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Results for “spatial sequencing”

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PubMed2004

Real-time cardiac MRI at 3 tesla.

Real-time cardiac and coronary MRI at 1.5T is relatively "signal starved" and the 3T platform is attractive for its immediate factor of two increase in magnetization. Cardiac imaging at 3T, however, is both subtly and significantly different from imaging at 1.5T because of increased susceptibility artifacts, differences in tissue relaxation, and RF homogeneity issues. New RF excitation and pulse sequence designs are presented which deal with the fat-suppression requirements and off-resonance issues at 3T. Real-time cardiac imaging at 3T is demonstrated with high blood SNR, blood-myocardium CNR, resolution, and image quality, using new spectral-spatial RF pulses and fast spiral gradient echo pulse sequences. The proposed sequence achieves 1.5 mm in-plane resolution over a 20 cm FOV, with a 5.52 mm measured slice thickness and 32 dB of lipid suppression. Complete images are acquired every 120 ms and are reconstructed and displayed at 24 frames/sec using a sliding window. Results from healthy volunteers show improved image quality, a 53% improvement in blood SNR efficiency, and a 232% improvement in blood-myocardium CNR efficiency compared to 1.5T.

Adipose Tissue↗

PubMed2001

Measurement of in-vivo local shear modulus by combining multiple phase offsets mr elastography.

To provide realistic surgical simulation, haptic feedback is important. In the existing surgical simulators, the fidelity of the deformation and haptic feedback is limited because they are based on the subjective evaluation of the expert-user and not on an objective model-based evaluation. To obtain elastic modulus of in-vivo human tissues, magnetic resonance elastography (MRE) was developed. MRE is a phase-contrast- based method that can visualize propagating strain waves in materials. The quantitative values of shear modulus can be calculated by estimating the local wavelength of the wave pattern. Low frequency mechanical motion must be used for soft tissue-like materials, because strain waves rapidly attenuate at higher frequency. Therefore, wavelength in MRE is long. It is difficult to estimate local wavelength with high spatial resolution especially from noisy MRE. In the MRE sequence, motion-sensitizing gradient (MSG) are synchronized with the mechanical cyclic motion. MRE with multiple initial phase offsets can be generated with increasing delays between the MSG and mechanical excitation. In this paper, we describe a method of measuring local wavelength with high spatial resolution by combining multiple phase offsets MRE. To confirm the reliability of this method, a computer simulation and phantom study were performed. The shear modulus measured with various elastic objects was well consistent with the value obtained by MRE and the mechanical method. The shear moduli of excised porcine liver and in-vivo human calf muscle were also analyzed by this method. on the subjective evaluation of an expert-user and not on objective model-based methods.

Acoustic Stimulation↗

PubMed2004

Analysis of the magic asymmetric gradient stimulated echo sequence with shaped gradients.

Recently a 13-interval magic asymmetrical gradient stimulated echo (MAGSTE) sequence has been proposed for accurate displacement measurements in the presence of spatially varying background gradients. In this paper, the commonly used trapezoidal and sine shaped gradients are studied for the MAGSTE sequence, and the magic asymmetrical gradient ratio and b-factor are provided. The derivation enables the MAGSTE sequence to be implemented on systems with non-negligible gradient rise times.

Diffusion↗

PubMed2006

Regulatory sequences driving expression of the sea urchin Otp homeobox gene in oral ectoderm cells.

PlOtp (Orthopedia), a homeodomain-containing transcription factor, has been recently characterized as a key regulator of the morphogenesis of the skeletal system in the embryo of the sea urchin Paracentrotus lividus. Otp acts as a positive regulator in a subset of oral ectodermal cells which transmit short-range signals to the underlying primary mesenchyme cells where skeletal synthesis is initiated. To shed some light on the molecular mechanisms involved in such a process, we begun a functional analysis of the cis-regulatory sequences of the Otp gene. Congruent with the spatial expression profile of the endogenous Otp gene, we found that while a DNA region from -494 to +358 is shown to drive in vivo GFP reporter expression in the oral ectoderm, but also in the foregut, a larger region spanning from -2044 to +358 is needed to give firmly established tissue specificity. Microinjection of PCR-amplified DNA constructs, truncated in the 5' regulatory region, and determination of GFP mRNA level in injected embryos allowed the identification of a 5'-flanking fragment of 184bp in length, essential for expression of the transgene in the oral ectoderm of pluteus stage embryos. Finally, we conducted DNAse I-footprinting assays in nuclear extracts for the 184bp region and detected two protected sequences. Data bank search indicates that these sites contain consensus binding sites for transcription factors.

Animals↗

PubMed2006

A spatial modality effect in serial memory.

In 2 experiments, the authors tested whether the classical modality effect-that is, the stronger recency effect for auditory items relative to visual items-can be extended to the spatial domain. An order reconstruction task was undertaken with four types of material: visual-spatial, auditory-spatial, visual-verbal, and auditory-verbal. Similar serial position curves were obtained regardless of the nature of the to-be-remembered sequences, with the exception that a modality effect was found with spatial as well as with verbal materials. The results are discussed with regard to a number of models of short-term memory.

Acoustic Stimulation↗

PubMed2026

Multimodal Analysis Reveals Aberrant Expression of SUMO2 and Its Significant Association With Key Mechanisms of Metabolic Pathways in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. However, the role of small ubiquitin-like modifier 2 (SUMO2), a core member of the small ubiquitin-like modifier (SUMO) family, regarding its expression patterns and metabolism-related functions in HCC remains inadequately understood. METHODS: A multidimensional analytical framework was applied, integrating immunohistochemistry (153 HCC vs. 21 non-HCC samples), proteomics (159 paired samples), bulk transcriptomics (3240 HCC vs. 2267 non-HCC samples), single-cell RNA sequencing (RNA-seq) (10 HCC vs. 8 non-HCC samples), spatial transcriptomics, and external CRISPR/Cas9 functional genomics data. Systematic analyses included standardized mean difference (SMD), pathway enrichment, pseudotime trajectory inference, in silico knockout, cell-cell communication, metabolic flux scoring, immune infiltration, clinical correlation, drug sensitivity prediction, and molecular docking. RESULTS: At the protein level, immunohistochemistry (nuclear positivity) and external proteomic data collectively demonstrated consistent SUMO2 overexpression in HCC. Consistent upregulation was also observed at the mRNA level across large-scale cohorts. Single-cell RNA-seq and spatial transcriptomics localized SUMO2 enrichment to malignant hepatocytes and tumor-dominant regions. CRISPR-mediated SUMO2 knockout suppressed proliferation in multiple HCC cell lines. Mechanistically, high SUMO2 expression was significantly associated with metabolic reprogramming involving glycolysis/gluconeogenesis, pyruvate metabolism, and the tricarboxylic acid cycle. SUMO2-high malignant hepatocyte subpopulations exhibited enhanced activity of the macrophage migration inhibitory factor signaling axis and enhanced iron-sensor interactions. Further, the immune infiltration analysis revealed a negative correlation between SUMO2 expression and M1 macrophages and a positive correlation between follicular helper T cells and regulatory T cells. Clinically, elevated SUMO2 levels were found to be associated with adverse prognostic features. Furthermore, high SUMO2 expression was associated with increased sensitivity to dasatinib, and molecular docking simulations predicted potential binding between SUMO2 and dasatinib, with a Vina score of -8.5 kcal/mol. CONCLUSIONS: SUMO2 is aberrantly expressed at the protein, mRNA, single-cell, and spatial transcriptomic levels in HCC and is significantly associated with metabolic reprogramming and altered migration inhibitory factor (MIF)-mediated intercellular communication, suggesting its potential as a novel biomarker for diagnosis and treatment.

Humans↗

PubMed2005

Mapping multiple visual areas in the human brain with a short fMRI sequence.

It is a fundamental insight of neuroscience that the cerebral cortex is divided into spatially separated and functionally distinct areas. In this study, we tried to map a large number of visual areas in individual subjects passively viewing a simple stimulus sequence during functional magnetic resonance imaging (fMRI) at 1.5 T. The blocked stimulus sequence contrasted static object photographs with video takes of movement through natural indoor and outdoor scenes, alternated with a control fixation task. Two runs of the 5-min sequence sufficed to invoke 29 distinguishable activations, 16 (13 bilateral) of which were observed in all 10 participants. At the ventral side, object responsive activations were organized along the lateral occipital-temporal surface and near the collateral and occipital-temporal sulci. The latter activations, corresponding to the lateral occipital complex, showed a different activation profile from those near the collateral sulcus, most likely corresponding to the color constancy areas V4/V8-V4alpha. A potentially new fusiform object area was seen in 6 subjects, even more anterior than the parahippocampal place area. At the dorsal side, consistent activations were mainly related to motion stimuli and included the well-known areas V3a, VIPS, POIPS, hV5+, STS and the cingulate sulcus. There was consistent activation in the parietal-occipital sulcus, containing the areas V6a and V6. In addition, all subjects showed activation in the superior-anterior precuneus. Thus, the short stimulus sequence robustly invoked multiple visual areas and can be used to map the organization of the visual system in normal and brain-damaged individuals.

Adult↗

PubMed1996

Neural and skin cell-specific expression pattern conferred by steel factor regulatory sequence in transgenic mice.

We have produced transgenic mice expressing a lacZ reporter gene under the control of a fragment of a Steel factor (SLF). The function of this gene is essential for the development of hematopoietic cells, germ cells, melanocytes and pacemaker cells of the intestine. The expression of the transgene, containing 2 kb DNA 5' regulatory sequence, was restricted to neural and skin tissues in appropriate spatial and temporal pattern compared with endogenous SLF mRNA expression. This indicates that the regulatory elements necessary for the neural and skin specific expression are present in this 2 kb DNA sequence, although strong position-dependence of transgene expression was observed. As we could not detect transgene expression in hematopoietic tissues and germ cells after extending 10 kb upstream, elements important for these organs must reside in other regions. Our results indicate that neural crest derived enteric ganglion cells provide SLF to the neighboring pace maker cells expressing c-kit, the receptor for SLF. Cells expressing the transgene in the intestine are ganglion cells derived from neural crest since homozygosity for the lethal spotting (Is) mutation results in loss of such ganglion cells in transgenic mice. We have also shown that the dermal papillae of the hair follicle expresses the transgene, suggesting its roles to support the c-kit dependent growth and development of melanocytes in the hair follicle.

Animals↗

PubMed1997

Molecular dissection of the AGAMOUS control region shows that cis elements for spatial regulation are located intragenically.

AGAMOUS (AG) is an Arabidopsis MADS box gene required for the normal development of the internal two whorls of the flower. AG RNA accumulates in distinct patterns early and late in flower development, and several genes have been identified as regulators of AG gene expression based on altered AG RNA accumulation in mutants. To understand AG regulatory circuits, we are now identifying cis regulatory domains by characterizing AG::beta-glucuronidase (GUS) gene fusions. These studies show that a normal AG::GUS staining pattern is conferred by a 9.8-kb region encompassing 6 kb of upstream sequences and 3.8 kb of intragenic sequences. Constructs lacking the 3.8-kb intragenic sequences confer a GUS staining pattern that deviates both spatially and temporally from normal AG expression. The GUS staining patterns in the mutants for the three negative regulators of AG, apetala2, leunig, and curly leaf, showed the predicted change of expression for the construct containing the intragenic sequences, but no significant change was observed for the constructs lacking this intragenic region. These results suggest that intragenic sequences are essential for AG regulation and that these intragenic sequences contain the ultimate target sites for at least some of the known regulatory molecules.

AGAMOUS Protein, Arabidopsis↗

PubMed1993

Requirement of the carboxyl terminus of a bacterial chemoreceptor for its targeted proteolysis.

The bacterium Caulobacter crescentus yields two different progeny at each cell division; a chemotactically competent swarmer cell and a sessile stalked cell. The chemotaxis proteins are synthesized in the predivisional cell and then partition only to the swarmer cell upon division. The chemoreceptors that were newly synthesized were located at the nascent swarmer pole of the predivisional cell, an indication that asymmetry was established prior to cell division. When the swarmer cell differentiated into a stalked cell, the chemoreceptor was specifically degraded by virtue of an amino acid sequence located at its carboxyl terminus. Thus, a temporally and spatially restricted proteolytic event was a component of this differentiation process.

Amino Acid Sequence↗

PubMed1999

Role of alpha2C-adrenoceptor subtype in spatial working memory as revealed by mice with targeted disruption of the alpha2C-adrenoceptor gene.

The role of the alpha2C-adrenoceptor subtype in mediating the beneficial effect of alpha2-adrenoceptor agonists on spatial working memory was studied in adult mice with targeted inactivation of the alpha2C-receptor gene (KO) and their wild-type controls (WT). A delayed alternation task was run in a T-maze with mixed delays varying from 20 s to 120 s. Dexmedetomidine, a specific but subtype nonselective alpha2-adrenoceptor agonist, dose-dependently decreased the total number of errors. The effect was strongest at the dose of 5 microg/kg (s.c.), and was observed similarly in KO and WT mice. KO mice performed inferior to WT mice due to a higher number of perseverative errors. Dexmedetomidine slowed initiation of the motor response in the start phase at lower doses in WT mice than in KO mice but no such difference was observed in the return phase of the task, suggesting involvement of alpha2C-adrenoceptors in the cognitive aspect of response preparation or in response sequence initiation. According to these findings, enhancement of spatial working memory is best achieved with alpha2-adrenoceptor agonists which have neither agonistic nor antagonistic effects at the alpha2C-adrenoceptor subtype.

Adrenergic alpha-Agonists↗

PubMed1988

Analysis and prediction of the location of catalytic residues in enzymes.

The catalytic residues of an enzyme are defined as the amino acids directly involved in chemical catalysis. They mainly act as a general acid--base, electrophilic or nucleophilic catalyst or they polarize and stabilize the transition state. An analysis of the structural features of 36 catalytic residues in 17 enzymes of known structure and with defined mechanism is reported. Residues that bind metal ions (Zn2+ and Cu2+) are considered separately. The features examined are: residue type, location in secondary structure, separation between the residues, accessibility to solvent, intra-protein electrostatic interactions, mobility as evaluated from crystallographic temperature factors, polarity of the environment and the sequence conservation between homologous enzymes of residues that were sequentially or spatially close to the catalytic residue. In general the environment of catalytic residues is similar to that of polar side chains that have low accessibility to solvent. Two algorithms have been developed to identify probable catalytic residues. Scanning an alignment of homologous enzyme sequences for peaks of sequence conservation identifies 13 out of the 16 catalytic residues with 50 residues overpredicted. When the conservation of the spatially close residues is used instead, a different set of 13 residues are identified with 47 residues overpredicted. A combination of the two algorithms identifies 11 residues with 36 residues overpredicted.

Algorithms↗

PubMed1982

Clustered genes require extragenic territorial DNA sequences.

This paper is concerned with the basic question as to whether there exists a complex interaction between DNA sequences which have little specific function and functional genes regarding the spatial arrangement of the gene. Since gene clusters are a characteristic and basic feature of gene structure in higher eukaryotes, the size of extragenic DNA sequences surrounding the individual genes of various clustered gene families were compared. The size of the intergenic region, which is composed of the extragenic DNA sequences flanking the 3'-end of one gene and those flanking the 5'-end of the other gene, of the paired genes increases as the genes becomes larger. However, such a gene size-dependent increase is not seen if the total gene size of the paired genes is less than 0.3 kb or greater than 4 kb. The results suggests that a higher eukaryote gene requires extragenic territorial DNA sequences surrounding it, which presumably are necessary to maintain the gene's active functions.

Animals↗

PubMed1995

headcase, an imaginal specific gene required for adult morphogenesis in Drosophila melanogaster.

The majority of adult organs of a holometabolic insect like Drosophila melanogaster are derived from specific imaginal cells. These cells differ from their larval equivalents in many important cellular characteristics, ranging from the nature of the cell cycle to the timing and pattern of cellular differentiation. Here we describe the cellular, molecular and genetic characterization of a gene, headcase (hdc), which is required for imaginal cell development. hdc is the first gene to be described which is specifically expressed in all imaginal cells; this has allowed us to identify many imaginal primordia in the embryo and larval development. The Hdc protein is an extremely basic (pI 9.6) cytoplasmic protein with no obvious sequence similarities or conserved motifs. Interestingly, the spatial-temporal pattern of hdc expression prefigures imaginal cell re-entry into the mitotic cell cycle and persists until the final cell divisions. hdc null alleles have been isolated and found to cause pupal lethality, with dead pharate adults exhibiting defects in the differentiation of many adult tissues, most notably in head development. Ectopic expression of hdc, provided by a hdc-minigene, rescues the pupal lethality. Imaginal disc morphology in null mutants appears normal, therefore loss of hdc expression does not affect imaginal cell growth, but instead interferes with the ability of the imaginal primordia to differentiate properly during pupal development, suggesting that hdc may be involved in hormonal responsiveness during metamorphosis.

Animals↗

PubMed1993

A zebrafish homologue of the Drosophila neurogenic gene Notch and its pattern of transcription during early embryogenesis.

We describe here the primary structure of a zebrafish homologue of the Drosophila neurogenic gene Notch and its pattern of mRNA accumulation during embryogenesis. The gene produces a 8.5 kb transcript encoding a putative transmembrane protein with a high degree of sequence similarity to members of the Notch family, comprising 36 EGF-like repeats, three lin-12/Notch repeats, six cdc10/SWI6 repeats, OPA repeats and a PEST sequence. Transcription of the zebrafish Notch gene is spatially and temporally regulated. A high density of transcripts, most probably of maternal origin, can already be detected in the 2-cell stage. During pregastrulation stages, RNA is present in all cells. However, following gastrulation, transcripts accumulate in specific regions of the embryo following a rapidly changing pattern. In some of these regions, cell divisions take place at the time of Notch expression, in others processes of cell differentiation. This holds true for various mesodermal derivatives, such as the prospective notochord, and for different neural primordia, such as the neural plate and the brain vesicles. This pattern of transcript accumulation suggests a role for the zebrafish Notch homologue in processes of regionalization and cell diversification.

Amino Acid Sequence↗

PubMed2006

Dynamics of emotional effects on spatial attention in the human visual cortex.

An efficient detection of threat is crucial for survival and requires an appropriate allocation of attentional resources toward the location of potential danger. Recent neuroimaging studies have begun to uncover the brain machinery underlying the reflexive prioritization of spatial attention to locations of threat-related stimuli. Here, we review functional brain imaging experiments using event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI) in a dot-probe paradigm with emotional face cues, in which we investigated the spatio-temporal dynamics of attentional orienting to a visual target when the latter is preceded by either a fearful or happy face, at the same (valid) location or at a different (invalid) location in visual periphery. ERP results indicate that fearful faces can bias spatial attention toward threat-related location, and enhance the amplitude of the early exogenous visual P1 activity generated within the extrastriate cortex in response to a target following a valid rather than invalid fearful face. Furthermore, this gain control mechanism in extrastriate cortex (at 130-150 ms) is preceded by an earlier modulation of activity in posterior parietal regions (at 40-80 ms) that may provide a critical source of top-down signals on visual cortex. Happy faces produced no modulation of ERPs in extrastriate and parietal cortex. fMRI data also show increased responses in the occipital visual cortex for valid relative to invalid targets following fearful faces, but in addition reveal significant decreases in intraparietal cortex and increases in orbitofrontal cortex when targets are preceded by an invalid fearful face, suggesting that negative emotional stimuli may not only draw but also hold spatial attention more strongly than neutral or positive stimuli. These data confirm that threat may act as a powerful exogenous cue and trigger reflexive shifts in spatial attention toward its location, through a rapid temporal sequence of neural events in parietal and temporo-occipital areas, with dissociable neural substrates for engagement benefits in attention affecting activity in extrastriate occipital areas and increased disengagement costs affecting intraparietal cortex. These brain-imaging results reveal how emotional signals related to threat can play an important role in modulating spatial attention to afford flexible perception and action.

Attention↗

PubMed2000

Characterization of signal properties in atherosclerotic plaque components by intravascular MRI.

Magnetic resonance imaging (MRI) is capable of distinguishing between atherosclerotic plaque components solely on the basis of biochemical differences. However, to date, the majority of plaque characterization has been performed by using high-field strength units or special coils, which are not clinically applicable. Thus, the purpose of the present study was to evaluate MRI properties in histologically verified plaque components in excised human carotid endarterectomy specimens with the use of a 5F catheter-based imaging coil, standard acquisition software, and a clinical scanner operating at 0.5 T. Human carotid endarterectomy specimens from 17 patients were imaged at 37 degrees C by use of an opposed solenoid intravascular radiofrequency coil integrated into a 5F double-lumen catheter interfaced to a 0.5-T General Electric interventional scanner. Cross-sectional intravascular MRI (156x250 microm in-plane resolution) that used different imaging parameters permitted the calculation of absolute T1and T2, the magnetization transfer contrast ratio, the magnitude of regional signal loss associated with an inversion recovery sequence (inversion ratio), and regional signal loss in gradient echo (gradient echo-to-spin echo ratio) in plaque components. Histological staining included hematoxylin and eosin, Masson's trichrome, Kossa, oil red O, and Gomori's iron stain. X-ray micrographs were also used to identify regions of calcium. Seven plaque components were evaluated: fibrous cap, smooth muscle cells, organizing thrombus, fresh thrombus, lipid, edema, and calcium. The magnetization transfer contrast ratio was significantly less in the fibrous cap (0.62+/-13) than in all other components (P<0.05) The inversion ratio was greater in lipid (0.91+/-0.09) than all other components (P<0.05). Calcium was best distinguished by using the gradient echo-to-spin echo ratio, which was lower in calcium (0.36+/-0.2) than in all plaque components, except for the organizing thrombus (P<0.04). Absolute T1 (range 300+/-140 ms for lipid to 630+/-321 ms for calcium) and T2 (range 40+/-12 ms for fresh thrombus to 59+/-21 ms for smooth muscle cells) were not significantly different between groups. In vitro intravascular MRI with catheter-based coils and standard software permits sufficient spatial resolution to visualize major plaque components. Pulse sequences that take advantage of differences in biochemical structure of individual plaque components show quantitative differences in signal properties between fibrous cap, lipid, and calcium. Therefore, catheter-based imaging coils may have the potential to identify and characterize those intraplaque components associated with plaque stability by use of existing whole-body scanners.

Carotid Arteries↗

PubMed1995

Implicit learning of a nonverbal sequence in younger and older adults.

Two experiments examined age-related differences in implicit serial learning using the M. J. Nissen and P. Bullemer (1987) task. Younger adults and 2 samples of older adults who differed in educational attainment, occupational status, and verbal ability were given a 10-trial repeating sequence embedded in 100-trial blocks. On each trial, participants pressed a key that matched a designated spatial location. Implicit learning was inferred from the difference in RT between a random sequence trial block and the immediately preceding block with the repeating sequence. Results indicated that negative transfer effects were comparable for the younger and higher ability older adults, but lower ability older adults showed less evidence of implicit learning. On an explicit task, younger and higher ability older adults were more accurate than the lower ability older adults. The implications of these findings for current views on implicit learning in adulthood are discussed.

Adult↗