Studies evaluating phonological contrast learning typically investigate either the predictiveness of specific pretraining aptitude measures or the efficacy of different instructional paradigms. However, little research considers how these factors interact-whether different students learn better from different types of instruction-and what the psychological basis for any interaction might be. The present study demonstrates that successfully learning a foreign-language phonological contrast for pitch depends on an interaction between individual differences in perceptual abilities and the design of the training paradigm. Training from stimuli with high acoustic-phonetic variability is generally thought to improve learning; however, we found high-variability training enhanced learning only for individuals with strong perceptual abilities. Learners with weaker perceptual abilities were actually impaired by high-variability training relative to a low-variability condition. A second experiment assessing variations on the high-variability training design determined that the property of this learning environment most detrimental to perceptually weak learners is the amount of trialby-trial variability. Learners' perceptual limitations can thus override the benefits of high-variability training where trial-by-trial variability in other irrelevant acoustic-phonetic features obfuscates access to the target feature. These results demonstrate the importance of considering individual differences in pretraining aptitudes when evaluating the efficacy of any speech training paradigm.

The processing of amyloid precursor protein (APP) to A␤ is an important event in the pathogenesis of Alzheimer's disease, but the physiological function of APP is not well understood. Our previous work has shown that APP processing and A␤ production are regulated by the extracellular matrix protein Reelin. In the present study, we examined whether Reelin interacts with APP, and the functional consequences of that interaction in vitro. Using coimmunoprecipitation, we found that Reelin interacted with APP through the central domain of Reelin (repeats 3-6) and the E1 extracellular domain of APP. Reelin increased cell surface levels of APP and decreased endocytosis of APP in hippocampal neurons in vitro. In vivo, Reelin levels were increased in brains of APP knock-out mice and decreased in APP-overexpressing mice. RNA interference knockdown of APP decreased neurite outgrowth in vitro and prevented Reelin from increasing neurite outgrowth. Knock-out of APP or Reelin decreased dendritic arborization in cortical neurons in vivo, and APP overexpression increased dendritic arborization. APP and Reelin have previously been shown to promote neurite outgrowth through interactions with integrins. We confirmed that APP interacted with ␣3␤1 integrin, and ␣3␤1 integrin altered APP trafficking and processing. Addition of an ␣3␤1 integrin antibody prevented APP and Reelin-induced neurite outgrowth. These findings demonstrate that Reelin interacts with APP, potentially having important effects on neurite development.

Smoking is the only modifiable risk factor associated with development, expansion, and rupture of abdominal aortic aneurysm (AAA), a leading cause of death in the human population. However, the causative link between cigarette smoke and AAA remains to be established. Here we report that, like angiotensin II (AngII), acute infusion of nicotine, a major component of cigarette smoke, resulted in significantly increased elastin degradation, enlargement of the aorta, aberrant expression of matrix metalloproteinase 2 (MMP2), and an increased incidence of AAA in ApoE knockout (ApoE−/−) and deficient in both ApoE and AMP-activated kinase (AMPK) α1 subunit (ApoE−/−/AMPKα1−/−) mice. Importantly, genetic deletion of AMPKα2 (ApoE−/−/AMPKα2−/−) markedly reduced the increase of maximal aortic diameter and incidence of AAA caused by nicotine or AngII in vivo. Transplantation of bone marrow cells from ApoE−/− mice into ApoE−/−/AMPKα2−/− mice or vice versa did not alter nicotine/AngII-induced AAA formation. Mechanistically, we found that both nicotine and AngII activated AMPK in cultured vascular smooth muscle cells (VSMC) and increased the nuclear co-localization of AMPKα2 and AP-2α, a key transcriptional factor essential for MMP2 expression. Biochemical and biological analysis revealed that AMPKα2 directly phosphorylated AP-2α at serine 219 and this phosphorylation increased AP-2α-dependent MMP2 gene expression in VSMC. We conclude that nicotine increases the incidence of AAA in vivo through activation of AMPKα2 and AP-2α. Moreover, our results provide the first demonstration of a causative link between nicotine and AAA in vivo.

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A superhydrophobic xerogel coating synthesized from a mixture of nanostructured fluorinated silica colloids, fluoroalkoxysilane, and a backbone silane is reported. The resulting fluorinated surface was characterized using contact angle goniometry, SEM, and AFM. Quantitative bacterial adhesion studies performed using a parallel plate flow cell demonstrated that the adhesion of Staphylococcus aureus and Pseudomonas aeruginosa were reduced by 2.08 ± 0.25 and 1.76 ± 0.12 log over controls, respectively. This simple superhydrophobic coating synthesis may be applied to any surface regardless of geometry and does not require harsh synthesis or processing conditions, making it an ideal candidate as a biopassivation strategy.