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At least 217 records · Page 12Linked to original sources

Utilization of a polyethylene enclosure for nerve tracing studies in the rat ovary.

A commonly used technique for mapping neuronal connections in the peripheral nervous system involves the injection of a tracer substance into a peripheral organ. The tracer is taken up by nerve terminals at the injection site and transported retrogradely to motor or sensory perikarya where it can be visualized. One of the pitfalls of this technique is that tracer may leak from the injection site, enter nerve terminals adjacent to the injection area and thus cause erroneous interpretations. Similarly, some tracers may enter blood vessels and be taken up by nerve cell bodies indiscriminately. In order to circumvent these potential problems in studies on the innervation of the rat ovary, a polyethylene enclosure for the organ was fabricated from a BEEM capsule. The retrograde tracer, True blue, was then applied topically on the ovarian surface inside the enclosure. In chronic experiments, specifically labeled ovarian nerve cell bodies were identified in dorsal root and preaortic ganglia. Utilization of this simple and effective enclosure eliminates the false-positive and non-specific labeling of perikarya due to diffusion and blood-borne transport of the tracer from the injection area.

Animals↗

The artificial worlds approach to emergent evolution.

Artificial worlds models of evolutionary systems are computer models that map the essential logical structure of ecological systems, defined as self-sustaining biological organizations. The artificial world comprises an artificial environment, with mass components, energy input, and physical states. It also comprises artificial organisms, including a genome, a phenome, and a (developmental) map that connects the genome to the phenome. Mass components are cycled and space is limited. The evolution process results, as in nature, from genetic variation combined with natural selection imposed by the finiteness of the environment. The selection criteria (fitness values) are not imposed, but rather emerge from the interactions of the organisms with each other and with the environment. The dynamics at the population level also emerges from these basic interactions. In this paper we describe the comparative properties of the EVOLVE family of artificial worlds models.

Artificial Intelligence↗

A fuzzy c-means (FCM)-based approach for computerized segmentation of breast lesions in dynamic contrast-enhanced MR images.

RATIONALE AND OBJECTIVES: Accurate quantification of the shape and extent of breast tumors has a vital role in nearly all applications of breast magnetic resonance (MR) imaging (MRI). Specifically, tumor segmentation is a key component in the computerized assessment of likelihood of malignancy. However, manual delineation of lesions in four-dimensional MR images is labor intensive and subject to interobserver and intraobserver variations. We developed a computerized lesion segmentation method that has the advantage of being automatic, efficient, and objective. MATERIALS AND METHODS: We present a fuzzy c-means (FCM) clustering-based method for the segmentation of breast lesions in three dimensions from contrast-enhanced MR images. The proposed lesion segmentation algorithm consists of six consecutive stages: region of interest (ROI) selection by a human operator, lesion enhancement within the selected ROI, application of FCM on the enhanced ROI, binarization of the lesion membership map, connected-component labeling and object selection, and hole-filling on the selected object. We applied the algorithm to a clinical MR database consisting of 121 primary mass lesions. Manual segmentation of the lesions by an expert MR radiologist served as a reference in the evaluation of the computerized segmentation method. We also compared the proposed algorithm with a previously developed volume-growing (VG) method. RESULTS: For the 121 mass lesions in our database, 97% of lesions were segmented correctly by means of the proposed FCM-based method at an overlap threshold of 0.4, whereas 84% of lesions were correctly segmented by means of the VG method. CONCLUSION: Our proposed algorithm for breast-lesion segmentation in dynamic contrast-enhanced MRI was shown to be effective and efficient.

Algorithms↗

Geometric diffusions for the analysis of data from sensor networks.

Harmonic analysis on manifolds and graphs has recently led to mathematical developments in the field of data analysis. The resulting new tools can be used to compress and analyze large and complex data sets, such as those derived from sensor networks or neuronal activity datasets, obtained in the laboratory or through computer modeling. The nature of the algorithms (based on diffusion maps and connectivity strengths on graphs) possesses a certain analogy with neural information processing, and has the potential to provide inspiration for modeling and understanding biological organization in perception and memory formation.

Algorithms↗

Determination of uranine tracer dye from underground water of Mecsek Hill, Hungary.

The underground water system of Mecsek Hill, Hungary was studied using spectrofluorometry. A quantitative dye-tracing technique was used to map the connections between ground water recharge points and the springs and wells. Excitation-emission matrices were used to establish optimal spectroscopic parameters for spectral measurements. Only an EEM gives full spectrofluorimetric information about the sample and makes possible the determination of the optimal wavelength parameters. The uranine concentration was determined by measuring the synchronous excitation spectra of water samples. It was found that under the 4 microg/L uranine concentration, no special chemical treatment was necessary if the pH values remained between 7 and 8. However, above this concentration, the solution should be diluted to avoid spectral distortion from the increasing absorbance of the sample. Long-term concentration measurements were conducted based on spectrofluorometry.

Fluorescein↗

Gene transfer: manipulating and monitoring function in cells and tissues.

1. The ectopic expression of genes has proven to be an extremely valuable tool for biologists. The most widely used systems involve electrically or chemically mediated transfer of genes to immortalized cell lines and, at the other end of the spectrum, transgenic animal models. As would be expected, there are compromises to be made when using either of these broad approaches. Immortalized cell lines have limited "physiological relevance" and transgenic approaches are costly and out of the reach of many laboratories. There is also significant time required for the de novo generation of a transgenic animal. 2. As a viable alternative to these approaches, we describe the use of recombinant adenovirus and Sindbis virus to deliver genes to cells and tissues. 3. We exemplify this approach with studies from our laboratories: (i) an investigation of Ca2+ handling deficits in cardiac myocytes of hypertrophied hearts using infection with recombinant adenovirus encoding either green fluorescent protein (GFP) or the sarcoplasmic/endoplasmic reticulum calcium-ATPase (Serca2a); (ii) a study of the mechanism of macrophage/microglial migration by infection of embryonic phagocytes with a GFP-encoding virus and coculture with brain slices to then track the movement of labelled cells; and (iii) we are also exploiting the natural tropism of the Sindbis virus to label neurons in hippocampal brain slices in culture to resolve high-resolution structure and to map neuronal connectivity. 4. Further development of these approaches should open new avenues of investigation for the study of physiology in a range of cells and tissues.

Adenoviridae↗

Genetic markers in Sjögren's syndrome: the question of its genetic heterogeneity.

Genetic factors may be implicated in the causation of Sjögren's syndrome (SS) as shown by familial clustering of the disease and certain HLA associations. Non-HLA genetic markers in SS have not previously been studied in detail. In this study of 122 unrelated patients with various categories of SS and 104 control subjects, 29 genetic markers were studied (11 blood groups, 5 serum proteins and 13 red-cell enzymes). Almost all systems showed a considerable range of gene frequency among the various subgroups of patients with SS but only a few attained statistical significance (C3 and GPT). Multivariate (kinship) analysis, however, showed clear distinction between the subgroups of SS, suggesting that they are genetically distinct entities.

Alleles↗

Infrared-guided laser stimulation of neurons in brain slices.

Infrared-guided laser stimulation is a new technique that allows precise and rapid stimulation of visualized neurons in brain slices. Infrared imaging of neurons with a new contrast system is combined with the photolytic release of caged neurotransmitters by an ultraviolet (UV) laser. Addition of caged neurotransmitters to the superfusion medium of neurons in brain slices allows local excitation in the micrometer range with a focused spot of UV light. In this way, the distribution of glutamate or gamma-aminobutyric acid (GABA) receptors on neuronal dendrites can be mapped. Furthermore, this technique can be used to map the connectivity of neuronal networks through the controlled stimulation of neighboring neurons. Because the laser stimulation can be performed much faster than can paired recording, it is also possible to search for synaptic connections between distant neurons that have a low probability of connectivity.

Animals↗

Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: a system-level analysis.

Two-component signal transduction systems, comprised of histidine kinases and their response regulator substrates, are the predominant means by which bacteria sense and respond to extracellular signals. These systems allow cells to adapt to prevailing conditions by modifying cellular physiology, including initiating programs of gene expression, catalyzing reactions, or modifying protein-protein interactions. These signaling pathways have also been demonstrated to play a role in coordinating bacterial cell cycle progression and development. Here we report a system-level investigation of two-component pathways in the model organism Caulobacter crescentus. First, by a comprehensive deletion analysis we show that at least 39 of the 106 two-component genes are required for cell cycle progression, growth, or morphogenesis. These include nine genes essential for growth or viability of the organism. We then use a systematic biochemical approach, called phosphotransfer profiling, to map the connectivity of histidine kinases and response regulators. Combining these genetic and biochemical approaches, we identify a new, highly conserved essential signaling pathway from the histidine kinase CenK to the response regulator CenR, which plays a critical role in controlling cell envelope biogenesis and structure. Depletion of either cenK or cenR leads to an unusual, severe blebbing of cell envelope material, whereas constitutive activation of the pathway compromises cell envelope integrity, resulting in cell lysis and death. We propose that the CenK-CenR pathway may be a suitable target for new antibiotic development, given previous successes in targeting the bacterial cell wall. Finally, the ability of our in vitro phosphotransfer profiling method to identify signaling pathways that operate in vivo takes advantage of an observation that histidine kinases are endowed with a global kinetic preference for their cognate response regulators. We propose that this system-wide selectivity insulates two-component pathways from one another, preventing unwanted cross-talk.

Caulobacter crescentus↗

Bradykinin signalling to MAP kinase: cell-specific connections versus principle mitogenic pathways.

Mitogenic signalling pathways from G protein-coupled receptors (GPCRs) to the mitogen-activated protein kinase (MAPK) cascade may involve alpha- or betagamma-subunits of heterotrimeric G proteins, receptor or non-receptor tyrosine kinases, adaptor molecules, phosphoinositide 3-kinases, protein kinase C, and probably other proteins. The majority of models describing the connection of different signalling proteins within a mitogenic pathway are based on experimental data obtained by co- and overexpression of epitope-tagged MAPK together with the respective GPCR and other signalling proteins of interest in transfectable cell lines. Here the link of the bradykinin B2 receptor (B2R) to MAPK in the COS-7 cell expression system is compared with mitogenic signalling pathways of bradykinin in various tumour cell lines. It becomes evident that in natural or tumour cells expressing individual amounts and different isoforms of signalling proteins completely other relations between B2R and MAPK may exist than in COS-7 cells, suggesting a high degree of cellular specificity in mitogenic signalling.

Animals↗

Synaptic Ras GTPase activating protein regulates pattern formation in the trigeminal system of mice.

The development of ordered connections or "maps" within the nervous system is a common feature of sensory systems and is crucial for their normal function. NMDA receptors are known to play a key role in the formation of these maps; however, the intracellular signaling pathways that mediate the effects of glutamate are poorly understood. Here, we demonstrate that SynGAP, a synaptic Ras GTPase activating protein, is essential for the anatomical development of whisker-related patterns in the developing somatosensory pathways in rodent forebrain. Mice lacking SynGAP show only partial segregation of barreloids in the thalamus, and thalamocortical axons segregate into rows but do not form whisker-related patches. In cortex, layer 4 cells do not aggregate to form barrels. In Syngap(+/-) animals, barreloids develop normally, and thalamocortical afferents segregate in layer 4, but cell segregation is retarded. SynGAP is not necessary for the development of whisker-related patterns in the brainstem. Immunoelectron microscopy for SynGAP from layer 4 revealed a postsynaptic localization with labeling in developing postsynaptic densities (PSDs). Biochemically, SynGAP associates with the PSD in a PSD-95-independent manner, and Psd-95(-/-) animals develop normal barrels. These data demonstrate an essential role for SynGAP signaling in the activity-dependent development of whisker-related maps selectively in forebrain structures indicating that the intracellular pathways by which NMDA receptor activation mediates map formation differ between brain regions and developmental stage.

Animals↗

Imaging methods in examining the anatomy and function of the lumbar spine.

Conventional plain radiography, with or without flexion and extension images, is still the primary imaging modality of the lumbosacral spine despite the modern imaging methods. This is due to the simplicity of the technique and the good anatomical detail of the bone structure. Despite the limited information content of the plain radiographs, they are needed to serve as anatomical maps in connection with computed tomography or magnetic resonance imaging. In some institutions magnetic resonance imaging is now the primary modality for the evaluation of the lumbosacral spine, in others computed tomography and myelography still have a primary role, often depending on the availability of the devices. Magnetic resonance imaging clearly shows the anatomy of the discs, spinal nerves and dural sac. The diagnostic precision achieved with computed tomography in the evaluation of a herniated disc may also be achieved with magnetic resonance imaging. Differentiation of epidural scar from recurrent or residual disc herniation in patients with previous laminectomy, which with computed tomography myelography has been unreliable, can be evaluated by using magnetic resonance imaging enhanced with gadolinium-DTPA. The identification of facet joint disease is, however, less efficient with magnetic resonance imaging. Computed tomography and magnetic resonance imaging are probably nearly comparable in their accuracy in the evaluation of patients with sciatica. If cost and availability were not limiting factors, magnetic resonance imaging could provide an excellent screening technique for identifying individuals who would benefit from the identification of risks or preclinical disease or from institution of preventive measures.(ABSTRACT TRUNCATED AT 250 WORDS)

Back Pain↗