Electrocardiogram and spatial vectorcardiogram of localized myocardial hypertrophy.
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Immunogold labeling of calcium-dependent neutral protease II (CDPII) with specific antibodies in near median longitudinal ultrathin sections of Allomyces arbuscula showed that the enzyme is predominantly localized in the growing hyphal and rhizoidal apices. The tips in both cell type had more enzyme than the distal regions and showed a gradient distribution. Labeling of the ultrathin sections and western blot analysis of purified subcellular fractions showed that CDPII is mainly cytosolic. Catalytic activity of the enzyme measured with synthetic substrate (Bz-Arg-pNA) showed that 90% of its activity is present in the soluble fraction, although a small amount is associated with the nuclei (0.2%), plasma membranes (0.7%) and microsomes (3.9%). This association is discussed in the context of the functional role of the enzyme and its possible localized activation. Western blot analysis of the crude extract and indirect immunofluorescence of the fixed permeabilized hypahe after treatment with CDPII showed that the alpha-tubulin is a specific target of the enzyme.
We studied resting, postexercise, difference (postexercise - rest) QRST isointegral maps, and the correlation coefficient between resting and postexercise maps. Study I Fifteen controls and 48 patients without previous myocardial infarction were studied. In coronary syndrome X group (n = 14), no patients showed an abnormally negative area on the postexercise map. In coronary ST depression group (n = 26), 12 patients (46%) showed an abnormally negative area on the postexercise map, and the correlation coefficient was low. Although all control, syndrome X, and coronary ST depression patients showed the global-downward type of difference map, coronary ST elevation patients (n = 8) showed the right-downward and left-upward type, right-upward and left-downward type, or reversed saddle type. Coronary ST depression is related to a globally marked decrease in local repolarization forces. Coronary ST elevation is associated with multidirectional changes in local repolarization forces. Study II Fifty-one patients with previous anterior infarction (29 with residual ischemia and 22 without) were studied. The incidence of the global-positive type of maps was increased and that of the saddle-type map was decreased from rest to postexercise in both groups. The global-upward type or right-downward and left-upward type of difference map was observed in both groups, but the reversed saddle type, right-upward and left-downward type, or global-downward type was observed in the residual ischemia group (34%, 24%, and 14%, respectively). Residual ischemia causes multidirectional changes or a global decrease in local repolarization forces. In both studies, multidirectional changes in local repolarization forces may be related to the vulnerability to ventricular arrhythmias.
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PURPOSE: Cell communication in the lens is critical for the life-long homeostasis of this tissue. Abundant gap junctions and cell-cell fusions are reported to be indispensable to the metabolic requirements and optical properties of the highly interconnected syncytial lens tissue. The expression of the recently characterized Panx1 and Panx2 gap junction proteins in the lens is, therefore, rather intriguing. Co-expression of pannexins and abundant connexins in the lens suggests that the two gap junction protein families have distinct roles in cell communication. METHODS: Panx1 and Panx2 expression was studied by in situ hybridization and quantitative RT-PCR. We examined properties and tissue distribution of Panx1 isoforms by Western blot analysis. Immunohistochemistry was used to visualize lens regions that accumulate Panx1 to study intercellular localization and spatial relationship with lens connexin gap junctions. RESULTS: Panx1 and Panx2 expression peaked in lens epithelial cells prior to differentiation. We detected one ubiquitously expressed Panx1 isoform and two additional isoforms that were only detected in the lens and the retina. Our results indicated that the ubiquitous 58 kDa and the oligomeric 120 kDa isoforms were plasma membrane-bound, resistant to Triton X-100 treatment, and was likely associated with cholesterol-enriched membrane microdomains. Immunohistochemistry revealed Panx1-specific punctuate labeling in the plasma membrane, and intensive labeling of the organelles in the epithelial and immature fiber cells. In addition, we detected Panx1 immunoreactivity in blood endothelial cells of the tunica vasculosa lentis capillaries and in blood erythrocytes. CONCLUSIONS: Despite similarity in detergent solubility of pannexins and connexins, the lack of spatial co-localization in the lens membranes suggested a distinct, non-redundant to connexin function for these proteins in the membrane.
This paper presents the first application of spatially correlated neutral models to the detection of changes in mortality rates across space and time using the local Moran's I statistic. Sequential Gaussian simulation is used to generate realizations of the spatial distribution of mortality rates under increasingly stringent conditions: 1) reproduction of the sample histogram, 2) reproduction of the pattern of spatial autocorrelation modeled from the data, 3) incorporation of regional background obtained by geostatistical smoothing of observed mortality rates, and 4) incorporation of smooth regional background observed at a prior time interval. The simulated neutral models are then processed using two new spatio-temporal variants of the Morany's I statistic, which allow one to identify significant changes in mortality rates above and beyond past spatial patterns. Last, the results are displayed using an original classification of clusters/outliers tailored to the space-time nature of the data. Using this new methodology the space-time distribution of cervix cancer mortality rates recorded over all US State Economic Areas (SEA) is explored for 9 time periods of 5 years each. Incorporation of spatial autocorrelation leads to fewer significant SEA units than obtained under the traditional assumption of spatial independence, confirming earlier claims that Type I errors may increase when tests using the assumption of independence are applied to spatially correlated data. Integration of regional background into the neutral models yields substantially different spatial clusters and outliers, highlighting local patterns which were blurred when local Moran's I was applied under the null hypothesis of constant risk.
A series of 4 experiments tested the effects of central catecholamine depletion on acquisition of an escape response in a spatial water maze. In Expt. 1, local infusions of 6-hydroxydopamine (6-OHDA) into the dorsal noradrenergic bundle (DNAB) enhanced efficient acquisition of the spatial water maze in a stressful condition (cold water), but had no effect in warm water. In Expt. 2, lesions of the ventral noradrenergic bundle did not affect acquisition of the maze, indicating that the changes observed in Expt. 1 were unlikely to have been the result of incidental damage to the noradrenergic innervation of the hypothalamus. Measures of core body temperature and plasma corticosterone were taken in parallel with the behavioral experiments and revealed that central noradrenaline (NA) depletion did not alter these responses to cold or warm water swims. Expt. 3 revealed a contrasting pattern of effects following dopamine (DA) depletion from the caudate-putamen: swimming speed was reduced in warm, but not cold water and maze acquisition was impaired, to an equal extent in warm and cold water. Finally, in Expt. 4, rats with 6-OHDA lesions of the DNAB were impaired in discriminating local cues in a simultaneous visual discrimination water maze. These results support the hypothesis that ceruleo-cortical NA depletion broadens the span of attention, particularly under stressful circumstances. In contrast, the results also indicate that striatal DA depletion mainly affects vigour of responding, as measured by swim speed, and that this effect can be reversed by the stressful effects of cold water.
Single-cell RNA-sequencing (scRNA-seq) techniques can measure gene expression at single-cell resolution but lack spatial information. Spatial transcriptomics (ST) techniques simultaneously provide gene expression data and spatial information. However, the data quality of the spatial resolution or gene coverage is still much lower than the quality of the single-cell transcriptomics data. To this end, we develop a ST-Aided Locator for single-cell transcriptomics (STALocator) to localize single cells to corresponding ST data. Applications on simulated data showed that STALocator performed better than other localization methods. When applied to the human brain and squamous cell carcinoma data, STALocator could robustly reconstruct the relative spatial organization of critical cell populations. Moreover, STALocator could enhance gene expression patterns for Slide-seqV2 data and predict genome-wide gene expression data for fluorescence in situ hybridization (FISH) and Xenium data, leading to the identification of more spatially variable genes and more biologically relevant Gene Ontology (GO) terms compared with the raw data. A record of this paper's transparent peer review process is included in the supplemental information.
The aim of this paper is to demonstrate the presence of a similar visual field effect on both spatial orientation and egocentric localization. A first experiment explored an orientation task (Visually Perceived Vertical or VPV determination) and compared the effects of a frame inclined either in the midfrontal plane (in this condition subjects assessed roll VPV) or in the median plane (subjects assessed pitch VPV) or in both combined planes (subjects assessed both roll and pitch VPV). A second experiment compared the frame effects specified above to the frame effect observed in an egocentric localization task (Visually Perceived Eye Level judgment) performed with a frame slanted in the median plane. The results showed that angular frame variations from -15 to +15 deg result in the same psychometric function for both orientation and localization tasks. In each experiment, correlations showed that individual differences occur in relation to an overall sensitivity to the visual field. Individual sensitivity may be accounted for by a ratio of visual to graviceptive information which remains constant whatever the perception plane (midfrontal or median plane) and whatever the task (spatial orientation or localization).
Individuals with Williams syndrome (WS) display poor visuo-spatial cognition relative to verbal abilities. Furthermore, whilst perceptual abilities are delayed, visuo-spatial construction abilities are comparatively even weaker, and are characterised by a local bias. We investigated whether this differentiation in visuo-spatial abilities can be explained by a deficit in coding spatial location in WS. This can be measured by assessing participants' understanding of the spatial relations between objects within a visual scene. Coordinate and categorical spatial relations were investigated independently in four participant groups: 21 individuals with WS; 21 typically developing (TD) children matched for non-verbal ability; 20 typically developing controls of a lower non-verbal ability; and 21 adults. A third task measured understanding of visual colour relations. Results indicated first, that the comprehension of categorical and coordinate spatial relations is equally poor in WS. Second, that the comprehension of visual relations is also at an equivalent level to spatial relational understanding in this population. These results can explain the difference in performance on visuo-spatial perception and construction tasks in WS. In addition, both the WS and control groups displayed response biases in the spatial tasks. However, the direction of bias differed across the groups. This finding is explored in relation to current theories of spatial location coding.
In this paper we discuss the properties of a recently introduced coupling scheme for spatially extended systems based on local spatially averaged coupling signals [see Z. Tasev et al., Int. J. Bifurcation Chaos Appl. Sci. Eng. (to be published); and L. Junge et al., Int. J. Bifurcation Chaos Appl. Sci. Eng. 9, 2265 (1999)]. Using the Ginzburg-Landau model, we performed an extensive numerical examination of this coupling scheme, i.e., a complete scan through the relevant coupling parameters. Furthermore, we demonstrate suppression and control of spatiotemporal chaos, e.g., stabilizing the homogeneous steady state and spatially localized control. As an application all model parameters of the Ginzburg-Landau equation are estimated given only the local information of the system.
Spatially varying directional selection together with restricted gene flow among populations is expected to lead to local adaptation. One environmental factor that potentially causes strong directional selection, but is little explored in evolutionary terms, is naturally and anthropogenically induced acidity. We studied local adaptation to acidity in four Swedish populations (two originating from areas that have suffered from severe anthropogenic acidification during the 1900s and two from areas which have remained neutral due to higher buffering capacity) of the moor frog Rana arvalis in a laboratory experiment by investigating whether differences in acid tolerance correspond to population origin. Embryos were raised from fertilization to hatching at three different pH levels (pH 4.0, 4.25 and 7.5), corresponding to levels experienced by these populations in nature, and acid stress tolerance was measured in terms of embryonic survival, hatchling size, and age. Evidence for local adaptation in all of these traits was found, the acid origin embryos having higher survival and less impaired growth performance under acid conditions than the neutral origin embryos. Our estimated rates of divergence (0.007-0.102 haldanes) suggest a rapid adaptation process in response to anthropogenic environmental change, and that the different traits have evolved at relatively similar rates.
One of the fundamental properties of spatial vision is the ability to localize objects in space. According to a recent proposal, accurate localization performance involves the operation of two systems: the attention system and the eye movement system. Upon stimulus presentation, attention is shifted to the target area: this provides coarse location information. Subsequently, a saccadic eye movement is executed: this provides fine location information. In this study we tested predictions derived from this model concerning the effects of precue information on localization performance. In a series of five experiments we manipulated duration of precue (71, 400, and 1,000 ms) and type of precue (spatial versus symbolic). Results showed that very short duration (i.e., 71 ms) spatial precues improved localization performance whereas very short duration symbolic precues did not. In contrast, the 1,000 ms duration precue condition showed similar amounts of precuing benefit for the spatial and symbolic precues. This pattern of differential precuing effects corroborated the two-process model of localization performance.
Specification of the end portions of the Drosophila body depends on the torso (tor) protein, a receptor tyrosine kinase that accumulates uniformly along the entire surface of the embryo but is activated only in the vicinity of the poles. Several genes are normally required for activating tor and appear to define a system in which a gene product tethered to the extracellular vitelline membrane at each end of the egg provides a local source for an extracellular tor ligand. This ligand would have to diffuse from the membrane to the cell surface of the embryo without losing its spatial localization. Here we report that the failure to accumulate tor protein at one or both poles leads to spatially inappropriate activity of more centrally located receptor. This ectopic activity depends on the same gene functions normally required for activating tor; thus we infer that it reflects inappropriate diffusion of the ligand to more central regions of the body. We conclude that the receptor not only transduces the spatial signal imparted by the tor ligand, but also ensures its correct localization by sequestering the ligand. Ligand trapping by receptor may also localize spatial signals in other patterning systems, including specification of the dorsal-ventral axis in Drosophila and of vulval cell fates in Caenorhabditis elegans.
The dynamic extraction of evoked potential is a problem of great interest in EEG signal processing. In this paper, a comprehensive method is presented which integrates spatial analysis and dipole localization to make full use of the spatial-temporal information contained in the multichannel stimulation records. A realistic double boundary head model is constructed through CT scans and a two-step method devised to overcome the ill-posed nature of the forward problem of EEG caused by the low conductivity of the skull. As a result, visual evoked potentials can be effectively extracted from only two consecutive records and the dynamic information of visual evoked potential thus procured. The efficiency of the presented method has been verified by means of computer simulation and a clinical experiment.
Auditory and visual target locations are encoded differently in the brain, but must be co-calibrated to maintain cross-sensory concordance. Mechanisms that adjust spatial calibration across modalities have been described (for example, prism adaptation in owls), though rudimentarily in humans. We quantified the adaptation of human sound localization in response to spatially compressed vision (0.5x lenses for 2-3 days). This induced a corresponding compression of auditory localization that was most pronounced for azimuth (minimal for elevation) and was restricted to the visual field of the lenses. Sound localization was also affected outside the field of visual-auditory interaction (shifted centrally, not compressed). These results suggest that spatially modified vision induces adaptive changes in adult human sound localization, including novel mechanisms that account for spatial compression. Findings are consistent with a model in which the central processing of sound location is encoded by recruitment rather than by a place code.
Recent theoretical studies have shown that dispersal between neighbouring local populations can promote the persistence of interacting metapopulations, even when the local dynamics are unstable and the environment is uniform. This persistence is associated with striking and self-organized spatial patterns in the densities of the local populations. Here we extend previous work on spatially distributed host-parasitoid interactions to wider questions of community structure, by considering various three-species systems: two parasitoid species attacking a common host species; two host species attacked by a single parasitoid species; or a host-parasitoid-hyperparasitoid interaction. In each of these cases, multispecies coexistence of the total populations can occur, even though the local population dynamics are unstable. Furthermore, co-existence tends to be accompanied by some degree of persistent spatial segregation of the competing species, despite the completely uniform environment. At its most extreme, this results in one species being confined to small, relatively static, "islands" within the habitat, giving the appearance of isolated pockets of favourable habitat. That dynamics can impose and maintain such "self-organizing" spatial segregation of competing species, has interesting implications for understanding the local abundance of natural populations.
Spatial and temporal control of transgene expression is one of the major prerequisites of efficient gene therapy. Recently, a noninvasive, physical approach has been presented based on local heat in combination with a heat-sensitive promoter. This strategy requires tight temperature control in vivo. Here, we use MRI-guided focused ultrasound (MRI-FUS) with real-time feedback control on a whole-body clinical MRI system for a completely automatic execution of a predefined temperature-time trajectory in the focal point. Feasibility studies on expression control were carried out on subcutaneously implanted rat tumors. A stable modified C6 glioma cell line was used carrying a fused gene coding for thymidine kinase (TK) and green fluorescent protein (GFP) under control of the human heat-shock protein 70 (HSP70) promoter. In vitro studies showed strong induction of the TK-GFP gene expression upon heat shock under various conditions and localization of the protein product in the nucleus. In vivo tumors were subjected to a 3-min temperature elevation using MRI-FUS with a constant temperature, and were analysed 24 hr after the heat shock with respect to GFP fluorescence. Preliminary results showed strong local induction in regions heated above 40 degrees C, and a good correspondence between temperature maps at the end of the heating period and elevated expression of TK-GFP.