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PubMed1985

Lower thresholds of motion for gratings as a function of eccentricity and contrast.

We investigated the lower threshold for motion (LTM) of gratings as a function of position in the visual field, spatial frequency and contrast and we compared motion thresholds for sine wave and square wave luminance profiles. For contrasts below 0.05 the lower threshold for motion was raised; the increase in threshold being dependent upon spatial frequency. At contrast levels above 0.05, LTM was found to be a constant velocity at any given spatial location but increased with eccentricity of view. Raised thresholds for motion at eccentric locations could be compensated by increasing the size of eccentric gratings in proportion to M-1, where M is the cortical magnification factor, a procedure which standardises the cortical representation at differing eccentricities. Thus LTM could be expressed as a constant cortical velocity for grating contrasts above 0.05 at all stimulus locations investigated. We interpret our data as support for a ratio model of velocity coding.

Adult↗
PubMed1994

Biochemistry of factor X.

Factor X circulates as a serine protease which is converted to the active form at the point of convergence of the intrinsic and extrinsic coagulation pathways. Subsequently, the enzymatic species, factor Xa, is involved in macromolecular complex formation with its cofactor factor Va, a phospholipid surface and calcium to convert prothrombin into thrombin. The gene encoding factor X shares a number of structural and organisational features in common with the other vitamin K-dependent coagulation proteins, suggesting that they have evolved from a common ancestral gene. Each of the exons encoding these proteins can be considered as a module coding for a homologous domain in each protein. These structural domains in factor X are responsible for specific functional properties including gamma-carboxylase recognition, calcium binding, phospholipid surface interaction, as well as cofactor and substrate binding. Studies of recombinant proteins and proteolytic fragments continue to provide significant insight into structure-function relationships of the protein modules within factor X.

Animals↗
PubMed2000

Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis.

BACKGROUND: Autoantibodies are a hallmark of autoimmune hepatitis, but most are not disease specific. Autoantibodies to soluble liver antigen (SLA) and to liver and pancreas antigen (LP) have been described as disease specific, occurring in about 30% of all patients with autoimmune hepatitis, but no standardised assays are available. Methods We tested 2000 serum samples from patients with various liver diseases and controls for SLA autoantibodies by inhibition ELISA. Serum samples positive for SLA antibodies were used for immunoscreening of cDNA expression libraries. Identified clones were tested against a panel of serum samples positive for SLA and LP autoantibodies and control serum samples, and the epitope mapped by deletion mutants and exonuclease digestion. FINDINGS: SLA and LP autoantibodies were identical. Of 2000 serum samples screened, 35 were positive for SLA autoantibodies. These positive samples came from patients with autoimmune hepatitis; three from patients with an overlap syndrome (primary biliary cirrhosis and secondary autoimmune hepatitis). Expression cloning and absorption experiments identified a 422 aminoacid protein present in two splice variants as the sole target antigen. Aminoacids 371-409 were critical for immune recognition. INTERPRETATION: The identified cDNA encodes the primary target antigen of SLA/LP autoantibodies. The SLA/LP antigen has a previously unknown aminoacid sequence, and presumably codes for an unindentified enzyme, suggested to be UGA-suppressor tRNA-associated protein. SLA/LP autoantibodies are disease specific and recognise a dominant epitope, suggesting a specific antigen-driven immune response. Identification of the SLA/LP target antigen will allow establishment of a reliable, widely available diagnostic assay. Furthermore, its role in the pathogenesis of autoimmune hepatitis can now be studied.

Autoantibodies↗
PubMed1979

Processing determinants of reading speed.

Two groups of university undergraduates differing in reading ability were tested on a number of reaction-time tasks designed to determine the speed of encoding visual information at several different levels. In addition, the subjects were given tests of sensory functions, verbal and quantitative reasoning ability, short-term auditory memory span, and ability to comprehend spoken text. The groups did not differ on the sensory tests. However, the faster reader group had faster reaction times on all of the reaction-time tasks, and the size of the fast-reader advantage increased with the mean reaction time. Faster readers also performed more accurately in verbal and quantitative reasoning, short-term auditory memory, and speech comprehension. Regression analyses suggested that the ability to comprehend spoken material and speed of accessing overlearned memory codes for visually presented letters represented two important independent correlates of reading ability in our sample of subjects. Two variables reflecting these abilities--the percentage of correct answers to a listening comprehension test and the reaction time for correct responses in a letter-matching task--accounted for nearly all of the variance in reading ability tapped by both of our reading tests. In a second experiment, no reaction-time difference was found between fast and average readers in a matching task requiring no long-term memory code access but considerable visual information processing as indexed by overall mean reaction time. The results supported the conclusion that one skill allowing fast readers to capture more information from each reading fixation is faster access to letter codes from print.

Concept Formation↗
PubMed1989

Molecular analysis of eight U1 RNA gene candidates from tomato that could potentially be transcribed into U1 RNA sequence variants differing from each other in similar regions of secondary structure.

From a tomato genomic library we isolated and characterized eight U1 RNA gene candidates (U1.1 to U1.8) all of which possessed the canonical plant U-snRNA transcription signals in their 5' and 3' flanking regions and exhibited nucleotide sequence conservation in the 5' splice site recognition sequence, in the Sm antigen binding site and in Loops B, C, D as well as in Stems III and IV of their coding region. Deviations from the U1 RNA consensus sequence were mainly localized to Loop A and Stems I and II, suggesting that the putative transcripts of the tomato U1.1-U1.8 genes would differ from each other in their capacity of binding to the U1 RNA-specific snRNP proteins.

Animals↗
PubMed2001

The Nod2 gene in Crohn's disease: implications for future research into the genetics and immunology of Crohn's disease.

The association of the Nod2 gene on chromosome 16 with increased susceptibility to Crohn's disease holds the promise of catalyzing fundamental genetic and therapeutic advances. Coding region variants in the leucine-rich repeat region of Nod2 may affect host interactions with bacterial lipopolysaccharide. Genetic differences in pattern-recognition proteins (such as Nod2) of the innate immune system represent an increasingly important paradigm for understanding host-environment interactions. The central problem for complex disease gene identification through genome-wide searches has been that of locus heterogeneity; it is hoped that this heterogeneity will recede with the identification of Nod2, as the first pieces of a puzzle accelerate placement of subsequent pieces. The potential for genetic approaches to positively impact the treatment of Crohn's disease and ulcerative colitis is unparalleled among complex, multigenic disorders.

Carrier Proteins↗
PubMed1998

Neural representation of objects in space: a dual coding account.

I present evidence on the nature of object coding in the brain and discuss the implications of this coding for models of visual selective attention. Neuropsychological studies of task-based constraints on: (i) visual neglect; and (ii) reading and counting, reveal the existence of parallel forms of spatial representation for objects: within-object representations, where elements are coded as parts of objects, and between-object representations, where elements are coded as independent objects. Aside from these spatial codes for objects, however, the coding of visual space is limited. We are extremely poor at remembering small spatial displacements across eye movements, indicating (at best) impoverished coding of spatial position per se. Also, effects of element separation on spatial extinction can be eliminated by filling the space with an occluding object, indicating that spatial effects on visual selection are moderated by object coding. Overall, there are separate limits on visual processing reflecting: (i) the competition to code parts within objects; (ii) the small number of independent objects that can be coded in parallel; and (iii) task-based selection of whether within- or between-object codes determine behaviour. Between-object coding may be linked to the dorsal visual system while parallel coding of parts within objects takes place in the ventral system, although there may additionally be some dorsal involvement either when attention must be shifted within objects or when explicit spatial coding of parts is necessary for object identification.

Brain↗
PubMed2000

Development of a single-code/default coding strategy in pigeons.

We tested the hypothesis that pigeons could use a cognitively efficient coding strategy by training them on a conditional discrimination (delayed symbolic matching) in which one alternative was correct following the presentation of one sample (one-to-one), whereas the other alternative was correct following the presentation of any one of four other samples (many-to-one). When retention intervals of different durations were inserted between the offset of the sample and the onset of the choice stimuli, divergent retention functions were found. With increasing retention interval, matching accuracy on trials involving any of the many-to-one samples was increasingly better than matching accuracy on trials involving the one-to-one sample. Furthermore, following this test, pigeons treated a novel sample as if it had been one of the many-to-one samples. The data suggest that rather than learning each of the five sample-comparison associations independently, the pigeons developed a cognitively efficient single-code/default coding strategy.

Animals↗
PubMed1987

Visual memory for pictorial stimuli in a serial choice reaction-time task.

Three experiments investigated the nature of the single-item visual recency effect in the serial choice reaction-time task (Rabbitt & Vyas, 1979; Walker & Marshall, 1982). The first experiment demonstrated that, like single letters varying in case, pictorial stimuli yield visual priming that is limited to consecutive stimuli and is unaffected by the presentation of an irrelevant stimulus in the response-stimulus interval. The second experiment confirmed that repeating a picture produces facilitation over and above repeating the object that it portrays. In addition, it was observed that name priming, but not visual or object priming, decreases with practice. This indicated that visual priming and object priming occur during identification. Finally, in Expt 3, an irrelevant picture was presented unpredictably in the response-stimulus interval. Previous results had suggested that this manipulation would provide evidence for distinct visual and object codes. Although the results were inconclusive, they do indicate that time intervals and presence of intervening information per se do not explain the loss of visual and object priming effects. It was suggested that the unpredictable irrelevant stimulus may have been disrupting a process whereby memory and perception interact directly at the level of a visual code.

Attention↗
PubMed2004

Effects of a gerF (lgt) mutation on the germination of spores of Bacillus subtilis.

One of the proteins of the membrane-bound receptors that recognize individual nutrients that trigger germination of spores of Bacillus subtilis contains the recognition sequence for diacylglycerol addition to a cysteine residue near the protein's N terminus. B. subtilis spores lacking the gerF (lgt) gene that codes for prelipoprotein diacylglycerol transferase exhibited significantly slowed germination in response to nutrient germinants as found previously, but germination of gerF spores with a mixture of Ca2+ and dipicolinic acid or with dodecylamine was normal, as was the spontaneous germination of gerF spores lacking all nutrient germinant receptors. The deleterious effects of the gerF mutation on nutrient germination were highest on germination triggered by the GerA nutrient receptor and were less so (but still significant) on germination triggered by the GerB nutrient receptor. However, there was little, if any, effect on GerK nutrient receptor-mediated spore germination. As predicted from the latter results, replacement by alanine of the cysteine residue to which diacylglycerol is thought to be added to these nutrient receptors had a large effect on GerA receptor function, less effect on GerB receptor function, and little, if any, effect on GerK receptor function.

Amines↗
PubMed1998

The effect of practice on the visual detection of near-threshold lines.

Two observers practised to detect small target lines of varying luminance presented either within a context of collinear inducing stimuli, or without the context in separate blocks. A two-alternative spatial-forced-choice procedure using the method of constant stimuli was employed. For blocks of 500 trials, reflecting individual performance on five successive days of training, the percentage of correct responses, and the response times were analyzed. After several thousands of trials, i.e. several weeks of practice, both observers managed to detect targets presented at their strongest luminance within the context condition. Without the context, these targets remained undetected. Response times (RT) vary nonsystematically during training. Once detection is observed at the highest target luminance, the accuracy of the individual responses (percentage of correct responses) systematically increases, and processing speed (RT) systematically decreases with increasing target intensity. These results show that, within the appropriate perceptual context, practice can lead to a better detectability of visual stimuli presented at luminance levels near detection threshold. This improvement is reflected by an optimization of the visual integration of the different luminance levels of the target (sensory coding), and processing speed (response routine) during training.

Adult↗
PubMed2003

Köbberling type of familial partial lipodystrophy: an underrecognized syndrome.

OBJECTIVE: The phenotypic expression of partial lipodystrophy is present in two familial syndromes: familial partial lipodystrophy type 1 (FPLD1), with fat loss from the extremities, and central obesity and FPLD type 2, with fat loss from the extremities, abdomen, and thorax. The latter disorder is associated with mutations in the LMNA gene. FPLD1 is thought to be rare. Here, we report 13 subjects with FPLD1, suggesting that this syndrome is more common than previously thought. RESEARCH DESIGN AND METHODS: Fasting glucose, plasma lipids, leptin, HbA(1c), and anthropomorphic measurements were evaluated in 13 subjects with clinical features of FPLD1 and are compared with two age-matched control groups, with and without diabetes. RESULTS: Only women with clinical features of FPLD1 have been identified. Although they lack extremity and gluteal subcutaneous fat, they do have truncal obesity. Skinfold thickness on the arm and leg was significantly less than that in control subjects. The ratio of skinfold thickness from abdomen to thigh was significantly higher in subjects, suggesting an easy method for identifying affected patients. FPLD1 subjects also had components of the metabolic syndrome, including hypertension, insulin resistance, and severe hypertriglyceridemia resulting in pancreatitis. Premature coronary artery disease was present in 31% of subjects. None of the subjects had coding mutations in the LMNA gene or in the gene coding for peroxisome proliferator-activated receptor (PPAR)-gamma. CONCLUSIONS: FPLD1 is more common than previously described, but the diagnosis is often missed. Early recognition and intensive treatment of hyperlipidemia and diabetes in FPLD1 is important for prevention of pancreatitis and early cardiovascular disease.

Anthropometry↗
PubMed1986

Structural analysis of human complement protein H: homology with C4b binding protein, beta 2-glycoprotein I, and the Ba fragment of B2.

We report here a partial primary structure for human complement protein H. Tryptic peptides comprising 27% of the H molecule were isolated by conventional techniques and were sequenced (333 amino acid residues). Several mixed-sequence oligonucleotide probes were constructed, based on the peptide sequence data, and were used to screen a human liver cDNA library. The largest recombinant plasmid (pH1050), which hybridized with two probes, was further characterized. The cDNA insert of this plasmid contained coding sequence (672 bp) for 224 amino acids of H. The 3' end of this clone had a polyadenylated tail preceded by a polyadenylation recognition site (ATTAAA) and a 3'-untranslated region (229 bp). Four regions of internal homology, each about 60 amino acids in length, were observed in the derived protein sequence from this cDNA clone, and a further seven from the tryptic peptide sequences. The consensus sequence for each of the repetitive units of H was four cysteines, two prolines, three glycines, one tryptophan, and two tyrosines/phenylalanines. Based on the mole percent values for each of these amino acids, it is likely that H is composed of about 20 repetitive units of this nature. Furthermore, the repetitive unit of H shows pronounced homology with the Ba fragment of B, the C4b binding protein, and beta 2-glycoprotein I. Therefore, it seems that at least portions of these proteins have evolved from a common ancestral DNA element.

Amino Acid Sequence↗
PubMed1997

[Familial hematuric nephropathies].

Alport syndrome is a hereditary hematuric nephritis progressing to end-stage renal failure, often associated with hearing loss and specific ocular changes. It is characterized by the presence of thickening and splitting of the glomerular basement membrane. Defects in type IV collagen, the main component of basement membranes, are responsible for the disease. The prevalence rate of Alport syndrome is 1/5,000 and it is the cause of about 2% of end-stage renal failure. The disease is heterogenous both at the clinical and genetic level. In most kindreds, it is transmitted as an X-linked dominant trait: males are severely affected whereas most females have a benign disease. The genes coding the different chains of type IV collagen have been cloned and several mutations have been characterized. Since prenatal counselling is now possible, the recognition of this severe familial under-diagnosed disease is of the upmost importance.

Biopsy↗