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At least 613 records · Page 34Linked to original sources
PubMed1995

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1985

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1995

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1989

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↗
PubMed1992

Interface corrosion of a modular head total hip prosthesis.

Wear and corrosion products released from metallic prosthetic joints can stimulate adverse reactions in the surrounding tissues that may eventually require revision of the prostheses. The authors report here a case of a modular total hip prosthesis removed after 35 months that showed evidence of corrosion and fretting at the Morse taper interface between the titanium alloy femoral stem and the cobalt-chromium ball.

Aged↗
PubMed1994

The EORTC QLQ-LC13: a modular supplement to the EORTC Core Quality of Life Questionnaire (QLQ-C30) for use in lung cancer clinical trials. EORTC Study Group on Quality of Life.

The EORTC Study Group on Quality of Life has developed a modular system for assessing the quality of life of cancer patients in clinical trials composed of two basic elements: (1) a core quality of life questionnaire, the EORTC QLQ-C30, covering general aspects of health-related quality of life, and (2) additional disease- or treatment-specific questionnaire modules. Two international field studies were carried out to evaluate the practicality, reliability and validity of the core questionnaire, supplemented by a 13-item lung cancer-specific questionnaire module, the EORTC QLQ-LC13. In this paper, the results of an evaluation of the QLQ-LC13 are reported. The lung cancer questionnaire module comprises both multi-item and single-item measures of lung cancer-associated symptoms (i.e. coughing, haemoptysis, dyspnoea and pain) and side-effects from conventional chemo- and radiotherapy (i.e. hair loss, neuropathy, sore mouth and dysphagia). It was administered to patients with non-resectable lung cancer recruited from 17 countries. In total, 883 and 735 patients, respectively, completed the questionnaire prior to and once during treatment. The symptom measures discriminated clearly between patients differing in performance status. All item scores changed significantly in the expected direction (i.e. lung cancer symptoms decreased and treatment toxicities increased) during treatment. With one exception (problems with a sore mouth), the change of toxicity measures over time was related specifically to either chemo- or radiotherapy. However, the single item on neuropathy did not measure adequately the full range of symptoms. The hypothesised scale structure of the questionnaire was partially supported by the data. The multi-item dyspnoea scale met the minimal standards for reliability (Cronbach alpha coefficient > 0.70), while the pain items did not form a scale with reliability estimates acceptable for group comparisons. In conclusion, the results form international field testing lend support to the EORTC QLQ-LC13 as a clinically valid and useful tool for assessing disease- and treatment-specific symptoms in lung cancer patients participating in clinical trials, when combined with the EORTC core quality of life questionnaire. In a few areas, however, the questionnaire module could benefit from further refinements. In addition, its performance over a longer period of time still needs to be investigated.

Adult↗
PubMed1995

Polyketide synthesis in vitro on a modular polyketide synthase.

BACKGROUND: The 6-deoxyerythronolide B synthase (DEBS) of Saccharopolyspora erythraea, which synthesizes the aglycone core of the antibiotic erythromycin A, contains some 30 active sites distributed between three multienzyme polypeptides (designated DEBS1-3). This complexity has hitherto frustrated mechanistic analysis of such enzymes. We previously produced a mutant strain of S. erythraea in which the chain-terminating cyclase domain (TE) is fused to the carboxyl-terminus of DEBS1, the multienzyme that catalyzes the first two rounds of polyketide chain extension in S. erythraea. This mutant strain produces triketide lactone in vivo. We set out to purify the chimaeric enzyme and to determine its activity in vitro. RESULTS: The purified DEBS1-TE multienzyme catalyzes synthesis of triketide lactones in vitro. The synthase specifically uses the (2S)-isomer of methylmalonyl-CoA, as previously proposed, but has a more relaxed specificity for the starter unit than in vivo. CONCLUSIONS: We have obtained a purified polyketide synthase system, derived from DEBS, which retains catalytic activity. This approach opens the way for mechanistic and structural analyses of active multienzymes derived from any modular polyketide synthase.

Cell-Free System↗
PubMed1995

Tyrosine kinases: modular signaling enzymes with tunable specificities.

Cytoplasmic tyrosine kinases are composed of modular domains; one (SH1) has catalytic activity, the other two (SH2 and SH3) do not. Kinase specificity is largely determined by the binding preferences of the SH2 domain. Attaching the SH1 domain to a new SH2 domain, via protein-protein association or mutation, can thus dramatically change kinase function.

Protein-Tyrosine Kinases↗
PubMed1994

A modular solid state detector for measuring high energy heavy ion fragmentation near the beam axis.

A multi-element solid state detector has been designed to measure fluences of fragments produced near the beam axis by high energy heavy ion beams in thick targets. The detector is compact and modular, so as to be readily reconfigured according to the range of fragment charges and energies to be measured. Preamplifier gain settings and detector calibrations are adjustable remotely under computer control. We describe the central detector, its associated detectors and electronics, triggering scheme, data acquisition and particle identification techniques, illustrated by data taken with 600 MeV/u 56Fe beams and thick polyethylene targets at the LBL Bevalac. The applications of this work to space radiation protection are discussed.

Algorithms↗
PubMed2004

Primary total hip arthroplasty using a modular proximally coated prosthesis in patients older than 70: two to eight year results.

Patients older than 70 years who underwent primary total hip arthroplasty using a modular proximally porous-coated femoral stem with an ingrowth hemispherical acetabular component were evaluated. This included 135 hips in 122 patients, with an average 5-year follow-up period. This study included 96 patients (107 hips) still living; 26 patients (28 hips) patients had died, and 8 patients were lost to follow up. In this study, 93% of patients had little or no pain, and 95% were extremely or very satisfied with the operation. Mean Harris Hip score was 83, with a Short Form-36 (SF-36) physical component and mental component summary score of 41 and 51, respectively. Osteolysis surrounding the femur was seen in 8 hips (7%) and around the acetabulum in 6 hips (5%). No components were loose or required revision.

Aged↗
PubMed2004

Surgical management of polyethylene wear and pelvic osteolysis with modular uncemented acetabular components.

Osteolysis, usually associated with polyethylene wear, has become one of the most prevalent complications associated with total hip arthroplasty inserted without cement. Management of osteolysis is challenging because the disorder tends to develop silently and surgical intervention can result in complications. In addition, long-term outcomes are unknown. We discuss the current knowledge and data available on polyethylene wear and pelvic osteolysis with modular uncemented acetabular components. We also outline an algorithm for evaluation and treatment of patients. In general, we see patients with well-fixed components every 2 years, and we base follow-up visits after 6 years on predicted polyethylene wear rates and the presence or absence of pelvic osteolysis.

Arthroplasty, Replacement, Hip↗
PubMed2004

Late dissociation of an alumina-on-alumina bearing modular acetabular component.

Alumina-on-alumina bearings for total hip arthroplasty have been introduced as a promising alternative to reduce wear debris and to increase the life expectancy of the prosthesis. We report a case of a late dissociation of an alumina-on-alumina bearing modular acetabular component, which occurred 2 years, 8 months after surgery. Detailed analysis of the retrieved prosthesis suggested that the cause of the failure may be strong rotational torque developed by a roughening of the bearing's alumina surface caused by edge loading (microseparation). The strong friction torque in articulation may explain the higher reported rate of mechanical loosening of the acetabular component in alumina-on-alumina bearing total hip prostheses.

Acetabulum↗