink)

This work combines two early pamphlets by F. H. Bradley, the foremost philosopher of the British Idealist movement. The first essay, published in 1874, deals with the nature of professional history, and foreshadows some of Bradley's later ideas in metaphysics. He argues that history cannot be subjected to scientific scrutiny because it is not directly available to the senses, meaning that all history writing is inevitably subjective. Though not widely discussed at the time of publication, the pamphlet was (...) influential on historian and philosopher R. G. Collingwood. The second pamphlet is Bradley's critique of Henry Sidgwick's The Methods of Ethics. Sidgwick was the first to propose the paradox of hedonism, which is the idea in ethics that pleasure can only be acquired indirectly. Published in 1877, this work is divided into three parts, treating Sidgwick's definitions, arguments, and his view of ethical science. (shrink)