Transforming growth factor beta signalling in vitro and in vivo: activin ligand-receptor interaction, Smad5 in vasculogenesis, and repression of target genes by the deltaEF1/ZEB-related SIP1 in the vertebrate embryo.

The identification and characterization of components of the transforming growth factor beta (TGFbeta) signalling pathway are proceeding at a very fast pace. To illustrate a number of our activities in this field, we first summarize our work aiming at the selection from a large collection of single residue substitution mutants of two activin A polypeptides in which D27 and K102, respectively, have been modified. This work has highlighted the importance of K102 and its positive charge for binding to activin type II receptors. Activin K102E, which did not bind to high-affinity receptor complexes, may be a valuable beta chain, when incorporated in recombinant inhibin to unambiguously detect novel inhibin binding sites at the cell surface. We then illustrate how Smad5 knockout mice and an overexpression approach with a truncated TGFbeta type II receptor in the mouse embryo can contribute to the identification of a novel TGFbeta-->TbetaRII/ALK1-->Smad5 pathway in endothelial cells in the embryo proper and the yolk sac vasculature. We conclude with a summary of our results with a Smad-interacting transcriptional repressor but focus on its biological significance in the vertebrate embryo.

Word-processing training and retraining: effects of adult age, experience, and interface.

Novice (Experiment 1) and experienced (Experiment 2) young, middle-aged, and older adults learned a new word-processing application in keystrokes, menus, or menus-plus-icons interface conditions. Novices showed strong age differences in the time to complete the 3-day tutorial and in declarative and procedural tests of word-processing knowledge. Menus and menus-plus-icons were superior to keystrokes condition. though interface did not interact with age. Experienced users showed age-related slowing in learning rate but minimal age differences in test performance when retrained on a new word-processing program. Age and computer experience accounted for much of the variance in both learning time and word-processing performance; interface type, speed of processing, and spatial generation ability made additional contributions. Experience interacted with age to predict performance. Implications for training and retraining older workers are discussed.

Expression of the inhibitory Smad7 in early mouse development and upregulation during embryonic vasculogenesis.

SMAD proteins are downstream targets of serine/threonine kinase receptors of the transforming growth factor beta (TGF beta) superfamily. Ligands activating these receptors regulate cell growth, differentiation and development in many tissues of various organisms. In mammals eight different Smad genes are known, each with different roles in mediating signalling between plasma membrane and nucleus. Smad6 and Smad7 are inhibitors of TGF beta family signalling. They are both expressed in human adult vascular endothelial cells, particularly after these cells have been subjected to shear stress (Topper et al. [1997] Proc Natl Acad Sci USA 94:9314-9319). Here we show by reverse transcriptase polymerase chain reaction and in situ hybridization that Smad7 mRNA is highly expressed in the developing vascular system of the mouse embryo but is also detectable much earlier in preimplantation embryos and during gastrulation. We also demonstrate by transient transgenesis that overexpression of Smad7 in mouse zygotes inhibits development beyond the 2-cell stage. This confirms earlier conclusions of similar, but complementary, experiments using a dominant negative type II TGF beta receptor demonstrating that TGF beta signalling is required for normal preimplantation development.

Age-related changes in perceptual and psychomotor performance: implications for engineering design.

Increased age is associated with declines in perceptual and psychomotor performance. We review several surveys of health and disability that provide functional descriptions on population trends in vision, hearing, fitness, mobility, and agility that complement laboratory studies of perceptual threshold functions. Women report and exhibit significantly greater disability than men (the exceptions being disabilities associated with hearing and flexibility), with the disability progression accelerating with age. For the growing proportion of older adults in the labor force, visual improvements can be achieved through improved lighting, increased size of visual detail, and glare avoidance. For hearing, restricting the frequency of sounds to the 1000- to 2000-Hz range, minimizing background noise, and eliminating reverberation seem prudent. For the retired population, emphasis should be placed on minimizing disability by promoting greater use of assistive devices and environmental redesign. Future laboratory studies of perceptual and psychomotor functions should attempt to sample more representatively and target underrepresented groups of older adults. New field studies are needed to bridge the gap between survey self-reports and laboratory studies and to determine the cost and benefits of redesign.

Age-related differences in the motoric aspects of transcription typing skill.

Eighty typists ranging in age from 21-71 years and in skill from 24-110 net words per minute participated in 2 experiments examining age-related differences in the motoric aspects of transcription typing skill. Age- and skill-related differences were examined for 2 simplified typing tasks: letter reaction time, which assessed latency to type a single keystroke, and digraph typing, which assessed the latencies to type 2 consecutive keystrokes. A finger tapping and choice reaction time task were also included. The results indicated that low-skill, older typists exhibited a deficit in both the translation and the execution components of motor performance, whereas high-skill, older typists exhibited a deficit in translation only. An additional task that manipulated preview of the text to be typed replicated the findings of Salthouse (1984), suggesting that older typists compensate for age-related slowing by beginning keystroke preparation sooner.