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DNA spatial considerations in the arrangement of G/C and A/T blocks.

Intensive computations have been carried out on eukaryotic and prokaryotic DNA sequences present in the GenBank database. These calculations were aimed at studying particular sequence patterns. Previously we have observed a trend in the relative positioning of DNA oligomers with respect to each other. Specifically, we have shown that there is a preference for A/T stretches to be inserted inside G/C blocks, partitioning the latter. This arrangement is preferred over having a longer G/C block with an A/T stretch next to it. That is (G/C)n(A/T)m(G/C)2 greater than (G/C)n + 2(A/T)m. Previously we have attributed this preferred pattern to nucleosome packaging of the DNA. Since the average length of the DNA involved in a single nucleosome formation is 200 bp, oligomers were scored in the analysis only if two identical ones occurred within that distance. Since, in addition, the total length of the oligomers studied is n + m + 2 less than or equal to 7, the counts of the longer oligomers were quite low. Here we have repeated the analysis on the newer, larger database, with that restriction removed. Our new analysis confirms and strengthens the older findings. Moreover, we have carried out DNA structural analysis of these trends, focusing on the twist and roll angular parameters. We have obtained these values from detailed structural computations on the Cray super computer. Some correlations between these values, DNA flexibility and the sequence trends are observed. We suggest that the positioning of the (A/T)m sequence stretch between the two (G/C) blocks affords greater flexibility in the spatial positioning of the G/C sequence elements.

Base Sequence↗

Optimization of three-dimensional T1-weighted gradient-echo imaging of the cervical spine.

Various parameters of the three-dimensional (3D) T1-weighted magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequence were evaluated to improve spatial resolution while maintaining T1 contrast and a short examination time in imaging of the cervical spine in volunteers. The most dramatic improvements in image resolution occurred by decreasing section thickness to 1.2 mm and increasing the in-plane matrix to 192 x 256, with a 230-mm field of view. The increase in imaging time due to the increased matrix was offset by the elimination of the preparation pulse and wait time, without dramatic changes in contrast-to-noise ratio or overall image quality. Optimum parameters included elimination of the preparation pulse and wait time, 12 degrees flip angle, 192 x 256 matrix, 1.2-mm section thickness, nonselective excitation (coronal acquisition), RF spoiling, and standard k-space ordering, for an examination time of 5 minutes 21 seconds.

Cervical Vertebrae↗

Incremental hydraulic jaw opener for MR imaging of the temporomandibular joint.

Magnetic resonance (MR) imaging in the open- and closed-mouth positions is the method of choice for visualizing the temporomandibular joint (TMJ). To analyze the TMJ in response to various degrees of mouth opening, the authors constructed a hydraulic incremental jaw opener. This apparatus enables obtaining of reproducible and stable positions of TMJ articulation. With modified gradient pulse sequences, the technique yields good spatial resolution of joint anatomy, including that of the articular disk. The application of a cine program allows cinematographic display of TMJ motion, which in conjunction with static open- and closed-mouth views can be useful in the diagnosis of TMJ dysfunction. The authors used the incremental jaw opener to examine the disk-condyle complex at each open-mouth position, with particular attention to extreme open-mouth positions.

Equipment Design↗

Incorporating lactate/lipid discrimination into a spectroscopic imaging sequence.

A spectroscopic imaging sequence incorporating a two-shot lactate editing method was used in two human brain studies to image lactate and NAA. The subtractive editing method allows separate images of lactate, NAA, and lipids to be collected during a single study with no SNR penalty. The sequence uses a spectral-spatial excitation for slice selection and water suppression, and employs inversion recovery and an echo time of 136 ms for additional lipid suppression.

Aspartic Acid↗

3D fluoroscopy with real-time 3D non-cartesian phased-array contrast-enhanced MRA.

For optimized CE-MRA of the chest and abdomen, the scan time and breath-hold must be coordinated with the arrival of contrast. A 3D fluoroscopy system is demonstrated that performs real-time 3D projection reconstruction acquisition, reconstruction, and visualization using only the standard scanner hardware and operator console workstation. Unlike 2D fluorotriggering techniques, no specification of a monitoring slab or careful placement of the imaging volume is required. 3DPR data are acquired continuously throughout the examination using an eight-channel receiver and 1 s interleaved subframes. The data are reconstructed using 1 s segments for real-time monitoring with 0.8-cm isotropic spatial resolution over the entire torso, allowing full-volume axial, coronal, and sagittal MIPs to be displayed simultaneously with minimal latency. The system later uses the same scan data to generate high-spatial-resolution time-resolved sequences of the breath-hold interval. The 3D fluoroscopy system was validated on phantoms and human volunteers.

Artifacts↗

Expression patterns of Hoxb genes in the Xenopus embryo suggest roles in anteroposterior specification of the hindbrain and in dorsoventral patterning of the mesoderm.

Hox genes are thought to participate in patterning the anteroposterior (a-p) axis during vertebrate embryogenesis. In this investigation, the spatial expression of six Hoxb genes was analyzed in early embryos of Xenopus laevis by in situ hybridization. Hoxb gene expression was first detected in late gastrulae/early neurulae, by which stage, the characteristic spatially colinear Hoxb gene expression sequence was already apparent. Dissection experiments indicated that the establishment of these localized expression patterns coincides with the acquisition of anteroposterior positional information along the main body axis. The Hoxb genes continued to be expressed in similar domains along the anteroposterior axis at all developmental stages examined, although there were some changes in expression at the cellular level. Interestingly, the 3' genes, Hoxb-1, Hoxb-3, and Hoxb-4 were expressed in very restricted domains in the future hindbrain, while Hoxb-5, Hoxb-7, and Hoxb-9 transcripts were present along the entire presumptive spinal cord. It was thus notable that the 5' Hoxb genes exhibited different types of expression domain than the 3' Hoxb genes. These observations suggest that there may be different mechanisms regulating the expression of the 3' and 5' Hoxb genes. Expression of all of the Hoxb genes analyzed, except Hoxb-4, was predominantly detectable in the central nervous system or in neural crest-derived structures. Hoxb-4 mRNA was detected in the central nervous system, but interestingly, the major expression site for this gene was the somites. The other Hoxb genes tested failed to show significant expression in the somitic mesoderm, although transcripts from genes 5' from Hoxb-4 were detected in other mesodermal tissues. In the vertebrate trunk, anteroposterior patterning of the CNS is thought to be regulated by the somites. The results obtained here for Xenopus embryos did not explicitly support the idea of a Hoxb code for the somites, although we cannot rule this out. Instead, interestingly, the data were consistent with a role for Hoxb genes in dorsoventral patterning of the mesoderm.

Animals↗

Lactate mapping with full sensitivity by spin-filtered NMR imaging.

The mechanism of the fourfold signal loss during the cyclic polarization-transfer (CYCLPOT) sequence for lactate filtering is analyzed using the spin-product-operator formalism. Based on the results of the analysis, a new sequence, RECYCLPOT (refocused CYCLPOT), is proposed and experimentally tested for lactate filtering with full sensitivity and specificity. Lactate mapping is performed by spin filtering using the RECYCLPOT sequence prior to imaging by spatial encoding.

Animals↗

Phyletic relationships of protein structures based on spatial preference of residues.

A structure-based scoring matrix MDPRE was derived from amino acid spatial preferences in protein structures. Sequence alignment and evolutionary studies by using MDPRE matrix gave similar results as those from ordinary sequence and structure alignments. It is interesting that a matrix derived from structure data solely could give comparable alignment results, strongly indicating the intimate connection between protein sequences and structures. The branch order and length from this approach were close to those obtained by a structure comparison method. Thus, by applying this structure-based matrix, the trees obtained should reflect evolutionary characteristics of protein structure. This approach takes advantage over a direct structure comparison in that (1) only a sequence and MDPRE matrix are needed, making it simple and widely applicable (especially in the absence of 3-dimensional protein structure data); (2) an established algorithm for sequence alignment and tree building could be employed, providing opportunities for direct comparison between matrices from different methodologies. One of the most striking features of this method is its capability to detect protein structure homologies when the sequence identities are low. This was well reflected in the given examples of the alignment of dinucleotide-binding domains.

Amino Acid Sequence↗

Sequential movement representations based on correlated neuronal activity.

We tested the hypothesis that sequential movements are represented in the correlated activity of motor cortical neurons. We simultaneously recorded multiple single neurons in the motor cortex while monkeys performed a two-segment movement sequence. Before any movement began the correlated spike firing between pairs of neurons differed when these sequences were planned as whole (planned) as compared to when they were planned one segment at a time (unplanned) even when the firing rates of these neurons did not distinguish between the two conditions. Moreover, the correlation strength was significantly larger when the directional preferences of the neurons matched the direction of the final segment of the sequence. Our results suggest that spatially distributed groups of MI neurons form dynamic correlation structures that distinguish different forms of sequential action.

Animals↗

Mapping drug-induced changes in cerebral R2* by Multiple Gradient Recalled Echo functional MRI.

A multiple Gradient Recalled Echo MRI sequence was used to map spatial and temporal changes in the rate of MR signal decay (R2*) in response to L-3,4-dihydroxyphenylalanine (levodopa) in the striatal dopaminergic system of a rhesus monkey unilaterally lesioned with 4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP). R2* decreased significantly in the right (dopamine depleted) putamen and caudate following levodopa. More focal areas of smaller R2* decline were also observed in these structures in the left hemisphere. The observed spatial and temporal patterns of R2* change support the view that the method is monitoring changes in neural activity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

What is the relationship between synaesthesia and visuo-spatial number forms?

This study compares the tendency for numerals to elicit spontaneous perceptions of colour or taste (synaesthesia) with the tendency to visualise numbers as occupying particular visuo-spatial configurations (number forms). The prevalence of number forms was found to be significantly higher in synaesthetes experiencing colour compared both to synaesthetes experiencing taste and to control participants lacking any synaesthetic experience. This suggests that the presence of synaesthetic colour sensations enhances the tendency to explicitly represent numbers in a visuo-spatial format although the two symptoms may nevertheless be logically independent (i.e. it is possible to have number forms without colour, and coloured numbers without forms). Number forms are equally common in men and women, unlike previous reports of synaesthesia that have suggested a strong female bias. Individuals who possess a number form are also likely to possess visuo-spatial forms for other ordinal sequences (e.g. days, months, letters) which suggests that it is the ordinal nature of numbers rather than numerical quantity that gives rise to this particular mode of representation. Finally, we also describe some consequences of number forms for performance in a number comparison task.

Adult↗

Establishing a clinical cardiac MRI service.

After several years of research development cardiovascular MRI has evolved into a widely accepted clinical tool. It offers important diagnostic and prognostic information for a variety of clinical indications, which include ischaemic heart disease, cardiomyopathies, valvular dysfunction and congenital heart disorders. It is a safe non-invasive technique that employs a variety of imaging sequences optimized for temporal or spatial resolution, tissue-specific contrast, flow quantification or angiography. Cardiac MRI offers specific advantages over conventional imaging techniques for a significant number of patients. The demand for cardiac MRI studies from cardiothoracic surgeons, cardiologists and other referrers is likely to continue to rise with pressure for more widespread local service provision. Setting up a cardiac MRI service requires careful consideration regarding funding issues and how it will be integrated with existing service provision. The purchase of cardiac phased array coils, monitoring equipment and software upgrades must also be considered, as well as the training needs of those involved. The choice of appropriate imaging protocols will be guided by operator experience, clinical indication and equipment capability, and is likely to evolve as the service develops. Post-processing and offline analysis form a significant part of the time taken to report studies and an efficient method of providing quantitative reports is an important requirement. Collaboration between radiologists and cardiologists is needed to develop a successful service and multi-disciplinary meetings are key component of this. This review will explore these issues from our perspective of a new clinical cardiac MRI service operating over its first year in a teaching hospital imaging department.

Cardiovascular Diseases↗

Efficient prediction of nucleic acid binding function from low-resolution protein structures.

Structural genomics projects as well as ab initio protein structure prediction methods provide structures of proteins with no sequence or fold similarity to proteins with known functions. These are often low-resolution structures that may only include the positions of C alpha atoms. We present a fast and efficient method to predict DNA-binding proteins from just the amino acid sequences and low-resolution, C alpha-only protein models. The method uses the relative proportions of certain amino acids in the protein sequence, the asymmetry of the spatial distribution of certain other amino acids as well as the dipole moment of the molecule. These quantities are used in a linear formula, with coefficients derived from logistic regression performed on a training set, and DNA-binding is predicted based on whether the result is above a certain threshold. We show that the method is insensitive to errors in the atomic coordinates and provides correct predictions even on inaccurate protein models. We demonstrate that the method is capable of predicting proteins with novel binding site motifs and structures solved in an unbound state. The accuracy of our method is close to another, published method that uses all-atom structures, time-consuming calculations and information on conserved residues.

Binding Sites↗

Distal regulatory regions restrict the expression of cis-linked genes to the tapetal cells.

The oleosin glycine-rich protein genes Atgrp-6, Atgrp-7, and Atgrp-8 occur in clusters in the Arabidopsis genome and are expressed specifically in the tapetum cells. The cis-regulatory regions involved in the tissue-specific gene expression were investigated by fusing different segments of the gene cluster to the uidA reporter gene. Common distal regulatory regions were identified that coordinate expression of the sequential genes. At least two of these genes were regulated spatially by proximal and distal sequences. The cis-acting elements (122 bp upstream of the transcriptional start point) drive the uidA expression to floral tissues, whereas distal 5' upstream regions restrict the gene activity to tapetal cells.

Arabidopsis↗

Temporal asymmetry in motion masking: a shortening of the temporal impulse response function.

Morgan and Chubb observed a striking temporal asymmetry in motion masking (Vis. Res. 39 (1999) 4217). Motion was produced with a two-frame sequence of gratings presented in spatial quadrature phase; the second grating (100 ms) was presented immediately after the first grating (100 ms), with no temporal overlap. The contrast threshold for detecting the direction of motion of the stimulus pair was facilitated when the first grating was of low-contrast and the second grating was of high-contrast, but strong masking occurred when the order was reversed, so the high-contrast grating came first. We replicated this result, but showed that the masking mostly disappeared when the two gratings temporally overlapped only slightly. The high sensitivity to the precise temporal pattern of the stimulus can be explained by a small temporal 'shortening' of the temporal impulse response function (IRF) as stimulus contrast is increased. The IRF is biphasic with a negative inhibitory lobe. When the first grating has high-contrast, its flash response (owing to the shortening of the IRF) may be in a fairly strong negative phase by the time that the positive response to the second, lower-contrast grating has reached appreciable strength--this reduces the magnitude of the motion signal generated by the two flashes and can account for the masking. A shortening of the IRF with increased contrast (a nonlinearity) is supported by psychophysical studies in humans and by recordings of magnocellular retinal ganglion cells in macaque, and the present results bolster this concept.

Contrast Sensitivity↗

Regulatory context is a crucial part of gene function.

Information about the time and place of gene transcription, which until recently was only possible by extensive experimental analysis, can now be predicted through in silico analysis. Using the human RANTES/CCL5 promoter, we show that organizational features of promoters derived from promoter sequences contain information about the spatial and temporal 'functional context' of expression.

Animals↗

Poroelastography: imaging the poroelastic properties of tissues.

In the field of elastography, biological tissues are conveniently assumed to be purely elastic solids. However, several tissues, including brain, cartilage and edematous soft tissues, have long been known to be poroelastic. The objective of this study is to show the feasibility of imaging the poroelastic properties of tissue-like materials. A poroelastic material is a material saturated with fluid that flows relative to a deforming solid matrix. In this paper, we describe a method for estimating the poroelastic attributes of tissues. It has been analytically shown that during stress relaxation of a poroelastic material (i.e., sustained application of a constant applied strain over time), the lateral-to-axial strain ratio decreases exponentially with time toward the Poisson's ratio of the solid matrix. The time constant of this variation depends on the elastic modulus of the solid matrix, its permeability and its dimension along the direction of fluid flow. Recently, we described an elastographic method that can be used to map axial and lateral tissue strains. In this study, we use the same method in a stress relaxation case to measure the time-dependent lateral-to-axial strain ratio in poroelastic materials. The resulting time-sequenced images (poroelastograms) depict the spatial distribution of the fluid within the solid at each time instant, and help to differentiate poroelastic materials of distinct Poisson's ratios and permeabilities of the solid matrix. Results are shown from finite-element simulations.

Elasticity↗

Rule learning in a serial reaction time task: an fMRI study on patients with early Parkinson's disease.

In the present study, we investigated implicit rule learning in patients with Parkinson's disease (PD) and healthy participants. Functional magnetic resonance imaging (fMRI) and a variant of the serial reaction time task were employed to examine the performance of previously learned regular sequences. Participants responded to successively appearing visual stimuli by pressing spatially corresponding keys. Unbeknownst to them, a cycling 12-item sequence was presented. In order to measure rule learning independently from initial visuomotor learning, participants were trained with the sequence prior to scanning. In the fMRI session, alternating blocks of regular and random stimuli were performed. Imaging revealed activations in the frontomedian and posterior cingulate cortex during performance of sequence blocks as opposed to random blocks. The magnitude of activations in these two areas was correlated with the behavioral index for rule learning. As has been reported earlier, the frontomedian cortex may be involved in the prediction of future stimuli and anticipation of corresponding actions, whereas the posterior cingulate activation may rather be related to memory retrieval. Additional activations of the right putamen and the inferior frontal sulcus were not related to behavioral performance. In patients with early PD, the behavioral data showed reduced training effects during pretraining, but intact rule learning during the fMRI session. Imaging revealed highly similar frontomedian and posterior cingulate activations in patients and controls, in the absence of significant striatal and inferior frontal activations in patients. Our findings support the view that in early PD, with the lateral striatofrontal dopaminergic projections being affected, medial dopaminergic projections involved in the application of previously learned rules may still be spared.

Aged↗