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Results for “spatial sequencing”

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At least 487 records · Page 27Linked to original sources

PubMed2006

A segment of the apospory-specific genomic region is highly microsyntenic not only between the apomicts Pennisetum squamulatum and buffelgrass, but also with a rice chromosome 11 centromeric-proximal genomic region.

Bacterial artificial chromosome (BAC) clones from apomicts Pennisetum squamulatum and buffelgrass (Cenchrus ciliaris), isolated with the apospory-specific genomic region (ASGR) marker ugt197, were assembled into contigs that were extended by chromosome walking. Gene-like sequences from contigs were identified by shotgun sequencing and BLAST searches, and used to isolate orthologous rice contigs. Additional gene-like sequences in the apomicts' contigs were identified by bioinformatics using fully sequenced BACs from orthologous rice contigs as templates, as well as by interspecies, whole-contig cross-hybridizations. Hierarchical contig orthology was rapidly assessed by constructing detailed long-range contig molecular maps showing the distribution of gene-like sequences and markers, and searching for microsyntenic patterns of sequence identity and spatial distribution within and across species contigs. We found microsynteny between P. squamulatum and buffelgrass contigs. Importantly, this approach also enabled us to isolate from within the rice (Oryza sativa) genome contig Rice A, which shows the highest microsynteny and is most orthologous to the ugt197-containing C1C buffelgrass contig. Contig Rice A belongs to the rice genome database contig 77 (according to the current September 12, 2003, rice fingerprint contig build) that maps proximal to the chromosome 11 centromere, a feature that interestingly correlates with the mapping of ASGR-linked BACs proximal to the centromere or centromere-like sequences. Thus, relatedness between these two orthologous contigs is supported both by their molecular microstructure and by their centromeric-proximal location. Our discoveries promote the use of a microsynteny-based positional-cloning approach using the rice genome as a template to aid in constructing the ASGR toward the isolation of genes underlying apospory.

Cenchrus↗

PubMed1987

Dissociation of item and order spatial memory in rats following medial prefrontal cortex lesions.

In order to test whether there is a correspondence in function of prefrontal cortex in rats and humans, rats with medial prefrontal cortex lesions were tested for item and order memory for a list of items (spatial locations in a maze). Results indicate that for order memory rats with medial prefrontal cortex lesions cannot remember the order of presentation of four or eight specific spatial locations. This inability to remember order information can be seen even when animals with lesions have to remember only two spatial locations, can self-order the sequence of four or eight spatial locations, or have been presented with the same study phase on every trial. In contrast, for item memory animals with medial prefrontal cortex lesions retain the first item of the list in the variable study phase situation and remember all the items of the list in a constant study phase situation. However, there are also deficits for the last items within a list in the variable study phase situation for both win-stay and win-shift procedures. This deficit might be a function of an impairment in the utilization of appropriate temporal strategies, which normally would facilitate recognition memory in the win-stay and win-shift tasks. In general, the data suggest a partial, but not complete, dissociation of item-order memory. Furthermore, the data suggest that the medial prefrontal cortex is involved in temporal structuring of information.

Animals↗

PubMed1997

GABAergic modulation of hippocampal population activity: sequence learning, place field development, and the phase precession effect.

A detailed biophysical model of hippocampal region CA3 was constructed to study how GABAergic modulation influences place field development and the learning and recall of sequence information. Simulations included 1,000 multicompartmental pyramidal cells, each consisting of seven intrinsic and four synaptic currents, and 200 multicompartmental interneurons, consisting of two intrinsic and four synaptic currents. Excitatory rhythmic septal input to the apical dendrites of pyramidal cells and both excitatory and inhibitory input to interneurons at theta frequencies provided a cellular basis for the development of theta and gamma frequency oscillations in population activity. The fundamental frequency of theta oscillations was dictated by the driving rhythm from the septum. Gamma oscillation frequency, however, was determined by both the decay time of the gamma-aminobutyric acid-A (GABA(A))-receptor-mediated synaptic current and the overall level of excitability in interneurons due to alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid and N-methyl-D-aspartate (NMDA)-receptor-gated channel activation. During theta population activity, total GABA(B)-receptor-mediated conductance levels were found to gradually rise and fall in rhythmic fashion with the predominant population frequency (theta rhythm). This resulted in periodic GABA(B)-receptor-mediated suppression of excitatory synaptic transmission at recurrent collaterals (intrinsic fibers) of pyramidal cells and suppression of inhibitory synaptic transmission to both pyramidal cells and interneurons. To test the ability of the model to learn and recall temporal sequence information, a completion task was employed. During learning, the network was presented a sequence of nonorthogonal spatial patterns. Each input pattern represented a spatial "location" of a simulated rat running a specific navigational path. Hebbian-type learning was expressed as an increase in postsynaptic NMDA-receptor-mediated conductances. Because of several factors including the sparse, asymmetric excitatory synaptic connections among pyramidal cells in the model and a sufficient degree of random "background" firing unrelated to the input patterns, repeated simulated runs resulted in the gradual emergence of place fields where a given cell began to respond to a contiguous segment of locations on the path. During recall, the simulated rat was placed at a random location on the previously learned path and tested to see whether the sequence of locations could be completed on the basis of this initial position. Periodic GABA(B)-receptor-mediated suppression of excitatory and inhibitory transmission at intrinsic but not afferent fibers resulted in sensory information about location being dominant during early portions of each theta cycle when GABA(B)-receptor-related effects were highest. This suppression declined with levels of GABA(B) receptor activation toward the end of a theta cycle, resulting in an increase in synaptic transmission at intrinsic fibers and the subsequent recall of a segment of the entire location sequence. This scenario typically continued across theta cycles until the full sequence was recalled. When the GABA(B)-receptor-mediated suppression of excitatory and inhibitory transmission at intrinsic fibers was not included in the model, place field development was curtailed and the network consequently exhibited poor learning and recall performance. This was, in part, due to increased competition of information from intrinsic and afferent fibers during early portions of each theta cycle. Because afferent sensory information did not dominate early in each cycle, the current location of the rat was obscured by ongoing activity from intrinsic sources. (ABSTRACT TRUNCATED)

Animals↗

PubMed2000

Nuclear topology of murine, cerebellar Purkinje neurons: changes as a function of development.

The interphase nucleus is a structurally ordered, three-dimensional structure, in which specific chromatin domains occupy distinct spatial positions that can, in turn, be modified with changes in cell function. A fundamental goal in developmental neurobiology is the identification of mechanisms that dictate the orderly expression of genes in a cell-specific manner. Given that different neuronal populations feature a characteristic spatial topology of centromeric sequences, the positioning of specific DNA sequences may constitute such a mechanism. We tested the hypothesis that the cell-specific nuclear topology in fully differentiated neurons is acquired before or during that stage at which neuron-specific sequences are first expressed. For this, we assessed the number and spatial distribution of centromeric domains in the murine, cerebellar Purkinje neuron as a function of postnatal development. Centromeric domains were localized by immunofluorescence of centromere-associated kinetochore proteins and visualized by confocal microscopy. Kinetochores are known to cluster in Purkinje neurons. Thus, the number of signals discerned is always less than the chromosome complement of the species. The number of signals observed in adults (10.8 +/- 0.46) (mean +/- SEM) is established by postnatal day 15 (P15), after a transient decrease from 11.44 +/- 0.44 at P0 to 8.78 +/- 0.24 at P3. The distribution of signals characteristic of the adult, with the majority located at the nucleolus, is established by P5 and is associated with a decrease in the fraction of signals at the nuclear periphery. These changes are temporally associated with the onset of processes such as dendritic differentiation and synaptic maturation and might serve the process of differentiation by placing specific sequences into transcriptionally competent, nuclear sites.

Aging↗

PubMed2005

Phylogenetic relationships and biogeography of Podarcis species from the Balkan Peninsula, by bayesian and maximum likelihood analyses of mitochondrial DNA sequences.

Wall lizards of the genus Podarcis (Sauria, Lacertidae) comprise 17 currently recognized species in southern Europe, where they are the predominant nonavian reptile group. The taxonomy of Podarcis is complex and unstable. Based on DNA sequence data, the species of Podarcis falls into four main groups that have substantial geographic coherence (Western island group, southwestern group, Italian group, and Balkan Peninsula group). The Balkan Peninsula species are divided into two subgroups: the subgroup of P. taurica (P. taurica, P. milensis, P. gaigeae, and perhaps P. melisellensis), and the subgroup of P. erhardii (P. erhardii and P. peloponnesiaca). In the present study, the question of phylogenetic relationships among the species of Podarcis encountered in the Balkan Peninsula was addressed using partial mtDNA sequences for cytochrome b (cyt b) and 16S rRNA (16S). The data support the monophyly of Podarcis and suggest that there are three phylogenetic clades: the clade A (P. taurica, P. gaigeae, P. milensis, and P. melisellensis); the clade B (P. erhardii and P. peloponnesiaca), and the clade C (P. muralis and P. sicula). By examining intraspecific relationships it was found that extant populations of P. erhardii are paraphyletic. Furthermore, subspecies previously defined on the basis of morphological characteristics do not correspond to different molecular phylogenetic clades, suggesting that their status should be reconsidered. The distinct geographic distribution of the major clades of the phylogenetic tree and its topology suggest a spatial and temporal sequence of phylogenetic separations that coincide with some major paleogeographic separations during the geological history of the Aegean Sea. The results stress the need for a reconsideration of the evolutionary history of Balkan Podarcis species and help overcome difficulties that classical taxonomy has encountered at both the species and subspecies level.

Albania↗

PubMed2026

PMGen: from peptide-MHC structure prediction to peptide generation.

MOTIVATION: Accurate structural modeling of peptide-major histocompatibility complex (pMHC) complexes is essential for structure-driven immunotherapy design, yet current prediction tools suffer from narrow class coverage, restricted peptide lengths, insufficient accuracy, and a lack of built-in structure-aware peptide sampling. Consequently, most mimotope and altered peptide ligand designs rely solely on sequence substitution, leaving spatial and biophysical insights from pMHC structures largely unexploited. RESULTS: We introduce peptide-MHC generator (PMGen), an integrated framework for structure prediction and structure-guided design of variable-length peptides across MHC Class I and II. PMGen enforces anchor constraints within AlphaFold2 through two complementary strategies, initial guess and template engineering, achieving state-of-the-art structural fidelity without model fine-tuning. On a comprehensive benchmark, PMGen outperforms all existing methods, yielding median peptide-core Cα RMSDs of 0.62 Å for MHC-I and 0.33 Å for MHC-II. We show that PMGen can recover incorrectly predicted anchor positions and that AlphaFold pLDDT scores enable sequence-independent binding-core identification. Applied to a published neoantigen/wild-type pair, PMGen accurately captures mutation-induced conformational changes. Beyond structure prediction, we show that ProteinMPNN sampling on PMGen-predicted backbones yields higher affinity peptides while preserving the parental 3D conformation. Using PMGen to generate 63 817 high-confidence pMHC structures as training data, we further improve ProteinMPNN's peptide sequence recovery from 0.14 to 0.64 on a test set of 85 unseen MHC-I alleles, highlighting the value of accurate predicted structures for downstream machine learning tasks. AVAILABILITY AND IMPLEMENTATION: PMGen is freely available at https://github.com/soedinglab/PMGen, with an interactive Colab notebook at https://colab.research.google.com/github/soedinglab/PMGen/blob/master/colab.ipynb.

Peptides↗

PubMed1989

Magnetic resonance imaging and magnetic resonance spectroscopy of bone tumors and bone marrow disease.

The authors have made use of an integrated magnetic resonance imaging/spectroscopy (MRI/MRS) examination to study seven patients with a variety of bone tumors. The spatial localization method used in the 31P portion of the examination was surface coil localization and a one-dimensional chemical shift imaging method (3 cases). The authors found that the precision of spatial localization was critical in many of these cases, since most of these bone tumors were surrounded by muscle tissue that contained high concentrations of phosphocreatine (PCr). For this reason, they suggest that the metabolite ratios should be referenced to the adenosine triphosphate (beta-NTP) resonance rather than PCr. The phosphate monoester (PME) to beta-NTP ratio was elevated as compared with normal muscle in all of the bone tumors studied. The authors found that all of these tumors exhibited pHs between 7.0 and 7.2, which are similar to the values found for normal muscle. They also show the feasibility of using a line-selective proton chemical shift imaging sequence with high spatial resolution for investigating changes in the fatty composition of bone marrow. This method is illustrated in an example of a patient with advanced avascular necrosis in the femoral heads.

Adolescent↗

PubMed2001

Dynamic spiral MRI of pulmonary gas flow using hyperpolarized (3)He: preliminary studies in healthy and diseased lungs.

An optimized interleaved-spiral pulse sequence, providing high spatial and temporal resolution, was developed for dynamic imaging of pulmonary ventilation with hyperpolarized (3)He, and tested in healthy volunteers and patients with lung disease. Off-resonance artifacts were minimized by using a short data-sampling period per interleaf, and gradient-fidelity errors were compensated for by using measured k-space trajectories for image reconstruction. A nonsequential acquisition order was implemented to improve image quality during periods of rapid signal change, such as early inspiration. Using a sliding-window reconstruction, cine-movies with a frame rate of 100 images per second were generated. Dynamic images demonstrating minimal susceptibility- and motion-induced artifacts were obtained in sagittal, coronal, and axial orientations. The pulse sequence had the flexibility to image multiple slices almost simultaneously. Our initial experience in healthy volunteers and subjects with lung pathology demonstrated the potential of this new tool for capturing the features of lung gas-flow dynamics.

Helium↗

PubMed2001

Splicing and 3' end formation in the definition of nonsense-mediated decay-competent human beta-globin mRNPs.

Premature translation termination codons are common causes of genetic disorders. mRNAs with such mutations are degraded by a surveillance mechanism termed nonsense-mediated decay (NMD), which represents a phylogenetically widely conserved post-transcriptional mechanism for the quality control of gene expression. How NMD-competent mRNPs are formed and specified remains a central question. Here, we have used human beta-globin mRNA as a model system to address the role of splicing and polyadenylation for human NMD. We show that (i) splicing is an indispensable component of the human beta-globin NMD pathway, which cannot be compensated for by exonic beta-globin 'failsafe' sequences; (ii) the spatial requirements of human beta-globin NMD, as signified by the maximal distance of the nonsense mutation to the final exon-exon junction, are less constrained than in yeast; and (iii) non-polyadenylated mRNAs with a histone 3' end are NMD competent. Thus, the formation of NMD-competent mRNP particles critically depends on splicing but does not require the presence of a poly(A) tail.

Base Sequence↗

PubMed2005

RNA nanotechnology: engineering, assembly and applications in detection, gene delivery and therapy.

Biological macromolecules including DNA, RNA, and proteins, have intrinsic features that make them potential building blocks for the bottom-up fabrication of nanodevices. RNA is unique in nanoscale fabrication due to its amazing diversity of function and structure. RNA molecules can be designed and manipulated with a level of simplicity characteristic of DNA while possessing versatility in structure and function similar to that of proteins. RNA molecules typically contain a large variety of single stranded loops suitable for inter- and intra-molecular interaction. These loops can serve as mounting dovetails obviating the need for external linking dowels in fabrication and assembly. The self-assembly of nanoparticles from RNA involves cooperative interaction of individual RNA molecules that spontaneously assemble in a predefined manner to form a larger two- or three-dimensional structure. Within the realm of self-assembly there are two main categories, namely template and non-template. Template assembly involves interaction of RNA molecules under the influence of specific external sequence, forces, or spatial constraints such as RNA transcription, hybridization, replication, annealing, molding, or replicas. In contrast, non-template assembly involves formation of a larger structure by individual components without the influence of external forces. Examples of non-template assembly are ligation, chemical conjugation, covalent linkage, and loop/loop interaction of RNA, especially the formation of RNA multimeric complexes. The best characterized RNA multiplier and the first to be described in RNA nanotechnological application is the motor pRNA of bacteriophage phi29 which form dimers, trimers, and hexamers, via hand-in-hand interaction. phi29 pRNA can be redesigned to form a variety of structures and shapes including twins, tetramers, rods, triangles, and 3D arrays several microns in size via interaction of programmed helical regions and loops. 3D RNA array formation requires a defined nucleotide number for twisting and a palindromic sequence. Such arrays are unusually stable and resistant to a wide range of temperatures, salt concentrations, and pH. Both the therapeutic siRNA or ribozyme and a receptor-binding RNA aptamer or other ligands have been engineered into individual pRNAs. Individual chimeric RNA building blocks harboring siRNA or other therapeutic molecules have been fabricated subsequently into a trimer through hand-in-hand interaction of the engineered right and left interlocking RNA loops. The incubation of these particles containing the receptor-binding aptamer or other ligands results in the binding and co-entry of trivalent therapeutic particles into cells. Such particles were subsequently shown to modulate the apoptosis of cancer cells in both cell cultures and animal trials. The use of such antigen-free 20-40 nm particles holds promise for the repeated long-term treatment of chronic diseases. Other potentially useful RNA molecules that form multimers include HIV RNA that contain kissing loop to form dimers, tecto-RNA that forms a "jigsaw puzzle," and the Drosophila bicoid mRNA that forms multimers via "hand-by-arm" interactions. Applications of RNA molecules involving replication, molding, embossing, and other related techniques, have recently been described that allow the utilization of a variety of materials to enhance diversity and resolution of nanomaterials. It should eventually be possible to adapt RNA to facilitate construction of ordered, patterned, or pre-programmed arrays or superstructures. Given the potential for 3D fabrication, the chance to produce reversible self-assembly, and the ability of self-repair, editing and replication, RNA self-assembly will play an increasingly significant role in integrated biological nanofabrication. A random 100-nucleotide RNA library may exist in 1.6 x 10(60) varieties with multifarious structure to serve as a vital system for efficient fabrication, with a complexity and diversity far exceeding that of any current nanoscale system. This review covers the basic concepts of RNA structure and function, certain methods for the study of RNA structure, the approaches for engineering or fabricating RNA into nanoparticles or arrays, and special features of RNA molecules that form multimers. The most recent development in exploration of RNA nanoparticles for pathogen detection, drug/gene delivery, and therapeutic application is also introduced in this review.

Gene Transfer Techniques↗

PubMed2004

Non-proteolytic, receptor/ligand interactions associate cellular membrane type-1 matrix metalloproteinase with the complement component C1q.

Membrane type-1 matrix metalloproteinase (MT1-MMP), a prototypic member of the membrane-tethered MMP family, is an essential component of a cellular proteolysis apparatus. Recognition of protein cleavage targets followed by proteolysis is a main function of MT1-MMP. For the first time, however, we present evidence that MT1-MMP and other structurally related membrane MMPs bind C1q, the recognition unit of the first component of complement C1 that initiates activation of the classical pathway of complement. These interactions involve the catalytic domain of MT1-MMP and the C1q globular domain. In silico modeling followed by mutagenesis and the in vitro and cell-based binding studies showed that the His(171)-Glu-Lys-Gln-Ala-Asp(176) and Val(223)-Arg-Asn(224) peptide sequences of MT1-MMP are directly involved in the binding with C1q. These sequence regions are spatially distant from the active site of the protease. As a result, the catalytically active and the catalytically latent forms of cellular MT1-MMP are both efficient in binding with C1q. In agreement, despite the MT1-MMP/C1q interactions, C1q is totally resistant to MT1-MMP proteolysis. The discovery of the unconventional, receptor/ligand-like interactions of MT1-MMP with C1q, an essential component of immunity, is a significant step toward a more complete understanding of the role of this membrane-tethered protease in cancer.

Amino Acid Sequence↗

PubMed2006

Diversity and evolution of West Nile virus in Illinois and the United States, 2002-2005.

Evolutionary analyses of West Nile virus (WNV) have been limited by uneven sampling across geographic regions and over time. In this study, an expanded data set of 68 WNV envelope gene sequences from the Midwest (Illinois) was created and combined with published sequences to investigate spatial and temporal structuring in the United States viral population. Results indicate an overall lack of geographic structure to WNV in the United States, supporting the notion of WNV as a rapidly expanding pathogen not significantly restricted in its spread by geographic distance. However, analyses of viral genetic diversity show a steady increase in WNV nucleotide-level diversity over time. Additionally, evolutionary rate calculations indicate that WNV has evolved at approximately 0.85 x 10(-3) substitutions/site/year, largely through neutral substitution and purifying selection. Overall, these results show WNV across the United States to be a panmictic viral population that is diversifying and evolving.

Analysis of Variance↗

PubMed2005

Local dynamics measured by hydrogen/deuterium exchange and mass spectrometry of creatine kinase digested by two proteases.

Hydrogen/deuterium exchange coupled to mass spectrometry has been used to investigate the structure and dynamics of native dimeric cytosolic muscle creatine kinase. The protein was incubated in D2O for various time. After H/D exchange and rapid quenching of the reaction, the partially deuterated protein was cleaved in parallel by two different proteases (pepsin or type XIII protease from Aspergillus saitoi) to increase the sequence coverage and spatial resolution of deuterium incorporation. The resulting peptides were analyzed by liquid chromatography coupled to mass spectrometry. In comparison with the 3D structure of MM-CK, the analysis of the two independent proteolysis deuteration patterns allowed us to get new insights into CK local dynamics as compared to a previous study using pepsin [Mazon et al. Protein Science 13 (2004) 476-486]. In particular, we obtained more information on the kinetics and extent of deuterium exchange in the N- and C-terminal extremities represented by the 1-22 and 362-380 pepsin peptides. Indeed, we observed a very different behaviour of the 1-12 and 13-22 type XIII protease peptides, and similarly for the 362-373 and 374-380 peptides. Moreover, comparison of the deuteration patterns of type XIII protease segments of the large 90-126 pepsin peptide led us to identify a small relatively dynamic region (108-114).

Amino Acid Sequence↗

PubMed2006

Generalized three-dimensional windowed Fourier transform for fringe analysis.

A 3D windowed Fourier transform is proposed for fringe sequence analysis, which processes the joint spatial and temporal information of the fringe sequence simultaneously. The 2D windowed Fourier transform in the spatial domain and the 1D windowed Fourier transform in the temporal domain are two special cases of the proposed method. The principles of windowed Fourier filtering and windowed Fourier ridges are developed. Experimental verification shows encouraging results despite a longer processing time.

Journal Article↗

PubMed1997

Visuomotor transformations for reaching to memorized targets: a PET study.

Positron emission tomography (PET) was used to identify cortical and subcortical regions involved in the control of reaching to visual targets. Regional cerebral blood flow (rCBF) was measured in eight healthy subjects using H2(15)O PET during the performance of three different tasks. All tasks required central fixation while a 400-ms target was flashed every 5 s at a random location around a virtual circle centered on the fixation target. Additional instructions differed according to the task: (i) visual detection of the target without overt responses; (ii) immediate pointing to the most recent target in the sequence, and (iii) pointing to the previous target in the sequence. By design, the two motor tasks differed in the cognitive processing required. In each trial of immediate pointing, the spatial location of only the most recent target needed to be processed. In each trial of pointing to the previous, instead, while the most recent target was stored in memory for the movement of the next trial, the previous target had to be retrieved from memory to direct the current movement. Limb trajectories were comparable between the two motor tasks in terms of most spatiotemporal parameters examined. Significant rCBF increases were identified using analysis of covariance and t statistics. Compared with visual detection there was activation of primary sensorimotor cortex, ventrolateral precentral gyrus, inferior frontal gyrus in the opercular region, supramarginal gyrus, and middle occipital gyrus, all these sites in the hemisphere (left) contralateral to the moving limb, and cerebellar vermis, during both immediate pointing and pointing to the previous. During immediate pointing there was additional activation of left inferior parietal lobule close to the intraparietal sulcus, and when compared with pointing to the previous, dorsolateral prefrontal cortex bilaterally. During pointing to the previous, instead, there was additional activation of supplementary motor cortex, anterior and midcingulate, and inferior occipital gyrus in the left hemisphere; superior parietal lobule, supramarginal gyrus, and posterior hippocampus in the right hemisphere; lingual gyri and cerebellar hemispheres bilaterally; anterior thalamus; and pulvinar. The activation of two partially distinct cerebral networks in these two motor tasks reflects the different nature of signal processing involved. In particular, the specific activation of intraparietal sulcus and prefrontal cortex in immediate pointing appears characteristic of a network for visuospatial working memory. By contrast, the corticolimbic network engaged in pointing to the previous could mediate spatial attention and the sequence of encoding, recording, and decoding of spatial memories required by a dual task with two competing targets.

Adult↗

PubMed1992

Temporal integration of spatially filtered visual images.

Factors which govern the temporal integration of spatial information were examined in a group of five experiments. A series of high-pass and low-pass spatially filtered versions of a visual scene were generated. Observers' ratings of these filtered versions of the scene for perceived image quality indicated that quality was determined both by the bandwidth of spatial information and the presence of high-spatial-frequency edge information. When sequences of three different versions of the scene were presented over an interval of 120 ms the perceived quality of the resulting composite image was determined both from the ratings of the individual components of that sequence and from the order in which these components were presented. When the order of spatial information in a sequence moved from coarse to fine detail the perceived quality of the composite image was significantly better than when the order moved from fine to coarse. This evidence of a coarse-to-fine bias in pattern integration was further investigated with a detection paradigm. The pattern of errors once again indicated that temporal integration of spatial information was superior when a coarse-to-fine mode of information delivery was employed. Taken together the data indicate that the pattern-integration mechanism has an inherent order bias and does not accumulate spatial information so efficiently when the 'natural' coarse-to-fine order is violated.

Attention↗

PubMed1996

The surface of beta-sheet proteins contains amphiphilic regions which may provide clues about protein folding.

A major bottleneck in the field of biochemistry is our limited understanding of the processes by which a protein folds into its native conformation. Much of the work on this issue has focused on the conserved core of the folded protein. However, one might imagine that a ubiquitous motif for unaided folding or for the recognition of chaperones may involve regions on the surface of the native structure. We explore this possibility by an analysis of the spatial distribution of regions with amphiphilic alpha-helical potential on the surface of beta-sheet proteins. All proteins, including beta-sheet proteins, contain regions with amphiphilic alpha-helical potential. That is, any alpha-helix formed by that region would be amphiphilic, having both hydrophobic and hydrophilic surfaces. In the three-dimensional structure of all beta-sheet proteins analyzed, we have found a distinct pattern in the spatial distribution of sequences with amphiphilic alpha-helical potential. The amphiphilic regions occur in ring shaped clusters approximately 20 to 30 A in diameter on the surface of the protein. In addition, these regions have a strong preference for positively charged amino acids and a lower preference for residues not favorable to alpha-helix formation. Although the purpose of these amphiphilic regions which are not associated with naturally occurring alpha-helix is unknown, they may play a critical role in highly conserved processes such as protein folding.

Amino Acids↗

PubMed1999

MR measurement of coronary blood flow.

The functional significance of coronary arterial stenosis can be evaluated by measuring the pharmacological flow reserve. Magnetic resonance (MR) imaging has a unique potential for noninvasive measurement of coronary blood flow and flow reserve in the native coronary artery and bypass graft. Restenosis after coronary balloon angioplasty and stenting in the left anterior descending artery can be detected noninvasively with serial MR measurements of the coronary flow reserve. Further refinement of the MR pulse sequences to improve spatial and temporal resolutions may permit accurate quantification of blood flow volume and flow reserve in all major coronary arterial branches. MR assessments of blood flow volume and flow pattern allow noninvasive detection of significant stenosis in the coronary artery bypass graft as well. By integrating MR blood flow measurement in the coronary sinus and cine MR assessment of left ventricular myocardial mass, altered myocardial micro-circulation in patients with diffuse myocardial diseases, such as hypertrophic cardiomyopathy and cardiac transplant, has been documented. J. Magn. Reson. Imaging 1999;10:728-733.

Animals↗