We have used a modified, dual pipette assay to quantify the strength of cadherin-dependent cell–cell adhesion. The force required to separate E-cadherin–expressing paired cells in suspension was measured as an index of intercellular adhesion. Separation force depended on the homophilic interaction of functional cadherins at the cell surface, increasing with the duration of contact and with cadherin levels. Severing the link between cadherin and the actin cytoskeleton or disrupting actin polymerization did not affect initiation of cadherin-mediated adhesion, but prevented it from developing and becoming stronger over time. Rac and Cdc42, the Rho-like small GTPases, were activated when E-cadherin–expressing cells formed aggregates in suspension. Overproduction of the dominant negative form of Rac or Cdc42 permitted initial E-cadherin–based adhesion but affected its later development; the dominant active forms prevented cell adhesion outright. Our findings highlight the crucial roles played by Rac, Cdc42, and actin cytoskeleton dynamics in the development and regulation of strong cell adhesion, defined in terms of mechanical forces.

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The Argentine Precordillera is a continental fragment rifted from the Ouachita embayment of the southern margin of Laurentia (North America) during Cambrian time [about 515 million years ago (Ma)] and accreted to the western margin of Gondwana (South America) during Ordovician time (about 455 Ma). Similarities of Cambrian stratigraphic successions and faunas, Grenville basement rocks, and dimensions link the Argentine Precordillera to the Ouachita embayment. Evidence of rifting during Cambrian time and of a wide ocean basin during Ordovician time indicates that the Precordillera traveled as an independent microcontinent to collide with Gondwana.

Background: Cadherin interactions with catenins are crucial for intercellular adhesion. Results: ␣E-catenin and vinculin cooperate to promote the time-dependent reinforcement of cadherin-mediated adhesions. Conclusion: ␣E-catenin and vinculin form a mechanoresponsive link between cadherin and the underlying actin cytoskeleton. Significance: The force-dependent modulation of ␣-catenin and vinculin recruitment contributes to the development of cadherin adhesion strength.

Seven new detrital-zircon U-Pb age analyses along with a compilation of previously published data from Mississippian-Permian sandstones in the Appalachian foreland (total n = 3564) define the provenance of Alleghanian synorogenic clastic wedges, as well as characterize the detritus available to any more extensive intracontinental dispersal systems. The samples are from the cratonward-prograding Mauch Chunk-Pottsville clastic wedge centered on the Pennsylvania salient, the cratonward-prograding Pennington-Lee clastic wedge centered on the Tennessee salient, and a southwestward-directed longitudinal fluvial system along the distal part of the foreland. Grenville-age detrital zircons generally are abundant in all samples; however, ages of the Taconic and Acadian orogenies are dominant in some samples but are minor to lacking in others. Taconic-Acadian ages are dominant in the Mauch Chunk-Pottsville clastic wedge, in parts of the longitudinal system, and in the upper part (above Middle Pennsylvanian) of the Pennington-Lee clastic wedge; but they are minor to lacking in the lower part (Upper Mississippian-Lower Pennsylvanian) of the Pennington-Lee clastic wedge. New Hf isotopic analy ses show a similar distinction between the two clastic wedges, supporting an interpretation of differences in provenance contributions during the early stages of basin filling. U-Pb ages and Hf isotopic ratios also indicate that the Mauch Chunk-Pottsville transverse dispersal fed the northern part of the longi tudinal system. A few samples in the distal southwestern part of the Mauch Chunk-Pottsville clastic wedge and adjacent parts of the longitudinal system have unusually large populations of grains with Superior and Central Plains ages. The relative distance and isolation of these samples from the Cana dian Shield, which is the primary source of Superior and Central Plains zircons, indicates likely recycling from synrift sediment, passive-margin strata, or Taconic-Acadian clastic wedges. Among the lesser components are a few grains with ages that correspond to Iapetan synrift igneous rocks and also to Pan-African-Brasiliano components of Gondwanan accreted terranes. Synorogenic zircons of the Alleghanian orogeny are very rare (seven grains in the total of 3564).

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