Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “modularity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed2006

Novel modular enzymes encoded by a cellulase gene cluster in Cellvibrio mixtus.

Hydrolysis of plant cell wall polysaccharides, a process which is of intrinsic biological and biotechnological importance, requires the concerted action of an extensive repertoire of microbial cellulases and hemicellulases. Here, we report the identification of the gene cluster unk16A, regA and cel5B in the aerobic soil bacterium Cellvibrio mixtus, encoding a family 16 (CmUnk16A) glycoside hydrolase (GH), an AraC/XylS transcription activator (CmRegA) and a family 5 (CmCel5B) endo-glucanase, respectively. CmUnk16A is a modular enzyme comprising, in addition to the catalytic domain, two family 32 carbohydrate-binding modules (CBMs), termed CBM32-1 and CBM32-2, a CBM4 and a domain of unknown function. We show that CBM32-2 binds weakly to laminarin and pustulan. CmRegA is also a modular protein containing a highly hydrophobic N-terminal domain and a C-terminal DNA-binding domain of the AraC/XylS family. The role of the identified enzymes in the hydrolysis of cell wall polysaccharides by aerobic bacteria is discussed.

Amino Acid Sequence↗
PubMed1980

A theory of modular evolution for bacteriophages.

The modular theory of virus evolution has clear experimental support among the temperate bacteriophages of the enteric bacteria. However, there is also similar genetic and DNA heteroduplex evidence for such evolution among other families of bacteriophages: the virulent bacteriophages of the enterics comprise several families: the T-even group, the T3-T7 group (which has many members among different species of bacteria, including bacteria as widely divergent as E. coli and Caulobacter crescentus. It nicely explains the diffusion of very similar homologous bacteriophages into hosts whose own DNAs have diverged very greatly from each other in nucleotide sequence. It also accounts for the rigorous maintenance of regulatory schemes while units of function (including regions coding for proteins) diverge more rapidly. It should also be noted that the considerations that make modular evolution seem advantageous for bacteriophages apply equally well to viruses of higher organisms. Furthermore, the kinds of heteroduplex similarity observed among animal viruses are reminiscent of what is found for bacteriophages. Viruses found in widely divergent hosts show much greater similarity than would be expected; quite possibly animal viruses also evolve as a population of interchangeable modules.

Bacteriophage lambda↗
PubMed2003

Reprogramming control of an allosteric signaling switch through modular recombination.

Many eukaryotic signaling proteins are composed of simple modular binding domains, yet they can display sophisticated behaviors such as allosteric gating and multi-input signal integration, properties essential for complex cellular circuits. To understand how such behavior can emerge from combinations of simple domains, we engineered variants of the actin regulatory protein N-WASP (neuronal Wiskott-Aldrich syndrome protein) in which the "output" domain of N-WASP was recombined with heterologous autoinhibitory "input" domains. Synthetic switch proteins were created with diverse gating behaviors in response to nonphysiological inputs. Thus, this type of modular framework can facilitate the evolution or engineering of cellular signaling circuits.

Actins↗
PubMed1998

Plasposons: modular self-cloning minitransposon derivatives for rapid genetic analysis of gram-negative bacterial genomes.

A series of modular mini-transposon derivatives which permit the rapid cloning and mapping of the DNA flanking the minitransposon's site of insertion has been developed. The basic plasposon, named TnMod, consists of the Tn5 inverted repeats, a conditional origin of replication, rare restriction endonuclease multiple cloning sites, and exchangeable antibiotic resistance cassettes. The broad host range and low target DNA sequence specificity of the Tn5 transposase, in combination with the flexibility afforded by the modular arrangement of TnMod, result in a versatile tool for the mapping of insertional mutations and the rapid recovery of clones from gram-negative bacteria.

DNA Transposable Elements↗
PubMed1993

Efficient transcriptional activation of many simple modular promoters by simian virus 40 large T antigen.

Simian virus 40 (SV40) large T antigen is a multifunctional protein which plays central roles during both lytic and transforming infections by SV40. It is a potent transcriptional activator and increases expression from the SV40 late promoter and from several cellular promoters. To understand better the transcriptional activation activity of large T antigen, we examined its ability to transactivate a set of simple modular promoters containing one of four upstream activation sequences coupled with one of three different TATA box sequences originally constructed and studied by Taylor and Kingston (Mol. Cell. Biol. 10:165-175, 1990). Large T antigen activated transcription from all of these simple promoters. The identity of the TATA box was a more important determinant of the final level of gene expression than was the identity of the upstream activating sequence element. We also determined the ability of a set of mutant SV40 large T antigens to activate a subset of these promoters. Several mutant SV40 large T antigens which had reduced ability to activate the complex SV40 late and Rous sarcoma virus long terminal repeat promoters showed reduced transcriptional activation activity on all of the modular promoters tested. We used a set of promoter derivatives of the human U6 small nuclear RNA promoter containing different TATA boxes and found that wild-type large T antigen could activate transcription from all of them, although to widely different levels of expression.

Animals↗
PubMed1982

Construction of a modular dihydrofolate reductase cDNA gene: analysis of signals utilized for efficient expression.

Dihydrofolate reductase (DHFR) modular genes have been constructed with segments containing the adenovirus major late promoter, a 3' splice site from a variable region immunoglobulin gene, a DHFR cDNA, and portions of the simian virus 40 (SV40) genome. DNA-mediated transfer of these genes transformed Chinese hamster ovary DHFR- cells to the DHFR+ phenotype. Transformants contained one to several copies of the transfected DNA integrated into the host genome. Clones subjected to growth in increasing concentrations of methotrexate eventually gave rise to lines containing several hundred copies of the transforming DNA. Analysis of the DHFR mRNA produced in amplified lines indicated the following. (i) All clones utilize the adenovirus major late promoter for transcription initiation. (ii) A hybrid intron formed by the 5' splice site of the adenovirus major late leader and a 3' splice site from a variable-region immunoglobulin gene is properly excised. (iii) The mRNA is not efficiently polyadenylated at sequences in the 3' end of the DHFR cDNA but rather uses polyadenylation signals downstream from the DHFR cDNA. Three independent clones produce a DHFR mRNA containing SV40 or pBR322 and SV40 sequences, and the RNA is polyadenylated at the SV40 late polyadenylation site. Another clone has recombined into cellular DNA and apparently uses a cellular sequence for polyadenylation. Introduction of a segment containing the SV40 early polyadenylation signal into the 3' end of the DHFR cDNA gene generated a recombinant capable of transforming cells to the DHFR+ phenotype with at least a 10-fold increase in efficiency, demonstrating the necessity for an efficient polyadenylation signal. Attachment of a DNA segment containing the transcription enhancer (72-base pair repeat) of SV40 further increased the biological activity of the modular DHFR gene 50- to 100-fold.

Adenoviridae↗
PubMed1985

TU elements: a heterogeneous family of modularly structured eucaryotic transposons.

We describe here a family of foldback transposons found in the genome of the higher eucaryote, the sea urchin Strongylocentrotus purpuratus. Two major classes of TU elements have been identified by analysis of genomic DNA and TU element clones. One class consists of largely similar elements with long terminal inverted repeats (IVRs) containing outer and inner domains and sharing a common middle segment that can undergo deletions. Some of these elements contain insertions. The second class is highly heterogeneous, with many different middle segments nonhomologous to those of the first-class and variable-sized inverted repeats that contain only an outer domain. The middle and insertion segments of both classes carry sequences that also are found unassociated from the inverted repeats at many other genomic locations. We conclude that the TU elements are modular structures composed of inverted repeats plus other sequence domains that are themselves members of different families of dispersed repetitive sequences. Such modular elements may have a role in the dispersion and rearrangement of genomic DNA segments.

Animals↗
PubMed2004

Dynamics of everyday life: rigorous modular modeling in neurobiology based on Bloch's dynamical theorem.

Natural, everyday sensorimotor behaviors, such as rising from sitting, typically have an intrinsic organization of several levels of analysis. Taking this intrinsic organization as key to understanding neural dynamics is neither a top-down nor a bottom-up approach, but rather a meshing of multiple centers and levels of analysis. Motor control requires body dynamics that are consistent with physical dynamics, besides the more microscopic levels of neural dynamics. The dynamics of separate movements have been investigated as if the ends can be capped off, separated from the rest of the individual's life. Is this dynamically correct? Even chaotic behavior is deterministic. However, the mathematics of nonlinear oscillations is not all of dynamics. This paper relates Bloch's dynamical theorem to the modular, conditional approach to sensorimotor and other neural functioning. Bloch's dynamical theorem lays a foundation for the piecewise study of structurally accurate dynamics in theoretical neurobiology. Piecewise studies can be used as a modeling option complementary to the methods of nonlinear oscillator dynamics. By applying Bloch's theorem, dynamics of movements analyzed piecewise can be extended into a smooth flow on any manifold, either as a whole or conditionally. Conditional dynamics makes dynamical modeling options explicit, often depending on what variables the organism can control, and allows one to take different modeling options at different junctures in analyzing the same phenomenon. For example, this approach allows the study of complex motor control problems to be reduced to modular constructions using singularities and flow lines. Dynamical contingencies are expressed using the mathematics of ordered structures. This paper presents Bloch's dynamical theorem and its relevance to model construction in theoretical neurobiology. Specific examples, integrated into physiological and behavioral context, are cited from the literature.

Models, Neurological↗
PubMed1998

Spinal cord modular organization and rhythm generation: an NMDA iontophoretic study in the frog.

Previous work using electrical microstimulation has suggested the existence of modules subserving limb posture in the spinal cord. In this study, the question of modular organization was reinvestigated with the more selective method of chemical microstimulation. N-methyl--aspartate (NMDA) iontophoresis was applied to 229 sites of the lumbar spinal cord gray while monitoring the isometric force output of the ipsilateral hindlimb at the ankle. A force response was elicited from 69 sites. At 18 of these sites, tonic forces were generated and rhythmic forces at 44. In the case of tonic forces, their directions clustered along four orientations: lateral extension, rostral flexion, adduction, and caudal extension. For the entire set of forces (tonic and rhythmic), the same clusters of orientations were found with the addition of a cluster directed as a flexion toward the body. This distribution of force orientations was quite comparable to that obtained with electrical stimulation at the same sites. The map of tonic responses revealed a topographic organization; each type of force orientation was elicited from sites that grouped together in zones at distinct rostrocaudal and depth locations. In the case of rhythmic sequences of force orientations, some were distinctly more common, whereas others were rarely elicited by NMDA. Mapping of the most common rhythms showed that each was elicited from two or three regions of the cord. These regions were close in location to the tonic regions that produced those forces that represented components specific to that rhythm. There was an additional caudal region from which the different rhythms also could be elicited. Taken together, these results support the concept of a modular organization of the motor system in the frog's spinal cord and delineate the topography of these modules. They also suggest that these modules are used by the circuitry underlying rhythmic pattern generation by the spinal cord.

Animals↗
PubMed1999

Universal modular glottiscope system: the evolution of a century of design and technique for direct laryngoscopy.

Since Kirstein introduced formal direct examination (autoscopy) of the glottis in 1895, a great number of laryngoscopes have been produced to view the vocal folds; however, none have had universal appeal. The primary goals for the designs have been to optimize exposure and to facilitate instrumentation of the glottis. An analysis of more than 50 laryngoscopes was done to assess key design characteristics that would ideally be present in a laryngoscope for optimally viewing the musculomembranous vocal folds. The Pro/Engineer and Pro/Mechanica computer programs were used to model the universal modular glottiscope. This new laryngoscope comprises a plurality of specially designed examining tubes that are bivalved proximally to improve utilization of hand instrumentation, and form a single tube distally to achieve internal distention of the supraglottal tissues. The distal lumen has an arcuate isosceles-triangular conformation to optimally expose the glottis. The base of the tube is detachable for the difficult intubation or the placement of bronchoscopes. The examining tubes vary in size and dimension to accommodate the diversity of human anatomy. The tubes are easily attachable to and detachable from an ergodynamically designed universal handle that can be joined to fulcrum laryngoscope holders or suspension gallows. The universal modular glottiscope evolved from the selective integration of optimal 20th-century design modifications of Kirstein's original autoscope. This new laryngoscope is ideally suited for phonomicrosurgery as well as for difficult intubation.

History, 20th Century↗
PubMed1988

A modular arrangement of neuronal processes in human cortex: disruption with aging and in Alzheimer's disease.

Studies were undertaken to assess whether or not neuron-specific immunostaining of the human brain can reveal unique cytoarchitectural features that may be affected by healthy aging and Alzheimer's disease (AD). Human prefrontal cortex (PFC) and anterior cingulate cortex (ACC) were stained with an antibody raised against the neurofilament protein 200,000 molecular weight subunit (NFP-200) using an avidin-biotin immunolocalization procedure. Immunostaining of cortex was neuron-specific and highlighted axons in particular. This staining has revealed an orderly arrangement of horizontal and vertical axon bundles which form latticelike compartments or modules throughout most of the matrix of the two cortical areas studied. The ACC shows this pattern to be intact in individuals through the ninth decade, while the PFC there was blurring of the modularity beyond the fifth decade. Irrespective of the age-related blurring of the latticelike arrangement of axons in PFC, neurologically normal elderly individuals nevertheless showed a highly organized appearance to the cortical matrix. By contrast, patients with AD showed a marked disruption of the modular arrangement of fibers in PFC, but not ACC. Differences between PFC fibers in controls and AD patients were also demonstrated with an axon-specific monoclonal antibody that reacted with phosphorylated epitopes of the NFP-200. The chaotic appearance of fiber staining in PFC seen in patients with AD was noted to be present in one subject who died in an early stage of the disease. The possible significance of this previously unknown aspect of cortical cytoarchitecture for normal cognitive functioning in humans is discussed.

Adolescent↗
PubMed2003

Percutaneous modular stent-grafts in the treatment of abdominal aortic aneurysms.

PURPOSE: To describe a newly designed bifurcated modular stent-graft and assess the feasibility and safety of its use in the treatment of abdominal aortic aneurysms (AAA). METHODS: Thirteen patients (10 men; mean age 61.2+/-16 years, range 57-78) with AAAs underwent treatment with a bifurcated stent-graft consisting of 4 components: an unsupported bifurcated stent-graft, an inner bare stent, and 2 stent-grafts. The system was placed sequentially through a percutaneously introduced 12-F sheath; the preloaded bifurcated main body of the stent-graft was deployed first, followed by the inner bare stent and individual stent-graft limbs through separate 10-F sheaths. Spiral computed tomography (CT) was performed before treatment and at 1 week, 3 months, and then at 6-month intervals. RESULTS: The stent-grafts were successfully deployed in all patients, although 3 types of procedure-related adverse events occurred: left limb kinking in 1, postimplantation syndrome (fever, leukocytosis, and decreased platelet count) in 5, and a small access site arteriovenous fistula in 1. Postprocedural angiography and 1-week follow-up CT scanning did not identify any endoleaks. At a mean 9.2+/-4.6-month follow-up, all devices were intact, with complete exclusion of the aneurysms and no endoleaks. CONCLUSIONS: This newly designed bifurcated modular stent-graft appears to be effective for percutaneous AAA repair; further investigation is warranted.

Aged↗
PubMed2006

Gene connectivity, function, and sequence conservation: predictions from modular yeast co-expression networks.

BACKGROUND: Genes and proteins are organized into functional modular networks in which the network context of a gene or protein has implications for cellular function. Highly connected hub proteins, largely responsible for maintaining network connectivity, have been found to be much more likely to be essential for yeast survival. RESULTS: Here we investigate the properties of weighted gene co-expression networks formed from multiple microarray datasets. The constructed networks approximate scale-free topology, but this is not universal across all datasets. We show strong positive correlations between gene connectivity within the whole network and gene essentiality as well as gene sequence conservation. We demonstrate the preservation of a modular structure of the networks formed, and demonstrate that, within some of these modules, it is possible to observe a strong correlation between connectivity and essentiality or between connectivity and conservation within the modules particularly within modules containing larger numbers of essential genes. CONCLUSION: Application of these techniques can allow a finer scale prediction of relative gene importance for a particular process within a group of similarly expressed genes.

Base Sequence↗
PubMed2005

Research protocol: EB-GIS4HEALTH UK - foundation evidence base and ontology-based framework of modular, reusable models for UK/NHS health and healthcare GIS applications.

EB-GIS4HEALTH UK aims at building a UK-oriented foundation evidence base and modular conceptual models for GIS applications and programmes in health and healthcare to improve the currently poor GIS state of affairs within the NHS; help the NHS understand and harness the importance of spatial information in the health sector in order to better respond to national health plans, priorities, and requirements; and also foster the much-needed NHS-academia GIS collaboration. The project will focus on diabetes and dental care, which together account for about 11% of the annual NHS budget, and are thus important topics where GIS can help optimising resource utilisation and outcomes. Virtual e-focus groups will ensure all UK/NHS health GIS stakeholders are represented. The models will be built using Protege ontology editor http://protege.stanford.edu/ based on the best evidence pooled in the project's evidence base (from critical literature reviews and e-focus groups). We will disseminate our evidence base, GIS models, and documentation through the project's Web server. The models will be human-readable in different ways to inform NHS GIS implementers, and it will be possible to also use them to generate the necessary template databases (and even to develop "intelligent" health GIS solutions using software agents) for running the modelled applications. Our products and experience in this project will be transferable to address other national health topics based on the same principles. Our ultimate goal is to provide the NHS with practical, vendor-neutral, modular workflow models, and ready-to-use, evidence-based frameworks for developing successful GIS business plans and implementing GIS to address various health issues. NHS organisations adopting such frameworks will achieve a common understanding of spatial data and processes, which will enable them to efficiently and effectively share, compare, and integrate their data silos and results for more informed planning and better outcomes.

Journal Article↗
PubMed2004

Modular decomposition of protein-protein interaction networks.

We introduce an algorithmic method, termed modular decomposition, that defines the organization of protein-interaction networks as a hierarchy of nested modules. Modular decomposition derives the logical rules of how to combine proteins into the actual functional complexes by identifying groups of proteins acting as a single unit (sub-complexes) and those that can be alternatively exchanged in a set of similar complexes. The method is applied to experimental data on the pro-inflammatory tumor necrosis factor-alpha (TNF-alpha)/NFkappaB transcription factor pathway.

Algorithms↗
PubMed1999

Complex modular cis-acting elements regulate expression of the cardiac specifying homeobox gene Csx/Nkx2.5.

The murine homeobox gene Csx/Nkx2.5 is an evolutionarily highly conserved gene related to the Drosophila tinman gene, which specifies cardiac and visceral mesoderm. Since Csx/Nkx2.5 plays an essential role in heart development, studying its regulation is essential for the better understanding of molecular mechanisms of cardiogenesis and the pathogenesis of congenital heart disease in humans. In this study, we characterized the murine Csx/Nkx2.5 gene and identified two novel untranslated exons, 1a, and 1b, resulting in three different Csx/Nkx2.5 transcripts. To examine the tissue-specific transcriptional regulation in vivo, we analyzed a total of 23 kb of Csx/Nkx2.5 upstream and downstream sequences by generating transgenic embryos carrying lacZ reporter constructs containing various lengths of flanking sequence. With 14 kb of 5' flanking sequence, lacZ expression was observed in the cardiac crescent at E7.5, and in the outflow tract, the interatrial groove, the atrioventricular canal and right and left ventricles, as well as in pharyngeal floor, thyroid primordia, and stomach at E10.5. In adult animals, lacZ expression of the transgene was limited to the atrioventricular junction and the subendocardium of the ventricular septum. Reducing the size of flanking sequence to 3.3 kb of intron 2 restricted lacZ expression to the outflow tract and the basal part of the right ventricle in E10.5 embryos. In contrast, the addition of 6 kb of 3' flanking sequence caused strong expression of the reporter gene in the entire right ventricle. Interestingly, Csx/Nkx2. 5 seems to be negatively regulated by its own gene product, because when lacZ was "knocked-in" to replace the entire coding exons, lacZ expression was much higher in the heart of homozygous embryos than that in the heterozygote. These results indicate that the transcriptional regulatory elements of Csx/Nkx 2.5 seems unexpectedly highly modular, and is temporally regulated in a dynamic manner by different enhancer regions. Since Csx/Nkx2.5-like genes are expressed in all species having a heart, their complex modular organization with multiple enhancers probably reflects progressive addition of regulatory elements during the evolution from a simple heart tube to a complex four-chambered organ.

Alternative Splicing↗
PubMed1995

Design of a non-constrained, non-cemented, modular, metacarpophalangeal prosthesis.

A non-constrained, non-cemented, modular prosthesis for replacement of the metacarpophalangeal joints of the fingers has been developed. The prosthesis is of a surface design which is modular in construction and is implanted into the bones with a press fit. The prosthesis is designed to be implanted into patients with traumatic injuries, post-traumatic osteoarthritis and into patients with rheumatoid arthritis at an early stage in the disease where the muscles and ligaments that surround the joint are still functional and can provide joint stability.

Arthritis, Rheumatoid↗
PubMed2006

Modular evolution and increase of functional complexity in replicating RNA molecules.

At early stages of biochemical evolution, the complexity of replicating molecules was limited by unavoidably high mutation rates. In an RNA world, prior to the appearance of cellular life, an increase in molecular length, and thus in functional complexity, could have been mediated by modular evolution. We describe here a scenario in which short, replicating RNA sequences are selected to perform a simple function. Molecular function is represented through the secondary structure corresponding to each sequence, and a given target secondary structure yields the optimal function in the environment where the population evolves. The combination of independently evolved populations may have facilitated the emergence of larger molecules able to perform more complex functions (including RNA replication) that could arise as a combination of simpler ones. We quantitatively show that modular evolution has relevant advantages with respect to the direct evolution of large functional molecules, among them the allowance of higher mutation rates, the shortening of evolutionary times, and the very possibility of finding complex structures that could not be otherwise directly selected.

Computational Biology↗