Cognitive approaches to the fractionation of visuo-spatial working memory.
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Cognition↗
Biomedical subjects
S J Pickering
Publications and source records attributed to S J Pickering.
AI-based algorithms for protein surface comparisons.
Many current methods for protein analysis depend on the detection of similarity in either the primary sequence, or the overall tertiary structure (the Calpha atoms of the protein backbone). These common sequences or structures may imply similar functional characteristics or active properties. Active sites and ligand binding sites usually occur on or near the surface of the protein; so similarly shaped surface regions could imply similar functions. We investigate various methods for describing the shape properties of protein surfaces and for comparing them. Our current work uses algorithms from computer vision to describe the protein surfaces, and methods from graph theory to compare the surface regions. Early results indicate that we can successfully match a family of related ligand binding sites, and find their similarly shaped surface regions. This method of surface analysis could be extended to help identify unknown surface regions for possible ligand binding or active sites.
Algorithms↗
Dissociable lexical and phonological influences on serial recognition and serial recall.
The impact of the lexicality of memory items on memory performance was compared in two paradigms, serial recall and serial recognition. Experiments 1 to 3 tested 7- and 8-year-old children. Memory accuracy was only mildly impaired in lists containing nonwords compared with words in a serial recognition task involving judgments of whether the items in two sequences were in the same order (Experiment 1), although a substantial advantage for word over nonword items from the same stimulus pool was found in serial recall (Experiment 2). A stronger influence of lexicality on serial recall than serial recognition was further demonstrated in Experiments 3A and 3B, and in 4A and 4B using adult participants. These experiments also established comparable degrees of sensitivity to the phonological similarity of the memory sequences in the two paradigms. The phonological similarity effect in serial recall was found to arise from increased phoneme order errors, whereas the lexicality effect was due principally to the greater frequency of phoneme identity errors for nonwords. It is proposed that the lexicality effect originates in the redintegration of item information just prior to recall, and that this process is largely bypassed in serial recognition.
Adult↗
Development of memory for pattern and path: further evidence for the fractionation of visuo-spatial memory.
Evidence from a number of sources now suggests that the visuo-spatial sketchpad (VSSP) of working memory may be composed of two subsystems: one for maintaining visual information and the other for spatial information. In this paper we present three experiments that examine this fractionation using a developmental approach. In Experiment 1, 5-, 8-, and 10-year old children were presented with a visuo-spatial working memory task (the matrices task) with two presentation formats (static and dynamic). A developmental dissociation in performance was found for the static and dynamic conditions of both tasks, suggesting that the activation of separable subsystems of the VSSP is dependent upon a static/dynamic distinction in information content rather than a visual/spatial one. A highly similar pattern of performance was found for a mazes task with static and dynamic formats. However, one strategic activity, the use of simple verbal recoding, may also have been responsible for the observed pattern of performance in the matrices task. In Experiments 2 and 3 this was investigated using concurrent articulatory suppression. No evidence to support this notion was found, and it is therefore proposed that static and dynamic visuo-spatial information is maintained in working memory by separable subcomponents of the VSSP.
Child↗
Preimplantation genetic diagnosis of compound heterozygous mutations leading to ablation of plakophilin-1 (PKP1) and resulting in skin fragility ectodermal dysplasia syndrome: a case report.
A new form of genodermatosis resulting from mutations in the gene plakophilin 1 (PKP1) has recently been identified. The clinical features of a functional knockout of PKP1 are a combination of skin fragility and a form of hypohydrotic ectodermal dysplasia. We have developed a single cell polymerase chain reaction (PCR) assay suitable for preimplantation genetic diagnosis (PGD) and here we report on the clinical application of this assay.
Biopsy↗
Working memory deficits in children with low achievements in the national curriculum at 7 years of age.
BACKGROUND: Close links between children's capacities to store and manipulate information over brief periods have been found with achievements on standardised measures of vocabulary, language comprehension, reading, and mathematics. AIM: The study aimed to investigate whether working memory abilities are also associated with attainment levels in the national curriculum assessments at 7 years of age. SAMPLE: Eighty-three children aged 6 and 7 years attending local education authority schools participated in the study. METHODS: Working memory skills were assessed by a test battery designed to tap individual components of Baddeley and Hitch's (1974) working memory model. Children were assigned to normal and low achievement groups on the basis of their performance on national curriculum tasks and tests in the areas of English and mathematics. RESULTS: Children with low levels of curriculum attainment showed marked impairments on measures of central executive function and of visuo-spatial memory in particular. A single cut-off score derived from the test battery successfully identified the majority of the children failing to reach nationally expected levels of attainment. CONCLUSIONS: Complex working memory skills are closely linked with children's academic progress within the early years of school. The assessment of working memory skills may offer a valuable method for screening children likely to be at risk of poor scholastic progress.
Aptitude Tests↗
Phonotactic influences on short-term memory.
The impact of phonotactic probabilities on serial recall was investigated in a series of experiments. In Experiments 1A and 1B, 7 and 8 year olds were tested on their serial recall of monosyllabic words and of nonwords varying in phonotactic frequencies. A recall advantage to words over nonwords remained when stimuli were balanced for phonotactic probability, but nonword recall showed superior accuracy for high over low probability nonwords, as in Experiment 2. The nonword frequency effect appears to reflect the frequency of constituent syllables rather than biphones. Both lexicality and high phonotactic frequency led to increased proportions of full over partial recall of the memory stimuli. These findings indicate that decayed memory traces in phonological short-term memory can be reconstructed using either lexical or phonotactic knowledge.
Attention↗
Verbal and visuospatial short-term memory in children: evidence for common and distinct mechanisms.
This study was designed to identify whether verbal and visuospatial short-term memory performance in children is served by common or distinct mechanisms. Five- and 8-year-old children were tested on their verbal recall of spoken letter names and digits, and on their recall of tapped sequences of blocks. The performance of the children on the verbal and visuospatial serial recall tasks was largely unrelated, extending evidence for dissociable memory systems found in adults. Detailed characteristics of recall, such as serial position functions, migration patterns, and distribution of error types, were similar in the tasks requiring recall of letters and of blocks, although order errors predominated in the block but not the letter recall task for the older children. These results appear to reflect the application of common processes specialized for the extraction of serial order information from the phonological and visuospatial components of short-term memory.
Adult↗
The distribution of alpha- and gamma-tubulin in fresh and aged human and mouse oocytes exposed to cryoprotectant.
The distribution of alpha- and gamma-tubulin in human and mouse oocytes has been investigated immunocytochemically. Comparisons have been made between freshly recovered and aged oocytes (both human and mouse), and also between human oocytes before and after exposure to cryoprotectant. Control fresh human oocytes had compact anastral spindles oriented orthogonal to the oolemma, with the pole adjacent to the oolemma being smaller than that directed towards the centre of the oocyte. Each pole was associated with a ring of particulate gamma-tubulin staining that extended a short distance into the body of the spindle. No alpha- and gamma-tubulin staining was found elsewhere in the ooplasm. Human oocytes which had failed to fertilize after an 18 h incubation with spermatozoa and had spent a further 6-8 h in culture showed an increased incidence of spindle abnormalities and of the proliferation of ooplasmic microtubules, which became more pronounced with age post-ovulation. The gamma-tubulin staining pattern of these aged human oocytes revealed greater staining over the whole of the spindle than in fresh oocytes. Examination of mouse oocytes aged in vitro or in vivo showed similar evidence of microtubule proliferation and disorganization, and the gamma-tubulin staining pattern was a sensitive indicator of ageing. The spindles of most fresh human oocytes exposed to 1.5 M dimethyl sulphoxide (DMSO) at 4 degrees C differed from controls in being slightly reduced in size or in having more pointed spindle poles with smaller diameters, both indications that some dismantling of the microtubules had occurred. The distribution of gamma-tubulin in these oocytes extended over more of the spindle. Restoration of DMSO-exposed oocytes to control medium at 37 degrees C for an extended period restored spindle structure to a state closely resembling that in controls. However, recovery of an exclusively polar gamma-tubulin staining did not occur. In both controls and DMSO-exposed human oocytes, chromosomes were arranged on the metaphase equatorial plate. In contrast, exposure of oocytes to 4 degrees C in the absence of DMSO caused dismantling of the spindle. It is concluded that (i) changes in microtubule organization with ageing of oocytes makes them unsuitable for use therapeutically after re-insemination or intracytoplasmic sperm injection, (ii) conditions of cryoprotectant addition previously found optimal for the stabilization of the spindle in the mouse oocyte also appear to be effective in stabilizing the spindle of the human oocyte, and (iii) the distribution of gamma-tubulin in relation to the spindle of the human oocyte appears to be sensitive to age and conditions.
Animals↗
Reliability and accuracy of polymerase chain reaction amplification of two unique target sequences from biopsies of cleavage-stage and blastocyst-stage human embryos.
Human embryos have been biopsied at either the cleavage or the blastocyst stage of development. One to two blastomeres were removed from cleavage-stage embryos and 2-6 cells from blastocysts. The biopsy specimens were subjected to gene amplification by the polymerase chain reaction (PCR) and a comparison made of amplification efficiencies of two unique target sequences, one located within the beta-globin gene and containing the sickle-cell locus and the other a polymorphic dinucleotide repeat. When the cleavage-stage biopsy sample consisted of an intact blastomere with a clearly discernible nucleus, an amplification efficiency of 89% was achieved for each target locus. This was similar to that achieved with cleavage-stage biopsy samples consisting of two blastomeres or with blastocyst biopsy samples consisting of 2-3 trophectoderm cells. When biopsy samples consisted of four or more trophectoderm cells, both target loci were amplified in all samples tested. When the biopsy sample was heterozygous at the dinucleotide repeat locus and the biopsy consisted of one or more intact cells with a clearly discernible nucleus, both alleles were amplified in > 80% of biopsy samples. When four or more trophectoderm cells were used for the PCR, both alleles were amplified in all heterozygous samples. Target sequences were never amplified from biopsy samples which lysed prior to transfer into the reaction tube. Analysis of DNA fragments amplified from the dinucleotide repeat locus indicated that in most cases faithful amplification of biopsy DNA template had taken place.(ABSTRACT TRUNCATED AT 250 WORDS)
Beta-Globulins↗
An analysis of multinucleated blastomere formation in human embryos.
Human embryos were disaggregated into component blastomeres 42-72 h after insemination. The blastomeres were scored for the number of nuclei present and blastomeres of known nuclear morphology were returned to individual culture drops for 16-20 h, after which they were scored for cleavage and nuclear morphology. In all, 48% of mononucleated blastomeres cleaved during this period, but only 76% of these produced two mononucleated daughter blastomeres; in the remainder, one or more of the blastomeres was abnormally nucleated. During overnight culture, 30% of multinucleated blastomeres and 30% of anucleate blastomeres cleaved, the majority producing abnormally nucleated daughter blastomeres. The majority of blastomeres which showed no sign of cleavage after overnight culture retained the same nuclear morphology as when originally disaggregated. However, a small number of mononucleated blastomeres contained two nuclei after culture, indicating that karyokinesis may have taken place in the absence of cytokinesis. Overall, approximately 30% of blastomeres with more than one nucleus seemed to arise by this mechanism, the remainder probably arising by errors of chromosome segregation and/or packaging at mitosis. In addition, 25/111 mononucleated daughter cells arose either after abnormal division of mononucleated parent cells or after division of multinucleated cells, suggesting that approximately 23% of newly formed mononucleated cells might be chromosomally abnormal. The results of DNA quantitation indicated that very few (12/131, 9.2%) blastomeres (whether uni- or multinucleated) had a DNA content outside the 2-4C range. The embryos used for these studies had been cultured in one of three commonly used in-vitro fertilization (IVF) media: modified T6, Earle's balanced salts or Universal IVF medium (a commercial medium from Medi-Cult). A retrospective analysis was carried out of the number of embryos containing multinucleated blastomeres at disaggregation and of the total proportion of isolated blastomeres which were multinucleated in three groups of embryos, each of which had been cultured in one of the IVF media. Both these parameters were found to vary between cohorts of embryos cultured in the different media. The mechanism(s) by which culture medium composition might affect multinucleation of human blastomeres is discussed, as is the significance of these data for reliable preimplantation diagnosis of genetic status.
Blastomeres↗
Use of a polymorphic dinucleotide repeat sequence to detect non-blastomeric contamination of the polymerase chain reaction in biopsy samples for preimplantation diagnosis.
Using the polymerase chain reaction (PCR), amplification of two different target DNA sequences has been achieved with high frequency using single human blastomeres as template for the duplex reaction. One sequence is located within the beta-globin gene and contains the sickle cell locus, the other is a polymorphic dinucleotide repeat, which, as well as acting as a positive control for amplification, was used to check the origin of the amplified DNA. A comparison of the sequences amplified from the blastomere with sequences amplified from parental samples confirmed that amplification of blastomeric sequences, but not extraneous contaminating DNA, had taken place in most cases. The efficacy of this system for detecting extraneous DNA was checked by deliberately contaminating single blastomeres with foreign cells. The presence of contamination was detected by the amplification of sequences not present in blastomeric DNA and which therefore must have been amplified from extraneous contaminating DNA.
Adenine↗
Cell-cycle control of a large-conductance K+ channel in mouse early embryos.
There have been few investigations into the role of ion channels in mammalian early embryonic development, despite studies showing that changes in ion channel activity accompany the early embryonic development of non-mammalian species and the proliferation of mammalian cells. Here we report that a large-conductance, voltage-activated K+ channel is active in unfertilized mouse oocytes but is rarely observed in later embryos. The channel activity is linked to the cell cycle, being active throughout M and G1 phases, and switching off during the G1-to-S transition. These changes in channel activity are accompanied by corresponding shifts in membrane potential. Inactivation of the channel during S/G2 can be prevented by exposing the oocytes to dibutyryl cyclic AMP or forskolin, an activator of adenylyl cyclase. Inhibition of protein synthesis with puromycin did not prevent inactivation of the channel at the end of G1 or its subsequent reactivation at the end of G2, indicating that the channel activity is not regulated by mitosis-promoting factor or cyclins.
Animals↗
Biopsy of the human blastocyst and polymerase chain reaction (PCR) amplification of the beta-globin gene and a dinucleotide repeat motif from 2-6 trophectoderm cells.
Cultured human blastocysts have been biopsied on day 5-6 post insemination and 2-6 extra-embryonic cells from the trophectoderm were removed and their DNA subjected to specific amplification by the polymerase chain reaction (PCR). Simultaneous amplification of part of the beta-globin gene and a dinucleotide repeat sequence has been achieved in a high percentage of cases when using the DNA from both trophectoderm cell biopsies and biopsied blastocysts as template for the PCR. A similar success rate was achieved when serial biopsies were taken from the same blastocyst, thus allowing one cell sample to be held in reserve for use should equivocal results be obtained. Over the entire experimental period (5 months), no contamination was experienced with biopsy or PCR procedures. Following biopsy of the trophectoderm cells all blastocysts had reformed a blastocoele cavity within 3-4 h of the biopsy procedure. Those blastocysts remaining in culture after this time showed a high incidence (78-83%) of hatching and outgrowth.
Anemia, Sickle Cell↗
Reliability of detection by polymerase chain reaction of the sickle cell-containing region of the beta-globin gene in single human blastomeres.
Human preimplantation embryos at various stages of development have been analysed using the polymerase chain reaction to amplify a 680 base pair fragment of the beta-globin gene. Successful amplification was achieved more frequently with DNA from intact embryos containing between one and 11 cells, single cumulus cells, oocytes which had failed to fertilize and polar bodies than from single blastomeres disaggregated from intact embryos and treated in an identical manner. The distribution of nuclei demonstrated using the nuclear chromophore diamino-phenyl-indole showed considerable inter-blastomere variation; however, no clear correlation between staining pattern and successful amplification was observed. The reason for the unreliable amplification of DNA from single blastomeres is unclear but this finding has important implications for preimplantation diagnosis of genetic disease.
Blastomeres↗
Zona pellucida modifications in the mouse in the absence of oocyte activation.
Mouse oocytes arrested in metaphase II exhibit zona hardening and a reduced fertilization rate after exposure to the cryoprotectant dimethylsulfoxide (Johnson J, In Vitro Fertil Embryo Transfer 6:168-175, 1989) but do not undergo parthenogenetic activation (Johnson and Pickering, Development 100:313-324, 1987). This paper shows that dimethylsulfoxide causes proteolytic modification of the zona pellucida glycoprotein ZP2 and inhibition of sperm binding. These effects of dimethylsulfoxide are caused by premature exocytosis of the cortical granules, a process that is initiated usually on fertilization. A model for the mechanism of action of dimethylsulfoxide is proposed based on the combined effects of cytoskeletal modification and osmotic shock. The presence of serum before and during the exposure to dimethylsulfoxide was found to reduce significantly these deleterious effects on the mouse zona pellucida without inhibiting the cortical granule release. These results highlight the suitability of dimethylsulfoxide as a tool to study the mechanisms leading to cortical granule release. Use of dimethylsulfoxide allows the separation of oocyte parthenogenetic activation from cortical granule release, and addition of serum allows separation of cortical granule release from the action of the cortical granule contents. Their use allows a dissection of the mechanisms underlying each of these three related events.
Animals↗
Cryoprotection of human oocytes: inappropriate exposure to DMSO reduces fertilization rates.
Human oocytes were exposed to the cryoprotectant dimethyl-sulphoxide (DMSO) at either 4 or 37 degrees C. Subsequent fertilization of these oocytes showed that exposure to DMSO at 37 degrees C was associated with a greatly reduced fertilization rate when compared to untreated control oocytes, whereas no such reduction was seen in oocytes exposed to DMSO at 4 degrees C. The significance of these results for the potential cryopreservation of human oocytes is discussed.
Cryopreservation↗
The incidence of abnormal morphology and nucleocytoplasmic ratios in 2-, 3- and 5-day human pre-embryos.
Human cleaving pre-embryos at 2 and 3 days and cavitated pre-embryos at 5 days post-insemination have been examined for cell number and the incidence of mononucleated cells. At least 60% of polynucleate or anucleate cells have been detected at all these stages and regardless of morphological grading at day 2. It is concluded that even by the time at which pre-embryo replacement would occur therapeutically, the majority of pre-embryos are unlikely to have full developmental potential. The possible origins of the abnormalities of nucleocytoplasmic ratios are discussed.
Blastocyst↗