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At least 703 records · Page 39Linked to original sources
PubMed2002

Transcription of the Drosophila CKI gene dacapo is regulated by a modular array of cis-regulatory sequences.

Organogenesis requires coordination between developmental programs and cell cycle progression. The Cip/Kip families of cyclin-dependent kinase inhibitor (CKI) are main effectors linking these two programs. In many instances, expression of Cip/Kip CKIs are increased abruptly in cells entering their last mitotic cycle, suggesting that CKI expression is developmentally regulated. Expression of Dacapo (Dap), a Drosophila Cip/Kip CKI, is transiently up-regulated immediately before cells enter G1 arrest. Here we report that dap transcription is controlled by modular arrays of tissues specific cis-regulatory elements. Furthermore, we identified pan-neural Prospero as a regulator of dap transcription in the developing nervous system, providing an example how tissue-specific developmental programs can be linked to cell cycle progression.

Animals↗
PubMed2001

A modular approach for representing and executing clinical guidelines.

In this paper, we propose an approach for managing clinical guidelines. We outline a modular architecture, allowing us to separate two conceptually distinct aspects: the representation (and acquisition) of clinical guidelines and their execution. We propose an expressive formalism, which allows one to deal with the context-dependent character of clinical guidelines and also takes into account different temporal aspects. We also describe our tool for acquiring clinical guidelines, which provides a user-friendly interface to physicians, and automatically detects many forms of syntactic and semantic inconsistencies in the guidelines being acquired. In the second part of the paper, we describe a flexible engine for executing clinical guidelines (e.g. for clinical decision support applications, for medical education, or for integrating guidelines into the clinical practice), focusing our attention on temporal issues.

Artificial Intelligence↗
PubMed1997

Modular organization of carbohydrate recognition domains in animal lectins.

In spite of the great diversity of animal lectins, a common characteristic is their ability to bind sugars by means of discrete, modular carbohydrate recognition domains, CRDs. Three different groups of animal lectins-galectins, P-type and C-type lectins- have different types of CRDs which they arrange in a number of combinations, in three dimensions, in order to increase the affinity for oligosaccharides associated with glycoconjugates. The necessity of combining multiple CRDs in a native lectin molecule in order to increase the affinity for multiple ligands is of great importance physiologically, since many of the carbohydrate structures associated with proteins exist in a variety of different conformations. Recent work has clarified the structural basis for carbohydrate recognition by some of these lectins.

Amino Acid Sequence↗
PubMed2001

Modular microsystem for epithelial cell culture and electrical characterisation.

We have realised a microsystem for the culture and electrical characterisation of epithelial cell layers for cell-based diagnostic applications. The main goal of this work is to achieve both cell culture and impedimetric and potentiometric characterisation on a single device. The miniaturised cell culture system enables the uses of scarce epithelial cells, as obtained from transgenic mice or from human biopsies. The device is completely modular and offers high flexibility: a polycarbonate membrane used as cell substrate is glued in between two moulded Polydimethylsiloxane (PDMS) layers to form a sandwich, which is placed between two stacks, containing the microfluidic channels and integrated measurement electrodes. The polycarbonate membrane sandwich can be removed, replaced or analysed at any time. We have characterised the impedimetric properties of our microsystem, demonstrated epithelial cell layer growth within it, and have done the initial electrical characterisation of epithelial cell layers.

Animals↗
PubMed1998

Monitoring of cellular signalling and metabolism with modular sensor-technique: the PhysioControl-Microsystem (PCM).

Microsensors provide instruments particularly suited for the noninvasive analysis of cell and tissue cultures. The outstanding benefit lies in the passive behaviour of continuously working transducers, which in turn allows the dynamic recording of function-specific cellular processes. The microsensor system presented in this paper is a modular arrangement of various planar and non-planar sensor elements surrounding small cell culture chambers. An optic access to the cultures (e.g. for high resolution light microscopy and spectro-photometric techniques) enables a parallel and comparative data acquisition. The system was originally designed for biomedical research in chemotherapy and pharmacology but it proved to be an effective device both for toxicological and environmental research.

Biosensing Techniques↗
PubMed1998

Engineering of modular polyketide synthases to produce novel polyketides.

Polyketides are important natural products produced by Actinomycetes and other organisms via the polymerization of coenzyme A-activated carboxylic acids. Modular polyketide synthases are large multifunctional enzymes that direct the biosynthetic process using a dedicated 'module' for each polymerization reaction, which specifies the unit to be polymerized, its oxidation state and stereochemistry. Over the past two years proof-of-principle has been demonstrated for technologies that modify or exchange modules to create hybrid enzymes that catalyze the biosynthesis of novel polyketides.

Journal Article↗
PubMed1999

Modular features of motor control and learning.

The study of complex motor behaviours has highlighted the role of modular representations both in the planning and in the execution of actions. Recent findings suggest the presence of functional modules within a variety of neural structures. Computational investigations are now addressing the issue of how these modules may act concurrently to generate a wide repertoire of behaviours.

Animals↗
PubMed2002

The modular logic of signaling proteins: building allosteric switches from simple binding domains.

Many eukaryotic signal transduction proteins have component-based architectures: they are built from combinations of protein interaction domains and catalytic domains. Intact, these proteins display the sophisticated allosteric behavior required for cellular regulation; the protein's output activity is tightly repressed under basal conditions, but can be robustly activated by a specific set of input effector ligands. A combination of structural, biophysical and computational studies is beginning to shed light on the fundamental principles governing this type of modular allostery.

Allosteric Regulation↗
PubMed2001

Modular phosphoinositide-binding domains--their role in signalling and membrane trafficking.

The membrane phospholipid phosphatidylinositol is the precursor of a family of lipid second-messengers, known as phosphoinositides, which differ in the phosphorylation status of their inositol group. A major advance in understanding phosphoinositide signalling has been the identification of a number of highly conserved modular protein domains whose function appears to be to bind various phosphoinositides. Such 'cut and paste' modules are found in a diverse array of multidomain proteins and recruit their host protein to specific regions in cells via interactions with phosphoinositides. Here, with particular reference to proteins involved in membrane traffic pathways, we discuss recent advances in our understanding of phosphoinositide-binding domains.

Amino Acid Sequence↗
PubMed1996

Large, complex modular structure of a fission yeast DNA replication origin.

BACKGROUND: In the budding yeast, Saccharomyces cerevisiae, each DNA replication origin is associated with an autonomously replicating sequence (ARS) element. Each element contains several modules, including an essential close match to the 11 base-pair (bp) ARS consensus sequence (ACS) and two or three short (< 20 bp) stimulatory motifs, within a stretch of approximately 150 bp or less. To determine whether a similar origin structure exists in the evolutionarily distant fission yeast, Schizosaccharomyces pombe, we used deletion and linker substitution scanning to identify the sequences important for the function of ars3002, a chromosomal replication origin. RESULTS: We detected two large (30-55 bp) essential regions and several additional stimulatory sequences within a 600 bp stretch of a restriction fragment containing ars3002. The two essential regions are similar to each other, and sequences similar to them are found in all known S. pombe ARS elements, suggesting that one or both of them may represent the S. pombe equivalent of the S. cerevisiae ACS. CONCLUSIONS: Like S. cerevisiae origins, the S. pombe origin, ars3002, possesses a modular structure, but the number and size of modules is greater for ars3002, and ars3002 is larger than S. cerevisiae origins. These observations suggest that origin function in S. pombe requires more protein-DNA interactions than in S. cerevisiae.

Base Sequence↗
PubMed1999

Vision: modular analysis--or not?

It has commonly been assumed that the many separate areas of the visual system perform modular analyses, each restricted to a single attribute of the image. A recent paper advocates a radically different approach, where all areas in the hierarchy analyse all attributes of the image to extract perceptually relevant decisions.

Consciousness↗
PubMed1999

Endoluminal repair of infrarenal abdominal aortic aneurysms using a modular stent-graft: one-year clinical results from a European multicentre trial.

This is a report of a prospective study to evaluate the safety and efficacy of the Medtronic AneuRx stent-graft. Patients with an infrarenal aneurysm with a proximal neck length of greater than 10 mm and a neck diameter not greater than 26 mm and iliac artery diameters of at least 6 mm were accepted for endovascular repair using the Medtronic AneuRx modular stent-graft. A total of 104 patients were included in the study. Transfemoral placement of the bifurcated stent-graft was successful in 102 of 104 patients. Two conversions were performed. The mean operating time was 148 min (range 75-480) and the mean blood loss was 605 ml (range 100-2900). The mean follow-up was 15 months (range 12-21). Complications were rare and no kinking or migration occurred. At follow-up, four endoleaks persisted after 12 months. The Medtronic AneuRx stent-graft is a safe and efficacious alternative to open abdominal aortic aneurysm repair with excellent early results.

Aged↗
PubMed2001

Functionalized oligoanthranilamides: modular and conformationally controlled scaffolds.

This paper describes the use of functionalized oligoanthranilamides as conformationally controlled scaffolds for molecular recognition. Oligomers of anthranilamides are stabilized by the formation of intramolecular six-membered hydrogen bonds in a linear strand conformation. Onto alternate anthranilic acid units, we have attached di- or tripeptide recognition units with the potential to form intramolecular hydrogen bonds to an intercalated peptide strand. Using 1H NMR dilution experiments in CDCl(3), we have observed chemical shift changes that are consistent with the formation of an extended hydrogen bonded sheet dimer. We also demonstrate that the bis-alanine functionalized strands are able to form discrete hydrogen bonded complexes with dipeptide substrates and to bind hexanoyl alanylalanine selectively over its benzyl ester. In the presence of excess hydrogen bond donors and acceptors, the oligoanthranilamide strand retained its linear conformation, pointing to the potential of this modular design as a useful and stable scaffold for molecular recognition studies.

Dimerization↗
PubMed2000

Solution structure of PCP, a prototype for the peptidyl carrier domains of modular peptide synthetases.

BACKGROUND: Nonribosomal peptide synthetases (NRPSs) are large modular enzymes responsible for the synthesis of a variety of microbial bioactive peptides. They consist of modules that each recognise and incorporate one specific amino acid into the peptide product. A module comprises several domains, which carry out the individual reaction steps. After activation by the adenylation domain, the amino acid substrate is covalently tethered to a 4'-phosphopantetheinyl cofactor of a peptidyl carrier domain (PCP) that passes the substrate to the reaction centres of the consecutive domains. RESULTS: The solution structure of PCP, a distinct peptidyl carrier protein derived from the equivalent domain of an NRPS, was solved using NMR techniques. PCP is a distorted four-helix bundle with an extended loop between the first two helices. Its overall fold resembles the topology of acyl carrier proteins (ACPs) from Escherichia coli fatty acid synthase and actinorhodin polyketide synthase from Streptomyces coelicolor; however, the surface polarity and the length and relative alignment of the helices are different. The conserved serine, which is the cofactor-binding site, has the same location as in the ACPs and is situated within a stretch of seven flexible residues. CONCLUSIONS: The structure of PCP reflects its character as a protein domain. The fold is well defined between residues 8 and 82 and the structural core of the PCP domain can now be defined as a region spanning 37 amino acids in both directions from the conserved serine. The flexibility of the post-translationally modified site might have implications for interactions with the cooperating proteins or NRPS domains.

Amino Acid Sequence↗
PubMed2001

Exploring the domain structure of modular nonribosomal peptide synthetases.

Recently, considerable insight has been gained into the modular organization of nonribosomal peptide synthetases (NRPS). The three-dimensional structures of domains associated with substrate adenylation and covalent binding have been solved as well as the structure of a priming enzyme required for the post-translational modification of NRPS. Taken together, these studies will help us to understand the architecture of these mega-enzymes.

Models, Molecular↗
PubMedDate not supplied

Modular shoulder arthroplasty.

One hundred consecutive Biomet modular shoulder arthroplasties were studied prospectively and were evaluated with a minimum 2-year follow-up (average 41 months). Fifty-seven women and 43 men with an average age of 64 years were evaluated for pain, activities of daily living, range of motion, cost, and complications. Fourteen patients had undergone previous surgery to the shoulder. Seventy patients underwent total shoulder arthroplasty, and thirty underwent hemiarthroplasty. Pain and range of motion demonstrated statistically significant improvement. Eight activities of daily living were rated on a 0 to 3 scale, and all were significantly improved. Complications were noted in 18 patients and included urinary retention, pulmonary embolus, rotator cuff tear, titanium synovitis, subluxation, and dislocation. Twelve shoulders underwent secondary procedures for rotator cuff repair, open reduction, and component revision for instability. Lucent lines were present in 62.5% of glenoids, 92.3% of cemented stems, and 0% of cementless stems on postoperative radiographs. No patients underwent revision surgery for component loosening, and no cases of humeral head-stem dissociation were seen. Ninety-five shoulders were rated by the patients as improved, and five were made worse.

Activities of Daily Living↗
PubMedDate not supplied

Dissociation of modular humeral head components: a biomechanical and implant retrieval study.

In vivo dissociation of the Morse-taper of shoulder arthroplasty modular humeral components has been reported. The incidence of this complication appears to be approximately 1:1000. The objective of this study was to identify conditions that might affect the Morse-taper interface strength in humeral components. Mechanical tests were performed to load and dissociate humeral heads from the humeral stems (titanium). The effect of loading rate, load amplitude, and number of impactions was investigated. Dissociation force was measured after the taper was contaminated with water, oil, blood, and bone cement particles. The mean dissociation force after two impactions with a mallet was 2926 +/- 955 N. Dissociation force was linearly proportional to impaction force. Repetitive loading beyond two impactions did not significantly increase taper strength. Contamination of the taper with as little as 0.4 ml of fluid could prevent fixation of the taper.

Biomechanical Phenomena↗
PubMed2001

Analysis of the prodiginine biosynthesis gene cluster of Streptomyces coelicolor A3(2): new mechanisms for chain initiation and termination in modular multienzymes.

BACKGROUND: Prodiginines are a large family of pigmented oligopyrrole antibiotics with medicinal potential as immunosuppressants and antitumour agents that are produced by several actinomycetes and other eubacteria. Recently, a gene cluster in Streptomyces coelicolor encoding the biosynthesis of undecylprodiginine and butyl-meta-cycloheptylprodiginine has been sequenced. RESULTS: Using sequence comparisons, functions have been assigned to the majority of the genes in the cluster, several of which encode homologues of enzymes involved in polyketide, non-ribosomal peptide, and fatty acid biosynthesis. Based on these assignments, a complete pathway for undecylprodiginine and butyl-meta-cycloheptylprodiginine biosynthesis in S. coelicolor has been deduced. Gene knockout experiments have confirmed the deduced roles of some of the genes in the cluster. CONCLUSIONS: The analysis presented provides a framework for a general understanding of the genetics and biochemistry of prodiginine biosynthesis, which should stimulate rational approaches to the engineered biosynthesis of novel prodiginines with improved immunosuppressant or antitumour activities. In addition, new mechanisms for chain initiation and termination catalysed by hitherto unobserved domains in modular multienzyme systems have been deduced.

Gene Deletion↗