SMAD6 transduces endothelial cell flow responses required for blood vessel homeostasis

Fluid shear stress provided by blood flow instigates a transition from active blood vessel network expansion during development, to vascular homeostasis and quiescence that is important for mature blood vessel function. Here we show that SMAD6 is required for endothelial cell flow-mediated responses leading to maintenance of vascular homeostasis. Concomitant manipulation of the mechanosensor Notch1 pathway and SMAD6 expression levels revealed that SMAD6 functions downstream of ligand-induced Notch signaling and transcription regulation. Mechanistically, full-length SMAD6 protein was needed to rescue Notch loss-induced flow misalignment. Endothelial cells depleted for SMAD6 had defective barrier function accompanied by upregulation of proliferation-associated genes and down regulation of junction-associated genes. The vascular protocadherin PCDH12 was upregulated by SMAD6 and required for proper flow-mediated endothelial cell alignment, placing it downstream of SMAD6. Thus, SMAD6 is a required transducer of flow-mediated signaling inputs downstream of Notch1 and upstream of PCDH12, as vessels transition from an angiogenic phenotype to maintenance of a homeostatic phenotype

Student and tutor perceptions of effective tutoring in distance education

Questionnaire responses of 457 students and 602 tutors were used to investigate conceptions of a 'good tutor.' In each case, factor analysis identified scales that reflected key constructs; cluster analysis identified subgroups with different patterns of scale scores; and discriminant analysis determined the scales that contributed the most to differences among the clusters. Both sets of data yielded conceptions of tutoring that were described as task-oriented and student-oriented, respectively. The students' data yielded an additional, career-oriented conception. The tutors' data yielded two additional conceptions that were described as knowledge-oriented and impersonal, respectively. The distribution of the tutors' conceptions (but not that of the students' conceptions) varied across different faculties, suggesting that tutors from different disciplines have different beliefs about effective tutoring. The study suggests that both tutors and students would benefit from having a better appreciation of the importance of support in facilitating learnin

Dynamics of 1,3-diphenylpropane tethered to the interior pore surfaces of MCM-41

The diffusive motions of covalently tethered 1,3-diphenylpropane (DPP) via a silyl-aryl-ether linkage in the mesopores of MCM-41 were studied by quasielastic neutron scattering. The geometric effect of pore radius was investigated with samples having pores that ranged from 1.6 to 3.0 nm in diameter and highest achievable DPP grafting density. The effect of molecular crowding was investigated in 3.0 rim diameter pores for surface coverage ranging from 0.60 to 1.61 DPP/nm(2). Temperature dependence was determined for large pore diameter samples from 240 to 370 K. As the DPP molecules remain attached over this entire temperature range, data were analyzed in terms of a model of localized diffusion inside a sphere. Only the motions of the DPP hydrogen atoms were considered because of the high sensitivity of neutron scattering to the presence of hydrogen. As atoms far from the attachment point have a greater range of motion than those nearer the tether, the radius of the sphere limiting the motion of individual hydrogen atoms was allowed to increase based on the atom's distance from the tether point Both smaller pore diameters and higher DPP grafting density resulted in larger amplitude motion while the diffusion coefficient was greatest in the largest pores at highest DPP density. These observations support a model where the DPP molecules prefer an orientation allowing close proximity to the MCM-41 pore surface and are forced into the pore interior by either the steric effect of small pore diameter or by increased competition for surface area at high molecule surface coverage