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A modularized infrared light matrix system with high resolution for measuring animal behaviors.

The current study provides a new modularized infrared light matrix system (about $200 cost) which is designed to measure the horizontal gross or fine movements, vertical motion, clockwise or anticlockwise turnings, freezing time, and total distance traveled in rats. The system records the sequences of animal's activity in a computer-aided system with a resolution of 0.2 s in time or 1.6 cm in space, and permanently stores all the resulting data in file. The behavioral apparatus was tested for its sensitivity and usability by amphetamine-injected rats. It was found that intraperitoneal administration of amphetamine (1.25-2.50 mg/kg), but not normal saline, produced a dose-related increase in either the horizontal gross or fine movements, vertical motion, clockwise or anticlockwise turnings, or total distance traveled. However, amphetamine injections produced a dose-related decrease in freezing time. Apparently, most of the amphetamine-induced responses obtained by other detecting apparatus can be reproduced easily by the present apparatus. The current detection system possesses the following advantages: a) high resolution, b) high expansion potential, and c) precise and simplified algorithms for behavioral parameter analysis.

Algorithms

Flexible ureteropyeloscopy with modular, "disposable" endoscope.

A flexible modular ureteropyeloscope has been utilized in 36 patients. The flexible tips of this instrument can be replaced and have been available in sizes 6.0F, 8.5F, and 11.0F. The instrument was passed successfully into the ureter in 37 of 38 patients. The most frequent indications were surveillance for fragments after lithotripsy and for diagnosis of radiographic abnormalities in the upper tracts. The high success rate in these patients supports wider application of these techniques and indicates the potential for therapeutic procedures through flexible ureteroscopes.

Disposable Equipment

The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin.

The Drosophila segment polarity gene armadillo is required for pattern formation within embryonic segments and imaginal discs. We have found that armadillo is highly conserved during evolution; it is 63% identical to human plakoglobin, a protein found in adhesive junctions joining epithelial and other cells. We have examined arm protein localization in a number of larval tissues and found that arm protein accumulation within cells shares many features with the accumulation of plakoglobin. We have compared the phenotype and molecular lesions responsible for the different arm mutations. Surprisingly, severely truncated proteins retain some function; the degree of function is strictly correlated with the length of the truncated protein, suggesting that the internally repetitive arm protein is modular in function. We present a possible model for the cellular role of arm.

Alleles

A modular numerical model of the cardiovascular system for studying and training in the field of cardiovascular physiopathology.

A modular numerical model of the cardiovascular system has been developed to reproduce the most important circulatory phenomena in terms of pressure and volume relationships. It is an easy tool to use, designed to be used with a friendly approach on any IBM or compatible personal computer: it offers a wide selection of graphical and numerical outputs and can be rearranged easily for a particular experiment. A set of subroutines related to different circulatory phenomena has been developed; they can be assembled easily together and communicate with each other by two variables. A full description of the existing subroutines is presented in this paper with three different application examples resulting from the rearrangement of the existing software modules: the first concerns the behaviour of the natural ventricle model itself and can be regarded as a ventricle stand-alone characterization test in terms of preload and afterload sensitivities, the second is related to the use of a pneumatic ventricle instead of the model of the natural ventricle, and the third is a full model of the cardiocirculatory system.

Cardiology

Effect of manufacturing tolerances on the micromotion at the Morse taper interface in modular hip implants using the finite element technique.

This study reports on the examination of the effect of manufacturing tolerances on the micromotion at the Morse taper interface in modular hip implants. The finite element technique was used as a tool of analysis. Special emphasis was placed on the consideration of the transient dynamic conditions under which a prosthesis works inside the human body. In order to simulate approximately the repetitive forces acting on a hip implant during the human walking cycle, a time-variant sinusoidal load was applied on the head of the taper. The locking of the Morse taper joint by the surgeon in the operating room at the time of implantation was simulated by specifying an axial displacement to the female taper component as an initial condition.

Biomechanical Phenomena

Characterization of Xenopus laevis complement factor I structure--conservation of modular structure except for an unusual insert not present in human factor I.

Factor I (C3b/C4b inactivator) is a regulatory protein of the classical and alternative complement pathways. In this paper, we report the sequence of Xenopus factor I cDNA and the deduced protein structure. The basic structure of human preprofactor I, NH2-heavy chain-cleavage peptide-light chain-COOH, is conserved in the frog. However, the frog heavy chain contains a highly charged segment of 29 amino acids, encoded by a poly dA-rich mRNA insert, which is not found in human factor I. The modular structure of the frog heavy chain was analyzed, and found to differ vis-à-vis previously published analyses of human factor I. We also evaluate the timing of factor I transcription during frog embryogenesis.

Amino Acid Sequence

Modular construction of nervous systems: a basic principle of design for invertebrates and vertebrates.

The modular construction of brain tissue is not solely a feature of vertebrate nervous tissue, but is characteristic of many invertebrate nervous systems as well. Modern vertebrate and invertebrate modules vary over several orders of magnitude in volume but vary less in diameter. Although the physiological and anatomical differences between the modules discussed herein are overpowering, their importance to nervous system functions are similar. Modules are the serial and parallel processing units that have allowed large-brained animals to evolve. Many invertebrate modules are discrete, hemispherical lobes, visible on the surface of the brain or nerve cord, whereas most mammalian modules are columnar or ellipsoidal tissue compartments that can only be visualized with specific anatomical methods. Lobes from the largest invertebrates can be more voluminous than any neocortical compartments, but these large lobes are usually not single modules. Large invertebrate lobes contain internal compartments that are single modules and of similar size to their vertebrate analogs. However, vertebrate cortical modules or columns, are far more numerous than the compartments in invertebrate brains and in several cases are known to be adjoined laterally into slabs of tissue that extend for several millimeters. Physiological data support the idea that neural modules are not just anatomical entities, but are active local circuits. The specific activities within each type of module will depend upon its neuronal components, both intrinsic and extrinsic, its functional roles and phylogenetic history. Many cellular and intercellular phenomena common to vertebrates and invertebrates underlie the development of modules. Neuronal and glial interactions and their interplay with the extracellular environment depend upon families of molecules with broad phyletic occurrences. The commonalities of growth mechanisms may to a large degree account for the widespread incidence of neuronal processing units. The strategy of enlarging a nervous system through the replication of the basic units is thought to be advantageous for several reasons. This plan allows nervous systems to economize on the branch sizes and lengths needed for interconnections, to ensure that appropriate targets are reached during development and to modulate specific circuits within a larger network.

Animals

A simple modular tissue bath developed for 'in vitro' studies of the isolated spinal cord.

A tissue bath for studies of the mammalian spinal cord in vitro is described. The modular construction of the bath permits considerable flexibility for accommodating different tissue preparations. The individual components of the bath are easily constructed and the design permits multiple compartment baths to be simply formed. The design principle on which the bath is based may have much wider application than that described.

Animals

Unraveling the modular design of glutamate-gated ion channels.

Glutamate receptors that function as ligand-gated ion channels are essential components of cell-cell communication in the nervous system. Despite a wealth of information concerning these receptors, details of their structure are just beginning to emerge. We propose that glutamate receptors comprise four modules: two modules that are related to bacterial periplasmic-binding proteins, one module that is related to the pore-forming region of K+ channels, and one regulatory module of unknown origin. A K(+)-channel-like domain inserted into a crucial region of a periplasmic-binding protein-like domain suggests a mechanism for transduction of binding energy to channel opening. This modular design also suggests an evolutionary link between a ligand-gated ion-channel family and voltage-gated ion channels.

Amino Acid Sequence

EyeChem 1.0: a modular chemistry toolkit for collaborative molecular visualization.

EyeChem is a network-aware and modular molecular visualization toolkit used within the Iris Explorer Visualization program. Use of the toolkit is illustrated via four typical EyeChem applications, which consist of Explorer maps constructed from chemically oriented modules and developed for use over the new generation of fast networks such as the UK SuperJanet system. EyeChem can also be used to prepare multimedia style visualizations in Quicktime or MPEG format of molecular properties and wavefunctions for archiving via the gopher+ wide area information system. The use of such information in electronic publishing of chemical information is discussed.

Chemistry

Torsional resistance and wear of a modular sleeve-stem hip system.

The torsional resistance and wear debris generation of the modular sleeve and stem S-ROM total hip system was evaluated. The results indicate that slippage of the sleeve-stem interface may occur under physiological loading conditions. Slippage is more likely to occur if the junction is contaminated by blood or tissue, or if the stem is disengaged and reimplanted into the sleeve. Significant wear debris was generated during cyclic fatigue loading. The wear debris was of the size (less than 10 mum) readily ingested by macrophages. Particles of these dimensions have been associated with osteolysis, implant loosening and pain. Based upon the findings of this study the implantation of this type system must be carefully considered.

Corrosion

tRNA-rRNA sequence homologies: evidence for an ancient modular format shared by tRNAs and rRNAs.

Homologies between tRNAs and rRNAs are identified in searches using various combinations of Escherichia coli, yeast, Halobacterium volcanii and bovine mitochondrial sequences. As in previously reported comparisons, the homologies are too frequent and long to be attributed to coincidence, and similar frequencies from inter- and intraspecies comparisons preclude evolutionary convergence as an explanation. In contrast to the earlier studies, patterns in the positioning of the homologies are now described. Graphing the positions of the homologies along orthogonal axes that represent numbers of bases in tRNA and rRNA shows recurring patterns in the alignments. Preferred spacings of integral multiples of 9 bases are found, suggesting a periodicity in the ancestral structure from which the tRNAs and rRNAs were derived. The periodicity also suggests persistence of a modular format in both classes of molecules that survived changes in sequence that occurred during evolution. A model is proposed for the generation of the ancestral molecule and the early evolution of the coding mechanism. Elongation by self-priming and self-templating gave a hairpin with a 9 base stem. Two additional cycles gave a 70-80 base tRNA-like structure. Additional cycles yielded a tandem repeat of this unit, roughly equivalent in size to the combined rRNAs of prokaryotes. The larger RNA would contain the information and materials for generating the smaller RNAs. It is proposed that multiple recombination among such molecules gave composite structures, presumed progenitors of today's t- and rRNAs. The distribution of the conserved domains among today's species argues for the existence of the ancestral molecule prior to divergence of lines leading to the various kingdoms. Their presence in the different nucleic acids suggests the existence of a nucleic acid with multiple functions prior to partitioning of these functions among the nucleic acids that exist today. The occurrence of overlaps, overlays and consensus alignments among the homologies provides the means for identifying contiguous and neighboring conserved regions and holds promise for the reconstruction of the sequence of an ancestral molecule.

Animals

Modular organization of the lytic enzymes of Streptococcus pneumoniae and its bacteriophages.

The nucleotide sequences of genes cpl7 and cpl9 of the Streptococcus pneumoniae bacteriophages Cp-7 and Cp-9, encoding the muramidases CPL-7 and CPL-9, respectively, have been determined. The N-terminal domains of CPL-7 and CPL-9 were virtually identical to that previously reported for the CPL-1 muramidase. The C-terminal domain of the CPL-7 muramidase, however, was different from those of the host amidase and the phage Cp-1 and Cp-9 lysozymes. Whereas all enzymes studied are characterized by repeated sequences at their C termini, the repeat-unit lengths are 20 amino acids (aa) in CPL-1, CPL-9 and in the host amidase, but 48 aa in CPL-7. Six repeated sequences represent the C-terminal domains of CPL-1, CPL-9 and the host amidase, and 2.8 perfect tandem repetitions that of CPL-7. The peculiar characteristics of the structure of CPL-7 muramidase correlate with its biochemical and biological properties. Whereas CPL-1, CPL-9 and the pneumococcal amidase strictly depend on the presence of choline-containing cell walls for activity, CPL-7 is able to degrade cell walls containing either choline or ethanolamine. These results support the previously postulated role for the C-terminal domain of these lytic enzymes in substrate recognition and provide further experimental evidence supporting the notion that the proteins have evolved by an exchange of modular units.

Amino Acid Sequence

A modular set of lacZ fusion vectors for studying gene expression in Caenorhabditis elegans.

We describe a series of plasmid vectors which contain modular features particularly useful for studying gene expression in eukaryotic systems. The vectors contain the Escherichia coli beta-galactosidase (beta Gal)-encoding region (the lacZ gene) flanked by unique polylinker segments on the 5' and 3' ends, and several combinations of a variety of modules: a selectable marker (an amber suppressor tRNA), a translational initiation region, a synthetic intron segment, the early polyadenylation signal from SV40, and 3' regions from two nematode genes. A segment encoding the nuclear localization peptide from the SV40 T antigen is incorporated into many of the constructs, leading to beta Gal accumulation in nuclei, which can facilitate identification of producing cells in complex tissues. To make functional beta Gal fusions to secreted proteins, we constructed plasmids with an alternate module encoding a synthetic transmembrane domain upstream from lacZ. This domain is designed to stop transfer of secreted proteins across the membrane during secretion, allowing the beta Gal domain of the fusion polypeptide to remain in the cytoplasm and thus function in enzymatic assays. We have used the vectors to analyze expression of several genes in the nematode Caenorhabditis elegans, and have demonstrated in these studies that lacZ can be expressed in a wide variety of different tissues and cell types. These vectors should be useful in studying gene expression both in C. elegans and in other experimental systems.

Amino Acid Sequence

Clusters of modular regulatory elements at DNA replication origins.

To study the specificity of eukaryotic origins of replication (ori), we have isolated a fraction of mouse DNA enriched in replication initiation sequences (RIS), and cloned and characterised some of these RIS. The sequences of three RIS were analysed for the presence of sequence elements common to other known eukaryotic ori. It was found that the three RIS were A+T rich and contained a number of sequence elements that may function in the initiation of DNA replication. The data support the idea that mammalian ori are organised from modular sequence elements.

Animals

A modular set of Flp, FRT and lacZ fusion vectors for manipulating genes by site-specific recombination.

Site-specific recombinases can serve as powerful tools to target genetic manipulations to specific cell populations in culture and in the organism. A series of vectors for engineering gene activation, deletion and integration in mammalian cells using Flp recombinase is described here. The vectors are modular in design so that specific cassettes can be linked depending on the application. Using these vectors, efficient Flp-mediated lacZ activation and beta-galactosidase (beta Gal) detection has been demonstrated in mammalian cell culture. These vectors should facilitate using Flp to mark cell populations, as well as to activate, remove or mutate genes in culture and in the mouse.

Amino Acid Sequence

Prediction of neurotoxic potency of hazardous substances with a modular in vitro test battery.

Neurotoxic action was investigated on different model nervous systems linked to a modular in vitro test battery. Voltage operated potassium channels and glutamate operated ion channels expressed in oocytes of the clawed frog Xenopus laevis by injection of cRNA (cloned RNA) or mRNA, respectively, as well as isolated neurons and isolated neuronal networks from the buccal ganglia of the snail Helix pomatia, were used as consecutive modules of different complexity. Lead (Pb2+) was chosen as a known neurotoxic model substance to evaluate the suitability of the test battery to predict the neurotoxic potency of hazardous substances, to establish dose-response relationships, and to investigate the basic mechanisms involved in neurotoxicity. All modules delivered consistent results: potassium currents were reduced by lead with a threshold concentration of 0.1 mumol/l. Membrane currents elicited by the glutamate receptor agonists kainate were decreased by lead with a threshold concentration below 0.1 mumol/l, while currents elicited by the agonist AMPA were not affected. Action potentials generated by the isolated B4 snail neuron showed a decrease of potential amplitude and a prolongation of potential duration after application of lead. The neuronal network controlling the feeding activities of the snail reacted with a decrease of the frequency of the spontaneously generated feeding depolarisations, thus showing the direct neurotoxic effect of lead on body functions and behaviour.

Animals

A modular stopped-flow system for use in routine pharmaceutical analysis.

A modular stopped-flow system for routine pharmaceutical analysis is presented. It consists of an inexpensive stopped-flow module which is fitted to a spectrophotometer or spectrofluorimeter and controlled by a simple computer. The automatic technique developed with this system is suitable for the individual and simultaneous determination of various pharmaceuticals (anti-asthmatics, psychotropics, hormones, analgesics, anaesthetics and antiseptics) with satisfactory results.

Autoanalysis