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Cine and tagged magnetic resonance imaging in short-term stunned versus necrotic myocardium.

We investigated the potential of Cine and 2D Tagged Cardiac Magnetic Resonance (CMR) Imaging to distinguish stunned from necrotic left ventricular (LV) myocardium in the early postischemic phase in an open-chest animal model (N = 12). Reversible and permanent occlusion of the LAD coronary artery resulted in global LV dysfunction in both groups without significant differences. LAD perfused segments revealed significant higher values for end systolic wall thickening (ESWT) and percentual systolic wall thickening in animals with stunned myocardium. Analysis of strain parameters showed significant regional differences (maximal principal strain lambda1, deviation angle beta) between postischemic and remote myocardium within both groups, however results were not significantly different comparing animals with stunned myocardium to animals with myocardial necrosis. In conclusion, at rest neither global LV functional nor regional strain parameters derived from Cine and 2D Tagged CMR Imaging can distinguish animals with short-term stunned myocardium from respective animals with necrotic myocardium. Diagnostic value of ESWT is limited due to the spatial resolution of the gradient-echo sequence used.

Animals↗

Enzymic and immunochemical properties of lysozyme. XVI. A novel synthetic approach to an antigenic reactive site by direct linkage of the relevant conformationally adjacent residues constituting the site.

Previous studies from this laboratory on the immunochemistry of specific chemical derivatives of native lysozyme and of the two disulfide peptide 62-68 (Cys 64-Cys 80) 74-97 (Cys 76-Cys 94) (i.e. (SS)2-peptide), have established an antigenic reactive site to comprise the spatially contiguous surface residues: Trp 72, Lys 97, Lys 96, Asn 93, Thr 89 and Asp 87. In the present work, the identity of the site was verified by an entirely different and novel approach. The aforementioned amino acids were linked directly into a single linear peptide with an intervening spacer where appropriate and substituting phenylalanine for tryptophan (i.e. Phe-Gly-Lys-Asn-Thr-Asp). This peptide (which does not exist in native lysozyme but simulates a surface region of the protein) possessed a remarkable inhibitory activity towards the reaction of lysozyme with its antisera. The immunochemical reactivity of the peptide was equal to the maximum expected reactivity of the site (i.e. a third of the total antigenic reactivity of lysozyme). These findings define quite conclusively and accurately the reactive site which is clearly composed of spatially adjacent residues that are distant in sequence reacting as if in direct linear linkage. The unequivocal establishment of this concept indicates that antigenic sites need not always be composed of residues in direct peptide linkage in the sequence. The nature of the site may depend on the protein. This unorthodox attack at the problem provides a novel and powerful approach for final delineation of the antigenic reactive sites (and perhaps other types of binding sites) in native proteins, following the completion of accurate narrowing down by chemical methods.

Amino Acid Sequence↗

Composite and classified color display in MR imaging of the female pelvis.

Because of its superior soft-tissue-imaging capabilities, MRI has proved to be an excellent modality for visualizing the contents of the female pelvis. In an effort to potentially improve gynecological MRI studies, we have applied color composite techniques to sets of spin-echo and gradient-echo gray-tone MR images obtained from various individuals. For composite generation, based on tissue region of interest calculated mean pixel intensity values, various colors were applied to spatially aligned images using a DEC MicroVAX II computer with interactive digital language (IDL) so that tissue contrast patterns could be optimized in the final image. The IDL procedures, which are similar to those used in NASA's LANDSAT image processing system, allowed the generation of single composite images displaying the combined information present in a series of spatially aligned images acquired using different pulse sequences. With our composite generation techniques, it was possible to generate seminatural-appearing color images of the female pelvis that possessed enhanced conspicuity of specific tissues and fluids. For comparison with color composites, classified images were also generated based on computer recognition and statistical separation of distinct tissue intensity patterns in an image set using the maximum likelihood processing algorithm.

Color↗

3D MPRAGE evaluation of lesions in the posterior cranial fossa.

Standard spin-echo images of the posterior cranial fossa are usually impaired by pulsation artifacts. We evaluated a heavily T1 weighted MPRAGE sequence (TR/TE/alpha/TI = 10/4/10-15 degrees/200-350) for detection of intracerebral lesions in the posterior fossa in 11 patients. Overall quality of the MPRAGE images was superior due to the lack of pulsation artifacts, high S/N and excellent gray-white matter contrast. Lesion detection was better in one patient, equal in six and inferior in four patients compared to SE technique. A cerebellar metastasis (8 mm) in one patient was completely blurred from pulsation artifacts on the SE images. Whereas multiple small lesions (< or = 4 mm) with discrete contrast enhancement were missed on the MPRAGE images in three patients. We conclude, that the MPRAGE sequence yields high quality images with isotropic spatial resolution in a reasonable time. But MPRAGE with these parameters can not replace standard SE images in screening the posterior fossa, because of a decreased sensitivity in the detection of small contrast-enhancing lesions.

Adolescent↗

Contamination potential of nitrogen compounds in the heterogeneous aquifers of the Choushui River alluvial fan, Taiwan.

This study aimed to analyze the contamination potential associated with the reactive transport of nitrate-N and ammonium-N in the Choushui River alluvial fan, Taiwan and to evaluate a risk region in developing a groundwater protection policy in 2021. In this area, an aquifer redox sequence provided a good understanding of the spatial distributions of nitrate-N and ammonium-N and of aerobic and anaerobic environments. Equiprobable hydraulic conductivity (K) fields reproduced by geostatistical methods characterized the spatial uncertainty of contaminant transport in the heterogeneous aquifer. Nitrogen contamination potential fronts for high and low threshold concentrations based on a 95% risk probability were used to assess different levels of risk. The simulated result reveals that the spatial uncertainty of highly heterogeneous K fields governs the contamination potential assessment of the nitrogen compounds along the regional flow directions. The contamination potential of nitrate-N is more uncertain than that for ammonium-N. The high nitrate-N concentrations (> or =3 mg/L) are prevalent in the aerobic environment. The low concentration nitrate-N plumes (0.5-3 mg/L) gradually migrate to the mid-fan area and to a maximum distance of 15 km from the aerobic region. The nitrate-N plumes pose a potential human health risk in the aerobic and anaerobic environments. The ammonium-N plumes remain stably confined to the distal-fan and partial mid-fan areas.

Environmental Monitoring↗

Contact hypersensitivity promotes hair regeneration through SPP1-secreting macrophages.

Allergic contact dermatitis, or contact hypersensitivity (CHS), is a pathological adaptive immune response that paradoxically induces hair regeneration, yet its underlying mechanisms remain unclear. We integrated high-resolution spatial transcriptomics and single-cell RNA sequencing to map the intricate interactions between immune cells, stroma, and hair follicles during CHS-induced hair growth in mice. Among all immunocytes, macrophages underwent the most prominent compositional and functional remodeling. We resolved five transcriptionally distinct macrophage subsets, with contact hypersensitivity driving a shift from homeostatic antigen-presenting cells toward a pro-inflammatory CD14+SPP1+ population. Trajectory analysis revealed divergent differentiation paths under homeostatic versus allergic conditions, highlighting the plasticity of skin macrophages. Mechanistically, CD14+SPP1+ macrophages secreted SPP1 (osteopontin), which engaged CD44 on hair follicle stem cells to activate PI3K-AKT signaling and trigger their proliferation. Notably, canonical pro-inflammatory cytokine signaling through TNF-&#x3b1; and IL-1 was dispensable for this process, underscoring the specificity of the SPP1-CD44 axis in immune-mediated hair regeneration. These findings reveal a macrophage-dependent mechanism of immune-mediated hair regeneration, offering therapeutic insights into immune-stem cell crosstalk.

Journal Article↗

A delivery device for presentation of tactile stimuli during functional magnetic resonance imaging.

We describe a novel stimulus delivery system designed to present tactile stimuli to a subject in the tunnel of a magnetic resonance imaging (MRI) system. Using energy from an air-driven piston to turn a wheel, the device advances a conveyor belt with a pre-determined sequence of stimuli that differ in their spatial features into the tunnel of the MRI. The positioning of one or several stimulus objects in a window near the subject's hand is controlled by a photoelectric device that detects periodic openings in the conveyor belt. Using this electric signal to position each presentation avoids cumulative positioning errors and provides a signal related to the progression of the experiment. We used a series of shapes that differed in their spatial features but the device could carry stimuli with a diversity of shapes and textures. This flexibility allows the experimenter to design a wide variety of psychophysical experiments in the haptic world and possibly to compare and contrast these stimuli with the cognitive treatment of similar stimuli delivered to the other senses. Appropriate experimental design allows separation of motor, sensory and memory storage phases of mental processes.

Electronics↗

Spatial serial order processing in schizophrenia.

The aim of this study was to examine serial order processing deficits in 21 schizophrenia patients and 16 age- and education-matched healthy controls. In a spatial serial order working memory task, one to four spatial targets were presented in a randomized sequence. Subjects were required to remember the locations and the order in which the targets were presented. Patients showed a marked deficit in ability to remember the sequences compared with controls. Increasing the number of targets within a sequence resulted in poorer memory performance for both control and schizophrenia subjects, but the effect was much more pronounced in the patients. Targets presented at the end of a long sequence were more vulnerable to memory error in schizophrenia patients. Performance deficits were not attributable to motor errors, but to errors in target choice. The results support the idea that the memory errors seen in schizophrenia patients may be due to saturating the working memory network at relatively low levels of memory load.

Adult↗

Orientation dependent modulation of apparent speed: a model based on the dynamics of feed-forward and horizontal connectivity in V1 cortex.

Psychophysical and physiological studies suggest that long-range horizontal connections in primary visual cortex participate in spatial integration and contour processing. Until recently, little attention has been paid to their intrinsic temporal properties. Recent physiological studies indicate, however, that the propagation of activity through long-range horizontal connections is slow, with time scales comparable to the perceptual scales involved in motion processing. Using a simple model of V1 connectivity, we explore some of the implications of this slow dynamics. The model predicts that V1 responses to a stimulus in the receptive field can be modulated by a previous stimulation, a few milliseconds to a few tens of milliseconds before, in the surround. We analyze this phenomenon and its possible consequences on speed perception, as a function of the spatio-temporal configuration of the visual inputs (relative orientation, spatial separation, temporal interval between the elements, sequence speed). We show that the dynamical interactions between feed-forward and horizontal signals in V1 can explain why the perceived speed of fast apparent motion sequences strongly depends on the orientation of their elements relative to the motion axis and can account for the range of speed for which this perceptual effect occurs (Georges, Seriès, Frégnac and Lorenceau, this issue).

Humans↗

Molecular and cellular properties of GnRH neurons revealed through transgenics in the mouse.

Recent advances in the use of gonadotropin-releasing hormone (GnRH) promoter-driven transgenics in the mouse are beginning to open up the once elusive GnRH neuronal phenotype to detailed molecular and cellular investigation. This review highlights progress in the development of GnRH promoter transgenic constructs and the understanding of murine gene sequences required for the correct temporal and spatial targeting of transgenes to the GnRH phenotype in vivo. Strategies enabling the identification of single, living GnRH neurons in the acute brain slice preparation are allowing gene profiling and electrophysiological experiments to be undertaken. Results so far indicate that, like other neurons, GnRH cells express a variety of sodium, potassium and calcium channels as well as GABAergic and glutamatergic receptors which are responsible for determining the membrane properties and firing characteristics of the GnRH neuron. Many of these receptors and channels appear to be expressed heterogeneously within the GnRH phenotype. Furthermore, several display distinct postnatal developmental expression profiles which are likely to be of consequence to the development of synchronized, pulsatile GnRH secretion in the adult animal.

Animals↗

Linear and nonlinear contributions to orientation tuning of simple cells in the cat's striate cortex.

Orientation selectivity is one of the most conspicuous receptive-field (RF) properties that distinguishes neurons in the striate cortex from those in the lateral geniculate nucleus (LGN). It has been suggested that orientation selectivity arises from an elongated array of feedforward LGN inputs (Hubel & Wiesel, 1962). Others have argued that cortical mechanisms underlie orientation selectivity (e.g. Sillito, 1975; Somers et al., 1995). However, isolation of each mechanism is experimentally difficult and no single study has analyzed both processes simultaneously to address their relative roles. An alternative approach, which we have employed in this study, is to examine the relative contributions of linear and nonlinear mechanisms in sharpening orientation tuning. Since the input stage of simple cells is remarkably linear, the nonlinear contribution can be attributed solely to cortical factors. Therefore, if the nonlinear component is substantial compared to the linear contribution, it can be concluded that cortical factors play a prominent role in sharpening orientation tuning. To obtain the linear contribution, we first measure RF profiles of simple cells in the cat's striate cortex using a binary m-sequence noise stimulus. Then, based on linear spatial summation of the RF profile, we obtain a predicted orientation-tuning curve, which represents the linear contribution. The nonlinear contribution is estimated as the difference between the predicted tuning curve and that measured with drifting sinusoidal gratings. We find that measured tuning curves are generally more sharply tuned for orientation than predicted curves, which indicates that the linear mechanism is not enough to account for the sharpness of orientation-tuning. Therefore, cortical factors must play an important role in sharpening orientation tuning of simple cells. We also examine the relationship of RF shape (subregion aspect ratio) and size (subregion length and width) to orientation-tuning halfwidth. As expected, predicted tuning halfwidths are found to depend strongly on both subregion length and subregion aspect ratio. However, we find that measured tuning halfwidths show only a weak correlation with subregion aspect ratio, and no significant correlation with RF length and width. These results suggest that cortical mechanisms not only serve to sharpen orientation tuning, but also serve to make orientation tuning less dependent on the size and shape of the RF. This ensures that orientation is represented equally well regardless of RF size and shape.

Animals↗

The segregation of the Escherichia coli origin and terminus of replication.

Escherichia coli chromosome replication forks are tethered to the cell centre. Two opposing models describe how the chromosomes segregate. In the extrusion-capture model, newly replicated DNA is fed bi-directionally from the forks toward the cell poles, forming new chromosomes in each cell half. Starting with the origins, chromosomal regions segregate away from their sisters progressively as they are replicated. The termini segregate last. In the sister chromosome cohesion model, replication produces sister chromosomes that are paired along much of their length. The origins and most other chromosomal regions remain paired until late in the replication cycle, and all segregate together. We use a combination of microscopy and flow cytometry to determine the relationship of origin and terminus segregation to the cell cycle. Origin segregation frequently follows closely after initiation, in strong support of the extrusion-capture model. The spatial disposition of the origin and terminus sequences also fits this model. Terminus segregation occurs extremely late in the cell cycle as the daughter cells separate. As the septum begins to invaginate, the termini of the completed sister chromosomes are transiently held apart at the cell centre, on opposite sides of the cell. This may facilitate the resolution of topological linkages between the chromosomes.

Base Sequence↗

[Possibilities of 3-dimensional ultrasound imaging].

This is a report on the clinical use of sonographic imaging. Experimental studies have shown that parallel sonographic sections are available only in vitro, which means no in-vivo three-dimensional reconstruction is possible as it is with magnetic resonance and computed tomography. The idea that a coordinated sequence of sections can be obtained by spatial rotation of the plane of sound so that the individual sections differ from one another by defined angular distances, enables three-dimensional reconstruction of sonographic in-vivo sections. A transducer was constructed that enables the production of sonographic sections rotating around a fixed center of rotation. Its clinical usefulness was tried and confirmed in the imaging of early pregnancies, benign and malignant carcinomas of the breast, and in imaging a gallbladder with a solitary gallstone. Three-dimensional imaging can be achieved either as a ring-shaped structure or with a continuous surface. This points to the possibility of diagnosing malformations early in pregnancy if the number of sections is sufficiently high. In tumour imaging the malignant tumour seems to be clearly distinguishable from the benign one; three-dimensional diagnosis is likely to furnish important additional criteria in diagnosis. Further clinical studies will have to verify this.

Breast Neoplasms↗

Chemical shift anisotropic mapping of a coherent optical absorber using magnetic field induced quantum beats.

A new method for mapping the spatial structure of optical coherent materials which relies on imposing a set of linear orthogonal gradient magnetic fields for a controlled hyperfine splitting of energy levels to create characteristic quantum beats when illuminated with a laser pulse with sufficient bandwidth to excite these levels is proposed. In this approach, a spectroscopic fingerprint of the dopant sites due to concentration and field susceptibilities in the sample is achieved through a Fourier decomposition of the radiative relaxation decay in an approach analogous to nuclear magnetic resonance spectroscopy due to the imposition of a controlled spatial-spectral encoding scheme. A three pulse sequence necessary to interrogate a gradient resolved voxel is also discussed. This three pulse approach can be combined with the conventional confocal imaging technique to provide information about the underlying chemistry of dopant distribution along each imaging plane which is useful in guiding the design and manufacturing process of optical crystals. In combination with gradient induced quantum beats, the entire inhomogeneous bandwidth can be interrogated. The proposed approach would scan this entire bandwidth at much faster rate enabling characterization of a large number of crystals than is currently possible through mechanical scanning with a confocal microscopy based spectroscopic technique as well as providing functional dopant profiling which is not currently possible with conventional approaches.

Journal Article↗

Information processing during face recognition: the effects of familiarity, inversion, and morphing on scanning fixations.

Where we make ocular fixations when viewing an object likely reflects interactions between 'external' object properties and internal 'top-down' factors, as our perceptual system tests hypotheses and attempts to make decisions about our environment. These scanning fixation patterns can tell us how and where the visual system gathers information critical to specific tasks. We determined the effects of the internal factors of expertise, experience, and ambiguity on scanning during a face-recognition task, in eight subjects. To assess the effects of expertise, we compared upright with inverted faces, since it is hypothesized that inverted faces do not access an orientation-dependent face-expert processor. To assess the effects of experience, we compared famous with novel faces, as famous faces would have stronger internal representations than anonymous ones. Ambiguity in matching seen and remembered faces was manipulated with morphed faces. We measured three classes of variables: (i) total scanning time and fixations; (ii) the spatial distribution of scanning; and (iii) the sequence of scanning, using first-order Markov matrices for local scan structure and string editing for global scan structure. We found that, with inverted faces, subjects redistributed fixations to the mouth and lower face, and their local and global scan structure became more random. With novel or morphed faces, they scanned the eyes and upper face more. Local scan structure was not affected by familiarity, but global scan structure was least random (most stereotyped) for novel upright faces. We conclude that expertise (upright faces) leads to less lower-face scanning and more predictable global patterns of information gathering. Experience (famous faces) leads to less upper-face scanning and more idiosyncratic global scan structures, suggesting a superseding influence of facial memories. With morphed faces, subjects return to the upper face to resolve ambiguity, implying a greater importance of this region in face recognition.

Adult↗

Imaging of H217O distribution in the brain of a live rat by using proton-detected 17O MRI.

Imaging of H217O has a number of important applications. Mapping the distribution of H217O produced by oxidative metabolism of 17O-enriched oxygen gas may lead to a new method of metabolic functional imaging; regional cerebral blood flow also can be measured by measuring the H217O distribution after the injection of 17O-enriched physiological saline solution. Previous studies have proposed a method for indirect detection of 17O. The method is based on the shortening of the proton T2 in H217O solutions, caused by the residual 17O-1H scalar coupling and transferred to the bulk water via fast chemical exchange. It has been shown that the proton T2 of H217O solutions can be restored to that of H216O by irradiating the resonance frequency of the 17O nucleus. The indirect 17O image thus is obtained by taking the difference between two T2-weighted spin-echo images: one acquired after irradiation of the 17O resonance and one acquired without irradiation. It also has been established that, at relatively low concentrations of H217O, the indirect method yields an image that quantitatively reflects the H217O distribution in the sample. The method is referred to as PRIMO (proton imaging of oxygen). In this work, we show in vivo proton images of the H217O distribution in a rat brain after an i.v. injection of H217O-enriched physiological saline solution. Implementing the indirect detection method in an echo-planar imaging sequence enabled obtaining H217O images with good spatial and temporal resolution of few seconds.

Animals↗

Scoring schemes of palindrome clusters for more sensitive prediction of replication origins in herpesviruses.

Many empirical studies show that there are unusual clusters of palindromes, closely spaced direct and inverted repeats around the replication origins of herpesviruses. In this paper, we introduce two new scoring schemes to quantify the spatial abundance of palindromes in a genomic sequence. Based on these scoring schemes, a computational method to predict the locations of replication origins is developed. When our predictions are compared with 39 known or annotated replication origins in 19 herpesviruses, close to 80% of the replication origins are located within 2% of the genome length. A list of predicted locations of replication origins in all the known herpesviruses with complete genome sequences is reported.

Algorithms↗

Cytochrome P450 1A4 and 1A5 in common cormorant (Phalacrocorax carbo): evolutionary relationships and functional implications associated with dioxin and related compounds.

The present study characterized cytochrome P4501A (CYP1A) isoforms from common cormorant (Phalacrocorax carbo) with regard to their evolutionary relationships and their roles in disposition of dioxin and related compounds (DRCs). Two clones isolated from a cormorant liver cDNA library were named CYP1A4 and CYP1A5 on the basis of greatest overall amino acid identity shared with chicken (Gallus gallus) CYP1A4 (78%) and CYP1A5 (78%), respectively. Spatial heterogeneity in phylogenetic signal along the sequences strongly indicated that cormorant CYP1A4 and CYP1A5 have undergone partial interparalog gene conversion, similar to chicken and mammalian CYP1As. Phylogenetic analysis of a putatively unconverted region produced a tree topology consistent with the orthology of avian CYP1A5s with mammalian CYP1A2s and avian CYP1A4s with mammalian CYP1A1s. Hepatic CYP1A4 and CYP1A5 mRNA levels in wild cormorants from Lake Biwa, Japan, were quantified to examine the effects of DRCs on isoform-specific expression and to evaluate the toxicokinetics of DRCs in which CYP1A expression is involved. Both CYP1A4 and CYP1A5 mRNA levels were positively correlated with total tetrachlorodibenzo-p-dioxin toxic equivalents and concentrations of each congener in most cases in the liver, suggesting the induction of both enzymes through a shared transcriptional mechanism. The lack of correlation of 2,3,7,8-tetrachlorodibenzofuran and 3,3',4,4'-tetrachlorobiphenyl (PCB77) to CYP1A gene expression is likely due to the rapid metabolism of these two congeners. Liver-to-muscle concentration ratios for most DRC congeners except PCB77 and mono-ortho coplanar polychlorinated biphenyls significantly increased with an elevation of CYP1A4 and CYP1A5 mRNA levels. The present data suggest that hepatic sequestration of some DRCs occurs in cormorant via binding to either CYP1A5 or both CYP1A4 and CYP1A5.

Amino Acid Sequence↗