How number line estimation skills relate to neural activations in single digit subtraction problems.

The Number Line (NL) task requires judging the relative numerical magnitude of a number and estimating its value spatially on a continuous line. Children's skill on this task has been shown to correlate with and predict future mathematical competence. Neurofunctionally, this task has been shown to rely on brain regions involved in numerical processing. However, there is no direct evidence that performance on the NL task is related to brain areas recruited during arithmetical processing and that these areas are domain-specific to numerical processing. In this study, we test whether 8- to 14-year-old's behavioral performance on the NL task is related to fMRI activation during small and large single-digit subtraction problems. Domain-specific areas for numerical processing were independently localized through a numerosity judgment task. Results show a direct relation between NL estimation performance and the amount of the activation in key areas for arithmetical processing. Better NL estimators showed a larger problem size effect than poorer NL estimators in numerical magnitude (i.e., intraparietal sulcus) and visuospatial areas (i.e., posterior superior parietal lobules), marked by less activation for small problems. In addition, the direction of the activation with problem size within the IPS was associated with differences in accuracies for small subtraction problems. This study is the first to show that performance in the NL task, i.e. estimating the spatial position of a number on an interval, correlates with brain activity observed during single-digit subtraction problem in regions thought to be involved in numerical magnitude and spatial processes.

The development of specialized brain systems in reading and oral-language.

Functional magnetic resonance imaging (fMRI) was used to examine differences between children (9-12 years) and adults (21-31 years) in the distribution of brain activation during word processing. Orthographic, phonologic, semantic and syntactic tasks were used in both the auditory and visual modalities. Our two principal results were consistent with the hypothesis that development is characterized by increasing specialization. Our first analysis compared activation in children versus adults separately for each modality. Adults showed more activation than children in the unimodal visual areas of middle temporal gyrus and fusiform gyrus for processing written word forms and in the unimodal auditory areas of superior temporal gyrus for processing spoken word forms. Children showed more activation than adults for written word forms in posterior heteromodal regions (Wernicke's area), presumably for the integration of orthographic and phonologic word forms. Our second analysis compared activation in the visual versus auditory modality separately for children and adults. Children showed primarily overlap of activation in brain regions for the visual and auditory tasks. Adults showed selective activation in the unimodal auditory areas of superior temporal gyrus when processing spoken word forms and selective activation in the unimodal visual areas of middle temporal gyrus and fusiform gyrus when processing written word forms.

Individual and developmental differences in semantic priming: empirical and computational support for a single-mechanism account of lexical processing.

Existing accounts of single-word semantic priming phenomena incorporate multiple mechanisms, such as spreading activation, expectancy-based processes, and postlexical semantic matching. The authors provide empirical and computational support for a single-mechanism distributed network account. Previous studies have found greater semantic priming for low- than for high-frequency target words as well as inhibition following unrelated primes only at long stimulus-onset asynchronies (SOAs). A series of experiments examined the modulation of these effects by individual differences in age or perceptual ability. Third-grade, 6th-grade, and college students performed a lexical-decision task on high- and low-frequency target words preceded by related, unrelated, and nonword primes. Greater priming for low-frequency targets was exhibited only by participants with high perceptual ability. Moreover, unlike the college students, the children showed no inhibition even at the long SOA. The authors provide an account of these results in terms of the properties of distributed network models and support this account with an explicit computational simulation.

Developmental differences in visual and auditory processing of complex sentences.

Children aged 8 through 11 (N = 250) were given a word-by-word sentence task in both the visual and auditory modes. The sentences included an object relative clause, a subject relative clause, or a conjoined verb phrase. Each sentence was followed by a true-false question, testing the subject of either the first or second verb. Participants were also given two memory span measures: digit span and reading span. High digit span children slowed down more at the transition from the main to the relative clause than did the low digit span children. The findings suggest the presence of a U-shaped learning pattern for on-line processing of restrictive relative clauses. Off-line accuracy scores showed different patterns for good comprehenders and poor comprehenders. Poor comprehenders answered the second verb questions at levels that were consistently below chance. Their answers were based on an incorrect local attachment strategy that treated the second noun as the subject of the second verb. For example, they often answered yes to the question "The girl chases the policeman" after the object relative sentence "The boy that the girl sees chases the policeman." Interestingly, low memory span poor comprehenders used the local attachment strategy less consistently than high memory span poor comprehenders, and all poor comprehenders used this strategy less consistently for harder than for easier sentences.

Developmental and lesion effects in brain activation during sentence comprehension and mental rotation.

The development of neurocognitive networks was examined in 2 cognitive paradigms: auditory sentence comprehension and mental rotation of alphanumeric stimuli. Patterns of brain activation were measured with whole brain echoplanar functional magnetic resonance imaging at 3 Tesla in 5 adults (20-28 years old), 7 children (9-12 years old), and 6 pediatric patients (9-12 years old) with perinatal strokes or periventricular hemorrhages. Healthy children and adults activated similar neurocognitive networks, but there were developmental differences in the distribution of activity across these networks. In the sentence task, children showed more activation in the inferior visual area suggesting an imagery strategy rather than a linguistic strategy for sentence processing. Furthermore, consistent use of a sentence comprehension strategy, whether correct or incorrect as compared to chance performance, was associated with greater activation in the inferior frontal area (Broca's) in both children and pediatric patients. In the mental rotation task, healthy adults showed more activation in the superior parietal and middle frontal areas and less activation in the supramarginal gyrus, suggesting adults were primarily engaged in visual-spatial manipulation and less engaged in the recognition of noncanonical views of stimuli. The pediatric patients showed patterns of activation consistent with organization of cognitive processing into homologous areas of the contralateral hemisphere.

Functional organization of activation patterns in children: whole brain fMRI imaging during three different cognitive tasks.

1. Patterns of brain activation were measured with whole brain echo-planar functional magnetic resonance imaging (fMRI) at 3.0 Tesla in healthy children (N = 6) and in one child with a left-hemisphere encephalomalacic lesion as sequellae from early stroke. 2. Three cognitive tasks were used: auditory sentence comprehension, verb generation to line drawings, and mental rotation of alphanumeric stimuli. 3. There was evidence for significant bilateral activation in all three cognitive tasks for the healthy children. Their patterns of activation were consistent with previous functional imaging studies with adults. 4. The child with a left-hemisphere stroke showed evidence of homologous organization in the non-damaged hemisphere.

Quick, automatic, and general activation of orthographic and phonological representations in young readers.

Second through 6th graders were presented with nonword primes (orthographic, pseudohomophone, and control) and target words displayed for durations (30 and 60 ms) that were brief enough to prevent complete processing. Word reading skills were assessed by 3 word and nonword naming tasks. Good readers exhibited more orthographic priming than poor readers at both durations and more pseudohomophone priming at the short duration only. This suggests that good readers activate letter and phonemic information more efficiently than poor readers. Good readers also exhibited an equal amount of priming at both durations, whereas poor readers showed greater priming at the longer duration. This suggests that activation was not under strategic control. Finally, priming was reliable for both high- and low-frequency targets. This suggests that readers activate consistent information regardless of target word characteristics. Thus, quick, automatic, and general activation of orthographic and phonological information in skilled readers results from the precision and redundancy of their lexical representations.

A comprehensive IgA service provided by a blood transfusion center.

IgA is best known in transfusion practice for its deficiency when anti- IgA antibodies cause severe anaphylactic reactions. Following the realization that IgA deficient products were needed on demand, blood donors were routinely screened, initially by latex agglutination inhibition and subsequently by hemagglutination inhibition using an Olympus PK-7200 blood grouping machine. IgA deficiency (<.0016 g/L) was found in 357 (with anti-IgA in 28%) of 301,310 donors, an incidence of 1 in 844. By screening new donors and directed call-up, group O, D- red blood cell (RBC) units are always in stock. During 1 year, the center supplied 79 units of RBCs and 64 units of fresh frozen plasma to a variety of patients with IgA deficiency, including three undergoing liver transplantation. The center also provides a reference service for IgA/anti-IgA status. The technique used (hemagglutination inhibition) has a sensitivity well below the threshold of standard quantitation methods. Samples were most commonly referred from departments investigating possible immunodeficiency and suspected transfusion reactions. Of 247 patients investigated, 122 had IgA deficiency, 43 with anti-IgA (of whom 5 had suffered a transfusion reaction). Donors and patients with anti- IgA were issued blood group cards warning that they should only receive IgA deficient products.

Acquisition of the mental state verb know by 2- to 5-year-old children.

The production of the cognitive internal state word know by four 2- to 5-year-old children and their parents was examined. The levels of meaning of cognitive words can be categorized hierarchically along the dimensions of conceptual difficulty and abstractness (see Booth & Hall, 1995). The present study found that children and their parents expressed low levels of meaning less frequently, whereas they expressed high levels of meaning more frequently as a function of age. The children's use of know was also correlated positively with (1) their number of different words produced suggesting that cognitive words are related to more general semantic processes, and (2) with parental use of those same cognitive words suggesting that parental linguistic input may be an important mechanism in cognitive word acquisition. Finally, young children tended to use know more to refer to themselves than to refer to others, whereas their parents tended to use know equally to refer to self and others. The importance of cognitive words in a theory of language acquisition is discussed.

IgA red cell autoantibodies and autoimmune hemolysis.

BACKGROUND: The objective of the study was to examine the interrelationships and clinical significance of IgA red cell antibodies in the autoimmune response. STUDY DESIGN AND METHODS: The records of 5235 patients referred to an immunohematology center over a 14-year period were critically examined for patients who had IgA autoantibodies, defined as elutable IgA immunoglobulins that would rebind to normal cells. RESULTS: One hundred twenty-four patients (61 male) aged 6 to 98 years had warm-reacting IgA autoantibodies. In 75 individuals, these were idiopathic; neoplasms were the most common associated conditions in the individuals with secondary IgA autoantibodies. IgA was the only immunoglobulin present in 6 patients; all others also had IgG and/or IgM coating their cells, and 102 individuals also had increased amounts of cell-bound complement. In a comparison by chi-square test of populations with haptoglobins of < 0.1 g per L, IgA was shown to act synergistically with IgG in producing hemolysis (p < 0.01). CONCLUSION: Autoimmune hemolysis due to IgA antibodies alone in rare, with red cell destruction occurring through mechanisms similar to those for IgG. Most commonly, IgA acts synergistically with other immunoglobulins (usually IgG) and complement; the hemolysis may be severe. Whether IgA autoantibodies alone can activate complement remains controversial, but increasing evidence suggests that they can, possibly via the alternative pathway, and that this activation may result in intravascular hemolysis.

Fillers and spaces in text: the importance of word recognition during reading.

Current theories of reading eye movements claim that reading saccades are programmed primarily on the basis of information about the length of the upcoming word, determined by low-level visual processes that detect spaces to the right of fixation. Many studies attempted to test this claim by filling spaces between words with various non-space symbols (fillers). This manipulation, however, confounds the effect of inserting extraneous characters into text with the effect of obscuring word boundaries by filling spaces. We performed the control conditions necessary to unconfound these effects. Skilled readers read continuous stories aloud and silently. Three factors were varied: (i) position of the fillers in the text (at the beginning, the end, or surrounding each word); (ii) the presence or absence of spaces in the text; and (iii) the effect of the type of filler on word recognition (from greatest effect to least effect: Latin letters, Greek letters, digits and shaded boxes). The effect of fillers on reading depended more on the type of filler than on the presence of spaces. The greater effect the fillers had on word recognition, the more they showed reading. Surrounding each word with digits or Greek letters slowed reading as much as filling spaces with these symbols. Surrounding each word with randomly chosen letters, while preserving spaces, slowed reading by 44-75%--as much as, or more than, removing spaces from normal text. Removing spaces from text with Latin-letter fillers slowed reading by only 10-20% more. We conclude that fillers in text disrupt reading by affecting word recognition directly, without necessarily affecting the eye movement pattern.

Autoimmune hemolytic anemia due to IgA class autoantibodies.

Autoimmune hemolytic anemia due to warm-reacting autoantibodies solely of the IgA class is very rare, and only five cases were identified among 5,177 patients referred during 13.5 years. All were females (ages 21-69 years) and all presented with idiopathic "Coombs negative" autoimmune hemolytic anemia, a diagnosis that was confirmed using monospecific anti-human IgA reagents. Red cell-bound IgG was reduced, but in two patients IgM was initially increased, an occurrence that was thought to reflect the developing autoimmune response. The autoantibodies had high affinity for red cells with very little free antibody detectable in the serum; in two instances Rh specificity was evident. Hemolysis was severe in four patients. Two of them had intravascular hemolysis, one of whom also had marked dyserythropoiesis and a transiently positive Ham's test. Although IgA autoantibodies caused hemolysis predominantly through immune adherence, on occasions they also seemed to be able to induce complement activation, possibly via the alternative pathway. Prednisolone was the mainstay of treatment, and was occasionally augmented with azathioprine and intravenous immunoglobulin. Blood transfusion was required in two patients, both of whom eventually required splenectomy that resulted in full remission. The one patient with mild hemolysis recovered without treatment.

Isolation of IgA1 from human serum by affinity chromatography using an immobilized extract of the albumin gland of Helix pomatia.

An extract of the albumin gland of Helix pomatia was linked to Sepharose-4B and used to prepare IgA from group O human serum; immunoelectrophoresis showed that the preparation was free of IgG and IgM. From studies with specific IgA subclass antisera and by comparison with the activity of jacalin-produced material the Helix pomatia extract was found to be IgA1 specific. The preparation had red cell anti-A, B specificity and was suitable for standardizing and controlling anti-human IgA reagents. Preparations using six different carbohydrates as eluants inhibited the agglutination reaction between anti-human IgA and IgA-coated red cells to varying degrees. The pattern of reactions suggested that N-acetyl glucosamine was the IgA binding site for Helix pomatia; this differed from its blood group A determinant (N-acetyl galactosamine) which was the same as that for the IgA1 reactive component of jacalin.

Studies on IgA class circulatory red cell antibodies--II. Properties of IgA class anti-A,anti-B.

The properties of IgA class red cell alloantibodies were determined using an anti-A,anti-B preparation confirmed to be free from IgG and IgM. The following characteristics were found: a thermal optimum of 37 degrees C; saline agglutination enhanced by anti-human IgA; activity substantially unchanged after 1 year's storage at 4 degrees C, but reduced by papain and destroyed by pepsin and by reduction and alkylation; neutralization by AB blood group substance; an inability to activate complement; and a distinctive pattern of apparent molecular sizes (reflecting dimeric and monomeric forms and complexes with serum proteins) which was significantly altered by the action of enzymes and by reduction and alkylation.

Studies on IgA class circulatory red cell antibodies--I. Preparation and identification of IgA class anti-A,anti-B.

To elucidate the role of IgA class alloantibodies in transfusion practice, anti-A,anti-B was prepared using pooled serum from healthy group O donors. IgG was removed by protein A and protein G, whilst IgM was extracted by concanavalin A and anti-human mu chain. The final preparation contained both IgA1 and IgA2; it had an IgA concentration similar to the original serum pool and an environment as near to normal as possible; the absence of IgG and IgM was confirmed by sensitive enzyme-linked antiglobulin tests, and extensive haemagglutination studies showed that anti-A,anti-B was the only red cell antibody present.

Reading unspaced text: implications for theories of reading eye movements.

According to current theories of reading, the reader's saccades are guided primarily by spaces between words, clearly the most prominent visual feature in most modern texts. This belief was investigated by recording eye movements with unprecedented accuracy and precision while subjects read spaced and unspaced passages both silently and aloud. Modest increases in fixation durations and decreases in overall reading speed were observed when unspaced texts were read. However, subjects read unspaced texts with the same level of comprehension and percentage of regressions as they read spaced texts. The only global eye movement parameter that changed appreciably when spaces were removed was progressive (rightward) saccade length. Progressive saccades were shorter in unspaced texts. However, unspaced texts were denser and narrower because they were constructed so as to contain the same number of words/line as the spaced texts. This meant that unspaced texts contained more informational characters/degree of visual angle. The observed decrease in progressive saccade lengh tended to be proportional to this increase in text density. Therefore, the number of saccades/line of text remained approximately the same in both spaced and unspaced texts. Furthermore, a detailed examination of local eye movement properties, i.e. where within words the subjects fixated and how many times they fixated words of different lengths, suggested that the same oculomotor strategy was used for reading spaced and unspaced texts. This was true for both silent reading and reading aloud. Thus, a model that could explain reading spaced texts could also explain reading unspaced texts with only a change of a single global parameter, namely, saccade length. We conclude that the current tendency to emphasize spaces as guides to reading eye movements must be reconsidered. Words, not spaces, may serve as the perceptual units that guide the line of sight through the text.

Cloning of a higher-plant plastid omega-6 fatty acid desaturase cDNA and its expression in a cyanobacterium.

Oligomers based on amino acids conserved between known plant omega-3 and cyanobacterium omega-6 fatty acid desaturases were used to screen an Arabidopsis cDNA library for related sequences. An identified clone encoding a novel desaturase-like polypeptide was used to isolate its homologs from Glycine max and Brassica napus. The plant deduced amino acid sequences showed less than 27% similarity to known plant omega-6 and omega-3 desaturases but more than 48% similarity to cyanobacterial omega-6 desaturase, and they contained putative plastid transit sequences. Thus, we deduce that the plant cDNAs encode the plastid omega-6 desaturase. The identity was supported by expression of the B. napus cDNA in cyanobacterium. Synechococcus transformed with a chimeric gene that contains a prokaryotic promoter fused to the rapeseed cDNA encoding all but the first 73 amino acids partially converted its oleic acid fatty acid to linoleic acid, and the 16:1(9c) fatty acid was converted primarily to 16:2(9c, 12) in vivo. Thus, the plant omega-6 desaturase, which utilizes 16:1(7c) in plants, can utilize 16:1(9c) in the cyanobacterium. The plastid and cytosolic homologs of plant omega-6 desaturases are much more distantly related than those of omega-3 desaturases.

Cloning of higher plant omega-3 fatty acid desaturases.

Arabidopsis thaliana T-DNA transformants were screened for mutations affecting seed fatty acid composition. A mutant line was found with reduced levels of linolenic acid (18:3) due to a T-DNA insertion. Genomic DNA flanking the T-DNA insertion was used to obtain an Arabidopsis cDNA that encodes a polypeptide identified as a microsomal omega-3 fatty acid desaturase by its complementation of the mutation. Analysis of lipid content in transgenic tissues demonstrated that this enzyme is limiting for 18:3 production in Arabidopsis seeds and carrot hairy roots. This cDNA was used to isolate a related Arabidopsis cDNA, whose mRNA is accumulated to a much higher level in leaf tissue relative to root tissue. This related cDNA encodes a protein that is a homolog of the microsomal desaturase but has an N-terminal extension deduced to be a transit peptide, and its gene maps to a position consistent with that of the Arabidopsis fad D locus, which controls plastid omega-3 desaturation. These Arabidopsis cDNAs were used as hybridization probes to isolate cDNAs encoding homologous proteins from developing seeds of soybean and rapeseed. The high degree of sequence similarity between these sequences suggests that the omega-3 desaturases use a common enzyme mechanism.

An enzyme-linked direct antiglobulin test for assessing erythrocyte bound immunoglobulins.

An enzyme-linked direct antiglobulin test (DAGT) for assessing erythrocyte-bound IgG, IgM and IgA is described. The test is carried out in microtitre plates using heavy chain-specific, alkaline phosphatase-linked, goat anti-human globulin reagents with p-nitrophenyl phosphate as substrate. Results are expressed in optical density (OD) units per 3.6 X 10(7) red cells. The method is reproducible, with coefficients of variation of 0.056, 0.093 and 0.087 for IgG, IgM and IgA respectively. The linear relationship between the amount of red cell-bound antibody and the OD reading for each immunoglobulin class shows that the method is suitable for quantitative studies. Healthy individuals were found to have small amounts of immunoglobulin bound to their red cells with mean values of 0.251, 0.087 and 0.128 OD units per 3.6 X 10(7) red cells for IgG, IgM and IgA respectively; there was no difference between male and female subjects. In the clinical situation, the enzyme-linked DAGT was considered to show significantly increased amounts of cell-bound immunoglobulin when the results were more than three standard deviations above the mean and the quantitative results permitted an accurate assessment of the progress and response to treatment of patients with autoimmune haemolysis.