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Biomedical subjects

Sharon Abrahams

Publications and source records attributed to Sharon Abrahams.

15 recordsLinked to original sources

Frontotemporal white matter changes in amyotrophic lateral sclerosis.

Cognitive dysfunction can occur in some patients with amyotrophic lateral sclerosis (ALS) who are not suffering from dementia. The most striking and consistent cognitive deficit has been found using tests of verbal fluency. ALS patients with verbal fluency deficits have shown functional imaging abnormalities predominantly in frontotemporal regions using positron emission tomography (PET). This study used automated volumetric voxel-based analysis of grey and white matter densities of structural magnetic resonance imaging (MRI) scans to explore the underlying pattern of structural cerebral change in nondemented ALS patients with verbal fluency deficits. Two groups of ALS patients, defined by the presence or absence of cognitive impairment on the basis of the Written Verbal Fluency Test (ALSi, cognitively impaired, n=11; ALSu, cognitively unimpaired n=12) were compared with healthy age matched controls (n=12). A comparison of the ALSi group with controls revealed significantly (p<0.002) reduced white matter volume in extensive motor and non-motor regions, including regions corresponding to frontotemporal association fibres. These patients demonstrated a corresponding cognitive profile of executive and memory dysfunction. Less extensive white matter reductions were revealed in the comparison of the ALSu and control groups in regions corresponding to frontal association fibres. White matter volumes were also found to correlate with performance on memory tests. There were no significant reductions in grey matter volume in the comparison of either patient group with controls. The structural white matter abnormalities in frontal and temporal regions revealed here may underlie the cognitive and functional imaging abnormalities previously reported in non-demented ALS patients. The results also suggest that extra-motor structural abnormalities may be present in ALS patients with no evidence of cognitive change. The findings support the hypothesis of a continuum of extra-motor cerebral and cognitive change in this disorder.

Adult↗

Sex differences in a human analogue of the Radial Arm Maze: the "17-Box Maze Test".

This study investigated sex differences in spatial memory using a human analogue of the Radial Arm Maze: a revision on the Nine Box Maze originally developed by called the 17-Box Maze Test herein. The task encourages allocentric spatial processing, dissociates object from spatial memory, and incorporates a within-participants design to provide measures of location and object, working and reference memory. Healthy adult males and females (26 per group) were administered the 17-Box Maze Test, as well as mental rotation and a verbal IQ test. Females made significantly fewer errors on this task than males. However, post hoc analysis revealed that the significant sex difference was specific to object, rather than location, memory measures. These were medium to large effect sizes. The findings raise the issue of task- and component-specific sexual dimorphism in cognitive mapping.

Adolescent↗

Allocentric spatial memory in humans with hippocampal lesions.

An immersive virtual reality (IVR) system was used to investigate allocentric spatial memory in a patient (PR) who had selective hippocampal damage, and also in patients who had undergone unilateral temporal lobectomies (17 right TL and 19 left TL), their performance compared against normal control groups. A human analogue of the Olton [Olton (1979). Hippocampus, space, and memory. Behavioural Brain Science, 2, 315] spatial maze was developed, consisting of a virtual room, a central virtual circular table and an array of radially arranged up-turned 'shells.' The participant had to search these shells in turn in order to find a blue 'cube' that would then 'move' to another location and so on, until all the shells had been target locations. Within-search errors could be made when the participants returned to a previously visited location during a search, and between-search errors when they revisited previously successful, but now incorrect locations. PR made significantly more between-search errors than his control group, but showed no increase in within-search errors. The right TL group showed a similar pattern of impairment, but the left TL group showed no impairment. This finding implicates the right hippocampal formation in spatial memory functioning in a scenario in which the visual environment was controlled so as to eliminate extraneous visual cues.

Adult↗

Sex, sexual orientation, and identification of positive and negative facial affect.

Sex and sexual orientation related differences in processing of happy and sad facial emotions were examined using an experimental facial emotion recognition paradigm with a large sample (N = 240). Analysis of covariance (controlling for age and IQ) revealed that women (irrespective of sexual orientation) had faster reaction times than men for accurate identification of facial emotion and were more accurate in identifying male faces than female ones, whereas men performed the same regardless of the sex of the face. However, there were no overall sex differences in accuracy. These findings suggest a limited role for sex in the perception of facial affect.

Adolescent↗

Biosocial factors, sexual orientation and neurocognitive functioning.

It has been proposed that sexual orientation related differences in cognitive performance are either due to the actions of prenatal factors early in development or the influence of gender role learning. This study examined the performance of 240 healthy, right-handed heterosexual and homosexual males and females (N = 60 per group) on a battery of cognitive tasks comprising mental rotation, judgement of line orientation (JLO), verbal fluency, perceptual speed and object location memory. Measures were also taken of the psychological gender, birth order, sibling sex composition and the 2nd to 4th finger length ratios of the right and left hands. A series of stepwise regression analyses revealed that sex and sexual orientation were the strongest predictors of cognitive performance, with IQ also contributing considerable variance. Psychological gender (M/F scores) added a small, but significant, amount of variance to mental rotation and perceptual speed scores in addition to these main factors, but prenatal hormone related indices, such as 2nd to 4th finger ratios, birth order and sibling sex composition added no independent predictive power. These findings are discussed in relation to biosocial influences on cognitive differences between heterosexuals and homosexuals.

Adolescent↗

Developmental instability is associated with neurocognitive performance in heterosexual and homosexual men, but not in women.

Little is known about the neurodevelopmental nature of human cognitive abilities. This investigation presents evidence consistent with a hypothesis that interindividual and within-sex cognitive variations are associated with vulnerabilities to environmental sources of developmental stress. A large sample of healthy heterosexual and homosexual men and women (N=240) completed a series of visuospatial and verbal tests. A composite fluctuating asymmetry (FA) measure was computed from the lengths of the finger digits. In heterosexual men, higher FA scores were associated with poorer line orientation judgment; and in homosexual men, with poorer verbal fluency and perceptual speed. No associations were found in heterosexual or homosexual women. These results suggest that developmental instability is linked to neurocognitive integrity in men, but not in women.

Adolescent↗

Performance differences between adult heterosexual and homosexual men on the Digit-Symbol Substitution subtest of the WAIS-R.

Previous evidence suggests that sexual orientation influences performance on a number of cognitive functions known to be sexually dimorphic. This investigation examined the performance of 240 right-handed subjects (60 heterosexual men, 60 homosexual men, 60 heterosexual women and 60 homosexual women) on one of the most commonly used neuropsychological tests to show normative sex differences, the Digit-Symbol Substitution test of the WAIS-R. Analysis of scaled Digit-Symbol scores revealed that heterosexual women and homosexual men outperformed heterosexual men. The magnitude of these differences were modest by standard criteria. No differences were found between heterosexual and homosexual women. The findings implicate within-sex variation in one test that relies on intact executive function.

Adolescent↗

Proanthocyanidin biosynthesis in plants. Purification of legume leucoanthocyanidin reductase and molecular cloning of its cDNA.

Leucoanthocyanidin reductase (LAR) catalyzes the synthesis of catechin, an initiating monomer of condensed tannin or proanthocyanidin (PA) synthesis, from 3,4-cis-leucocyanidin and thus is the first committed step in PA biosynthesis. The enzyme was purified to near homogeneity from PA-rich leaves of the legume Desmodium uncinatum (Jacq.) DC, partially sequenced and the corresponding cDNA cloned. The identity of the enzyme was confirmed by expressing active recombinant LAR in Escherichia coli and in tobacco and white clover. The enzyme is a monomer of 43 kDa (382 amino acids) and is most active synthesizing catechin (specific activity of approximately 10 micromol min+1 mg of protein+1) but also synthesizes afzelechin and gallocatechin. LAR is most closely related to the isoflavone reductase group of plant enzymes that are part of the Reductase-Epimerase-Dehydrogenase (RED) family of proteins. Unlike all other plant isoflavone reductase homologues that are about 320 amino acids long, LAR has an additional 65-amino acid C-terminal extension whose function is not known. Curiously, although Arabidopsis makes PA, there is no obvious LAR orthologue in the Arabidopsis genome. This may be because Arabidopsis seems to produce only an epicatechin, rather than a dual catechin/epicatechin-based PA similar to many other plants.

Amino Acid Sequence↗

Functional magnetic resonance imaging of verbal fluency and confrontation naming using compressed image acquisition to permit overt responses.

Verbal fluency and confrontation naming, two tests of word retrieval, are of great utility in the field of cognitive neuroscience. However, in the context of functional magnetic resonance imaging (fMRI), movement artefact has necessitated the use of covert paradigms, which has limited clinical application. We developed two overt fMRI paradigms that allowed for performance measurement and hence were appropriate for use with patient groups. The paradigms incorporated a blocked-design and compressed-acquisition methodology where cues were presented and responses made in a "silent" period allowing for performance measurement. The slow response pace was specifically designed for older and potentially cognitively impaired participants. Verbal fluency was associated with activation in the middle frontal gyrus (Brodmann areas 46 and 9), anterior cingulate gyrus and inferior frontal gyrus (area 44 and 45). Confrontation naming activated areas of the temporo-occipital cortices (areas 18, 19, and 37) and the inferior frontal gyrus. The two paradigms successfully activated regions involved in executive and word retrieval processes and overcame the potential artefacts resulting from overt speech during image acquisition, providing useful neuropsychological tools to investigate cognitive deficits in clinical populations.

Acoustic Stimulation↗

Sexual orientation related differences in spatial memory.

The purpose of this study was to investigate and extend previously reported sex differences in object location memory by comparing the performance of heterosexual and homosexual males and females. Subjects were 240 healthy, right-handed heterosexual and homosexual males and females. They were instructed to study 16 common, gender-neutral objects arranged randomly in an array and subsequently tested for object recall, object recognition and spatial location memory. Females recalled significantly more objects than males, although there were no group differences in object recognition. Decomposition of significant interactions between sex and sexual orientation on spatial location memory (controlling for differences in object recall, age and IQ) revealed that heterosexual females and homosexual males scored better than heterosexual males, and no different from each other. There were no differences between homosexual and heterosexual females. The findings suggest that homosexual males and heterosexual females encode, store and retrieve positional and relational information about spatial layouts similarly, pointing to within-sex variations in the neural architecture underlying spatial memory.

Female↗

Sexual-orientation-related differences in verbal fluency.

This study examined the performance of 60 heterosexual men, 60 gay men, 60 heterosexual women, and 60 lesbians on 3 tests of verbal fluency known to show gender differences: letter, category, and synonym fluency. Gay men and lesbians showed opposite-sex shifts in their profile of scores. For letter fluency, gay men outperformed all other groups; lesbians showed the lowest scores. For category fluency, gay men and heterosexual women jointly outperformed lesbians and heterosexual men. Finally, gay men outperformed all other groups on synonym fluency, whereas lesbians and heterosexual men performed similarly. A difference between heterosexual men and women was demonstrated on category and synonym fluency only. The findings implicate within-sex differences in the functioning of the prefrontal and temporal cortices.

Adult↗

The Arabidopsis TDS4 gene encodes leucoanthocyanidin dioxygenase (LDOX) and is essential for proanthocyanidin synthesis and vacuole development.

The anthocyanin and proanthocyanidin (PA) biosynthetic pathways share common intermediates until leucocyanidin, which may be used by leucoanthocyanidin dioxygenase (LDOX) to produce anthocyanin, or the enzyme leucoanthocyanidin reductase (LAR) to produce catechin, a precursor of PA. The Arabidopsis mutant tannin deficient seed 4 (tds4-1) has a reduced PA level and altered pattern PA accumulation. We identified the TDS4 gene as LDOX by complementation of the tds4-1 mutation either with a cosmid encoding LDOX or a 35S:LDOX construct. Independent Arabidopsis lines with a T-DNA insertion in the LDOX gene had a similar phenotype, and one was allelic to tds4-1. The seed phenotype of ban tds4 double mutants showed that LDOX precedes BANYULS (BAN) in the PA pathway, confirming recent biochemical characterisation of BAN as an anthocyanidin reductase. Double mutant analysis was also used to order the other TDS genes. Analysis of the PA intermediates in tds4-1 revealed three dimethylaminocinnamaldehyde (DMACA) reacting compounds that accumulated in extracts from developing seeds. Analysis of Arabidopsis PA and its precursors indicates that Arabidopsis, unlike many other plants, exclusively uses the epicatechin and not the catechin pathway to PA. Transmission electron microscopy (TEM) showed that the pattern observed when seeds of tds4 were stained with DMACA was a result of the accumulation of PA intermediates in the cytoplasm of endothelial cells. Fluorescent marker dyes were used to show that tds4 endothelial cells had multiple small vacuoles, instead of a large central vacuole as observed in the wild types (WT). These results show that in addition to its established role in the formation of anthocyanin, LDOX is also part of the PA biosynthesis pathway.

Alleles↗

The structure of the major anthocyanin in Arabidopsis thaliana.

The major anthocyanin in the leaves and stems of Arabidopsis thaliana has been isolated and shown to be cyanidin 3-O-[2-O(2-O-(sinapoyl)-beta-D-xylopyranosyl)-6-O-(4-O-(beta-D-glucopyranosyl)-p-coumaroyl-beta-D-glucopyranoside] 5-O-[6-O-(malonyl) beta-D-glucopyranoside]. This anthocyanin is a glucosylated version of one of the anthocyanins found in the flowers of the closely related Matthiola incana.

Anthocyanins↗

Identification and biochemical characterization of mutants in the proanthocyanidin pathway in Arabidopsis.

Proanthocyanidin (PA), or condensed tannin, is a polymeric flavanol that accumulates in a number of tissues in a wide variety of plants. In Arabidopsis, we found that PA precursors (detected histochemically using OsO(4)) accumulate in the endothelial cell layer of the seed coat from the two-terminal cell stage of embryo development onwards. To understand how PA is made, we screened mature seed pools of T-DNA-tagged Arabidopsis lines to identify mutants defective in the synthesis of PA and found six tds (tannin-deficient seed) complementation groups defective in PA synthesis. Mutations in these loci disrupt the amount (tds1, tds2, tds3, tds5, and tds6) or location and amount of PA (tds4) in the endothelial cell layer. The PA intermediate epicatechin has been identified in wild type and mutants tds1, tds2, tds3, and tds5 (which do not produce PA) and tds6 (6% of wild-type PA), whereas tds4 (2% of wild-type PA) produces an unidentified dimethylaminocinnamaldehyde-reacting compound, indicating that the mutations may be acting on genes beyond leucoanthocyanidin reductase, the first enzymatic reduction step dedicated to PA synthesis. Two other mutants were identified, an allele of tt7, which has a spotted pattern of PA deposition and produces only 8% of the wild-type level of type PA as propelargonidin, and an allele of tt8 producing no PA. Spotted patterns of PA deposition observed in seed of mutants tds4 and tt7-3 result from altered PA composition and distribution in the cell. Our mutant screen, which was not exhaustive, suggests that the cooperation of many genes is required for successful PA accumulation.

Alleles↗

An unusual case of a wasp phobic.

This study concerns a woman with a very specific phobia of free-flying wasps. Her underlying and disabling belief was that she was allergic to wasp venom and, if stung, would certainly die. A behavioural approach, such as systematic desensitization and exposure, was not thought suitable because of the patient's pattern of fear. Instead, the treatment of choice was an allergy test to directly challenge her belief. The allergy test was negative and led to a dramatic improvement which was maintained 1 year after treatment.

Adult↗