Nerve growth factor nonresponsive pheochromocytoma cells: altered internalization results in signaling dysfunction.

Variant rat pheochromocytoma (PC12) cells which fail to respond to nerve growth factor (NGF) (PC12nnr5) (Green, S. H., R. E. Rydel, J. L. Connoly, and L. A. Greene. 1986. J. Cell Biol. 102:830-843) bind NGF at both high and low affinity sites. Although still undefined at the molecular level, these have been referred to as type I (high) and type II (low) receptors. They are apparently composed of two membrane-bound proteins, p75 and the protooncogene trk, both of which bind NGF, and apparently contribute singularly or in concert to the two observed affinities, and to the promotion of the NGF effects. In native PC12 cells, only the high affinity receptors are apparently capable of mediating internalization and degradation. PC12nnr5 cells also display type I binding, but the subsequent internalization is not the same fashion as in the parental cell line, nor is it subjected to lysosomal degradation. Rather it is initially sequestered during the first 15 min, and is eventually released intact into the medium. In contrast, EGF is bound, internalized, and degraded by PC12nnr5 cells, albeit less efficiently than in the parent cells. These observations argue that the defect(s) preventing the PC12nnr5 variants from responding to NGF prevents competent internalization, which in the case of NGF, may be required for the full expression of activity. The absence of trk, as one alteration in PC12nnr5 cells (Loeb, D. M., J. Maragos, D. Martin-Zanca, M. V. Chao, L. F. Parada, and L. A. Greene. 1991. Cell. 66:961-966), is consistent with this conclusion

Emerson, Virtue, and Evil: Thoughts for a Rescue Operation

Interpretations of Emerson\u27s theme of self-reliance which generate charges that he understood neither evil nor virtue are inappropriate. A fairer reading should keep in mind the Neo-Platonism of Plotinus, which gave to Transcendentalism a dynamic emanation/return schema and to mankind a place of privilege in knowing and valuing Nature

Heroism as Moral Paradox

Often involving sacrifice, heroism is not easily understandable in secular ethical theory, e.g. in Utilitarian, Deontological or Virtue Theory. The consequences of heroism may be useful or not; heroic actions are not duties; and heroism is neither a Golden Mean nor the habitual activity of good persons. If, though, we reverse direction, allowing moral status to a hero\u27s self-imposed duty, the good consequences of his heroism are rational in Utilitarian terms

John Cotton and the Work Ethic

The Protestant work ethic, as identified by Max Weber, has its first and, arguably, best American articulation in the work of the Reverend John Cotton (1584-1652). Revisiting key writings of this Boston minister-scholar, we see the origin of American valuation of wealth, work, and success

Introduction: Becoming an Atheist

One of America\u27s great intellectuals, Ralph Waldo Emerson created Transcendentalism, the underpinning of the Romantic movement and America\u27s 19th century Renaissance. Not so well known is his anguished departure from the Christianity of his youth. This book corrects this oversight by showing connections between the faith of his youth and the central themes of Transcendentalism. This is a book not only about Emerson\u27s intellectual and spiritual journey but about the essence of New England Transcendentalism

The Special Education Program In The Secondary Schools Of Des Moines, Iowa, As Carried Out At North High School

44 leave

Ethics Across the Curriculum, or, On Being Bilingual

Both philosophical ethical systems and religious ethics are eminently desirable in higher education today. And, like two languages, and despite the differences, they can and should complement each other. In an increasingly secular milieu, our graduates will have to be bilingual

Locke and the Problem of Toleration

More than ever before, being able to draw a distinction between the tolerable and the intolerable is necessary. Unfortunately the traditional understanding, as identified with the Enlightenment view first articulated by John Locke, presents merely formalistic criteria. Lacking substantive criteria, our contemporary understanding of toleration is inadequate to our needs

Homeless street children in Nepal : use of allostatic load to assess the burden of childhood adversity.

As challenges to child well-being through economic disadvantage, family disruption, and migration or displacement escalate world wide, the need for cross-culturally robust understanding of childhood adversity proportionately increases. Toward this end, developmental risk was assessed in four contrasting groups of 107 Nepali children ages 10–14 years that represent distinctive, common conditions in which contemporary children grow up. Relative cumulative burden (allostatic load) indexed by multiple dimensions of physical and psychosocial stress was ascertained among homeless street boys and three family-based groups, from poor urban squatter settlements, urban middle class, and a remote rural village. Biomarkers of stress and vulnerability to stress included growth status, salivary cortisol, antibodies to Epstein–Barr virus, acute phase inflammatory responses (alpha1-antichymotrypsin), and cardiovascular fitness and reactivity (flex heart rate and pressor response). Individual biomarkers of risk and allostatic load differed markedly among groups, were highest in villagers, and varied by components of allostatic load. Such data suggest a need for critical appraisal of homelessness and migration as a risk factor to youth, given prevailing local conditions such as rural poverty, and represents the only multidimensional study of childhood allostatic load and developmental risk in non-Western settings