How do common and rare genetic polymorphisms contribute to quantitative traits or disease risk and progression? Multiple human traits have been extensively characterized at the genomic level, revealing their complex genetic architecture. However, it is difficult to resolve the mechanisms by which specific variants contribute to a phenotype. Recently, analyses of variant effects on molecular traits have uncovered intermediate mechanisms that link sequence variation to phenotypic changes. Yet, these methods only capture a fraction of genetic contributions to phenotype. Here, in (...) reviewing the field, it is proposed that complex traits can be understood by characterizing the dynamics of biochemical networks within living cells, and that the effects of genetic variation can be captured on these networks by using protein–protein interaction (PPI) methodologies. This synergy between PPI methodologies and the genetics of complex traits opens new avenues to investigate the molecular etiology of human diseases and to facilitate their prevention or treatment. (shrink)

Two recent papers by Michael Burke bearing upon the persistence of people and commonplace things illustrate the fact that the quest for synchronic ontological economy is likely to encourage a disturbing diachronic proliferation of entities. This discussion argues that Burke's promise of ontological economy is seriously compromised by the fact that his proposed metaphysic does violence to standard intuitions concerning the persistence of people and commonplace things. In effect, Burke would have us achieve synchronic economy (rejection of coincident entities) by (...) postulating strongly counterintuitive transtemporal claims of numerical diversity. The argument is made that the price of Burkean economy is too high. (shrink)

Only those whose work and interests have led them to notice it, will have realised, in all probability, the remarkable extent to which the term organization has gained currency, or acquired new and special emphasis, throughout the entire range of scientific and sociological literature during the last ten or twenty years.In biology and bio-chemistry organization has been discussed or used as a technical term, mostly since 1930 by at least thirty well-known authors; amongst the more prominent are Huxley, Wilson, Woodger, (...) Cannon, Waddington, McDougall, Needham, Block, Hopkins and Sherrington. Under this magic term some authors refer to the physico-chemical nature of the cell or cytoplasm, and usually with special reference to selective or directive catalysis; others to the general constitution or structure of the organism and almost indistinguishable from general morphology and physiology; others to embryological development as such ; others more especially to “relations” between cells, organs and structural parts, often in an abstract sense; others refer more particularly to a hypothetical integrating and/or co-ordinating factor : a few refer to re-constitution from dissociated cells as observed in experiments with Sponges and Hydroids. (shrink)

Eric Olsen argues from the fact that we once existed as fetal individuals to the conclusion that the Standard View of personal identity is mistaken. I shall establish that a similar argument focusing upon dead people opposes Olson’s favored Biological View of personal identity.

Two recent papers by Michael Burke bearing upon the persistence of people and commonplace things illustrate the fact that the quest for synchronic ontological economy is likely to encourage a disturbing diachronic proliferation of entities. This discussion argues that Burke’s promise of ontological economy is seriously compromised by the fact that his proposed metaphysic does violence to standard intuitions concerning the persistence of people and commonplace things. In effect, Burke would have us achieve synchronic economy (rejection of coincident entities) by (...) postulating strongly counterintuitive transtemporal claims of numerical diversity. The argument is made that the price of Burkean economy is too high. (shrink)