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PubMed2001

Bone structure of the distal radius and the calcaneus vs BMD of the spine and proximal femur in the prediction of osteoporotic spine fractures.

The aim of this study was to compare structure measures obtained from high-resolution MR images of the calcaneus and the distal radius with bone mineral density (BMD) of the spine and hip in the prediction of osteoporotic spine fracture status. High-resolution MR images of the calcaneus and radius were obtained in 24 post-menopausal women with spine fractures and 22 age-matched controls. Imaging was performed at 1.5 T using a T1-weighted spin-echo sequence (slice thickness 1 mm, in-plane spatial resolution 195 x 195 microm(2)). Structure analysis was performed using parameters analogous to standard histomorphometry. Bone mineral density of the spine was obtained using quantitative CT and of the hip with dual-energy X-ray absorptiometry. Significant differences between both patient groups were obtained with BMD and all structure parameters ( p<0.05). Using receiver operating characteristic analysis to determine the diagnostic performance in differentiating both groups, the best results were found for BMD of the spine, one of the radial structure measures and a combination of the calcaneal structure measures. In this study BMD of the spine and structure measures of the distal radius were best suited to predict the osteoporotic fracture status of the spine. A combination of BMD and structure measures did not yield any additional information on fracture status.

Absorptiometry, Photon↗

PubMed2005

Three-dimensional muscular architecture of the human tongue determined in vivo with diffusion tensor magnetic resonance imaging.

The myoarchitecture of the tongue is believed to consist of a complex network of interwoven fibers, which function together to produce a near limitless array of functional deformations. These deformations contribute mechanically to speech production and to oral cavity food handling during swallowing. We have previously imaged the 3D myoarchitecture of the mammalian tongue in excised tissue with diffusion tensor MRI, a technique which derives the 3D orientation of intramural fibers as a function of the extent to which a direction-specific MR signal attenuates under diffusion-encoding magnetic gradients. The resulting 3D diffusion tensor defines the relative orientations of the myofiber populations within a region of tissue. In this study, we have extended the use of this method to assess lingual myoarchitecture in normal human subjects in vivo. Subjects were imaged using a diffusion-sensitive stimulated-echo pulse sequence with single-shot echo-planar spatial encoding in the midsagittal plane. Differences in lingual fiber orientation were manifested by graduated changes in fiber direction throughout the tissue, without clear anatomical demarcations between regions of the tissue. The anterior tissue was composed generally of orthogonally oriented fibers surrounded by an axially oriented ring of tissue, whereas the posterior portion of the tissue was composed mostly of fibers projecting in the superior and posterior directions. The bulk of the tissue displayed a highly homogeneous, vertically oriented set of fibers, including the anteroinferior region of the tissue and extending nearly to the superior surface. Further analysis of the tissue in terms of diffusion anisotropy demonstrated that the tissue could be represented by varying degrees of anisotropy, with a tendency toward high anisotropy in the dorsal and anteroventral periphery and low anisotropy in the central region of the tissue. These findings demonstrate that the muscular anatomy of the tongue can be displayed as a continuous array of structural units, or tensors, representing fibers of varying orientations throughout the tissue.

Adult↗

PubMed1989

Effects of scopolamine, d-amphetamine, and apomorphine on alternation and position biases.

The sequencing of arm entries in a symmetrical Y-maze was examined in mice treated with either scopolamine, d-amphetamine or apomorphine. These treatments could potentially alter both alternation tendencies and rotational tendencies. Therefore, a measure of spontaneous alternation was evaluated which was computed by taking an average of the right going percent alternation and the left going percent alternation. The number of arm entries was increased by amphetamine, unchanged following scopolamine and reduced by apomorphine. All three drugs reduced spontaneous alternation tendencies and increased the magnitude of a bias to turn consistently in the same direction (rotational tendency). All three drugs thus altered the sequencing of arm entries from patterns consistent with spatial alteration to patterns consistent with egocentrically defined responses. These results indicate that the measure of spontaneous alternation which was an average of the right going percent alternation and the left going percent alternation is a better index of alternation tendencies. Thus, when an animal is not able to navigate on the basis of an extrapersonal (allocentric) system as a result of drug treatment, it will revert to an egocentric system.

Amphetamines↗

PubMed2004

NEUROD1 acts in vitro as an upstream regulator of NEUROD2 in trophoblast cells.

The basic helix-loop-helix (bHLH) transcription factors NEUROD1, NEUROD2 and ATH2 are expressed during first trimester human placental development. We determined the transactivation potential of each of these factors in trophoblasts by measuring changes in the endogenous gene activity using absolute quantification by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) after transient transfection. In these assays, NEUROD1 was found to transiently transactivate NEUROD2 in trophoblast cells. Promotor truncation assays, using luciferase constructs, showed the presence of two domains in the NEUROD2 promotor, which showed increased activity after NeuroD1 transfection. Each of these NeuroD1-responsive domains contains an E-box sequence. The NEUROD2 transactivation data fit with the spatial expression pattern of NEUROD1 and NEUROD2, since they are expressed in endovascular trophoblasts. This expression pattern, as well as the present transactivation results, might suggest the presence of a NEUROD differentiation cascade during first trimester human placental development.

Basic Helix-Loop-Helix Proteins↗

PubMed2006

Sleep-dependent consolidation of contextual learning.

Memory consolidation is facilitated by sleep. Specifying the functional domain of sleep-dependent consolidation (SDC) is important for identifying the neural mechanisms underlying this phenomenon. Previous work indicates that SDC may be limited to conditions in which learning is explicit. In the present study, we tested the hypothesis that SDC may also occur with implicit learning when learning benefits from the formation of contextual associations, a function associated with the hippocampus. Three versions of the serial-reaction-time task (SRTT) were examined, and SDC was assessed by comparing performance after 12 hr breaks that included or did not include sleep. SDC was observed in the Explicit condition. Two implicit conditions were compared. In the Implicit Noncontextual condition, participants performed a concurrent tone-counting task with the pitch of each tone selected at random, precluding cross-dimensional associations. In the Implicit Contextual condition, participants responded to the color of the cues while the spatial location of the cues followed a correlated sequence. Whereas learning was observed in both implicit conditions, SDC was restricted to the contextual condition. Given that the formation of contextual associations is dependent on the hippocampus, we suggest that SDC is a hippocampus-mediated process.

Awareness↗

PubMed2004

Impulsivity in youth predicts early age-related cognitive deficits in rats.

Impulsivity is a feature of psychiatric disorders such as mania, addictive behaviors or attention deficit-hyperactivity disorder (ADHD), which has recently been related to complaints of forgetfulness in adults. We investigated whether impulsiveness exerts a long-term influence on cognitive function in rats in a longitudinal study. Impulsivity, assessed by the ability to complete a sequence of presses to obtain food (conditioning box), spatial working memory (8-arm radial maze) assessed with varying degree of attentional load and recognition memory (Y-maze) were tested at different ages. Marked individual differences in impulsivity were observed at youth and remained stable at middle-age despite a general decline in the trait. Working memory scores of impulsive and non-impulsive rats did not differ in youth, whereas by middle-age the impulsive group had impaired working memory and was more sensitive to a higher attentional demand. Thus, impulsiveness in youth predicts cognitive performance in middle-age. These findings may help refine the search for early biological substrates of successful aging and for preventive follow-up of subjects at risk of impaired cognitive aging.

Age Factors↗

PubMed2004

Variability and genetic structure of the population of watermelon mosaic virus infecting melon in Spain.

The genetic structure of the population of Watermelon mosaic virus (WMV) in Spain was analysed by the biological and molecular characterisation of isolates sampled from its main host plant, melon. The population was a highly homogeneous one, built of a single pathotype, and comprising isolates closely related genetically. There was indication of temporal replacement of genotypes, but not of spatial structure of the population. Analyses of nucleotide sequences in three genomic regions, that is, in the cistrons for the P1, cylindrical inclusion (CI) and capsid (CP) proteins, showed lower similar values of nucleotide diversity for the P1 than for the CI or CP cistrons. The CI protein and the CP were under tighter evolutionary constraints than the P1 protein. Also, for the CI and CP cistrons, but not for the P1 cistron, two groups of sequences, defining two genetic strains, were apparent. Thus, different genomic regions of WMV show different evolutionary dynamics. Interestingly, for the CI and CP cistrons, sequences were clustered into two regions of the sequence space, defining the two strains above, and no intermediary sequences were identified. Recombinant isolates were found, accounting for at least 7% of the population. These recombinants presented two interesting features: (i) crossover points were detected between the analysed regions in the CI and CP cistrons, but not between those in the P1 and CI cistrons, (ii) crossover points were not observed within the analysed coding regions for the P1, CI or CP proteins. This indicates strong selection against isolates with recombinant proteins, even when originated from closely related strains. Hence, data indicate that genotypes of WMV, generated by mutation or recombination, outside of acceptable, discrete, regions in the evolutionary space, are eliminated from the virus population by negative selection.

Citrullus↗

PubMed2000

Diagnostic utility of tumor vascularity on magnetic resonance imaging of the breast.

The objective of this study was to examine the relation of tumor vascularity on magnetic resonance imaging (MRI) with differential diagnosis malignant from benign lesions and tumor invasiveness in breast carcinoma. Forty-nine patients with breast cancer or benign lesion (median 49 yrs) were examined with dynamic MRI. Scanning of the entire breast was performed at 1.5 T with a three-dimensional fast spin echo sequence, using an original polarity altered spectral and spatial selective acquisition (PASTA) technique for fat suppression. Subsequently 0.1 mmol/Kg Gd-DTPA was administered and 3-6 images were obtained. The presence or absence of intratumoral, marginal and peritumoral vascularity on MRI was recorded. The excised specimen was histopathologically examined for the size of lesion, the presence and extent of local invasion. Tumor size on MRI correlated closely with the size at morphologic examination (r = 0. 96). Intratumoral (p = 0.04), marginal (p = 0.05) and peritumoral vascularity (p = 0.01) were less common in benign than in malignant lesions. Among the latter, intratumoral (p = 0.01) and marginal (p = 0.03) vascularity were more common in invasive carcinomas than in DCIS. In the subset of invasive carcinomas (n = 31); however, the tumors exhibiting intratumoral vascularity were markedly larger (p = 0.03). The presence of intratumoral and marginal vascularity on MRI can help predict both the differential diagnosis malignant from benign lesions and the presence tumor invasion in breast carcinomas.

Adolescent↗

PubMed1999

Measuring facial expressions by computer image analysis.

Facial expressions provide an important behavioral measure for the study of emotion, cognitive processes, and social interaction. The Facial Action Coding System (Ekman & Friesen, 1978) is an objective method for quantifying facial movement in terms of component actions. We applied computer image analysis to the problem of automatically detecting facial actions in sequences of images. Three approaches were compared: holistic spatial analysis, explicit measurement of features such as wrinkles, and estimation of motion flow fields. The three methods were combined in a hybrid system that classified six upper facial actions with 91% accuracy. The hybrid system outperformed human nonexperts on this task and performed as well as highly trained experts. An automated system would make facial expression measurement more widely accessible as a research tool in behavioral science and investigations of the neural substrates of emotion.

Adult↗

PubMed1991

Metastable motion anisotropy.

The phenomenon of apparent motion can arise when two spatially separated visual tokens are presented in temporal sequence. If tokens at opposite corners of a hypothetical square are presented simultaneously followed by simultaneous presentation of tokens at the remaining two corners, an apparent motion percept may occur along either the vertical or horizontal axis. The display is perceptually metastable since most observers will perceive motion along only one axis at a time. The metastable display, however, produces anisotropic results, in that with central fixation, vertical motion is seen more frequently than horizontal motion. The ratio of the vertical to horizontal length of the sides of a rectangle needed to achieve equal frequencies of motion judgments along the respective axes falls in the range of 1.18-1.92 for different observers in our experiments. It appears that signal transmission across the vertical midline is a major determinant of the vertical bias, since the anisotropic effects disappear when the fixation point is sufficiently offset along the horizontal meridian so as to cause a fully homonymous representation of all of the metastable tokens. One of the factors may be signal degradation or delay in callosal transmission which could reduce the strength of the motion signal along the horizontal axis. In addition, there appears to be a strip along the vertical midline with a width of 30-50 min arc within which reduced levels of anisotropy are found. The possibility that this strip is a consequence of a zone of naso-temporal overlap in the projection of the retina to the brain along the vertical meridian will be discussed.

Anisotropy↗

PubMed1986

Two-dimensional 1H NMR studies of cytochrome c: assignment of the N-terminal helix.

The 1H resonances of 11 sequential amino acids in the N-terminal helix of horse ferrocytochrome c were studied by two-dimensional nuclear magnetic resonance techniques. All the main-chain protons from Lys-5 through Ala-15 and many of the side-chain protons were assigned. J-Correlated spectroscopy (COSY) was used to distinguish protons on neighboring bonds and to recognize amino acid types. Nuclear Overhauser effect spectroscopy (NOESY) was used to define spatially contiguous protons and to determine amino acid sequence neighbors. The relayed coherence experiment (relay COSY) was used to resolve many ambiguities in intraresidue J-coupled connectivities and interresidue NOE connectivities. This required no explicit knowledge of the solution structure. The pattern of NOEs found is consistent with a regular alpha helix between glycine-6 and lysine-13; H bonding continues at least through alanine-15 [see Wand, A.J., Roder, H., & Englander, S. W. (1986) Biochemistry (following paper in this issue)]. Chain disorder occurs at the N-terminus. There is no indication of significant spin diffusion among the backbone amide and alpha-protons of this 12.4-kilodalton protein even at the longest NOE mixing time used (140 ms).

Amino Acid Sequence↗

PubMed1999

A novel E-type endo-beta-1,4-glucanase with a putative cellulose-binding domain is highly expressed in ripening strawberry fruits.

Two full-length cDNA clones (faEG1 and faEG3, respectively) have been isolated by screening a cDNA library representing transcripts from red strawberry fruits. Southern blot analysis of genomic DNA suggests that the strawberry endo-beta-1,4-glucanases (EGases) are encoded by a multigene family. The cognate genes are predominantly expressed during the ripening process proper, although, in the case of faEG3, some expression has also been observed in large green fruits and, at low amounts, in young vegetative green tissues. In agreement with other ripening-related genes in strawberry, also the expression of faEG1 and faEG3 is down-regulated by treatment with an auxin analogue (1-naphthaleneacetic acid, NAA). Differences in temporal expression of the two EGase genes in fruits are not accompanied by differences in spatial expression. The pattern of expression and the sequence characteristics of the two polypeptides suggest that the two strawberry EGases operate in a synergistic and coordinate manner. The protein encoded by faEG1 looks like one of the usual higher-plant EGases (average molecular mass of 54 kDa), while the protein encoded by faEG3 has a greater deduced molecular mass (about 68 kDa) due to the presence of an extra peptide of about 130 amino acids at the C-terminus. Such unusual peptide shows some features also found in microbial cellulases and contains a putative cellulose-binding domain. We propose that the faEG3-encoded EGase might especially hydrolyse the xyloglucans coating the cellulose microfibrils, thus rendering the cell wall more susceptible to the subsequent hydrolytic activity of the faEG1-encoded EGase.

Amino Acid Sequence↗

PubMed2002

[Twelve years experience in Switzerland: Quo vadis BSE?].

When the first BSE case in Switzerland became public in 1990, it precipitated a chain of events with many diverse consequences. During this time, we continued to gain knowledge, implement new measures, and make practical recommendations in order to attempt to control the disease. This was made possible by the establishment of a huge data base containing information on all cases of BSE that had been diagnosed in Switzerland, as well as by the use of information from experiences in other countries. Analysis of these data allowed the sequence of events to be described temporally and spatially and an epidemiological evaluation to be made. These data also allow predictions to be made regarding the future of BSE in Switzerland, although these predictions must be interpreted cautiously.

Animals↗

PubMed1982

Binding with lysozyme of antibodies against surface-simulation peptides representing the lysozyme antigenic sites.

Previously it had been shown that native lysozyme has three discontinuous antigenic sites (comprising spatially adjacent residues that may be distant in sequence) that were mimicked by surface-simulation synthetic peptides that had the capacity to bind the bulk (97-99%) of the antibody response against native lysozyme. In the present work these three surface-simulation synthetic peptides were coupled to succinoylated bovine serum albumin, and the conjugates were injected into rabbits. Antibodies against each peptide reacted, as expected, only with that peptide, but it was also found that the antibodies could bind with lysozyme, and the complete specificity of this binding was rigorously established. The advantages of these findings in conformational and immunological investigations are outlined.

Antibodies↗

PubMed2000

[(23)sodium MRI for infarct imaging of the human heart].

PURPOSE: Sodium is elevated in acute/subacute myocardial infarction due to three distinct mechanisms: Breakdown of ion homeostasis with accumulation of intracellular sodium, extracellular edema formation and, during scar formation, increase of extracellular vs. intracellular space as cardiomyocytes are replaced by connective tissue. 23Na MRI has previously been shown to have the potential to demonstrate myocardial infarction in an animal model. Aim of this study was, therefore, to demonstrate myocardial infarction with the use of 23Na-MRI in patients. MATERIAL AND METHODS: 10 patients were examined 14 +/- 7 days after first myocardial infarction using a 23Na surface coil at 1.5 T. Double angulated short axis images of the entire heart were imaged using an ECG-triggered 3d-FLASH-sequence (FOV, 450 mm; matrix, 64 x 128; spatial resolution, 3.5 x 7 mm2; slice thickness, 16 mm; 32 acquisitions). Areas of elevated sodium signal intensity were correlated with infarct-related wall motion abnormalities imaged by Cine MRI in breathhold-technique. RESULTS: All patients showed an area of elevated sodium signal intensity that correlated well with the clinically determined localization of myocardial infarction as well as with regional wall motion abnormalities detected by Cine MRI. CONCLUSIONS: Elevated 23Na MR image signal intensity demonstrates subacute myocardial infarction in patients.

Aged↗

PubMed1985

Apparent motion of subjective surfaces.

Apparent motion of an illusory surface was produced by presenting two spatially separated illusory squares in an appropriately timed sequence. Control experiments showed that the effect arose from the illusory contours themselves and not from motion of the cut sectors on the discs. When a template of this movie was superimposed on 'wallpaper' composed of a regular matrix of spots, the spots appeared to move with the illusory surface even though they were physically stationary. This effect ('motion capture') suggests that the motion of certain salient features in the visual field gets spontaneously attributed to even static elements in the vicinity.

Fixation, Ocular↗

PubMed2004

Compound library development guided by protein structure similarity clustering and natural product structure.

To identify biologically relevant and drug-like protein ligands for medicinal chemistry and chemical biology research the grouping of proteins according to evolutionary relationships and conservation of molecular recognition is an established method. We propose to employ structure similarity clustering of the ligand-sensing cores of protein domains (PSSC) in conjunction with natural product guided compound library development as a synergistic approach for the identification of biologically prevalidated ligands with high fidelity. This is supported by the concepts that (i) in nature spatial structure is more conserved than amino acid sequence, (ii) the number of fold types characteristic for all protein domains is limited, and (iii) the underlying frameworks of natural product classes with multiple biological activities provide evolutionarily selected starting points in structural space. On the basis of domain core similarity considerations and irrespective of sequence similarity, Cdc25A phosphatase, acetylcholinesterase, and 11beta-hydroxysteroid dehydrogenases type 1 and type 2 were grouped into a similarity cluster. A 147-member compound collection derived from the naturally occurring Cdc25A inhibitor dysidiolide yielded potent and selective inhibitors of the other members of the similarity cluster with a hit rate of 2-3%. Protein structure similarity clustering may provide an experimental opportunity to identify supersites in proteins.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1995

Contact with the N termini in the central E domain enhances the reactivities of the distal D domains of fibrin to factor XIIIa.

The reaction of Factor XIIIa with fibrin is the last enzyme-catalyzed step on the coagulation cascade, leading to the formation of a normal blood clot. The finding that fibrin is preferred by the cross-linking enzyme about 10-fold over the circulating fibrinogen suggests the operation of a unique substrate-level control for the orderly functioning of the physiological process in the forward direction. An important task is to elucidate the molecular mechanism for the transmission of the signal generated by the thrombin-catalyzed cleavage in the central E domain of fibrin to the distant Factor XIIIa-reactive glutamine residues. By focusing on the substrate sites present in gamma chain remnants of D type domains of fibrinogen and by employing the approach of fragment complementation with the regulatory E domain, which represents the thrombin-modified portion of fibrin, we have now succeeded in reconstructing in solution the phenomenon of kinetic enhancement for the reaction with Factor XIIIa. Two D type preparations (truncated fibrinogen, approximately 250 kDa and D', approximately 105 kDa) were obtained by digestion of human fibrinogen with endo Lys-C. Neither product could be cross-linked by Factor XIIIa, but as shown by the incorporation of dansylcadaverine, both were acceptor substrates for the enzyme. The plasmin-derived D (approximately 105-kDa) product, however, could be cross-linked into DD dimers. In all cases, the admixture of E fragments exerted a remarkable boosting effect on the reactions with Factor XIIIa. Even with native fibrinogen as substrate, cross-linking of gamma chains was enhanced in the presence of E. Nondenaturing electrophoresis was used to demonstrate the complex forming potential of E fragments with fibrinogen, truncated fibrinogen, D', or D. The GPRP tetrapeptide mimic of the GPRV N-terminal sequence of the alpha chains in the E fragments, abolished both complex formation and the kinetic boosting effect of E on the reactions of substrates with Factor XIIIa. Thus, the N-terminal alpha chain sequences seem to act as organizing templates for spatially orienting the D domains, probably during the protofibrillar assembly of the fibrin units, for favorable reaction with Factor XIIIa.

Binding Sites↗