Search PubMed⌕ Search

Biomedical subjects

K Christianson

Publications and source records attributed to K Christianson.

6 recordsLinked to original sources

Thematic roles assigned along the garden path linger.

In the literature dealing with the reanalysis of garden path sentences such as While the man hunted the deer ran into the woods, it is generally assumed either that people completely repair their initial incorrect syntactic representations to yield a final interpretation whose syntactic structure is fully consistent with the input string or that the parse fails. In a series of five experiments, we explored the possibility that partial reanalyses take place. Specifically, we examined the conditions under which part of the initial incorrect analysis persists at the same time that part of the correct final analysis is constructed. In Experiments 1a and 1b, we found that both the length of the ambiguous region and the plausibility of the ultimate interpretation affected the likelihood that such sentences would be fully reanalyzed. In Experiment 2, we compared garden path sentences with non-garden path sentences and compared performance on two different types of comprehension questions. In Experiments 3a and 3b, we constructed garden path sentences using a small class of syntactically unique verbs to provide converging evidence against the position that people employ some sort of "general reasoning" or pragmatic inference when faced with syntactically difficult garden paths. The results from these experiments indicate that reanalysis of such sentences is not always complete, so that comprehenders often derive an interpretation for the full sentence in which part of the initial misanalysis persists. We conclude that the goal of language processing is not always to create an idealized structure, but rather to create a representation that is "good enough" to satisfy the comprehender that an appropriate interpretation has been obtained.

Cognition↗

Misinterpretations of garden-path sentences: implications for models of sentence processing and reanalysis.

Theories of sentence comprehension have addressed both initial parsing processes and mechanisms responsible for reanalysis. Three experiments are summarized that were designed to investigate the reanalysis and interpretation of relatively difficult garden-path sentences (e.g., While Anna dressed the baby spit up on the bed). After reading such sentences, participants correctly believed that the baby spit up on the bed; however, they often confidently, yet incorrectly, believed that Anna dressed the baby. These results demonstrate that garden-path reanalysis is not an all-or-nothing process and that thematic roles initially assigned for the subordinate clause verb are not consistently revised. The implications of the partial reanalysis phenomenon for Fodor and Inoue's (1998) model of reanalysis and sentence processing are discussed. In addition, we discuss the possibility that language processing often creates "good enough" structures rather than ideal structures.

Humans↗

Crystallographic analysis of reversible metal binding observed in a mutant (Asp153-->Gly) of Escherichia coli alkaline phosphatase.

Here we present the refined crystal structures of three different conformational states of the Asp153-->Gly mutant (D153G) of alkaline phosphatase (AP), a metalloenzyme from Escherichia coli. The apo state is induced in the crystal over a 3 month period by metal depletion of the holoenzyme crystals. Subsequently, the metals are reintroduced in the crystalline state in a time-dependent reversible manner without physically damaging the crystals. Two structural intermediates of the holo form based on data from a 2 week (intermediate I) and a 2 month soak (intermediate II) of the apo crystals with Mg2+ and Zn2+ have been identified. The three-dimensional crystal structures of the apo (R = 18.1%), intermediate I (R = 19.5%), and intermediate II (R = 19.9%) of the D153G enzyme have been refined and the corresponding structures analyzed and compared. Large conformational changes that extend from the mutant active site to surface loops, located 20 A away, are observed in the apo structure with respect to the holo structure. The structure of intermediate I shows the recovery of the entire enzyme to an almost native-like conformation, with the exception of residues Asp 51 and Asp 369 in the active site and the surface loop (406-410) which remains partially disordered. In the three-dimensional structure of intermediate II, both Asp 51 and Asp 369 are essentially in a native-like conformation, but the main chain of residues 406-408 within the loop is still not fully ordered. The D153G mutant protein exhibits weak, reversible, time dependent metal binding in solution and in the crystalline state.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

A molecular sensor system based on genetically engineered alkaline phosphatase.

Binding and signaling proteins based on Escherichia coli alkaline phosphatase (AP; EC 3.1.3.1) were designed for the detection of antibodies. Hybrid proteins were constructed by using wild-type AP and point mutants of AP [Asp-101 --> Ser (D101S) and Asp-153 --> Gly (D153G)]. The binding function of the hybrid proteins is provided by a peptide epitope inserted between amino acids 407 and 408 in AP. Binding of anti-epitope antibodies to the hybrid proteins modulates the enzyme activity of the hybrids; upon antibody binding, enzyme activity can increase to as much as 300% of the level of activity in the absence of antibody or can decrease as much as 40%, depending on the presence or absence of the point mutations in AP. The fact that modulation is altered from inhibition to activation by single amino acid changes in the active site of AP suggests that the mechanism for modulation is due to structural alterations upon antibody binding. Modulation is a general phenomenon. The properties of the system are demonstrated by using two epitopes, one from the V3 loop of human immunodeficiency virus type 1 gp120 protein and one from hepatitis C virus core protein, and corresponding monoclonal antibodies. The trend of modulation is consistent for all hybrids; those in wild-type AP are inhibited by antibody, while those in the AP mutants are activated by antibody. This demonstrates that modulation of enzyme activity of the AP-epitope hybrid proteins is not specific to either a particular epitope sequence or a particular antibody-epitope combination.

Alkaline Phosphatase↗

Modulation of enzyme activity by antibody binding to an alkaline phosphatase-epitope hybrid protein.

An epitope from the HIV-1 gp120 protein V3 loop has been inserted onto the surface of bacterial alkaline phosphatase at different positions in the vicinity of the enzyme active site, creating hybrid proteins that can bind to an anti-gp120 monoclonal antibody. One of the hybrid proteins, API1, has a 13 amino acid V3 loop sequence inserted between residues 407 and 408 of alkaline phosphatase. The enzymatic activity of this protein is modulated upon antibody binding. API1 maintains the full activity of the wild type alkaline phosphatase but in the presence of the anti-gp120 antibody, the enzyme activity is inhibited by 40-50%. Thus, the hybrid enzyme can be used to detect the presence of antibody in solution. The concept of signalling proteins may have a wide application. Two models for the mechanism of modulation, steric hindrance and allosteric regulation, are discussed.

Alkaline Phosphatase↗

Structural and biochemical differentiation of the guinea-pig colon during foetal development.

We have studied some aspects of the morphological and biochemical differentiation of the foetal guinea-pig colonic epithelium. At day 40 the epithelium was organised in ridges and appeared pseudo-stratified. Folding of the epithelium, followed by villus formation, occurred between days 45 and 55, and by day 50 mucus-secreting goblet cells appeared at the bases of the colonic villi. By day 55 most epithelial cells, including goblet cells, possessed numerous microvilli which, by day 65, had become organised into well developed brush-borders. Between day 55 and term (day 65-68) mucosal depth increased markedly and the colon attained its final glandular morphology. Biochemical studies showed the specific activities of the microvillar hydrolases to be much lower in the washed colon than in either foetal meconium or small intestine at all times during development. Furthermore, a membrane fraction highly enriched in microvillus hydrolase activities was prepared from foetal colonic meconium using techniques originally devised to isolate the foetal small intestinal microvillus membrane. This meconial subfraction was almost identical in polypeptide composition to the highly-purified foetal small intestinal microvillus membrane. Identification of the colonic microvillus membrane was hampered by the absence of reliable membrane markers. Nevertheless, a fraction 14-fold enriched in aminopeptidase activity was prepared from day 40 foetal colon and its polypeptide composition compared by SDS-PAGE to that of the small intestinal microvillus membrane at the same age.

Aminopeptidases↗