Premise typicality as feature inference decision-making in perceptual categories.

Making property inferences for category instances is important and has been studied in two largely separate areas-categorical induction and perceptual categorization. Categorical induction has a corpus of well-established effects using complex, real-world categories; however, the representational basis of these effects is unclear. In contrast, the perceptual categorization paradigm has fostered the assessment of well-specified representation models due to its controlled stimuli and categories. In categorical induction, evaluations of premise typicality effects, stronger attribute generalization from typical category instances than from atypical, have tried to control the similarity between instances to be distinct from premise-conclusion similarity effects, stronger generalization from greater similarity. However, the extent to which similarity has been controlled is unclear for these complex stimuli. Our research embedded analogues of categorical induction effects in perceptual categories, notably premise typicality and premise conclusion similarity, in an attempt to clarify the category representation underlying feature inference. These experiments controlled similarity between instances using overlap of a small number of constrained features. Participants made inferences for test cases using displayed sets of category instances. The results showed typicality effects, premise-conclusion similarity effects, but no evidence of premise typicality effects (i.e., no preference for generalizing features from typical over atypical category instances when similarity was controlled for), with significant Bayesian support for the null. As typicality effects occurred and occur widely in the perceptual categorization paradigm, why was premise typicality absent? We discuss possible reasons. For attribute inference, is premise typicality distinct from instance similarity? These initial results suggest not.

Comparing methods of category learning: Classification versus feature inference.

Categories have at least two main functions: classification of instances and feature inference. Classification involves assigning an instance to a category, and feature inference involves predicting a feature for a category instance. Correspondingly, categories can be learned in two distinct ways, by classification and feature inference. A typical difference between these in the perceptual category learning paradigm is the presence of the category label as part of the stimulus in feature inference learning and not in classification learning. So we hypothesized a label-induced rule-bias in feature inference learning compared to classification and evaluated it on an important starting point in the field for category learning - the category structures from Shepard, Hovland, and Jenkins (Psychological Monographs: General and Applied, 75(13), 1-42, 1961). They classically found that classification learning of structures consistent with more complex rules resulted in poorer learning. We compared feature inference learning of these structures with classification learning and found differences between the learning tasks supporting the label-bias hypothesis in terms of an emphasis on label-based rules in feature inference. Importantly, participants' self-reported rules were largely consistent with their task performance and indicated the preponderance of rule representation in both tasks. So, while the results do not support a difference in the kind of representation for the two learning tasks, the presence of category labels in feature inference tended to focus rule formation. The results also highlight the specialized nature of the classic Shepard et al. (1961) stimuli in terms of being especially conducive to the formation of compact verbal rules.

Pre-spliceosomal binding of U1 small nuclear ribonucleoprotein (RNP) and heterogenous nuclear RNP E1 is associated with suppression of a growth hormone receptor pseudoexon.

Pseudoexons occur frequently in the human genome. This paper characterizes a pseudoexon in the GH receptor gene. Inappropriate activation of this pseudoexon causes Laron syndrome. Using in vitro splicing assays, pseudoexon silencing was shown to require a combination of a weak 5' pseudosplice-site and splicing silencing elements within the pseudoexon. Immunoprecipitation experiments showed that specific binding of heterogenous nuclear ribonucleoprotein E1 (hnRNP E1) and U1 small nuclear ribonucleoprotein (snRNP) in the pre-spliceosomal complex was associated with silencing of pseudoexon splicing. The possible role of hnRNP E1 was further supported by RNA interference experiments in cultured cells. Immunoprecipitation experiments with three other pseudoexons suggested that pre-spliceosomal binding of U1 snRNP is a potential general mechanism of suppression of pseudoexons.

Calcium absorption by Cav1.3 induces terminal web myosin II phosphorylation and apical GLUT2 insertion in rat intestine.

Glucose absorption in rat jejunum involves Ca(2+)- and PKC betaII-dependent insertion of GLUT2 into the apical membrane. Ca(2+)-induced rearrangement of the enterocyte cytoskeleton is thought to enhance paracellular flow. We have therefore investigated the relationships between myosin II regulatory light chain phosphorylation (RLC(20)), absorption of glucose, water and calcium, and mannitol clearance. ML-7, an inhibitor of myosin light chain kinase, diminished the phloretin-sensitive apical GLUT2 but not the phloretin-insensitive SGLT1 component of glucose absorption in rat jejunum perfused with 75 mM glucose. Western blotting and immunocytochemistry revealed marked decreases in RLC(20) phosphorylation in the terminal web and in the levels of apical GLUT2 and PKC betaII, but not SGLT1. Perfusion with phloridzin or 75 mM mannitol, removal of luminal Ca(2+), or inhibition of unidirectional (45)Ca(2+) absorption by nifedipine exerted similar effects. ML-7 had no effect on the absorption of 10 mM Ca(2+), nor clearance of [(14)C]-mannitol, which was less than 0.7% of the rate of glucose absorption. Water absorption did not correlate with (45)Ca(2+) absorption or mannitol clearance. We conclude that the Ca(2+) necessary for contraction of myosin II in the terminal web enters via an L-type channel, most likely Ca(v)1.3, and is dependent on SGLT1. Moreover, terminal web RLC(20) phosphorylation is necessary for apical GLUT2 insertion. The data confirm that glucose absorption by paracellular flow is negligible, and show further that paracellular flow makes no more than a minimal contribution to jejunal Ca(2+) absorption at luminal concentrations prevailing after a meal.

Apical GLUT2 and Cav1.3: regulation of rat intestinal glucose and calcium absorption.

We have proposed a model of intestinal glucose absorption in which transport by SGLT1 induces rapid insertion and activation of GLUT2 in the apical membrane by a PKC betaII-dependent mechanism. Since PKC betaII requires Ca(2+) and glucose is depolarizing, we have investigated whether glucose absorption is regulated by the entry of dietary Ca(2+) through Ca(v)1.3 in the apical membrane. When rat jejunum was perfused with 75 mM glucose, Ca(2+)-deplete conditions, or perfusion with the L-type antagonists nifedipine and verapamil strongly diminished the phloretin-sensitive apical GLUT2, but not the phloretin-insensitive SGLT1 component of glucose absorption. Western blotting showed that in each case there was a significant decrease in apical GLUT2 level, but no change in SGLT1 level. Inhibition of apical GLUT2 absorption coincided with inhibition of unidirectional (45)Ca(2+) entry by nifedipine and verapamil. At 10 mM luminal Ca(2+), (45)Ca(2+) absorption in the presence of 75 mM glucose was 2- to 3-fold that in the presence of 75 mM mannitol. The glucose-induced component was SGLT1-dependent and nifedipine-sensitive. RT-PCR revealed the presence of Ca(v)beta(3) in jejunal mucosa; Western blotting and immunocytochemistry localized Ca(v)beta(3) to the apical membrane, together with Ca(v)1.3. We conclude that in times of dietary sufficiency Ca(v)1.3 may mediate a significant pathway of glucose-stimulated Ca(2+) entry into the body and that luminal supply of Ca(2+) is necessary for GLUT2-mediated glucose absorption. The integration of glucose and Ca(2+) absorption represents a complex nutrient-sensing system, which allows both absorptive pathways to be regulated rapidly and precisely to match dietary intake.

Stress and glucocorticoid inhibit apical GLUT2-trafficking and intestinal glucose absorption in rat small intestine.

We have proposed a new model of rat intestinal sugar absorption in which high glucose concentrations promote rapid insertion of GLUT2 into the apical membrane, so that absorptive capacity is precisely regulated to match dietary intake. Construction and building work during expansion and refurbishment of our department permitted opportunistic experiments on the effects of building-induced stress on the GLUT2 component of absorption. In fed rats perfused with 75 mM glucose in vivo, stress rapidly inhibited glucose absorption 36.4 +/- 3.0% compared with control rats. Selective inhibition of the GLUT2 component with phloretin demonstrated that stress inhibited the GLUT2 component by 42.8 +/- 3.8%, which correlated with a corresponding diminution in apical GLUT2 levels: the SGLT1 component and its level were unaltered by stress. Effects of stress were reversed by the administration in drinking water of metyrapone, which inhibits 11-beta-hydroxylase. Injection of dexamethasone into control rats 60 min before perfusion resulted in absorption and transporter properties indistinguishable from stressed rats. Our data are consistent with the view that stress activates the hypothalamus-pituitary-adrenal (HPA) axis, causing release of glucocorticoid. The ensuing inhibition of GLUT2 trafficking and absorption seems necessary to prevent enhanced intestinal delivery of glucose to the circulation from antagonizing the essential stress response of glucorticoid in mobilizing peripheral energy stores for emergency purposes.