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Results for “spatial sequencing”

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At least 1,477 records · Page 82Linked to original sources

PubMed1999

Flow effects in localized quadratic, partial Fourier MRA.

A pulse sequence for inflow-enhanced magnetic resonance angiography, including localized quadratic encoding, partial-Fourier slice selection, and spiral in-plane encoding, is analyzed. The through-plane encoding method is discussed in a space-spatial frequency context to illustrate some of its properties. This pulse sequence has the advantages of being faster and more robust to turbulent flow than conventional inflow-enhanced methods. Simulations show the effect of different parameters on the modulation-transfer function of the resulting images. A flow phantom is used to verify some of the simulation results.

Computer Simulation↗

PubMed1994

Receptive-field maps of correlated discharge between pairs of neurons in the cat's visual cortex.

1. To investigate the functional significance of temporally correlated discharge between nearby cells in the visual cortex, we obtained receptive-field maps of correlated discharge for 68 cell pairs in kittens and cats. Discharge from cell pairs was measured by a single extracellular electrode. A reverse correlation procedure was used to relate neural discharge to particular stimuli within a random sequence of briefly flashed bright and dark bars. Bicellular receptive fields (BRFs) were mapped by applying reverse correlation to approximately synchronous discharge from two cells. Unicellular receptive fields (URFs) were simultaneously mapped by separately applying reverse correlation to the discharge of each cell. 2. The receptive fields of the two neurons within each pair were initially studied by varying the orientation and spatial frequency of drifting sinusoidal gratings. After these tests a random sequence of appropriately oriented bars was used to evoke discharge suitable for reverse correlation analysis. For most cell pairs, the temporal pattern or strength of correlated discharge produced by such stimulation is different from that observed with stimulation by sinusoidal gratings. This indicates that visually evoked correlated discharge between nearby cells is stimulus dependent. 3. BRFs were classified according to their pattern of spatial sensitivity into three groups that roughly correspond to the single-cell receptive-field types of the lateral geniculate nucleus (LGN; center-surround) and visual cortex (simple and complex). These classifications were compared with the receptive-field types of the single cells within each pair. LGN-type and simple-type BRFs were only seen for pairs in which at least one of the cells was simple. Conversely, complex-type BRFs were only seen for pairs in which at least one of the cells was complex. 4. Because the reverse correlation procedure can be used to characterize the spatiotemporal receptive-field structure of simple cells, we were able to compare both the spatial and temporal properties associated with the URFs and BRFs of simple cell pairs. The spatiotemporal structure of the BRF of a simple-cell pair can largely be predicted on the basis of the two URFs. Although this prediction suggests the possibility that BRFs are stimulus artifacts, a shuffle procedure, in which multiple repetitions of random sequences were presented, verifies the neural origin of BRFs. BRFs emerge from specific neural pathways and are not simply a consequence of unicellular response preferences. 5. Five measures were derived from the reverse correlation analysis of simple-cell receptive fields: width, duration, optimal spatial and temporal frequency, and optimal velocity.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed2004

Local sequence-structure motifs in RNA.

Ribonuclic acid (RNA) enjoys increasing interest in molecular biology; despite this interest fundamental algorithms are lacking, e.g. for identifying local motifs. As proteins, RNA molecules have a distinctive structure. Therefore, in addition to sequence information, structure plays an important part in assessing the similarity of RNAs. Furthermore, common sequence-structure features in two or several RNA molecules are often only spatially local, where possibly large parts of the molecules are dissimilar. Consequently, we address the problem of comparing RNA molecules by computing an optimal local alignment with respect to sequence and structure information. While local alignment is superior to global alignment for identifying local similarities, no general local sequence-structure alignment algorithms are currently known. We suggest a new general definition of locality for sequence-structure alignments that is biologically motivated and efficiently tractable. To show the former, we discuss locality of RNA and prove that the defined locality means connectivity by atomic and non-atomic bonds. To show the latter, we present an efficient algorithm for the newly defined pairwise local sequence-structure alignment (lssa) problem for RNA. For molecules of lengthes n and m, the algorithm has worst-case time complexity of O(n2 x m2 x max(n,m)) and a space complexity of only O(n x m). An implementation of our algorithm is available at http://www.bio.inf.uni-jena.de. Its runtime is competitive with global sequence-structure alignment.

Algorithms↗

PubMed1999

Structure-based prediction of DNA target sites by regulatory proteins.

Regulatory proteins play a critical role in controlling complex spatial and temporal patterns of gene expression in higher organism, by recognizing multiple DNA sequences and regulating multiple target genes. Increasing amounts of structural data on the protein-DNA complex provides clues for the mechanism of target recognition by regulatory proteins. The analyses of the propensities of base-amino acid interactions observed in those structural data show that there is no one-to-one correspondence in the interaction, but clear preferences exist. On the other hand, the analysis of spatial distribution of amino acids around bases shows that even those amino acids with strong base preference such as Arg with G are distributed in a wide space around bases. Thus, amino acids with many different geometries can form a similar type of interaction with bases. The redundancy and structural flexibility in the interaction suggest that there are no simple rules in the sequence recognition, and its prediction is not straightforward. However, the spatial distributions of amino acids around bases indicate a possibility that the structural data can be used to derive empirical interaction potentials between amino acids and bases. Such information extracted from structural databases has been successfully used to predict amino acid sequences that fold into particular protein structures. We surmised that the structures of protein-DNA complexes could be used to predict DNA target sites for regulatory proteins, because determining DNA sequences that bind to a particular protein structure should be similar to finding amino acid sequences that fold into a particular structure. Here we demonstrate that the structural data can be used to predict DNA target sequences for regulatory proteins. Pairwise potentials that determine the interaction between bases and amino acids were empirically derived from the structural data. These potentials were then used to examine the compatibility between DNA sequences and the protein-DNA complex structure in a combinatorial "threading" procedure. We applied this strategy to the structures of protein-DNA complexes to predict DNA binding sites recognized by regulatory proteins. To test the applicability of this method in target-site prediction, we examined the effects of cognate and noncognate binding, cooperative binding, and DNA deformation on the binding specificity, and predicted binding sites in real promoters and compared with experimental data. These results show that target binding sites for several regulatory proteins are successfully predicted, and our data suggest that this method can serve as a powerful tool for predicting multiple target sites and target genes for regulatory proteins.

Base Sequence↗

PubMed1985

Primary structure of the soybean nodulin-23 gene and potential regulatory elements in the 5'-flanking regions of nodulin and leghemoglobin genes.

The nodulin-23 gene of soybean is one of the most abundantly transcribed genes induced during symbiosis with Rhizobium. Using a plasmid (pNod25) from a nodule cDNA library, we have isolated the nodulin-23 gene from a soybean genomic library. Nucleotide sequence analysis of the cDNA and of the genomic clone indicated that the coding region of this gene is 669 bp long and is interrupted by a single intron of about 530 bp. The deduced protein sequence suggests that nodulin-23 may have a signal sequence. The 5'-flanking sequence of two other nodulin genes, nodulin-24 encoding for a membrane polypeptide and one of the leghemoglobin genes (LbC3), were obtained. Comparison of these sequences revealed three conserved regions, one of which, an octanucleotide (GTTTCCCT), has 100% homology. The conserved sequences are arranged in a unique fashion and have a spatial organization with respect to order and position, which may suggest a potential regulatory role in controlling the expression of nodulin and leghemoglobin genes during symbiosis.

Amino Acid Sequence↗

PubMed1995

Structural requirements for mitomycin C DNA bonding.

Information of the specific structure of the activated mitomycin species leading to selective DNA bonding has been secured by determining the bonding sequence selectivities of modified mitomycins in which the identity, spatial orientation, and state of unsaturation of the C-9 and C-9a substituents in the mitomycin were varied. Both mitomycin-9a-sulfonate (8) and mitomycin D (9) gave DNA bonding profiles comparable to those obtained for mitomycin C (1) under reductive conditions, indicating that neither the stereochemistry of the C-9 and C-9a substituents nor the identity of the leaving group at C-9a influenced the site(s) of DNA bonding. These results indicated that aromatization of the dihydropyrrole ring in mitomycin C precedes DNA binding and mitomycin C-1 bonding.

Base Sequence↗

PubMed1999

ADC mapping by means of a single-shot spiral MRI technique with application in acute cerebral ischemia.

Diffusion-weighted MRI based on single-shot echo planar imaging (EPI) has been established as a useful tool to study acute cerebral ischemia. However, EPI is prone to spatial distortion and ghosting artifacts. In this study, a pulse sequence for diffusion-weighted imaging (DWI) based on a single-shot spiral readout is presented. Using this technique, multislice apparent diffusion coefficient (ADC) mapping can be performed in an interleaved fashion with the same temporal resolution as EPI. Other advantages associated with ADC mapping by the single-shot spiral method include minimal ghosting artifacts, reduced spatial distortion, and capability to scan in arbitrary planes. This technique has been successfully tested in five normal volunteers and three stroke patients. It has been demonstrated that the single-shot spiral technique is capable of producing high quality DWI and ADC trace maps (128 x 128) in the axial, sagittal, and coronal planes, which facilitate clinical diagnosis.

Acute Disease↗

PubMed2006

Effects of historical climate change, habitat connectivity, and vicariance on genetic structure and diversity across the range of the red tree vole (Phenacomys longicaudus) in the Pacific Northwestern United States.

Phylogeographical analyses conducted in the Pacific Northwestern United States have often revealed concordant patterns of genetic diversity among taxa. These studies demonstrate distinct North/South genetic discontinuities that have been attributed to Pleistocene glaciation. We examined phylogeographical patterns of red tree voles (Phenacomys longicaudus) in western Oregon by analysing mitochondrial control region sequences for 169 individuals from 18 areas across the species' range. Cytochrome b sequences were also analysed from a subset of our samples to confirm the presence of major haplotype groups. Phylogenetic network analyses suggested the presence of two haplotype groups corresponding to northern and southern regions of P. longicaudus' range. Spatial genetic analyses (samova and Genetic Landscape Shapes) of control region sequences demonstrated a primary genetic discontinuity separating northern and southern sampling areas, while a secondary discontinuity separated northern sampling areas into eastern and western groups divided by the Willamette Valley. The North/South discontinuity likely corresponds to a region of secondary contact between lineages rather than an overt barrier. Although the Cordilleran ice sheet (maximum approximately 12,000 years ago) did not move southward to directly affect the region occupied by P. longicaudus, climate change during glaciation fragmented the forest landscape that it inhabits. Signatures of historical fragmentation were reflected by positive associations between latitude and variables such as Tajima's D and patterns associated with location-specific alleles. Genetic distances between southern sampling areas were smaller, suggesting that forest fragmentation was reduced in southern vs. northern regions.

Animals↗

PubMed1999

Structural constraints on RNA virus evolution.

The recently discovered hepatitis G virus (HGV) or GB virus C (GBV-C) is widely distributed in human populations, and homologues such as HGV/GBV-CCPZ and GBV-A are found in a variety of different primate species. Both epidemiological and phylogenetic analyses support the hypothesis that GB viruses coevolved with their primate hosts, although their degree of sequence similarity appears incompatible with the high rate of sequence change of HGV/GBV-C over short observation periods. Comparison of complete coding sequences (8,500 bases) of different genotypes of HGV/GBV-C showed an excess of invariant synonymous sites (at 23% of all codons) compared with the frequency expected by chance (10%). To investigate the hypothesis that RNA secondary-structure formation through internal base pairing limited sequence variability at these sites, an algorithm was developed to detect covariant sites among HGV/GBV-C sequences of different genotypes. At least 35 covariant sites that were spatially associated with potential stem-loop structures were detected, whose positions correlated with positions in the genome that showed reductions in synonymous variability. Although the functional roles of the predicted secondary structures remain unclear, the restriction of sequence change imposed by secondary-structure formation provides a mechanism for differences in net rate of accumulation of nucleotide substitutions at different sites. However, the resulting disparity between short- and long-term rates of sequence change of HGV/GBV-C violates the assumptions of the "molecular clock." This places a major restriction on the use of nucleotide or amino acid sequence comparisons to calculate times of divergence of other viruses evolving under the same structural constraints as GB viruses.

Base Sequence↗

PubMed2002

Assessment of fine motor skill in musicians and nonmusicians: differences in timing versus sequence accuracy in a bimanual fingering task.

While professional musicians are generally considered to possess better control of finger movements than nonmusicians, relatively few reports have experimentally addressed the nature of this discrepancy in fine motor skills. For example, it is unknown whether musicians perform with greater skill than control subjects in all aspects of different types of fine motor activities. More specifically, it is not known whether musicians perform better than control subjects on a fine motor task that is similar, but not identical, to the playing of their primary instrument. The purpose of this study was to examine the accuracy of finger placement and accuracy of timing in professional musicians and nonmusicians using a simple, rhythmical, bilateral fingering pattern and the technology that allowed separate assessment of these two parameters. Professional musicians (other than pianists) and nonmusicians were given identical, detailed and explicit instructions but not allowed physically to practice the finger pattern. After verbally repeating the correct pattern for the investigator, subjects performed the task on an electric keyboard with both hands simultaneously. Each subject's performance was then converted to a numerical score. While musicians clearly demonstrated better accuracy in timing, no significant difference was found between the groups in their finger placement scores. These findings were not correlated with subjects' age, sex, limb dominance, or primary instrument (for the professional musicians). This study indicates that professional musicians perform better in timing accuracy but not spatial accuracy while executing a simple, novel, bimanual motor sequence.

Adult↗

PubMed2006

Phylogeography of the deer mouse (Peromyscus maniculatus) provides a predictive framework for research on hantaviruses.

Phylogeographical partitioning of Sin Nombre and Monongahela viruses (hantaviruses) may reflect that of their primary rodent host, the deer mouse (Peromyscus maniculatus). Lack of a comprehensive assessment of phylogeographical variation of the host has precluded the possibility of predicting spatial limits of existing strains of these viruses or geographical regions where novel viral strains might emerge. The complete cytochrome b gene was sequenced for 206 deer mice collected from sites throughout North America to provide a foundation for future studies of spatial structure and evolution of this ubiquitous host. Bayesian analyses of these sequences partitioned deer mice into six largely allopatric lineages, some of which may represent unrecognized species. The geographical distributions of these lineages were probably shaped by Quaternary climatic events. Populations of mice were apparently restricted to refugia during glacial advances, where they experienced genetic divergence. Expansion of these populations, following climatic amelioration, brought genetically distinctive forms into contact. Occurrence of parallel changes in virus strains can now be explored in appropriate regions. In New Mexico, for example, near the location where Sin Nombre virus was first discovered, there are three genetically distinctive lineages of deer mice whose geographical ranges need to be delineated precisely. The phylogeography of P. maniculatus provides a framework for interpreting geographical variability, not only in hosts, but also in associated viral variants and disease transmission, and an opportunity to predict the potential geographical distribution of newly emerging viral strains.

Animals↗

PubMed1993

Active motion of polymorphonuclear leukocytes in response to chemoattractant in a micropipette.

A novel experimental method of producing and observing the active motion of polymorphonuclear leukocytes (PMNs) using a micropipette technique has been recently developed (Usami et al., 1992). The present paper develops a quantitative theory for the chemoattractant gradients and cell locomotion observed in these experiments. In previous experimental methods (e.g., the Boyden chamber, the Zygmond chamber and the Dunn chamber) for study chemotaxis of leukocytes, fibroblasts, and PMNs, the exact nature of the concentration gradient of the chemoattractant is unknown. The cells may themselves modify the local gradient of the chemoattractant. In experiments using the micropipette, an internal source of chemoattractant provides well-defined boundary and initial conditions which allow the computation of the chemoattractant concentration gradient during the active locomotion of the PMNs. Since the cell completely fills the pipette lumen, convection is limited to the motion of the cells themselves. In coordinates moving with cell, it is assumed that diffusion is the only mechanism of mass transport of the chemoattractant (fMLP). Computations of the fMLP concentration during locomotion of the cell were carried out for a range of rates of fMLP binding by the receptors expressed on the front face of the cell membrane. The results show that the front face of the cell is subjected to increasing fMLP concentration during the cell motion. The sequence of events involve receptor binding of fMLP, signal transduction, polymerization of the cell cytoskeleton at the membrane of the front face, spatially dependent adhesion to the pipette wall, and localized contraction of the cytoskeleton. This sequence of events leads to the steady locomotion of the leukocytes in the micropipette. The computation of the distribution of the fMLP concentration during cell locomotion with constant velocity in micropipette experiments shows that the cell is exposed to increasing concentration of fMLP. This suggests that chemotaxis maybe induced by temporal gradient of an attractant.

Cell Movement↗

PubMed1988

Calculation of the three-dimensional structure of Saccharomyces cerevisiae cytochrome b inserted in a lipid matrix.

Cytochrome b is an integral membrane protein, which forms the core of the ubiquinol-cytochrome c oxidoreductase (cytochrome bc1) complex. A computer-aided three-dimensional modeling procedure was carried out in four steps. First, the candidate hydrophobic helices were searched for throughout the protein primary sequence by a computer procedure based upon the method of Eisenberg; second, a secondary helical structure was imposed to the transmembrane peptides; third, the helical segments at a lipid-water interface were oriented, and finally the possible interactions between helices with similar properties were investigated. This procedure enabled the identification of nine hydrophobic segments, of which eight are membrane-spanning helices while one has amphipathic properties. Three hydrophilic receptor-binding domains were also identified. Based upon their hydrophobicity profiles, the transmembrane helices could be associated in pairs inside the lipid bilayer. In our folding model proposed for cytochrome b, all mutation sites are not only located on the same side of the membrane but are also in close proximity in the three-dimensional structure. Inhibitor resistance mutational sites which were recently characterized (di Rago, J.-P., and Colson, A.-M. (1988) J. Biol. Chem. 263, 12564-12570) have been located on this model. Moreover, the receptor-binding domains and the mutation sites are close neighbors in the three-dimensional spatial representation.

Amino Acid Sequence↗

PubMed2003

Functional diversity of endothelin pathways in human lung fibroblasts may be based on structural diversity of the endothelin receptors.

Posttranslational modifications of the endothelin receptors A and B from human lung fibroblasts were investigated before and after stimulation of the cells with (dA)(30)-5'-S-EMC-endothelin-1. The patterns of phosphorylation and palmitoylation of both receptors were much more complicated than expected. In both the stimulated and the unstimulated states, multiple isoforms differing in the number and location of posttranslational modifications were present. MS analyses suggested rapid changes in these isoforms following stimulation. Overall, the ETA receptor was modified at 20 sites (15 phosphorylation, five palmitoylation sites) and ETB at 17 sites (13 phosphorylation, four palmitoylation sites). Part of the structural diversity involved hypermodification of short sequence regions, and it is suggested that this could represent a mechanism for incremental modulation of receptor activity. It is postulated that the observed structural diversity over disparate parts of the receptor sequences forms the basis for parallel stimulation of different signaling pathways at spatially and functionally distinct ET receptors differing in posttranslational modifications.

Amino Acid Sequence↗

PubMed1998

Navigation and acquisition of spatial knowledge in a virtual maze.

Spatial behavior in humans and animals includes a wide variety of behavioral competences and makes use of a large number of sensory cues. Here we studied the ability of human subjects to search locations, to find shortcuts and novel paths, to estimate distances between remembered places, and to draw sketch maps of the explored environment; these competences are related to goal-independent memory of space, or cognitive maps. Information on spatial relations was restricted to two types: a visual motion sequence generated by simulated movements in a virtual maze and the subject's own movement decisions defining the path through the maze. Visual information was local (i.e., no global landmarks or compass information was provided). Other position and movement information (vestibular or proprioceptive) was excluded. The amount of visual information provided was varied over four experimental conditions. The results indicate that human subjects are able to learn a virtual maze from sequences of local views and movements. The information acquired is local, consisting of recognized positions and movement decisions associated to them. Although simple associations of this type can be shown to be present in some subjects, more complete configurational knowledge is acquired as well. The results are discussed in a view-based framework of navigation and the representation of spatial knowledge by means of a view graph.

Adolescent↗

PubMed2004

Separable enhancer sequences regulate the expression of the neural bHLH transcription factor neurogenin 1.

Ngn1 is a basic helix-loop-helix (bHLH) transcription factor expressed in specific regions within the developing brain and spinal cord, sensory ganglia, and olfactory epithelium. We have identified sequences both 5' and 3' of the mouse ngn1 gene that function in regulating ngn1 expression, and each of these sequences contains distinct regulatory cassettes for different subregions of the expression domain. Enhancers for expression in ngn1 domains of the midbrain, hindbrain, trigeminal ganglia, and ventral-neural tube appear redundant and are spread both 5' and 3' of the ngn1 coding sequence. In contrast, a single discrete dorsal-neural tube enhancer was located in the 5' sequence that is conserved among mouse, human, chick, and zebrafish ngn1 genes. Functionally, this enhancer is both necessary and sufficient for driving expression of a heterologous reporter in transgenic mice specifically to the dorsal domain of ngn1 expression in the spinal neural tube. Thus, sequences are identified that can be used to direct temporally and spatially restricted expression of heterologous genes to the developing neural tube.

Animals↗

PubMed2006

Laminar specificity in monkey V1 using high-resolution SE-fMRI.

The lamination of mammalian neocortex is widely used as reference for describing a wide range of anatomical and physiological data. Its value lies in the observation that in all examined species, cortical afferents, intrinsic cells and projection neurons organize themselves with respect to the laminae. The comprehension of the computations, carried out by the neocortical microcircuits, critically relies on the study of the interlaminar connectivity patterns and the intralaminar physiological processes in vivo. High-resolution functional neuroimaging, enabling the visualization of activity in individual cortical laminae or columns, may greatly contribute in such studies. Yet, the BOLD effect, as measured with the commonly used GE-EPI, contains contributions from both macroscopic venous blood vessels and capillaries. The low density of the cortical veins limits the effective spatial specificity of the fMRI signal and yields maps that are weighted toward the macrovasculature, which thus can be significantly different from the actual site of increased neuronal activity. Spin-echo (SE) sequences yielding apparent T2-weighted BOLD images have been shown to improve spatial specificity by increasing the sensitivity of the signal to spins of the parenchyma, particularly at high magnetic fields. Here we used SE-fMRI at 4.7 T to examine the specificity and resolution of functional maps obtained by stimulating the primary visual cortex of monkeys. Cortical layers could be clearly visualized, and functional activity was predominantly localized in cortical layer IV/Duvernoy layer 3. The choice of sequence parameters influences the fMRI signal, as the SE-EPI is by nature sensitive to T2* in addition to its T2 dependency. Using parameters that limit T2* effects yielded higher specificity and better visualization of the cortical laminae. Because the demands of high-spatial resolution using SE severely decreases temporal resolution, we used a stimulus protocol that allows sampling at higher effective temporal resolution. This way, it was possible to acquire high-spatial and high-temporal resolution SE-fMRI data.

Animals↗

PubMed2005

Numerical simulation of PRESS localized MR spectroscopy.

Numerical simulations of NMR spectra can provide a rapid and convenient method for optimizing acquisition sequence parameters and generating prior spectral information required for parametric spectral analysis. For spatially resolved spectroscopy, spatially dependent variables affect the resultant spectral amplitudes and phases, which must therefore be taken into account in any spectral simulation model. In this study, methods for numerical simulation of spectra obtained using the PRESS localization pulse sequence are examined. A comparison is made between three different simulation models that include different levels of detail regarding the spatial distributions of the excitation functions, and spin evolution during application of the pulses. These methods were evaluated for measurement of spectra from J-coupled spin systems that are of interest for in vivo proton spectroscopy and results compared with experimental data. It is demonstrated that for optimized refocusing pulses it is sufficient to account for chemical shift effects only, although there is some advantage to implementing a more general numerical simulation approach that includes information on RF pulse excitation profiles, which provides sufficient accuracy while maintaining moderate computational requirements and flexibility to handle different spin systems.

Aspartic Acid↗