The investigations included in this dissertation ask how young children learn to understand and communicate about events in their world. Specifically, I consider the development of and relationship between children's nonlinguistic event representation (i.e., one's subjective conceptualization of experience corresponding to the physical world) and early verb learning ability using behavioral and electrophysiological methodologies in children (24- to 42-months) and adults. Chapter 1 takes the format of a review paper aimed at clarifying the role of spatial- and social-cognitive processes in two areas of development addressed in this dissertation : event representation and verb learning. Understanding the relationship between these two areas of development provides a framework for the empirical investigations that follow. The first set of empirical studies investigate children's nonlinguistic event representation. Chapter 2 investigates neurophysiological responses to intact and disrupted actions embedded within a novel event in children and adults using event-related potentials (ERPs). Chapter 3 extends these results to investigate the allocation of attention to two features within dynamic events - movement versus boundaries - in children and adults using a visual preference paradigm. The second set of studies explore children's ability to learn novel verb labels for actions using behavioral and electrophysiological paradigms. Chapter 4 investigates spatial- (i.e., perceptual) and social-cognitive (i.e., conceptual) processes in toddlers' mapping of concepts to real-world events using a behavioral re-enactment paradigm. Finally, to gain a better understanding of the neurophysiological changes that take place in the development of children's verb-learning ability, Chapter 5 examines age-related changes in cortical processing of real and novel verb-to-action associations between 2.5- and 3.5-years of age. This is a period that is pivotal for emerging verb usage, action understanding, and cognitive development, yet the maturational changes that support word learning in general, and verb-learning in particular, are poorly understood. Together these investigations help to advance current understanding of behavioral and neurophysiological processes involved in children's nonlinguistic event representation and subsequent verb learning abilities at a critical point in language acquisition

Na-K-2Cl cotransporter-1 (NKCC) has been detected at exceptionally high levels in the gastric mucosa of several species, prompting speculation that it plays important roles in gastric secretion. To investigate this possibility, we 1) immunolocalized NKCC protein in the mouse gastric mucosa, 2) compared the volume and composition of gastric fluid from NKCC-deficient mice and their normal littermates, and 3) measured acid secretion and electrogenic ion transport by chambered mouse gastric mucosa. NKCC was localized to the basolateral margin of parietal cells, mucous neck cells, and antral base cells. In NKCC-deficient mice, gastric secretions of Na+, K+, Cl-, fluid, and pepsinogen were markedly impaired, whereas secretion of acid was normal. After stimulation with forskolin or 8-bromo-cAMP, chambered corpus mucosa vigorously secreted acid, and this was accompanied by an increase in transmucosal electrical current. Inhibition of NKCC with bumetanide reduced current to resting levels but had no effect on acid output. Although prominent pathways for basolateral Cl- uptake (NKCC) and apical Cl- exit [cystic fibrosis transmembrane conductance regulator (CFTR)] were found in antral base cells, no impairment in gastric secretion was detected in CFTR-deficient mice. Our results establish that NKCC contributes importantly to secretions of Na+, K+, Cl-, fluid, and pepsinogen by the gastric mucosa through a process that is electrogenic in character and independent of acid secretion. The probable source of the NKCC-dependent nonacidic electrogenic fluid secretion is the parietal cell. The observed dependence of pepsinogen secretion on NKCC supports the concept that a nonacidic secretory stream elaborated from parietal cells facilitates flushing of the proenzyme from the gastric gland lumen.

The objective of this study is to characterize the timing and extent of radiologic MS disease recurrence during the 24-week natalizumab treatment interruption period in RESTORE. RESTORE was a randomized, partially placebo-controlled exploratory study. Natalizumab-treated patients with no gadolinium-enhancing (Gd+) lesions at screening (n = 175) were randomized 1:1:2 to continue natalizumab (n = 45), switch to placebo (n = 42), or switch to other therapies (n = 88) for 24 weeks. MRI assessments were performed every 4 weeks. Predictors of increased numbers of Gd+ lesions during natalizumab treatment interruption were evaluated. The numbers of Gd+ lesions were compared with retrospectively collected pre-natalizumab MRI reports and data from placebo-treated patients from two historical randomized clinical trials. Gd+ lesions were detected in 0 % (0/45) of natalizumab patients, 61 % (25/41) of placebo patients, and 48 % (39/81) of other-therapies patients during the randomized treatment period. Gd+ lesions were detected starting at week 12; most were observed at week 16 or later. Thirteen percent (14/107) of patients had >5 Gd+ lesions on ≥1 (of 6) scans during the randomized treatment period versus 7 % (7/107) of patients pre-natalizumab (based on medical record of a single scan). Younger patients and those with more Gd+ lesions pre-natalizumab were more likely to have increased MRI activity. Distribution of total and persistent Gd+ lesions in RESTORE patients was similar to placebo-treated historical control patients. In most patients, recurring radiological disease activity during natalizumab interruption did not exceed pre-natalizumab levels or levels seen in historical control patients.