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Transmural distribution of 2-deoxyglucose uptake in normal and post-ischemic canine myocardium.

This investigation was performed to determine (i) whether 31P spatially localized 31P NMR spectroscopy could be utilized to determine the transmural distribution of 2-deoxyglucose (2DG) uptake in the in vivo canine heart and (ii) whether transmural 2DG uptake would be affected by a preceding ischemic insult. 2DG was infused and the accumulation of 2-deoxyglucose-6-phosphate (2DGP) was monitored (by means of spatially localized 31P NMR) in control hearts, in pharmacologically hyperperfused hearts, and in hearts subjected to four (5 min) occlusions of the left anterior descending coronary artery. Myocardial blood flow was measured with radioactive microspheres. In control hearts, subendocardial (ENDO) 2DGP contents were significantly higher than those in the subepicardium (EPI) being 3.8 +/- 0.3 and 2.2 +/- 0.2 mumol/g, respectively; the ENDO/EPI ratio of 2DGP was 1.70 +/- 0.21. During hyperperfusion blood flow increased approximately four-fold but 2DGP accumulation was not altered. ATP levels in post-ischemic myocardium were significantly decreased (ENDO more than EPI) and 2DGP accumulation in each layer was increased (p < 0.01 vs control); however, the ENDO/EPI ratio of 2DGP was not altered. 2DG infusion induced a marked elevation of blood insulin and norepinephrine levels. These data demonstrate that in the presence of high blood levels of 2DG and insulin: (i) 2DGP accumulation can be measured in the in vivo canine heart; (ii) in normal hearts 2DG uptake is more pronounced in the inner layers of the left ventricular wall (this transmural 2DG uptake gradient is not due to subendocardial hypoperfusion); and (iii) 2DG uptake is greater in the post-ischemic heart but the ENDO/EPI gradient of 2DG uptake is not altered indicating that the more severe ischemic insult in the subendocardium does not result in a disproportionate increase in 2DG uptake in that region of the myocardium. Although 2DG uptake patterns in this model most probably reflect those of glucose (at comparable glucose and insulin levels), quantitative extrapolations with regard to the rate of glucose uptake are not possible from the present data.

Animals↗

Modulation of urokinase-type and tissue-type plasminogen activator occurs at an early stage of progressing stages of chronic venous insufficiency.

Chronic venous insufficiency (CVI) progresses through a series of clinical stages, from healthy skin to poorly healing leg ulcers. The aim of this study was to analyse the distribution pattern and activity level of urokinase-type (uPA) and tissue-type plasminogen activators (tPA) in normal skin and in tissue biopsies of progressing stages of CVI, prior to and including venous ulceration. Biopsies 6 mm thick were taken from 14 healthy volunteers and 37 patients with 5 different stages of CVI: telangiectases; stasis dermatitis; hyperpigmentation; lipodermatosclerosis; and leg ulcer. Changes in the enzymatic activity and spatial localization of uPA and tPA during the progression of CVI were examined using in situ histological zymography. Normal skin and skin with telangiectases showed a punctate PA activity, consisting of both uPA and tPA activity. As CVI progressed, an increase in the distribution of uPA and a decrease in tPA activity was observed. The spatial localization of uPA was widespread within the dermis of biopsies from stasis dermatitis and lipodermatosclerosis and was associated in particular with the dermoepidermal junction. Hyperpigmented skin revealed a pattern of PA expression similar to that of healthy skin. However, leg ulcer specimens exhibited peak levels of uPA with little tPA. Furthermore, a plasminogen-independent protease activity that was not present in any of the earlier stages of CVI appeared. Our results indicate that there are profound changes in PA activity during the progression of CVI and that these changes begin early in CVI, for example, in stasis dermatitis. We hypothesize that the balance or imbalance of the PA activity in the later stages of CVI is an important pathogenic factor for the development of venous leg ulcer.

Adult↗

Spatial distribution of cell adhesion molecules on the peritoneal surface in the cecal perforation-induced peritonitis.

For understanding the immunological functions of the peritoneum, spatial localization of integrins and their ligands was studied by immuno-SEM on the peritoneal surface of mice with cecal perforation-induced peritonitis. The cecal peritoneum 24 hr after perforation was stained with specific antibodies against LFA-1, Mac-1, VLA-4, ICAM-1, VCAM-1, and fibronectin diluted with cold University of Wisconsin (UW) solution in conjunction with immuno-gold labeling. The spatial localization of those cell adhesion molecules was detected by backscatter electron (BSE) imaging with field emission scanning electron microscope (FESEM). Numerous leukocytes with diverse surface ultrastructure were observed on the peritoneal surface by FESEM. Some leukocytes were in contact with mesothelial cells, and others adhered to the exposed underlying connective tissue. The BSE imaging showed the ubiquitous distribution of Mac-1 on all membrane domains of leukocytes, i.e., cell body, ruffles, and microvilli. In contrast, predominant expressions of LFA-1 and VLA-4 were discernible on ruffles/microvilli of some leukocytes. The mesothelial cells remaining in the inflamed area expressed both ICAM-1 and VCAM-1 on their microvilli. The fibronectin was detected on presumable collagen fibers and/or fibrin over the exposed smooth muscle layer as well as on fibrin extending between leukocyte aggregation. The spatial microlocalization of integrins was clarified on the leukocytes emigrated in peritonitis, and their ligands were detected on the inflamed peritoneum.

Animals↗

Monitoring positional information during oogenesis in adult Drosophila.

About 184P[lac, ry+]A insertions (O'Kane & Gehring, 1987) have been incorporated into the genome via P element-mediated transformation. The temporal-spatial localization of beta-galactosidase, synthesized by these insertions during oogenesis, is described. 32% present control levels of endogenous beta-galactosidase expression and 68% show novel patterns. 13% of the insertions are germline-specific; 33%, follicle-cell-specific; 20% are expressed in both germ line and follicle cells; and 2%, specific to the germarium. Several lines exhibit strict temporal-spatial localizations of beta-galactosidase; notably those expressed in specific populations of follicle cells. The results are discussed with respect to some of the positional information encoded in the genome to which the insertions respond, the use of the insertions as markers for cell differentiation and the potential of the technique for isolating new genes involved in egg production.

Animals↗

Flow requirements in ventricular fibrillation: An in vivo nuclear magnetic resonance analysis of the left ventricular high-energy phosphate pool.

STUDY OBJECTIVE: We sought to determine whether flow rates of approximately 60% of normal values are sufficient to preserve the left ventricular myocardial high-energy phosphate pool during ventricular fibrillation (VF). METHODS: Mixed-breed swine (weight 22. 4+/-2.5 kg) were anesthetized with alpha-chloralose, placed in a state of VF, and perfused with extracorporeal circulation at a target flow of 50 mL.kg(-1).min(-1). In vivo whole-wall (average of left ventricular wall) and spatially localized phosphorous-31 nuclear magnetic resonance (NMR) spectra were acquired at baseline and during VF. RESULTS: Mean flow during VF was 58+/-20 mL.kg(-1). min(-1) (+/-SD; 95% confidence interval, 44 to 71) or about 60% of baseline cardiac output (n=13). Whole-wall adenosine triphosphate (ATP) decreased during perfused VF (P <.05), whereas creatine phosphate (CP) remained unchanged from baseline. With spatially localized NMR, the ratios of CP/ATP were similar at baseline in all layers (endocardium --> epicardium) of the left ventricular wall. However, during perfused VF, subepicardial CP/ATP ratios increased by 14% to 40% compared with baseline values, whereas subendocardial CP/ATP ratios remained unchanged (1% to 3% increase). An additional 4 animals perfused at 72+/-10 mL.kg(-1).min(-1) (+/-SD; 95% confidence interval, 56 to 92) during VF had preservation of CP and ATP levels. CONCLUSION: Flow levels equivalent to 60% of baseline cardiac output were insufficient to maintain normal high-energy phosphate levels in the in vivo fibrillating myocardium. At this level of flow, myocardial high-energy phosphate loss is nonhomogeneous within the left ventricular wall.

Adenosine Triphosphate↗

Noninvasive measurements of transmural myocardial metabolites using 3-D (31)P NMR spectroscopy.

A completely noninvasive three-dimensional (3-D) static magnetic field magnitude spatially localized (31)P spectroscopy technique has been developed and applied to study the in vivo canine myocardium at 9.4 T. The technique incorporates both Fourier series windows and selective Fourier transform methods utilizing all three orthogonal gradients for 3-D phase encoding. The number of data acquisitions for each phase-encoding step was weighted according to the Fourier coefficients to define cylindrical voxels. Spatially localized (31)P spectra can be generated for voxels of desired location within the field of view as a postprocessing step. The quality of localization was first demonstrated by using a three-compartment phantom. The technique was then applied to in vivo canine models and yielded (31)P cardiac spectra with an excellent signal-to-noise ratio. The in vivo validation experiments, using an implanted 2-phosphoenolpyruvate-containing marker, demonstrated that the technique is capable of measuring at least two transmural layers of left ventricular myocardium representing the subepicardium and subendocardium.

Adenosine Triphosphate↗

Dissociation of object and spatial visual processing pathways in human extrastriate cortex.

The existence and neuroanatomical locations of separate extrastriate visual pathways for object recognition and spatial localization were investigated in healthy young men. Regional cerebral blood flow was measured by positron emission tomography and bolus injections of H2(15)O, while subjects performed face matching, dot-location matching, or sensorimotor control tasks. Both visual matching tasks activated lateral occipital cortex. Face discrimination alone activated a region of occipitotemporal cortex that was anterior and inferior to the occipital area activated by both tasks. The spatial location task alone activated a region of lateral superior parietal cortex. Perisylvian and anterior temporal cortices were not activated by either task. These results demonstrate the existence of three functionally dissociable regions of human visual extrastriate cortex. The ventral and dorsal locations of the regions specialized for object recognition and spatial localization, respectively, suggest some homology between human and nonhuman primate extrastriate cortex, with displacement in human brain, possibly related to the evolution of phylogenetically newer cortical areas.

Adult↗

Random noise selective excitation pulses.

Several methods for the spatial localization of NMR signals from well-defined regions of tissue within extended specimens have been proposed. Most of these techniques are prone to signal error which can arise from large volumes of sample that surround the region of interest. These errors can theoretically be reduced by several orders of magnitude by the application of a radiofrequency prepulse. The pulse acts to randomize the unwanted spin magnetization prior to the application of a spatial localization technique.

Magnetic Resonance Spectroscopy↗

The chemical landscape of plant surface metabolites: Acylsugars as models of ecological function and structural diversity.

Plants produce a multifunctional assortment of specialized metabolites that play important roles in defense, environmental adaptation, and ecological interactions. Among these compounds, acylsugars, nonvolatile metabolites produced primarily in glandular trichomes of Solanaceae species, have emerged as informative model systems for understanding plant surface chemistry. Differences in acyl chain length, branching pattern, saturation, and attachment position generate extensive chemical diversity that influences herbivore deterrence, pathogen resistance, and the physicochemical properties of leaf surfaces. Recent advances in analytical chemistry, particularly liquid chromatography-ion mobility-tandem mass spectrometry (LC-IM-MS/MS), have greatly improved the ability to separate structurally related acylsugar isomers and characterize metabolite complexity at high resolution. When integrated with genomics, transcriptomics, and emerging spatial metabolomics approaches, these analytical tools provide new insights into acylsugar biosynthesis, pathway regulation, evolutionary diversification, and ecological function across plant species. This review positions acylsugars, particularly those of Solanum species, as model systems for understanding how structural diversity, spatial localization, and specialized metabolism shape ecological and physiological function at plant surfaces. We examine acylsugar structural diversity, biosynthetic pathways, ecological and physiological functions, and interactions with environmental and atmospheric processes. Major challenges, including extensive isomeric complexity, incomplete pathway characterization, and difficulties linking chemical structure to biological function, are discussed alongside emerging opportunities in integrative omics, crop improvement, sustainable pest management, and environmental monitoring. Overall, acylsugars provide a powerful model for linking molecular structure, spatial localization, and ecological function, offering broader insight into how specialized metabolism shapes plant adaptation, defense, and environmental interactions.

Acylsugars↗

Age, exercise, and coding performance.

We investigated the effects of exercise on the coding performance of young and older subjects. Hypotheses were tested that exercise either facilitates spatial localization or reduces susceptibility to distraction in older subjects. In a balanced design, we administered Digit Symbol and Symbol Digit coding tasks to exercisers and nonexercisers at two age levels under conditions of low or high within-task interference. The findings showed higher performance by the exercisers than by the nonexercisers only at the older age level and only with the Symbol Digit task. These findings support the hypothesis that exercise compensates for a loss of spatial localization skills with age. We found no evidence that susceptibility to distraction either increased with age or was affected by chronic exercise.

Adult↗

Local and spatial factors determining HIV-1 protease substrate recognition.

Insertional mutagenesis of the Escherichia coli thymidylate synthase (TS) was used to address substrate recognition of HIV-1 protease in a well characterized structural context. By modifying the TS conformation while maintaining its enzymic activity, we investigated the influence of protein folding on protease-substrate recognition. A slight destabilization of the TS structure permitted the cleavage of a target site, which was resistant in the native TS. This result supports a dynamic interpretation of HIV-1 protease specificity. Exposure time of the potential cleavage site, which depends on the stability of the global conformation, must be compatible with the cleavage kinetics, which are determined by the local sequence. Cleavage specificity has been described as the consequence of cumulative interactions, globally favourable, between at least six amino acids around the cleavage site. To investigate influence of local sequence, we introduced insertions of variable lengths in two exposed loops of the TS. In both environments, insertion of only two amino acids could determine specific cleavage. We then inserted libraries of dipeptides naturally cleaved by the HIV-1 protease in order to assess the limitations of established classifications of substrates in different conformational contexts.

Amino Acid Sequence↗

Noradrenaline depletion blocks behavioral sparing and alters cortical morphogenesis after neonatal frontal cortex damage in rats.

The possibility that cortical noradrenaline (NA) is necessary for sparing of function that occurs after neonatal frontal cortex damage was examined. Spatial localization by rats with frontal cortex damage on postnatal day 7 (P7) was better than that by rats with similar damage sustained as adults. The sparing was abolished in rats depleted of cortical NA by means of neonatal 6-hydroxydopamine (6HDA) administration. The blockade of sparing in the P7 frontal operates was associated with a smaller brain, thinner cortex, and reduced cortical dendritic branching relative to saline-treated P7 frontal operates. NA depletion alone in unoperated rats did not affect spatial learning but did reduce brain size and dendritic branching. Rats with frontal lesions on P4 did not show sparing of spatial localization, and 6HDA administration had no additional behavioral effect. Overall, these data are consistent with the notion that NA has some general function in maintaining some forms of plasticity in posterior cortex.

Animals↗

Sodium-23 magnetic resonance imaging of the eye and lens.

In order to develop a better understanding of cataract and to evaluate the effectiveness of potential drugs, noninvasive techniques must be devised to detect early metabolic changes. As a prelude to these goals, sodium-23 imaging experiments operating at 29.8 MHz (2.7 teslas) were performed on the bovine eye and lens. A spatially localized transverse relaxation time (T2)-weighted spin-density map of the sodium-23 within the lens is presented, with a resolution better than 250 micron. Due to the presence of short-T2 (3 msec) components within the lens, only the use of the planar-integral projection reconstruction (PPR) imaging scheme allowed sufficiently short echo-times (1 msec) to permit sodium-23 signal detection. These noninvasive imaging results show differences in the apparent sodium concentration within the lens that are consistent with separate, invasive measurements of sodium concentration. Separate analysis (with no spatial localization) at 79.4 MHz (7.2 teslas), using a shift reagent (dysprosium) to distinguish extracellular from intracellular sodium, indicates that approximately 62% of the detected sodium-23 signal is intracellular. These results are consistent with observations based on invasive measurements and further support the existence of the pump-leak system and a sodium gradient within the lens.

Animals↗

The Drm-Bowl-Lin relief-of-repression hierarchy controls fore- and hindgut patterning and morphogenesis.

The elucidation of pathways linking patterning to morphogenesis is a problem of great interest. We show here that, in addition to their roles in patterning and morphogenesis of the hindgut, the Drosophila genes drumstick (drm) and bowl are required in the foregut for spatially localized gene expression and the morphogenetic processes that form the proventriculus. drm and bowl belong to a family of genes encoding C(2)H(2) zinc finger proteins; the other two members of this family are odd-skipped (odd) and sob. In both the fore- and hindgut, drm acts upstream of lines (lin), which encodes a putative transcriptional regulator, and relieves its repressive function. In spite of its phenotypic similarities with drm, bowl was found in both foregut and hindgut to act downstream, rather than upstream, of lin. These results support a hierarchy in which Drm relieves the repressive effect of Lin on Bowl, and Bowl then acts to promote spatially localized expression of genes (particularly the JAK/STAT pathway ligand encoded by upd) that control fore- and hindgut morphogenesis. Since the odd-family and lin are conserved in mosquito, mouse, and humans, we propose that the odd-family genes and lin may also interact to control patterning and morphogenesis in other insects and in vertebrates.

Animals↗

Dynamic tracking in interventional MRI using wavelet-encoded gradient-echo sequences.

This work describes a newly developed magnetic resonance imaging (MRI) data-acquisition strategy which replaces the standard Fourier phase-encoding with the spatially localized coefficients of wavelet-encoding and offers a new technique for image guidance when combined with a dynamic tracking algorithm. By using this new technique, only a specific fraction of the entire raw data set needs to be updated and reconstructed to visualize the movement of an interventional device during an MR guided procedure. The combination of wavelet-encoding and a dynamic tracking algorithm was implemented in two-dimensional and three-dimensional gradient-echo sequences on a 0.2-T open C-arm-shaped MR system (Siemens, Erlangen Germany) and tested in phantom and in vitro experiments. When applying the wavelet-encoding direction parallel to the movement of a straight interventional device, only those spatially localized wavelet-coefficients mainly affected by the interventional device are updated. This led to potential increases of the image frame rate by a factor of up to seven.

Animals↗

The role of cell cycle-regulated expression in the localization of spatial landmark proteins in yeast.

In Saccharomyces cerevisiae, Bud8p and Bud9p are homologous plasma membrane glycoproteins that appear to mark the distal and proximal cell poles, respectively, as potential sites for budding in the bipolar pattern. Here we provide evidence that Bud8p is delivered to the presumptive bud site (and thence to the distal pole of the bud) just before bud emergence, and that Bud9p is delivered to the bud side of the mother-bud neck (and thence to the proximal pole of the daughter cell) after activation of the mitotic exit network, just before cytokinesis. Like the delivery of Bud8p, that of Bud9p is actin dependent; unlike the delivery of Bud8p, that of Bud9p is also septin dependent. Interestingly, although the transcription of BUD8 and BUD9 appears to be cell cycle regulated, the abundance of BUD8 mRNA peaks in G2/M and that of BUD9 mRNA peaks in late G1, suggesting that the translation and/or delivery to the cell surface of each protein is delayed and presumably also cell cycle regulated. The importance of time of transcription in localization is supported by promoter-swap experiments: expression of Bud8p from the BUD9 promoter leads to its localization predominantly to the sites typical for Bud9p, and vice versa. Moreover, expression of Bud8p from the BUD9 promoter fails to rescue the budding-pattern defect of a bud8 mutant but fully rescues that of a bud9 mutant. However, although expression of Bud9p from the BUD8 promoter fails to rescue a bud9 mutant, it also rescues only partially the budding-pattern defect of a bud8 mutant, suggesting that some feature(s) of the Bud8p protein is also important for Bud8p function. Experiments with chimeric proteins suggest that the critical element(s) is somewhere in the extracytoplasmic domain of Bud8p.

Actins↗

Localization of spatial attention processes with the aid of a probe technique.

A sudden visual onset is thought to 'attract attention to its location' within less than 100 ms. We attempted to measure the effect of this attentional process on the event-related potential (ERP) to a probe presented about 140 ms after the onset, and to delineate the spatiotemporal characteristics of such an effect, if any. ERPs were recorded from 30 channels from 6 subjects while they performed a target detection task. Both targets and probes could be located in each of the 4 quadrants (eccentricities 6.1 degrees and 7 degrees, respectively). For a given single target, the subsequent probe was either presented near the location of the target ('valid target') or at the diagonal opposite ('invalid target'). Appropriate 'neutral' conditions (probes preceded by no target, or by simultaneous targets in all quadrants) were applied, and ERPs to probes were corrected for the contribution of the ERPs to targets. The earliest effect of (in)validity was found at about 120 ms after probe onset for lower field probes. This effect consisted of enhanced posterior positivity for valid relative to neutral relative to invalid conditions. This positivity was superposed on a contralateral, extrastriate negative ongoing wave peaking at about 150 ms ('N150'). Source localization suggested that the (in)validity effects originate from deep medial parietal areas. The source corresponding to the N150 activity was not influenced by (in)validity. An earlier deflection to the probe at 80 ms ('NP80') depended on location, but not on (in)validity, and seemed to be of striate origin. Results are discussed in terms of a model postulating an attention-independent 'input module' from which activation is fed to a 'location module' embodying the actual attention mechanism.

Adult↗

Integrated MR imaging and spectroscopy with chemical shift imaging of P-31 at 1.5 T: initial clinical experience.

A section-selective three-dimensional phosphorus-31 chemical shift imaging (CSI) experiment was evaluated as the spatial localization method for spectroscopy in an integrated clinical magnetic resonance (MR) imaging and spectroscopy examination. The results of a CSI experiment can be displayed as either spectra related to specific voxels or "metabolite maps," in which the relative concentration of a given metabolite is displayed as an overlay of the MR image. This method was applied to the study of a soft-tissue mass and to a meningioma. The total imaging time in each case was 17 minutes with a voxel size of 27 cm3 in the extremity and 64 cm3 in the brain. The total time to set up this part of the study was about 10 minutes. No additional shimming was necessary when the center of the field of view selected for the CSI experiment was located at or near isocenter. The promising results obtained with this approach make the CSI method an attractive choice of spatial localization method.

Adult↗